Abstract:

Neurosurgeons are uniquely positioned to make important and novel contributions to the study of normal human brain physiology. Some of the most powerful investigative methods employed routinely in experimental animal brain research laboratories involve the use of invasive techniques that cannot be applied directly to human subjects. However, in certain clinical settings many of these invasive experimental methods can be modified and adapted for use in neurosurgery patients in ways that do not increase the risks of surgery and allow investigators to pursue neuroscience research questions that cannot be addressed using non-invasive methods.

In order to achieve maximum scientific benefit from invasive basic brain research studies conducted in neurosurgical patients it is necessary to optimize all aspects of experimental planning and implementation processes. This desired level of operational performance is beyond the capacity of any individual neurosurgeon or neuroscientist. Each contemporary neuroscience topical area is enormously complex and to be effectively pursued requires the skills and knowledge of investigators with high levels of expertise that collective encompass a broad range of scientific and technical fields. In the face of ever increasing research enterprise complexity individual investigators and institutions have, of necessity, become more specialized and adopted strategies to focus resources in targeted topic areas. With rare exception, individual institutions do not have all of the specialized researchers and translational research infrastructure required to conduct brain research in neurosurgical subjects in a manner that is scientifically impactful and merits the support of extramural peer-review funding agencies.  

A decade ago a group of neurosurgeons, neurologists and neuroscientists from the University of Iowa (UI) in the midwest United States, and Newcastle University and University College London in the United Kingdom (UK), set out to explore the feasibility of establishing a new multi-institutional collaborative research program to study how sound and language information is processed within the human brain. The strategy was to leverage specialized resources at the UI to conduct invasive brain physiology research in neurosurgical patient-subjects, and the complimentary scientific expertise of UK based investigators in the wide range of non-invasive auditory systems research methods used in human subjects, as well experimental animal auditory research capabilities. Another key element in the collaborative strategy was to harness rapidly evolving internet based videoconferencing and large volume data transfer capabilities to functionally integrate the collaborative group in a way that closely approximates a fully on-site organizational structure.   

Over time this organizational strategy has proven to be successful. The collaborative group regularly publishes findings in the peer-review neuroscience literature that advance our understanding of auditory information processing with the human brain. The program is now supported through extramural grants awarded by the U.S. National Institutes of Health, U.S. National Science Foundation, U.S. Defense Department, Wellcome Trust and European Union. In this presentation the specific challenges faced, and overcome, in successfully implementing and developing this program will be described. This will include a description of the specialized facilities and equipment required, support staff structure, communication and work flow methods, and role of trainees such as post-doctoral fellows. Using this type of program building strategy it is now technically feasible for functional neurosurgeons at any institution to collaborate in a highly effective manner with neuroscientists anywhere else in the world.

Background: Deep Brain Stimulation (DBS) in rat models for neurological disorders contributes to the understanding of the pathophysiological mechanisms and subsequent progress of therapy. Physical restraint by stimulation via a cable connected to an external stimulation device may has negative impact on rat's wellbeing. Therefore, portable or even fully implantable devices have been developed. These devices are limited with regard to the range of experimental settings at least to some extent. We here tested the impact of stereotaxic implantation of electrodes and subsequent cable bound stimulation over two weeks on wellbeing of rats.

Method: Adult male Sprague Dawley rats were stereotaxically implanted with electrodes into the subthalamic nucleus under chloralhydrate anaesthesia (360mg/kg). After two weeks of recovery stimulation (130 Hz square wave pulses, pulse width 80µs, 80-160µA) or sham-stimulation started via a cable, which was connected to the electrodes by a socket on the rat's skull on one side, and the stimulation device on the other side. A swivel was interposed between cable and stimulation device allowing the rat to move freely in its home cage without twisting the cable. Throughout the whole procedure all rats were daily assessed for clinical score, body weight and nest building with Enviro-Dri^®.

Results: Stereotaxic implantation of electrodes induced only slight weight loss (3.3%± 0.6 S.E.M.) during the first two postoperative days. Thereafter, body weight steadily increased by 10-15%, with no effect of cable connection or actual stimulation. Clinical score and nest building behavior were not affected by electrode implantation or cable-bound stimulation/sham-stimulation.

Conclusion: Tethering electrodes by a cable to an external stimulation device does not affect the wellbeing of rats as assessed by daily evaluation of body weight, clinical score and nest- building behavior.These findings may be used for ethical justification of cable-bound stimulation and recording devices, which do not bear technical constraints to experimental settings as for example needed for evaluation and adaptation of closed loop systems. 

The project was supported by grants of the Deutsche Forschungsgemeinschaft (FOR 2591, GZ: SCHW1176/7-1).

The basal ganglia circuitries are known for their involvement in motor, cognitive-associative and limbic functions. Specifically, they play a role in time perception, temporal chunking, rhythm processing, and sensory and attentional gating. Here, we wanted to determine whether temporal speech information is represented in the neural responses in human basal ganglia nuclei.

                In patients with Parkinson’s disease (n=8), dystonia (n=3), and Tourette syndrome (n=3) implanted bilaterally for deep brain stimulation (DBS), we obtained local field potential recordings from the subthalamic nucleus (STN; n=8, 48 bipolar contacts) or the globus pallidus internus (GPi; n=6, 36 bipolar contacts), while they listened to two-speaker speech streams. One stream was task relevant, the other served as distractor. Temporal response functions (TRFs) were estimated for each contact separately. These TRFs describe the mapping between the word onsets of both speaker streams and the neural responses at the respective DBS contacts.

                All subjects showed sustained neural responses in the beta to low gamma range (15-60 Hz) to speech compared to baseline (p < 0.05). Encoding models based on TRF estimation showed that these neural responses track the word onsets in the two speech streams (34/48 STN contacts (71%), 23/36 GPi contacts (64%), p<0.05). Next, speech stream tracking was compared between the two speakers at contacts showing significant word onset tracking. This analysis revealed that 27 of 34 STN contacts (79%) and 10 of 23 GPi contacts (44%) showed selectivity for one of the two speaker streams (p<0.05). A similar number of contacts showed speaker selectivity for the task-relevant speech stream (STN: 14, GPi: 7) as for the distractor speech stream (STN: 13, GPi: 3).

                Our findings provide evidence that neural responses in human STN and GPi contain information on temporal speech information (i.e., word onsets) during continuous speech presentation and that speaker selectivity is present in these subcortical structures. This selectivity may be important for gating task-relevant and suppressing task-irrelevant information and thus for attentional selection.

The effects of magnetothermal deep brain stimulation of the STN on c-Fos gene expression

Huajie Liu ^1,2, Yasin Temel¹, Ali Jahanshahi¹, Sarah Hescham¹

¹Department of Neurosurgery, Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands

²European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands

Deep brain stimulation (DBS) has long been used to alleviate symptoms in patients suffering from neurological and neuropsychiatric disorders, but is afflicted by its mechanical invasiveness and the inability to selectively target specific subregions in a brain structure. In the present study, we demonstrate minimally invasive and remote neural excitation through magnetothermal deep brain stimulation (mDBS). The approach uses an alternating magnetic field to heat magnetic nanoparticles on the membrane of heat-sensitized neurons expressing the capsaicin receptor TRPV1. Specifically, we injected a lentivirus carrying TRPV1 labeled with mCherry unilaterally in the subthalamic nucleus of wild-type mice. Four weeks later magnetic or non-magnetic nanoparticles were injected into the same region in mDBS mice (n = 7) or sham (n = 6), respectively. Mice were exposed to an alternating magnetic field for 3 minutes before sacrifice. Immunohistochemical analysis revealed elevated expression of c-Fos protein levels in mDBS treated mice compared to sham in the primary motor cortex. These findings suggest that magnetothermal neurostimulation provides a platform for using nanotechnology to activate cells and allows for cell-specific modulation of deep brain tissue.

Key words: magnetothermal deep brain stimulation, c-Fos, subthalamic nucleus

Topic: Basic Science

Objective: We here investigated the effect of bilateral 6-hydroxydopamine (6-OHDA) lesions, a rat model for Parkinson`s disease (PD), on impulsivity and attention in an auditory oddball paradigm.

Background: In PD, the progressive loss of dopamine (DA) neurons in the substantia nigra leads to disturbed motor function, but cognitive disturbances, including attentional deficits and impulsivity, are increasingly recognized as disabling factors. Rats with 6-OHDA induced nigrostriatal lesions of dopamine neurons are used for modelling PD, and recent studies also indicate cognitive impairment in this model.

Methods: Rats were trained in a 3-class auditory oddball paradigm, where they had to nose poke a hole after an infrequent correct tone, which was rewarded by a pellet, but to ignore a frequent standard tone and infrequent distractor tone. After reaching a criterion of 90% correct hits, retrograde degeneration of DA neurons in the substantia nigra were induced by bilateral striatal injection of 6-OHDA (10 µg in 1µl PBS; n=12), sham-lesioned rats (controls; n=8) received vehicle. Four weeks after surgery the rats were re-tested in the oddball paradigm.

Results: After 6-OHDA lesions, rats show deteriorated attention, as indicated by a significant decrease in the hit rate to the correct tone. Additionally, the number of impulsive nose pokes was reduced compared to controls, which would indicate less impulsive behavior.

Conclusions: We conclude that rats with bilateral 6-OHDA lesions may be used also to investigate the biological basis of attentional deficits in PD, and to develop and test new therapeutic strategies for these symptoms ranging from pharmacological treatment to neurosurgical intervention.

The centromedian-parafascicular complex (CM-Pf) of the intralaminar thalamus is activated during attentional orienting and processing of behaviorally relevant stimuli. The CM-Pf is therefore suggested to be a part of a subcortical cognitive control loop that might influence basal ganglia-cortical functions. Here, we investigated the involvement of the human CM-Pf in processing of task relevant information during an auditory three-class oddball paradigm.

Simultaneous intracranial local field potentials (LFPs) and scalp electroencephalography (EEG) recordings were obtained in 6 patients (2 woman; mean age=48±12 years) who received deep brain stimulation (DBS) electrodes in the CM-Pf for the treatment of neuropathic pain syndromes. Within a few days after surgery, they performed an auditory three-class oddball paradigm with externalized DBS electrodes. Subcortical and cortical event-related potentials (ERPs) were analyzed upon presentation of one frequent standard stimulus (900Hz; 72%) and two infrequent salient stimuli (600Hz and 1200Hz; 14%), either being a target stimulus that requires a button press, or a distractor stimulus.

Analysis revealed high accuracy (>70%) for all participants. Target stimuli elicited a P3 response over parietal regions in the EEG. Recordings in the CM-Pf revealed highest amplitudes to target stimuli as well. Responses in the CM-Pf were modulated in a similar way compared with the cortical response. A cross correlation analysis revealed that the early CM-Pf signal correlates with the cortical P3 response after presentation of the target stimulus, but not after the distractor or standard stimulus.

We suggest that the human CM-Pf specifically is involved in goal-oriented action selection and attentional mechanisms. Auditory information may therefore be labelled as behavioral relevant in subcortical circuits before being distributed to cortical areas; possibly via thalamo-striatal loop mechanisms. Our findings not only support the notion that the CM-Pf can switch the basal ganglia system to bottom-up control based on salient events, as previously suggested by Kimura and colleagues (2004 in Neuroscience Research), but that the stimulus in addition has to be of a significant meaning to the subject.

A brain-machine interface (BMI) is a device, which interfaces directly with brain to control an external efforter (e.g. a robotic arm or computer).  Position or touch sense is important for clinical applications of the BMI because ideal prosthetic limbs should be perceived as natural extensions of the users' bodies. We have started to design a cortical modulator using optogenetics- a new method for the manipulation of neurons to dial in potential sensory input in a bi-directional manner. Optogenetics technique reduces most of the key problems associated with electrical brain stimulation: there is no associated electrical artifact to interfere with the electrophysiological recordings, nor any tissue damage from the current injection. It also allows for precise control of the spatial pattern of stimulation.Here we report data from initial bench testing and implantation for the flexible ECoG with LED in both the rat and non-human primate. We have shown that the flexible ECoG is effective as a chronic implant in rats, providing high fidelity neural recordings for up to 7 weeks. The initial results suggest that the new ECoG array can be successfully translated from rodents to accommodate the technological challenges associated with successfully interfacing with the non-human primate brain.

Background: In rodent cancer models a weight loss of 20% is usually used as humane endpoint. We recently reported an intracranial rat glioblastoma model that can be used to test the anti-tumor effects of local therapeutic strategies. Our standard criteria for rat sacrifice in this model are mainly based upon short term deterioration of the clinical score in combination with a slight weight loss, although weight losses of 20% almost never occur. Clinical scoring, however, is mainly based on subjective assessments and thus requires an experienced observer. Therefore, we here tested, whether the daily determination of more quantifiably observer-independent species-specific burrowing behavior or motor behavior have an advantage over clinical score and weight assessment.

Method: Glioblastoma BT4Ca cells were stereotactically implanted into the prefrontal cortex of adult male BDIX rats anaesthetized with cloralhydrate (360mg/kg). Starting with the day of surgery, all rats were daily assessed for body weight, clinical score, gravel burrowed from a hollow tube, locomotor distance in the open field and ataxia measures on the balance beam test. Endpoint criterion was assessed as described before.

Results: Implantation of BT4Ca cells reliably induced fast growing tumors with endpoints after 12-18 days at a tumor induction rate of 100%. Measures of burrowing behavior and motor activity were not superior to clinical scoring with regard to endpoint determination, since they deteriorated either in parallel (motor behavior) or even after first deterioration of the clinical score (burrowing). Nevertheless, more detailed inspection of the weight on different test days indicated that a mean absolute deviation of ≥2.5 in a window of four time points before a query point, in combination with a relative risk regarding the 80% weight threshold of ≥17% are well suited to find between 75-100% of actual endpoints in our study.

Conclusion: A robust criterion for endpoint determination in intracranial tumor models is not only necessary for ethical and legal considerations but also to achieve high-quality measures for scientific use. We here present a body weight analysis function that may be easily and reliably used for endpoint determination in rodent cancer models without confounding observer-dependent factors.

S. Helgers and S. R. Talbot equally contributed to this work.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the degeneration of dopaminergic nigrostriatal neurons. Previous studies have shown that ghrelin which is an endogenous 28-amino-acid peptide, has a beneficial effect on gastric motility and results in the reduction of neuronal degeneration in various animal models. The aim of this study was to investigate morphological and biochemical effects of ghrelin on gastrointestinal motility and myenteric plexus neurochemical alteration in 6- hydroxydopamine (6-OHDA)-induced PD rats. Male Wistar albino rats were stereotaxically 6-OHDA infused into the right medial forebrain bundle. Ghrelin and 6-OHDA+Ghr groups were administered 10 ng/kg ghrelin (s.c.) for twenty eight consecutive days. At the end of the experiment, after apomorphine-induced rotational behavior and colonic motility tests, brain, gastric and colonic tissues were collected from rats with transcardiac perfusion (4% paraformaldehyde) for histological investigations. Tyrosine hydroxylase (TH) immunoreactivity in the striatum and substantia nigra pars compacta (SNpc) were done to assess neuronal damage. TH, vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS) and glial fibrillary acidic protein (GFAP) immunohistochemistry were applied on sections from gastric and colonic tissues. In another set of rats, gastric emptying rate was measured. Our results indicated that rotational behaviour induced by apomorphine in 6-OHDA-injected rats was decreased with ghrelin treatment (p<0.01). In 6-OHDA-treated rats, gastric emptying was delayed with respect to control rats (p<0.05), while ghrelin treatment in 6-OHDA-induced rats abolished the delay in gastric emptying (p<0.001). In the 6-OHDA group, decreased TH immunoreactivity in the right striatum and substantia nigra areas increased with ghrelin administration. Increased VIP-immunoreactivity and decreased nNOS immunoreactivity was observed in the 6-OHDA group compared to the controls in the myenteric plexus of colon (p<0.05). Parallel with fecal output findings, nNOS immunoreactivity in the 6-OHDA+Ghr group rats was increased compared to 6-OHDA group (p<0.05). Increased antral myenteric plexus VIP immunoreactivity (p<0.05) and decreased nNOS immunoreactivity in the 6-OHDA group compared to controls was reversed with ghrelin administration (p<0.05). Increased GFAP immunohistochemistry in the myenteric plexus of the colonic muscle layer of 6-OHDA rats was evident, as well as decrease in TH expression, which were both reversed after ghrelin treatment. These results suggest that ghrelin is beneficial on decreased gastrointestinal motility observed in 6-OHDA-induced rats and the effects are parallel with neurochemical alterations in the myenteric plexus. Further studies are needed to reveal the detailed mechanism of ghrelin neuroprotection.

Introduction: We present a teenage patient in whom the preoperative assessment (including SEEG) located the epileptogenic zone at the dominant left temporal lobe including its posterobasal area. A cortical resection was carried out through an awake craniotomy to prevent postoperative reading impairment

Case Report: A 15-year-old right-handed female patient with pharmaco-refractory focal   motor and dyscognitive seizures that began at the age of 3 years, of probable origin in the dominant left temporal lobe including its posterior-basal area according to non-invasive studies and SEEG performed in April 2017. The results were assessed at the Multidisciplinary Meeting of the Epilepsy Unit, and awake craniotomy was recommended for language and reading mapping prior to resection.  No postoperative neurological deficits appeared, and the patient has remained seizure-free since surgery (6 months postoperative).

Discussion: This has been the first awake surgery performed by our Paediatric Unit. Adequate preparation and coordination of the team and intellectual development and collaboration of the patient have been fundamental to the success of this surgery. In our opinion, this technique is feasible in paediatric patients with a certain degree of maturity and collaboration when intraoperative language mapping is required.

Conclusion: Epilepsy surgery in awake paediatric patients is possible when they reach a certain degree of maturity and collaboration. This technique can be useful when epileptogenic zone is near to language areas.

Introduction: Rasmussen Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the contrary, Gliomatosis cerebri (GC) is a rare primary glial neoplastic process that is diffuse and infiltrative. Although the etiology of these two entities is different, the clinical and radiologic presentation may be similar.

Objectives: To emphasize the importance of the clinical, radiological and histopathological differential diagnosis between these entities in order to establish the appropriate diagnosis, prognosis and therapeutic approach.

Methods: We present two paediatric patients with a history of refractory continuous partial epilepsy with MRI findings of extensive cortical and subcortical thickening with T2 hyperintensity without meningeal involvement. Once infectious and inflammatory encephalitis were excluded, the proposed differential diagnosis was RE in an inflamatory stage or GC. Given the nonspecific findings, a diagnostic procedure was performed.

Results:  The histological study in case 1 showed a lymphocytic infiltrate in perivascular and intraparenchymal cortex, accompanied by neuronal loss, gliosis and microglial nodules, making the diagnosis of Rasmussen’s encephalitis. The histological study of case 2 showed a diffuse glial proliferation with foci of cellular anaplasia, performing pathological diagnosis of diffuse astrocytoma with gliomatosis cerebri growth pattern (WHO 2016).

Conclusions: A progressive focal epilepsy in a child associated with ipsilateral hemiparesis suggests the diagnosis of RE. However, other entities such as GC can mimic RE in an early stage, in which there is no atrophy yet. In ER, the treatment is surgical and the prognosis excellent, while in the GC the treatment is radio and chemotherapy and the prognosis is poor. Since treatment and prognosis differ substantially, brain biopsy is mandatory when these entities are suspected. 

Purpose: To determine the frequency of two GABA transporter single-nucleotide polymorphisms (SNP-alleles rs2697153 G>A in GAT-1 and rs2272400 in GAT-3 C>T) in drug-resistant temporal lobe epilepsy (TLE) patients.
Methods: DNA was isolated from 138 TLE patients’ neocortical tissue (31 with a history of febrile seizures (FS⁺), 107 without (FS^-)), and 94 non-epileptic controls’ blood/buccal swaps. DNA was amplified by polymerase chain reaction (PCR) and digested with allele-specific restriction enzymes (RFLP). P-values were obtained using the Chi-Square test or Fisher´s Exact test.
Results: GAT-1 SNP alleles were differently distributed in patients compared to controls (p< 0.05). Results showed that the GAT-1 AA genotype was significantly more frequent in patients than in controls (40% vs 23 %, p< 0.05). The GAT-3 CT genotype was significantly more frequent in the FS⁺ group (14%) than in the FS^- group (2%, p< 0.01).
Conclusions: The results suggest that GAT-1 and -3 SNPs are associated with TLE. In fact, GAT-3 c1572T may be a contributing factor to TLE following febrile seizures. However, the pathophysiological consequences of these SNPs remain to be elucidated.

Introduction:

The relationship between temporal lobe epilepsy (TLE) and cognitive impairment it is widely known. On the other hand, diffusion tensor imaging (DTI) studies have reported substantial white matter abnormalities in the epileptogenic network of subjects with TLE. So, our goal is to analyze the diffusion parameters of some white matter fiber tracts and to correlate them, with memory deficits in patients with TLE.

Material and methods:

Presurgical MRI studies with DTI sequence were performed in 19 patients with TLE. The fractional anisotropy (FA) and the mean diffusivity (MD) of the following fascicles were calculated: arcuate (AF), cingulum (CG), fornix (FORX), inferior frontooccipital (IFOF), inferior longitudinal (ILF), parahipocampal (PHC) and uncinate (UF). The WMS-III neuropsychological test was performed for the evaluation of short and long-term verbal and non verbal memory (LM I, LM II, VR I and VR II). In 11 patients, the MRI showed the existence of signs suggestive of MTS, whereas the remaining 8 studies were informed as normal (nl-TLE). A Spearman correlation was performed to test if there was an association between the DTI and the WMS-III. Finally, multiple linear regression analyses were performed to determine the contribution of each fiber tract to cognitive performances. Statistical significance was set to p < 0.05.

Results:

Lower LM I score, were associated with lower MD of the left-IFOF, while lower LM II score, were related to higher values of FA in bilateral CG, right-UF, right-PHC and lower MD in left-CG. Regarding non verbal memory, lower values in VR I scores were associated to lower values in MD in right-CG and right-IFOF. No correlation was found between VR II score and diffusion measurements. Differences between MTS (m-TLE) and nl-TLE subgroups were also investigated; in m-TLE group, lower LM II scores, were associated with alterations in bilateral CG, bilateral PHC, left FORX and right AF and UF, meanwhile, bilateral ILF, bilateral FORX, and left UF were correlated in nl-TLE subgroup. 

Regression analysis revealed that right-AF, right-IFOF and left-FORX explain the 85% of the variability in the LM I; right-PHC, right-UF and left-CG explain the 48% of the LM II; and finally, right-CG and right-IFOF, explain the 58% of the variability in the VR I.  

Conclusions:

Our results suggest that the structural damage of some white mater fiber tracts is related with the deterioration of both short and long-term memory in patients with TLE. This damage is correlated in higher degree to verbal memory than to non verbal memory. Furthermore, patients with MTS, have greater deterioration of the white matter fiber tracts as compared to patients with no lesions in the temporal lobe.

In Bratislava, Slovakia, the first center for the surgical treatment of focal epilepsy in the Eastern Block was established at Komenius University Children's Hospital after the Second World War in the 1950s. The department included 130 beds for pediatric surgery, 18 of which reserved for neurosurgical patients. The team consisted of Josef Žucha, the head of the department, Vincent Grunert his deputy, and neurologist Leondegar Cigánek, who was responsible for preoperative evaluation, intraoperative EEG conduction, and postoperative management. Cigánek maintained close contact with HH Jasper, the EEG specialist from the Montreal group by that time. The preoperative evaluation and the range of surgical procedures was at the level of the leading Western centers in Europe and America. The main contribution of this group was the introduction of the newly developed neuroleptic drug chlorpromazine for intraoperative sedation before its antipsychotic effects became known. In contrast to standard anesthetics, clorpromazine did not affect the EEG. Thus, for the first time, the epileptic focus could be resected even in children and in non-cooperative patients under corticography. Between 1955 and 1966, this team performed about 100 neurosurgeries for the management of refractory epilepsy. These included structural lesionectomy, focus resection on the cortex under EEG control, temporal lobe resection, including of temporomesial structures, and eventual subpial resections beyond the temporal lobe. In addition, they also successfully performed callosotomies and hemispherectomies. Although it has been forgotten in the meantime, it was one of the world's leading centers for the surgical treatment of epilepsy, despite adverse working conditions imposed by the communist system in the 50s and 60s.

SEEG approach is not only a surgical technique, but it is based on a well-defined epileptological and surgical methodology. SEEG philosophy calls for the formulation of hypothesis on the principal localization of the EZ and on its possible alternatives. SEEG exploration is then directed to the verification of these hypotheses and is not planned for “dense coverage” of the cortical surface. The same attitude characterizes the surgical technical aspects of SEEG implant. The previous knowledge of cortical convolutions and sulci, eloquent areas, deep seated structures and subcortical pathways, functional studies, PET areas of altered metabolism, and vessels is mandatory. These aspects allow reconstructing at best the anatomo functional characteristics of the brain. This is the Talairach’s approach based on the “reperage”.

The methodology developed at the Sainte Anne Hospital in Paris allowed to progress from the traditional approach, limited to the assessment of the superficial cortex, to a more 3-dimensional (3D) and network-based approach.
Modern 3D multimodal imaging and postprocessing can now be implemented for both advanced diagnostics and surgical planning. Moreover, robotic assistance can be used for the implantation of the electrodes, thus making the procedure faster and safer, without compromising accuracy. Modern technological tools facilitate the workflow, but the main concepts of this methodology are still valid. We use algorithms completely automated with software applications to expand the multimodal integration of data so that MRI, Cone-Beam-CT angiography, fMRI and DTI-FT data can all be coregistered together. It is now possible to obtain real 3D viewing by multi-planar reconstructions (MPR), volume and surface rendering. The tool holder for the surgical implantation is now fixed onto the passive robotic arm of the stereotactic image-guided system, so that the number of possible trajectories is no more discrete (as using the classic double grid), but virtually infinite with any desired obliquity. This way, it is possible to achieve the perfect knowledge of the recording contact localizations and the lowest possible rate of complications, essentially  represented by hemorrhages in the SEEG approach.

The aim of this presentation is to describe our present workflow. We will underline the methodological continuity with basic Talairach and Bancaud principles, highlighting how modern tools can help in saving time and improve safety, accuracy and the amount of information. Moreover, we report our quantitative results regarding geometrical accuracy at the cortical entry point with this new methodology.

Objective: Subjectively, we encounter more blood vessels during the surgical planning of epilepsy patients compared to other indications for deep brain stimulation (DBS).  Here we quantified and compared the vasculature of the brain parenchyma during DBS electrode descent in epilepsy and Parkinson’s disease.

Methods: A retrospective anatomical observational study in 15 epilepsy and 15 Parkinson’s patients was performed. The amount, location and diameter of blood vessels for both targets in both patient groups were visually quantified using Medtronic’s Framelink Version 5. A comparison was made using SPSS version 23.0 with descriptive statistics, independent samples T-tests and Mann Whitney U tests. P-value < 0,05 was considered statistical significant.

Results: There is a significant greater amount of total vessels in the epilepsy group (10.0, SD ± 4.12 versus 5.5, SD ± 1.47, P = 0.009) and also for both targets separate (ANT: 6.4, SD ± 2.87 versus 3.4, SD ± 1.40,P = 0.009, and STN: 3.6, SD ± 1.55 versus 2.1, SD ± 0.52, P = 0.003). Deep vasculature was significant more in epilepsy (ANT: 3.1, SD ± 0.99 versus 1.3, SD ± 0.80, P = 0.002 and STN: 2.5, SD ± 1.46 versus 1.2, SD ± 0.68,  P = 0.002) with only more big vessels in epilepsy for STN targets (2.7, SD ± 1.67 versus 1.6, SD ± 0.83, P = 0.005).

Conclusion:  The brain of epilepsy patients seems to be more vascularized, compared to Parkinson’s patients, which can make the surgical planning for DBS more challenging.

We report the case of a 65-year old woman suffering from pharmacotherapy-resistant epilepsy with bilateral tonic-clonic seizures caused by progressive severe leukoencephalopathy who was treated with deep brain stimulation (DBS) for status epilepticus.

The patient suffered from two episodes of non-convulsive status epilepticus ten and six month prior to admission. After a third episode with therapy refractory status epilepticus the patient was admitted to our institution under treatment with levetiracetam 3g/d, lacosamide 400mg/d valproate 2000mg/d and perampanel 6mg/d.  The patient was initially awake and responsive but in a confusional mental state with severe neuropsychological deficits (loss of anterograde episodic memory, apraxia, severe visuoconstructive deficits). EEG examination on admission showed bilateral diffuse epileptiform potentials with temporo-parietal focus in a frequency of 2/s, consistent with non-convulsive status epilepticus. Anticonvulsive treatment was extended with midazolam (10mg/h), phenytoin (750mg bolus injection and 300mg/d continuously), phenobarbital (600mg bolus injection and 300mg/d continuously) and brivaracetam 200mg/d. Due to ongoing electrographic status epilepticus, we initiated deep burst suppression anesthesia with thiopental (1-2 burst /min) for 72h. EEG after thiopental coma showed persistent non-convulsive status epilepticus.

Based on few, but encouraging reports, we evaluated DBS as an individual experimental treatment approach. Previous cases showed beneficial effects in the centro-median thalamus, the anterior thalamus or the hippocampus. The anterior thalamus was chosen in our case due to the temporo-parietal location of the epileptic focus and the anatomical connectivity from the anterior thalamus to the temporal cortex (Papez’ circuit). Electrode implantation was performed using MR-based direct targeting and stereotactic intraoperative CT.

Stimulation was initiated intraoperatively (3V, 145Hz contacts 2 and 10). One day after DBS, the patient suffered from recurrent bilateral tonic-clonic seizures and electrographic ongoing status epilepticus. After adaptation of the stimulation parameters to more caudal electrodes and lower amplitude (1V, 145Hz, contacts 3 and 11) the status epilepticus was finally resolved. The patient showed immediate marked improvement in cognition within the next days and normalization of the neuropsychological performance to baseline level within the next 3 months.

This case underlines the feasibility and efficacy of anterior thalamic DBS for the treatment of super-refractory status epilepticus.

Objective:

Defining the epileptogenic zone (EZ) is a key part of preoperative evaluation in epilepsy surgery. This is especially challenging for focal cortical dysplasia (FCD), which are characterized by subtle malformations of the cortical layers in MRI. Nevertheless, FCD show high intrinsic epileptogenicity (Blümcke et. Al, 2011) that can be recorded as fast-ripple oscillations (FRO) in intracranial EEG. The occurrence of FRO is linked to the epileptogenic zone of the lesions (Chassoux et. Al. 2000).

The purpose of this study is the detection of FRO and burst activity by stereotactic guided microelectrode recordings (MER) to improve the estimation of the EZ.    

Methods: 

In 6 patients with focal epilepsy and MRI based diagnosis of FCD type IIb the presurgical workup included implantation of stereotactic EEG electrodes or stereotactic guided lesioning of the FCD. 

In each patient, we used one preplanned perilesional trajectory to perform MER intraoperatively before implantation of the diagnostic electrodes. Detection of FRO and burst activity was performed with wavelet-based time-frequency analysis and results were correlated to the preoperative MRI defined EZ. Stereotactic planning and manual segmentation of the lesion was performed with Brainlab-Software. The MER (Inomed) were analysed in MATLAB (Mathworks) with Ripplelab-Toolbox. 

Results:

We detected high-amplitude spike burst activity with frequencies from 250 to 500 Hz in the majority of patients with suspected FCD IIb. Additionally, in a subgroup of patients non-spiking FRO were recorded. The form and latency of the FRO reassembled detected oscillations through intracranial EEG recordings in previous studies (Brazdil et al, 2010). Comparison of the data to the MRI showed high correlation to the suspected EZ of the FCD.

Conclusion:

This study demonstrates the feasibility of FRO and burst activity detection in FCD with MER-technique. The localization of detected FRO resembles the occurrence of known typical epileptogenic potentials during intracranial EEG recordings. These findings might introduce a new technique to map cortical dysplasia. The use of  MER may improve accuracy in tailoring the FCD before surgery in future clinical practice.

Blümcke, I., Thom, M., Aronica, E., Armstrong, D. D., Vinters, H. V., Palmini, A., et al. (2011). The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia, 52(1), 158–174.  

Chassoux, F., Devaux, B., Landré, E., Turak, B., Nataf, F., Varlet, P., et al. (2000). Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating the dysplastic cortex. Brain : a Journal of Neurology, 123 ( Pt 8), 1733–1751.

Brázdil, M., Halámek, J., Jurák, P., Daniel, P., Kuba, R., Chrastina, J., et al. (2010). Interictal high-frequency oscillations indicate seizure onset zone in patients with focal cortical dysplasia. Epilepsy Research, 90(1-2), 28–32. 

Objective. The objective of the present study is to report the first two patients in Latin America with bilateral thalamic electrode implantation for treatment of refractory epilepsy.

Backgrounds. 30% of patients with epilepsy have a poor clinical control with antiepileptic drugs (AEDs) alone. Surgery can be of aid in such cases. Epileptic syndromes without structural lesions, bilateral or multiple foci are not candidates for ablative surgery. So non-resective techniques are next therapeutic step. Neuromodulation of the anterior nucleus of thalamus its a novel form of palliative treatment for such patients.

Materials and Methods. We report two cases of deep brain stimulation(DBS) on anterior nucleus of thamlamus and their clinical outcome at two years. The first case a 46 year-old patient with history of carbon monoxide intoxication that evolved with refractory generalized seizure. MRI showed bilateral temporomesial sclerosis. Surface VEEG and SEEG showed bitemporal discharges without lateralization. The second patient was a 22 year-old man, with a history of 8 years of refractory falls and tonic-clonic seizures. MRI, surface VEEG and PET, wouldn't determine laterality of the epileptogenic focus. Finally SEEG showed bifronto-temporal foci. Based on the results obtained in the global evaluation of both patiends, DBS was indicated.

Results: Both DBS system implanted were tolerated very well, without intraprocedural nor post-surgical complications. Both patients presented a meaningful reduction in the number of crisis presented monthly, although they remained under anti epileptic medication. They were classified as class III, Engel classification, after 2 years.

Conclusion. Deep brain stimulation of the anterior nucleus of thalamus is a safe non ablative surgical technique for refractory epilepsy. The international literature demonstrated its effectiveness in the control of the frequency and duration of the crisis, constituting one more tool in the palliative treatment of this type of chronic disorders. Although patients weren’t free of AEDs there quality of life improved, justifying this invasive procedure.

Functional hemispherectomy (FH) is a therapeutic tool of potential relevance for patients with unilateral hemispheric lesions suffering from refractory epilepsy. However, data on this procedure is scarce and much remains to be understood in order to optimize patient selection and maximize therapeutic gains. To address this issue, we hereby report our single-center experience.

We performed a descriptive and inferential retrospective analysis of the refractory epilepsy cases submitted to FH in our center. Epidemiological and clinical characteristics, surgical findings and complications were summarized and results were analyzed. We compared post-operative seizure outcomes at 6 months, 1 year and at last follow-up according to Engel surgical outcome scale and reduction of antiepileptic drugs (AED).

A total of seven patients submitted to FH were identified. Six patients were male and mean age at seizure onset was 5.2 years. Mean age at surgery was 24.9 years, resulting in an average interval between symptoms onset and FH of 19.7 years. Epilepsy was largely of focal structural etiology, including cortical dysplasia and post-traumatic lesions, mostly pertaining to the left hemisphere (5 cases). Seizures were of focal onset with impaired awareness, motor onset without progression to bilateral tonic-clonic events in 3 cases; focal onset with impaired awareness, motor onset and progression to bilateral tonic-clonic events in 2 cases; generalized onset tonic-clonic in one case; and unclassified in another case. Pre-operative seizure frequency was on average 54.3 per month. The average number of pre-operative AED used was 3.1. One post-operative surgical wound site infection was registered. Mean follow-up duration was 63 months. At 6 months, Engel IA class was achieved in 4 patients (57.1%); the remaining cases classified as Engel ID, IVA and IVB. Results were stable at one-year post-surgery but aggravated at last follow-up, with 2 patients at Engel IA, one at Engel ID, one at Engel IVA and 3 at Engel IVB. AEDs were reduced in 5 patients at 6 months, 4 patients at 1 year and in 3 patients at end follow-up.  On multivariate analysis, Engel at 1 year was predicted by the Engel at 6 months (p=0.03) An Engel class I at 6 months was associated with less seizure recurrence at end follow-up (p=0,04). Pediatric patients had less post-op complications (p= 0.04) and had significantly less seizure prevalence than adult patients at 6 months after surgery (p=0.02), but not at 1 year nor at end follow-up. AEDs dosage reduction was associated with the Engel classification at 6 months (p=0.03). Considered the patients that initially achieved seizure-elimination, a survival curve analysis seizure recurrence for half the cohort had occurred at 30 months post-surgery.

FH appears to be an important option for selected cases of refractory epilepsy. Ours is a short series that nonetheless allows some reflection on the subject. More studies are needed in order to understand which variables help predict better outcomes and optimize surgical benefit.

Introduction: Vagus nerve stimulation (VNS) is an established treatment for intractable epilepsy. However, there is limited data on the very long-term outcome of children who have undergone VNS. Methods: We retrospectively reviewed consecutive children who underwent VNS for intractable epilepsy at King's College Hospital from April 2004 to December 2007. Results: 68 children underwent VNS for intractable epilepsy during this period. Records were available for 65. The median age at surgery was 13 (range 5-18). The median follow-up period was 10 years (range 0-13; 33 had >=10 year follow-up). The median age on onset of epilepsy was 1 year (range 0-13). The median time from epilepsy onset to VNS surgery was 10 years (range 3-16). The mean number of AEDs before VNS compared to last follow-up was unchanged at 3. The number of monthly seizures at last follow-up improved in 33 patients (51%), including 6 (9%) who were seizure free and 20 (31%) who had >50% reduction in seizures. Seizures worsened in 2 (3%) and did not change in 21 (32%). The change in seizure frequency could not be determined in 9 patients (14%). Adverse events occurred in 11 patients (17%) and included cough (7 patients), dysphonia (2), infection (2) and lead failure (2). 32 patients (49%) had battery changes, including 3 who required 2 battery changes over the follow-up period. The median duration to first battery change was 8 years. The VNS was not being used at last follow-up in 19 patients (29%). The reasons for this were lack of efficacy (8), improvement in seizures (3), awaiting battery change (3), lead failure (2), worsening behaviour (1), cosmetic reasons (1), had callosotomy (1). 37 patients (57%) felt that the VNS had been of overall benefit. 19 (29%) felt it had not been of overall benefit and benefit could not be determined in 9 (14%) patients. Conclusions: These results suggest that treatment with VNS remains a useful adjunct for intractable epilepsy and may contribute to seizure reduction and overall benefit in a significant number of children for whom there is no other alternative treatment. There remains a substantial number in whom VNS is not effective, which underscores the importance of preoperative counselling.

Introduction

Intracranial recording (including subdural strips, grids and SEEG with depth electrodes) forms an important part of pre-surgical evaluation of epilepsy. The utility of this investigation and its impact on outcomes are not well understood.

Methods

We performed a retrospective review of consecutive patients who underwent intracranial recording for pre-surgical evaluation of epilepsy at King’s College Hospital from 2015 to 2017.

Results

54 patients underwent intracranial recording during this period. The median age was 26 (range 7-68; 12 (22%) were <=18 years old). 40 patients had depth electrodes only, 2 patients had strip electrodes only and 12 patients had a combination of grid, strip and/or depth electrodes. 31 patients (57%) were offered surgical resection following intracranial recording, of which 25 had surgery. 14 patients (26%) were offered neuro-stimulation (including VNS, DBS and cortical stimulation), 2 patients (4%) had thermo-coagulation and 7 patients (13%) had no surgery. Of those that had surgical resection, the median follow-up was 7 months (range 1-35). 10 patients (41%) had good outcomes (Engel 1 or 2), 14 (56%) had less good outcomes (Engel 3 or 4) and 1 had unknown outcome. The indications for intracranial recording for those who underwent surgical resection were localise to lobe including lateralisation (5 patients; of which 3 good, 1 less good, 1 unknown outcome) mapping where MRI was negative (10; of which 4 good, 5 less good outcome), mapping around a lesion (2; of which 1 good and 1 less good outcome), mapping where a previous resection was done (6; of which 1 good and 5 less good outcome), multiple lesions (2; of which 1 good and 1 less good outcome).

