Introduction

Deep brain stimulation (DBS) systems can be operated in voltage and current mode, and the electric field (EF) steered by redesigning the contacts on the leads. The aim of this study was to exemplify the possibilities with patient-specific computer simulations by using the finite element method (FEM) in the investigation of the EF around DBS leads and its influence from tissue type, stimulation mode and active contact surface. 

Methods

Two leads with steering function; 6180 (St Jude Medical, USA) and SureStim1 (Medtronics Eindhoven Design Center BV, The Netherlands) and the conventional 3389 lead (Medtronics Inc, USA) were used for the investigation. Both equivalent contact configurations as monopolar settings, and different steering posibilities, were considered. The leads were applied in two brain targets of the same patient i.e. the zona incerta (Zi) where the actual lead was implanted, and a virtually calculated target, the ventral intermediate nucleus (VIM) of the thalamus. The simulation study was approved by the local ethics committe (2012/434-31) and the patient gave informed written concent. A brain model consisting of electrical conductivity values of the grey and white matter, cerebrospinal fluid and blood was created by classifying the preoperative stereotactic 3T MR image with the in-house developed MatLab software [1]. Based on Leksell coordinates, extracted from the postoperative co-registerd CT-MRI lead artefacts in Surgiplan (Elekta Instrument AB, Sweden), the three leads were placed in Zi and VIM in the brain model. Simulations of the EF surrounding each lead and target were done at equivalent amplitudes in voltage and current modes [2] by use of Comsol Multiphysics (Version 5.2, Comsol AB, Sweden). All simulations were done in the chronic stimulation time point corresponding to four weeks post surgery. The results were displayed with 0.2 V/mm isolevels in axial, coronal and sagittal directions. The setting of the isolevel was based on neuron model simulations [3]. The shape, volume and maximal radial distance were calculated for each simulation and compared between stimulation modes, targets and leads with and without steering.

Results

The simulations show that equivalent monopolar contact configurations on the three leads result in similar EF distribution, but with systematic larger volumes in current mode compared to voltage mode. Due to tissue variations in the target region, there was a small difference in volume and shape between the two targets. The volumes were systematically a few percentage larger in Zi compared to VIM. The steering function for lead 6180 is examplified in Fig. 1. In these simulations one segment of the split ring (contact 5) of 6180 was set to 3V and compared to a setting with all three segments active with the same amplitude. In current mode eqvivalent EF isosurface for the steering function was found for an amplitude of 1.1 mA. Additional examples of the steering function and its implications on the EF from stimulation mode and tissue types will be presented in the poster.

Conclusions

Simulations showed that in current mode, smaller contact surface area achieve a larger electric field extension in comparison to voltage mode. The electric field extension is influenced by the surrounding tissue regardless of the operating mode.

References

[1] K. Wårdell, E. Diczfalusy, and M. Åström, "Patient-Specific Modeling and Simulation of Deep Brain Stimulation " in Studies in Mechanobiology, Tissue Engineering and Biomaterials, ed: Springer-Verlag, 2011.

[2] F. Alonso, S. Hemm-Ode, and K. Wårdell, "Influence on deep brain stimulation from lead design, operating mode and tissue impedance changes - a simulation study," Brain Disorder & Therapy, vol. 4:3, 2015.

[3] 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, vol. 62, pp. 664-72, Feb 2015.

Current data indicate high effectiveness of the surgical treatment of patients with temporal lobe epilepsy. Anterior temporal lobectomy and selective amygdalohippocampectomy are the typical operations in this disease. Stereotactic interventions in the area of a hippocampus and amygdaleum are the alternative to open surgery, and they have a long history. Such operations had a pathophysiological basis; however, in recent years in the world practice, an interest in such interventions almost disappeared. The reason is the relatively low efficacy, compared with the open surgery in these patients.

On the other hand, there are many positive sides in a minimally invasive approach, implemented when performing stereotaxy. Stereotactic interventions are performed under local anesthesia and much smaller in duration, compared with lobectomy. Besides, it was found that a temporal lobectomy may be associated with risk of the growth of cognitive, neuropsychological and visual disorders. In addition, in the cases of lack of effectiveness of stereotaxis, the patients may be performed to repeated stereotactic operations or to an open surgery subsequently.

Now we can talk about the resurgence of stereotactic operations in patients with temporal lobe epilepsy, with the use of modern surgical equipment. There are data about performing radiofrequency (Parrent A.G., Blume W.T., 1999; Liscak R. et al., 2010) or laser (Willie J.T. et al., 2014, Grosse R.E. et al., 2016) thermoablation of amygdalohippocampal complex, with the use of the temporal or occipital stereotactic approaches.

From 1998 to 2010 at the clinic of the N.P. Bechtereva Institute of the Human Brain of the Russian Academy of Sciences (St. Petersburg) we have operated 21 patients with drug resistant temporal lobe epilepsy using two-stage stereotactic operations. The first stage included the implantation of the deep brain electrodes to record epileptic activity in uncus, amygdaleum and the hippocampus, with subsequent stereotactic ablation of the identified epileptogenic zones with the cryosurgical method, during the second stage of treatment. Lateralization of the operation was determined by the data set of EEG, MRI and fluoro-deoxyglucose PET. Surgery was performed using stereotactic temporal approach. The average total volume of ablation in mediobasal temporal region was 4.5-6 cm³. Despite the fact that no one patient after surgery demonstrated neurological and psychological deterioration, the outcome of operations were rather unsatisfactory – the result IA class on the Engel scale was achieved in only 33.3% of patients. We concluded that the possible reasons were, first, insufficient correct selection of patients for surgery, and secondly, too small volume of destruction in the target points. A number of authors suggest that the entorhinal cortex and other adjacent to amygdalohippocampal complex structures also play the role in the epileptogenesis and spread of epileptic activity and so they have to be regarded as the stereotactic targets.

Given these considerations, in 2016, we resumed conducting stereotactic destructions in patients with temporal lobe epilepsy, using modern equipment for operations and 3 T MRI stereotactic localization of targets. We used the cryoprobe forming tissue destructions up to 6 cm³ in each target point. 4 patients have been operated on, and destructions in the whole hippocampus and the uncus of parahippocampal gyrus were completed with the total amount of destruction about 12-18 cm³. Destructions in the amygdaleum have not been conducted in this group of patients, because of the absence of epileptic activity in this structure, according to the registration with the deep brain electrode. One patient underwent a combined surgery with the resection of the pole of the temporal lobe and stereotactic cryodestruction of the hippocampus. We noted that the used probe working with the temperature of the solid carbon dioxide forms the foci of cryodestruction with standard sizes and shapes, with a clear demarcation that allowed us to carry out a thorough preoperative planning of stereotactic interventions.

To date, all the patients are free of seizures, with no complications occurred in the postoperative period. Thus, significant advantages of stereotactic surgery for temporal lobe epilepsy are the safety and best toleration by patients compared to open surgery. The use of new operating techniques allows to increase the therapeutic outcome of such interventions.

Introduction and Objectives

The study of complex refractory epilepsies frequently requires data form invasive EEG. The regions of interest can be monitored with depth electrodes. These electrodes are usually implanted with stereotactic frames or robotized systems that are not readily available in many centres with a smaller surgery volume. 

Over the last years, neuronavigation has proven to be a valuable tool capable of replacing classic stereotactic frames in less precision demanding surgeries.

In this work we analyse the precision of non-frame based system for the implantation of stereo-EEG (SEEG) electrodes in our centre.

Material e methods

The retrospective analysis included all patients with medically refractory focal epilepsy who underwent implantation of depth electrodes for extraoperative EEG monitoring between June 2012 and January 2016. Trajectory planning was done with either Cranial™ 4 or Synergy Cranial™ 2.2 from Medtronic® and implantation of Dixi® or Alcis® electrodes was done with Mayfield® head clamp and Vertek® II articulated arm. All patients underwent early post-operative image control of implantation that was fused with pre-operative imaging. Analysis of demographics included entry-point and target accuracy, depth of each trajectory, procedure-related complications and quality of EEG recording.

Results

Fifty-one SEEG electrodes were implanted in 6 patients. Their mean age was 27.5 years (8-49 years old). On average, 8.25 electrodes were implanted per patient. The average time of implantation planning was 45 minutes. The average operative time was 141 minutes (range 104-178 minutes) with an average of 17 minutes per electrode (range 14.86-19.17 minutes). Measured accuracy obtained from entry point in 4 patients (35 electrodes) and target in 5 patients (45 electrodes) demonstrated a median entry point error of 2.41 mm and a median target point error of 2.51 mm. Planned target regions were reached in all 51 trajectories and there weren’t any procedure-related complications. Seizures were detected in more than one electrode in all 6 patients and a strategy was possible to delineate with data obtained from this SEEG.

Four patients were further operated with focal resections (2 are in Engel I and 2 in Engel III), one was implanted with DBS in ANT with seizure severity improvement and one refused resective surgery.

Discussion and Conclusions

This technique of implantation of SEEG depth electrodes has the necessary accuracy to achieve the goals of this type of EEG monitoring. In spite of having a lower accuracy compared to the classic systems, knowing the error margin allows us to establish security boundaries in order to avoid vascular structures. The simpler workflow of the neuronavigated implantation of depth electrodes can make this kind of investigation readily available in more epilepsy centres, improving their ability to treat even more complex cases.

Objectives: Presentation of an unusual case of a late intracranial infection in a patient with history of epilepsy surgery.

Methods: A 48 year old female patient with medically-resistant extratemporal epilepsy underwent two stages operation in 2012. In stage I, she underwent a left fronto-temporal craniotomy and subdural electrodes were placed over the left fronto-temporal cortical area. Following a week of intracranial recordings she underwent, stage II operation with left frontal multiple subpial transection (Morrell operation) and anterior 1/3 corpus callosotomy. She had an uneventful post-operative course and the epileptic activity was successfully controlled with anticonvulsive therapy. Recently, she presented with a swelling of her left frontal scalp, pyrexia (38.5^oC), generalized weakness and memory deficits. Her brain CT scan revealed an epidural collection.

Results: She underwent surgical exploration in the operating theater. Skin necrosis adjacent to her old skin incision was noted. Following debridement of the necrotic areas a purulent subcutaneous collection was found and evacuated. The bone flap of the old craniotomy was removed and osteomyelitic foci were identified. The epidural space had an abundant collection of pus that was also evacuated. After meticulous irrigation and debridement, the dura matter remained intact. The bone flap was discarded and the skin sutured properly. Staphylococus hominis was cultivated from the wound. Antibiotic therapy with vancomycin and metronidazole was commenced, according to sensitivities. Post-operatively, the patient had 2 seizures that were successfully controlled with anticonvulsants. She remained afebrile after the 2nd week.