Conclusions

Intracranial recording is helpful in guiding the type of most appropriate surgical intervention. A significant proportion of patients who have surgical resection have less good outcomes. In our series, the indication for intracranial recording did not predict surgical outcome except for mapping where a previous resection was done, for which most patients had poor outcomes. The various factors that may lead to poor outcome in individual patients require further detailed study and are difficult to evaluate in population studies.

Introduction: Neuronavigation has become an important tool in the surgical management of brain lesions. It provides intraoperative orientation, assists the surgeon in planning a precise and safe approach to the targeted lesion by defining the surrounding neurovascular structures and helps to ovoid eloquent areas of the brain during surgery. The aim of this study is to evaluate the application, usefulness and the effectiveness of neuronavigation in brain lesions surgery.

Methods: a prospective study of 173 patients undergoing Neuronavigation Assisted (NNA) neurosurgical intervention in the department of neurosurgery to the University hospital of Blida ( Algeria), between 2007 and 2012, is presented.

Results: there were 67 females and 106 males. The mean age was 34 years ( 06-74 years). The mean time of planning was 09,7 minutes. The procedures included NNA-microsurgery in 87 cases (50, 3%), NNA-Endoscopy in 50 cases ( 28,9%) and NNA-biopsy (frameless image guided)  in 36 cases (20,8%). The mean operative time was 147 minutes (54-230 minutes).The applications of NNA were: glioma in 81 cases(46,8%), metastasis in 26 cases (15%), meningioma in 09 (05,2%) and other lesions in 57 (33%). An accurate histological diagnosis was possible in 96,5%. The neurological status was improved in 68,2%, unchanged in 19,7% and worsened in 12,1%. There was no mortality and the morbidity was relates to the depth of lesion, the localization in eloquent area and brain shift.

Conclusion: the neuronavigation provides important information that can improve the safety and efficacy of brain tumor surgery.

Background and objectives.

  Stereotactic biopsy is a versatile and minimally invasive technique that allows the histological diagnosis and therapeutic handling of intracranial lesions, safely and effectively. Since its emergence, this technique has been able to combine and adapt its essential principles to the technological advances at every moment.

  Our objective is to determine the usefulness of the ¹⁸F-fluorodeoxyglucose PET-CT, combined with MRI, as an imaging strategy to optimise the place of stereotactic biopsy sampling and, therefore, the technique´s diagnostic yield, in patients with multiple intracranial lesions or controversial differential diagnosis on conventional neuroimaging techniques.

Methods.

   In a single center series spanning 6 years, we have reviewed 67 consecutive stereotactic biopsies. ¹⁸F-FDG PET-CT guidance was used in 14 procedures.

The Leksell stereotactic system and a Sedan/Nashold biopsy needle were employed.

The selection of the most suitable targets was established considering the PET-CT and 3T-MRI findings. These tests were later fused with a stereotactic CT scan. The coordinates were obtained by means of the Cranial 3.0 planning programme.

We analyzed a total of 50 anatomical, radiological and technical variables for each case by means of SPPS.24.

Results.

  Our series was composed of 10 (71.4%) men and 4 (28.6%) women, with an average age of 52.7 years; range 15 -74 years. The most relevant clinical symptomatology referred to by the patients on admission were motor deficits (28.6%; n = 4). On neurological examination, the most common finding was the absence of findings (50%; n = 7), followed by motor deficits (21.4%; n = 3).

The lesions operated on mainly presented multiple locations (71.4%; n = 10). The most frequently biopsied anatomical regions were the basal ganglia (37.5%; n = 5) and thalamus (21.4%; n = 3).

After the definitive histological study of the sample, the most common diagnoses were lymphoma (42.9%; n = 6), followed by high grade glioma (35.7%; n = 5). We had an extremely rare case of adult supratentorial extraventricular WHO grade II ependymoma.

We obtained a diagnostic yield of 100%, with a transitory morbidity of 7.1% (n = 1) and a mortality of 0%.

Conclusions.

  Stereotactic biopsy constitutes a perfectly consolidated procedure in Neurosurgical Departments. The selection of the most appropriate target and  trajectory are fundamental factors for the success of this surgical procedure.

Combined ¹⁸F-FDG PET-CT and magnetic resonance imaging improve and provide the identification of the most pathological areas and / or lesions in the patient's brain, optimize the selection of the target and ensure the quality of the sample. All that, improve the diagnostic yield of this technique. However, ¹⁸F-FDG PET-CT includes high radiation doses and relatively high cost. Considering these limitations, its indication must be individualized and endorsed for each patient by the Neuro-oncology Committees.

Objective:Repetitive transcranial magnetic stimulation (rTMS) allows for non-invasive mapping of positive and negative cortical language sites. It has been used to preoperatively assess language function in patients suffering from language eloquent brain lesions. The value of preoperative rTMS language mapping still requires further exploration.

Methods:Consecutive patients that underwent preoperative rTMS language mapping between January 2014 and October 2017 were evaluated. Surgical, imaging and functional data was prospectively recorded. All patients suffering from language eloquent brain lesions that underwent surgery under general anesthesia supported by the preoperatively acquired rTMS language map were eligible for the herein presented analysis. The preoperative rTMS language map was used for intraoperative neuronavigation.   

Results:Collectively, 60 patients underwent rTMS-supported surgery under general anesthesia. Patients suffered from cerebral metastasis (17), glioblastoma (23), low-grade glioma (8), cavernous malformation (5), AVM (3), high-grade glioma WHO III (2), DNET (1) and astroblastoma (1). A left-sided lesion was present in 57/60 of the cases (95%). In 3/60 of the cases (5%), patients suffered from right-sided lesions, were left-handed and presented speech disturbances preoperatively. In total, 43 of all patients (71.7%) had preoperative language deficits. After surgery, language function deteriorated in 4 out of 43 patients (9.3%). A new language deficit occurred in 2 out of 17 patients (11.8%). Postoperatively, in 28 out of 43 patients (65.1%) language performance improved within the first week. After two months, 80% of the patients experienced additional language improvement. Finally, 86.3% of the cohort had regular language function at two months follow-up.

Conclusion: Preoperative rTMS language mapping likely contributes to a favorable language outcome in patients undergoing resection of language eloquent lesions under general anesthesia. Further research is required to substantiate these findings.

Objective:Preoperative navigated transcranial magnetic stimulation (nTMS) is an established non-invasive method to map the motor cortex. To date, there are few larger cohorts demonstrating the beneficial value of nTMS supported resection of motor eloquent lesions. Here, we seek to extend the current evidence of preoperative nTMS application for motor eloquent brain lesions. 

Methods:Consecutive patients that underwent preoperative nTMS motor mapping between June 2013 and September 2017 were evaluated. Surgical, imaging and functional data was prospectively recorded. All patients suffering from motor eloquent brain lesions that underwent surgery supported by the preoperatively acquired nTMS motor map were eligible for the herein presented analysis. The preoperative nTMS motor map was used for intraoperative neuronavigation.   

Results:Collectively, 100 patients underwent nTMS-supported surgery. Patients suffered from cerebral metastasis (39), glioblastoma (27), meningioma (13), low-grade glioma (6), high-grade glioma WHO III   (5), cavernous malformation (4), lymphoma (2), AVM (2), DNET (1) and astroblastoma (1). Preoperatively, 52/100 patients (52%) presented a motor deficit. Motor function improved in 14/52 of the patients (26.9%) and completely recovered in 13/52 of the patients (25.0%) within the first postoperative week. Motor function remained unaltered in 20/52 of the patients (38.5%) and deteriorated in 5/52 of the patients (9.6%). Follow-up motor examination was available in 23/39 of the postoperative paretic patients (59.0%)). After two months, 18/23 of those patients (78.3%) experienced additional motor function recovery. A new motor deficit occurred in 8/42 of patients (19.0%) without presurgical motor deficit. At two months follow-up, in 7/8 of those patients (87.5%) motor function improved. A persistent motor deficit was present in 4/42 of the patients (9.5%).

Conclusion: Preoperatively acquired nTMS motor maps support surgical treatment of motor eloquent brain lesions. A favorable neurological outcome is achievable in both patients with and without a priorly existing motor deficit.

Introduction: Project RONNA – robotic neuronavigation, innovative and commercially competitive robotic system for applications in neurosurgery, was initiated by a group of researchers within the Department of Robotics and Production System Automation at the Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb.

Methods and results: The RONNA system was tested through rigorous preclinical trials which resulted in numerous improvements and in the development of the new RONNA G3 system. RONNA G3 is used for stereotactic neuronavigation procedures and in its basic version has three main components: a) a robotic arm on a universal mobile platform, b) a planning and navigation system and c) a global optical tracking system (OTS). One specific characteristic of the RONNA G3 system in respect to most current state of the art robotic neurosurgical systems is an additional mobile platform equipped with a compliant and sensitive robotic arm. The extended version of the RONNA G3 which uses the compliant robotic arm is intended for automated robotic bone drilling applications and manipulation of surgical instruments. The second arm was not used in this case study. The global optical tracking system uses an infrared stereo camera and two reference frames, one attached to the patient in form of a "x" shaped localizer and the other to the robotic arm. The OTS is only used for coarse positioning of the robot with respect to the patient in the global localization phase of the procedure. We have further developed a specific infrared stereovision system which uses macro lenses in order to obviate any errors that may arise from the low resolution and wide field of view of the global OTS.  

Conclusion: Benefits of using the RONNA system in neurosurgery are: better and faster performance of surgical procedures, less invasive procedures, faster recovery of the patient (shorter hospital stay, reduced costs), better utilization of operational resources of the hospital, mastering new skills within a clinical team and introduction of new technologies in medical practice.

INTRO

A crucial stage of Deep Brain Stimulation (DBS) treatment is post-operative selection of stimulation settings. Once the electrode location is fixed, altering stimulation parameters, and consequently the stimulation field, is the only means of fine-tuning treatment outcome. Post-operative stimulation selection is time-consuming for the clinician and demanding on the patient. It is traditionally performed using mono-polar review, systematically testing all available electrode contacts. This process is currently not informed by neuroanatomical information about the electrode contact locations. There is a clear question as to whether this could helpfully inform stimulation settings. As segmented electrodes with more contact options, and therefore even greater numbers of parameter configurations emerge, this may become a critical issue. Furthermore, in a subset of patients, post-stimulation management is problematic, and may benefit from insights about the patient's specific neuroanatomical patterns.

In this study, we perform a retrospective analysis of DBS electrode locations and stimulation amplitudes relative to the STN in 12 Parkinson’s Disease patients, with the STN defined using four methods: (1) an atlas-based (fully automated) segmentation of the STN and (2) an atlas-based motor STN, (3) a manual segmentation of the STN and (4) a motor STN defined for each patient using tractography. We examine the correspondence between the contacts ultimately chosen by clinicians after extensive testing and those suggested by neuroanatomical information. The overarching aim is to explore whether neuroanatomical information can be used to guide contact testing in post-operative stimulation management.

We use a new open-access toolbox, PaCER (Precise and Convenient Electrode Reconstruction) that combines state-of-the-art image processing of standard MRI and CT scans (from pre- and post-operative DBS procedures). PaCER provides easy-to-access 3D visualisations of implanted electrodes relative to surrounding neuroanatomy. This tool can automatically locate and reconstruct the implanted electrodes accurately.

RESULTS

There was a significant positive correlation between the stimulation amplitude (M=2.98V, SD=.54) at an active contact and the target center-of-gravity, as calculated using the atlas-STN (M=2.29mm, SD= 1.17; Pearson's r = 0.43, p = 0.04) and the manual-STN methods (M=2.44mm, SD=1.22; Pearson's r = 0.52, p = 0.01), but not for the atlas-motor or the tractography-motor-STN. We therefore suggest that the closer the active contact is to the center of the (atlas or manual) STN, the less voltage is applied to achieve therapeutic benefit. We ranked the electrode contacts based on their proximity to the STN target structures. We found that the majority of electrode contacts chosen to deliver stimulation were closest or second closest to the target center-of-gravities, defined using any of the four methods. For the atlas-STN and atlas-motor-STN, we found that 64% and 55% of the active contacts were closest to the target center-of-gravity respectively. For the manual and tractography-motor STN, 41% and 36% of the active contacts were closest. The most distant contact from the calculated center-of-gravities was never chosen to deliver stimulation.

DISCUSSION

Our findings indicate that information on each electrode contact's location might be useful in guiding clinicians during post-operative stimulation testing. We argue that atlas-based methods can provide adequate information for this purpose. We demonstrate that a new, open-source tool (PaCER) can be used to easily integrate multimodal neuroimaging data into clinical practice, thereby opening avenues for future research and clinical optimisation. 

The key benefits of ultra-high field magnetic resonance imaging (MRI) are the increased spatial resolution, contrast and signal that can be accomplished within a suitable timeframe ^[1]. Such principles are essential when imaging small basal structures that are common targets for deep brain stimulation (DBS), such as the subthalamic nucleus (STN). Plantinga and colleagues (2016) ^[2] found that using Diffusion Weighted Imaging (DWI) at 7T allowed for a tripartite parcellation of the STN for Parkinson’s disease (PD) patients. The structurally subdivided the STN in to functionally distinct motor, cognitive and limbic areas based on their connectivity with the cortex. Such a method is of unquestionable benefit to the application of DBS surgeries. Subdividing the STN in to its constituent parts can help ensure the lead is placed, and stimulation is spread only within the motor area of the STN, which can maximize the efficacy of the treatment while simultaneously eliminating the occurrence of psychiatric side effects associated with STN DBS. The present study goes further by identifying and subdividing the STN in to its constituent parts with DWI and resting state functional (rs-f) MRI at 7T for PD patients scheduled for DBS of the STN. The MRI protocol has been optimized for clinical use and is approved by the local Medical Ethics Committee at the MUMC. Data collection and analysis for piloting is ongoing and the initial results have been promising. The proposed study aims to provide a case example of a single patient. The patient to be included in the complete pre-operative planning protocol for 7T MRI is scheduled for May, and their surgery performed in July. The results of this patient will be used for our presentation at the ESSFN in September 2018. Comparisons between coordinates identified on the 7T with pre-operative 3T MRI, as well as their intra-operative microelectrode recordings (MER) will be conducted to assess the superiority of 7T MRI over 3T and to ensure 7T offers anatomically correct information.

The methodological pipeline is explained in the following section. The scans will be collected on a Magnetom 7T Siemens system (Erlangen, Germany). A sub-millimeter 3D T2* slab gradient echo sequence incorporating phase image reconstruction for multi-echo data (ASPIRE) will be acquired, from which Quantitative Susceptibility Maps can be computed for optimum STN identification. A whole-brain multi-contrast sequence also within the sub-millimeter range is included via an adapted multi echo magnetization prepared 2 rapid gradient echo (ME-MP2RAGE) sequence, which allows for more accurate across-contrast and field strength fusion than a T1 contrast image can achieve alone. Both a DWI and a resting-state functional (rs-f) MRI sequence will be acquired. Connectivity analyses will be achieved using a combination of Free Surfer, FSL and MRrtrix3. The STN will be manually segmented on the T2* and QSM images, which will be registered to the DWI and rs-fMRI images via the multi-contrast sequence. Cortical regions of interest (ROIs) will be subdivided and masked into distinct areas using validated cortical atlases and then registered to the patients DWI and rs-fMRI images. Tractography and functional coupling are calculated per connectivity profile, between the STN and each ROI and used to compute a quantitative connectivity matrix of STN structure and function, which is back projected and used for sub-parcellation.

We do not doubt that the increased quality available at 7T will better visualize the STN compared to 3T. With regards to dividing the STN in to its functional subcomponents, we have yet to see whether it is possible given the spatial resolution, how accurate it is according to the known anatomy, and how reproducible our method is. We will discuss the potential and limitations of utilizing such methods within the Medtronic stealth station system. An assessment of movement artifacts incurred during the scanning procedure will be provided. Future additions to the project include validation of 7T based targeting with MER and long term follow ups.

1. Forstmann, B. U., Isaacs, B. R., & Temel, Y. (2017). Ultra High Field MRI-Guided Deep Brain Stimulation. Trends in biotechnology, 35(10), 904-907

2. Plantinga, B. R., Temel, Y., Duchin, Y., Uludağ, K., Patriat, R., Roebroeck, A., ... & Harel, N. (2016). Individualized parcellation of the subthalamic nucleus in patients with Parkinson's disease with 7T MRI. Neuroimage

Introduction: Brain imaging, especially advances in MRI  acquisitions with diffusion-weighted imaging (DWI), has a crucial role in the presurgical assessment of patients with neurosurgical diseases. Semi-automated methods to register imaging data into a common space is enabling the creation of multimodal three-dimensional patient-specific datasets. These datasets can be resampled in 3D to align with local anatomic spaces for precise intracranial navigation and register to stereotactic spaces for frame-based or frameless interventions. This highly complex environment evokes a need for careful planning along with well-designed archiving support in software implementation.

Goals: Our motivation is to divide surgical planning into (1) preplanning phase with DWI to MRI image fusion and (2) stereotactic planning phase with CT-MRI fusion followed by registration  of stereotactic frame or tracking camera space to CT. The preplanned, archived study with registered DWI is inserted later into stereotactic planning to start with tractographic analysis. The preplanning phase contains the critical computations for correction of DWI gradient table based on DWI registration.

Methods: Integrated computations are: (1) CUDA-based calculations of DWI to MRI registration (https://sourceforge.net/projects/ezys/), (2) multi-threaded tractography as implemented in (http://jdtournier.github.io/mrtrix-0.2/) and (3) study archiving at different phase of planning which is based on Microsoft data serializing library functions (https://docs.microsoft.com/en-us/visualstudio/). DWI to MRI registration is done with  optional brain mask in two steps: registration  of fractional anisotropy map (FA) to MRI followed by registration of the whole DWI dataset to FA. Correction of gradient table can be performed in this preplanning step without optimization (according to registration transform of DWI reference dataset, FA) or with optimized rotation. During gradient table optimization the best global fiber connectivity is used as metric similarly to calculation of others (Jeurissen et al.: Registration based correction of DWI gradient orientations. Proc. Intl. Soc. Mag. Reson. Med. 19, 2011, p.1944). Archive file with MRI-DWI fusion parameters can be imported during CT-based stereotactic planning. The calculation verifies the common MRI data path involved in preplanning and stereotactic planning studies and reinterpolates DWI data if the reference voxelsize is different in stereotactic planning. Targeted subvolume can be selected for DWI fusion and realigned in orthographic views of CT-MRI fusion during stereotactic planning. Region of interests (ROI) as SEED, INCLUDE or EXCLUDE type subvolumes can be set on multimodal datasets and tractography is executed. The computations are added in modular form to a surgical planning application providing for simple interface according to reasonable workflow (www.surgifront.com).

Results: Tractographic analysis has been smoothly integrated into our surgical planning/navigation application. During preplanning DWI data are registered to MRI and correction of gradient table has been performed. Unregistered or  registered DWI volumes and mask files are converted and stored in a compressed study archive along with imaging parameters. Just before surgery the CT-MRI fusion is calculated and the CT volume with markers is registered with surgical space of stereotactic frame or space of reference sensor viewed by tracking camera. The MRI-DWI study archive is imported for tractography. The fiber models are visualized in pre-registered CT-MRI views for trajectory planning and different navigation views during navigated tracking/resampling interventions in frameless mode. The DWI-MRI fusion study can be prepared in a less stressful period before the surgery with detailed accuracy tests and leaving time for correction and archiving the best choice.

Conclusion: Early preplanning with DWI volumes and creating archive study file can improve the usability of tractographic analysis in surgical planning with CT diagnostics prepared just before stereotactic surgery.

Stereotactic surgery is a widely used neurosurgery technique which is mainly used to reach or operate different structures in the brain. In this surgical technique, desired locations in the brain are targeted in terms of three-dimensional coordinate systems. These desired coordinates are obtained via unique calculation methods defined for each stereotactic system, by its manufacturer. There are two main calculation methods during the use of stereotactic surgery devices which are; manual calculation methods and computer-based calculations. In this study, we addressed the question for the computer-based calculations whether there is an effect of slice thickness of the radiological images to the accuracy of stereotactic electrode implantation, and if yes, to which extent. Stereotactic CT and non-stereotactic MR images of a DBS lead implanted citrullus lanatus were obtained with different slice thicknesses. One specific part of the implanted DBS lead was defined as target and the coordinates from CT scans with different slice thicknesses were recorded. We found that there were no significant difference in between recorded stereotactic coordinates even in comparison to the scans with higher slice thickness values than the recommendations.

Background: Deep brain stimulation (DBS) can be an effective treatment in selected patients with refractory Parkinson’s tremor or essential tremor. However, regarding more complex and rare tremor syndromes the use of DBS is less well recognized. Besides from the multiple reported targets, a variable result on tremor reduction has been described. In the literature suggestions have been made for an individualized approach including tremor features. Here, we present a complex case of deep DBS for a unilateral right-sided rubral-like tremor, due to a hemorrhage in an intrinsic brainstem carvernoma with expansion to the red nucleus, in a 34-year-old patient using 3 Tesla tractography.

Methods: We performed a left-sided VIM/PSA DBS using 3 Tesla imaging (Ingenia, Philips) for the planning, including DWI and DTI HARDI sequences. With Iplannet (Brainlab) we performed dentatorubrothalamic tractography (DRTT). DRTT tracking showed a more superficial course of the tractus (Figure 1 and 2). Our very successful but unusual superficial intra-operative testing made us implant the electrode more above target than usual (central trajectory, Medtronic 3387, electrode 0 on target minus 3).

Results: Direct postoperative results between on and off state, taking the lesion effect into account, showed a very good tremor reduction, especially in the arm (video). Since the operation has only been recently we are still gathering the long-term results.

Conclusion: A patient tailored DBS approach using tractography for less common indications with no general accepted target, like in this complex case, could result in good treatment effect.

Neuronavigation systems can be used to determine the position of brain tumors during surgical procedures relative to preoperative imaging, typically magnetic resonance images. These systems employ an electromagnetic or optical device to track the surgical tools and model the patient’s head and its content as a rigid body. During surgery, cerebrospinal fluid drainage, use of diuretics, and tumor resection cause the brain to deform and therefore invalidate the estimated rigid transformation. Brain deformation during surgery, known as brain shift, along with registration and tracking errors reduces the accuracy of image-guided neurosurgery based on neuronavigation systems. The development of intraoperative imaging techniques is desirable because they guide the surgeon toward obtaining a more complete resection while helping to prevent damage to normal brain. Intraoperative ultrasound appears to be a promising technology to compensate for brain shift as it is relatively inexpensive and does not require changes to the operating room. Awareness of artifacts in ultrasound images that may occur during tumor resection is a necessity for successful and safe surgery when using iUS for resection control. We investigate the use of intraoperative 3D-ultrasound to compensate for brain shift during neurosurgical procedures. We present a novel feature-based method for achieving robust, fully automatic deformable registration of intraoperative neurosurgical 3D ultrasound images.

Nine patients (3 females, 6 males; mean age, 44 years) scheduled for resection of suspected/known primary or metastatic brain tumor in a multi-modality image-guided surgical suite were included in this study. After histologic examination, it was determined that 4 patients had low-grade gliomas, 4 had high-grade gliomas and 1 had metastatic brain tumor. Mean tumor volume was 19.5 cm³, ranging from 0.1 cm³ to 57.0 cm³. Fig.1 shows the representative axial slices from the preoperative MR of the nine subjects. During surgery, freehand ultrasound sweeps were acquired, before and after opening of the dura membrane, during resection and prior to intraoperative MR. Sweeps contained between 100 and 300 frames of 2D ultrasound data and were reconstructed at a voxel size of 0.5x0.5x0.5mm³. A typical example of pre- and partial post-resection ultrasound and the initial misalignment is shown in Fig.2. 3D ultrasound images consist of image patterns that are challenging to localize or register across datasets. We use a feature-based registration to identify a globally optimal spatial mapping between 3D iUS images, based on a sparse set of feature correspondences. Figure 3 shows a collection of 3D features automatically extracted from iUS. A total of 1620 automatically extracted feature correspondences between ultrasound images were manually validated by eleven radiologist and non-radiologist physicians. For each pair of ultrasound images, 10 unique landmarks were manually identified to establish a ground truth registration solution. Eligible landmarks include deep grooves and corners of sulci, convex points of gyri and vanishing points of sulci. The mean target registration error (mTRE) between those landmarks before and after registration was determied. The quality of the alignment of the pre- and post-resection 3D ultrasound images was also visually assessed by two neurosurgeons. Cross-sections of the post-resection ultrasound volume were overlaid on (1) the original pre-resection ultrasound, (2) the pre-resection ultrasound after the proposed feature-based transform. The experts accessed the registration accuracy at (1) anatomical landmarks such as the sulcal patterns, vessels, choroid plexus, falx, and configuration of ventricles and (2) the tumor boundary.

Using manually labelled corresponding landmarks in the pre- and post-resection ultrasound images, we show that our feature-based registration reduces the mTRE from an initial value of 3.3mm to 1.5mm. From a total of 20 pairs of ultrasound images, the alignment of 4 cases were classified as ‘good’ and 16 cases were classified as ‘great’ after 3D feature-based registration.

3D features were shown to provide efficient non-rigid registration of 3D-iUS images while requiring low computational time for features extraction and matching. We presented a novel registration method for 3D iUS images achieved from a sparse set of automatically extracted feature correspondences to correct for brain shift in image-guided neurosurgery.

To date, the development of medical technology clearly shows a trend towards the introduction of robotics and automation. In particular, this trend also included equipment used in stereotactic operations. The history of the emergence and gradual introduction of stereotactic robots and available publications suggest that this is not momentary desire to be in vogue and not a publicity stunt of producers, but objectively occurring process.

At first glance, it may seem that currently available stereotactic robots are not recouping the very high sale price. In addition, it is necessary to take into account the increasing dependence of the success of the operation on the correct work of equipment. But on other hand, if to look at the problem more closely, we can conclude that stereotactic robots have a number of advantages that are essential for operations. Among them there are: decrease in the labor consumption of the operating procedure, reducing the possibility of accidental errors associated with the human factor, high accuracy of the guidance at intracerebral target points, reduction in the time spent on the operation. So taking into account the imminent reduction in the cost of robotic equipment in future, it is possible to forecast clear prospects for their implementation in a clinic.

According to their ideology, stereotactic robots are the development of frameless stereotaxy branch. When designing such robots the following tasks should be solved: the method of spatial reference between stereotactic imaging and the coordinate system of the robotic manipulator; the mechanical rigidity of the manipulator structure; sufficient number of degrees of freedom of movements of the manipulator; ensuring the patient safety in cases of the equipment failure.

In 1993, concern "CSRI "Elektropribor" in cooperation with the stereotactic department of the Institute of Human Brain of the Russian Academy of Sciences (St. Petersburg) had developed and started serial production of the stereotactic manipulator "Oreol". A total of 17 manipulators were manufactured, which were used in various clinics in Russia and CIS countries. The feature of detachable marking the patient's head when working with this stereotaxis allowed to perform the stereotactic imaging of the patient brain in the frameless conditions. The manipulator had 6 degrees of freedom of movement of a stereotactic tool, of which 3 were used to guide the instrument at the target points and 3 - to adjust the trajectories of stereotactic approaches and introduction of the instrument into the brain.

From 2017 CSRI "Elektropribor and the Institute of Human Brain are working together to develop a robotic stereotactic manipulator for neurosurgical operations on the basis of the manipulator "Oreol". For spatial registration and stereotactic guidance, it is decided to use an external neuronavigation system. The manipulator is a compact structure attached to the head holder of the operating table. This solution allows reducing the cost of the system and simplifying its integration into a modern neurosurgical operating room.  The kinematic units of the manipulator contain microdrives with position sensors and a friction brake mechanisms. The degrees of freedom of movements of the manipulator ensure guidance at the target points and trajectory selection using program emulation of movement along the isocentric arc. The spatial reference allows to use both skin markers and rigidly fixed fiducials connected with skull bones or dental impression of patient for intraoperative registration of the patient's head. Registration based on the patient's head surface shape is also available.

Tests of the working prototype of the robotic manipulator are carried out. Phantom tests showed an average error of aiming at a target point within 1 mm, subject to registration with the use of fixed fiducials of navigation systems, and preoperative scanning of the phantom using CT and MRI. It is planned to start serial production of the device within the next few years. It is supposed to use the manipulator to perform the tasks of both functional and non-functional stereotaxis.

Background: For safe DBS planning an accurate visualization and localization of vessels is mandatory. Contrast enhanced (ce) MRI depicts both arteries and veins. Computed tomography angiography (CTA) detects arteries with high geometric accuracy. We routinely combine both modalities for DBS planning. In this study we analyzed the number and location of vessels visible in ceMRI and CTA in each trajectory.

Materials and Methods: A total of 222 trajectories in a consecutive series of 113 patients who underwent DBS operations from March 2014 to February 2017 were included. In all patients a preoperative T1-weighted 3D ceMRI sequence, a CTA and a postoperative native CT scan were available. In all 222 trajectories the number of veins and arteries in a 10 mm diameter around the planned trajectory was counted in both modalities (ceMRI and CTA). If a vessel was visible in both modalities the distance was measured.

Results: A total of 371 vessels were counted in a total of 222 trajectories. 240 vessels (65%) were visible in both modalities. In 134 vessels we detected a difference of the vessel’s location with an average distance of 1.24 mm (SD 0.58). 81 vessels (22%) were visible only in ceMRI, 50 vessels (13%) only in CTA. We had a total of 4 bleedings in 3 patients (1.8% per lead) of which 1 was symptomatic (0.45%). All of them were implants into the subthalamic nucleus, one with a posterior approach. In all but one we performed microelectrode recording.

Conclusion: The majority of vessels were visible in both modalities. However, in more than half of these cases the location was not identical. Here, the location in CTA can be regarded as ground truth. Moreover, both CTA and ceMRI depicted vessels not seen in the other imaging modality. We therefore assume that the combination of both imaging modalities for DBS planning increases the chance to detect vessels along the planned trajectories, thus reducing the risk of intracranial bleeding. This assumption is supported by our low bleeding rate of 1.8%.

Introduction

The superolateral medial forebrain bundle (slMFB) is an important structure for the regulation of reward and motivation and emerges as a target region for major depression (MD) [1] and possibly for obsessive compulsive disorder (OCD) [2]. Diffusion MRI (dMRI) based tractography is a non-invasive method of visualizing structural connectivity in the brain. It can guide white matter DBS targeting and might be a valuable tool in preoperative planning and navigation. Despite these promising opportunities, dMRI tractography is still not fully mature and the quality of automated white matter bundle segmentation is still questionable. It was shown that tracking algorithms running on brain-like numerical phantoms with known ground truth heavily suffer from false positives/negatives [3]. In this work we follow an alternative approach to tractography and use machine learning (ML) to directly map the dMRI data onto a directional saliency map of tract presence, in this work slMFB. We apply this idea to a set of four patients suffering from OCD who were treated with slMFB DBS and investigate the plausibility for machine learning approach as a true alternative to the conventional deterministic planning  (BrainLab Elements) and other advanced tracking algorithms.

Method and Data

We developed an extension of the trainable non-linear filter described in [3] to learn fields, such that the filter’s output can be used for classical tensor-based streamline tractography. The filter is rotation covariant, that is, the response of the filter (the tract image) always rotates according to the input (the brain). While not sounding very subtle, this property is indispensable for any tracking algorithm, however for an ML approach not trivially to fulfill. We built such a filter to detect the superolateral medial forebrain bundle [4]. The machine - HAMLET (Harmonic hierArchy MultiscaLE Tracking) - was trained on a subset of 20 healthy controls based on an automatic selection procedure (described in [4]). Only 2-order information is used, i.e. any ordinary clinical protocol, which allows to estimate a diffusion tensor, is already sufficient. We applied the filter on a set of four OCD patients that underwent MFB stimulation. All patients had preoperative dMRI and anatomical T1w and T2w scans. Electrode locations were extracted from postoperative CTs. The output of the filter is tracked by a simple streamline approach. For comparison we used global tractography as described in [4] to automatically segment the slMFB. 

Results

Clinical, patient 1 (f, 31y/o) showed a 56.3% YBOCS (Yale Brown Obsessive Compulsivity Score) improvement on 3 months follow up (43.5 preop, 19 at three months FU). Patient 2 (m, 32 y/o) showed a 23% improvement at three months FU and a 33.3% improvement at twelve months F/U (preop 39; 30 at three months, 26 at 12 months). The extracted slMFB is visualized in the companion Figure: the predicted tract detection image overlayed a T2w image, and the corresponding streamline tractography. Comparing with GT, the first observation is that the results produced by HAMLET are cleaner, less curly and more smooth. In general, the results of HAMLET are less cluttered and has a visual appearance which is similar to ordinary streamline tractography. The overall gross anatomy predicted by both approaches are comparable. For example, in patient 2 both methods agree that the left electrode in part misses the target region (possibly reflected in less clinical improvement). 

Discussion

We presented preliminary results of a fully automated tract delineation procedure based on ML. The new approach can reflect the anatomy of the underlying structure of interest in a novel way. The idea is to learn the occurrence of the target structure - in our case the slMFB - from examples and then use this learned anatomical prior knowledge to find the structure in unseen subjects. It might in the future replace the lengthy tractography pipelines in use by a one-step prediction step. The presented results look very promising and the individual anatomy is well reflected.

[1] Schlaepfer TE, et al. Biol Psychiatry. 2013 Jun 15;73(12):1204–12.

[2] Coenen VA, et al. CNS Spectr. 2016 Jun 8;493(03):1–8.

[3] Skibbe, Henrik, and Marco Reisert. Journal of Mathematical Imaging and Vision 58.3 (2017): 349-381.

[4] Coenen VA et al. NeuroImage: Clinical. Elsevier; 2018 Mar 19;18:770–83.

[5] Maier-Hein, Klaus, et al. biorxiv (2016): 084137.

Objective: To report our next findings and share our experience in our research for optimizing the imaging logistics perioperative deep brain stimulation (DBS) surgeries using a cone-beam-CT (CBCT) scanner available in our hybrid operating theatre.

Methods: In continuation of our previous results (poster presentation on the last ESSFN congress), the successful fusion of a stereotactic CBCT and “normal” CT, we used our same research design to test magnetic resonance imaging (MRI) fusion. We only changed our phantom, which needed to be MRI compatible, into a Citrullus Lanatus (watermelon).  We mounted a Leksell stereotactic frame (Elekta, Sweden) on our phantom with the CT indicator and placed it in the CBCT (Allura Xper FD20, Philips, the Netherlands). Prior, we performed a MRI scan with the same phantom (3 Tesla, Ingenia, Philips). Both scans were uploaded into two different commercial navigation software programs.

Results: With some effort and thoroughly analysis of the acquired images we successfully fused the stereotactic CBCT with MRI using one of the software programs. The accuracy of the fusion was good and clinical usable as assessed by three independent reviewers experienced in DBS surgery.  Key to the fusion is to use the “raw” image data containing geometrical information.

Conclusion: We believe that CBCT can be a very useful and novel imaging method in DBS surgeries, including stereotaxy. Especially, in centers which already have a CBCT device. However, beside some practical obstacles to overcome, further research in a clinical setting is needed.

Object: The aim of this study was to compare three different methods to assess the geometrical distortion of two 1.5T and one 3T magnetic resonance (MR) scanners and to evaluate the co-registration accuracy. Overall uncertainty of each particular method was also evaluated.

Methods: Three different MR phantoms were used in this study: two commercial CIRS skull phantom and PTGR known target phantom and one in-house made cylindrical Perspex phantom. All phantoms were fixed in the Leksell stereotactic frame and examined by CT Siemens SOMATOM unit and two 1.5T Siemens AVANTO and SYMPHONY and 3T Siemens SKYRA MRI systems. The images were evaluated in the Leksell  GammaPlan software, and the geometrical deviation of the selected points from the reference values were determined. The deviations were further investigated for both definitions including fiducial based and co-registration based in the case of the CIRS phantom images.

Results: The accuracy of the CT scanner was determined as 0.10, 0.30 and 0.30 mm for X, Y and Z coordinates, respectively. The total estimated uncertainty in distortion measurement in one coordinate was in our study determined to be 0.32 mm and 0.14 mm for methods using and not using CT as a reference imaging, respectively. Slightly more significant distortions were observed when using the 3T than both of 1.5T MR units. However, all scanners were comparable within the estimated measurement error. Observed deviation/distortion for individual X, Y and Z stereotactic coordinate was for all three scanners and all three employed measurement methods typically within 0.50 mm. The total radial deviation/distortion was typically within 1.00 mm. The maximum total radial distortion was observed when CIRS phantom was used, it was 1.08±0.49, 1.15±0.48 and 1.35±0.49 for Symphony, Avanto and Skyra, respectively. The co-registration process proved to improve image stereotactic definition in the case when fiducial based stereotactic definition is not that accurate. It was demonstrated for 3T stereotactic imaging in this study. The best results were shown for 3T MRI images co-registration with CT images improving image stereotactic definition by about 0.50 mm.

Conclusion: All three used methods/phantoms were evaluated as satisfactory for the image distortion measurement. The method using PTGR phantom has the lowest uncertainty since no reference CT imaging is needed. Image co-registration can improve stereotactic image definition when fiducial based definition is not accurate. The study was supported by the Czech Science Foundation (GACR16-13323S).

Deep brain stimulation (DBS) is an important therapy for movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). DBS is also expanding towards psychiatric illness. A multimodal approach is imperative in order to make surgery and follow up efficient, safe and with optimal patient outcome. In the Project we aim at bringing together big DBS data for clinical support i.e. to go from “mental imagination” to “intuitive visualization” [1]. Data from MRI (T1, T2, WAIR, DTI), brain atlases, tractography and patient-specific electric field (EF) simulations [2] will be combined with intraoperative physiological data and patient scoring in a comprehensive analysis for optimization of DBS therapy, and increased understanding of the brain´s function. The work will proceed in parallel but interactive work packages with partners from an international multidisciplinary team with a broad expertise in both technical and clinical DBS-research. This project will give unique opportunities to investigate the anatomical spread of the EF for new DBS lead designs (steering and ring-mode) and stimulations modes (voltage and current) [3], and to match EF with the clinical and physiological assessments of movement, neuronal activity and cerebral microcirculation [4]. Present work aims at defining the dentatorubrothalamic tract and combines this with patient-specific EF simulations in the Zi. Furthermore an improvement atlas for the Vim region originating from intraoperative test stimulations, accelerometer recordings and EF simulations is set up [5]. Other project activities are linked to patient-specific simulations for probabilistic determination in the Vim, Zi and STN in movement disorders and GPi in Tourette syndrome [6]. A demonstrator will include open access APPs for patient-specific EF simulations and statistically created improvement maps for clinical support of the most likely stimulation regions for brain targets used in PD and ET, and possibly also targets for psychiatric illness. To persue this project, biomedical engineers and neurosurgeons work together. An overview of the project and the first results will be presented at the meeting. https://liu.se/en/research/dbs

The project is supported by The Swedish Foundation for Strategic Research, The Swedish Research Council and ALF-Region Östergötland.

References

1. Hemm, S. and K. Wårdell, Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools. Med Biol Eng Comput, 2010. 48(7): p. 611-24.

2. Åström, M., L.U. Zrinzo, S. Tisch, E. Tripoliti, M.I. Hariz and K. Wårdell, Method for patient-specific finite element modeling and simulation of deep brain stimulation. Med Biol Eng Comput, 2009. 47(1): p. 21-8.

3. Alonso, F., M.A. Latorre, N. Göransson, P. Zsigmond and K. Wårdell, Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study. Brain Sci, 2016. 6(3).

4. Zsigmond, P., S. Hemm-Ode and K. Wårdell, Optical Measurements during Deep Brain Stimulation Lead Implantation: Safety Aspects Stereotact Funct Neurosurg, 2018. Jan 5;95(6):392-399. 

5. Hemm, S., D. Pison, F. Alonso, A. Shah, J. Coste, J.J. Lemaire and K. Wårdell, Patient-Specific Electric Field Simulations and Acceleration Measurements for Objective Analysis of Intraoperative Stimulation Tests in the Thalamus. Front Hum Neurosci, 2016. 10: p. 577-591.

6. Akbarian-Tefaghi, L., H. Akram, J. Johansson, L. Zrinzo, Z. Kefalopoulou, P. Limousin, E. Joyce, M. Hariz, K. Wårdell and T. Foltynie, Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome. Stereotact Funct Neurosurg, 2017. 95(4): p. 251-258.

Introduction: Myoclonus-dystonia syndrome (MDS) is a movement disorder with onset in childhood or adolescence, characterized by the presence of myoclonic jerks and/or dystonia. It is considered a type of primary dystonia with normal neuroimaging. Epsilon-sarcoglycan mutations (SGCE) are the most frequent genetic alterations, identified in up to 80% of paediatric cases. Myoclonic jerking interfere the daily life activities with negative impact in quality of life. Non-specific treatments are available nowadays, with limited efficacy and poor tolerance. Bilateral deep brain stimulation (DBS) of the posterior-ventral internal Globus Pallidus (GPi) has been proven an effective option with potential long-term benefit.

Objectives: To describe the effectiveness of bilateral GPi stimulation in two paediatric patients with myoclonus-dystonia and SGCE mutation, assisted by the robotic arm Neuromate^® of Renishaw^®.

Methods: We describe two paediatric patients affected of MDS SGCE+ (DYT11) treated with bilateral GPi DBS system implantation assisted by robotic arm Neuromate^® (Renishaw^®). We compare the pre-surgical Unified Myoclonus Rating Score (UMRS) with its postoperative evolution at 3 and 6 months.

Results: In both cases there has been a significant clinical improvement with reduction in the UMRS scale for action myoclonus at 1 month (84, 96%) and at 6 months (95, 100%).  An improvement in functional tests was also observed at 1 month (62, 40%) and at 6 months (94, 75%).

Conclusions: Frameless robotic arm-assisted implantation of bilateral GPi DBS for the treatment of MDS (DYT11) has been as safe and effective as conventional stereotactic frame implantation.

Introduction: The occurrence of cerebral tumors in patients with chronic deep brain stimulation (DBS) has been reported in few patients. Despite it is very difficult to determine whether DBS would be the cause of tumor development or it is just coincidence, there have been publications advocating the one or the other. Here, we report the development of a pilocytic astrocytoma in close vicinity of a DBS electrode during the course of chronic DBS.

Case report: A 38-year-old man with refractory dystonic head tremor underwent bilateral implantation of quadripolar DBS electrodes in the thalamic ventral intermediate nucleus (Vim) guided by stereotactic CT and macrostimulation. He benefited markedly from chronic DBS (amplitude, 2.5 V; pulse width, 210 µs; frequency, 130 Hz). The pacemaker was replaced twice due to battery depletion at 2 and 7 years after the initial surgery.

At age 46 he was admitted with head and neck pain, attention defcits and sensory disturbances ongoing for the last one year. Craniocerebral CT investigation revealed a 4.5 x 5 cm sized rightsided subcortical tumor. Surgery was performed with neuronavigation guidance and the tumor was subtotally removed via a right parietooccipital craniotomy. The postoperative period was uneventful and there were no postoperative neurological deficits or complications. The neuropathological examination revealed a pilocytic astrocytoma WHO Grade I. Postoperative MRI imaging demonstrated a small remnant of the tumor which did not increase in size during follow-up up to 1 year. He had ongoing benefit of his tremor with continued DBS.

Discussion: Pilocytic astrocytomas constitute approximately 25% of all pediatric and 1.5% of all adult brain tumors. A recent review demonstrated that the number of cases with adult pilocytic astocytoma is barely 450 in the literature. It is a relatively rare tumor to encounter in adulthood. Does this hint to a causal relationship with DBS? To the best of our knowledge, there have been only three case reports published indicating such a co-occurrence. In all of these three reports, the tumors were high-grade glial tumors.

It is estimated that about 160.000 patients have been treated with DBS worldwide to date. The resulting probability to develop a brain tumor would amount to 0,0025%. According to an estimated projection with regard to the 10-year prevalence data of CNS tumors, however, rather a formation probability of 0,025% would have been expected. Thus, no causal relationship between DBS and brain tumor formation would be derived. Considering these findings from a different perspective might also allow the interpretation that chronic application of electric current via DBS electrodes could, in general, rather have a protective effect for brain tumor formation.

Objective

Despite its application for several decades, it is still not fully understood which cerebral structures are responsible for the therapeutic effect in deep brain stimulation (DBS). Although targeting mainly includes grey matter structures such as the subthalamic nucleus (STN), the role of white matter tracts has been featured lately. Probabilistic tractography serves as a valuable tool to depict white matter connections. The goal of this study was to analyze structural connections involved in rigor suppression in STN DBS.

Material and Methods

We retrospectively analyzed diffusion tensor data of 21 patients with Parkinson´s disease, who had received bilateral STN-DBS. Probabilistic tractography was performed based on seeds on each individual electrode contact. In addition, we  evaluated each contact concerning the proportional suppression of rigidity. Based on this data, effective and ineffective contacts were compared regarding the connectivity pattern focussing on fiber tracts rather than cortical areas. 

Results

Imaging and clinical data of 21 patients (42 hemispheres, 168 contacts) could be analyzed retrospectively. Reduction of rigor (> 50%) compared to base line was observed in 83.8% of the electrode contacts 

The following fiber bundles were significantly more frequently associated with clinically effective alleviation of rigidity: fasciculus anterolateralis, fasciculus thalamicus, fibers to the lamina medialis thalami, pallido-thalmic fibers and the anterior limb of the internal capsule. Interestingly, the localization of contacts relative to the STN anatomy did not show significant differences in terms of rigor suppression. 

Conclusion

Our data suggest that certain brainstem-, thalamic- and frontal connections might be involved in rigor suppression. This information could be useful in target planning for deep brain stimulation and also in post-operative programming of the stimulation parameters in the future.

Objective:  Evaluate the global changes in the connectivity of the large-scale structural network in Parkinson's disease (PD) and testing the hypothesis that the benefits of DBS in patients with PD go beyond simple deep stimulation, generating changes in certain neuronal tracts.

Background: DBS of the subthalamic nucleus (STN) is currently a cutting-edge, evidence-based therapeutic option for motor and non-motor symptoms in patients with PD. However, the exact anatomical regions associated with patient improvement go beyond simple stimulation of the nucleus and the modulated brain networks have not been described accurately. Therefore it is necessary to use new methods which can elucidate the associations between specific network changes such as tractography.

Method: Retrospective study of 31 patients divided into 3 groups: 7 with bilateral ECP (group A), 12 non-operated patients with PD (group B), and 12 healthy controls (group C), matched according to age, gender and score on H&Y scale. The DTI images of the healthy controls were obtained from the global database Image & Data Archive (IDA). In all cases, a 1.5 T brain MRI with DTI was performed. DICOM images will be processed with the FSL5.0 software. The statistical analysis is done with the TBSS tool. The "JHU White Mather Tractography atlas", among others, was used to correlate the significant areas with the affected tracts.

Results: The total group consists of 23 men and 8 women. The mean follow-up time in group A is 4.2 years while in group B it is 4.83 years. Relevant analyzes were obtained in all made between the three groups. Group A versus group B: group A showed a higher fraction of anisotropy (AF), in the cerebral right hemisphere, highlighting the right corticospinal tract. There are also differences in thalamic radiations and in both corticospinal tracts. When we compared group B versus group C,  group B presents a greater FA in the left corticospinal, radiata crown, the left fronto-occipital fascicle and both upper and lower longitudinal fascicles. 

Conclusions: In our series, PD patients treated with bilateral NST-ECP showed a relevancy higher AF, in different areas of cerebral white matter, inside and outside of motor regions, which could be related to its therapeutic effect and to other effects observed with brain stimulation. This study shows that ECP should be understood as a stimulation of neural networks.

There are different types of tremor, such as resting, cerebellar or intentional tremor. This alterations can be disabling, leaving the patient without functionality. Many occasions the pharmacological management of this disorder is not optimal, which is a window of opportunity for surgical management. A first option of neurosurgical treatment has been thalamotomy, which has a success rate of up to 93%, but this is associated with permanent complications up to 23%, especially if a bilateral lesion is made. We propose the RAPRL injury as a target for the treatment of tremor originated from pathologies other than Parkinson´s disease. A lesion of the prelemniscal radiations (RAPRL) was performed using a ZD stereotactic system in 6 patients with a history of little or no response to pharmacological management. Immediate favorable results were obtained in more than 85% of the cases with return to normal life in a few days and reduction or elimination of medical treatment; one patient presented an intraoperative complication, but it reverted spontaneously in few days. This indicates that the radiofrequency lesion of RAPRL is a safe procedure that represents a surgical treatment option for those patients who do not have resources for a DBS system, in addition, it has the advantage of  incorporation to normal life almost immediately and less need or elimination of pharmacological treatment.

Introduction Deep brain stimulation (DBS) is an accepted standard therapy for movement disorders, such as Parkinson’s disease, essential tremor or dystonia that gives an outstanding improvement of motor outcome and quality of life ^1-3. Complications after DBS are reported to occur in 5 to 15 % of patients ^4-6.The rate of intracranial haemorrhage after deep brain stimulation is between 1.5 and 4.77 % per patient.^7-9Here, the rate of bleeding that lead to a permanent deficit is between 0.4 and 2.53 % ^{4, 9-12}.

As intracranial bleedings are concerning complications after DBS, it is necessary to improve management in order to avoid bleedings.  Therefor we decided to implement a platelet function analyser test (PFA 100) screening before operation. In cases with disturbed results the ambulance for coagulation was consulted for further instructions. We conducted this study to reveal differences in rates of bleedings in both groups.

Methods We retrospectively analysed complications focusing on intracranial bleedings following DBS surgery from 2010 to 2017 in a single-centre university hospital setting. Medical records of all patients who underwent DBS surgery were systematically reviewed. The shortest follow-up time was 2 months.

Results 113 patients had a PFA 100 analyses preoperative. In 18 cases (15.9 %) in the first measurement elongated PFA 100 closure times were normal in a second investigation. In 10 cases (8.8 %) the investigations revealed a mild von Willebrand disease. In these cases operations were performed under oral intake of tranexamic acid, starting one day before operation continued to five days after operation. In the control group (299 patients) in average 3.0 microelectrodes were used (0 to 5). In our group with PFA 100 screening we used in average 2.5 microelectrodes (0 to 3). Bleedings without permanent deficits were found in 7 cases in our control group (2.34 %) and in 2 cases (1.77 %) in our group with the PFA 100 test. Bleedings with permanent deficits occurred in 4 cases in our control group (1.38 %) and in our study group in 0 cases (0 %).

Conclusion In our study the rate of bleedings with deficits could be reduced from 1.38 % to 0 % by the preoperative use of a PFA 100 test. As bleedings certainly need to be avoided, a measurement of platelet function could help to increase safety of deep brain stimulation.

Background and Objectives.

  Glutaric acidemia type 1 (GA1) is a rare inherited autosomal recessive metabolic disease. It is characterized by deficiency of riboflavin dependent glutaryl-CoA dehydrogenase (GCDH).  It has an estimated prevalence of 1 in 100,000 newborns. Untreated, 90% of patients will develop neurological disease with acute striatal injury and subsequent complex movement disorders, with generalized dystonia being the dominant extrapyramidal symptom. Ablative procedures have been performed with unsatisfactory long-term results, as long as the effect of deep brain stimulation has been only anecdotally reported.

  We present a case of GA1 and generalized dystonia that was submitted to bilateral globus pallidus internus deep brain stimulation (GPi-DBS).

Materials and Methods.

  The patient is a 22 years old woman with no family history of metabolic disorders or early neonatal deaths. Her disease had an early onset (7^th month of life), and began with acute encephalopathy due to gastroenteritis. Later, the patient suffered psychomotor regression and generalized dystonia, while her intellect remained intact.

The neuroimaging tests (MRI) showed abnormal high signal intensity and atrophy at basal ganglia along with three subependymal lesions and a partial absence of the septum pellucidum.

  The targeting method involves the implantation of the Leksell G stereotactic head frame and the anatomical planning of the targets on the most suitable sequences of the MRI fused with a stereotactic CT scan, followed by their neurophysiological location in the operating room.

  The case was evaluated with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), severity and disability scores, before and after surgery (0.5, 1, 3 years). The clinical follow-up has been performed from 2015 to present. The data were assessed with SPSS24.

Results.

  Microelectrode mapping through the pallidal complex did not show the characteristics discharge rates and patterns typical of these neurons. Postoperative control images demonstrated that the anatomical position of the electrodes was appropriate.

After bilateral GPi-DBS the patient experienced an important clinical benefit and significant improvement in the rating scores that were attained from the surgery to present.

Conclusions.

  Glutaric acidemia type I is a very uncommon disease. Patients characteristically develop generalized dystonia during infancy resulting in a high morbidity and mortality.

Our results suggest that bilateral GPi stimulation is a useful and effective therapeutic strategy for cases such as this one, despite striatal changes typical of GA 1 and physiological data obtained in the intraoperative setting.

Objective: Camptocormia is a disabling syndrome characterized by forward flexion that can be an idiopathic or associated with numerous diseases like movement disorders, especially Parkinson's disease (PD). Treatment options are usually futile and L-dopa shows little or no effect. Posture improvement could be expected in bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) in PD patients with camptocormia. Outcome results are inconsistent, especially for STN. The aim of this study was to determine the efficacy of bilateral STN DBS in alleviating the degree of camptocormia in two PD patients.

Patients and methods: Two patients (67-year-old female and a 66-year-old male) suffering from PD in the last ten years and more were subjected to bilateral STN DBS procedure. The positions of electrodes were verified with a postoperative magnetic resonance imaging. The results were objectivized by measuring thoracolumbar flexion angle before and after operation and using all recommended scales for the international survey of DBS.

Results: The degree of forward flexion of the spine has substantially decreased and the quality of life, motor symptoms and functioning improved in both patients.

Conclusion: STN DBS should be considered as a potential treatment option for PD patients with camptocormia. Further analysis is needed to conclude what PD patients are candidates for bilateral STN or GPi stimulation in the treatment of camptocormia.

Introduction. The potential neuroprotective effect of STN lesions in Parkinson´s disease is currently generating great interest. The parkinsonian condition is associated with enhanced glutamate (excitatory) release due to STN overactivity which could induce toxicity to dopaminergic cells and should contribute to Parkinson´s disease progression.

Material and Methods. In the presentation we review rodens studies performed with 6-OHDA and their neuroprotective effect with STN lesion and monkeys treated with MPTP and STN alteration.  Research studies demonstrated that neuroprotection and striatal depletion are opposite concepts to restore degenerative processes affecting dopaminergic neurons.

Studies in animals demonstrated that STN hyperactivity may be an early process in parkinsonian condition and rather than being dependent on striatal depletion it may occur correlated with the loss of dopaminergic neurons.

Results. In the presentation we describe new approach as non invasive surgery, opening up paths for an early treatment of PD.  We suggest the hypothesis that an intervention in the STN might be able to reduce glutamate release and delay disease evolution.

Background: End-stage heart failure with severe symptoms (class IV according to New York Heart Association functional classification) and no remaining alternative treatment options may be indication for heart transplantation. Performing further functional neurosurgical procedures in  such patients after heart transplantation and on continuous anti-plateled therapy is very challenging. to treat the underlying and handicapping movement disorder like pharmacologically – resistant rest/postural tremor.

Objectives and Methods:  Here, we describe the first case of a patient after heart transplantation who was previously  diagnosed with tremor dominant Parkinson’s disease and underwent gamma-knife Vim- thalamotomy and unilateral subthalamic deep brain stimulation  in the left hemisphere. The Vim - thalamotomy brought only modest benefit. Subsequently performed unilateral subthalamic deep brain stimulation reduced completely right sided debilitating rest/postural tremor in long-term follow-up.

Results and conclusions: The functional procedures in a challenging patient even after heart transplantation and on antiplated therapy can be safely done under special precautions. If less invasive gamma-knife thalamotomy have failed more aggressive approach like placement of deep brain  stimulation lead can produce amelioration of handicapping rest/postural tremor.  

Background: The true incidence of hemorrhagic venous infarctions in deep brain stimulation (DBS) procedures is very difficult to determine. These hemorrhagic venous complications are very rare and often grouped as all hemorrhagic complications.

Method: We report the clinical cases of 2 patients with Parkinson’s disease (PD) who received unilateral globus pallidus DBS and developed hemorrhagic venous infarctions.

Results: In these 2 patients a small injury to a dural outflow venous structure or a superficial brain vein resulted in hemorrhagic venous infarctions. We present the management of these rare complication with detailed radiologic follow-up. The first patient made a full recovery but the second patient deceased 5 months after DBS surgery to due aspiratory pneumonia.

Conclusion: We stress that careful planning of a stereotactic trajectory reduces significantly hemorrhagic complications in DBS surgery but not fully exclude some side effects like venous hemorrhagic infarctions which may result in prolong hospitalization or death. 

Background: The goals of the present study were to assess the health-related quality of life (HRQoL) with the Parkinson’s Disease Questionnaire 39 (PDQ-39) after unilateral subthalamic deep brain stimulation (STN DBS) and to identify correlations between the changes in UPDRS (Unified Parkinson’s Disease Rating Scale) scores and separate PDQ 39 QoL dimensions and PDQ summary index (SI) score at short-term follow-up (FU1) and long-term follow-up (FU2).

Material and Methods: We evaluated 33 patients with PD after unilateral STN DBS. All patients were assessed at baseline and at FU1 and at FU2. HRQoL levels were determined by applying PDQ-39 and PD progression was evaluated by parts I-IV of the UPDRS.

Results: All dimensions of PDQ-39 as well as PDQ-39 SI score were highly significantly improved at FU1. The same improvements were mostly visible at FU2 except for psychosocial functioning. The PDQ-39 SI score was reduced by 40 % (p<0.01) at FU1 and by 25 % (p<0.01) at FU2. A significant reduction between the UPDRS baseline scores and the UPDRS follow-up scores was noticed for medication off and on conditions under unilateral STN DBS. Interestingly, we did not find strong positive correlations between the improvements of the UPDRS scores and individual PDQ-39 dimensions as well as PDQ-39 SI score.

Conclusion: Improvements in PDQ-39 dimensions and PDQ-39 SI score are maintained at FU1 and except for the aspects of psychosocial functioning at FU2. Different correlations between the improvements of separate UPDRS scores on PDQ-39 dimensions require future studies in larger study groups.

Key words: Parkinson’s Disease Questionnaire 39, unilateral subthalamic deep brain stimulation, health-related quality of life, surgery for Parkinson’s disease, deep brain stimulation.

Background: We present our experience in patients operated for movement disorders who developed intracerebral hemorrhagic complications seen on intraoperative stereotactic computed tomography performed immediately after a deep brain stimulation (DBS) lead placement before introduction of generalized anesthesia for implantation further components of DBS hardware.

Material and Methods: Patients who underwent DBS lead implantation form January 2009 till December 2017 were included in the present study. Mostly all surgeries were performed in staged fashion. All patients were operated adopting strictly the same surgical technique. No  microelectrode recordings (MER) were done. For all surgeries the Leksell Stereotactic G frame and neuronavigation software (Medtronic, Stealthstation) were utilized. The intraoperative stereotactic computed tomography was done to check the exact position of the implanted DBS lead and ruled out any hemorrhagic complications. 

Results: There were 222 patients who underwent 322 DBS lead implantation in 316 stereotactic procedures. 6 patients showed hemorrhagic complications recognized on  intraoperative stereotactic CT performed immediately after a DBS lead placement. The hemorrhagic complication rate was 2.7 % per patient and 1.8 % per lead implanted. Overall, among 6 patients with hemorrhagic complications there were 2 large intracerebral bleedings located along the stereotactic trajectory extending to the stereotactic target. Moreover, 1 patient suffered intracerebral bleeding located subcortically. 1  patient had a paraventricular bleeding, and 1 patient  subarachnoid bleeding. We encountered 1 bleeding along stereotactic trajectory. Among 6 patients with hemorrhagic complications 2 patient suffered permanent right-sided paresis with dysarthria. 1 patient with large intracerebral bleeding  passed away 2 months after DBS lead placement. The permanent deficits rate per patient was 0.9 % and 0.6 per lead implanted.

Conclusions: The most feared complication of stereotactic surgery for movement disorders remains the development of intracerebral hematoma. Intraoperative stereotactic CT can not only visualized in the stereotactic space the implanted DBS lead but also rule out an early hemorrhagic complication. This can postpone the implantation of further DBS hardware in general anesthesia immediately after detaching the stereotactic frame and properly manage patients with early hemorrhagic complications due to DBS lead placement.

Background:
Conventional deep brain stimulation (DBS) is an established treatment for advanced stage Parkinson’s disease (PD). Conventional DBS is however limited by a delicate balance between beneficial and adverse effects, habituation over time and limited battery longevity. These limitations might be overcome by adaptive DBS. Adaptive DBS aims to automatically adapt stimulation parameters based on the patient’s fluctuating clinical state. Feedback input signals are therefore needed, which are related to PD symptoms.

We developed a multi-modal Parkinson monitoring system, which should represent PD symptomatology in the daily living environments of PD patients. The multi-modal monitoring system consists of three wearable sensors and an experience sampling method (ESM) smartphone application. The combination of wearables and ESM in PD patients has not been described before. The ultimate goal is to use this system as input signal for adaptive DBS, but first its feasibility has to be tested. We therefore aim to 1) test the feasibility of the multi-modal Parkinson monitoring system and 2) test to what extent we are able to identify and correlate PD symptoms in and between wearable and ESM data.

Methods:
The feasibility of the multi-modal Parkinson monitoring system is currently tested in 20 PD patients for 2 consecutive weeks. The participants wear one wearable sensor at the chest and one at each wrist during the day. The newly developed wearable sensors (IDEE Engineering Department, Maastricht, The Netherlands) include both an accelerometer and gyroscope and produce raw data. The participants also use a smartphone-based ESM application, a digital diary methods which subjectively assesses both motor and non-motor symptoms at 7 semi-random times a day by short repetitive questionnaires. These questionnaires include specific questions on PD motor symptoms, but also on general motor functioning and well-being and affect. The questionnaires are momentary assessments and only stay available for 15 minutes. In this way, we aim to collect subjective data with minimal recall-bias. In addition to the random questionnaires, participants are asked to complete a morning and evening questionnaire, covering respectively questions about for example sleep and OFF periods of that day.

Results:
First, we will express the feasibility of the multi-modal monitoring system in percentages of completed ESM questionnaires and in amount of time correctly measured by wearables. In addition, experiences of the participants regarding the monitoring system will be evaluated at the end of the study, resulting in user experiences and acceptance rates. The collected raw sensor data will be analyzed on PD motor symptoms, like tremor and gait. The collected ESM data will be analyzed for fluctuations in and between days regarding motor symptoms. If both modalities appear to be feasible we will analyze the correlation between the objective and subjective data.

Conclusion:
This study is the first one combining wearables with ESM in PD patients. We will examine whether this multi-modal Parkinson monitoring system is feasible and to what extent we are able to identify and correlate PD symptoms in wearable and ESM data. We aim to get insight into the PD symptom fluctuations within and between days using our monitoring system.

Introduction:
Conventional deep brain stimulation (cDBS) of the subthalamic nucleus (STN) is an established treatment for advanced stage Parkinson’s disease (PD). cDBS is however limited by a delicate balance between beneficial and adverse effects, habituation over time and limited battery longevity. It is therefore crucial to find an alternative for cDBS. The limitations of cDBS might be overcome by closed-loop or adaptive deep brain stimulation (aDBS). aDBS aims to automatically adapt stimulation parameters based on real-time fluctuations in a patient’s symptomatic clinical state. This is achieved by frequently or even continuously updating stimulation parameters using feedback input signals related to PD symptoms. The development of a valid aDBS system in PD however faces major challenges such as creating suitable input signals and the implementation of these input signals into beneficial output. We will discuss the most recent developments regarding potential input signals and possible stimulation parameter algorithms for aDBS in PD. In addition, future needs that are necessary for the clinical implementation of aDBS in PD will be discussed.

Input signals:
Potential input signals for aDBS include local field potentials (LFP), cortical recordings (electrocorticography), surface electromyography, neurochemical recordings, wearable sensor data and eHealth and mHealth devices. Currently, aDBS controlled by STN-LFP, cortical recordings and wearables show the most potential.
Regarding aDBS based on STN-LFP, proof of concept studies showed more effectiveness and efficiency with on the same time less side effects compared to cDBS when shortly using aDBS. Chronical implementation however requires further understanding of associations between STN-LFP and clinical symptoms and the effect of voluntary movement and aDBS itself on the LFP. In addition, aDBS systems based on STN-LFP might demand an additional monitoring method such as wearables, because of the limited correlation of tremor and STN-LFP. For aDBS based on cortical recordings, clinical experience and understanding is limited. However, the huge theoretical potential in monitoring motor and non-motor PD symptoms is promising and deserves further exploration. Regarding aDBS controlled by wearables, proof of concept studies based on only tremor detection showed feasibility, effectiveness and efficiency of aDBS. To expand the potential for also non-tremor-dominant patients, algorithms monitoring other cardinal motor symptoms than tremor need further development and clinical validation. For tremor-dominant patients, clinical trials with longer follow-up periods should be performed to prove superiority of aDBS over cDBS.

Stimulation parameter modulation:
Most published research on aDBS only discussed potential input signals although the importance of possible stimulation paradigms. Possible stimulation paradigms are amplitude (including phase-dependency), frequency and pulse-width modulation. Amplitude modulation is the only stimulation paradigm used in aDBS so far. Understanding of and experience with different amplitude modulation approaches like ON/OFF, gradual and continuous amplitude modulation will expand soon. Frequency and pulse-width modulation have not yet been considered in aDBS but might have additional value for individually tailored stimulation paradigms.

The future potential of aDBS in PD
Although impressive progress in aDBS for PD has been made last decade, important challenges have to be overcome before chronic application. Deciphering PD phenotypes in relation to input signals will greatly impact on the algorithm building development. Clearly, a single input signal will not cover the heterogeneity of PD. In the development of a valid aDBS system in PD, thoughtful combining and selecting of input signals is therefore inevitable.

Deep brain stimulation (DBS) delivered by means of directional electrodes has been introduced with the aim to conform the electromagnetic fields to obtain tailored stimulation: It has been demonstrated that directional leads (d-Leads) may improve the clinical outcome, reducing collateral effects and widening the therapeutic window in movement disorders. Previous reports deal with short-term results. In the present cooperative study we report mid-term follow-up results.

11 patients treated with d-leads DBS for movement disorders were enrolled in the study. Patients were affected from advanced  Parkinson’s disease (PD – 8 cases) and tremor (post-traumatic in 2 cases and secondary to MS in 1). Results after a short-term follow up of the same patients have been previously reported elsewhere. Preoperative mean UPDRS III was 48; Preop SF36 was 259. DBS was performed in STN, Gpi and Vim/Zi bilaterally; anatomical stereotactic reperage was obtained with volumetric T1/T2 MRi; intraoperative multitracks MERs and stimulation were performed to refine the targets. Intraoperative Xray controls confirmed the proper positioning of D-leads (C marker downward). Follow-up  (FU) controls were at 3-6-12-18 and 24 months.

11 patients ranged 18 months FU while only 3 pts reached 24 months FU. Mean UPDRS III at 18 months was 24 and at 24 months was 19. SF36 at 18 was 106 and at 24 was 103. The improvement of all the scores with respect to preop values was significant both at 18 and at 24 months. Further improvement was experted after 24 months FU. The electrode configurations were directional in all cases. Two patients suffered for hygroma (1) and small hemorrage (1). No significant increase of energy was necessary in any case.

Mid-term FU of D-Leads DBS confirm the data obtained after short-term FU. D-Leads DBS seems to obtain better clinical outcomes – mainly because less collateral effects – and the results are stable in time. The higher impedance on D-leads does not request increase in energy delivering along the time.

Introduction: Motor fluctuations are important in the course of Parkinson’s disease (PD) and often influence quality of life. Dopaminergic medication causes motor fluctuations and often deep brain stimulation (DBS) will not resolve the fluctuations in total. Monitoring and evaluating these motor fluctuations can be challenging since the classical golden standard, the Unified Parkinson’s Disease Rating Scale (UPDRS), is a momentary assessment instrument. It considers a single assessment as representative for symptom severity and is not able to capture within day or day-to-day motor fluctuations. Other questionnaires have time frames of one or more weeks or months, where recall bias is known to influence subjective grading. 

The experience sampling method (ESM) is a diary-method which assesses subjective experiences of patients, multiple times a day, at semi-randomized moments. By presenting the patient the same short questionnaire about his/her symptoms at that specific moment, ESM aims to collect subjective measurements with minimal recall bias. As such, ESM constitutes a valuable addition to recent technological developments that are able to objectively monitor symptoms continuously, such as wearable sensors (Delrobaei et al., 2018) and smartphone-based assessments for e.g. motor symptoms and speech (Zhan et al., 2018). 

We developed an ESM questionnaire that focuses on Parkinsonian motor symptoms in order to detect fluctuations within and between days. We will test the feasibility and internal validity of this questionnaire and method in an upcoming pilot combining our ESM with wearable sensors.

Methods: In ESM methodology, apart from sampling experiences, it is also important to assess the context of the sampling moments, as well as to avoid that the formulation of items influences the patient’s answer. We started with identifying the most relevant indicators of a ‘good’ or ‘bad’ day regarding motor symptoms. Both patient and clinician input were used to identify these indicators. To identify these most relevant topics, we studied relevant well-designed available literature (Ferreira et al., 2015) and conducted semi-structured interviews with patients and clinicians. Consequently, we defined the required content of the questionnaire. Based on discussions during meetings with the ‘ESM expert group’ at our institution, we formulated the questions and added questions regarding context and activities.

Results: See figure 1. Most of the questions intend to obtain subjective information about the burden of motor symptoms. Other questions focus on the current activity or company of the patient and on positive and negative affect. Patients will be instructed to answer the questions about how they feel at that moment. 

Discussion: First, the feasibility of this ESM method among PD patients has to be assessed, based on the percentages of completed questionnaires and the subjective experience reported by patients. This was only done once before in a pilot study by Broen et al. (2016). Second, we will have to analyze the data for internal validity. We aim to do this by looking at fluctuations within each question. There has to be a certain fluctuation between ‘symptomatic’ and ‘non-symptomatic’ moments in order to differentiate between them. Also, we will analyze the association between positive and negative affect and between affect and motor symptoms. We have to evaluate potential bias of positive or negative affect on the subjective judgment of motor symptoms.

When this ESM method seems feasible and valid in PD patients, continuousobjective measurements could be combined with semi-continuous subjective measurements. This could help to interpret the subjective burden of objectively measured symptoms. In this way, additional ESM monitoring could optimize possible therapeutic adjustments based on objective measurements.

Conclusion: We developed an ESM questionnaire specific to PD with the intention to detect subjective experience of motor fluctuations within and between days. The ultimate goal is to optimize the interpretation of objective measurements and optimize therapy adjustments. 

Broen et al, 2016: Unraveling the Relationship between Motor ..., PLoS One, 11(3).

Delrobaei et al, 2018: Towards remote monitoring of Parkinson's ..., J Neurol Sci, 384, 38-45. 

Ferreira et al, 2015: Clinical Parameters and Tools for ..., J Parkinsons Dis, 5(2), 281-290. 

Zhan et al, 2018: Using Smartphones and Machine Learning ..., JAMA Neurol.

 Objective

To report the clinical experience in our center (CINAC-HM Puerta del Sur) in the treatment of essential tremor (ET) with Magnetic Resonance guided Focused Ultrasound (MRgFUS).

 Background

 Patients suffering from medically-refractory and disabling ET can benefit from surgical treatments such as radiofrequency thalamotomy and thalamic DBS (1). The appearance of MRgFUS, an incisionless technique for lesioning deep brain structures without the need of surgery, has paved the way for the rebirth of ablative approaches for Movement Disorders. A recent double-blind sham-controlled randomized clinical trial has confirmed the safety and effectiveness of MRgFUS unilateral thalamotomy for the treatment of ET (2).

 Methods

 Patients with disabling ET that had not responded to at least two trials of medical therapy underwent unilateral VIM-thalamotomy with MRgFUS. Tremor severity was assessed through the Clinical Rating Scale for Tremor (CRST) at baseline, 1, 3, 6 and 12 months after treatment. The scale is divided into 3 parts: A) quantification of tremor at rest, with posture, and with intention in nine body parts; B) task performance; C) functional disability. A visual analogue scale for the assessment of overall quality of life (VAS-QUEST) (ranging from 0 to 100%, with higher scores indicating better perceived quality of life) was also given pretreatment and one year after procedure. Treatment-related adverse events were also registered. Paired T-test was used for comparison from baseline to last follow-up.

 Results

Tweny-one ET patients were included [table 1]. Total CRST score showed improvement from 54.9 ± 16.5 at baseline to 28.2 ± 18.4 at 12 months (mean reduction of 51.7 %). CRST-A score for the treated hemibody was reduced from 6.8 ± 2.4 to 1.7 ± 1.8 (75.6%). CRST-C score improved from 17.9 ± 4.6 to 5.6 ± 6.1 (72.1 %) [table 2]. The VAS-QUEST improved from 42.6 ± 21.1 before treatment to 68.3 ± 21.2 at last follow-up. The most frequent adverse event immediately after treatment was gait unstability (16 patients, 76%); which was moderate (lateralization and wide-based gait) in 5 cases. In one patient, mild ataxia (abnormal tandem gait) persisted at 1 year [table 3].

 Conclusions

Our results support previous evidence showing that MRIgFUS is safe and effective for the treatment of ET and allows improvement in daily living disability

References

1. Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol 2011;10(2):148-61.
2. Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016 Aug 25;375(8):730-9.

Objective

To describe the effect of VIM thalamotomy by MRI-guided Focused Ultrasound (MRIgFUS) on Multiple Sclerosis (MS) tremor in a single patient.

Background

Tremor is the most frequently described movement disorder in MS (from 25% to 58%¹ depending on the series) and can be medically refractory and highly disabling. Both thalamic deep brain stimulation and radiofrequency thalamotomy have shown to provide sustained benefit in selected patients². The recent development of MRIgFUS allows performing ablations in deep brain structures through an incisionless approach, reducing the risks related to surgery. This could be of special importance in already damaged brains, such as those of MS patients.

Methods

A 28-year-old female diagnosed with MS was selected for MRIgFUS VIM thalamotomy to treat right upper limb tremor refractory to medical treatment and highly disabling. Assessment was performed both at baseline and 3 months after treatment through the Fahn-Tolosa-Marin scale (FTM scale), as well as with EMG and accelerometer recordings.

Results

Abolition of tremor was achieved intraprocedure after initial therapeutic sonications. The benefit was sustained by three months, with a 81.8% of improvement in the score of the FTM scale for the treated hand (FTM part A= 11 at baseline vs 2 at 3 months). Accelerometer and EMG tremor recording supported the clinical improvement. After treatment, the patient was able to use her hand normally.  Mild-to-moderate dysarthria occurred after procedure, but it had practically resolved by 3 months.

Conclusions

This is, to our knowledge, the first report of a MS associated-tremor successfully treated with MRIgFUS thalamotomy. This poses a potentially new therapeutic option for MS patients suffering of tremor refractory to medical treatment.

¹Pittock S, McClelland R, Mayr W, et al. Prevalence of tremor in multiple sclerosis and associated disability in the Olmsted County population. Mov Disor. 2004; 19:1482-1485

²Schuurman PR, Bosch DA, Merkus MP, Speelman JD. Long-term follow-up of thalamic stimulation versus thalamotomy for tremor suppression. Mov Disord. 2008 Jun 15;23(8):1146-53.

Objective: The objective this report is to describe collected outcomes from a large scale registry of a Deep Brain Stimulation (DBS) system capable of Multiple Independent Current Source Control (MICC) in the management of symptoms of levodopa-responsive Parkinson's disease (PD). 

Background: The effectiveness of Deep Brain Stimulation (DBS) for reducing motor complications of Parkinson's disease (PD) has been substantiated by randomized controlled trials (Schuepbach et al.,2013). Additionally, motor improvement is sustained for up to 10 years (Deuschl et al. 2013). Large patient data registries may facilitate insights regarding real world, clinical use of DBS. Furthermore, no registry database currently exists for a multiple-source, constant current DBS system. 

Methods: The Vercise DBS Registry is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific Corporation. The Vercise DBS system (Boston Scientific) is a multiple-source, constant-current system. Subjects were followed up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms was evaluated. Clinical endpoints evaluated at baseline and during study follow included Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. 

Results: To date, 290 patients have been enrolled in the registry and this report will provide an overview of the data collected so far from implanted patients within this cohort. At 1 year post-implant, 36.2% improvement in MDS-UPDRS III scores (stim on/meds off) compared with baseline was reported. This improvement in motor function was supported by an improvement in quality of life as assessed by PDQ39 Summary Index (5.6 point improvement, n =146) at 1 year. Roughly 90% of patients and clinicians reported improvement as compared with Baseline. 

Conclusions: This DBS registry represents the first comprehensive, large scale collection of real-world outcomes and evaluation of safety and effectiveness of a multiple-source, constant-current DBS system.

Objective: The objective of this report is to assess the initial real-world outcomes using a directional lead with a Deep Brain Stimulation (DBS) system capable of multiple independent current source control (MICC) for use in managing symptoms of levodopa-responsive Parkinson's disease (PD). 

Background: Deep Brain Stimulation (DBS) systems have historically used ring-shaped electrodes that produce stimulation fields with limited control over field shape and volume of tissue activated. Directional current steering may permit a more personalized DBS approach with respect to individualized shape and pattern of electrical field and corresponding volume of tissue activated. Here we report initial real-world outcomes using a directional lead with a DBS system capable of multiple independent current source control (MICC) for use in managing symptoms of levodopa-responsive Parkinson's disease (PD). 

Methods: The Vercise DBS Registry is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific. Subjects in this cohort were implanted with a directional lead included as part of a multiple-source, constant-current directional DBS system (Vercise Cartesia, Boston Scientific). Subjects were followed up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms was evaluated. Clinical endpoints evaluated at baseline and during study follow-up included Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. Adverse events are also collected. 

Results: A total of over 100 subjects have been enrolled in this specific cohort. A 6.1 ± 12.11 (n = 73) point improvement was noted in the PDQ-39 Summary Index at the 6-month interval compared with Baseline and this improvement continued up to 1 year post-implant. Subjects, clinicians, and caregivers reported over 90% improvement in the symptoms at 6 months post-lead implant as compared with Baseline and this was maintained up to the 12-month interval. Additional data is to be presented. 

Conclusions:  Enabling fractionalization of current using MICC can permit the application of a well-defined, shaped, electrical field. Use of a directional lead allows for the steering of current in horizontal directions by combining segmented leads and MICC.

Objective: To evaluate impedance changes throughout the course of a programming visit as a part of a larger directional lead exploration study. 

Background: Historically, DBS systems have delivered stimulation using cylindrical electrodes, which may stimulate neurons around the entire circumference of the lead. In this study, we test a directional DBS lead, which adds radially segmented electrodes designed for selective stimulation in directions orthogonal to the lead trajectory. One of the considerations for this new technology is the impedance magnitude observed through the segmented contacts compared to the cylindrical contacts, as well as how these impedances change while the stimulation through the contact is adjusted. 