Conclusions: Skin erosion along old skin surgical incision and epidural empyema formation could be an uncommon late complication, following consecutive epilepsy operations. In our case, surgical debridement with empyema evacuation, craniectomy and antibiotic therapy, secured patient full recovery.   

Objectives

A pilot study evaluating the efficacy of intracranial stimulation at treating medically refractory epielpsy in children 

Methods

A retrospective analysis of eight children who underwent intracranial electrical stimulation for the investigation and treatment of their refractory epilepsy at King's College Hospital between 2014 and 2015.

and 2015. Five had subacute cortical stimulation (SCS) during intracranial video-telemetry with efficacy

of stimulation evaluated by counting interictal discharges and seizures (both clinical and subclinical).

Three other children underwent deep brain stimulaton (DBS) of the centromedian (two patients) or

anterior (one patient) thalamic nuclei. The incidence of interictal discharges was evaluated visually and

quantified automatically.

Results: Three patients had thalamic DBS (one with idiopathic generalized epilepsy, one with

presumed symptomatic generalized epilepsy and one with right fronto-temporal epilepsy) and 5

patients had SCS (one with temporal lobe epilepsy and four with frontal lobe epilepsy). Among the

three children with DBS, two had >60% improvement in seizure frequency and severity and one had

no improvement. Among the five children undergoing SCS, four showed improvement in seizure frequency

(>50%), severity of seizures and interictal epileptiform discharges (>75%) while one chid did not show

improvement. Procedures were well tolerated by all children.

Conclusion: Cortical and thalamic stimulation appear to be effective and well tolerated in children

with refractory epilepsy. Subacute cortical stimulation can be used to identify the focus and predict the effects of resective

surgery. Further larger studies are necessary.

Introduction:  There is considerable debate over the extension of mesial temporal structures needed for epilepsy control in MTLE. Outcomes have been reported in the literature that corresponds with very dissimilar resection lengths of hippocampus and amygdala resections. A few works have tried to relate hippocampal linear resection length to outcome and found no direct relation, but there are still no reports on high-filed MRI measured volume of resection of mesial structures and its relation with outcome.

Objectives:

1. To determine if the volume of hippocampal and amygdala resection in MTLE correlates with outcome, namely with seizure control and post-operative deficits
2. To review the long term outcomes of a single center series of resective epilepsy surgery

Methods:

Resection volume determination was performed on pre and post-operative high resolution isotropic coronal T1 3 tesla MRI, using ITK-Snap software; MRI structures were segmented with 3 plane orthogonal verification, according to EADC- ADNI harmonized protocol for hippocampal segmentation volumes were then correlated with outcomes

For the surgical series review, a database was created with patient data and statistical analysis performed with SPSS

Results:

1-     Volume measurements: Post-operative hippocampal volumes ranged from 722 to 2956mm3 and post-operative amygdala volumes ranged from 215 to 2600mm3. Worst post-operative seizure control correlated with larger post-operative hippocampal remnants while no differences were found with post-operative amygdala volumes.

2 – Case series: A total of 177 patients (50% male, 48.3% female) were included with a mean age of 39.24 years old.  The main clinical manifestation was complex partial seizures (59.4%), with a mean value of 12.7 seizures/ month.  There is a prevalence of mesial temporal sclerosis epilepsy in 47.8% patients, extra temporal epilepsy being the second most frequent type of epilepsy.  In this group 43.9% of patients were submitted to amygdalohippocampectomy with anterior temporal lobectomy, followed by lesionectomy in 36.7% of cases.

Better results were achieved in mesial temporal lobe epilepsy with 85% of patients in Engel 1 at 5 years follow up and worse results came from extra temporal epilepsy, in line with published literature. 

Conclusions:

Volume evaluation of mesial temporal lobe structures in MTLE can be a useful predictor of seizure control and be used as a relevant clinical tool, paving the way to tailored patient resections.

In our series, surgery resulted in good (extra temporal epilepsy) to excellent (MTLE) seizure control with minimal morbidity and no mortality. Further efforts should be developed to perform surgery for refractory epilepsy earlier in the course of the disease. 

A 1947 historical paper by American neurosurgeon Ernest Spiegel is reputedly the first description of human medical use of a stereotactic device, thirty years after Sir Victor Horsley and Robert Clarke employed it to create an animal brain atlas. Nevertheless, both the principles and application of stereotaxy date from the late XIX^th century.

The invention and first surgical use of a stereotactic device are due to Gaston Contremoulins, a 26-year-old self-taught scientist who worked at the department of experimental physiology of Paris Medical University. The technique was published in 1897 in scientific and popular newspapers, which focused on two remarkable procedures of stereotaxy-assisted intracranial bullet removal.

We describe this original technique and the key concepts formulated through it, as well as the epistemological context of their birth. Surprisingly, the founding project of what proved to be a major advance in neurosurgery was not supported by conventional scientific institutions and it had to be crowdfunded, through non scientific media.

Despite the fast and massive spread of the technique in France (more than 37,780 patients benefited from intracranial or extracranial stereotactic procedures during World War I), its international diffusion in the scientific community was limited, and the potential developments of this revolutionary technique were not immediately explored.

This can be imputed to the lack of openness of medical academic institutions to a self-taught scientist, as well as the complex historical context.

This highlights how much cross-disciplinary research and creative culture are key for significant medical breakthrough.

Introduction

Deep brain stimulation (DBS) is an established therapy for various movement disorders (e.g Parkinson's disease, dystonia and essential tremor) and its further applications, especially in psychiatric diseases, is currently being explored. However, its underlying therapeutic mechanisms in the brain network remain largely unclear. Changes of cerebral blood flow in several regions of the cortex and the basal ganglia have been demonstrated with DBS using positron emission tomography (PET) or single photon emission computed tomography (SPECT) in some previous studies, but their results were not always consistent with each other. Here, we performed a functional magnetic resonance imaging (fMRI) experiment to further our understanding of the effect of electrical stimulation in the basal ganglia at the full brain scale.

Materials and methods

Two male rhesus monkeys (Macaca mulatta) participated in this study. Prior to the experimental sessions, a head-post and a recording chamber were implanted under general anaesthesia. Then, in the fMRI sessions, we measured blood oxygen level-dependent (BOLD) effect at 3.0-Tesla with a single surface coil during electrical microstimulation in the internal segment of the globus pallidus (GPi) under light general anaesthesia. Before each MRI scanning, an MR-compatible bipolar stimulating electrode was inserted in the somatomotor region of the GPi. After verifying its position with a T1-weighted image, we acquired full brain EPIs (1.5mm isotropic voxels, TR=2.4s) in a block design alternating 30s of ON/OFF stimulation. We used two types of stimulation paradigm: 1) 120Hz stimulation with various values of total electrical energy delivered (TEED), and 2) stimulation at three different frequencies (20, 120 and 260Hz) with constant TEED.

Results

The 120Hz stimulation of the somatomotor region of the GPi significantly increased the BOLD signal in several areas in the cortex and subcortical structures. Regarding the cortex, activations were seen in a lateral part on both sides of the central sulcus, the primary motor and sensory cortices, not only in the ipsilateral hemisphere but also in the contralateral hemisphere. In the subcortical structures, the GPi stimulation led to activations in the ventrolateral nucleus of the thalamus and subthalamic nucleus ipsilaterally. Moreover, we found increased activation in the contralateral cerebellar cortex. In most of these activated areas, the more TEED was delivered, the larger change of the BOLD signal was produced by the 120 Hz stimulation. On the other hand, there was an obvious effect of stimulation frequency; in spite of the same TEED, maximal increase in BOLD signal was observed at the 120 Hz stimulation, and less activations were induced by the 20 and 260 Hz stimulations.

At the same time, the GPi stimulation induced deactivations in some areas in the temporal and parietal cortices, but there was no clear frequency-dependent effect on the deactivations.

Conclusions

Our study has revealed significant increase in BOLD effect in several areas of the cortico - basal ganglia - thalamic loop and cerebellum during electrical stimulation in the somatomotor area of the GPi. This effect was stimulus frequency-dependent, showing stronger influence at 120 Hz. This is consistent with the clinical observation on patients with DBS in which stimulation at 100-200 Hz is the most effective.

OBJECTIVE: Deep Brain Stimulation (DBS) is a cost-effective strategy for the treatment of different neurologic disorders. Hovewer, DBS procedures are associated with high costs of implantation and replacement of the internal pulse generator (IPG). Different manufacturers propose the use of rechargeable IPGs. The objective of this study is to compare the implantation costs of non-rechargeable IPGs versus the estimated costs of rechargeable IPGs in different categories of patients to evaluate if an economic advantage for the health care system could be derived.

METHODS: The study looked at 149 patients who underwent a surgical procedure for IPG replacement. In a hypothetical scenario, rechargeable IPGs were implanted instead of non-rechargeable IPGs at the time of DBS system implantation. Another scenario was outlined in a perspective period of time, corresponding to the patients' life expectancy. Costs were calculated, and inferential analysis was performed.

RESULTS: A savings of 234,194 euros, including the cost of management of complications, was calculated during a follow-up period of 7.9 years. In a comprehensive life expectancy period of 47 years, a savings of 5,918,188 euros would be obtained (P<0.05). Long-terrm group data point out that a relevant savings would be expected from implantation of rechargeable IPGs in dystonic patients (P<0.05) and in patients with Parkinson disease (P<0.05), and a savings is projected to occur in other categories of patients (P<0.05).

CONCLUSIONS: Implantation of rechargeable IPGs presents clinical advantages compared with non-rechargeable devices. A huge economic savings can be realized with the implantation of rechargeable IPGs in categories of patients implanted with IPGs for DBS.

Animal models with constant, long-lasting motor deficits together with the right tests to assess behavioral abnormalities are needed to study the effectiveness of potential therapies to restore motor functions. In the current study, controlled cortical impact (CCI) was applied in rats to induce damage to the forelimb area of the motor cortex and the dorsal striatum. Motor behavior was assessed before and after CCI using fine motor skill tests such as the adhesive removal test, the cylinder test and the Montoya staircase test as well as the automated gait analysis system CatWalk XT over a 6 week period.

CCI caused a variety of unilateral motor deficits, which were characterized in detail by using various fine motor skill tests. Neither forelimb impairments, nor general changes in gait were detected with the CatWalk XT.

In this paper, we present both the methodology to induce long-lasting forelimb impairments as well as a comprehensive evaluation of which behavioral tests are suitable to measure unilateral motor deficits in rats after CCI.

Effects of 5 weeks fornix deep brain stimulation in a transgenic Alzheimer rat model

Background: Deep brain stimulation (DBS) is promising therapy in patients with Alzheimer’s disease (AD). Few studies have suggested that stimulation of the forniceal area might slow down the cognitive decline of AD patients, but its biological effects on memory circuits remain unclear.

Objective: To study the behavioral and histological effects of continuous chronic DBS of the fornix in a transgenic Alzheimer murine model and wild type (WT) rats.

Methods:  We used a transgenic Alzheimer rat model TgF344-AD that manifests age-dependent cerebral amyloidosis, taupathy, gliosis and apoptotic loss of neurons in the cerebral cortex and hippocampus, as well as cognitive disturbance. All the 18 month-old rats were surgically implanted in stereotactic conditions, using a portable microstimulator for chronic DBS in freely moving rats, allowing a chronic continuous stimulation for 5 weeks. Cognitive tests (open field and Novel Object recognition test) were performed before surgery, and after 2 and 5 weeks. At 5 weeks the animals were sacrificed for immunohistochemical study. Implanted but non stimulated rats were used as controls.

Results: We confirmed the above described differences between transgenic AD rats not stimulated and WT rats not stimulated. Moreover we found that DBS in the transgenic rat model led to a significantly reduce in ABeta deposition: 30% +- 12% p<0.001; decrease neuroinflammation markers (using Iba1 and GFAP antibodies): 150%/50% ( p< 0.001) respectively as compared to non stimulated rats. DBS in the transgenic rat model prevented neuronal loss (with NeuN immunostaining) and synaptic (Synaptophysin staining) loss p< 0.001.  Cognitive tests suggested an improvement of memory in the DBS transgenic rat model but did not differ significantly between groups.

Conclusion: In the Tg-F344-AD rat model, 5 weeks of forniceal DBS decreased amyloidosis and inflammatory responses, prevented neuronal and synaptic loss in the cortex and hippocampus. These findings show a neuroprotective effect of forniceal DBS in this transgenic Alzheimer rat model.

Conservative and surgical treatment of Neurodegeneration with Brain Iron Accumulation (NBIA) is difficult and frequently ineffective. The authors present a group of patients with clinically and radiologically diagnosed NBIA with genetically confirmed PANK2 mutation, treated with deep brain stimulation.

Materials and methods: Twelve patients with confirmed PANK2 mutation (NBIA-PKAN) were treated with deep brain stimulation between 2008 and 2015. Age of the patients varied from 8 to 24 years. The clinical condition of the patients was evaluated with scales and video recorded. At all cases the permanent electrodes were implanted to the subthalamic nuclei or globus pallidus. The surgical procedure was undertaken under general anesthesia. The target was identified with direct and indirect method. Intrasurgical macrostimulation and microrecording were used for neurophysiological evaluation of the target. Postsurgical local field potentials were recorded in all cases.

Results: Neither neurological deterioration nor surgical complication were noted among the group. Caregivers of the patients noted subjective improvement of the clinical state of the subjects that was confirmed with tailored scales. More significant improvement was noted among STN group compared to GPi group.

Conclusions: Subthalamic or pallidal deep brain stimulation reduces dystonic movements among NBIA patients. The technique carries minimal surgical risk, and improves quality of life of the patients.

Introduction:

Bilirubin-induced neurological damage (BIND, kernicterus) is today a rare cause of dyskinetic cerebral palsy due to aggressive treatment of perinatal hyperbilirubinemia.  Neurological sequelae include extrapyramidal movement disorder, sensorineural hearing loss and impaired upward gaze. Surgical treatment of the dystonic-dyskinetic movement disorder has been reported successful with a high degree of variability.

Patient and Methods

An 11-year-old patient suffering from dyskinetic cerebral palsy was treated with deep brain stimulation (DBS) surgery using multiple array microelectrode recording for the placement of bilateral four-contact electrodes in the GPi. During the placement of the right DBS electrode a slight anterior deviation of the electrode tip was observed in the lateral fluoroscopy. Postoperative MRI showed an anterolateral deviation of the right electrode into the GPe. The right DBS stimulation could not be activated due to side effects. The right electrode was repositioned through a rigid insertion cannula eleven months after first surgery without the use of microelectrode recording. Four months of clinical follow-up are available for the assessment of clinical benefit and side effects of bilateral DBS therapy.

Results: After repositioning of the electrode the patient shows minor but steady clinical improvement. However, stimulation induced side effects with acute or delayed onset lead to repeated reprogramming of the stimulator. Normalization of body weight and minor improvements of activities of daily living are the most apparent clinical improvements so far.

Conclusion:

Effects of DBS surgery for secondary dystonia are less pronounced and predictable than for the treatment of primary dystonia. In this case frequent clinical evaluation for the presence of therapeutic effects and side effects warrants slow but continuous progress in clinical response. However, relevant therapeutic effects in these patients are often not properly represented in the scaling systems of dystonia rating. 

Deep brain stimulation (DBS) surgeries are multi-faceted and the various steps are interconnected. This process has proven to be dynamic over time. Since its first implementation, the method of DBS surgery has undergone changes. Some key technical changes were three-dimensional (3D) neuroimaging modalities, high-gain amplification of electrophysiological signals, and advanced programming possibilities. The authors have performed hundreds of cases (>900 DBS surgeries) in seventeen years. Since then, we have encountered many expected and unexpected, specific and general technical problems. Some of these technical problems were related to the stereotactic frame, stereotactic localizer and planning station. In this study, we describe the technical problems of DBS surgerıes in detail and share our experience with these complications and their management for groups who are willing to start a DBS program or who have recently started.

Objective: Camptocormia is a disabling syndrome characterized by forward flexion that can be an idiopathic condition 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, contrary to some individual reports which indicate that some degree of improvement in posture 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 and data is scarce. The objective of this article is to determine the efficacy of bilateral STN DBS in alleviating the degree of camptocormia in PD patients. Results and outcome of two PD patients with camptocormia who underwent bilateral STN DBS are presented. 

Patients and methods: A 67 year old female and a 66 year old male, both suffering from PD in the last 15 and 8 years, respectively, 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.

Objective: To assess the surgical morbidity and comorbidity in patients with various disease entities of movement disorders, epilepsy and obsessive-compulsive disorders that underwent deep brain stimulation (DBS) in a single DBS center of Taiwan.

Methods: From Feb 2002 to May 2016, a total of 191 patients in our institute were included for analyzed retrospectively. All patients underwent standard DBS procedures with intra-operative microelectrode recordings.

Results: Among surgical morbidity, symptomatic hemorrhage 2.1%(4/191), lead mal-positioned 2.6%(5/191) and hardware infection 2.6%(3/191). There had no surgical related mortality. In STN-DBS for Parkinson’s disease (N=158), post-operative general surgical morbidity was 36.1% (57/158), which included: weight gain (more than 5 kg) 25.3% (40/158), mania/hypomania 7.6%(12/158), transient confusion 7.0% (11/158), depression 3.8%(N=6) and pulmonary edema 1.9%(3/158). Stimulation related morbidity was 41.8% (N=66), which included hypophonia 15.8%(N=25), dyskinesia 12%(19/158), dysarthria 12%(19/158), sialorrhea 10.8%(17/158) and decreased memory 10.1% (16/158). The comorbidity within the follow-up period up to 14 years was 51.4%(72/140), which included patients who expired, demented, received bone/spine surgery and diagnosed as cancer. Eighteen patients were loss from follow-up.

Conclusions: The associated morbidity and comorbidity was significant in DBS patients. Stimulation related morbidity was high in PD STN-DBS, nevertheless, most of these was transient, and could be improved after change in stimulation parameters. Though the incidence of intracranial hemorrhage was low, it remained as a high risk morbidity in DBS surgery. 

Background

We have proved in our previous report that dorsolateral subthalamic(STN) neuronal activity enhanced by median nerve stimulation (MNS) could characterizes Parkinson’s disease during deep brain stimulation with general anesthesia. However, the vigorous passive range of motion test (PROM) and/or intense MNS might exert awakening effects to the patient who was lightly anesthetized.

Purpose

To find the most effective way to identify the sensory-motor portion of STN, yet, with less stimulation effect to the depth of anesthesia during microelectrode recording (MER).

Method

Prospective study (TCRD 104-35, IRB 103-122-A, Tzu Chi General Hospital, Hualien, Taiwan)

A 3T MR image was used for pre-op target planning. In which, will be fused to CT scan with frame-based localizer at the day of surgery. Regular induction and endotracheal intubation for general anesthesia was performed, and then maintained with volatile anesthetic agent and muscle relaxant only. The depth of anesthesia was monitored by heart rate (HR), mean arterial pressure (MAP), and minimal alveolar concentration (MAC) of the volatile anesthetic agent.  Neuronal firings were recorded within STN. Provocation test of PROM, MNS were performed at random.

Result

A total of 13 patients were enrolled in this study. Mean age at surgery and disease duration were: 55.6±9.4 year-old and 8.8±2.4 years, respectively. Average MER trajectory was 1.0±0.2. Recorded depth of STN was 5.4±0.7 mm. Depth of anesthesia was maintained within 0.5~0.9MAC (0.7±0.1MAC). A total of 1113 neuronal firings were recorded (N=642 without test; N=106 with PROM; N=236 with MNS; N=129 with both PROM+MNS). When compared to baseline (without test), PROM significantly increased HR by 2.7344 (p=0.0043), MAP by 2.4400 (p=0.0175). MNS significantly increased HR by 2.0878 (p=0.0028) and MAP by 7.8896 (p=0.0000). When PROM and MNS were performed consecutively, HR significantly increased by 6.2645 (p=0.0000), and MAP by 7.3521 (p=0.0000). However, no patient was apparently awakened during the provocation test of MER procedures.

Conclusion

During MER for STN-DBS, median nerve stimulation could be an effective, yet convenient and save provocation test to identify the sensory-motor topography of STN. Though MAP was significantly higher than PROM during MNS, it was brief and transient. No apparent wakefulness was noted in all patients. 