Methods: DIRECT-DBS is a prospective, randomized, multi-center, double-blind study employing a crossover design. A total of 12 subjects have been enrolled and implanted per standard of care with bilateral directional DBS leads (Vercise Cartesia, Boston Scientific) connected to a pulse generator providing an independent current source for each of 16 contacts. Impedance values through all of the contacts are taken at various time points throughout the course of each clinical visit. 

Results: Examination of the results collected thus far show significant differences in impedances; the average impedance on a ring contact was 1.24 ± 0.13 kilo-Ohms and on a segmented contact was 2.93 ± 0.49 kilo-Ohms, a 137% increase. The difference in impedance between segmented contacts within the same row was as large as 1.56 Ohms. The data also shows greater variability in impedance for contacts which are being actively programmed; the average range of impedances within a programming visit increased 41.8% for active vs inactive cylindrical contacts (28.7 to 40.8 Ohms) and 35.6% for segmented contacts (128.4 to 174.1 Ohms)

Conclusions: The observed variations in contact impedance would make programming directional leads with a voltage controlled system difficult. Moreover, the data shows that there can be differences in impedance on contacts within the same segmented row and that the relationship between these impedances can change over time, thus altering the volume of tissue activated, if a single current source is being used. The clinical relevance of these stimulation changes would need to be assessed in future clinical trials.

Objective: To evaluate changes in therapeutic window values for changes in directional Deep Brain Stimulation (DBS) stimulation.

Background: Historically, DBS systems have delivered stimulation using cylindrical electrodes, which may stimulate neurons around the entire circumference of the lead. In this study, we test a directional DBS lead, which adds radially segmented electrodes designed for selective stimulation in directions orthogonal to the lead trajectory. One way to show clinical proof of the additional capabilities of directional leads is to examine the therapeutic windows of varying directional stimulation settings. 

Methods: DIRECT-DBS is a prospective, randomized, multi-center, double-blind study employing a crossover design. A total of 12 subjects have been enrolled and implanted per standard of care with bilateral directional DBS leads (Vercise Cartesia, Boston Scientific) connected to a pulse generator providing an independent current source for each of 16 contacts. Visits occur in 3 major periods: during implant, at 3-5 months, and at 1 year. At 3 months, multiple single-day programming visits will be undertaken to optimize directional programming, based on observed clinical responses. In one of the visits, various directional stimulation settings are explored at the optimal longitudinal level, first in 90 degree increments, then in 30 degree increments. These fine explorations require precise fractionalization of the current between sets of segmented electrodes. At each of these settings, the therapeutic window is calculated as the difference between the minimum amplitude which gives full rigidity control and the minimum amplitude that elicits a limiting side effect. 

Results: Examination of the results collected thus far show differences in therapeutic windows at the various directional stimulation settings. These differences can manifest in changes as small as 30 degrees in the rotational direction. 

Conclusions: These results show that directional stimulation is a useful advancement in DBS technology as it may enable the user to elicit differential clinical responses which may not have been observed with other programming changes.

【PURPOSE】 This study aims to assess the efficacy of thalamotomy by magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) for refractory essential tremor (ET).

【SUBJECT and METHOD】 We examined 13 patients who were followed-up 1 year after undergoing ventral intermediate nucleus thalamotomy with MRgFUS for refractory ET, Clinical Rating Scale for Tremor (CRST), skull density ratio (SDR), maximum energy, maximum temperature, volume of coagulation spot, and their correlation at Ohnishi Neurological Center. We considered P < 0.05 as statistically significant.

【RESULTS】 We examined 13 patients (9 males and 4 females; mean age, 61.2 ± 11.0 years). The mean duration of the disease was 21.7 ± 15.0 years, and the mean SDR was 0.41 ± 0.05. The average maximum energy was 18.1 ± 9.0 kJ, the average maximum temperature was 56.8°C ± 1.7°C, and the average volume of the coagulation spot immediately after treatment was 62.2 ± 23.3 mm³. The average pretreatment CRST was 51.8 ± 16.5 points, which was considerably improved as 14.8 ± 7.2 (improvement rate, 71.6% ± 10.8%), 16.2 ± 12.5 points (improvement rate, 71.4% ± 16.5%) even after 1 year, and the effect persisted. After 1 year, we observed only one case with improvement rate <50%. In addition, only 1 patient experienced the numbness of the lips as a long-term complication. In cases with low SDR, the CRST improvement rate tended to be slightly lower. The higher the maximum temperature, the significantly increased the volume of the coagulation spot, but no significant correlation existed between them and CRST.
【CONCLUSIONS】 MRgFUS thalamotomy for ET is effective as well as the results of large-scale trials reported previously.

Neurosurgical interventions have been used to treat PD for over a century. We examined the changing landscape of surgery for PD to appraise the value of various procedures in the context of advances in our understanding and technology. We assessed the number of articles published on neurosurgical procedures for PD over time as an albeit imprecise surrogate for their usage level. We identified over 8,000 publications associated with PD surgery. Over half the publications were on DBS. The field of DBS for PD showed a rapid rise in articles, but is now in a steady state. Thalamotomy and, to a lesser extent, pallidotomy follow a biphasic publication distribution with peaks approximately 30 years apart. Articles on gene therapy and transplantation experienced initial rapid rises and significant recent declines. Procedures using novel technologies, including gamma knife and focused ultrasound, are emerging, but are yet to have significant impact as measured by publication numbers. Pallidotomy and thalamotomy are prominent examples of procedures that were popular, declined, and re-emerged and redeclined. Transplantation and gene therapy have never broken into clinical practice. DBS overtook all procedures as the dominant surgical intervention and drove widespread use of surgery for PD. Notwithstanding, the number of DBS articles appears to have plateaued. As advances continue, emerging treatments may compete with DBS in the future.

INTRODUCTION: Essential tremor is a common disease for elderly people that is observed in 5% or more of those aged over 65 years. In most cases, tremors appear in upper extremities. However, in 30% of patients, tremors appear in the head which can be a huge hindrance in daily life. Especially in patients of head tremor, even minor symptoms often affect social life and work. In this presentation, we discuss surgical cases of essential head tremor which is resistant to medication therapy with a case report and literature review.　

CASE DESCRIPTION: A 70-year-old woman developed lateral head tremor when she was 64 years old. Even though various examinations were performed at the previous hospital, the cause was unknown. Because the symptomatic improvement could not be achieved with alotinolol and clonazepam, she was introduced to our hospital and diagnosed with head tremor (no-no type). Deep brain stimulation in bilateral thalamic ventral intermediate nuclei (so-called Vim-DBS) was performed when she was 67 years old. The tremor improved rapidly after stimulation started. Mild dysarthria and dysphonia were recognized as postoperative complications, but they improved by adjusting stimulation. She has visited the outpatient for the following 3 years and the symptoms has been well controlled.

DISCUSSION: Essential tremor is one of the most common involuntary movements. The symptoms occur often in upper limbs, but head tremor can be observed in about 30% of patients. Medication therapy with beta blockers and clonazepam is commonly performed, but the effect is limited. Approximately half of the cases with medication therapy alone have only poor control. On the other hand, improvement rate with surgical treatment is extremely high. For tremors in the head and trunk, good control is proved with DBS targeting bilateral Vim. In this case, there is no recurrence of symptoms even in follow-up for 3 years after the operation, which suggests the possibility of long-term efficacy of bilateral Vim-DBS to head tremor.

Background: It is common to find VR spaces in basal ganglia of Parkinson’s disease patients. However, when it was found in the location of an intended target, a question arises about an alternate planning strategy and its influence on the postoperative outcome. Our study attempts to answer some of these questions. 

Methods: Eighty patients with idiopathic Parkinson’s disease underwent deep brain stimulation of bilateral sub-thalamic nuclei (STN) in a single centre. The MRI was done preoperatively which was fused with 3D CT acquired after frame fixation. The MR protocol had T2W and T1W contrast sequences in 3D axial acquisitions of 1mm thickness. It was our protocol to optimize the target by selection of target location lateral or medial to the VR space if the later was found in the intended target locations.  The MRI of all these patients were retrospectively analyzed by a Neurosurgeon and a Neuroradiologist, both unaware of the postoperative outcomes.  The clinical outcome was recorded as pre and post-operative Unified Parkinson’s Disease Rating Scale scores. This was compared between the groups of patients without VR space in STN (group A) and the group (B) with the abnormality.

Results: All eighty patients had VR spaces in the basal ganglia. The most common sites were the posterior putamen and external pallidal region (67). Other locations were substantia nigra (20), STN (18), internal pallidum (5) in the order of frequency. In 3 patients the abnormality was severe with ‘starry sky appearance’ of basal ganglia. The VR spaces of STN were classified into small (<2mm) (3) and large(>2mm) (15) based on size and based on locations, into the target (15 – group B) and other sites in STN (3). Only the results of those with an abnormality in target sites were compared with those without the abnormality.

All patients with these abnormalities correlated with advanced disease in terms of severity and duration with a minimum of 8 years (range 8 to 16 years). Mean UPDRS in the off stage of group A and B was 54.50 and 75.43 respectively, (P=0.04), and in on stage was 29.30 and 31.22, respectively (P=0.688). Postoperatively optimum UPDRS reached was 23.17 and 40.78 (P=0.207). Though the overall clinical outcome did not differ significantly, there was a tendency for suboptimal outcome in presence of VR spaces in STN (p=0.05) requiring multiple frequent visits for programming and long latency period for treatment response.

Conclusions: The influences on the postoperative outcome following deep brain stimulation are multifactorial. The suboptimal response noticed in our patients can be partly explained due to the influence of these fluid-filled spaces causing a variable distribution of electrical field. This possibility should be included as a crucial part of the counselling for patients having advanced disease with MRI showing these abnormalities.  

INTRODUCTION:

Dyskinesias are involuntary and uncontrolled movements that appear in Parkinson Disease (PD) patients and are typically related to long term levodopa use. Deep brain stimulation of the subthalamic nucleus has proved to be effective in the treatment of motor symptoms of PD and therefore in the reduction  of levodopa dosis postoperatively, which improves side effects as dyskinesias.

Directional stimulation allows steering current in horizontal directions and neurophysiological recordings through these segmented electrodes can be very useful to guide the stimulation parameters.

We present our results in 19 patients with PD implanted with directional leads and the correlation between beta activity power and postoperatively dyskinesias.

METHODS:

Between March 2016 and March 2018, 19 PD patients have been bilaterally implanted with directional segmented leads. None presented postoperative complications. Local field potentials were recorded from directional contacts and beta activity guided stimulation parameters. 

RESULTS:

From 19 patients, 85%  presented good clinical efficacy when stimulating with contacts with highest beta activity.  11 patients presented with early postoperative dyskinesias due to local field potentials stimulation parameters. In these 22 subthalamic nucleus, 17 contacts presented with dyskinesias while stimulating, and 11 of 17 contacts showed the highest beta activity power. In our serie, 65% of patients with dyskinesias during the first moth postoperatively were related to stimulation with contacts showing highest beta activity. We have considered post-operative stun effect as well as an important factor related to dyskinesias in early programming. Stimulation parameters had to be initially modified to avoid disabling dyskinesias. 

CONCLUSION:

Directional segmented leads have proved to increase therapeutic window and recordings of beta activity may help to alleviate early programming burden. In our serie we have found a correlation between power of beta activity in segmented leads and dyskinesias. We consider that this may be taken into account when early programming, as this can difficult initial selection of stimulation parameters.

Objectives 

Benign tremulous parkinsonism (BTP) is a unique subtype of Parkinson disease, characterized by a prominent both resting and postural tremor with some mild other parkinsonism.  The progression of symptoms is typically slow, and majority of them show poor response to L-dopa therapy.  From a point of functional neurosurgery, it is also quite challenging disease entity to see whether subthalamic nucleus (STN) deep brain stimulation (DBS) can alleviate even L-dopa resistant Parkinson symptoms.  The objective of this paper is to assess the clinical outcome of four patients with BTP who underwent DBS. 

Methods

 We encountered four patients (one female, three male) with BTP.  One of them received STN-DBS, but the others received thalamic Vim nucleus or posterior subthalamic area (PSA) DBS. 

Results

 Tremor of these patients were well controlled with either Vim, PSA and STN DBS, but the other parkinsonian symptoms showed very mind improvement after one of these DBS.  None of these DBS even STN-DBS were effective to gait or postural disturbance. 

Conclusions

 STN DBS were not so effective to the other Parkinson symptoms except resting tremor for the patient with BTP.  It revealed that STN-DBS are not effective to the L-dopa resistant symptoms even these are categorized as parkinsonism.  From these surgical outcomes, we deeply doubt BTP could be categorized to the subtype of Parkinson disease instead of tremor diseases. 

Introduction

The dentato-rubro-thalamic tract (DRT) has been described as a relevant DBS target for tremor control in the past. We report two patients who presented with a stimulation-induced progressive cerebellar syndrome consisting of gait ataxia, dysarthria and cerebellar tremor: A 76-year-old female with essential tremor (ET) with bilateral thalamic DBS of the DRT and a 73-year-old male with tremor dominant Parkinson’s disease (PD) with a combined bilateral DBS of DRT and subthalamic nucleus (STN). The cerebellar syndrome emerged approximately 10-12 months after surgery, while initial postoperative tremor control was excellent.

Methods

Two cerebral FDG-PETs were performed in both patients: 1.) with activated DRT-DBS and 2.) 72 hours after deactivation (stimulation of the STN still being active in the PD patient).  Voxel-based changes of normalized glucose metabolism as a marker of regional neuronal activity were assessed using a SISCOM-based analysis. The connectivity of activation (z-score > 2.5) and deactivation (z-score < -2.5) hotspots in conjunction with the volume of activated tissue (VAT) was determined by means of DTI-based global tractography using postoperative cranial computed tomography (for electrode positions) and preoperative MRI. Tremor analyses (Fahn-Tolosa-Marin-Tremor-Rating-Scale, FTMTRS) and a gait analysis (video based markerless motion capture system) was performed in both conditions and additionally immediately after deactivation of DBS. 

Results

PET analysis of the patient with ET showed increased neuronal activity bilaterally in the thalamus with activated DBS while activity in the left precentral gyrus increased upon DBS cessation. In contrast, the patient with PD showed higher neuronal activity in the left precentral region with activated DRT-DBS. Precentral activation hot spots on the left had a robust fiber connection with the ipsilateral volume of activated tissue in both patients (DRT, supplementary figure 1). Further regions with changes of neuronal activity on PET without detectable fiber connection to the VAT are listed in supplementary table 1. In the tremor analysis the ET patient showed an exacerbation of tremor immediately after DBS deactivation but with a partial recovery over 72 hours of paused stimulation. In contrast the patient with PD did not develop an exacerbation of tremor upon deactivation, with a slight improvement increasing over 72 hours. In the video based gait analysis we found an exacerbation of gait ataxia in the patient with ET directly after deactivation of DRT-DBS recovering over 72 hours. As a contrast the patient with PD showed a direct improvement of gait ataxia after deactivation of DRT-DBS, interestingly with a partial decline after 72 hours. 

Discussion

The management of stimulation-induced progressive cerebellar syndrome under VIM/DRT-DBS for tremor poses a major challenge in affected patients. Here we present two cases with a stimulation-induced progressive cerebellar syndrome under DRT-DBS that show contrasting results upon deactivation of DRT-DBS. On FDG-PET areas in the left precentral region with tractographic relation to the VAT were differentially activated across the patients. The origin of further regions with changes of neuronal activity without connection to the VAT is incompletely understood and may have been due to e.g. higher order connections, secondary (e.g. cognitive) effects or artefacts. The ongoing stimulation of the STN in the patient with PD across study conditions may additionally have contributed to the differential effects. The origin of the cerebellar syndrome under DRT-DBS might underly different pathophysiology, depending on the disease treated. Our results are preliminary due to the very small number of patients. However, they also highlight that different networks are involved in the pathophysiology of parkinsonian and essential tremor as well as in stimulation-induced progressive cerebellar syndrome. 

AIM
Optimal intracerebral electrode location is essential to alleviate symptoms after DBS surgery for movement disorder. With the advent of intraoperative MRI and CT scan, the information about the electrode precise location is becoming more reliable and could eventually replace the neurological examination performed during the surgery.  The aim of this study was to compare the relative value of the clinical examination to the intraoperative O-arm acquisitions merged with the preoperative MRI, to judge the best therapeutic effect of the electrode. 

METHODS and RESULTS
20 patients, 13 Parkinson Disease (PD) and 7 Essential Tremors (ET) were studied between 2015 and 2017. All PD and ET patients had an awake bilateral electrode implantation in the STN and VIM respectively.  In the STN the correlation between the clinical examination and the intraoperative images was observed in 25 over 26 electrode trajectories. In turn, in the VIM, the radio-clinical correlation was only observed on 11 electrode trajectories over 14. 

CONCLUSION
This study suggests that the prediction of a precise and effective electrode placement is better in the STN than in the VIM. This observation is certainly the result of the visualisation of the target. Indeed STN is well delimitated on a T2 MRI and can visually be targeted, which is not the case for the VIM, which is in most of the cases indirectly targeted.
In conclusion, if in the VIM, clinical testing remains essential for a correct electrode placement, in the STN, the use of O-arm fused with MRI is precise enough to open the question of the usefulness of the intra operative neurological examination. 

Introduction: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well-established treatment option for motor symptoms in advanced Parkinson’s disease (PD). However, the effect of STN-DBS on non-motor symptoms shortly after the operation and on follow-up has so far not been clearly established. 

Materials and Methods: This is a three-year follow-up, observational, exploratory study. The patients were evaluated pre operatively (ON and OFF medication), and 6, 12, 24 and 36 months thereafter (ON medication, ON stimulation), on scales for motor [MDS-UPDRS-III, Hoehn and Yahr  (H&Y) scale], and non-motor [Non-motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Beck’s Depression Inventory (MDI), Hamilton Anxiety Scale (HAS), Stark Apathy Scale (SAS), SCales for Outcomes in PArkinson's disease-Psychiatric Complications (SCOPA-PC), PD Sleeping Scale 2 (PDSS2)] symptoms/signs. PDQ39 was used to assess quality of life. Proximate improvement 6 months after the operation (pairwise t-test), and improvement on follow-up up to 36 months after the operation (Linear Mixed Model) was assessed. The level of significance was set to p=.05.

Results: In total, 35 consecutive bilateral STN-DBS PD patients (15 females, mean age at operation 58.3±7.3, mean disease duration 13.6,±4.4) were evaluated.  Six months after the operation, there was improvement of the motor condition as assessed by H&Y scale (p=.021), (but not MDS-UPDRS-III, p=.178), and overall improvement of non-motor symptoms as measured by NMSS, p=.019. In addition, there was improvement of depression (BDI, p=.023), anxiety (HAS, p=.013), psychiatric complications (SCOPA-PC, p=.007), sleeping (PDSS2, p=.003) as well as quality of life (PDQ39, p=.001). There was a trend towards increasing of apathy (SAS, p=.064). No change in general cognitive abilities was noted (MoCA, p=.723). On follow-up up to 36 months postoperatively, compared to 6 months after surgery, there was no further significant change on neither motor nor non-motor scales. 

Conclusions: six months after the operation, in addition to the motor improvement, there was also improvement of non-motor symptoms as assessed by NMSS, as well as improvement of depression, anxiety, psychiatric complications, sleeping, and quality of life. Albeit non-significant, after the operation, apathy showed a trend to increase; no change in cognition was noted. In addition, there was no change in neither motor, nor non-motor symptoms/signs and quality of life on follow-up, up to 36 months after the operation, suggesting that the improvement in both motor and non-motor symptoms ensues early after operation and remains stable thereafter. 

Background: While there is common consent to the efficacy of deep brain stimulation (DBS) to treat various neurological disorders, different methods of lead implantation are used along neurosurgical centres. Although electrophysiological tools such as microelectrode recording (MER) or macrostimulation (MS) during awake DBS surgery are widely applied, their concrete impact is controversially discussed.

Purpose: To systematically evaluate the impact of MER and MS on intraoperative lead placement in DBS.

Methods: We included 101 patients undergoing bilateral subthalamic nucleus DBS with MER and MS under local anesthesia for Parkinson’s disease in a retrospective observational study. We analyzed intraoperative weighted motor outcomes between anatomically planned (PSP) and definite stimulation points (DSP), lead adjustment rates, UPDRS-III and levodopa equivalent daily dose (LEDD) as well as the predictive value of intraoperative stimulation sites and adverse events (AE) up to six months postoperatively.

Results: Lead adjustment was performed in 47 of 101 patients and 65 of 202 implanted leads (59 due to MS, 6 due to MER results). Adjusted electrodes showed a significant improvement from initial insufficient response (18.08 mean ± 3.78% standard error mean vs. 31.47 ± 2.78%; p < 0.001) resulting in a number needed to treat of 9.6 per electrode. The intraoperatively identified optimal stimulation points still covered the active contacts in 87% after 6 months. Follow-up UPDRS-III (pre DBS ON/OFF 23.3 ± 1.1 vs. post DBS ON/ON 15.6 ± 0.8; p < 0.001) and LEDD (pre DBS ON/OFF 1262.3 ± 60.9 mg/d vs. post DBS ON/ON 487.7 ± 39.2 mg/d; p < 0.001) also improved significantly at 6 months. Stimulation or surgery related AE occurred in 15 patients including 4 intracranial hemorrhages (1 symptomatic). No correlation between AE, duration of surgery or number of stimulation sites was found.

Conclusion: Our findings strongly suggest that MER and MS have an important impact on the intraoperative decision of final lead placement. They prevent poor stimulation outcome in a substantial number of leads. The identified stimulations sites show a high predictive value for the optimal chronic stimulation target. Follow-up UPDRS-III results, LEDD reductions and DBS related AE correspond well to previously published data.

Introduction
This study aimed to evaluate a novel method of using Tissel fibrin sealant (Baxter Healthcare, Deerfield, Illinois, USA) to seal the burrhole during DBS electrode placement. One of the factors affecting accuracy in DBS surgery is intraoperative CSF leakage. There are different techniques used to overcome this issue but to our knowledge the method presented here using a sub- and epidural burrhole injection is not described before in the litterature.

Methods
We conducted a retrospective analysis of 20 consecutive patients. Re-operations were excluded. The mean patient age was 59,8 ranging 46,3-70,5. Females were 60 % of this cohort. The patients underwent bilateral DBS electrode implantation at the Department of Neurosurgery, Turku University Hospital, Turku, Finland. The targets were STN 70 %, GPi 20 % and cZI 10 %. Our standard procedure included the use of Tissel sealant after the placement of the guide tubes. The novel approach was designed to reduce CSF leakage during the procedure. The tip of a blunt needle was bent and inserted epidurally immediatelly after the opening of the dura. 1 cc of the fibrin sealant was injected during 360 degree rotation of the needle. The burrhole was the gently compressed for one minute for the sealant to cure. The guide tubes were then inserted throuh the sealant and the rest of the surgery was performed as before.

All patients were imaged intraoperatively (O-arm, Medtronic, Memphis, USA) after the insertion of the electrodes. The images were analysed using the Medtronic Stealth planning station (ver. 3.0.2 Medtronic, Memphis, USA) by 3D volumetric measurement. Volumes of air were determined from 1-millimeter axial slices within the limits of the inner cortex of the scull. The areas were determined manually without interpolation by investigators (JFr and THä). Artifacts caused by the electrodes were excluded.

Results 
The mean amount of postoperative air in the patient group (N=5) treated with Tissel gluea as sealant applied after the insertion of the guide tubes were 9,74 cc (SD 12,19) compared to 0,20 cc (SD 0,25) in the gyrusplasty group (N=15).

Conclusion
This novel technique shows in this study that the gyrusplasty group has markedly less CSF leakage. No adverse reactions or complications were observed. This technique can cause less brainshift due to almost no CSF leakage intraoperatively compared to standard use of fibrin glue as a sealant placed epidurally in the burrholes after insertion of the guide tubes.

Background: Choreoathetosis is common in patients with cerebral palsy, and medical treatment is mostly unsatisfactory. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has shown some effect, but there is still a need to optimize treatment strategies.

Objective: We aimed to assess, whether the thalamic ventral intermediate nucleus (Vim) might be an alternative DBS target in choreoathetosis.

Methods: Three patients with cerebral palsy and choreoathetosis underwent implantation of DBS electrodes concurrently in the GPi and Vim. Final selection of stimulation site and switches during follow-up with correspondent clinical outcomes were assessed.

Results: In one patient Vim was chosen as initial chronic DBS target. Since clinical benefit was not yet satisfying, stimulation was switched to GPi resulting in further clinical improvement (BFM: pre-OP 99.5, Vim 82.5, GPi 80). In one patient GPi was selected and kept on follow-up due to some therapeutic effect (BFM: pre-OP 132, GPi DBS 121). One patient with initial GPi stimulation was switched to Vim, but likewise did not improve significantly (BFM: pre-OP 142, GPi 140, Vim 134) and stimulation was discontinued.

Conclusions: The GPi still represents the most convenient DBS target in patients with choreoathetosis. Vim DBS did not show a relevant long-term benefit for daily life in our cohort. Further alternative DBS targets need to be considered in acquired dystonia .

Introduction: Pantothenate kinase-associated neurodegeneration (PKAN) is caused by mutations of the pantothenate kinase 2 (PANK2) gene. This neurodegenerative disease causes progressive generalized dystonia, which is intractable to medical treatment. Pallidal stimulation (GPi DBS) has been performed in selected cases with variable results.
Herein, we present early surgical results of two patients with PKAN, who were treated with GPi DBS surgery.

Patients and Methods: Two patients were clinically diagnosed with PKAN and screened for PANK2 mutations. They were classified according to age of onset and progression rate of the disease. DBS electrode leads were placed at predefined targets bilaterally to GPi with the use of stereotactic CT auto-fused with frameless magnetic resonance imaging (MRI). Final electrode positions were controlled with a CT scan and its fusion to the preoperative images again through the image fusion program. Then impulse generator was implanted and connected to the DBS electrode leads. The day after the surgery, the implanted impulse generator was turned on. The patients were clinically evaluated with the use of the Burke-Fahn-Marsden Dystonia Rating Scale-movement scoring system before and after surgery. Patients were then followed up in the outpatient clinic regularly.

Results: There were two male patients at the ages 9 and 27. One patient had the early onset type of PKAN and the other had the late onset type. Both patients clinically deteriorated during the past year; however, deterioration was more dramatic and sudden in the patient with early onset PKAN. There was an overall improvement in both the appendicular and axial symptoms of the two patients. No side effects were observed in either of the patients. Clinical improvement was limited in the patient with early onset PKAN.

Conclusion: GPi DBS is an established treatment of PKAN, especially for patients with prominent appendicular symptoms. However, improvement may be very limited in the rapidly progressive early onset type. Although the follow-up period was too short to draw any conclusions, early surgery performed before clinical deterioration may help to achieve better clinical results.

Deep brain stimulation (DBS) is a rapidly emerging area of clinical neuroscience and has evolved to be an effective intervention to treat neurological symptoms in patients with advanced Parkinson’s disease (PD) and other movement disorders. Yet, the underlying mechanisms behind its therapeutic and side effects are not completely understood. A good approach to gain more insights in the cellular and network effects of DBS would be by using transgenic mouse lines. Recently, a few studies have been done using DBS in mouse models of PD, which have led to speculations on mechanisms behind DBS. However, all DBS studies conducted so far in mice have been either acute or unilateral stimulation experiments. Long-term DBS studies, which could resemble the clinical condition, are lacking. The main reason for this is that mice have a small skull size and thin cranium, which makes it extremely difficult to chronically implant and externally connect them to stimulating devices.     

Therefore, we developed an approach to perform repetitive long-term DBS in freely moving mice. In our study, we implanted an in house custom made bipolar electrode bilaterally in the STN of mice that were treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) and healthy controls. Subsequently, we stimulated half of the animals with clinically relevant parameters 3-5 times a week with a duration of 20 minutes for 2 months. The stimulation parameters were adjusted to mice based on current density calculations and previous experience in our laboratory (current intensity 80 microampere, frequency 130 Hz, and pulse width 60 microseconds). To validate the effectiveness of the STN stimulation in mice, we performed an open field test.

We found that DBS of the STN significantly increases distance moved in the open field test for both the MPTP treated mice and healthy controls. Besides that, none of the mice had lost their electrodes. Taken together, these results show that our DBS implantation method and stimulation paradigm is a valid model for future studies regarding underlying mechanisms of DBS. 

Background and Objective     

Deep brain stimulation (DBS) within the pallidum represents the most effective treatment for primary dystonia. The effect of lead location on clinical improvements is still debated.

Methods         

18 patients (median age 49.5 years) with cervical (n= 11) and generalized dystonia (n= 7; n= 7; two DYT1 mutation carriers (MC), one DYT6 MC) have been implanted with electrodes for DBS of the pallidum. Mean and median follow-up was 7.9 and 8.5 years, respectively (range 3-11 yrs). Mean stimulation parameters were: 3.8 mA, 123 usec and 155 Hz. For patients stimulated in a constant voltage mode the applied current (mA) was calculated based on impedance and Ohm‘s law. Bipolar stimulation was performed on 4 leads. Patients were grouped into responders (>50% improvement in BFM-DRS or TWSTR), intermediate responders (25–50%) and non-responders (<25%). Magnetic resonance and computed tomography images of individual patients were coregistrated. The leads were automatically detected with 'Lead Localization' and anatomical objects were created using 'Anatomical Mapping' (software modules were provided by Brainlab, Munich, Germany). The anterior and posterior commissures were defined manually and the volume of tissue activated (VTA) was modeled by a proprietory algorithm developed at Brainlab (Munich, Germany).

Results

None of the patients experienced stimulation-induced side effects that had limited DBS programming. No adverse events from co-stimulation of the internal capsule were observed. All leads passed through the internal or external pallidum and extended into the subpallidal area. VTAs in responders (n=11), intermediate responders (n=3) and non-responders (n=4) intersected with the posterior internal and external pallidum and the subpallidal area. The internal capsule was practically excluded from the VTAs. The VTAs of non-responders and intermediate were contained within the range of VTAs observed for reponders and, thus, did not differ in their locations. The VTAs of responders and intermediate responders intersected with the internal pallidum to 28.5%, the external pallidum to 13.2% and the subpallidal area to 58.3%. Of note, in non-responders the overlap with the internal pallidum was higher (36.1%; external pallidum 6.0% and subpallidal area 57.9%). The average coordinates for all active contacts relative to the midcommisural point were: x= 21.4 mm, y= 4.1 mm and z= –3.3 mm. Average x, y or z-coordinates of responders and non-responders differed by ≤ 0.7 mm. Clinical improvment did not correlate with lead location in any of the three directions in space. In responders, the size of VTAs was moderately correlated (r= 0.57; p<0.01) with lead location in the anterior direction indicating that the stimulation parameters of more anteriorly located contacts were higher.

Conclusions

Lead locations at the latero-inferior margin of the posterior internal pallidum resulted in favorable clinical effects, but comparable lead locations were also found in non-responders. The VTAs of non-responders covered more of the internal pallidum than VTAs of responders. More than half of the VTAs intersected with the subpallidal area containing pallidothalamic projections. The absence of dysarthria may be explained by the fact that VTAs did not cover the internal capsule. Our data hint towards factors other than lead location that may be relevant for clinical improvement. 

Background

Hemifacial spasm (HFS), an involuntary movement disorder characterized by unilateral spasms of the muscles innervated by the facial nerve, is likely to cause social anxiety disorder due to its significant facial disfigurement and may have a significant influence on a patient’s health-related quality of life (HRQoL). The goal of this study was to assess the severity of social anxiety symptoms and HRQoL in a prospective study with three years of follow-up in twenty-five consecutive patients who underwent microvascular decompression (MVD) because of HFS.

Methods

Patients who underwent MVD from January to May 2015 were included in this study. Demographic data were collected before surgery. Clinical data, including the standardized measures of anxiety and depression (Hospital Anxiety Depression Scale, HADS), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and the severity of HFS were assessed before surgery, six months and three years after surgery. HRQoL data were also collected before surgery, six months and three years after surgery using the Korean version of the short form 36 (SF-36).

Results

Six patients (21.4 %) scored 60 or greater on the preoperative LSAS and were considered to have generalized social anxiety disorder (high-LSAS group). The duration of symptom was significantly higher in the high-LSAS group than in the low-LSAS group (7.8 ± 2.2 vs. 4.1 ± 2.6; p = 0.011). The high-LSAS group was more likely to have psychological comorbidities and had more impaired quality of life than the low-LSAS group at preoperative evaluation. Six months after MVD, a significant improvement, compared to preoperative scores, was observed for the total LSAS score (p = 0.007) and anxiety subscale score of HADS (p =0.012) in the high-LSAS group. Other significant improvements were also observed in role-emotional (p = 0.039) and mental component summary (p = 0.024) of the SF-36 in the high-LSAS group compared to the low-LSAS group. These improvements at short-term after surgery, are at least maintained over a 3-year follow-up period.

Conclusions

This study shows that HFS patients seem to gain benefits from MVD not only for their facial disfigurement but also for social anxiety symptoms that may be associated with mental health improvements in their quality of life for long-term follow-up period.

Impairments of gait and balance are among the most incapacitating and least well-understood symptoms of Parkinson's disease (PD). The high risk of fall-related injuries severely limits the ambulation and everyday independence of individuals suffering from such deficits.

Well-established therapies addressing Basal Ganglia dysfunction in PD, which for decades have been optimized to alleviate upper-limb deficits, are highly effective for the symptomatic treatment of motor signs. However, they often fail to improve, or can even aggravate, locomotor deficits. This failure is presumably due to important divergence in the nature and dynamics of the circuits involved in the control of leg function during gait compared to upper limb movements.

Here we aimed to understand the neural signatures underlying leg motor function and dysfunction, both during static isometric movements and across locomotor activities of daily living. We combined detailed biomechanical recordings of leg motor patterns in patients who underwent Deep Brain Stimulation (DBS) surgery, including whole-body kinematics and bilateral leg muscle activity, along with local field potentials (LFPs) recorded from the leg region of the motor cortex and Subthalamic Nucleus. We evaluated the correlates between neural and neurobiomechanical states across different locomotor tasks requiring varying levels of motor effort and voluntary control, both with and without DBS.

Our results highlight clear spatiotemporal cortical and subcortical neural signatures in LFPs that exhibit strong correlations with effort --and effort-related deficits-- for the different joints of the leg. Changes in beta and gamma bands showed consistent modulations at well-defined phases of the gait-cycle, which strongly correlated with the amount of propulsion and vigor exerted during locomotion. In turn, these signatures help predict gait impairments.

There results shed light on the neural dynamics underlying gait deficits on patients with PD, and hold promises to open new avenues for the development of targeted neuromodulation strategies that effectively address these deficits using closed-loop control systems.

(Funding: the European Union H2020 Marie Sklodowska Curie Action -- MSCA-IF-2017-793419).

Objetive; to determine the practicabillity of using an image guide programming setting in our clinical practice.

Background;The applicability of DBS leads and systems that allow a more precise and accurate deliver of current to therapeutic targets is still unkown .Directional DBS promises several advantages: reduced adverse effects and elimination of manual programming. However, these has not been completely achieved yet. And nowadays the challenge is to effectively and rapidly program these devices.

Methods: 5 patients ( 4 Parkinson and 1 esential tremor) were bilaterally implanted with directional leads (Vercise cartesia ™ Directional Lead) ; PC ( 1 IPG) and Vercise Gevia™ (4 IPG) , Boston Scientific, Marlborough, USA) in the subthalamic nucleus (STN) ( 4PD patients) and Vim (ET patient) between May/2017 and February/2018. They underwent an extended programming session of their DBS system in the practically defined medication off state ( PD patients)(> 12 hours of medication withdrawal) 3 to 5 days (mean,3.2) postsurgery. The programming session was scheduled when the stun effect of electrode placement was decreasing.

The programming session followed the procedure of a standard monopolar review, in which for each electrode configuration current thresholds are determined for complete rigidity and bradykinesia control and the first adverse event limiting further current increase.

Different stimulation directions at each level were tested by restricting cathodal current to each of the three segments, on both segmented contacts.

Brainlab Elements will be used considering the synergy with GUIDE XT , as Guide XT CE clearance is expected in the next few weeks. This will allow us to compare our manual programming with a patient-image guide programming.

Results: Will be pressented at the congress

Conclusions: More studies are needed to analyze the applicability of directional DBS. Focusing on the fact that longer programming session might be needed initially, does not give justice to the oportunities that we may be able to offer to our patients with directional steering of the therapeutic  current.

Nowadays the challenge is to effectively and rapidly program these devices.

BACKGROUND Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s Disease (PD) is a highly effective surgical treatment. During surgery, test stimulation with the microelectrode tip is often performed to select optimal trajectory and depth to implant the definitive lead. After surgery, a systematic monopolar contact review is performed in a similar way in order to select the best electrode. It is unknown whether results of intraoperative testing are comparable to the results of the postoperative contact review and can thus be used to identify the best electrode for chronic stimulation.

AIM To compare results of intraoperative and postoperative stimulation in order to evaluate the potential predictive value of intraoperative test stimulation and thus make the postoperative testing more efficient and less time consuming.

METHODS All consecutive PD patients who received STN DBS at the Haga Teaching Hospital / Leiden University Medical Centre DBS centre between September 2012 and December 2017 were retrospectively analysed. Intraoperative stimulation was performed using the microelectrode’s stimulation tip (semi-microstimulation). Postoperatively, the electrode for chronic stimulation was chosen based on the results of the standard monopolar contact review. The threshold for optimal improvement of rigidity, the thresholds for both capsular and non-capsular side-effects, and the width of the therapeutic window between stimulation at the selected electrode and stimulation at the corresponding intraoperative depth were compared using survival analyses. The therapeutic window was defined as the difference in amplitude between the threshold for optimal improvement of rigidity and the threshold for debilitating side-effects and was compared between intraoperative and postoperative stimulation using Wilcoxon signed ranks test.

RESULTS 192 patients were operated in the selected period. After exclusion due to other indications or targets (n=47) or missing standard operating records (n=26), 119 patients (mean (SD) age 60.5 (6.5) years, 31.9% female) remained. All patients received bilateral STN DBS. The intraoperative depth with the largest therapeutic window corresponded in 34% of cases to the postoperative selected electrode and in 41% of the cases to the immediate dorsal electrode . The intraoperative depth with the lowest threshold for rigidity corresponded in 38% of cases to the selected electrode and in 34% to an immediate dorsal electrode. Postoperatively, capsular side-effects were induced at higher stimulation intensity than during intraoperative stimulation (Hazard Ratio (HR) 1.45 (95% Confidence Interval (95%CI) 1.14 – 1.84), whereas the threshold for optimal relief of rigidity showed a similar trend that did not reach significance (HR 1.17, 95% CI 0.90-1.50). The threshold for non-capsular side-effects was not significantly different between intraoperative and postoperative stimulation (postoperative vs. intraoperative stimulation HR 0.80, 95%CI 0.50-1.29). Likewise, the size of the therapeutic window was not significantly different (p=0.899).

CONCLUSION In the majority of cases, intraoperative stimulation may identify the optimal final electrode or the immediate dorsal electrode, thereby reducing the postoperative search space for the electrode to use for chronic stimulation. Induction of capsular side-effects occurs at higher stimulation intensities during postoperative stimulation than during intraoperative test stimulation, whereas relief of rigidity and induction of non-capsular side-effects occurred at similar stimulation intensities. The observed differences between stimulation through the microelectrode and stimulation through the definitive lead could be explained by differences in Volume of Tissue Activated (VTA) or different interaction of electric fields within the VTA with different fibres. Prospective studies are needed to confirm our findings.

Introduction

In STN-DBS for Parkinson’s Disease (PD) positioning of electrodes remains a challenge.

As well indirect targeting with X Y Z coordinates as direct MRI visualization prove insufficient to obtain a satisfying accuracy.

Considering interindividual variability in location, shape, dimensions, and iron content of the STN, a 3D-atlas can improve planning of the trajectory.

Materials  and methods

Since 2017 we implanted multidirectional 8 contact electrodes (Cartesia®,  Boston Scientific),  bilateral in the STN of 23 consecutive patients, using anatomical target planning with  the 3D Brainlab Atlas®), functional positioning verification with Micro-Electrode Recording (MER),  awake macrostimulation evaluation (Micro-macro-electrode® Inomed) with postoperative Atlas-based verification of lead positioning.

The preoperative stereotactic planning was performed combining coordinates calculation, direct MRI  STN visualization and optimalization with a 3D-Brain-Atlas, tailored to the shape of the patient’s brain (segmented ellipsoidal 3D-print).

The intraoperative anatomical data (virtual projection of the electrode) were compared  to the MER and clinical macrostimulation results .

Postoperatively, depth and location in regard to STN-somatopy and surrounding structures were defined; moreover, the direction of the multidirectional electrode marker was determined with a novel method, based on CT-artifacts.

Results

Using our methods we optimized the trajectory and positioning of the split contacts within the postero-supero-lateral STN, allowing steering of current  regarding STN somatotopy, the location of the distal contact in the Substantia Nigra  effective in gait freezing and of the proximal contact in the Zona Incerta, effective in tremor reduction.

We found a significant reduction in side effects between the ring and directional stimulation (p < 0,019).

Conclusion

Combination of optimal anatomical data using 3D Brain-Atlas, functional verification (MER-macrostimulation) and tridirectional stimulation with anatomical reverification improves the results of STN DBS.

Background

Replacement of implanted pulse generators (IPG) for deep brain stimulation (DBS) requires meticulous dissection of overlying soft tissues to avoid damage to surrounding extension leads. The PEAK (Pulsed Electron Avalanche Knife) PlasmaBlade^TM (Medtronic Inc., Minneapolis, MN, USA) is a novel low-thermal-injury electrosurgical device that uses high frequency pulses of radiofrequency energy to precisely cut and coagulate soft tissues. Unlike the traditional monopolar electrosurgery device which is contraindicated in this procedure, PlasmaBlade’s design and functionality minimises the risk of damage to hardware, i.e. IPG and extension leads, or transference of energy to tissues via hardware, allowing contact of the tip of PlasmaBlade to the IPG or extension leads when dissecting the surrounding soft tissues. PlasmaBlade therefore facilitates quicker operation and decreased bleeding compared to conventional sharp dissection techniques. In our unit, replacement of IPG is usually performed under local anaesthesia and PlasmaBlade device is routinely used. Despite its reported safety, patients can experience adverse clinical symptoms with PlasmaBlade use, during IPG replacement procedure under local anaesthesia.

Methods

We conducted a retrospective single-centre analysis of patients who underwent IPG replacement under local anaesthesia, to evaluate the occurrence of adverse clinical symptoms with PlasmaBlade use.

Results

30 patients underwent IPG replacement with PlasmaBlade under local anaesthesia between September 2016 to May 2018. Mean age was 64.2 years and 19 patients (63%) were male. DBS targets were subthalamic nucleus in 23 patients (76.7%), ventral intermediate nucleus (VIM) of thalamus in 5 patients (16.7%) and globus pallidus interna (GPi) in 2 patients (6.7%). IPG replacement procedure was done under local anaesthesia alone in 23 patients (76.7%) and local anaesthesia plus conscious sedation in 7 patients (23.3%). PlasmaBlade 4.0 device on cutting mode only, at power level 3 to 5 was used in these cases.

5 patients (16.7%) experienced adverse clinical symptoms, namely electric-shock like tingling sensation during the procedure when PlasmaBlade was used. PlasmaBlade was abandoned and soft tissue dissection completed with sharp dissection in these patients. Among the 5 patients, 3 had bilateral subthalamic nucleus DBS for Parkinson’s disease, 1 had left GPi DBS for dystonia and 1 had left VIM DBS for dystonic arm tremor. Indication for IPG replacement was battery depletion in all 5 patients. These 5 patients had their original DBS system implanted before 2008. Since 2008, the newer Medtronic extension leads (model 37086) have been used in our department. Kinetra (Medtronic Inc., Minneapolis, MN, USA) was the IPG device needing replacement in all these patients.

There were no occurrences of hardware damage, haematoma or wound infection in all patients.

Conclusion

PlasmaBlade is a useful surgical tool for IPG replacement. However, with the procedure performed under local anaesthesia, use of PlasmaBlade can cause adverse clinical symptoms in patients. Clinicians should be wary of PlasmaBlade use in patients who have their DBS system implanted before 2008, and forewarn them of potential adverse symptoms.

Deep brain stimulation (DBS) is used for symptomatic treatment of movement disorders. In many centers, the optimal DBS position is identified by intra-operative stimulation tests, which are performed at several positions along the planned trajectories toward the target structure with various stimulation amplitudes. The aim of the study was to propose a methodology summarizing all available intra-operative data of different patients to an atlas to provide targeting guidelines in the thalamus.

Data was collected for 8 patients (6 Essential Tremor, 2 Parkinson's Disease) who underwent bilateral implantation toward the ventral intermediate nucleus (Vim) (16 trajectories). Stereotactic MRI (T1, WAIR [1]; 1.5T, Siemens Sonata) were acquired prior to DBS surgery. An acceleration sensor was mounted on the contralateral wrist of the patient during intraoperative test stimulation to quantify tremor improvement. Written informed consent was obtained from the patients (ref.: 2011-A00774-37/AU905). A conductivity model of each patient's brain was derived from the intensity values of the T1 image. Finite element simulations were performed using these models for the positions and amplitudes (between 0 and 3 mA) with the best improvement. A 0.2 V/mm isolevel [2] was used to visualize the electric field. Improvement maps of each patient’s brain were visualized by affecting to each voxel in simulation results the maximum improvement measured. These maps were further enhanced by 14 subthalamic structures per side labeled by the neurosurgeon [3]. The resulting Improvement Map was visualized together with the patients' anatomy and the implant position providing a summary of the intraoperative testing [4]. An example view of this visualization is presented in Figure 1. In order to proceed to group analysis, a normalization pipeline for the improvement maps was designed as a two-step process: the first step uses the MNI152 template [5] and tools from FSL [6] to proceed to an initial linear registration. The T1 image for each patient was aligned and then registered to the MNI template. The WAIR image was then aligned to the aligned T1 and the registration transformation was applied. Both transforms were also applied to the anatomical structures. A result of this first normalization is presented in Figure 2 for the ventro intermediate nucleus (Vim). Those results show the necessity of a finer registration step, allowing local displacement of voxels in order to provide a better definition of the anatomical labels after normalization. In the second step, several normalization templates as well as non-linear group registration tools were evaluated in order to obtain the best probabilistic definition of the labeled sub-thalamic structures after application of the disformation field. Future work will focus on transferring the improvement values and spatial distribution of the electric field to the anatomical atlas to create an improvement atlas, and select appropriate statistical methods to visualize it. The atlas will present a summary of the complete patient pool, to be used as an assistance tool during planning. As the number of patient increases, this type of atlas will help analzing the mechanisms of action.

[1] F. Vassal et al., “Direct stereotactic targeting of the ventrointermediate nucleus of the thalamus based on anatomic 1.5-T MRI mapping with a white matter attenuated inversion recovery (WAIR) sequence,” Brain Stimulat., Oct. 2012.

[2] M. Åström, E. Diczfalusy, H. Martens, and K. Wårdell, “Relationship between Neural Activation and Electric Field Distribution during Deep Brain Stimulation,” IEEE Trans. Biomed. Eng., Feb. 2015.

[3] J.-J. Lemaire, L. Sakka, L. Ouchchane, F. Caire, J. Gabrillargues, and J.-M. Bonny, “Anatomy of the Human Thalamus Based on Spontaneous Contrast and Microscopic Voxels in High-Field Magnetic Resonance Imaging:,” Oper. Neurosurg., Mar. 2010.

[4] A. Shah et al., Improving DBS targeting using 3D visualization of intraoperative stimulation tests, vol. 94. European Society for Stereotactic and Functional Neurosurgery (ESSFN), 2016.

[5] G. Grabner, A. L. Janke, M. M. Budge, D. Smith, J. Pruessner, and D. L. Collins, “Symmetric Atlasing and Model Based Segmentation: An Application to the Hippocampus in Older Adults,” in Medical Image Computing and Computer-Assisted Intervention, 2006.

[6] S. M. Smith et al., “Advances in functional and structural MR image analysis and implementation as FSL,” NeuroImage, Jan. 2004.

Introduction :

Gait and balance disorders resistant to dopamine medication and subthalamic nucleus deep brain stimulation (DBS) occur in advanced Parkinson’s disease (PD), which are associated with falls resulting in high morbidity and mortality. There are currently no effective treatments available for these symptoms. Experimental data in a number of species implicates the pedunculopontine nucleus (PPN) in the pathophysiology of gait and balance disorders. The PPN is located in the lateral mesencephalon, ventral to the cuneiform nucleus, and these two nuclei forming the mesencephalic locomotor region (MLR). PPN-DBS was proposed in 2005 for treating gait and balance disorders in advanced PD. Altogether, the results of clinical trials from different teams have proved heterogeneous and disappointing, and differences in targeted brain areas make it difficult to determine whether there exists an optimal brainstem target for treating gait and balance disorders. We recorded MLR neural modulations in PD patients during a virtual gait task in order to characterize spatial differences in activity changes, and to relate these to the distribution of cholinergic neurons obtained from postmortem human brainstems.

Materials and Methods

We recorded local field potentials (LFP) postperatively in 4 PD patients with dopamine-resistant gait disorders and falls operated for PPN-DBS. The patients performed a virtual gait task in which they were asked to imagine walking down a hallway with the help of a movie showing their progress in a virtual environment. Patients performed the task both OFF- and ON-dopamine medication. Time-frequency maps were calculated using a multi-taper algorithm. The contacts of the definitive electrode were localized in each patient by registering the postoperative helicoidal CT and the preoperative MRI. We also registered histological data (density of PPN cholinergic neurons) obtained from postmortem studies in non-PD controls to examine the relation between neural modulations and regions of peak cholinergic cell density.

Results

Our results show an increase of power in the alpha and low beta frequency band during imagination of gait. This pattern of activity was mostly observed in the dipoles located closest to the peak density of cholinergic neurons in the PPN.

Conclusion :

Our data show that the caudal PPN, that is the region with the highest cholinergic density, is a region where neural activity is modulated during imaginary locomotion. Our data suggest that the caudal PPN may be an effective target for modulating locomotion in parkinsonian patients.

Introduction

Accurate placement of deep brain stimulation electrodes with the intended target is believed to be a key variable related to post-operative outcomes.  However, methods with which to perform and verify electrode localisation based on neuroimaging data are not universally established. The aim of this study was to determine the applicability of applying post-op lead localisation to a standard clinical pathway using routinely acquired MRI data and open source software.  

Methods

A retrospective cohort study was performed of a consecutive series of patients with Parkinson’s disease that underwent deep brain stimulation of either the GPi or STN between 2016 and 2017. Surgery was performed as a single stage procedure under general anaesthesia with implantation of electrodes by either St Jude/Abbott, Medtronic or Boston. Planning was performed using Medtronic® FrameLink software based on pre-operative 3 Tesla MRI data (MPRAGE and SWI sequences) with stereotactic atlas references of the relevant nucleus. A Leksell frame was used in combination with pre-operative and post-operative volumetric CT imaging for trajectory planning and verification, respectively. Image processing was performed using the Lead-DBS toolbox in combination with diffeomorphic to a standard space template, semi-automated electrode reconstruction, finite element model reconstruction of stimulation fields, and visualisation on the DISTAL subcortical nucleus atlas. Image processing was performed on a high performance computing cluster. Institutional ethical approval was granted as a review of service study.

Results

In total 28 participants (17 STN, 11 GPi) met the inclusion criteria (12 female). Mean age was 63 years, mean disease duration was 12 years, and mean follow-up was 11 months. A single device infection occurred and the patient was excluded from the analysis but there were no neuropsychiatric or other complications. Image processing errors were present in 5 participants (4 registration failures and 1 incomplete dataset) that required exclusion from analysis, resulting in a total analysed cohort of 22 participants (14 STN, 8 GPi). Clinical outcomes included an average improvement in UPDRS part III (motor scores) of 50% an average improvement in PDQ3 quality of life scores of 26%. Electrode localisation revealed accurate placement in the target nucleus in 39 of 44 electrodes. Mean distance from target to nucleus was 0.47 (+/-0.65) mm.

Conclusions

Electrode implantation under general anaesthesia with indirect targeting results in clinically meaningful improvements in validated outcomes, comparable with published studies using various alternative methodologies. Clinical outcomes are corroborated by accurate electrode placement, verified using histological atlas and subcortical nucleus reconstructions. Image based electrode localisation is feasible in routine clinical practice, using standard neuroimaging data, but requires additional time and computational resources. Future clinical applications of this pathway include prospective quality assurance of electrode location and quantitative audit of amendments to clinical care pathways, for instance refinements in surgical implantation technique. Ultimately, incorporation of electrode localisation data is likely to be a core component of strategies to facilitate individual direct target planning and optimisation of programming to further refine patient outcomes. 

Radiofrequency thalamotomy provides excellent and sustained clinical results in patients with tremor dominant movement disorders.

This study correlated lesion size on post-operative MRI with radiofrequency heating parameters (temperature and time) and evaluated MRI changes in lesion size and connectivity from 2-4 weeks after surgery to six months' follow-up.  T1, T2, FLAIR, FGATIR, DWI and DTI imaging was used for this purpose and Brainlab Elements fibre tracking and volume of tissue activation software to correlate heating parameters to lesion size.

We present the results of four patients who underwent thalamotomies for tremor performed by a single surgeon at a single centre during an eight month period. Three patients had Parkinson's disease and one patient had essential tremor. We present the indications, outcome and complications and discuss the results with a literature review and comparison with Gamma Knife and ultrasound and contextualisation with regard to deep brain stimulation.

For decades, Deep brain stimulation (DBS) has been applied to reduce motor symptoms and improve life-quality in patients suffering from Parkinson’s disease (PD). In common clinical practice, optimal stimulation settings are manually defined to minimize motor symptoms requiring time-consuming, trial-and-error testing by experienced neurologists. While this procedure has been widely successful in addressing easily measurable motor symptoms, it is unfit to detect non-trivial dysfunctions of non-targeted neural circuits that lead to stimulation-induced side effects. Quantification of the dynamics of the targeted circuits and their response to stimulation could offer a new tool to minimize common cognitive and motor side effects and improve therapeutic efficacy. To date most of these quantification have been restricted to single-site measurements, commonly from deep structures. However, mounting evidence suggests that subthalamic nucleus (STN) DBS results in antidromic activation of the cortex with a critical effect on the reduction of pathological cortico-STN coherence. We thus hypothesize that coupling cortical to subcortical recordings might be better suited to cope with the dynamic cortico-thalamic nature of PD symptoms and the effects of STN-DBS.

To test this hypothesis, we recorded superficial cortical activity using electroencephalography (EEG), pre- and post-DBS implantation, with multiple stimulation configurations in PD patients. We found a significant increase in the power of beta oscillations in the fronto-central area as compared to a group of control healthy subjects. During therapeutically effective STN-DBS, the cortical beta-band increase was reversed by stimulation and the level of reductions of the abnormal cortical oscillations was proportional to the amount of improved motor symptoms measured by UPDRS. Instead, ineffective stimulation patterns resulted in unchanged cortical oscillations suggesting that the efficacy of STN-DBS correlate with specific cortical activation patterns.  All the brain activity patterns elicited by STN-DBS could be reliably captured by superficial electroencephalography. We then designed a patient-specific computational model of STN-DBS, which included representations of axonal pathways derived from Diffusion MRI. Simulations confirmed projection of stimulation effects to frontal cortical structures that correlated with the beta-band changes that we observed. These findings confirm our hypothesis that cortical circuit dynamics is profoundly influenced by DBS therapy and should thus be considered for quantitative optimization of stimulation parameters. We are currently combining these superficial cortical recordings with local-field potential recorded from the STN to further explore cortico-STN dynamics. The identified cortico-STN stimulation biomarkers would offer a clinically viable tool to optimize DBS therapies minimizing non-trivial dysfunctions of non-targeted neural circuits. 

Thalamic deep brain stimulation (DBS) is the dominant neurosurgical therapy for medically refractory essential tremor (ET). Atlas-based thalamic segmentation and computational models of volumes of tissue activation (VTA) have improved understanding of structure-function relationships between DBS lead locations, stimulation parameters, and clinical efficacy. Atlas-based approaches normalize anatomic variability among patients, providing explanations that hold for the study population as a whole. However, individual patient findings may prove difficult to explain with the atlas-based approach. In this study, we present the first fully individualized, atlas-independent methodology for thalamic segmentation and VTA modeling in DBS. Atlas-independent thalamic segmentation and VTA calculations were performed for 10 patients, using individual 3T diffusion tensor magnetic resonance imaging (DTI) datasets, a modified k-means clustering algorithm, and individual patient conductivity tensor fields. Atlas-independent models were compared to results for the same 10 patients obtained using a traditional atlas-based approach. Both methods provided reliable results across the study population. Centroid locations for 9 of 13 thalamic nuclei were statistically invariant between atlas-independent and atlas-based segmentations. The centroids of 4 remaining nuclei showed statistically significant differences between individualized and atlas-based localization. All 10 atlas-independent VTAs at clinically determined stimulation settings were localized to the motor thalamus. By contrast, only 9 out of 10 atlas-based VTAs overlapped with the motor thalamus. Differences in explanatory power between the two methods were most striking in subjects whose thalamic anatomy differed significantly from the atlas. We conclude that while traditional atlas-based thalamic segmentation and VTA modeling provide a reliable means of DBS targeting and mechanistic study, improved precision may be possible with an atlas-independent approach based on individual DTI data.

Objective: To precisely predict optimal subthalamic deep brain stimulation (STN DBS) activation regions for treatment of Parkinson disease (PD) by identifying associations between electrophysiological activity and regions of therapeutic tissue activation.

Methods: Atlas-independent tissue activation models of 23 STN DBS implants across 16 PD patients were generated using tissue properties derived from 3T diffusion tensor MRI and clinically determined DBS programming parameters. Electrophysiological features from 641 deep brain sites were extracted from microelectrode recordings obtained during lead placement surgery and then mapped to tissue activation models via direct visualization of the STN and DBS lead. LASSO regression techniques identified several predictive single and cross-frequency features that mapped to clinically effective stimulation sites. A support vector machine using these features was then used to predict the regions of clinically effective tissue activation.

Results: Logistic LASSO identified seven electrophysiological predictors of therapeutic VTAs: alpha, beta, high gamma, high frequency band (HFB), alpha x beta, beta x HFB, and high gamma x HFB. A support vector classifier using these features could predict therapeutic sites of activation with 83% sensitivity and 77% specificity in a test set of six implants. A probabilistic predictor achieved 0.89 AUC with the test data using this machine-learning methodology.

Conclusion: Our study suggests novel electrophysiological features of therapeutic activation regions that can be used to predict optimal STN DBS locations and amplitudes to facilitate DBS programming.

Aim: To determine the stereotactic location of kinesthetic cell clusters within the STN and examine their potential role in predicting clinical outcome of DBS.

Background: During stereotactic STN-DBS procedures in the awake patient, microelectrode recording (MER) may be used to determine the electrophysiological target. Kinesthetic cells can be identified to confirm the location of the microelectrode in the sensorimotor (dorsolateral) part of the STN. Despite this common intraoperative practice, it is not known if the presence of kinesthetic cells predicts a good clinical outcome.

Methods: we retrospectively investigated the clustering of kinesthetic cells within the STN by averaging the corresponding stereotactic coordinates on 3 Tesla MRI (T2 and SWI sequences). In order to minimize bias due to interindividual anatomical variability, we used the medial STN border as an alternative point of reference, and compared it with the standard point of reference (midcommissural point, MCP). The stereotactic coordinates of the medial STN border were determined by finding the maximum diameter of the Red Nucleus (RN) in the axial plane and draw a line perpendicular to the AC-PC line, coinciding with the anterior border of the RN (Bejjani’s line) and intersecting with the medial STN border on axial and coronal planes. Subgroups of arm-related, leg-related, and mixed kinesthetic cell clusters were created, as well as a group of non-kinesthetic cells. We will calculate the Euclidean distance between the center of the theoretic kinesthetic cell cluster and the center of the active DBS contact, and correlate the results with the Levodopa Equivalent Daily Dose (LEDD) reduction at one year follow up with adjustment for age, disease duration, pre-operative Levodopa responsiveness, and contralateral Euclidean distance between the theoretic kinesthetic cell cluster and the center of the active DBS contact (in bilateral STN DBS cases). In this, LEDD reduction is used as a surrogate endpoint of clinical effectiveness, as this objective measure is available in all cases.

Results: our preliminary data show a kinesthetic cell cluster at 3.5±1.1 mm lateral, 1.1±1.4 mm anterior, and 2.0±2.0 mm to the medial STN border on T2 imaging. On SWI imaging, this cluster is found at 3.8±1.5 mm lateral, 1.1±1.4 mm anterior, and 3.1±1.9 mm superior to the medial STN border. Using the MCP as a reference, a cluster is seen at 12.2±1.1 mm lateral, 1.3±1.5 mm posterior, and 1.8±1.8 mm inferior to MCP. Arm-related cells cluster latero-anterosuperior to leg-related cells (3.7±1.1 mm lateral, 1.3±1.3mm anterior, and 2.3±1.9 mm superior to the medial STN border on T2 for arm-related cells, compared to 3.0±1.0 mm lateral, 1.1±1.3 mm anterior, and 1.8±1.7 mm superior to the medial STN border for leg-related cells). Similar distribution patterns of arm- and leg-related cells were found on SWI and using the MCP as reference point (data not provided). Non-kinesthetic cells averaged at 3.2±1.9 mm lateral, 0.8±1.7 mm anterior, and 1.4±2.4 mm superior to the medial STN border on T2, and at 3.6±2.2 mm lateral, 0.6±1.7 mm anterior, and 2.4±2.2 mm superior to the medial STN border on SWI. Relative to the MCP, stereotactic non-kinesthetic cell coordinates averaged at 12±2.2 mm lateral, 1.9±1.6 mm posterior, and 2.7±2.1 inferior. The preliminary data were extracted out of 25 cases of STN-DBS surgery, comprising of 23 left and 24 right brain-side DBS lead placements. Eighty-seven arm-related, 65 leg-related, and twenty-four mixed arm/leg cells were included.

Conclusion: overall, our preliminary results show a clustering of kinesthetic cells within the STN latero-anterodorsally compared to non-kinesthetic cells within the STN. Arm-related cells cluster more laterally within the STN and leg-related cells more medially. These results are in concordance with the current available literature on the STN topography. Using the medial border of the STN as an alternative point of reference, our data were corrected for the relative position of the STN across individuals. Further analysis of the Euclidean distance from the center of the kinesthetic cell cluster to the center of stimulation (i.e. active DBS contact) and the correlation with the LEDD reduction at one year follow up will provide essential insight in the role of kinesthetic cells within the STN as a predictor of clinical outcome in patient with PD undergoing DBS surgery.

Background

Dopaminergic therapy and Deep Brain Stimulation ameliorate motor manifestations in Parkinson’s disease, but their effects on axial symptoms are unpredictable and often not sustained in the long term. Spinal cord stimulation (SCS) may be a new therapeutic approaches a positive effect on motor symptoms was reported on isolated cases of patients suffering from Parkinson Disease (PD) associated with resistant limb pain.

The objective of this study was to investigate the therapeutic effect and the safety of SCS on gait disturbances including freezing of gait in advanced PD patients.

Methods

We investigated the effect of SCS in 5 painless patients with PD and disabling gait disorders in a standardized manner. A SCS system was implanted at the T10 level and parameters adjusted according to a protocol based on our previous experience in lower limbs pain treatment (100Hz, 300μs, amplitude adjusted to a subthreshold value). Comprehensive evaluation at basetime and following IPG implantation included usual PD scales  (motor score-part III of the MDS-UPDRS, Freezing of Gait Questionnaire (FOG-Q) and PDQ 39 score) and a walking test,the SWS Test (“stand-walk-sit“) to evaluate temporospatial gait parameters checked by videotapes. Endpoints were assessed Off and On Dopa at base time before surgery and Off and On stimulation, Off and On Dopa,60 days post implantation.

Results 

Surgical procedures and stimulation were uneventful. We recorded a significant and sustained positive response in all patients.

With SCS alone, all patients exhibited significant improvement in the MDS UPDRS score (23.22%), even more marked with L-Dopa (36.8%). The axial signs (items 9 to13) were also significantly improved by SCS alone of 29.8% and by SCS plus L-Dopa by 42.5%. The FOG-Q did’nt reach significativity with an improvement of 3.6%. All patients experienced a significant improvement of PDQ39 from 72.2 to 57 (p=0.03). The sub-score of the PDQ39 concerning mobility (1 to 10) significantly improved from 29.6 to 22.6 (p=0.03).

The SWS in Off dopa condition could not be achieved by 2 patients according to their impairements at base time. After SCS, all patients achieved the SWS in On or Off Dopa condition, meaning an improvement of the condition. Administration of L-Dopa reduced the number of steps by 18%, SCS alone decreased by 12,4% and SCS coupled with of L-Dopa by 20%. L-Dopa reduced the duration of SWS by 19,3%, SCS alone decreased by 23,6% and SCS coupled with L-Dopa by 29.8%.

Discussion

This pilot study demonstrated that SCS is safe and effective to improve mobility and quality of life in advanced PD patients. Two other pilot studies resulted in similar outcomes. Optimal lead placement and SCS device adjustments seemed crucial for successful stimulation. Advanced explorations are required to disentangled gait symptoms and dopa dependance derived from freezing and other PD cardinal symptoms. These preliminary works provided promising results that could serve as a basis and give raise for conducting larger and longer randomized studies as new paresthesia free SCS systems are promising. Although the mechanisms of  SCS efficacy were not elucidated, the spinal Central Pattern Generator (CPG) could be a therapeutic target in PD gait disorders.

Disclosure 

The authors have no conflicts of interest relevant to this study. 

The investigations were supported by Fondation Ophtalmologique Adolphe de Rothschild. 

Implantable medical devices were kindly donated for free by Abbott (France).

Introduction

The Renishaw neuromate® robot has been designed for stereotactic applications in neurosurgery. Its accuracy in frame-based implantation of intracranial depth electrodes for deep brain stimulation (DBS) is quoted to be better than 1 mm¹. This compares favourably to other methods of stereotactic implantation such as the Leksell Frame² and CRW Frame³. Our aim was to quantify the accuracy of DBS electrode implantation utilising the neuroinspire™ software and neuromate® robot for movement disorder when compared to our planned target in paediatric patients.

Methods

All patients (=<18 years) DBS procedures for dystonia planned on the neuroinspire™ software and subsequently implanted utilising the Renishaw neuromate® robot since May 2017 were identified. All patients had DBS electrodes implanted with the aid of Renishaw guide tubes. The electrodes were secured in place with a dog-bone plate screwed to the skull. Patients had a post-operative CT scan with the intra-operative O-arm which was then fused to the pre-operative imaging and plan. Coordinates of the planned electrode entry and target were obtained from the neuroinspire™ software. The actual lead entry and final target implantation coordinates were then obtained following image fusion on the neuroinspire™ software. Absolute and directional errors in X (medial-lateral), Y (anterior-posterior) and Z (dorsal-ventral) coordinates were measured, and Euclidean error calculated for each individual electrode.

Results

Fifteen patients that underwent DBS implantation under general anaesthesia were identified. Median age was 11 years (range, 8 – 18 years) and ten (67%) were female. Targets for implantation were bilateral globus pallidus internus for each patient (n = 30). All patients were implanted with DBS systems manufactured by Medtronic. Overall median Euclidean error for DBS electrode implantation was 2.13mm (range, 0.71 – 4.85; p<0.001). There was no significant difference in Euclidean error between left- and right-sided electrodes (p = 0.346). The absolute errors in X (med 1.25 mm, range 0.10-4.10), Y (med 0.80 mm, range 0-2.70) and Z (med 1.45 mm, range 0-3.90) planes were individually significant (p < 0.001). There was overall anterior displacement of leads (med 0.55 + 0.85 mm, p = 0.001) but no significant directional bias in X (p = 0.219) or Z (p = 0.077) planes.

Conclusions

The demonstrated discrepancy between the planned and actual lead location are slightly improved compared to a series previously reported using the Leksell Frame in a similar patient cohort⁴. Several compounding factors could be contributing to this error such as drilling techniques and electrode fixation which if addressed should increase accuracy further, and these need to be evaluated. The neuromate® Robot is a reliable and accurate alternative to the Leksell Frame.

References

1. Daniel von Langsdorff et al (2014) In vivo measurement of the framebased application accuracy of the Neuromate neurosurgical robot. Journal of Neuroscience October 31, 2014; DOI: 10.3171/2014.9.JNS14256
2. Bot et al (2015) Analysis of stereotactic accuracy in patients undergoing deep brain stimulation using Nexframe and the Leksell frame. Stereotact Funct Neurosurg July 29, 2015; DOI: 10.1159/000375178
3. Kelman et al (2010) Analysis of stereotactic accuracy of the Cosman-Robert-Wells frame and Nexframe frameless systems in deep brain stimulation surgery. Stereotact Funct Neurosurg. June 24, 2010; DOI: 10.1159/000316761
4. Lumsden DE et al (2013) Accuracy of stimulating electrode placement in paediatric pallidal deep brain stimulation for primary and secondary dystonia. Acta Neurochir May 2014, 155(5):823-36

Incidence of electrode problems, and revision techniques in paediatric robot-assisted DBS surgery

Jonathan Ellenbogen, Anna Oviedova, Harutomo Hasegawa, Margaret Kaminska, Sarah Perides, Daniel Lumsden, Jean-Pierre Lin, Keyoumars Ashkan, Richard Selway

Introduction

DBS is an established treatment for children with dystonia. The incidence of electrode/extension problems is relatively high, 18.4% in our 10-year series of 129 children who underwent GPi DBS for dystonia. We review our cases of hardware problems requiring revision surgery and consider the technical aspects of revising the electrodes, including a frameless technique using the Renishaw Guide tubes. 

Methods

We performed a retrospective review of children (<=18 years old) who underwent DBS insertion for dystonia at King’s College Hospital from May 2005 to April 2018 and presented with hardware problems. 

Results

Of 166 paediatric patients with DBS, 25 patients had hardware problems, and of these 21 (13%) patients had specifically electrode problems requiring replacement/revision of one or more electrodes. 7 patients had lead migration and a further 7 patients had a lead fracture with or without lead migration. 7 patients had high impedances requiring revision, without obvious lead migration of fracture.

15 patients had original DBS insertion with the Leksell Stereotactic System utilising the Medtronic Stimlock for lead fixation. 6 patients had DBS inserted with the Renishaw Sterotactic Robot and utilised the Renishaw Guide Tubes, in these patients who required lead replacement it was possible to revise the electrode without using stereotactic apparatus. As the guide tubes are implanted in the correct trajectory it is possible to measure the distance required to advance/implant the lead within this to target without the need for full stereotactic reimplantation.

Conclusions

Electrode dysfunction is relatively common in children with DBS and a systematic approach is required to identify the cause. When an electrode requires repositioning or replacement, the procedure can be performed in the conventional manner with a stereotactic frame, or freehand without a frame if a Renishaw Guide tube is used at time of first insertion.

Deep brain stimulation (DBS) is a new treatment technique for disabling movement disorders or intractable pain. This surgery has some hardware-related complications including skin infection or erosion, lead fracture, migration of the devices, and hardware malfunctions with the incidence ranging from 2.7% to 50%. Scalp erosion and infection related to the bulky connector may be associated with differences at the implanted site and in the technique used to secure the connector and some neurosurgeons have attempted to drill a trough or a groove in the cranial surface to decrease the profile of the connector. We reviewed two patients ’ conditions and treatment.

The surgical procedure for both cases was made in two parts. In first part two electrodes were implanted to the target with the aim of the calculated coordinates under local anaesthesia. After the wounds were closed the patient underwent to general anaesthesia for the second part of the surgery. In this part, the stimulator (Activa® PC Medtronic or Vercise™ Boston Scientific) was putted to subclavicular region after it connected to the permanent leads by extension cables.

Both patients’ pulmonary and functional performances were increased after surgery and did not affected because of the scalp erosion. Their  Modıfıed Hoehn And Yahr Stage were 2.5 (Mild bilateral involvement with recovery on retropulsion (pull) test).

Case 1: A male at 58 years old. Applied with a complaint of erosion at the wound site and removal of the connection point with appear from the outside one month after bilateral STN DBS surgery. The revision surgery was done to close the skin, but after 1 month, the connection point came out of the skin again. So the groove is formed and the connection point is buried in this Groove. Post-op 3rd month follow-up the wound is still without problem.

Case 2: A female at 56 years old. Applied with a complaint of erosion at the wound site and removal of the connection point with appear from the outside third week after bilateral STN DBS surgery. The revision surgery was done to close the skin, but after 1 month, the connection point came out of the skin again (figure 1-a). So the groove is formed and the connection point is buried in this Groove (figure 1-b). Post-op 6th month follow-up the wound is still without problem.

Conclusion: Hardware-related complications associated with the connector may occur in DBS procedures and they need to be prevented. The groove technique, which involves securing an electrode connector using a groove or a trough in the cranial bone, offers an effective and safe method to avoid electrode connector-related complications during DBS surgery. Furthermore it may avoid the occipital pain and prevent discomfort caused by the connector in the retro-auricular region when the patients are in supine position or wearing glasses.

Objective: To assess the feasibility and efficacy of a novel closed-loop programming algorithm (CLPA) for directional lead deep brain stimulation (DBS) based on objective feedback using a finger-mounted motion sensor. 

Background: Subthalamic nucleus (STN)-DBS is a standard therapeutic option for appropriately selected patients with advanced Parkinson's disease. Recent advancements in DBS technology have enabled additional combinations of stimulation settings, although the identification of optimal stimulation parameters has become more complicated. In particular, the advent of multiple source devices and leads with segmented contacts greatly increase the permutations of available parameters. Development of a computer-guided CLPA based on objective feedback from a finger-mounted motion sensor may make DBS programming easier and faster. 

Methods: CLOVER-DBS is a prospective, randomized, multi-center, double-blind study employing a crossover design. Up to 36 subjects will be enrolled who have been implanted with bilateral directional DBS leads (Vercise Cartesia, Boston Scientific) connected to a pulse generator providing an independent current source for each of 16 contacts in the STN for at least 6 months. These subjects have been previously optimized per the center's standard of care (SOC) with unchanged programming settings over 4 weeks. The CLPA would suggest iterative stimulation settings based on the motor outcome at previous settings, as measured by an accelerometer (Kinesia, Great Lakes NeuroTechnologies). The number of programming steps needed to achieve the final setting identified as optimal are tracked. Additionally, motor outcomes are measured by accelerometer as well as by the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) by a blinded neurologist, at baseline and after each programming method, in a random order. 

Results: This evaluation has no prospective statistical hypothesis, but collects number of programming steps, UPDRS-III, and quantitative accelerometer-based measures of bradykinesia and tremor. The preliminary data obtained so far will be reported. 

Conclusions: The CLOVER-DBS study will compare programming effort and clinical responses from stimulation settings generated by the CLPA and the SOC. Results will inform algorithm development and future studies.

Objective:

After incomplete spinal cord injury (SCI), locomotor function often remains severely impaired. In a preclinical study in adult rats (Bachmann et al., 2013), unilateral electrical deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) could profoundly improve locomotion after severe incomplete spinal cord injuries.

Method:

The cantonal ethics committee approved a prospective first-in-man proof-of-concept study. Five patients with incomplete SCI above the level T10 who completed rehabilitation and have a WISCI II and SCIM III above 2, respectively, will receive unilateral implantation of a DBS-electrode in the MLR. Acute and long term effects of 50 Hz-stimulation on improvement of walking, QOL, bladder- and sexual function will be assessed before and at several timepoints after surgery. We aim at an improvement of walking by 30% in the 6-minute walking test 6 months postoperatively compared to the preoperative baseline.

Results:

The first implantation is scheduled for end of May 2018. Study background, stimulation target and modalities, patient screening and preliminary experiences from the first patient will be demonstrated.

Conclusion:

Pre-clinical studies on MLR-DBS in incomplete SCI are promising. Patient recruitment for a first study in men is currently on-going.

Objective:

Striatal dysfunction has been related to the pathophysiology of tics in Tourette`s syndrome (TS). Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) complex, which projects to the striatum, is used clinically to alleviate tics in TS. Apomorphine-induced deficient sensorimotor gating, measured as prepulse inhinbition (PPI) of startle, has been used to model TS in rats. We recently showed that DBS of the rat CM-Pf alleviates PPI in this model. We here investigated the effect of CM-Pf stimulation on single neuronal activity and oscillatory activity of striatal fast spiking interneurons (FSIs) and medium spiny neurons (MSNs) in this model.

Methods

We  recorded putative MSNs and FSIs single unit activity in the dorsomedial striatum (DS-Str) together with local field potentials (LFPs) and sensory motor electro-corticogram (SMCtx- ECoG) under urethane anesthesia  (1.4 g/kg, i.p.)  in rats before and after apomorphine injection (1mg/kg). Thereafter, 60 sec CM-Pf-stimulation (130 Hz, 100 µA current, with 120 µs biphasic square wave pulses) was applied and the neuronal activity was recorded. 

Results

While apomorphine had little effect on striatal single unit activity, CM-Pf stimulation significantly increased the firing rate and decreased the percentage of spikes in bursts of putative FSIs in the DM-Str. Injection of apomorphine increased the theta (4-8Hz) frequency coherences of SMCtx- ECoG with DM-Str-LFPs and the spike phase-locking to theta oscillatory activity, which was both reduced by CM-Pf stimulation.

Conclusions

Our findings suggest that CM-Pf stimulation modulates neuronal activity in the striatum in the context of a rat model showing traits of TS. These neuronal interactions may allow to better understand the mechanisms of CM-Pf DBS on the striatum in neuropsychiatric disorders with deficient sensorimotor gating.

Background: Oscillatory activity of local field potentials (LFPs) plays a central role in regulating different states of brain function. In neurological and neuropsychiatric disorders neuronal oscillations between subcortical basal ganglia (BG) and cortical circuits are disturbed.

Objective: We here investigate the changes in oscillatory activity in the motor cortex (MCtx) and the sensorimotor cortex (SMCtx) of rats after acute injection of the dopamine (DA) receptor antagonist haloperidol (Halo) and subsequent injection of the DA receptor agonist apomorphine (APO).

Methods: Six male Sprague Dawley rats (260-300g) were used in this study. Rats were anesthetized with chloral hydrate (370 mg/kg; i.p.) and a sixteen channel surface electrocortigram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of one hemisphere. Five days after surgery, individual free moving rats were recorded for 30 min in three conditions: (1) basal activity, (2) after injection of Halo (0.5 mg/kg), and (3) with additional injection of APO (1mg/kg). Spontaneous basal oscillatory activity and average number of bursts were analyzed in the MCtx and SMCtx area.

Results: Injection of Halo decreased oscillatory theta band activity (4-8Hz) and enhanced beta (12-30Hz) and gamma (30-100Hz) in MCtx and SMCtx, which was compensated by APO (p <0.001). Further analysis showed a higher count of bursts in beta and gamma oscillatory activity after Halo in the MCtx and SMCtx. APO only compensated this measure for beta bursts in the SMCtx, while not affecting gamma burst count in both regions and beta burst count in the MCtx.

Conclusion: Our results provide evidence that blockade of dopamine predominantly elevates beta and gamma and suppresses low frequency theta oscillations in motor cortical areas. Further, our results propose that exaggerated beta and gamma frequency and higher number of bursts in the cortical networks may be involved in altered sensorimotor and cognitive information processing in neurological and neuropsychiatric disorders.

INTRODUCTION

In the last decades, mapping of functions has become mandatory during intracranial tumour resection in eloquent areas.  Both mono- and bipolar stimulation techniques have their advantages and shortcomings; in subcortical resection with underlying fascicles and in skull base tumours with hidden cranial nerves, stimulation parameters have to be optimized and the interval between stimulation and resection minimized. Alternation of mono- and bipolar stimulation on one single device can optimize the accuracy and ergonomy .