Belly dancer’s dyskinesia (BDD) is a kind of focal dyskinesia affecting the abdominal wall and also may include diaphragmatic myoclonic jerks (or flutter) which can result in chest and/or abdominal pain and dyspnoea. Clinically, frequent, intermittent and often rhythmic involuntary undulations of the abdomen are observed. Several pathological conditions described in the literature, including idiopathic and psychogenic cases.

A 36-year-old woman presented with a 7-year history of daytime involuntary abdominal dyskinetic movements. The repeated local Botulinium toxin injections had minimal temporary beneficial effect. Cranial and spinal MRI failed to show circumscribed lesion, all laboratory tests including copper, ceruloplasmin, thyroid, and blood smear were unremarkable.

Fluoroscopy confirmed diaphragmatic contractions on both sides. The clinical symptoms were evaluated according to the Burke-Fahn-Marsden (BFM) dystonia rating scale. The dyskinesia were recorded prior and after surgery and measured with infrared video-based computerized real time passive marker-based analyser of motions (RTPAM) with the sampling rate of 50/s. One midline and 8-8 lightweight retroflective markers were placed on both sides as abdominal landmarks. The detailed motion analysis with spectrograms has been performed with a software implemented in MATLAB (Mathworks, Sherborn, MA, USA)

As drug approaches were only of transient and limited effect, the patient was selected for surgery Bilaterally quadripolar leads (model 6147, St. Jude Medical, Inc., USA) were implanted to the posteroventral lateral GPi with a frameles MRI to frame-based CT fusion guided (Vister 3D home-developed planning software) stereotactic method (MHT system, Bad Krozingen, Germany). Intraoperatively bilateral microrecording (Neurospot, Neurostar, Tübingen, Germany) and stimulation screening has been used for refinement of optimal electrode tip position . In the same session under general anaesthesia the electrodes were connected to Brio dual channel rechargeable neurostimulator, implanted bilaterally in the subclavicular region. In the postoperative period no surgery-related side effects were observed. Postopertaive high resolution CT-scanning confirmed the proper electrode position.

The BFM score showed a total reduction of abdominal dyskinesia at 6-months, and long lasting benefit at the 1-year follow-up. RTPAM showed substantial regression of acceleration for all markers, and abolishment of the dominant frequency of the dyskinetic movements. The cross-coherence and correlation between symmetrical markers, and between markers within the right and left sides, significantly was decreased.

Conclusions: Bilateral GPi-DBS can be considered as a treatment option in belly dancer’s dyskinesia. RTPAM is a useful tool for registration of involuntary abdominal movements and for detection of treatment effectiveness.

TREMOR12 is a smartphone app developed for measuring tremor. It measures 4 parameters (acceleration, rotation, rotation speed, and gravity) in 3 axes (X, Y, Z). All samples are time-stamped and measurements are performed at approximately 100Hz.In contrast to other available smartphone apps that serve this purpose, TREMOR12 allows to export the raw data as comma-separated value (CSV) file for offline analysis. The purpose of this app is to expand tremor quantification beyond the level of frequency and amplitude by searching for detailed patterns that correlate to diagnostic or therapeutic consequences.

The obvious drawback of a smartphone application for tremor measurement is the practical limitation to perform chronic measurements during daily life activities. A smartwatch-based app would be more portable and suitable for chronic measurements. However, specific concerns arise when porting a smartphone app for tremor measurement to a smartwatch app meant for telemonitoring of tremor. Concerns relate to battery drainage, data transfer, device capacities and sampling strategies.

We will present our preliminary experience with these issues when porting TREMOR12 to a smartwatch-based app for chronic telemonitoring of tremor.

BACKGROUND: The ventral intermediate nucleus (Vim) of the thalamus is the traditional target for Deep Brain Stimulation (DBS) for the treatment of pharmacologically refractory essential tremor (ET). Recent evidence suggests that the posterior subthalamic area (PSA) might be a better target for tremor reduction. The PSA contains the dentato-rubro thalamic tract (DRTT), also called the cerebellothalamic tract, which is the main fiber bundle that forms the superior cerebellar peduncle. Previous studies demonstrated a significant correlation between the degree of connectivity to the DRTT at the stimulating electrode and the reduction of tremor.

OBJECTIVE: To compare the effect of the Vim and the PSA as a target in a consecutive series of patients with a DBS treatment for ET.  The efficacy outcome will be investigated by means of clinical parameters.

METHODS:  Twenty patients with a clinical diagnosis of ET were included in this retrospective study. All patients underwent bilateral DBS, in 15 patients Vim was used as DBS target, while in 4 subjects PSA was used. In one subject the Vim was targeted on one side, and the PSA on the other side. The outcome was measured by using the Essential Tremor Rating Scale (ETRS) and the Glass scale. At the same time quality of life assessment took place, using the Quality of Life in Essential Tremor questionnaire (QUEST) score. The coordinates of the active contacts were determined by analysing the post-operative imaging using the iPlan Stereotaxy software (Brainlab AG, Germany).

RESULTS: Currently we are analysing the data and we will have the final results by mid July. We will present results regarding the outcome differences expressed in ETRS, QUEST and Glass scale in relation to the selected target. In addition, reported side-effects will be compared. Our preliminary results suggest that stimulation in the Vim target has better outcome regarding the ETRS reduction (%) and QUEST score in comparison to the PSA stimulation. Regarding the Glass scale, no significant difference has been discovered. 

CONCLUSION: Based on our preliminary results both the ventral intermediate nucleus and the posterior subthalamic area are effective in reducing tremor. Whether one target is superior to the other is currently being investigated. These results will be presented during the meeting. 

The use of dexmedetomidine during deep brain stimulation for Tourette syndrome: a case report

¹M.J. Bos, ²M.L.F. Janssen, ³A.Y. Smeets, ¹W.F. Buhre, ³Y. Temel ³L. Ackermans,

Departments of ¹Anesthesiology and Pain Medicine, ²Neurology and ³Neurosurgery

Maastricht University Medical Center, Maastricht, The Netherlands

ABSTRACT

Introduction

Deep brain stimulation is effective in reducing the key symptoms in selected cases of severe Tourette syndrome. The surgical approach can be challenging due to the presence of severe tics.  Often the patients are operated on with local anesthetics and conscious sedation. However, there is no  “gold standard” for anesthetics which should be used. The goal of anesthesia should be to achieve conscious sedation to suppress the tics as much as possible but to allow for intraoperative testing. In addition, anesthesia should not interfere substantially with neurophysiological measurements. Here, we describe a case report in which dexmedetomidine is used in a patient with Tourette syndrome and discuss the advantages of this drug as anesthetic for awake deep brain stimulation procedures in Tourette syndrome.

Case Description

This 19 year old male developed tics around the age of eight. Tics started with simple motor tics like head shaking, but later they extended to the rest of his body. They became more severe during childhood and adolescence. He suffered from severe and almost continuously present motor tics like eye blinking, head shaking and jerks of shoulders, arms, abdomen and legs and he had mild vocal tics like sniffing and coughing. First and second line medication treatment and behavioural therapy were not effective in the past.

The patient was scheduled for deep brain stimulation. An awake approach with local anesthetics and continuous infusion of dexmedetomidine 0,5mcg/kg/u was used. Bilateral electrodes were placed in the globus pallidus internus. During the procedure, tics were suppressed adequately, the patient was conscious and no evident interference was observed with micro-electrode-recordings. It was clearly possible to record globus pallidus externus and internus neuronal activity and no activity was found at the level of the laminae.  No perioperative adverse events occurred.

Conclusion

The used anesthetic, Dexmedetomidine, an α2-agonist, is a sedation agent which can be used in deep brain stimulation surgeries for patients with Tourette syndrome due to a favorable mechanism of action. Dexmedetomidine has sedative and analgesic properties without inducing respiratory depression. It mimics a sleeping sensation in which patients are easily arousable allowing appropriate clinical testing. Importantly, there is a dose dependent suppression of tics.  Compared to other sedative agents such as propofol, benzodiazepines and volatile agents, dexmedetomidine does not activate the gamma-aminobutyric acid (GABA) receptors.  Activation of GABA, the major inhibitory neurotransmitter within the basal ganglia, can worsen or abolish micro electrode recordings. 

Selected patients undergoing deep brain stimulation (DBS) may benefit from simultaneous stimulation of different anatomical targets. In the past the capabilities of available DBS devices were limited to two leads with total 8 contacts, and optimal programming employing multiple stimulation frequencies had required the implantation of two separate pulse generators. Thus, in September 2011, we chose to implant a novel, rechargeable DBS device (Synapse™ System, Nuviant Medical, Niel, Belgium), in a 35 year-old male suffering from medically refractory dystonic tremor associated with torticollis and irregular myoclonic jerks of the head and both arms. The system is based on 16 independent current sources for stimulation, and supports the placement of four 4-channel leads enabling differential control of 4 leads (diameter, 1.3 mm; electrode height, 1.25 mm; distance, 0.5mm) that were placed bilaterally into the ventrolateral thalamus (VIM) and bilaterally into the globus pallidus internus (GPi) in a single session under local anaesthesia. Stimulation was kept off until a microlesioning effect had resolved after four weeks. Bilateral monopolar VIM stimulation was initiated (2.4mA, 90microsec, 180Hz) at four weeks post-implant, and resulted in an immediate near-complete resolution of tremulous and irregular-jerky head motions that has been maintained up to the last followup in June 2016. At approximately 17 weeks post-implant, bilateral monopolar GPi stimulation was added for the relief of the remaining cervical dystonia and intermittent myoclonic jerks. GPi stimulation was continued bilaterally with 1.6 mA (left GPi) and 1.8 mA (right), 90 microsec and 130 Hz to date. Symptom relief has been sustained for almost 5 years until the last follow-up in June 2016, and it is dependent on stimulating both targets. Tremor recurred immediately after cessation of VIM thalamic stimulation. This new device represents a technological advance in the field of neurostimulation and has proven to be reliable and effective for the long-term application of multi-focal DBS. As DBS targets may require specific stimulation parameters devices such as Synapse™ will be useful for the conversion of 'competing' DBS targets into 'complementing' targets. 

The O-arm surgical imaging system® is a multidimensional platform that provides the opportunity of visualizing the electrodes in real time in deep brain stimulation surgery. The objective of this study is to investigate in our center the value of this tool, by comparing the clinical improvement of a group operated on with this technology and a control group. After one year follow-up, the results were analyzed.