MATERIALS AND METHODS

We designed monopolar stimulation on the tip of the Ultrasonic Aspiration device (CUSA°), first in subcortical stimulation for supratentorial tumours, later during intracapsular stimulation for posterior fossa lesions, particularly vestibular schwannomas,  and for spinal tumours.

We applied the classical parameters : cathodal, short train of 5, pulse duration 500µsec, interstimulus interval 4 msec, mostly intermittent due to risk of seizures (even subcortically), sometimes continuous. Since the tumour resection device coincides with the stimulation device, the accuracy is maximal (no switch of instruments), the stimulation-resection interval minimised to 0 (simultaneuous stimulation and resection) and the ergonomy improved by significantly shortening the duration of the procedure. Since 2004 we have used this method in over 500 patients without any intra-operative complications.

Since 2015, stimulation on tip of suction probe is commercially available; we use the combination of both  probes for bipolar stimulation : the  CUSA-tip as one pole, the suction tip as the other pole.

Monopolar stimulation is  more sensitive and reliable for MEP motor mapping, whereas bipolar stimulation is more specific, more localized and preferable in language mapping, although more seizure-inducing.

In suptratentorial tumours, our technique consists of primary use of monopolar stimulation with the 1mm/1 mA rule, starting from  10 mA and decreasing until 5 or even 3 mA, where the resection area is closest to underlying fascicle projected in navigation head-up display .
When a positive reaction is triggered , that point is registered in the navigation system, the CUSA being navigated after calibration. Then we switch to bipolar stimulation (CUSA + suction tip) with the  classical Ojemann stimulation parameters ( 60 Hz, 1 msec, 2-10 mA), with the CUSA-stimulation at the center, the suction tip being moved in a circular way for better localization of the underlying fascicle, the response being maximal in the direction of that fascicle. Registration of the second point indicates the probable direction of the fascicle.

In base of the skull  tumours, e.g. vestibular schwannomas, the same principle is used: first monopolar stimulation allowing coarse cranial nerve detection , then circular bipolar stimulation with the suction tip at different angles to determine the supposed  trajectory of the nerve.

RESULTS

We used combined mono- bipolar stimulation CUSA-tip/suction tip in 23  patients, as well during resection of supratentorial lesions ( gliomas, metastases) as infratentorial, particularly cerebello-pontine tumours.

This method allows us to resect the tumour up to the extreme functional limit for supratentorial lesions, and to accurately localize cranial nerves underlying the capsula in cerebello-pontine tumours.

CONCLUSION

Combination of the high sensitivity monopolar stimulation and the specificity of bipolar stimulation with the usual instruments (CUSA-tip + suction tip) offers the possibility to maximize function-controlled resection and reducing surgery time.

Introduction :

The posterior limb of the internal capsule and the enclosed pyramidal tract (PT) are important neighboring structures of the internal pallidum. Its proximity to globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes is closely related to both beneficial and side-effects. Test stimulation during surgery, especially in “awake” patients, is often performed trying to reveal thresholds for positive and negative effects of stimulation. In anesthetized patients test stimulation using the typical DBS parameters may pose difficulties in detection and interpretation of responses.  In contrast, motor evoked potentials (MEPs) achieved using short-trains of high-frequency stimulation are widely used in glioma surgery for semi-quantitative assessment of the proximity to PT in patients under general anesthesia (GA).

We present our technique of using MEPs evoked through the implanted DBS electrodes as an electrophysiological marker for the proximity to PT and its different parts and as a surrogate marker of optimal position in the GPi.

Material and Method :

We report herein 8 patients implanted with bilateral GPi DBS for dystonia – 2 primary and 6 secondary cases. All of them were implanted using anatomical (MRI based) targeting and frame-based system – Leksel G frame. GA was used in all cases. For GA constant infusion of propofol and fentanyl were used, limiting muscle relaxants for intubation only.  DBS leads – model 3389 Medronic with contact width 1.5 mm and interspace of 0.5 mm were used in all cases. Stimulation was performed using high frequency short train technique – trains of 6 pulses – pulse width 0.5 ms, interstimulus interval 3.5 ms. Time-matched recordings – MEPs were recorded from subdermal needle electrodes in 4 body muscles – m. orbicularis oris, m biceps brachii, thenar muscles, m. tibialis anterior. Stimulation current was elevated starting from 0 to 20 mA and the threshold for stimulation of the different parts of the PT was documented. Based on our experience with glioma surgery we have empirically considered MEP threshold in the range of 3-6 mA to be close enough but not inside the internal capsule. In all cases intraoperative computed tomography (CT) with the frame was performed for confirmation of lead placement .

Results :

MEPs through DBS leads during surgery were easily recorded in all 8 cases with a total number of 64 DBS lead contacts stimulated. Motor thresholds for the most distal two lead contacts which aimed to be at the anatomical target were on average: thenar – 4.1 (1,8-8.5) mA, biceps brachii – 4.6 (2.8-9mA), orbicularis oris – 4.2 (0.5-8) mA, m. tibialis ant. – 8.1 (6.2- 18.0). Proximal lead contacts showed more variable MEP thresholds which can easily be explained by variability in entry sites and trajectories.   In 6 cases there was marked symmetry between left and right responses (difference of less than 1,5 mA for all thresholds from lowermost two contacts). In this group intraoperative CT revealed low targeting error and symmetrical placement of the leads. In the other 2 cases there was either bigger than 1,5 mA left-right difference or difference in the muscle group stimulated with the lowest threshold implying either difference in laterality or anterior-posterior placement of the leads. In one patient we had on the left side very low threshold for facial muscles and thenar – 0.5 mA and 1.8 mA respectively and a marked anterior shift of MEP responses compared to the other side. In that case CT showed a significant (3mm) anteromedial placement of DBS lead in comparison with the intended target and the contralateral lead. That lead was immediately repositioned. Since no good data exist on optimal MEP thresholds for DBS placement no intraoperative judgement or actions were undertaken solely on the basis of MEPs.

Conclusions :

MEP thresholds from PT are feasible and reliable electrophysiological marker for the proximity of the internal capsule in DBS lead implantation in the GPi. More data is needed for establishing the threshold and part of the PT activated first for defining the optimal DBS target using this method.

Introduction: Although neuroimaging is main feature for the diagnosis of intracranial lesions, lesion tissue biopsy is necessary for accurate pathological diagnosis. Thus, stereotactic biopsy is an integral part of the clinical diagnosis of intracranial lesions. Technique of biopsy have changed from conventional burr-hole to usage of twist-drill craniostomy, as simple, minimally invasive procedure. To evaluate the new technique for brain biopsies at our institution utilizing the twist drill craniostomies and comparing with older burr hole craniostomies.

Patients and methods: Prospective nonrandomized study was performed. We included a total of 150 patients. The inclusion criteria for patients were CT evidence of supratentorial intracranial lesions and requirement for brain biopsy for pathological diagnosis. Every patient underwent stereotactic biopsy. The biopsies were performed as frame based twist drill craniostomies. Afterwards, the results were compared with the conventional burr-hole open craniostomy performed in our institution.

Results: Diagnostic tissue was obtained in all cases; all patient reported minimal discomfort during the procedure. There was no operative mortality or morbidity, and there were no complications. The time needed in this procedure was less than 10 minutes. The bone hole with 2.5 mm diameter does not affect the integrity of the skull.

Conclusion: Our experience with this type of procedure proved it to be simple, efficient, safer, faster and more convenient for the patient comparing to the conventional burr hole craniostomy biopsies. Also, the twist-drill craniostomy allows more liberty for the choice of the position of the craniostomy involved into the possibly following tumor reduction surgery.

Introduction: Meningiomas are the second most common primary cerebellopontine angle (CPA) tumors. Surgical resection of primary CPA tumors require: appropriate patient selection based on general and neurological status, radiological findings and optimal peri-and postoperative care. In order to maintain leading role of microsurgical treatment of CPA lesions the treatment has to be highly efficient and burden with minimal surgical risk.

Objective: To evaluate efficacy and safety of retrosigmoid approach to CPA meningiomas.

Materials and methods: 23 CPA meningioma patients were surgically treated between 2008-2014.. Mean age of the group was 55,30±12,95. Retrospective pre- and postoperative data of the group were collected. Intraoperative stimulation of the facial nerve was performed in all cases. Statistical analysis of neurological function of V-XI cranial nerves, tumor diameter, postoperative hydrocephalus and progression rate based on postoperative MRI and CT were performed.

Results: Simpson I-II extend of resection was achieved among 15 patients with CPA meningioma, Simpson III among 9 patients and partial resection (Simpson IV-V) among 2 patients. Good or serviceable hearing (A+B from AAO-HNS classification) was observed among 14 patients (87,5%). Good facial nerve function (HB I-II) was gained among all patients. Progression of meningiomas occurred in 3 patients– 2 after Simpson I-II resection, 1 after partial resection. Progression of the tumor was observed among deaf patients (p=0,047).

Conclusions: Microsurgical treatment of CPA meningiomas is highly effective. The extent of resection is the most determinant risk factor for progression. Meningioma’s diameter less than 30 mm was the predicting factor for hearing preservation.  The risk of deterioration of VII cranial nerve function is higher among VS group. The scope of resection has no impact on hearing or facial nerve function preservation.

Introduction: Vestibular schwannomas (VS) are the most common primary cerebellopontine angle (CPA) tumors. Surgical resection of primary CPA tumors require: appropriate patient selection based on general and neurological status, radiological findings and optimal peri-and postoperative care. In order to maintain leading role of microsurgical treatment of VS the surgery has to be highly efficient and burden with minimal surgical risk.

Objective: To evaluate efficacy and safety of retrosigmoid approach to primary CPA tumors.

Materials and methods: 50 VS patients were surgically treated between 2008-2014. Mean age of the VS group was 52,88±13,28. Retrospective pre- and postoperative data of VS group were collected. Intraoperative facial nerve stimulation was performed in all cases. Statistical analysis of neurological function of V-XI cranial nerves, tumor diameter, postoperative hydrocephalus and progression rate based on postoperative MRI and CT were performed.

Results: Gross total resection was achieved among 25 patients with VS, subtotal resection (>95% of tumor volume) among 24 patients, partial resection in 1 patient. Good or serviceable hearing (A+B from AAO-HNS classification) were observed among 7 patients (42%). Good facial nerve function (HB I-II) was gained among 31 patients (68,9%) with negative correlation between extent of resection and postoperative good function of VII cranial nerve. Hydrocephalus was observed among 3 patients (6%). Progression of VS was observed in 10 patients– 5 were treated with stereotactic radiosurgery, 1 patient was qualified for second surgery and 4 were treated with fractionated radiotherapy. The incidence of progression depended on extent of resection.

Conclusions: Microsurgical treatment of VS is highly effective. The extent of resection is the most determinant risk factor for progression. Size of the tumor is the most determinant risk factor for hearing preservation. The scope of resection has no impact on hearing or facial nerve function preservation.

Introduction: Vestibular schwannomas (VS) and meningiomas are the most common primary cerebellopontine angle (CPA) tumors. Presenting symptoms and surgical results vary depending on tumor origin and type.

Objective: To compare efficacy and safety of retrosigmoid approach to VS and CPA meningiomas.

Materials and methods: 50 VS and 23 CPA meningioma patients were surgically treated between 2008-2014. Mean age of the VS group was 52,88±13,28. Mean age of the CPA meningioma group was 55,30±12,95. Retrospective pre- and postoperative data of both: VS and CPA meningiomas groups were collected. Statistical analysis of neurological function of V-XI cranial nerves, tumor diameter, postoperative hydrocephalus and progression rate based on postoperative MRI and CT were performed and confronted.

Results: Gross total resection was achieved among 25 patients with VS, subtotal resection (>95% of tumor volume) among 24 patients, partial resection in 1 patient. Good or serviceable hearing (A+B from AAO-HNS classification) were observed among 7 patients (42%). Good facial nerve function (HB I-II) was gained among 31 patients (68,9%) Gross total resection (Simpson I-II) was achieved among 15 patients with CPA meningioma, subtotal resection (Simpson III) among 9 patients, partial resection among 2 patients. Good or serviceable hearing (A+B from AAO-HNS classification) was observed among 14 patients (87,5%). Meningioma’s diameter less than 30 mm was the predicting factor for hearing preservation. Good facial nerve function (HB I-II) was gained among all patients. Progression of meningiomas occurred in 3 patients– 2 after Simpson I-II resection, 1 after partial resection.

Conclusions: Hearing loss is more common symptom in VS group.  The effectiveness of microsurgical resection of CPA meningiomas is higher than VS. The extent of resection is the most determinant risk factor for progression in both groups. The risk of VII nerve palsy is higher among VS group. Hearing preservation is more feasible in CPA meningioma group compared to VS patients. Size of the tumor is the most determinant risk factor for hearing preservation in both groups. The scope of resection has no impact on hearing or facial nerve function preservation. Progression of the tumor was observed among deaf patients with CPA meningiomas (p=0,047). CPA meningiomas tend to have better prognosis than VS.

Stereotactic brain biopsies for histopathological diagnosis are a common technique in case of intracranial lesions, particularly in those not amenable for resection. Tumor seeding alongside the surgical trajectory after fine-needle aspiration is a known problem in several visceral tumors. Whereas in these cases a complete resection of the biopsy trajectory may later be performed, this strategy is not feasible in stereotactic brain biopsy. We report a case of tumor seeding along the entire biopsy tract after stereotactic biopsy of a brainstem metastasis. A 68-year-old male patient with a concomitantly diagnosed kidney lesion presented with a singular lesion in the brainstem. After confirmation of metastasis by stereotactic biopsy, stereotactic radiosurgery (SRS) was applied. The primary tumor was treated by laparoscopic nephrectomy. Three months after SRS, the patient presented with a secondary clinical deterioration for only a few weeks. The MRI scan showed tumor seeding along the entire biopsy tract. Salvage treatment including hypofractionated stereotactical irradiation and seven cycles of bevacizumab was administered to obtain symptom control. Massive seeding of tumor after stereotactic biopsy accordingly rare, taking into account that stereotactic biopsy is a very common neurosurgical intervention. Nonetheless, we think that the potential risk has to be kept in mind, as it might be neglected.

INTRODUCTION:

The surgical treatment of cystic intracranial tumours includes catheter insertion and percutaneous aspiration, marsupialisation and ventriculo-cystostomy, all of which require accurate surgical targeting for optimum results. Management of these lesions can be challenging due to cyst re-accumulation, mis-targeting, an inability to perforate the cyst wall using standard ventricular catheters, catheter blockage, catheter migration and implantation associated haemorrhage. We describe a novel method of robot assisted stereotactic drainage of cystic lesions using an open-ended guide tube designed for functional neurosurgery modified to allow cyst aspiration.

METHODS:

We report a 5 patient case series encompassing paediatric and adult neurosurgical practice. Guide tubes (NeuroGuide, Renishaw) were implanted using the NeuroInspire (Renishaw) stereotactic platform with a NeuroMate (Renishaw) robot. Catheter/guide tube trajectories were planned using pre-operative high resolution MRI and CT angiography in the same method used for DBS surgery. Guide tubes were delivered on a tungsten carbide rod and fixed to the calvarium with an integral press-fit hub. Cyst content was aspirated via the open ended guide tube or by a secondarily fitted in line reservoir. Target accuracy was determined by intraoperative CT co-registered with the pre-operative plan. The frequency of catheter blockage, implant associated haemorrhage, adverse clinical events, and cyst drainage efficacy was recorded prospectively.

RESULTS:

5 consecutive patients (Age range 4-66 years) with cystic tumours are reported: 3 brainstem (Diffuse Midline Glioma), 1 supratentorial (glioblastoma) 1 suprasellar (craniophyringioma) The median pre-drainage cyst volume was 4.3cm³ (range 2.7 - 5.4cm³). The mean cyst volume reduction after drainage was 3.0cm³. Guide tube implantation was accurate with a mean target accuracy variation of 0.2mm (0.02-0.5mm). There was no incidence of guide tube migration, implant associated haemorrhage or infection. 1 patient (age 6 years, cystic brainstem glioma) had a transient post-operative bulbar deficit following cyst aspiration. No episodes of guide tube blockage were encountered on repeated aspiration.

DISCUSSION:

Robot assisted implantation of an open-ended guide tube on a rigid guide rod allows highly accurate targeting and successful perforation of tumour cyst walls. We hypothesise that long term patency of the guide tube/catheter may be due to the design incorporating an open tip instead of small side perforations, which can easily become blocked. Low rates of blockage may also be due to the guide tube material, carbothane, which has been shown to have a very low tissue binding properties and low rates of blockage in pre-clinical studies. Migration of the guide tube is prevented by press-fitting the hub into the skull.

Conclusions:

We present a case series describing a novel robotic implanted open-ended guide tube for management of cystic brain lesions. The technique was accurate, safe and effective. The guide tube could additionally be used to administer intra-cystic chemotherapy e.g. for craniopharyngioma. Further research is required to compare this novel method with conventional methods of cystic tumour management. 

Bienemann, A., E. White, M. Woolley, E. Castrique, D. E. Johnson, M. Wyatt, G. Murray, H. Taylor, N. Barua and S. S. Gill (2012). "The development of an implantable catheter system for chronic or intermittent convection-enhanced delivery." J Neurosci Methods 203(2): 284-291.

Background:

       Molecular analyses of the material obtained by classical brain tumor surgery are well known. The challenge poses the molecular evaluation of the tissue material obtained from brain tumors by a stereotactic biopsy.Since1997 the authors have conducted over 2,500 stereotactic  biopsies of brain tumors. Since November 2017, apart from the classic, histopathological examination, they have also begun to perform genetic tests.

Aim:

The aim of our study was to analyze whether the diagnostically difficult material obtained by stereotactic biopsy brain tumors can provide reliable genetic analysis.

Material and  Methods:

In 38 patients with a glial brain tumor a stereotactic biopsy procedure was performed. On average, between 8 and 10 samples were taken from each patient. The methylation of the MGMT promotor, the presence of the codon 1p10q and the IDH1/IDH2 mutation was analyzed.

The specimen were treated according to the procedure of formalin-fixed and paraffin-embedded tissue. All the samples were classified by histological examination and graded according to the WHO 2016 guidelines.DNA was isolated from paraffin-embedded tissue samples using Maxwell® 16 FFPE Plus LEV DNA Purification Kit and with the Maxwell® 16 Instrument (Promega). The samples of DNA were cleaned and concentrated using DNA Clean&concentrator™  Kit (ZymoResearch) in order to obtain eluted DNA suitable for PCR.As a reference (standard control) for MLPA reactions DNA isolated from the blood of healthy volunteers was used.

The MLPA SALSA P088-C1 kit (MRC-Holland, Amsterdam, Netherlands), which contains nineteen 1p probes, eleven 19q probes, three 1q probes and two 19p probes and the probes to detect mutations in IDH1 and IDH2 genes,was used for the analysis of the material.As a control, 14 probes for different chromosomal locations were used.MLPA  was carried out according to the manufacturer’s protocol, using 50ng for each DNA of standard control and tumour sample, respectively. One microliter of the amplified sample product was analyzedusing ABI 3130 (Applied Biosystem) and as an internal size standard the LIZ-500 Genescan (Applied Biosystem). The standardization of the tumor samples was performed on 4-6 control sample data (standard control).Data analysis was carried out using the MRC-Coffalyser.Net program.

Results:

In 36 cases genetic test results correlated with the histopathological examination. Histopathological diagnosis confirmed low grade glioma in 7, high grade glioma in 11 and glioblastoma grade IV in 18 cases, respectively. Genetic tests revealed the presence of methylation of MGMT in 5 out of 7 cases of low grade glioma, in 5 out of 11 patients with high grade glioma and in 10 out of 18 cases of glioblastoma. The  codeletion 1p/19q was  present in 2  out  of 7 cases of low grade glioma,  in 4 out of 11 patients with high grade glioma and in 1 patient with glioblastoma only.

The IDH-1  mutation   was  present in 5 patients with low  grade  glioma and high grade glioma each, and only in 1 with glioblastoma, respectively.

The IDH-2 mutation was  found neither in the  low  grade  glioma or glioblastoma patients,  but in 1 case of high of grade glioma.

In  2  out  of  all 38 cases  the histopathological examination revealed glial  brain  tumor  without  genetic confirmation.  However, in 1 case molecular tests excluded it and in another one, additional genetic tests are being carried out.

No complications resulting from larger than normal tumor samples were observed.In  the  past  5-6  samples were usually taken from each patient.

Of the 38 patients analyzed, 2 had tumor removal. Genetic studies after surgery were consistent with those obtained from a stereotactic biopsy.

 Conclusions:

The results that the authors obtained are encouraging. The collection of a larger number of samples  did not cause complications. Genetic testing appears to be complementing classical, histopathological diagnosis.

Abstract:

The field of functional neurosurgery has been transformed by the development and clinical deployment of devices that are capable of safely and selectively modulating targeted neural structures. With auditory brain stem implants and deep brain stimulators, for example, it is technically feasible and now routine practice to place electrode contacts directly within targeted brain regions and use an implanted pulse generator to chronically deliver electrical stimuli to the selected site. This is not the case when neural structures within the human spinal cord are targeted for neuromodulation. All existing clinical spinal cord stimulator systems deliver electrical stimuli through electrodes placed in the extradural space. The dura serves as an electrical resistance barrier positioned between the electrode contacts and the underlying spinal cord. In addition, a layer of highly conductive cerebrospinal fluid (CSF) separates the dura from the spinal cord, resulting in electrical shunting of electrical stimuli. The net operational effect, as demonstrated in many stimulus delivery modeling studies, is that less than 2 percent of the human spinal cord can be selectively modulated using existing devices.

In this report, the work of a multi-disciplinary, multi-institutional collaborative spinal cord neuromodulation research and device development group will be presented. This group was established for the purpose of identifying and overcoming barriers that to-date have precluded the development and deployment of a direct human spinal cord neuromodulation system. Any successful direct spinal neuromodulation system must effectively address two aspects of human spinal canal and spinal cord anatomy and function; mobility of the cord within the thecal sac, and the risk of CSF leak. In a series of human subject imaging studies and through bench top model development and testing, the dynamic range of spinal cord motions within the canal were measured and replicated using the surrogate spinal cord model. A device concept was developed whereby a thin electrode array is placed on the dorsal surface of the spinal cord, and held in place in a manner that accommodates spinal cord movement using a compliant bundle of conductive intradural leads. The size and configuration of the surface array conformed to that of the auditory brainstem implant manufactured by Cochlear Corporation. Prototypes of this novel device were implanted and its mechanical and materials properties tested acutely and chronically using an in-vivo sheep model. In separate ovine studies, we also demonstrated the ability of intradural spinal cord stimulation to modulate cortical somatosensory evoked potentials at much lower power levels than with epidural stimulation.

More recently the group has designed and begun benchtop testing of an alternative implant design that enables placement of an electrode array that abuts the inner surface of the spinal dura and can be implanted using minimally invasive surgical techniques. A unique compression gasket feature creates a watertight dural seal that withstands hydrostatic pressures far in excess of the physiological CSF range within the thoracolumbar spinal canal. A special version of this new approach incorporates one or more standard epidural electrodes which can be used to optimize the stimulation pattern. With both electrode array design variants, electrical stimulation modeling demonstrates significant improvements in the capacity to deliver currents directly to targeted dorsal column axons, without activating non-targeted dorsal rootlets, and with more than an order-of-magnitude decrease in power consumption. An added benefit of intradural methodology is that it eliminates the risk of lead migration, which is a significant reason for failure of therapy in standard epidural stimulation. Potential applications presently under study include improved therapy for neuropathic pain, better control of spasticity resulting from spinal cord injury, and enhanced motor control in those with neurodegenerative diseases and syndromes.

Objective:

Accurate targeting is pivotal in functional stereatactic neurosurgery. But not just hitting the target is essential, also the trajectory to the target needs consideration. Transventricular approach has been thought to lead to an increased risk of intracerebral haemorrhage by several authorities, although this has debated by others. Here we investigate the comparative occurance of haemorrhage with or without transventricular apporaches in a large series of patients operated over two decades.

Methods:

In 550 patients out of a total of 585 patients, who underwent DBS electrode implantation or radiofrequency lesioning, it could be determined retrospectively whether or not the trajectory transverses the ventricles. Patient were operated over a period of 20 years in three different centers, performed or supervised by the same neurosurgeon using the same technique. Targets were determined by CT-stereotactic surgery with a standardised approach which did not consider to avoid a transventricular trajectory. Postoperative CT scans obtained within 24 hours after surgery were searched for transventricular approach and for haemorrhage of any size at any site.

Results:

Patients were operated for movement disorders (478), pain syndromes (48) or psychiatric disorders (24). 25% of the leads placed in the internal globus pallidus (GPi) passed the ventricles, 91 % of the leads in the nucleus ventralis intermedius (Vim) passed theventricles and 90% of the leads in the subthalamic nucleus (STN). Out of 357 patients with a transventricular lead placement, 13 patients had an intracranial haemorrhage (3,64 %). In the other 193 patients, where the electrodes did not pass the ventricle, 6 patients had an intracranial haemorrhage (3,11 %). In the transventricular group haemorrhage manifested as a small haemorrhage at the target site (6), subdural haematoma (2) or ventricle haematoma (5). In the non-transventricular group haemorrhage manifested as haematoma at the target site (5) or subdural haematoma (1). Haemorrhage was asymptomatic in all patients except in 1 patient in the transventricular group, who had a persistent mild hemiparesis on the right side.

Conclusions:

In this large cohort of patients we could show that there is no significantly increased risk for an intracranial haemorrhage by choosing a transventricular approach for DBS lead placement.

ABSTRACT

Objective: The incidence of postoperative nausea and vomiting (PONV) after retromastoid craniectomy with microvascular decompression (MVD) is high, and confuse physicians with postoperative injuries of the neural structures. We performed this prospective double-blind randomized controlled trial to identify the effect of preoperative prophylactic transdermal scopolamine (TDS) patch on PONV after MVD. We hypothesized that preoperative prophylactic TDS patch will reduce the rate of PONV after MVD.

Methods: We recruited 38 patients undergoing MVD for hemifacial spasm or trigeminal neuralgia between October 2016 and March 2018 after screening of 43 patients. They were randomized to two groups: TDS group (n=19, application of a TDS patch on the contralateral mastoid area to the scheduled MVD side on the day before surgery) and placebo group (n=19, application of a placebo patch with the same manner of the TDS group). Nausea (as a self-reporting visual analogue scale; range, 0 [no nausea] to 10 [worst nausea]), vomiting, and antiemetic use were the primary endpoints and were recorded upon arrival to the postanesthesia care unit (PACU), on transfer to the general ward, and then, 4-hour interval until 48 hours.

Results: The placebo group had a tendency of higher nausea score than the TDS group along the entire observation period. Especially, the nausea VAS of the TDS group, checked on transfer to the general ward, was significantly lower than that of the placebo group (0.93±1.71 versus 2.52±2.85, respectively; p=0.046). The difference of the nausea VAS appeared again at 32 hours after transfer to the general ward (0±0, TDS group versus 0.38±0.76, placebo group; p=0.050). There was no difference between the groups in terms of vomiting.

However, the rate of rescue antiemetic use was significantly lower in the TDS group (n=2 [10.5%]) than the placebo group (n=9 [47.4%] (p=0.029). In addition, the mean number of antiemetic use was also significantly reduced in the TDS group (0.16±0.50 versus 1.37±2.19 of the placebo group; p=0.029). This difference was obvious especially within 4-hour interval (0.11±0.46, TDS group versus 0.63±0.83, placebo group; p=0.022). There was no patient who experienced side effects related with a TDS patch.

Conclusion: The preoperative prophylactic use of a TDS patch was safe and effective in reducing the incidence of PONV and the number of rescue antiemetic use during the first 48 hours after MVD.

Voxel based morphometry is widely studied in many neurologic and psychiatric disorders. In the search for new possible objective makers to identify best candidates for STN-DBS surgery, brain MRI morphometric characteristics was not previously explored.

The aim of the study was to identify brain morphometric characteristics that are associated with better motor outcomes after STN-DBS for Parkinson’s disease.

Material and methods:

Adult patients diagnosed with Parkinson’s disease were recruited for this prospective observational cohort study from the Departments of Neurosurgery and Neurology of the Lithuanian University of Health Sciences Hospital, Kaunas, Lithuania. The study enrollment took place between January 2015 and August 2016. During the study period, 32 PD patients underwent the DBS implantation surgery at our department. Twenty-two Parkinson’s disease patients underwent DBS implantation in the STN and comprised the study group.  All Parkinson’s disease patients underwent preoperative brain MRI. The UPDRS III motor subscale difference (delta) was calculated before surgery and 6 months after intervention both in “on” and “off” medication states.  Automated voxel based subcortical segmentation analyses and cortical parcellation were carried out using the FreeSurfer image analysis software (v6.0, Harvard, MA). The UPDRS III subscale (delta) correlations with brain morphometric characteristics were evaluated in univariate and  multivariate analyses with adjustment for patients age, gender, disease severity and intracranial volume.

Results:

Two Parkinson’s disease patients were excluded from further analysis, because they did not match image processing and analysis quality control. Volumetric analysis showed significant differences in cortical thickness in STN-DBS patients with better motor improvement in 4 gyruses with on-medication state: on the right hemisphere, (superior parietal (beta 0.49, p=0.02; beta 0.63, p=0.05) , inferior temporal (beta 0.52, p=0.01;beta 0.79, p=0.02) and lateral occipital (beta 0.54, p=0.01; beta 0.71, p=0.04)) and on the left hemisphere (lateral occipital (beta 0.62, p=0.004; beta 0.87, p=0.008)).  White matter volume analysis showed that patients with greater white matter volume in the left superior parietal (beta 0.58, p=0.007; beta 0.72, p=0.05) region had better motor response after STN-DBS. Moreover, larger surface area on the right superior parietal (beta 0.48, p=0.04; beta 0.66, p=0.03 and beta 0.62, p=0.004; beta 0.68, p=0.004) and lingual areas (beta 0.5, p=0.02; beta 0.86, p=0.01 and beta 0.69, p=0.001; beta 0.78, p=0.005) in on and off medication states correlates with greater delta UPDRS III score, respectively, implicating that this area can be the most important for predicting STN-DBS motor outcome.

Conclusions:

Better motor state improvement in Parkinson’s disease patients after STN-DBS implantation surgery might be associated with thicker cortex in both sides of the lateral occipital gyruses and right hemisphere superior parietal and inferior temporal gyruses as well as higher white matter volume in the left superior parietal area. Bigger surface area  in the right superior parietal and lingual areas implicit importance of both hemipsheres superior parietal area in predicting STN DBS motor response results. This very small pilot study must be replicated within bigger patient groups to improve statistical power

Introduction

Hardware infections are a serious complication in the field on neuromodulation, as this may interfere with the patient therapy and significantly increase treatment costs. To identify the incidence of hardware-related infections in spinal cord (SCS), peripheral nerve field (PNFS) and deep brain stimulation (DBS) and to determine the most common infectious agents. Furthermore, to establish the best treatment strategies for their management.

Methods

Medical records of all patients who underwent SCS, PNFS and DBS surgery at the Dept. of Stereotactic and Functional Neurosurgery at the University Hospital of Cologne, from January 2012 through August 2017, were retrospectively reviewed.

Results

The incidence of surgical-associated infections was 2.6% (69 patients/2,638 surgeries). Antibiotic treatment alone was successfully performed in two of 69 patients (2.8%). Surgical wound revision or complete removal of the stimulation system, in combination with antibiotics, was required in the other 67 patients (97.2%). Wound revision was performed in 30 patients (43.4%) and complete removal of the system in 37 patients (53.6%). Age and comorbidity showed no correlation with the final outcome. The main agents identified in the wound revision without removal group were Staph. epidermidis (43.3%), standard flora/no agent (23.3%) and Staph. aureus (13.3%), while the main agents identified in the wound revision with removal group were Staph. aureus (43.2%), Staph. epidermidis (18.9%) and standard flora/no agent (16.2%) (p<0.05 for both groups). In 15 cases, a revision without removal was primarily performed but ultimately ended in a complete removal of the device. In these cases, Staph. aureus was also the main agent responsible for the infection (33.3%) (p>0.05). Patients without removal of the system received antibiotics for 4.1 weeks in average, while patients that required a complete removal received antibiotics for an average of 2.3 weeks.

Conclusions

SCS, PNFS and DBS are safe surgical procedures with a low incidence of hardware-related infections. The vast majority of infections require a surgical intervention in combination with antibiotics. The main agents responsible for wound infections are Staph. aureus and Staph. epidermidis. In cases were Staph. aureus was incubated, the larger number of cases required a complete removal of the system, either primarily or during a secondary procedure.

Objective: Acute high systolic blood pressure (BP) is an important risk factor for intracranial hemorrhage (ICH) in deep brain stimulation (DBS) surgery. Therefore, to minimize pain and hypertensive conditions, sufficient local anesthesia management that does not affect intraoperative evaluation and electrophysiological data is crucial.

Purpose: To compare hemodynamic parameters along with intraoperative need for analgesics of two different methods of local anesthesia for awake DBS.

Methods: We performed a retrospective observational study on 47 patients (LA: n = 29; SB: n = 18) undergoing awake DBS surgery at a single center. We analyzed differences in intraoperative heart rate (HR), systolic blood pressure and blood pressure peaks > 160mmHg as primary endpoints. As secondary end points, we analyzed the need of intraoperative antihypertensive medication as well as intra- and postoperative analgesics.

Results: SB patients had significantly lower mean systolic BP values (LA 153.7 mean ± 2.2 mmHg standard error mean vs. SB 140.7 ± 3.4 mmHg; p = 0.001) and shorter duration of hypertensive states (LA 37.7 ± 4.6% vs. SB 13.4 ± 3.0%; p = 0.013) compared to LA patients. Patients in the LA group required significantly more antihypertensive medication to stabilize BP than SB patients (LA 20.5 ± 3.9 mg/h vs. SB 3.4 ± 0.6 mg/h; p < 0.001). Two ICHs occurred in LA patients whereas no ICH was seen in the SB group. The intraoperative dose of paracetamol, metamizole and remifentanil did not differ between the two groups except when the impulse generator was implanted the same day, if so, SB patients needed significantly less remifentanil during the second intervention (LA 0.583 ± 0.049 mg/h vs. SB 0.223 ± 0.044 mg/h; p = 0.003).

Conclusion: Our results strongly suggest that SB might be superior to LA for awake DBS surgery according to BP control and provides better hemodynamic conditions. In both groups, the need for intraoperative analgesics showed no difference during lead implantations. If the impulse generator implantation additionally was performed the same day, SB patients required less opioids during the second procedure.

Section of filum terminale and sacral neuromodulation in patients with possible occult tethered cord syndrome.

C. Ruggiero, P. Spennato, RS Parlato, M. Abbenante, A.M. Cotrufo, G. Cinalli

Background: Occult tethered cord syndrome, in which there is normal neuroanatomic imaging despite clinical and urodynamic evidence of neuropathic bladder behavior, is controversial. A recent randomized trial did not show any objective difference in urological outcome between medical management plus or  minus filum section, even questioning the concept of occult tethered cord syndrome. Despite this, in the last decade, it has been our clinical practice to offer section of the filum terminale in pediatric patients with neurological bladder and normal anatomy of the lumbo-sacral spine on magnetic resonance image. In more recent cases, in case of failure, a sacral nerve stimulator is offered.  

Objective: To retrospectively evaluate efficacy and safety of section of filum terminale and eventually sacral neuromodulation in patients with possible occult tethered cord syndrome. 

Clinical material:  From 2008 to 2017, 10 pediatric patients, aged between 4 and 13 years (average age 8 years) affected by urinary retention or overreactive bladder, were operated on by section of filum terminale. These patients had been selected by urologists and underwent medical therapy for at least 6 months. Preoperative investigations included: magnetic resonance image of the entire spine (in some cases, sequences obtained in prone position were included), urodynamic study and somatosensory evoked potentials of posterior tibial nerve and of pudendal nerve. 

Results: All the patients, but one, experienced immediate relief of their symptoms. However in 4 patients symptoms recurred, in 3 of them within 6 months from surgery and in one case 6 years after surgery. Two patients in which symptoms recurred were treated by implantation of an electrical stimolator of the sacral nerve (Interstim II - Medtronic), with complete relief of symptoms.

Conclusion: Our experience with section of filum terminale in patients with possible occult tethered cord syndrome is positive with more than half of the patients experiencing long lasting relief of symptoms. Further studies are requested to confirm these data. The patients with recurrence or persistence of urological dysfunction may be considered good candidates to sacral neuromodulation. 

Deep brain stimulation (DBS) programming sessions involve patient observation, assessment of the effectiveness of programed parameters and changes to programming parameters in order to achieve best treatment outcomes. A number of DBS devices are now available for use in Australia. This has created an opportunity to ensure a device is selected that best suits individual patients, their disorder and ability to manage their longterm DBS therapy. However this requires skilled and experienced DBS programming clinicians with expereince in using the devices available to a DBS impalnting centre.Frequent DBS centre programming appointments may be required during the first 12 months post implantation. This requires dedicated time from the programming clinicans to properly evaluate the status of the patient's symptom management. Time management of these appointments needs to be taken into account to ensure adeqaute adjustments are made and the outcome acceptable for the patient. This is also important to ensure an economically sustainable service is able to be provided One aspect of time management of appointments is the actual DBS clinician programming device and patient's IPG connectivity. This connection process can add valuable minutes to a programming sesion. Attending to multiple patient appointments over a day each requiring clinician programmer connectivity, assesment, observationa and programming changes needs to be a considered. Close physical contact with the patient is often required depending on the programming platform used. A delay in connectivity between the programming device and the patient's IPG if delayed, in some instances, can result anxiety for the patient and extend appointment times. We will discuss the time spent on connectivity, programming of the IPG and routine device checks with a variety of Australian approved DBS devices. Patient feedback on the DBS programming session expereinces will also be discussed.

 Accuracy in the stereotactic functional neurosurgery is very crucial factor to achieve expected clinical improvement. Some factors have been reported to lead inaccurate surgery: image processing, stereotactic frame and intracranial brain shift during the surgery. Minimizing these factors maximize surgical accuracy which eventually leads to the clinical benefits. We need to determine the quantity of image distortion of MRI/CT images. The weight of the needle holder and metallic arc device, deflection of insertion needle also influence the accuracy in stereotactic surgery. Intracranial air intrusion and brain shift have been known as the factors to enhance the inaccuracy. In the present study, we report the practical tips of patients’ body position during stereotactic neurosurgery to minimize intracranial air intrusion and improve surgical accuracy.

Saudi Arabia is a developing country in the south west of Asia. It occupies a land of more than 2 million km² and has the population of more than 30 million. Modern medical services started in the country relatively late. The discovery and production of oil facilitate a rapid development in modern medical services providing state of the art medical treatment to the local people. Neurosurgery service as a separate subspecialty service started in the seventies of last century. However, stereotactic and functional neurosurgery was born in 1983, When the late Prof. F. John Gillingham (1916 – 2010) was appointed professor of surgical neurology, College of Medicine, King Saud University in Riyadh. He brought with him a stereotactic frame, the Guiot-Gillingham stereotactic apparatus and started surgery for Parkinson disease.  In the same year (1983) a young Saudi neurosurgeon the late Prof. Khalaf R. Almoutairi (1948-2018) had just arrive back home after completing his neurosurgery training in Germany. He was trained under Prof. C. Ostertag in stereotactic procedures. As chief of neurosurgery at the military hospital in Riyadh, Dr Almoutairi started the service of stereotactic and functional neurosurgery. The services included stereotactic biopsy, lesioning for movement disorders, epilepsy surgery and stereotactic radiosurgery for oncology and neurovascular indications.  In 2002, A comprehensive movement disorders program was established at King Faisal Specialist Hospital and Research Centre. The first successful deep brain stimulation procedure was carried out in that year.

Currently, stereotactic and functional neurosurgery services are widely practiced in Saudi Arabia with more than one centers in every one of the three major cities provide different services like movement disorders, epilepsy surgery, radiosurgery, pain procedures etc.

A review of the history augmented with photos. current status supported with statistics and future goals  with possible obstacles will be presented.

Introduction: Sodium fluorescein (Na-Fl) is a sodium salt and an organic fluorescent. A newly developed microscope (PENTERO 900, Carl Zeiss, Meditec, Oberkochen, Germany) equipped with a special filter (YELLOW-560 nm), designed to detect low-dose Na-Fl for the demarcation of tumor tissue, was previously introduced, and more promising reports have been published regarding extensive tumor resection with the use of this system. Na-Fl can also be used for videoangiography purposes intraoperatively for various vascular pathologies like aneurysms, arteriovenous malformations or their combinations. Trigeminal and glossopharyngeal neuralgies (TN-GPN) are most common facial pain syndromes characterized by a paroxysmal shock-like pain limited to the innervation area of these nerves. Usually a vascular contact between arteries or veins and these nerves were found to be responsible of these pain syndromes. With the advancement of microsurgical techniques, the microvascular decompression procedure, which has the rationale to eliminate the neurovascular contact, has been eventually become an effective treatment for facial pain syndromes with considerably favorable outcomes. The current study aimed to better visualize the vascular compression in facial pain syndromes with the employement of Na-Fl.

Patients and Methods:Three patients underwent microvascular decompression surgery with Na-Fl guidance in two different centers. Two patients (one patient with TN and one patient with GPN) were operated in Istanbul and one patient (TN) was operated in Regensburg. There were 1 male and 2 female patients, with the ages 55, 36 and 44. The both patients with trigeminal neuralgia had pain in the distribution of V2-3 branches. All patients had a history of extensive medical treatment. All patients underwent standard microsurgical procedures through 2- to 3-cm diameter suboccipital craniectomies performed below the junction of the transverse and sigmoid sinuses. After exposure of glossopharyngeal/trigeminal nerves, a videoangiography with Na-Fl was performed. 1 ml (100 mg/1-2 mg/kg) of Na-Fl 10% was injected intravenously through a central venous catheter in order to perform a videoangiography. Generally within 30 seconds cerebral arterial, capillary and venous phases of the angiography was visible under YELLOW 560 nm filter. YELLOW 560 nm filter allows real-time surgical manipulation of the vascular structures. After neurovascular contact was identified, the vascular structures caused compression were displaced away from the nerves with the use of a piece of polytef (Teflon) pledgets placed in between. 

Results: The Na-Fl videoangiography was effective to demonstrate the vascular conflict in detail in each instance. No side effects or adverse reactions were encountered after the intravenous use of Na-Fl. Na-Fl videoangiography found useful and feasible for its use in the microsurgery of facial pain syndromes. In all patients, the operation was effective by means of pain control. No recurrences were encountered during the follow-up period. 

Conclusions: Microvascular decompression has been used in the surgical treatment of facial pain syndromes over decades. Its effects were known also well. With the application of Na-Fl videoangiography, the neurovascular conflict may be more clearly and detailed demonstrated. Na-Fl videoangiography is easy to perform and its cost is relatively low. Na-Fl guidance with the use of the YELLOW-560 filter is safe and effective during microvascular decompression surgery. It can be used as a technical adjunct in microvascular decompression surgery.

attached

Background: Clonidine is a centrally acting alpha(2)-agonist antihypertensive drug used for opioid/alcohol withdrawal and for intrathecal administration in the treatment of chronic neuropathic pain. Cases of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy after pump removal or due to pump malfunction are extremely rare.

Case report: A 58-year-old woman with chronic neuropathic pain was treated for a 10 year period with intrathecal morphine and clonidine in combination (daily dose of 53,624 mg and 22,343 µg). At the end of battery life, the patient was scheduled for pump replacement (Medtronic Synchromed 2). After replacement, the pump was reprogrammed 2 hours after surgery with the same dosis rates and concentrations of medication as before. The patient then complained about back pain, twitching of back muscles and nausea. Piritramid (7,5mg) and Zopiclon (7,5mg) were administrated. Shortly thereafter blood pressure increased to 249/118 mmHg, pulse frequency to 140 bpm, O2 saturation decreased to 74% and temperature rose to 37,7 °C. The patient became obtunded and presented myoclonic movements of the whole body (see video). She was intubated and ventilated and was admitted to the ICU. Serum CK, CK-MB, Troponine-T and Myoglobine were markedly elevated. She was extubated on the following day and had retrograde amnesia for the past few days. The neurological status was normal and the myoclonus had completely subsided. The pump showed no signs of malfunction.

Conclusion: Withdrawal of continuous clonidine and morphine may manifest within a very short period after cessation of drug administration. It may result in the subacute onset of a life-threatening situation characterized by obtundation and generalized myoclonus. Early intervention can reverse this unusual withdrawal syndrome and may lead to rapid recovery.

Objective

The aim of this study was to investigate changes of synaptic area of the spinothalamic tract and its thalamocortical pathway (STT) in the thalamus in chronic patients with putaminal hemorrhage.

Methods

Twenty four patients with a lesion in the ventral posterior lateral nucleus (VPL) of the thalamus following putaminal hemorrhage were recruited for this study. The subscale for tactile sensation of the Nottingham Sensory Assessment (NSA) was used for the determination of somatosensory function. Diffusion tensor tractography of the STT was reconstructed using the Functional Magnetic Resonance Imaging of the Brain Software Library. We classified patients according to 2 groups: the VPL group, patients whose STTs were synapsed in the VPL; and the non-VPL group, patients whose STTs were synapsed in other thalamic areas, except for the VPL.

Results

Thirteen patients belonged to the VPL group, and 8 patients belonged to the non-VPL group. Three patients were excluded from grouping due to interrupted integrity of the STTs. The tactile sensation score of the NSA in the non-VPL group (10.50 ± 0.93) was significantly decreased compared with that of the VPL group (19.45 ± 1.33) (P < 0.05).

Introduction: Central neurogenic pain can be treated with neuromodulation procedures invasive or non-invasive. MCS-motor cortex stimulation and DBS–deep brain stimulation belong to intracranial methods. Main indications for MCS are central post stroke pain, neuropathic facial pain, phantom limb pain or brachial plexus or spinal cord injury pain. In chronic neuropathic pain good response on MCS has been observed in over 50% with postoperative follow-up of 1 year. The mechanisms underlying the analgesic effect of MCS has not yet been elucidated. Stimulation of cortico-subcortical fibers inhibits hyperactive sensory units in the thalamus. Tonic stimulation with low frequency in MCS has been applied for years. At present generators of burst frequency are available in SCS - spinal cord stimulation. Necessity to replace depleted batteries of motor cortex tonic stimulators enabled us to apply other paradigms of stimulation including burst mode. In literature there are no reports on the effects of burst MCS. SCS with burst waveform has been more effective than tonic in neuropathic pain. The pattern of SCS burst stimulation is such that 500Hz stimulation is delivered in groups of five pulses with 1-ms pulse width, with bursts repeated 40 times per second. Objective of the study was to evaluate the effects of burst stimulation applied on motor cortex in patients with central neurogenic pain. Material and methods: We have evaluated series of 5 patients (females n=2, males n=3 ) belonging to the group of 14 cases (females n=5, males n=9) who underwent surgical procedure of MCS in our department in years 2005-2017. Selected for the study were 5 patients with thalamic pain n=3, with atypical facial pain n=2 (anaesthesia dolorosa and neuropathic trigeminal neuralgia). These patients were able to choose the most effective program of stimulation: tonic or burst. Pain intensity was assessed with the visual analogue scale (VAS) after the stimulation with IPG with burst mode. Outcome was based on personal choice of patients who were selecting the most frequent applied program causing maximal pain relief. Results: In our series in 3 out of 5 patients prefered burst mode of motor cortex stimulation finding it more effective. Preoperative intensity of pain in VAS was assessed by all patients as 9 to 10 cm. Patients H.L. – 60 years old female with atypical facial pain and with tonic MCS for 10 years had VAS=6 on five tonic programs and VAS=4 on burst , M.I – 55 years old male with thalamic pain on tonic MCS for 5 years had VAS=7 on tonic  and 5 on burst , M.S. – 61 years old male with thalamic pain and tonic MCS for 8 years had VAS=5 on tonic and VAS= 2 on burst, M.M- 62 years old male with thalamic pain and MCS for 4 years had VAS=7 on both tonic and burst, M.K- 48 years old female with anaesthesia dolorosa on  face with MCS for 2 years had VAS=6 on both tonic and burst.Discussion: MCS is the treatment of last resort for chronic central pain that is refractory to pharmacological treatment and that can not be treated with other stimulation techniques as spinal cord stimulation and peripheral nerve stimulation. After a long-term MCS, habituation on stimulation takes place what decreases positive, analgesic effect of neuromodulation. In our series we examined patients with central neurogenic i.e: thalamic syndrome after stroke or traumatic brain injury, and central neuropathic facial pain. Out of 14 patients who received MCS, 5 were submitted to the burst stimulation of the cerebral cortex. Two of them didin’t find burst mode as a superior. Primary waveform of MCS was tonic stimulation with frequency of 10 to 50Hz, but the alternative program with intra-burst rate 500Hz was more frequent giving them satisfactory pain relief. Although the results were not excellent in majority of patients with all types of central pain after tonic MCS, patients demanded reimplantation of IPG when battery was depleted. Contemporary neurostimulation systems allow patients to participate actively in therapeutic process. Patient – controlled, neuromodulative analgesia helps patients become more independent.Conclusions: The most preferred option in our series was burst stimulation. The analgesic effect after burst stimulation was noticeable, but it wasn’t significantly greater than after tonic stimulation in chronic, refractory pain. This study has shown that the burst stimulation of the cerebral cortex can be a promising modality when tonic stimulation is not sufficient.

Percutaneous gasserian rhizotomy procedures (thermorhizotomy or balloon compression) used to treat refractory classical trigeminal neuralgia are usually guided by fluoroscopy and based on bone landmarks. However in some cases, percutaneous puncture of the foramen ovale may be difficult and may require direct visualization of the foramen. Here we describe the successive steps and workflow of a technique combining intraoperative CT scan (O-Arm, Medtronic, Minneapolis) and neuronavigation guidance to improve percutaneous puncture of the foramen ovale.

Methods: Under sedation, the patient’s head is immobilized with the Mayfield radiotransparent head holder. The patient’s fiducial is then fixed on the head holder and the needle is calibrated to allow its tracking by the neuronavigation system (Stealthstation, Medtronic). O-Arm CT scan 3D acquisition is then performed to allow visualization of the target in the foramen ovale (bone window images). Trajectory is then defined with the neuronavigation software by determination of the latero-labial entry point (soft tissue window images). Percutaneous puncture of the foramen ovale is performed under neuronavigation guidance. Classical lateral O-Arm fluoroscopy may be used to check the depth and location of the needle’s tip within the Meckel’s cave. Once the needle is within the gasserian ganglion, rhizotomy is performed as usual, the patient being awake or asleep.

Discussion/ Conclusion: this technique allows direct visualization of the foramen ovale and its navigated percutaneous puncture. It may be particularly useful in older patients with recurrent neuralgia and history of multiple previous percutaneous procedures in who fluoroscopy guided puncture may fail. However the radiation dose and OR occupation time are higher than classical fluroroscopy guidance.

Objective:

Neuropathic deafferentiation pain manifesting as “intercostal neuralgia” may occur after breast surgery, thorax trauma or herpes zoster infection. Dorsal root ganglion (DRG) stimulation has been introduced recently as a treatment for refractory pain and has replaced selective ganglionectomy within few years. Here we report on the use of “rescue” ganglionectomy after secondary failure of DRG.

Methods:

A 55-year-old man had a 5-year history of severe refractory “intercostal neuralgia” after thorax trauma. Infiltration of the T 10 and T 11 ganglion with local anesthesia provided temporary relief of pain. Subsequently, DRG electrodes (St. Jude/Abbott) were implanted via a transcutaneous approach for chronic stimulation of T 10 and T 11. After two years of partial relief, the effect of stimulation vanished. It was decided then to remove the electrodes and to perform ganglionectomies at the corresponding levels.

Results:

Postoperatively and at follow-up (3 months), there was consistent improvement of pain of about 70% (VAS, pre- vs. postoperative 9/10 vs. 3/10).

Conclusions:

Chronic DRG stimulation provides pain relief in the majority of patients with segmental neuropathic pain. Our report clearly exemplifies that ganglionectomy still is a valid option in those patients in whom the effect of chronic stimulation vanishes on the long-term.

Introduction: Failed back surgery syndrome (FBSS) is a term that describes a chronic pain condition defined as persistent or recurring low back pain, with or without sciatica following one or more spine surgeries. Even as spine surgery advances, the rate of FBSS has not declined. It has considerable impact on the patient health and well-being as well as to increased cost to the health care system. Spinal cord stimulation(SCS) is one of the most effective techniques to manage this entity.

Materials and methods: 26 patients with FBSS were selected for implantation of a spinal cord stimulator. They were evaluated in various items. Including pain intensity, pain medication consumption, quality of life and psychological profile. They were treated using different spinal cord stimulation devices at the Department of Neurosurgery of Italian Hospital of Buenos Aires from 2008 to 2018. We review the epidemiology of our patients. To assess number of previous back surgery, original cause of pain, time to implantation, age, employment, and other social characteristics that may determine the combined cost of spinal cord stimulator implantation in a third world country.

Results: Of 26 patients analized 53,8% presented clear benefits with SCS, 19,2% interventions were unsuccessful and 26,9% were partially successful. Either it provided proper pain cover in some of the affected territories. Or, it provided momentary improvement, with posterior return to previous pain levels.

The cause of the original spine surgery was distributed in 3 main categories. 14 patients, degenerative spine disorders. 8 traumatic fractures and 3 spinal tumors. The mean number of previous spine surgerys were 2,07. With a maximum of 4. The mean number of years between the first spine surgery, and SCS were 6,65. 6 patients requiered more than one SCS procedure done (most of those were from another center).

Conclusion: Development of FBSS is dependent of multiple factors that may arise preoperative, intraoperative, and postoperative. For that, treatment and good functional outcomes remain challenging. SCS is the best surgical option to treat this entity. Its efficacy has been proven in the past 14 years. But cost-effectiveness remains a mayor factor in determining its application in those cases that persist refractory to conservative approaches. Beginning at 2 years and continuing throughout follow up in most studies, SCS is cost-effective comparing to conventional medical management. Even in complex health care systems such as those of latin-america.

Introduction: Motor Cortex Stimulation (MCS) has been used for the treatment of numerous refractary chronic pain disorders with good results ^(1,2,4,5).  These central neuromodulation processes have multifactorial effects on central pain processing and descending pain inhibition⁽⁴⁾ . Clinical studies and systematical reviews have been published in order to confirm or discuss the efficacy of MCS in patients suffering from neuropatic pain.

Materials and methods: Four patients with refractory chronic center pain regarding of thalamic pain, atypical facial, post stroke and pain of central diabetic vasculopaty were selected to MCS. They were evaluated as to multidimensional evaluation including pain intensity, prior pain medication,quality of life and psychological evaluation. They  were treated with MCS at the Department of Neurosurgery of Italian Hospital of Buenos Aires from 2009 to 2018. The procedures were conducted with the use of  intraoperative neurophysiological monitoring. The outcomes were assessed in terms of visual analog scale scores. The long-term follow-up ranged from five to ten years. 

Trought a small craniotomy, the primary motor cortex was exposed and recognized by electrophisiologic intraoperative mapping. Two electrodes were implanted over the motor representation contralateral to the painful area. Following surgical implantation of the MCS lead, patients can be trialed with external extension leads to determine the best stimulation analgesic options.The electrode are connected to an implantable pulse generador or battery placed subcutaneosly in the infraclavicular or abdominal tissue. Stimulation was usually set in a cycling mode of 1–3 off and 10–3 on, with a low frequency from 40–50 Hz to 90Hz, pulse wave ranging from 90 to 240 ms, and a variable amplitude A = from 0.5 to 8.0.

Results: The application of neuromodulation techniques for the treatment of chronic pain requires knowledge of the anatomy of the nociceptive and motor system of the brain⁽³⁾ .  The mechanisms underlying the analgesic effect of MCS are not completely understood. In our own experience   All patients showed pain improvement greater than 50%. Only one patient had posoperative skin infection over the wire, but it wasn´t necesary to remove it. Another patient presented transient seizerus during posoperative stimulation. 

Conclusion: MCS can alleviate chronic pain in selected patients. The bipolar stimulation is therefore likely to generate both direct and indirect waves that active corticospinal and corticothalamic fibers, initiating a cascade of physiologic andneurochemical events eventually leading to analgesic effects^(1). Equally, Conclusive effectiveness studies are still needed to demonstrate the best targets as well as the reliability of the results with these approaches ⁽²⁾.

Bibliography:

1) Kurt, E., Henssen, D. J., Steegers, M., Staal, M., Beese, U., Maarrawi, J., ... & Holsheimer, J. (2017). Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain: Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review. World neurosurgery, 108, 254-263.

2) Moore, N. Z., Lempka, S. F., & Machado, A. (2014). Central neuromodulation for refractory pain. Neurosurgery Clinics, 25(1), 77-83.

3) Hassanzadeh, R., Jones, J. C., & Ross, E. L. (2014). Neuromodulation for intractable headaches. Current pain and headache reports, 18(2), 392.

4) Sukul, V. V., & Slavin, K. V. (2014). Deep brain and motor cortex stimulation. Current pain and headache reports, 18(7), 427.

5) PaczkowskiE, D., & RusinekE, M. (2015). Motor cortex stimulation in patients with chronic central pain

Introduction: The radiofrequency as a percutaneous procedure for the chronic pain treatment is being used for more than 30 years. The most frequent indications are the chronic pain in the spine. The most used therapeutic targets are the medial branch of the dorsal root  for the facetary syndrome, this is the pain that origin´s at the facetary joint; the the dorsal root ganglion for the radicular pain; and the dorsal branch of C2 for the occipital neuralgia. The are two types of procedures for the radiofrequency ablation depending where the pain target is: a)Continuous radiofrequency ablation that generates denervation through thermocoagulation of the facetary joint sensitive nerve; or b)Pulsed radiofrequency that produces a neuromodulation that lows the pain transmission at the radicular nerve ganglion.

Technically these procedures are simple and have low complexity, and can be guided by CT, fluoroscopy or US depending the therapeutic target.

Objective: The aim of this research is presenting our experience at the different therapeutic targets used for the pain treatment in the spine, describing the technique and result in short and long term.

Methods: 871 patients with spine pain were analyzed. They received radiofrequency ablation treatment, using continuous or pulsed radiofrequency, since January of 2010 to January of 2018 at the HIBA. We studied the complications and the results at short and long term. We used de Visual Analogue Scale (VAS) to assess the pain. We also describe the special technique of the procedure.

Results: Radiofrequency ablation treatment was performed in 871 patients with pain at the cervical spine level (n= 59), the dorsal spine level (n= 16) and in the lumbar spine level (n= 796). 25 patients with cervical spine pain(42%) had also radicular pain, and 293 patients with lumbar spine pain had radicular pain too (36%). All the patients with dorsal spine pain had intercostal neuralgia. All the patients that suffered cervicalgia and lumbalgia was performed continuous radiofrequency ablation for the denervation of the facetary joint at the particular spine level. Although the patients that presented radicular spine pain, pulsed radiofrequency  of the affected nerve roots were performed. All the procedures were made by fluoroscopy. We only had two (2) complications in cervical blocks. 63.3 % of the patients had a long term follow-up.

Conclusion: The radiofrequency ablation for the spine pain treatment it's a low complexity, safe and a efficient procedure. It's not only a therapeutic option, also it plays an important role as a diagnostician of potential surgical targets in patients with chronic pain, allowing us to identify the pain source. Likewise, it´s a therapeutic option before the surgical treatment choices,that are more complex and have more morbidity.

Introduction

Complex regional pain syndrome (CRPS) is a chronic painful condition that usually occurs after trauma or minor or major surgery. Multifactorial condition characterized by disturbances and changes in the sympathetic, somatosensory and motor nervous system, progressively deteriorating the quality of both physical and mental life of these patients. for this, in our center the treatment is multidisciplinary (including neuromuscular kinesiology, endocrinology, psychiatry, neurology, pain treatment clinic) and can range from motor kinesiology, pharmacological treatment (bisphosphonates, NSAIDs, etc.) to surgery for stimulation of the posterior spinal cord.

Objective

To analyze the role of spinal neurostimulation in the multidisciplinary treatment of CRPS.

Materials and methods

A retrospective analysis of patients diagnosed with CRPS treated with spinal neurostimulator implanted in the Italian hospital of Buenos Aires from 2011 to 2017 was carried out. The response to the treatment was evaluated by the improvement of the symptoms (greater than 50% of initial VAS (analogical visual scale)) and reduction of vasomotor symptoms.

Results

Of a total of 9 patients treated, 7 (78%) presented marked symptomatic improvement, 1 (11%) patient did not respond to neurostimulator therapy, another (11%) presented little improvement in symptoms. 5 (71%) patients remain in multidisciplinary follow-up (endocrinology, psychiatry, pain treatment clinic). Regarding complications, 1 (11%) patient required replacement of electrodes due to system dysfunction and there were no infectious complications.

Conclusion

Spinal neurostimulation has shown to be effective as part of the overall treatment of CRPS, with low complication rate, pain reduction (77% in our series, another 73%), allodynia, muscle dysfunction, with improved blood flow and decreased of edema.

Introduction: Temporomandibular joint syndrome (TMJS) is a functional disorder that involves the masticatory muscles, the temporomandibular joint or both. It is most often caused by myoarthropathy of the masticatory system and the most common symptom is intense pain in the face that can extend to the scalp side. In order to alleviate these symptoms, many options have arisen, including peripheral nerve stimulation (PNS) of the auriculotemporal branch, which causes paresthesia covering the painful area and constitutes an useful alternative to temporomandibular joint (TMJ) surgery. Nevertheless, some complications may impede a good pain control with PNS, and other neuromodulation options should be considered.  We report the successful treatment of a TMJS patient with  right PNS and right DBS of the ventroposterolateral thalamic nucleus (VPL-DBS). The combination of DBS and PNS in facial pain management has, to the best of our knowledge, never been reported in the literature.

Methods: We present a 35 year old female with a history of bilateral facial pain due to TMJS, joint noise and restricted jaw motion. She underwent different medical and surgical treatments, including anti-inflammatory drugs, intra-articular steroid injections, physiotherapy and bilateral TMJ artroscopy. Despite those treatments, her pain aggravated with constant and electrical pain in the masseteric region, which she rated with a score of 8/10, and exacerbations of 10/10,  on the visual analogue scale (VAS) The patient was referred for neurosurgical evaluation, and treatment with PNS of the auriculotemporal branch was proposed. The surgery was performed in a single surgery, under general anesthesia and radioscopy guidance, by placing bilateral octopolar cylindric leads which were connected to a pulse generator (PG) in the subclavicular subcutaneous area. Nine months after surgery, despite significant improvement in her bilateral facial pain control (VAS 2/10), her bilateral PNS system was removed due to painful cervical stiffness. Three months later, bilateral PNS system was reimplanted by using elastic extensions connecting the electrodes and PGs, achieving facial pain relief (VAS 1/10). Nevertheless, the patient developed severe allodynia affecting left temporal and cervical areas, related to the electrode and the extension wire, which forced to the removal of her left PNS system, after what her left facial pain aggravated. Right PNS did not need to adjust parameters, due to an optimal pain coverage and significant decrease in the intensity of facial pain. A DBS procedure was proposed to the patient, aiming to stimulate the VPL thalamic nucleus under local anesthesia to avoid the implantation of cables in her left hemibody. Three microelectrodes were inserted through the planned trajectory, performing microrecording and evoked somatosensory potentials, using a LeadPoint 3.0 system. Macrostimulation was performed at 3.5 mm below the target, achieving paresthesias and pain relief on her face at 0.5 mA and 100 Hz. A directional electrode was inserted into the target and fixed to cranium with regular titanium microplates. Finally, under general anaesthesia, the intracranial electrode was connected to a tunneled extension and an IPG in the right abdominal area. The patient was discharged four days after the surgery and followed up at 2, 4, 8 and 12 weeks after DBS.

Results: Following the surgery, the patient remained asymptomatic for 6 weeks. Chronic stimulation was started eight weeks after DBS surgery when the patient complained of a relapse of her left facial pain; settings were programmed based on the patient’s perception of paraesthesia in her painful area. Monopolar stimulation (contacts c+ 2a-, pulse width 90 microseg, frecuency 90 Hz, intensity 0.95mA) provided facial pain relief without side effects. One month after the DBS parameters were programmed, the patient reported a more than 90% of improvement in left facial pain (VAS 1/10).

Conclusions: Pain in the face area is a very complex phenomenon, and a variety of pain syndromes may be interrelated. PNS of auriculotemporal branch may represent a useful treatment in patients with TMJS, which does not preclude from performing second step procedures such as DBS of VPL thalamus. Thalamic DBS may be a safe and effective neuromodulation therapy that could play a role in the treatment of chronic facial pain when other less invasive treatment modalities have been exhausted.

Microvascular decompression (MVD) is widely used for managing classical refractory trigeminal neuralgia (TN). However, predictors of post-operative results are incompletely understood. To further investigate this question, we hereby report our single-center experience. We performed a descriptive and inferential retrospective analysis of the classical TN cases submitted to MVD (TN-MVD). in our center. Epidemiological and clinical characteristics, surgical findings and complications were summarized and results were analyzed, according to the Barrow Neurological Institute Pain Intensity Score (BNIPIS).

A total of 47 patients submitted TN-MVD were identified. Average age at procedure was 65.6±10.5 years. Mean follow-up duration was 108.5±53.6 months. On the immediate post-op period, 86.0% of patients achieved adequate pain control (BNIPIS ≤ 3). At one-year follow-up, 75.6% reported a BNIPIS ≤ 3. On multivariate analysis, age at procedure over 65 year was associated with good response at 12 months (p<0.035). Among patients with immediate post-op pain resolution, 35.9% reported symptoms recurrence during follow-up. We identified characteristics significantly associated with recurrence, for p<0.05: female gender, dental trigger absence and previous arterial hypertension history. On a logistic regression model, hypertension remained independently associated with recurrence (OR=34.9, 95%CI 1.42-58.95). Additionally, hypertension was independently associated with neuralgia presentation at an older age (mean age 52.4 vs 65.6 years, 95%CI 47.3-57.5 vs 59.8-71.4, p=0.02); symptom onset after 65 years is more frequent on hypertensive patients (65% vs 0%, p=0,007); and triggers are more commons on normotensive patients (83% vs 50%, p=0.048). Furthermore, among hypertensive patients who initially achieve BNIPIS score 1, average time between symptoms onset and surgery (TSOS) is greater in those who eventually experience pain recurrence (14±2.4 vs9±1.8 anos, p=0.02). When stratified by progressive TSOS cut-offs, recurrences increase linearly until a TSOS of 4 years and then pain recurrence accelerates considerably.

Microvascular decompression is a valuable resource for managing refractory trigeminal neuralgia. Post-op recurrence is a relevant but poorly studied problem. Arterial hypertension, a potentially modifiable risk factor, might be a recurrence predictor, possibly by modulating local vascular phenomena. Our understanding of its role remains incomplete: whether an external aggravating factor or the byproduct of a physiopathologically diverse, more surgery-resistant, disease, hypertension might have a particular role in trigeminal neuralgia natural history, as is suggested by different ages at presentation and trigger prevalence between hypertensive and non-hypertensive patients. Additionally, hypertensive patients might be more vulnerable to longer TSOS. More studies are needed to further clarify these questions.

Introduction: In the last two decades, the application of ozone has emerged as a potential analgesic therapeutic option for patients with low back pain, mainly due to its analgesic and anti-inflammatory properties. Although ozone therapy claims for validation, its low cost and such minimally invasive procedure open a new horizon in the arsenal care of pain in the failed back surgery syndrome (FBSS).

Objective: To evaluate the effect of epidural ozone therapy on pain and disability among patients with failed back surgery syndrome.

Method: We studied 19 patients with FBSS undergoing injection of ozone via epiduroscopy through sacral hiatus assessment. Patients were evaluated preoperatively and 21 days after the procedure, using the following instruments: Visual Analogue Scale, Brief Pain Inventory, Roland-Morris Questionnaire Disability, Oswestry Disability Index (ODI), Neuropathic Pain Symptom Inventory and Douleur Neuropathique 4.

Results: Patients got significant relief concerning pain intensity, but no significant improvement was observed on functional scales. Patients with predominantly non-neuropathic pain (PNNP) presented a significant reduc­tion on pain and disability according to ODI, whereas in the predominantly neuropathic pain (PNP) group this reduction was not significant.

Conclusion: Our results suggest that epidural ozone therapy can be a good option to reduce pain intensity in patients with FBSS, also decreasing disability among those with PNNP. The homogeneity of our sample may explain the low benefit observed on daily activities performance, but more studies are needed to analyze all benefits of ozone on low back pain treatment and its influence on neuropathic pain. 

Background

Pain is often one of the most debilitating symptoms in patients with advanced oncological disease.  Patients with localized pain due to malignancy refractory to medical treatment can benefit from selective percutaneous cordotomy that disconnects the ascending pain fibers in the spinothalamic tract.

Objectives

Over the past 3 years, we have been performing percutaneous radiofrequency cordotomy with the use of the O-Arm intraoperative imaging system that allows both 2D fluoroscopy and 3D reconstructed computerized tomography (CT) imaging.

We present our experience using this technique focusing on technical nuances and complications.

Methods

Retrospective analysis of all patients who underwent percutaneous cordotomy between March 2015 and March 2018.

Results

Thirty-two patients underwent percutaneous cordotomy procedures. Two patients developed intraoperative delirium and were unable to tolerate the procedure. In 29/30 completed procedures we achieved excellent immediate pain relief (96%). At one month post-op, 24/28 (86%) patients available for follow-up were free of their original pain, and at 3-months 9/12 (75%) patients available for follow-up were still free of their original pain. Mirror pain developed in 8/30 patients (26%), but was mild in 5/8 cases and controlled with medications. We had 1 serious complication (4.3%) of ipsilateral hemiparesis.

Conclusion

Percutaneous cordotomy using the O-Arm is safe and effective in the treatment of intractable oncological pain.

Objective: Spinal Cord stimulation is commonly used, safe and effective procedure applied for medically intractable failed back surgery as well as other neuropathic pain syndromes. Recently, a novel stimulation paradigm has been developed that is paresthesia free has more pronounced effect on neuropathic pain.

Traditional SCS required trial stimulation to eliminate patients with failed respond which can be 33% of qualify objects. After implantation of permanent system, therapy suffer of high rate of complications which severely impact of patient satisfaction, safety and healthcare costs. (S. M. Hayek at al.).

 The aim of the study was  to access clinical outcomes, efficacy and safety of wireless paresthesia-free spinal cord stimulation with adjustable frequency for the treatment of chronic neuropathic pain.

Material and method: Thirty one objects with chronic neuropathic pain was  qualify to SCS procedure and underwent implantation of  new wireless, micro-sized stimulator with adjustable frequency 5 – 10 000 Hz without traditional trial SCS.

The electrode (4 or 8 contacts) consisting of an implantable stimulator, powered wirelessly  by external  power generator was implanted on thoracic (TH9-TH10) or cervical (C2-C4) levels.

Patients were offered 3 different programs consisting  different waveforms : 30- 60 HZ with 400us or up to 10 KHz 20 us.  Intensity was relevant on patient preference.

During first month each subject had 2-4 programming session to optimize therapy and choose most effective programs.

 Key outcome measurements took place after 3 months and  included VAS scale, Oswestry Disability index measuring functionality, Leitinen Scale and patients satisfaction and complication occurrences.

Results: Twenty three from thirty one patients respond on therapy (74%) and reach satisfying improvement between 60-90%. Delivered stimulation was paresthesia free and while range of parameters allow to patients chose most efficient therapy.

Four patients (12%) not respond on therapy and failed first part of study. One patient has got 30% of improvement.

The analysis of the Laitinen questionnaire showed more than 50% of improvement in all  4 accessed areas of life. Oswestry Disability index were significantly reduced compared with baseline value.

Complications: three complications was observe during observation (8%): one lead migration, one infection and one lead malfunction.

During observation same malfunction of external powered generator was observed. Malfunction generators was exchange by cost of Producer and was not related to medical complications.

Conclusion: Novel, minimal invasive wireless stimulator has shown to be an efficacious and safe treatment for chronic neuropathic pain. Wide range of adjustable frequency provide sustainable pain relief without paresthesia. Limited number of implantable components and external powered generator can decrease number of medical complications.

The treatment of agressive behavior often requires of a wide range of therapies and medications. Neuroablative surgery represents an alternative of a select group of patients. To evaluate de effectivinness of neuroablative procedures in the control of agressive behavior, the impact of these on pshycological, social and occupational , and also to report  the appereance of adverse effects scondary to them. A cross- sectional, observational, analytical, retrospective and retrolective study was carried out,  with a non-probabilistic sample of 3 consecutive cases of patients who met the inclusion crietria for this study. A convenience sampling technique was used. The effects of neuroablative surgical procedures over agressive behavior were evaluated by applying the Overt  Agression Scale (OAS) Scale and the effects  over  psichologycal , social and occupational /school functioning through the Global  Assessmentof Functioning (GAF)  scale. The differences between the OAS and GAF scores before and after the surgical procedure were evaluated with a Wilcoxon test for a nonparametric variables . In these 3 patients a noticeable postoperative improvement was registered. The values obtained in the OAS an GAF scores, decreased and increased respectivily during the follow-up. We consider that these interventions are safe and effective. To validate our findigns, more studies that use standarized agressive behavior  measurements scales are needed.

[Background]

Intractable severe tics associated with Tourette syndrome sometimes interfer to maintain the minimum standards of wholesome and cultured living. Deep brain stimulation has been recently indicated to ameliorate such troublesome symptoms when any pharmaceutical and psychological approaches resulted in ineffectiveness. Tourette syndrome had been believed as pure psychiatric disorder classically, whereas the latest research suggest the pathological rationale that Tourette syndrome results from dysfunction of the cortical-striatal-thalamic-cortical circuit. The purpose of the present study is to realize whether Tourette syndrome is the truely neurological disorder without any personal deviation or not.

[Patients and Methods]

All cases were treated and examined at the Department of Neurosurgery, National Center of Neurology and Psychiatry by the author. Deep brain stimulation was approved by the institutional review board of on December 2007 and March 2013.Inclusion and exclusion criteria of deep brain stimulation were modified from previous studies(Ackermans, Temel, & Visser-Vandewalle, 2008; Maciunas et al., 2007; Mink et al., 2006) and previously reported(Kaido et al., 2011).

 Tic severity was assessed by YGTSS(Leckman et al., 1989) preoperatively. MMPI (Schiele, Baker, & Hathaway, 1943) was also examined to assess personality of the patients. The clinical scales were examined 10 scales to measure common diagnoses as below. Scale 1 Hs (Hypochondriasis) measures concern with bodily symptoms. Scale 2 D (Depression) measures depressive symptoms. Scale 3 Hy (Hysteria) measures awareness of problems and vulnerabilities. Scale 4 Pd (Psychopathic Deviate) measures symptoms of conflict, struggle, anger, and respect for society's rules. Scale 5 Mf (Masculinity/Femininity) measures stereotypical masculine or feminine interests/behaviors. Scale 6 Pa (Paranoia) masures level of trust, suspiciousness, and sensitivity. Scale 7 Pt (Psychasthenia) masures worry, anxiety, tension, doubts, and obsessiveness. Scale 8      Sc (Schizophrenia) measures a person's unusual/odd cognitive, perceptual, and emotional experiences. Scale 9 Ma (Hypomania) measures a person's energy. Scale 0 Si (Social Introversion  ) measures whether people enjoy and are comfortable being around other people. The validity scales contain four scales to check the validity as below. Scale ? (Cannot say) measures questions not answered to detect non-responding. Scale L (Lie) measures faking good of a patient. Scale F (Infrequency) measures faking bad of a patient. Scale K (Correction) measures a subtle and valuable correction for defensiveness. All patients were targeted at the centromedian-parafascicular complex (CM-Pfc)-ventral oral thalamic nuclei of the thalamus using the Schaltenbrand and Wahren atlas in accordance with previous literature(Servello, Porta, Sassi, Brambilla, & Robertson, 2008; Vandewalle, van der Linden, Groenewegen, & Caemaert, 1999). Data are expressed as means ± 95% confidentce interval (CI).

[Results]

The author could obtain preoperative MMPI data from 13 patients (10 males and 3 females) among 18 patients underwent deep brain stimulation (DBS). The age of onset of tics ranged from 5 to 13 years old (mean 7.5). The age at DBS was 19-34 years old (mean 26.8). YGTSS of motor tics was 17-24 (mean 20.9), phonic tics was 15-24 (mean 20.2), and impairment was 30-50 (mean 40.8). The follow-up period was from 14 to 96 months (mean 41.5). 

 Some patients had higher T-scores than 70 of common upper normal range in several scales. Patterns of MMPI was not unique but variable. The scores of validity scales were as below: Scale ?, 49.5 (CI: 53.0-46.1); Scale L, 47.7 (CI: 52.5-42.9); Scale F, 56.2 (CI: 63.4-48.9); Scale K, 49.8 (CI: 57.4-42.1). The scores of clinical scales were as below: Scale 1 Hs, 53.5 (CI: 60.0-46.9); Scale 2 D, 58.1 (CI: 68.1-48.1); Scale 3 Hy, 62.3 (69.8-54.8); Scale 4 Pd, 57.2 (62.1-52.3); Scale 5 Mf, 52.0 (CI: 58.1-45.9); Scale 6 Pa, 64.7 (71.7-57.7); Scale 7 Pt, 65.2 (72.4-58.0); Scale 8 Sc, 59.8 (66.2-53.5); Scale 9 Ma, 54.4 (61.9-46.8); Scale 0 Si, 50.0 (55.7-44.3). Any scale did not overrange 70 in each mean T-score. In comparison of all clinical scales, Scale 7 Pt and Scale 6 Pa were significantly higher than Scale 0 Si (p≦0.050, ANOVA), namely Scale 7 Pt and Scale 6 Pa tend to be relatively high among clinical scales.

Introduction.Patients with chronic, severe and refractory anorexia nervosa (AN) are being included in a clinical trial where deep brain stimulation (DBS) is performed in the subgenual cingulate (CSG) or in the nucleus accumbens (Nacc), depending on the patient clinical profile .

Objective.The main objective was to assess safety and efficacy. The relationship between the response and the clinical and image variables were studied as secondary objectives.

Methodology.4 Patients with refractory AN, of more than 10 years of evolution, and severe or extreme disease were operated on by DBS, choosing as target the CSG or the Nacc depending on the associated comorbidity or type of AN. The evaluation of patients was monthly, until 1 year of follow-up. The scales studied were: HAMA-17, HAMA, YBOCS, YBC-EDS, SF36, TCI-R, Impusilvity of Barrat, Body image of Gadner, Interoception (MAIA) . Preoperative and at 6 months neuropsychological evaluation was carried on. All patients had preoperative difussion tensor image study .The main variable was the Body Mass Index (BMI). In case of response, the study included a double blind that takes place 6 months after the stimulation, where for 3 months the system is off and the subsequent 3 months on or vice versa. A response is considered if : an increase of 10% in the maximum BMI of the last year prior to surgery or to achieve a maintained curve of BMI in patients with a descending curve of BMI since diagnosis.

Results.2 Patients showed response criteria (both 10 months of follow-up), 2 patients did not showed response criteria (5 months and 1 week of follow-up). There was 1 complication: prosthesis decubitus . No complications related with stimulation were reported. The improvement of psychometric scales was in accordance with the evolution of BMI

Conclusion. Although we have preliminary results, it seems that DBS in some patients with chronic, severe and resistant AN can be an effective treatment .It would be of great interest to know which variables influence the type of response to DBS.