Material and methods

Twenty consecutive Parkinson disease patients that received deep brain stimulation with one year follow-up were selected. Electrode placement was optimized using the O-arm imaging system. They were compared to 20 consecutive patients operated on under 2D fluoroscopy as a control group. In both groups variation of the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) was measured, in addition to the number of microrecording tracks and the length of the surgery.

Results

A median basal off reduction of 42% was observed in the O-arm group vs 24% in the control at one year follow-up, which was statistically significant (p<0.005). The reduction of the length of the surgery was statistically significant, being 1h and 10 minutes less in the O-arm group. The number of tracks needed per electrode was reduced from 2,47 to 1,99.

Conclusions

The O-arm can be easily included in the workflow of deep brain stimulation surgery. It gives the opportunity of visualizing the electrodes in real time. In our center it has helped to improve our results and refine our procedure. It has helped reducing the surgical time and number of tracks, as well as improving the clinical state of our patients. Further studies are needed to establish the fusion error.

The evaluation of both therapeutic- and adverse effects of test stimulation is normally regarded as the most important factor during deep brain stimulation surgery when deciding whether or not the electrode placement is satisfactory. Symptom evaluation is usually performed by a neurologist, who relies on experience and knowledge to provide a subjective measure of the evaluated parameters. However, several studies have shown that clinical evaluations of symptomatology of movement disorders is accompanied by both inter- and intra-rater variability (Little 2012, Kwon 2014). Objective quantification of baseline symptomatology as well as changes in symptoms due to electrode placement and subsequent stimulation can contribute to reduce this variability and further improve surgical accuracy and more importantly clinical outcomes. The aim of our study is to investigate the practicality and sensitivity of a tailor made wrist rigidity device for the objective assessment of resistance to passive wrist movement during DBS surgery.

Our device consists of an acrylic mechanical system with a potentiometer built into the low friction hinge between a hand- and forearm-plate that measures wrist joint angle. The hand is positioned between two acrylic cylinders and forearm is secured to a separate plate using straps, allowing only a flexion/extension movement in the wrist joint. The hand-plate also includes a handle with an integrated bi-directional force-gauge for the examiner to perform the wrist flexion/extension movements by moving the hand-plate. Appropriate measurements are taken at three time points during surgery with and without contralateral co-activation (simultaneously squeezing the other hand) 1) before insertion of the electrode 2) directly following insertion prior to test stimulation and 3) during test stimulation at target level. Our measures do not replace the standard clinical evaluations by the neurologist, but instead are performed complimentary to standard assessment. Each measurement consists of 12 flexion/extension movements by the examiner at a constant pace of 50 beats per minute, dictated by a metronome.

We have currently collected rigidity data from 2 volunteers. The first dataset was recorded from a patient with Parkinson’s disease who had already undergone DBS 6 months earlier. We assessed the rigidity of this patient in a medical ON and OFF state followig a routine clinical consultation. The second patient was recorded during surgery at the three time points described earlier. We intend to collect data for this pilot study from at least 5 more patients using the device and aim to present a detailed report of the results at the time of the XXII Congress of the European Society for Stereotactic and Functional Neurosurgery in October this year.     

If proven practical and effective, these methods could supplement and improve the current subjective assessments during surgery and set a new standard, but also contribute to predict clinical outcomes and improve patient management.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used surgical treatment for severe Parkinson’s disease (PD). However, post-operative motor improvement can vary greatly between patients, which might be caused by varying locations of the stimulating contact point. Research into the relation between motor improvement and active contact point (ACP) location using standard anatomical landmarks (AC-PC) may suffer from inaccuracy caused by anatomical variations between patients. Studies using the MRI-defined STN may also suffer from inaccuracy because the STN can be hard to identify in preoperative MRI. Therefore, in this study, we use the intraoperative microelectrode recordings (MER) to create a detailed estimation of STN size and location and then study the relation between motor improvement and ACP location relative to this MER-defined STN.

Methods: For this study, we used 43 STNs of 26 patients, from the Dutch NSTAPS trial that had 1) assessment of PD motor symptoms preoperative and one year postoperative, 2) CT imaging of the implanted lead one year postoperative and 3) intraoperative MER that measured STN activity on at least three channels.
STN size and location was estimated by automatically transforming a general biconvex lens-shaped STN to fit optimally on the MER measurement sites scored as either inside or outside the STN. The one year postoperative CT was fused with preoperative T1 MRI including stereotactic frame, stereotactic ACP location was manually determined and combined with the patient specific MER-defined STN. Finally, the STN and the ACP location together were transformed back to the original biconvex lens shape. This way, the ACP locations of the entire group could all be studied relative to one general STN shape (figure 1).
Per STN, the DBS-induced motor improvement was defined as the combined off-levodopa improvement on the UPDRS III of strictly contralateral motor symptoms as a percentage of the preoperative combined contralateral off-levodopa UPDRS III score.
Location data was statistically analyzed using both standard multiple regression and independent samples T-tests. For the latter, two groups were defined based on the percentage of motor improvement: DBS-responders who showed a contralateral improvement of 50% or more (n = 27) and non-responders who improved less than 50% (n = 16).

Results: For the group of DBS-responders, the mean ACP location one year after surgery was 0.8 mm lateral, 1.5 mm anterior and 2.1 mm dorsal to the center of the MER-defined STN. Independent samples T-tests showed that the ACP location relative to the general STN in the non-responder group was significantly more medial (smaller x-coordinate) than in the responder group (p = 0.045). No significant differences were found in the y- and z-coordinates representing the anterior-posterior and the dorsal-ventral directions respectively.
Standard multiple regression showed that the x-, y- and z-coordinates of the ACP location together explain 37% of the variance in contralateral motor improvement (adjusted R square = 0.365, p < 0.0005). Further evaluation of the three directions in this regression showed that both the x- and the z-coordinates of ACP location made a significant unique contribution to the prediction of motor improvement. A more medial ACP location had the most pronounced negative contribution to the prediction of motor improvement (beta = -0.66, p < 0.0005), thus predicting less motor improvement. A more dorsal ACP location also predicted less motor improvement although its contribution was smaller (beta = -0.36, p = 0.016).

Discussion: In this study we showed that a relation between ACP location and motor improvement can be found when determining the ACP locations relative to the MER-defined STN. The advantage of this method is that it takes into account the anatomical variations in STN location without depending on high quality MRI images.
In DBS surgery it is important to target the anterior part of the dorsolateral STN, which corresponds to the sensorimotor area. Stimulation on contacts that are located more medial or more dorsal results in significantly less motor improvement. This has implications for both the lead placement during surgery and the postoperative selection of contacts for stimulation. During surgery, the MER-defined STN could be helpful in preventing too medial implantation and during contact selection the MER-defined STN could be used to prevent too dorsal stimulation.

Background: Essential tremor (ET), characterised by postural and/or action tremor, is the most common movement disorder. The pathophysiology of ET is poorly understood. However, several brain regions along the cerebello-thalamo-cortical network have been hypothesised to be involved in the generation of tremor oscillations. Evidence for involvement of different regions within this loop has been derived from various animal, neuropathological, structural and functional neuroimaging studies.

ET can be disabling to the grade of necessitating invasive Deep Brain Stimulation (DBS). DBS in the caudal zona incerta (cZi) has shown a considerable reduction in tremor for patients with otherwise medically intractable tremor. The mechanisms underlying the effects of DBS remain unclear.

 Objectives: Investigating, by using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), whether regions within the cerebello-thalamo-cortical network are influenced by therapeutic DBS during tremor-inducing movements.

 Methods: Fourteen patients with cZi-DBS for ET underwent 1.5T fMRI. During fMRI, the patients executed right arm tremor-inducing movements (postural holding and aiming movements) as well as a baseline resting task. Tremor and hand movements were recorded by an MR-compatible single-axis accelerometer attached to the ulnar side of the right hand.

The tasks were performed with the stimulation turned on and off, with the initial stimulation setting (on/off) counterbalanced across patients. The fMRI design consisted of three blocks (postural, aim and rest) with 20 seconds duration and 10 repetitions each. fMRI data were pre-processed and analysed using a general linear model implemented in SPM12.

 Results: Clear therapeutic effects of cZi-DBS, in terms of tremor intensity reduction, were measured by the accelerometer in patients with ET. Preliminary fMRI analysis showed interaction effects between postural holding and DBS where BOLD activity increased in the posterior parts of the middle and inferior frontal gyrus when performing postural holding while DBS was turned on.

Interaction effects between postural holding and DBS, mainly driven by DBS effects during the resting condition, were also seen as increased BOLD activity in primary motor cortex, premotor cortex and cerebellum when performing postural holding while DBS was turned on. On the other hand, BOLD activity decreased in Crus I within the ipsilateral cerebellum when performing the same task while DBS was turned on. The latter effect within the cerebellum was mostly driven by DBS actions during the postural holding.

The average effect of DBS across all conditions (postural, aim and rest) was observed as an increased BOLD activity in frontotemporal areas bilaterally, mostly outside the motor network.

 Conclusions: Effects of therapeutic cZi-DBS observed as modulated BOLD activity in several frontotemporal regions including the motor network and also in the cerebellum. This study supports the notion of DBS acting upon modulation of the cerebello-thalamo-cortical loop in ET. 

Objective: The present study was conducted to assess the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on cognitive functions in PD patients using a PD control group.

Methods: All PD patients included in study fulfilled the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria for PD. Ten wait-listed patients PD patients (control group) and 10 PD patients with DBS implantation (DBS group) participated in the study. Surgical procedure was based on planning with custom-developed Vister-3D software frameless MRI to CT image fusion and with RM and MHT stereotactic systems. Intraoperatively 3 to 5-channel microelectrode recording has been applied with registration of Neurospot (Neurostar) recording equipment. Model 3389 electrodes were implanted bilaterally in all cases and were connected to Activa PC dual channel implantable pulse generators. 

A neuropsychological battery was used to assess cognitive functions, including general mental ability (Mini Mental State Examination), verbal (digit span) and spatial short-term memory (Corsi block-tapping task), working memory (n-back task) and executive functions (phonemic and semantic verbal fluency, Stroop task, Trail Making B task).  Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two task-administration points in the control group.

Results: There was no significant difference between the DBS and the control groups’ performance in tasks measuring the main cognitive functions. The DBS group showed a significant decline only on the semantic verbal fluency task after surgery compared to its own baseline level (p < .05).  .

Conclusions: Our results are  in line with findings of previous studies. The findings are discussed considering different possible effects of the STN DBS on frontosriatal networks.