Background:

Gilles de la Tourette syndrome (GTS) is a neurologic condition characterized by both motor and phonic tics, typically starting in childhood but persisting into adulthood in approximately 20% of patients.

  Deep brain stimulation (DBS) is a treatment option for refractory GTS. Although refractory phonic and vocal tics severely impair the quality of life of patients, operative treatment and the duration of DBS is controversial because the tics may resolve with age. In some effective cases, the stimulation can be stopped without any clinical deterioration. Here, we report the case of three patients with GTS who remained symptom free after withdrawal of DBS for various reasons.

Case Presentation:

              Case 1: A 30-year-old male with GTS was treated with bilateral thalamic centromedian parafascicular complex (CM-Pf) DBS at 20 years of age for his severe self-biting tics. DBS was effective, and his Yale Global Tic Severity Scale score dropped to zero six years after surgery. After seven years of treatment, he suffered from device infection. The power of DBS was decreased step by step until the device was turned off. The patient has remained symptom free for two years.

              Case 2: A 29-year-old female with GTS was treated with bilateral CM-Pf DBS at the age of 19. She also suffered from obsessive–compulsive disorder. DBS reduced her symptoms, and the clinical improvement was maintained for 10 years after treatment. The patient found it difficult to repeat internal pulse generator (IPG) replacement surgery and hoped to be on an off-stimulation status. She decided to keep the DBS setting off after the last IPG replacement. She has remained free of tic symptoms for 6 months now.

              Case 3: A 36-year-old male with GTS was treated with bilateral CM-Pf DBS at the age of 32 for his self-biting tics. He could not eat solid food and had lost weight before DBS was initiated. DBS obliterated his tic completely for 3 years. He hoped to turn off the DBS device because he did not want to repeat IPG replacement. The voltage of the DBS setting has been decreased and the battery has ran out, but he remains symptom free.

Conclusion:

These cases suggest that DBS is a temporary, but not necessarily a life-long, treatment option for patients with severe GTS. DBS may be terminated when the improvement of patient’s symptoms is sustained for a long period.

Introduction: As part of our preparation to select the optimal stimulation parameters in patients with Parkinson's disease (PD), who underwent deep brain stimulation (DBS), we perform a monopolar contact review by independently testing each of the 16 stimulation contacts (using directional leads , Boston Scientific) a few months after surgery.  In most cases adverse events at higher stimulation intensities have motor characteristics. In this particular case behavioral changes during mapping were the most dominant features.

Case report: The patient is a 63 years old female with a 5 years history of tremor dominant PD and motor fluctuations. Her pre-operative anti-PD medication consisted of rasagiline 1 mg, amantadine 100 mg three times a day and levodopa/carbidopa/entacapone 100/25/200 mg four times a day. Her past medical history included depression, treated with duloxetine 60 mg per day and mild head trauma 2 years after the diagnosis of PD. She underwent STN DBS 5 years after onset of symptoms for tremor and dyskinesia reduction. 

Methods: Each electrode is designed with 8 contactpoints: the distal en proximal contacts are circulair(ringE), whereas the middle two are each segmented in three contacts(dirE) (see figure). Both electrodes were placed in the posterolateral part of the STN, using anatomical 3D brain atlas (Brainlab), microelectrode recordings and macrosimulation. Using a novel method of localizing the markers post-operatively, we identified the left marker in the posteromedial direction and the right marker in the posterior direction, allowing us to identify the direction of each contactpoint. Each contactpoint was activated increasing the stimulation intensity up to an improvement of symptoms or advers events. Stimulation parameters consisted of direct current stimulation (mA) with a pulsewidth of 90 µs and a frequency of 130 Hz. Post-operative CT in combination with the anatomical 3D brain atlas identified the electrode localization and depth of the tip.

Results: The tip and part of the second level of the right electrode is located in the substantia nigra (SN), whereas only the tip of the left electrode is located in the SN. The right electrode appeared slightly medial to the preferred posterolateral position.

Suprathreshold stimulation characteristics on the left:

ringE 1: visual disturbances, reduction of tremor, relaxed

dirE 2 (2, 3, 4 in ring mode): tremor reduction, mild visual disturbances

Contactpoint 2: extreme somnolence, no tremor reduction

Contactpoint 3: falls asleep, tremor reduction

Contactpoint 4:immediate crying, nausea

dirE 3 (5, 6, 7 ring mode): unclear vision, sleepy, tremor reduction

Contactpoint 5: extreme sadness and crying

Contactpoint 6: crying

Contactpoint 7: less emotional, but heavy feeling in the head

ringE 8:slight uneasy feeling, but no sadness

Right side:

ring E 9: laughing, disinhibited, tremor reduction

dirE (10,11,13 in ring mode): tremor stil present, paresthesia L hand+, bursts in tears   

Contactpoint 10: heavy feeling in contralateral arm, gloomy

Contactpoint 11: sleepy, heavy feeling

Contactpoint 12: heavy feeling of the eyes, fatigue

dirE (13, 14, 15 in ring mode): acute laughing

Contactpoint 13: reduction of tremor, feels very good and awake, however strong emotions and facial dyskinesias

Contactpoint 14: very emotional, sad

Contactpoint 15: very emotional

ringE 16: extremely sad, nausea

On the basis of these findings the stimulation settings were adjusted and the contactpoints with extreme emotional response were not activated.  Mainly electrodepoints 3, 4 and 7 and ringE 1 on the left and 14, 15 and dirE 10,11, 12 (ring mode) was activated. This combination gave a tremor reduction, and no emotional adverse events. Her levodopa was stopped and amantadine reduced to 100 mg per day.

Conclusion: Directional stimulation mapping with individual contact stimulation can identify various emotional features not identified in ring mode stimulation. SN stimulation also exhibit mild behavioral changes. Stimulation of various contactpoints in more medial direction may have activated (i.e. inhibitied) the limbic part of the STN. Directional stimulation may not only identify motor feautures in the STN topographically, but non-motor symptoms (behavioral changes, sleep disturbances) also appear to be topographically present within the STN. Further studies with a large group of patients are needed to confirm our findings.

We report the first case of a patient with severe, intractable Tourette Syndrome with comorbid Obsessive Compulsive disorder, who recovered from both disorders with gamma-knife (GK) stereotactic radiosurgery following deep brain stimulation (DBS). This case highlights the possible role of the internal capsule within the neural circuitries underlying both TS and OCD, and suggests that in cases of treatment-refractory TS and comorbid OCD, bilateral anterior capsulotomy using stereotactic radiosurgery may be a viable treatment option.

Background: Psychiatric disorders are diagnosed based on symptom clusters that are subjectively reported by patients and their relatives. In the absence of objective biomarkers, questionnaires and clinical consultations are used to extract this information to guide management and evaluate clinical trials. This approach is limited, in particular by a susceptibility to reporting bias and a reliance on episodic assessments.

Digital phenotyping offers a novel means of identifying the early warning signs of a psychiatric disease, in real life and in real time for each patient. It is defined as the ‘moment-by-moment quantification of the individual-level human phenotype in-situ using data from smartphones and other personal digital devices’. The data obtained from these devices can be combined with medical records, molecular and neuroimaging data to produce a comprehensive patient phenotype.

Schizophrenia is a chronic psychiatric disorder characterised by periods of symptom exacerbation including delusions, hallucinations, disorganised thought and negative symptoms such as avolition. Therefore, communication metrics could represent quantifiable and objective biomarkers of disease and correlating changes in behaviour with disease state could provide novel methodology for clinical observation in psychiatry, with greater sensitivity than traditional techniques.

In this study, digital phenotyping was used to investigate how communication behaviour varies over time in a single patient to identify potential clinical biomarkers.

Methods: As proof of principle, a schizophrenic patient was recruited for a three-month period of smartphone data collection using a smartphone application called Beiwe, downloaded onto the patient’s personal phone.

Digital phenotyping relies upon the acquisition and analysis of objective behavioural data streams obtained from personal device sensors. Smartphone sensors and phone usage patterns generate complex multivariate data which is used to triangulate data streams for cross validation and optimisation of clinical correlations of disease. In this paper, text log data analysis is reported.

Text messaging behavioural metrics (herein referred to as Text Features) were extracted from the raw text logs. The Text Features extracted were ‘outgoing text number’, ‘outgoing text lengths’, ‘text out-degree’ (number of distinct phone numbers that received outgoing text messages from the subject), ‘incoming text number’, ‘incoming text lengths’, ‘text in-degree’ (number of distinct phone numbers that sent text messages to subject), ‘number of outgoing texts that received a reply’ and ‘responsiveness of subject’.

As a single biomarker of communication behaviour, text frequency was modelled as a Nonhomogenous Poisson Process. To identify likely change points within the data set, Akaike Information Criterion (AIC) was used. Correlation matrices were then produced for all Text Features to identify global behavioural change. Statistical analysis was completed using R studio.

Results: Whilst accounting for time of day, day of the week and weekly cycle, a statistically significant downward trend in text frequency was detected during the three month period for this patient (P = 0.0014).

AIC was applied to this longitudinal text log data set to identify multiple change points. Change points were identifiable at two timepoints during the three months. The precise date and time of these change points were identifiable.

Correlation matrices for the time periods between each change point demonstrated a change in correlation between Text Features over time, indicating a global change in certain components of behaviour. Notably, before the first change point, outgoing text number and outgoing text lengths showed strong positive correlation with the text in-degree and the incoming text message lengths. After the change point, this correlation was reversed.

Conclusions: This study demonstrates the potential role of digital phenotyping in psychiatric disorders. It is now possible to detect objective changes in communication behaviour using personal smartphones across the course of a disease, which could be used to monitor disease progression and relapse. Digital phenotyping may be of particular utility in trials of neurosurgical interventions for psychiatric disorders where sensitive biomarkers, mapped to Research Domain Criteria, could allow for precise monitoring of post-operative outcomes.

Introduction: The neurobiological mechanisms underlying clinical effects of psychotherapy are scarcely understood. In particular, modifying effects of psychotherapy on the electrical activity of neurons has not been studied so far. We here present data of an innovative experimental paradigm along the example of one patient with treatment resistant obsessive-compulsive disorder (trOCD) who underwent implantation of bilateral electrodes for deep brain stimulation (DBS). The patient had not received metacognitive therapy (MCT) before.

Methods:  DBS electrodes were implanted bilaterally with stereotactic guidance in the bed nucleus of the stria terminalis/ internal capsule (BNST/IC). The time frame between surgical implantation and electrode connection with a stimulation unit (5 days) was used for the experimental procedure. Electrodes were externalized via extension cables, yielding the opportunity to measure local field potentials (LFPs) directly from the BNST/IC via microelectrode recordings. The experimental procedure was designed as follows: a) baseline recording of LFPsfrom the BNST/IC. b) LFP recording during presentation of specific, individualized OCD pictures selected from the Maudsley Obsessive–Compulsive Stimuli Set mixed with neutral pictures taken from the international affective pictures system (IAPS). c) Application of 4 units with elements of MCT during 3 consecutive days. d) post-MCT microelectrode recordings from the BNST/IC.

Results: We found increased frontal activity during OCD related visual stimulus condition compared to neutral visual stimulus, which was condensed in an increased anteriorisation of the brain electrical field. After application of MCT, the frequency and amplitude of LFPs from the BNST/IC was reduced.

Discussion: Implantation of electrodes for treating pathologic neuronal circuits associated with psychiatric disorders offer the opportunity to gather data from neuronal structures, and to compare pre-post effects of treatment. We here demonstrate for the first time effects of reaction to visual OCD stimuli on the electrical activity of neuronal structures that are presumably involved in the etiology of OCD. Further, we demonstrate that applying only 4 sessions with elements of MCT alter LFPs in frequency and amplitude, thereby suggesting that MCT may alter neuronal activity associated with OCD. These results may give important cues for the neurobiological underpinnings of psychotherapy. 

Introduction: This is a report of two cases of treatment-resistant Obsessive-Compulsive Disorder (OCD) treated with Deep Brain Stimulation (DBS). Follow-up of 6 months was performed with adjustment of stimulation parameters and turn-off trial blinded to patient and raters.

Case description:

Case 1 is a 38-year-old Caucasian female with Graves’ disease, allergic rhinitis, luteal phase insufficiency. First OCD symptoms were present in the age of 16, treatment started in 21. During 17-year treatment the patient was resistant to pharmacotherapy (selective serotonin reuptake inhibitors – SSRI and clomipramine, in combination with both generations of antipsychotics). Cognitive-Behavioural Therapy (CBT) did not bring significant improvement. The patient met criteria for DBS, including severity of symptoms (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS=35) and impaired functioning (Global Assessment of Functioning, GAF=35). Implantation of electrodes was performed, targeting ventral part of anterior limb of internal capsule (ALIC) and nucleus accumbens, bilaterally. One contact was located in nucleus accumbens, and the remaining 3 contacts in ALIC. Two Medtronic Activa SC single-channel non-rechargeable stimulators have been implanted. Bilateral stimulation has been started 2 weeks after the surgery, with starting voltage=3,5V, pulse width=90ms and frequency=130Hz. Psychiatric assessment was performed in 2-weeks periods. At treatment onset only subjective improvement of mood and anxiety have been observed, resulting in progressive increase of DBS parameters. 2 months after the onset of stimulation, with voltage=4,5V, significant objective and subjective improvement of OCD symptoms (Y-BOCS=21), mood, anxiety and quality of life have been observed. Patient found employment only for several weeks. Following evaluations revealed insufficient CBT compliance and psychogenic factors that together contributed to aggravations of OCD (Y-BOCS score up to 28), regardless of DBS parameters increase. Poor insight and compliance has been observed, resulting from preoperative personality features and little motivation for treatment. Patient increased doses of medications on her own. After 6 months of stimulation turn-off trial was performed with patient and raters blinded. Aggravation of anxiety and depressive symptoms was observed few hours after turning the device off. 2 days later patient was hospitalized due to severe OCD exacerbation (Y-BOCS=40) and suicidal ideations. Stimulation was restored, resulting in significant improvement of mental state within few hours (Y-BOCS=20).

Case 2 is a 27-year-old Caucasian male. No significant somatic history. Presented first symptoms of OCD in the age of 8, started treatment in the age of 15, when diagnosed with OCD and social anxiety disorder. 12-year treatment resulted only in temporary improvement, subsequent obsessions and compulsions were developed. SSRIs, clomipramine, antipsychotics, normotymics and regular CBT brought no significant effect. The patient met criteria for DBS therapy, including severity of symptoms (Y-BOCS=28) and impaired functioning (GAF=40). Implantation technique, target and stimulator used were the same as in Case 1. Bilateral stimulation has been started two weeks after the surgery, with starting voltage= 3V, pulse width=60ms and frequency=130Hz. Fast response after 1 month of stimulation was observed, starting with subjective reduction of anxiety and depression, followed by significant improvement in control of OCD symptoms and CBT compliance. With voltage increased to 3,5V: Y-BOCS=12 and GAF=50. Good insight and treatment motivation with excellent compliance has been observed throughout the whole follow-up period. Turn-off trial is scheduled for May 2018.

Discussion and conclusions:

These two cases illustrate the importance of performing 3 types of treatment for OCD simultaneously: DBS, CBT and pharmacotherapy. According to DSM-V criteria, poor insight was presented by Case 1 and good insight by Case 2. Differences in insight level and personality features could have resulted in motivation and compliance quality. In Case 1 CBT discontinuation has lead to OCD aggravations, while DBS parameters remained the same and turn-off trial proved importance of DBS in long-term treatment. In Case 2 DBS improved the quality of CBT compliance, while CBT was unsuccessful prior to stimulation. Interdisciplinary, complex care should be considered in severe, treatment-resistant OCD.

Introduction. Obsessive-compulsive disorder (OCD) is a severely debilitating neuropsychiatric disorder whose lifetime prevalence is estimated at 2%. After standard treatment protocols, 10% of patients remain therapy-refractory. For these patients, deep brain stimulation (DBS) emerged in the late 1990s as a therapeutic alternative.

Objective. To report on long-term DBS treatment and results for a group of severely disabled therapy-refractory OCD patients recruited and followed at the University Hospital of Montpellier, France.

Design. This is a prospective observational study reporting on the DBS outcome in OCD over a five-year minimum time period.

Patients. The study included seven patients (age 34 to 60 years) suffering from OCD with the following criteria: substantial suffering and functional impairment, chronic treatment-resistance confirmed by experienced psychiatrists according to published criteria; meeting the recommendations for surgery after evaluation by a multidisciplinary team from the Montpellier University Hospital. Follow-up was reported for six subjects. One patient was excluded from analyses due to attrition.

Interventions. Between June 2003 and January 2008, patients were recruited for DBS and underwent MRI-guided bilateral simultaneous implantation of two pairs of quadripolar electrodes performed under general anesthesia by stereotactic surgery. In the absence of definite agreement on the most effective DBS target for OCD, a combination of two DBS targets was chosen for each subject to explore their contribution to the underlying pathological neural circuitry of OCD.

Main outcome measures. Response to DBS was assessed by the difference between OCD score at baseline and after DBS, as rated by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Responders were defined by a score decrease of at least 35% on the Y-BOCS.

Results. Mean (± standard deviation) Y-BOCS score decreased by 48%, from 31.2 ±1 at baseline to 16.3 ±10.6 at 12 months after DBS, and by 55% (mean 14 ±13.9) from baseline to last follow-up visit. Three out of the six subjects met criteria of responsiveness with a Y-BOCS decrease of 73.5% (mean 23 ±9.2) from baseline to 12 months post-DBS, and a decrease of 93.6% (mean 29.3 ±4) from baseline to last follow-up visit. Finally, among responders, subthalamic nucleus (NST) stimulation was effective for two out of three subjects. Simultaneous stimulation of two distinct anatomical targets did not yield better clinical outcome. Protracted DBS efficacy was documented for at least 73 months (about 6 years), and up to 178 months (14 years and 10 months). Between baseline and last follow-up visit, depressive symptoms assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) significantly improved in the group as a whole (p=0.049), as well as anxiety measured with the Hamilton Anxiety Rating Scale (HAM-A) (p= 0.03). Global functioning evaluated with the Global Assessment of Functioning (GAF) significantly improved in the three responders (p= 0.03). No major adverse effects occurred, except for patients who had cleaning compulsions. For them, surgical revisions of the scars were needed, and parts of the DBS system removed due to infections (3/6).

Conclusion. Observational study of six severe therapy-refractory OCD patients treated with DBS confirmed long-term efficacy and relative safety of the procedure.

Background:  The success of Deep Brain Stimulation (DBS) in movement disorders has renewed the interest in DBS for psychiatric disorders. Mayberg et al reported the results of subgenual DBS in treatment resistant depression in their seminal paper [1].  However, this same target was published by Lauri Laitinen in the 1950s-1970s[2]. 

Our aim was to verify Laitinen’s anatomical target and to report on a patient who underwent this procedure.

Material and methods: Helsinki University Hospital records were searched for psychosurgical cases performed between 1970-74. Alive consenting patients were invited for interview and a brain MRI. The lesion size and location was analyzed from T2 images using Agfa Impax and Brainlab stereotaxy software

Results: In the study period 223 stereotactic operations of which 211 were performed by Laitinen. Of these operations, 44 were cingulotomies. We found only five patients alive, one of which consented to participate. 

The patient had undergone subgenual cingulotomy in 1971 for obsessive thoughts, anxiety, and compulsions, and received at the time a diagnosis of “schizophrenia psychoneurotica”. According to patient files, the patient had previously severe symptoms, frequent hospitalizations and suicide attempts despite conservative treatment.

According thesurgical records the operation was done using pneumoencephalography for visualization of the anterior and posterior commissure and carotid angiography for visualization of the pericallosal arteries, genu of corpus callosum and the interhemispheric fissure. The lesioning was done at several depths on both hemispheres. During the coagulations, the patient reported initial sensation of warmth and that anxiety first decreased and then resolved completely. 

In the interview 38 years after the surgery patient reported that she was practically symptom-free for eight years after the surgery and suffering later only of mild symptoms. Additionally, the patient was never hospitalized after the surgery for psychiatric reasons. Bilateral subgenual subgenual lesions (254 and 160 cubic mm, respectively) were found in the Brain MRI. In relation to the midcomissural point the coordinates of the center of the lesions were for right and left respectively: 7,1 & 7,9 mm lateral; 0,2 mm inferior & 1,4 mm superior, and 33,0 & 33,9 anterior. Fig 1.

Conclusions: The patient reported satisfactory results for a psychiatric disease, that in retrospect, could better correlate with obsessive-compulsive disorder, anxiety and depression. The lesion was found to be in the expected location, overlapping the DBS target for depression [3]. 

The anterior dorsal cingulum above the genu of corpus callosum was a more common the target for various psychiatric conditions such as obsessive-compulsive disorder, anxiety, depression, drug addiction and chronic pain [4]. However, thecingulum above the genu consists of mainly cognitive whereas the limbic functions reside subgenually [5]. The subgenual has also a major role in depression, recovery from depression and sadness [6]and so is an inviting target for psychiatric disorders.

Our results verify of correct placement of Laitinen’s subgenus cingulotomy target, similar to current target used in DBS for depression.

1.     Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al.: Deep brain stimulation for treatment-resistant depression. Neuron 2005 Mar 1;45:651–660. 

2.     Laitinen LV: Stereotactic lesions in the knee of the corpus callosum in the treatment of emotional disorders. The Lancet 1972 Feb 26;1:472–475. 

3.     Hamani C, Mayberg H, Snyder B, Giacobbe P, Kennedy S, Lozano AM: Deep brain stimulation of the subcallosal cingulate gyrus for depression: anatomical location of active contacts in clinical responders and a suggested guideline for targeting. J Neurosurg 2009 Dec;111:1209–1215. 

4.     Ballantine HT Jr., Cassidy WL, Flanagan NB, Marino R Jr.: Stereotaxic Anterior Cingulotomy for Neuropsychiatric Illness and Intractable Pain. J Neurosurg 1967 May;26:488–495. 

5.     Bush G, Luu P, Posner M: Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci (Regul Ed) 2000 Jun;4:215–222. 

6.     Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, et al.: Reciprocal Limbic-Cortical Function and Negative Mood: Converging PET Findings in Depression and Normal Sadness. American Journal of Psychiatry 1999 May 1

Aim

We set out to determine if there was any difference between mothers and fathers of adult children with OCD in the way they accommodate their child’s OCD symptoms.

Background

Obsessive compulsive disorder (OCD) has a lifetime prevalence of 1-3 %, but it can have profound effects on the family members of people affected.

‘Family Accommodation’ is a recognised modification of behaviours by relatives and carers in direct response to the patient’s symptoms; typically, rituals. Although it is likely to occur in a range of mental disorders, it is a concept largely associated with OCD. Higher levels of Family Accommodation (FA) are associated with: greater symptom severity in the patient; less favourable treatment outcomes; higher levels of functional impairment; and increased family distress.

Method

We used the Family Accommodation Scale – Self Rated (FAS-SR; Pinto, 2013) to rate the severity of FA in patients and their parents who were presenting to the Advanced Interventions Service for assessment. This 19-item scale measures two main domains: 2) The relative’s report of their relative’s symptom severity; and 2) A self-reported assessment of their own accommodation in terms of frequency and severity of their own behaviours in response to their relative’s symptoms. Overall severity of symptom burden was measured using the self-report Yale-Brown Obsessive-Compulsive Scale (Y-BOCS-SR).

Results

The sample consisted of 11 patients (six male and five female) where concurrent ratings on the FAS-SR were available from both parents. The mean (± SD) age of patients was 32.1 ± 9.2 years, and range from 20 years to 46 years. The mean (± SD) score on the Y-BOCS-SR was 28.2 ± 10.9. Seven (63.6%) ratings were performed before treatment, and 36.4% of ratings were performed during or after a course of treatment.

On average, mothers rated accommodation approximately 50% higher than fathers. Only one father rated accommodation higher than the mother. In seven parents, the difference between maternal and paternal ratings was less than 50%, but in four parents the mother rated accommodation between 100% and 660% percent higher than the father.

Discussion

On average, mothers rated their accommodation 50% higher than fathers, with around one-third reporting levels of accommodation that were at least twice that of the father. This may highlight a parent-specific factor which have the potential to act as a maintaining factor for a less favourable outcome. It is possible that these patterns may reflect shared predispositions to anxiety.

Conclusion

Although gender differences among OCD patients are well documented, we believe that factors associated with parental gender may also be important to consider; especially when planning specialist treatment for complex and chronic disorders.

Observed differences in the reporting of accommodating behaviours between parents should be factored in to any discussions about neurosurgical treatment pathways; both pre- and post-operatively. It would seem as though some mothers are especially prone to accommodating their male child’s symptoms and this could not only influence decision making, but it could have effects on post-operative outcome if not managed sensitively.

Background

Historically, Neurosurgery for Mental Disorder (NMD) has had a chequered history and despite modern techniques, attitudes towards lesion surgery have often been negative. Several surveys of attitudes towards psychiatric neurosurgery have been conducted in Scotland, but none have focused on attitudes of nurses; who will often provide much of the pre- and post-operative care for patients undergoing neurosurgery. Further, nurses may be an important influence on decision-making by patients.

Method

We used a short paper-based survey. First, we asked nurses similar questions to those used by the Clinical Resource and Audit Group Working Report on Neurosurgery for Mental Disorder from 1996. Second, we asked additional questions to assess attitudes regarding the role of nursing staff within a psychiatric neurosurgical pathway, and we also asked respondents if they believed it should be included in undergraduate training.

The survey was completed by three groups of staff: 1) inpatient and outpatient nurses working within General Adult Psychiatry; 2) outpatient nurses working within Old Age Psychiatry; and 3) nursing students within the Universities of Dundee and Abertay.

We also compared the results of this survey with the responses provided previously by psychiatrists in the mid-1990s.

Results

One hundred and seven questionnaires were returned. The majority (80%) of respondents were female. 69% of nurses surveyed were under the age of 45 and 36% had been qualified for 10 years or more. 38% were student nurses.

Overall, attitudes towards NMD were positive. It was considered an acceptable procedure by 84% of respondents, and only 17% thought that it should not be carried out. Only 1-in-20 nurses believe that MH nurses should not be involved in psychiatric neurosurgery and 79% of respondents disagreed with the view that NMD is unjustified and should never have been conducted. Around 90% of respondents supported the view that mental health nurses should have a range of roles in supporting patients undergoing neurosurgery.

Responses differed between groups of nurses. Qualified nurses were more likely to strongly agree with the statement that NMD was an acceptable treatment (48% vs 29%), although overall agreement was similar. Similarly, qualified nurses were twice as likely to strongly disagree with the statement that NMD was an unjustified procedure (27% vs 15%). Although endorsement of NMD did not differ markedly between different specialties, the ward with greatest experience of treating NMD patients (pre- and post-op) had the most positive attitudes.

There was no clear difference between the contemporary view of mental health nurses and the historical views of consultant psychiatrists. Overall, positive attitudes to psychiatric neurosurgery were stable over time.

Conclusions

This survey indicated that nurses generally hold positive attitudes towards neurosurgery, irrespective of specialty and experience. Importantly, they view themselves as having a role in supporting people on this treatment pathway. There was also a view that advanced treatments such as psychiatric neurosurgery should be included in undergraduate training.

Gamma knife capsulotomy (GKC) has been used for 25 years for treatment of otherwise intractable obsessive-compulsive disorder (OCD). Early procedures carried out at Butler and Rhode Island Hospitals using a bilateral “single shot” targeting only the middle third of the anterior limb of the internal capsule (ALIC) were effective for 1 out of 15 patients; adding on bilateral ventral “shots” increased the effectiveness of the procedure, to where approximately 50 percent of patients demonstrated a full clinical response (>35 percent improvement on the Yale-Brown Obsessive Compulsive Scale, YBOCS). Subsequent clinical outcomes using a “double shot” procedure, targeting both the middle and ventral portion of the ALIC have been favorable: 50-60 percent of patients demonstrate a full response at one year. In this study we prospectively tested the hypothesis that bilateral single shot ventral lesions in the base of the ALIC would lead to clinical improvement in a two site open label study (Butler and Rhode Island Hospitals; University of São Paulo). The patient sample met the same strict selection criteria as our prior studies. Eleven patients received bilateral, “single shot” radiosurgical lesions in the ventral third of the ALIC and adjacent ventral striatum, 8-10 mm anterior to the posterior border of the anterior commissure, using a dose of 150 Gy. Mean age at surgery was 34.27 years (SD=7.38), with age of onset of initial OCD symptoms at 11.73 years (SD=6.45). Mean pre-surgical YBOCS OCD severity was 32.55 (SD=3.93), representing extremely severe symptoms, which had remained chronic despite aggressive conventional treatments. These clinical features were consistent with those in past surgical samples. YBOCS severity declined from 32.55 to a mean of 30.18 (SD=3.06) after one year (p=0.09). There were no full responders (>35% YBOCS decline), while two (18%) were partial responders (25-35% YBOCS decline). These results contrast with those of prior studies where larger, “double shot” lesions, which included the current target but extended more dorsally, were effective. Continued research into individualization of surgical targeting is needed to determine if a larger lesion (covering more prefrontal-subcortical tracts) and/or a more optimally placed lesion (with respect to specific fiber pathways involving specific ventral prefrontal regions) is necessary for clinical response.

Introduction:  The management of patients with refractory obsessive compulsive disorder (OCD) has shown improvement with bilateral deep brain stimulation (DBS) in the inferior thalamic peduncle (ITP).  In our experience, 3 patients who underwent surgery improved their Y-BOCS Yale-Brown Obsessive Compulsive Scale score but only one needed very hight voltage in order to do that.  Objective:  To report the clinical observation in one of the three patients who underwent DBS for refractory OCD in the ITP who requiered 9 volts in order to improve the symptoms.  Methods:  3 patient operated between October 2013 and November 2014 with (DBS) in the (ITP) due to refractory (OCD) were followed-up with for a period of 55 to 42 months.  Y-BOCS, was taken before surgery and every six months after surgery.  Other scales of quality of life and health status were taken.  A multidisciplinary group manages the patient befor, during and after surgery.  With Leksell frame impanted, Philips 3 Tesla MRI is performed and the target is planned with surgiplan software.  Fhc microrecording system is used.  3387 Medtronic electrode is implanted bilaterally.  Results:  The second case improved only 40% with regular paramethers of stimulation but when the voltage was increased to 9 volts the improvement reached 90%. For the three cases Quality of Life EW-5D-5L, hte state of health ESH and the Y-BOCS improved in the post surgical between 70-90%, 60-90%, 70-95% respectively.  One of the cases presented foreign body reaction with exposure of the distal part of the lead and infection that made it necessary to remove the system.  Conclussion:  Bilateral (DBS) in the (ITP) has shown signficatn improvement in refractory (OCD).  When the outcomes are not as we expcted one option should be to increase the voltage in order to obtain improvement of symptoms without having major side effects.  This is only an observation and more studies an more cases should be carried out.  

Introduction

In the pre-L-dopa era, Spiegel reported in 1963 the effect of a lesion in the thalamic part of field H on tremor, rigidity, and other extrapyramidal disorders of Parkinson’s disease (PD). It was so-called campotomy. In the L-dopa era, deep brain stimulation of the subthalamic nucleus for PD attracted attention. The reports of the treatment of pallido-thalamic tract (PTT) ablation were limited. We performed pallidothalamic tractotomy (Forel-H field) for PD using magnetic resonance-guided focused ultrasound (MRg-FUS) technique. The clinical course of the first patient is reported.

Patient history and pre-operative symptoms

A 45-year-old man had been ill for six years. He noticed tremor of the right upper and lower extremities at 38 years of age. His symptoms were diagnosed as PD, and treatment was started with L-dopa/decarboxylase inhibitor (DCI) and a dopamine agonist at 40 years of age. He had been busily working as the owner of a construction company. He complained of severe insomnia and headache, and every day he took a double dose of Brotizolam 0.25mg.

Neurological findings

Severe cogwheel rigidity was observed in the trunk and upper and lower extremities, affecting the right side more. Rigidity of the right lower extremity was severe, and it was very hard to passively stretch the right ankle. Tremor affected both extremities, especially the right lower extremity. Bradykinesia was severe on the right side. Repetitive movements like diadochokinesis (DDK), finger tapping, leg agility, and toe tapping were slower, with dysrhythmia on the right side. During walking, he dragged the right leg without arm swings, but he had no freezing gait. Abnormal postures were observed, such as forward bent posture, right thalamic hand, and dorsiflexion of the right hallux. He was independent in daily living.

Anti-Parkinsonian treatment was started three years later, and he noticed the wearing-off phenomenon. In the off-phase, the tremor worsened, and the right lower limb was stiff, like dystonia, and the right hallux showed painful dorsiflexion.

The MDS-UPDRS score was 21 points in the on-phase and 42 points in the off-phase. The dyskinesia score was 0, and the L-dopa-induced painful dystonia score was 4. He had no psychiatric symptoms.

Medical treatment was not sufficiently effective, and dystonia in the off-phase was severe and affected his daily living. He did not want electrodes in his brain and chose the treatment.

Surgery

Surgery was performed using the ExAblateMRg-FUS system with the patient awake. The target was the left PTT. The tentative targets were 1 mm below the midpoint of the AC-PC line and 9.0 mm lateral to the midline. The exposure of focused ultrasound was performed 10 times, including positioning. One exposure was stopped by the patient due to headache. The temperature exposure increased from 45°C to 52°C.

Postoperative symptoms

He was discharged the day after surgery, and he played golf with his father after four days of hospital discharge and enjoyed it. The off-phase and painful dystonia were entirely gone, and the severe headaches decreased. He still took sleeping pills, but falling asleep was easier. His posture became normal. During walking, there was no dragging of the right lower extremity, and the swing of the upper limbs became natural. He had no thalamic hand, no painful dystonia, no tremor of the right lower extremity, and slight tremor of the left lower extremity. Rigidity improved bilaterally. While taking L-dopa/DCI, muscle stretch became almost normal. The amplitude and rhythm of all repetitive movements improved bilaterally. One month later, the MDS-UPDRS score was 7.

Adverse events

After the operation he had light headaches in the evening. Postoperative neurological examination showed that the tendon reflexes of both upper and lower extremities were hyperactive, with a positive Tromner reflex on the right upper extremity and no Babinski sign bilaterally. No weakness was found.

Conclusion

PTT ablation by FUS is effective for parkinsonian symptoms and is non-invasive.

Improvements by ablation were observed not only on the operation side, but also the non-operation side.

To evaluate the efficacy of Gamma Knife radiosurgery (GKRS) as treatment in patients with 10 or more metastatic brain tumors.

Between February 2014 and January 2016, 20 patients were treated with GKRS for 10 or more brain metastases. We retrospectively analyzed the data from these patients, with survival and tumor control as primary endpoints. Brain volumes treated with 8 Gy and 12 Gy were measured to explore volume of treated tissue as a contributing factor to tumor control. Pre-treatment and post-treatment magnetic resonance imaging (MRI) studies were reviewed at intervals of 3 months, as were patient records on site.

Of the 20 patients treated, 3 were excluded due to insufficient follow-up data. For the 17 included patients the median age was 61 (range 19-76). These patients were treated for a total of 323 tumors, with a median of 17 tumors per patient (10-34). The median survival for these patients was 12.5 months (1.3-16.9). Patient survival was censored at the time of data collection, and the true upper limit of survival is higher than recorded here. The mean percent of brain volume treated was 0.9, with a median of 0.41 (0.07 – 3.38). The mean percent of brain volume that received a dose of 12 Gy was 5.0 (0 – 21.0), and of 8 Gy was 9.0 (1.0 – 31.0). For each of the first three 3-month intervals, the median percent of tumor control was 97%, 96%, and 100%, respectively in the patients with available data.

GKRS effectively treats and controls brain tumors, even in patients presenting with 10 or more tumors simultaneously. The number of tumors initially present was not found to have a significant correlation with general tumor control.

Gamma Knife Thalamotomy for tremor: a literature review

Cateno C. T. Petralia MRCS MD,¹ Neil Kitchen FRCS MD,^1,2,3 Jonathan A. Hyam FRCS PhD ^1,2,3,4

1. Victor Horsley Department of Neurosurgery, The National Hospital, Queen Square, London, UK

2. Queen Square Radiosurgery Centre, The National Hospital, Queen Square, London, UK

3. Institute of Neurology, University College London, UK

4. Unit of Functional Neurosurgery, The National Hospital, Queen Square, London, UK

Objectives:

Functional neurosurgery is seeing a renaissance in lesioning procedures. Gamma Knife Thalamotomy (GKT) is such an example for patients with intractable disabling tremor who are unsuitable or unwilling to undergo open neurosurgery. The aim of this review was to identify the different dosing configurations and target locations reported in the literature and their relation to tremor benefit and adverse effects.

Methods:

Inclusion: relevant studies including case-report, patient series, prospective studies, retrospective studies, and case-controlled studies of patients in which GKT was performed for essential tremor or tremor secondary to another pathology. In all of the papers included in this review, the authors recorded the dose of radiation, the target, and the aetiology. Search key words related were “tremor”, “Parkinson’s disease”, “essential tremor” and the intervention performed “gamma knife”, “radiosurgery”, “thalamotomy”.

Results:

Search key words related 21 studies were included. The mean percentage tremor improvement across all of the studies was 79% (range 0% to 100%). Overall incidence of adverse effects was 12% (range 0% to 52%). Mean radiation dose was 140 Gy ranging between 100 Gy and 200 Gy. All studies targeted the ventral intermediate (VIM) nucleus of the thalamus. The target was identified in all studies using MRI and in most of the cases (85%) with reference to the stereotactic atlas. 16 studies reported the coordinates of the target. 14 studies targeted above the level of the anterior commissure–posterior commissure (AC-PC) line (7 targeted 2-3mm above AC-PC; 6 targeted 3-5mm above AC-PC); 2 studies targeted at the AC-PC level, conferring 50% & 100% efficacy and 12% & 8% adverse effects; one study targeted from 2mm below to 4mm above AC-PC level (conferring 100% efficacy and 3% adverse effects).

Adverse effects were associated with highest doses, bilateral lesions, and unintended/misplaced lesion. Higher radiation doses were related to an increased rate of lesions larger than expected in patients who did suffer complications the targeting did not accurately produce the intended lesion. There was no obvious single targeting strategy which produced better outcomes, however, the combination of MRI and stereotactic atlas seems to provide the better outcomes (Ohye et al. 2005). When bilateral lesions were performed the chances of adverse effects are considerably increased. The worst outcomes were related to a radiation dose of 200 Gy or bilateral lesions.

Conclusion:

Efficacy of GKT can be high with a low overall adverse effect rate. Variations in targeting strategy did not provide one clearly superior method. Lesions conferring significant adverse effects were seldom what the planning practitioners had intended. Bilateral lesions have a higher adverse effect rate, as per other modalities of lesioning.

The Gamma Knife Unit at the Department of Neurosurgery, Medical University Vienna looks back on 26 years of experience in radiosurgical treatment. In this timeframe several thousand patients with brain metastases (BMs) have been treated. Since the implementation of the Gamma Knife Perfexion® in 2012 the modern radiosurgical treatment era has commenced. Apart from developments in the radiosurgical treatment there has been significant progress in the oncological management of cancer patients since the introduction of immunotherapy and personalized targeted therapy. So far, even though concurrent treatment with radiosurgery and targeted drugs or immunotherapy is increasingly performed, available safety information is scarce. We have recently established a database of all patients with brain metastases treated in the modern radiosurgical and oncological era from 2012 onwards. So far the database includes 1038 patients and over 4000 radiosurgically treated BMs. In the modern radiosurgical era melanoma has presented itself as the second most frequent primary tumor of BMs (15%), at least in our series. Especially melanoma patients are increasingly treated with immune therapy. We provide radiological and clinical outcome data of melanoma patients with BMs treated in the modern radiosurgical and oncological era. The vast majority of melanoma patients were treated with immune therapy or targeted therapy prior and after radiosurgical treatment.  We especially focus on complications after radiosurgery in patients with immune therapy or targeted therapy.