Acknowledgement: This work was supported by research grant KTIA_NAP B_13-2-2014-0020 to Mihály Racsmány as PI.  Gyula Demeter is a grantee of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences

Background: Despite of the expressive development of the diagnostic imaging in the last decades, the stereotactic targets of the thalamus are still considered invisible. At present stereotactic atlases still used based on indirect methods for planning ventrointermediate (Vim) nucleus – deep brain stimulation (DBS) surgery.

Objectives: Retrospective study to evaluate the ability of non-linearwhole-brain MNI152 atlas registration to improve individual targeting, of the “tailor-made” anatomical fusion suitable for preoperative planning.

Methods: 15 patients - altogether 25 implanted DBS leads - with pure essential tremor were treated with Vim-DBS. The tremor score was assessed pre-and postoperatively.  The tremor amplitude reduction reached 90% in the follow-up period. The position of the active contacts were allocated in the postoperative CT-space and thereafter the non-linear registration in the MNI152 standard space with FMRIB Software Library. The registrations were verified manually with visual control. All of the active contact’s position were measured in three planes in the registered MNI152 standard space and patient individual CT-space. References were the intercommissural line, the third ventricle wall, the AC-PC plane and we calculated (target-PC)/(AC-PC) ratio.

Results: In our investigation the standard deviation of the active contact position in the MNI152 atlas space was reduced in each plane compared with the patient’s individual space. In addition, we found numerous locations of the active contacts wide of the ideal anatomical lead trajectory in the MNI152 standard space, after successful registration. In this case the 7 mm or wider third ventricle in AC-PC, the unparallel or irregular third ventricle wall was considered. The AC-PC distance, the cerebral atrophy, the shape of the cranium had no effect on the fine registration of the thalamus.

 Conclusions: The non-linear whole brain atlas registration before the operation would provide useful tool for stereotactic atlases based “individual” planning for Vim-DBS surgery in selected population.

Acknowledgement: This work was supported by research grant KTIA_NAP B_13-2-2014-0020

Objectives:

Deep brain stimulators consist of a quadripolar electrode implanted in the brain parenchyma connected to an implantable pulse generator (IPG).  The IPG acts as both power source and waveform generator.  Non-rechargeable IPG’s require periodic replacement at the end of battery life, which carries both surgical risks and financial implications. Advancements in battery technology have led to replacement of the widely used Medtronic Kinetra with the Activa PC IPG system.  Although previous studies have compared battery life in single channel DBS systems and in the treatment of different neurological conditions there has been no analysis of dual channel DBS systems^1,2.  We have therefore compared battery life in these two commonly utilised dual channel IPG systems and whether choice of DBS target and pathology impacts on battery drainage. This may inform choice of DBS systems depending on the underlying disease process.

Methods:

All patients who underwent insertion of DBS in our neurosurgical centre were identified from a centrally recorded database.  Only those who had insertion of bilateral Medtronic Kinetra or Activa PC DBS stimulators for STN stimulation to treat Parkinson’s disease (PD) or GPi stimulation to treat Dystonia were included in the final analysis. Time between replacement of IPG systems due to low battery life was recorded in days. Battery life was then assessed using a Kaplan-Meier approach, with those patients whose batteries had not been replaced by the end of follow-up censored at this point. The median (95% Confidence Interval) battery life was then estimated from the Kaplan-Meier curves, and comparisons between groups made using log-rank tests. Statistical analysis was performed using IBM SPSS 22, with p<0.05 deemed to be statistically significant.

Results:

Data was available for 183 patients with bilateral STN DBS stimulators for PD and 11 patients with bilateral GPi stimulators for dystonia.  For the treatment of PD the Kinetra cohort (N=83), had a median battery life of 6.6 years (95% CI: 6.5 – 6.7) . This was significantly longer than the Activa PC cohort (N=100), which had a median battery life of 4.5 years (95% CI: 4.4 – 4.5) (p<0.001).  Six patients in the Activa PC group had the interleaving programme applied for the treatment of PD, resulting in a significantly shorter battery life of 3.7 years (95% CI: 2.7 – 4.8).

Data were available for an additional 5 Kinetra patients with dystonia who had a battery replacement. A significant difference in battery life was detected between the groups (p<0.001), with a median battery life of 3.7 years (95% CI: 2.3 – 5.1) in patients with dystonia, compared to 6.6 years (95% CI: 6.5 – 6.7) in those with PD.

Conclusions:

The Activa PC IPG demonstrates a significantly reduced battery life of 2.1 years in comparison to the Kinetra IPG in STN stimulation for PD.  Use of the interleaving function led to a further significant decrease in the Activa PC battery life by a median of 0.8 years.  In addition, stimulation of GPi for treatment of dystonia results in a significantly shorter battery life of 2.9 years when compared to STN stimulation for PD in the Kinetra cohort, suggesting the DBS target and underlying pathology impacts on battery drainage.  The clinician should therefore carefully consider potential battery life of the  IPG system being used when treating different neurological conditions.  Use of rechargeable DBS systems for management of dystonia may be more appropriate if the patient is able to comply with recharging, aiming to reduce the morbidity associated with more frequent IPG replacement.

References

1. Longevity analysis of currently available deep brain stimulation devices . Stereotact Funct Neurosurg. 2011;89(1):1-5. doi: 10.1159/000321710. Epub 2010 Dec 1. Halpern CH1, McGill KR, Baltuch GH, Jaggi JL.
2. Battery life following pallidal deep brain stimulation (DBS) in children and young people with severe primary and secondary dystonia. Daniel E. Lumsden,  Margaret Kaminska , Kylie Tustin , Hortensia Gimeno , Lesley Baker,  Keyoumars Ashkan & Richard Selway & Jean-Pierre Lin. Childs Nerv Syst (2012) 28:1091–1097

We describe an 61-year-old male with twelve year history of idiopathic Parkinson Disease who underwent for bilaterally STN (Figure 1a,b). 3 days after surgery he was discharged without any complication. Two days later he was admitted to emergency department after a car accident. No abnormality was detected in his neurological examination except symptoms of parkinsonism. Cranial CT of patient revealed a hyperdense left acute subdural hematoma (SDH) with a midline shift of 8 mm (Figure 1b). He was hospitalized and follwed-up clinically and radiologically. No increment was detected radiologically in the size of hematoma. Repeated CT scans demonstrated progressive resolution of the hematoma (Figure 1c). When SDH was completely absorbed the DBS battery has been run. No side effect was observed and the optimal response of DBS was achieved.  Our case  showed that although there is a potential risk of electrode displacement due to SDH, urgent surgical evacaution must not be considered immediately.

There are no established guidelines for the management of subdural hematoma in patients with DBS implantation. With a subdural hematoma, the brain will shift ventromedially; since DBS leads are tethered to the skull, the ipsilateral lead will have a relative dorsal displacement from its original target site (1). In the literature rewiew the authors stated that, ıf a life-threatening conditions develops due to  SDH, surgical evacuation should be recommended as the fisrt option and check the electrodes radiologically and electrophyscology. İn our case, there was no neurological findings depends on subdural hematoma thus only neurological and radiological follow was sufficient.

Introduction:
The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures.
Methods:
A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed.
Results:
Most of the commonly established projections of the subthalamic nucleus, substantia nigra and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus.
Discussion:
This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projection of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.

High frequency chronic deep brain stimulation of subthalamic nucleus (DBS STN) has become a routine method for the treatment of advanced PD, leading to striking improvements in motor function and quality of life of patients. The subthalamic nucleus is a key node in the functional control of motor activity in the basal ganglia. The dopamine loss that occurs in PD augments STN activity and its inhibition, by for example DBS, suppresses the motor signs in human patients, together with animal models of Parkinson's disease

It is hypothesized that this augmented STN activity in turn, may cause further damage to the vulnerable dopaminergic neurons; glutamate output from STN to the substantia nigra contributes to the neurotoxic process underlying dopaminergic cell death in Parkinson's disease, thereby creating a scenario for an ongoing cycle of neuronal loss in the SNc The inhibition of STN neurons by DBS may result in the suppression of their glutamate output, and hence lessen the nigral cell death. In addition, there is also evidence that high-frequency activation of glutamatergic synapses triggers the release of BDNF, a protein brain-derived neurotrophic factor capable of protecting neurons from degeneration. Here we review the clinical evidence of neuroprotection secondary to DBS STN.

Methods: We will consider only the long term evaluation studies (>4years) that have also a proper off medication/off stim evaluation. The systematic review identified 12 studies that cover the set criteria. All clinical trials reported symptomatic positive results, even when compare with best medical therapy, but did not precisely address the neuroprotection.

Results: The study by Merola et al is the only one that has investigated the comparative potential disease modifying effect of DBS STN vs best medical therapy. They found a comparable pattern of progression of motor scores and cognitive/behavioral alterations in treated and non-treated groups with no reduction of the motor scores during off medication/off stimulation evaluation59]. In general, in all the other "neuroprotection" studies, evaluation during off stimulation/off medication after >4years did not show disease modifying effects when considering motor scores. In fact, Zibetti, Gervais-Bernard found a worsening of motor scores (7%) after 5 year of follow up and Visser-Vandewalle reported a 26% (albeit not significant) worsening after 4 years. The remaining studies found stable motor score or non-significant improvement after >4years post DBS STN .One key short term study, addressing the issue of disease modification specifically, was by Hilker. In a prospective two center study, disease progression was determined by means of serial 18F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. The results suggested an annual progression rates relative to baseline of 9.5-12.4% in the caudate and 10.7-12.9% in the putamen, within the range of previously reported data from longitudinal imaging studies in PD.

Conclusion: Unlike many experimental, preclinical examples, evaluation of DBS STN neuroprotection has proven problematic in the clinical situation. We are very much limited by the clinical measures that are currently at our disposable. Up until an accurate measure of neuroprotection can be found clinically, we are left with the situation of any potential neuroprotective effects being masked and entangled by the "symptomatic effects" of DBS STN.

Key words: Neuroprotection, Deep Brain Stimulation, Parkinson disease, long term clinical studies 

Dystonia is one of the most common disorders in clinical  practice of movement disorders. Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both.

It can be very disabling, especially in young, socially active patients.

Medical treatment of multifocal, generalized and segmental dystonia is very difficult, because medications have very low effect. Botulinum toxin was considered as an effective treatment of focal and segmental forms of dystonia. Sometimes needed very high doses of botulinum toxin for clinical effect or patient develops resistance to it.  

From 2012 in Federal center of Neurosurgery, Tyumen deep brain stimulation established as medical option for treatment of movement disorders, pain, epilepsy. Since 2012 to 2015 there was treated 58 patients with dystonia resistant to previous medical treatment.

Over 40 deep brain stimulation systems were implanted to treate dystonia patients and 18 generators replaced for previously operated people. Of 40 patients 36 operated because of primary dystonia (focal – 2, segmental –5 , multifocal -7  , generalized -22 ), secondary dystonia – 4 patients (2 of them with tardive dystonia). In our study we used Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS),  Cervical Dystonia Impact Scale (CDIP-58), Fahn-Marsden Dystonia Rating Scale (FMDRS).  All patients were divided into four groups (depending on the clinical effect): excellent improvement – 35%, good– 32,5% , moderate– 27,5% , unsatisfactory– 5%.  There was no surgical complications. The effect of stimulation was stable in all patients (4 patients with severe dystonia had recurrence of symptoms after switching off stimulation). We did not observe serious adverse events during stimulation.

In our series deep brain stimulation considered as safe and effective treatment of primary dystonia and secondary dystonia.

The authors present the case of  patient with subcutaneous fibrosis, which developed  around extension cables in patient treated with DBS for essential tremor, 5 months after surgery. The fibrosis limited the movement of the neck and during head rotations, it caused pain in the scalp, especially around the scars above Stimlocks. Painful sensations led to removal  and replacement of extension cables along different subcutaneous trajectory. Overview of published literature is analysed with a proposal of the solution of abovementioned complication. 

Background

Deep brain stimulation (DBS) is a common neurosurgical treatment for the tremor of Parkinson’s disease, essential tremor, and tremor of other causes. The outcome depends on optimal placement of the permanently implanted electrode. Many centers perform DBS surgery under local anesthesia in order to confirm the therapeutic effect with intraoperative stimulation testing. Visual inspection—the method generally used to rate changes in tremor during stimulation testing—is subjective, and its accuracy depends on the evaluator’s experience [1]. This study presents the results of quantitatively estimating improvement in tremor during intraoperative stimulation tests in 15 patients. In addition, its influence on identifying the final position of the permanently implanted electrode is described.

Method

We designed a 3D acceleration sensor system that is attached to the patient's forearm during surgery [2]. During intraoperative stimulation tests, at each different position, accelerometric data are synchronously recorded with the changing stimulation current amplitude. The method was applied in 15 DBS procedures in 2 centers (University Hospital Bern, Switzerland & University Hospital Clermont-Ferrand, France); the data were analyzed offline to assess improvements in tremor and to identify tremor-suppressing stimulation current-amplitudes. For correlation analysis, the quantitatively and visually determined improvements in tremor were categorized into: no improvement, low improvement, average improvement, high improvement and tremor arrest. The quantitatively identified tremor-suppressing current-amplitudes were compared to those identified by visual inspection, in order to determine the influence these findings would have had on the position chosen for permanent electrode implantation if they had been used for intraoperative decision-making. As this was a purely observational study, the accelerometric measurements were not, in fact, allowed to alter the surgical procedures in any way.

Results

A total of 359 evaluations were available for a comparison of the improvement in tremor identified by accelerometry vs. visual inspection. Of these evaluations, 156 (43.5%) were assigned the same categorie by both methods; 296 (82.5%) fell in the same or neighboring categories; and 63 (17.5%) were at least 2 categories apart. The quantitatively identified tremor-suppressing current-amplitudes were significantly lower than the visually identified ones (1.13 ± 0.8 mA vs. 1.7 ± 0.8 mA [mean ± SD]). Of the 26 finally chosen positions for permanent lead implantation, 15 would have been different had the accelerometric data been considered.

Discussion and Conclusion

The improvement of tremor brought about by test stimulation was rated in the same category by visual inspection and by quantitative measurement (accelerometry) in only 43.5% of the evaluations that we made in this study. In some of the evaluations where there was only mild tremor at baseline, the stimulation-induced improvement in tremor was classified by visual inspection as tremor arrest, while accelerometry revealed a very mild residual tremor. This fact explains many of the instances in which the tremor ratings obtained by the two methods were only 1 category apart, but it cannot account for the 17.5% of evaluations that were 2 or more categories apart.

The quantitative assessment of tremor as performed here yields different findings from assessment by visual inspection alone. The tremor-suppressing stimulation current-amplitudes are lower, and this, in turn, can often affect the chosen site for permanent electrode implantation. Thus, quantitative tremor assessment can affect, and perhaps improve, targeting in DBS without altering the routine surgical procedure. This tentative conclusion awaits confirmation by further studies. Moreover, aside from its potential direct clinical utility, quantitative tremor assessment DBS surgery might be a useful adjunct to the clinical testing of new types of DBS electrode.

References

1. Griffiths, R. I. et al (2012). Automated assessment of bradykinesia and dyskinesia in Parkinson’s disease. Journal of Parkinson’s disease, 2(1), 47–55. doi:10.3233/JPD-2012-11071 .

2. Shah, A. et al (2013). A method to quantitatively evaluate changes in tremor during deep brain stimulation surgery. 6th International IEEE/EMBS Conference on Neural Engineering, 1202–1205. doi:10.1109/NER.2013.6696155 .

Background

In the past three decades, over 100,000 movement disorder patients like Parkinson's disease (PD) have been treated by deep brain stimulation (DBS). Despite an increasing use of DBS, the fundamental mechanisms underlying therapeutic and adverse effects as well as the optimal stimulation site remain largely unknown. Among other techniques, computational simulations of the distribution of electric entities have been used to analyze long term chronic stimulation results in relation to the anatomy surrounding the stimulating contact. To our knowledge such methods have never been applied to study clinical results obtained during intraoperative stimulation tests. Therapeutic effects of stimulation are in general visually evaluated based on subjective clinical rating scales which are known for their inter- and intra-rater variability. While very few research groups have attempted intraoperative quantitative tremor evaluation, no research group has used computational simulations of the distribution of electrical entities during such stimulation tests. This study presents a method to correlate simulations of the electric field distribution during intraoperative stimulation tests with quantitatively evaluated symptom improvement and patient specific anatomy to get more information regarding mechanisms of action and in turn optimize DBS target selection.

Method

During DBS surgery of 3 essential tremor patient at the University Hospital in Clermont-Ferrand, France, a previously developed accelerometer based quantitative tremor evaluation technique was used¹. The ventro-intermediate nucleus (VIM) and its anatomic neighbors were manually outlined based on spontaneous MRI contrasts and using a high field (4.7 Tesla) atlas. For each paitient, two parallel trajectories were planned per hemisphere with 7-8 stimulation test positions per trajectory spanning the region of interest. During the intraoperative stimulation tests, accelerometer data were recorded in sync with the stimulation current amplitude. Tremor improvement was postoperatively quantified compared to baseline tremor. For two stimulation amplitudes (low and high improvement) per position the effect of intraoperative stimulation tests in relation to the patient’s anatomy was studied along with the Department of Biomedical Engineering at Linkoping University. A computational model of the intraoperatively used exploration electrode was developed to simulate electric-field isosurface (0.2V/mm) in the brain for the previously identified stimulation current amplitudes at the different test positions. Due to the large number of simulations, each voxel in the region of interest may be part of several isosurfaces -each surface depicting one amplitude responsible for one improvement in tremor. To simplify visualization and interpretation, a maximum improvement map was generated, where each voxel was assigned to the isosurface representing the maximum improvement. Anatomical images, delineated structures, trajectories and improvement maps were visualized together in Paraview (Vtk based visualization software). The resulting visualization was evaluated by clinicians.

Results

The software allowed 3D visualization as well as orthographic slices parallel to the trajectory.  Clinicians confirmed that it enables the identification of the most effective stimulation areas with respect to the anatomy. A visual analysis of the improvement map for all the patients indicate that the highest improvement in tremor is observed when the region inferior, posterior and medial to the VIM is stimulated, i.e. the region where prelemniscal radiations merge with the VIM. 

Discussion and conclusion

The proposed concept based on quantitative tremor evaluation, electric field simulations and patient specific anatomical data proposed provides a unique way to visualize a multitude of information in an interactive and adaptable way.  The application of the method to 3 patients shows that the region where prelemniscal radiations merge with the VIM may be optimal for reducing tremor. This is also observed by other researchers. By applying this new method on more patients, the analysis of a high amount of intraoperative data might help to elucidate the mechanism of action of DBS.

References

1. Shah, A. et al. (2013). A method to quantitatively evaluate changes in tremor during deep brain stimulation surgery. 6th International IEEE/EMBS Conference on Neural Engineering, 1202–1205. doi:10.1109/NER.2013.6696155 .

Aim: The aim of this study was to evaluate the long-term efficacy of unilateral deep brain stimulation (DBS) of the caudal Zona incerta (cZi) for treatment of tremor-dominant Parkinson’s disease (PD).

Method: 13 patients with medically refractory and predominantly unilateral tremor-dominant PD were included and assessed before surgery and at 1 year and at long term follow up 3-8 years after surgery. The mean age at the time of surgery was 67 years (range 59-75 years). The cZi was identified anatomically on stereotactic T2-weighted transaxial MRI images medial and slightly posterior to the visualized posterior tail of the subthalamic nucleus at the horizontal level of the maximal diameter of the red nucleus. The electrode location was verified with an intra-operative stereotactic CT. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS-III) combining OFF/ON medication and OFF/ON stimulation. Friedman’s test was used for statistical evaluation of non-parametric values and the Wilcoxon signed rank test as a post-hoc analysis. Analysis of variance for repeated measurements was used for continuous variables with the Bonferroni correction method as a post hoc test. A p-value ≤0.05 was considered statistically significant.

Results: Long-term follow-up were performed at a mean time of 62 months after surgery.  

   Contralateral tremor-scores were reduced from 7.8 off med/off stim to 1.5 (80% p≤0.001) off med/on stim at one year and from 7.4 to 1.8 (76% p≤0.001) at long-term follow-up. The corresponding figures when combining stimulation and medication were 0.7 (91% p≤0.001) at one year and 0.9 (88% p≤0.001) at long-term follow-up.

   Contralateral hand tremor at rest were reduced from 3.2 off/off to 0.5 off/on (86% p≤0.002) at one year and from 2.8 to 0.5(82% p≤0.002) at long-term follow-up. The corresponding figures when comparing on med/on stim were 0.3(90% p≤0.002) at one year and 0.1(97% p≤0.001) at long-term follow-up.

  Contralateral action-tremor were reduced from 3.4 off/off to 0.5 off/on (84% p≤0.001) at one year and from 2.9 to 0.8 (72% p≤0.002) at long-term follow-up. The corresponding figures when comparing on/on were 0.4 (89% p≤0.001) at one year and 0.6 (79% p≤0.002) at long-term follow-up.

   Contralateral bradykinesia had a minor but significant reduction at both one year and long-term follow-up with stimulation alone. The symptom reduction was further increased when combining stimulation with medication.

  Contralateral rigidity had a minor reduction at one year but the effect was non-significant at long-term follow-up both with stimulation alone and combination with medication.

  Total UPDRS-III score was reduced from 42.5 off med/off stim to 27.7 off med/on stim (35% p≤0.001) at one year and from 46.5 to 35.4 (24% p≤0.001) at long-term follow-up. The corresponding figures on med/on stim were 17.2 (59% p≤0.05) at one year and 28.7 (38% p≤0.002) at long-term follow-up.

   Mean stimulation parameters were 2,8 V, 71,5 uS and 148,5 Hz at one year and 2,7 V, 76 uS and 146,9 Hz at long-term follow-up. These differences were non-significant.

Conclusion:

Unilateral cZi DBS continues to be an effective treatment for patients with severe Parkinsonian tremor even many years after surgery. The effect is pronounced regarding tremor, even if minor improvements are also seen regarding bradykinesia.

Background: Dystonia is a heterogeneous group of movement disorders, which is specified by sustained or intermittent muscular contractions, causing involuntary abnormal movements and/or postures. Indications for neurosurgical treatment in dystonia include inefficacy/insufficiency of pharmacological treatment, widespread distribution of pathological movements, limitation in activities of daily living and self-service due to dystonic movements. Main clinical goal of the surgery is prevention of permanent disability and improving in the quality of life of dystonia patients.

Objective: To analyze the experience of neurosurgical treatment of dystonia patients in Burdenko Neurosurgical Institute.

Patients and methods: 179 patients with different types of dystonia were operated in the period from 2003 to 2015: 56 patients with isolated (primary) generalized dystonia; 44 with isolated segmental dystonia; 41 with isolated focal/cervical dystonia; 7 with myoclonic or tremulous dystonia; 2 with basal ganglia calcification; 6 with the other neurodegenerative dystonia; 4 with tardive dystonia, 14 with dyskinetic cerebral palsy (CP); 5 with the other acquired dystonia. Disease duration ranged from 2 to 57 years; age at surgery ranged from 7 to 67 years. We assessed clinical outcome in patients with the minimum three-year follow-up available. Burke-Fahn-Marsden rating scale was used to evaluate dystonia severity. For cervical dystonia, TWSTRS and Tsui scales were applied. Postoperative changes in functional and motor state were assessed using Global outcome scale (GOS).

Results: Majority of the patients with primary (isolated) dystonia received DBS GPi (134 patients, 95%). Ten of them had a history of previous stereotactic lesioning surgery. Main clinical improvement was observed in the first 6 months of DBS GPi. 86 patients were available for evaluation in long-term follow-up. Motor improvement in patients with generalized dystonia after 3 years was 59.7±15.7%, in patients with segmental dystonia – 66.5±17.5%, according to BFMDRS. In cervical dystonia, motor improvement after 3 years of DBS GPi was 55.5±22.1%, according to TWSTRS, and 60.9±19.9%, according to Tsui scale. 88% of patients had stable excellent or good motor and functional outcome in long-term follow-up (up to 12 years, GOS). Negative predictive factors for DBS GPi efficacy in primary dystonia appeared to be longer disease duration, earlier age of onset, and severity of motor impairment. Four patients required implantation of the second pair of GPi-electrodes for optimizing clinical outcome.

One patient with previous thalamotomy underwent bilateral DBS STN with 66% improvement.  

In 6 patients with predominantly tonic pharmacoresistant cervical dystonia, selective peripheral denervation of cervical muscles was performed alone (3 patients) or in addition to DBS GPi (3 patients).

Among non-primary dystonia, high DBS GPi efficacy was observed in patients with tardive dystonia. Mean improvement in motor BFMDRS was up to 90%. In BGC-associated dystonia, initial response to DBS GPi was good, however, deteriorated in the later time course.

In the other neurodegenerative and acquired dystonia associated with structural brain lesions, functional outcome of DBS GPi was poor with minimal motor improvement.

In patients with predominant dystonic tremor or myoclonus and distal limb dystonia, DBS of ventral lateral thalamic nuclei was preferred.

Two patients with unilateral limb dystonia (incl. hemidystonia, action-specific/occupational dystonia) underwent unilateral Vop-thalamotomy with good functional outcome.

For dyskinetic CP patients, intrathecal baclofen pump therapy or selective combined (dorsal and ventral) rhizotomy was applied alone or in combination with stereotactic procedures (DBS or lesioning) and peripheral neurotomy;

Conclusion: At present, DBS GPi has the largest evidence of efficacy and safety for dystonia. Selection of the other surgical approaches and targets is possible on the individual basis. Thalamic targets are to consider in tremulous/myoclonic dystonia or limb dystonia. There is still no clear evidence for DBS of subthalamic nucleus in dystonia. Stereotactic lesioning procedures have limited application and need to be performed unilaterally to avoid neurological complications. Surgical outcome in non-primary dystonia varies individually; in CP, often staged surgical procedures are needed. For maximal efficacy the timeliness of surgical intervention is important. Preoperative evaluation of surgical candidates should be carried on by experienced multidisciplinary team.

INTRODUCTION

Deep brain stimulation of the ventral intermediate nucleus of the thalamus provides a suitable therapeutic option in tremor dominant movement disorders. However Holmes-tremor, as a condition of traumatic or ischemic origin, still proves to be difficult to manage using conventional techniques. Individual anatomical differences and lesions in various components of neural networks regulating fine movements can contribute to an even more complicated clinical picture.

METHODS

2 patients, a 16 year-old boy and 35 year-old woman, suffering from medically intractable Holmes-tremor were selected for deep brain stimulation. The 16 year-old patient started to develop a right upper extremity tremor 3 months after a car accident. The female patient has started to show signs of a left upper extremity tremor accompanied by a dystonic posture 2 years after a brainstem cavernoma bleeding at the level of the red nucleus. 3D T1 (1x1x1 mm, isotropic voxels), contrast enhanced T1, SWI (0,68x0,68x1,5 mm), and DTI (32 directions, 2x2x2 mm, isotropic voxels) MRI sequences were acquired preoperatively from both subject on a Siemens Verio 3T scanner. DTI analysis has been carried out using FSL 5.0.9 (FMRIB Software Library, Oxford), while cortical parcellation was done using Freesurfer 5.3.0 (Martinos Center for Biomedical Imaging, Harvard University). Subcortical seed regions for probabilistic functional segmentation of the thalamus and visualization of dentate-rubro-thalamic tract were delineated manually. Probabilistic tracking has been carried out using FSL ProbtrackX with default settings and modified Euler streaming. Results of tractography were fused with anatomical T1 images, stereotactic targets were identified on a Medtronic Planning Station running Framelink 5 (Medtronic Inc., Minnesota). For proper lead placement, intraoperative microelectrode recording, macrostimulation, and fluoroscopy were utilized.

RESULTS

Probabilistic tractography was able to visualize the dentate-rubro-thalamic tract in both patients, however, it was only partially traceable in our female patient due the extensive lesion at the level of the red nucleus. Distinct functional subgroups within the thalamus were also identified providing  a well estimated location of the ventral intermediate nucleus. Intraoperative microelectorde recording and macrosimulation correlated with the tractography, while tremor was reduced significantly due to microlesional effect and stimulation. Final lead and stimulation contact positions were evaluated on postoperative CT-tractography fusion images showing both leads residing in the ventral intermediate nucleus, the dentate-rubro-thalamic and thalamo-cortical pathways 6 weeks after surgery.

CONCLUSION

Using novel imaging techniques, thalamic nuclei and the dentate-rubrothalamic tract can be properly identified. Probabilistic tractography, while identifying important components of the affected neural networks, can provide a safe and viable option in the surgical management of Homes-tremor, resulting in long lasting tremor control.

Introduction: Advanced Parkinson’s disease (PD) is an indication for advanced interventions such as deep brain stimulation in the subthalamic nucleus (STN DBS) or infusion of levodopa-carbidopa intestinal gel (LCIG). Observations regarding neuropsychiatric effects after respective treatment consist of conflicting or insufficient data. Additional knowledge regarding neuropsychiatric effects may help identify appropriate candidates for these treatments. Aims: To compare the possible differences in neuropsychiatric profile and quality of life (QoL) after intervention between STN DBS and LCIG patients. To determine possible neuropsychiatric effects of respective intervention by comparing neuropsychiatric profiles in respective patient group to controls. Material and Methods: A cohort of 40 patients with advanced PD, 13 STN DBS, 12 LCIG and 15 controls were investigated. Neuropsychiatric effects were investigated by computer-based assessment of working memory and impulsivity. In addition, values from a depression rating scale and QoL scales were collected. Results: No significant differences were detected regarding neuropsychiatric profile or QoL in comparisons between STN DBS and LCIG patients (P > 0.05). In three group comparisons including the control group, trends towards differences in self-rated QoL were found indicating highest self-rating in LCIG patients and lowest in the controls (P = 0.054). Conclusions: No significant differences between patient groups could be observed. Trends indicating better QoL in patients with advanced treatment were observed. Prospective randomized studies in larger patients cohorts with neuropsychiatric evaluation before and after respective treatment are warranted to fully determine clinical effects of these therapies. 

Introduction. The evolution of cognitive abilities after the deep brain stimulation (DBS) in Parkinson’s Disease (PD) is a challenging matter in particular for subjects implanted at the subthalamic nuleus (STN): controversial findings and the fear of a possibly negative impact emerged from the literature that is poor of long-term follow-up studies. Objective: The primary objective was to follow the evolution of the cognitive abilities and disability after ten years of STN-DBS, through a perspective observational study over ten years of follow-up. Secondarily we studied the relationship between the cognitive evolution and the evolution of disability in this kind of subjects.

Methods. Study design: prospective cohort study with follow-up to 10 years. Subjects with PD were enrolled in the study if they underwent consecutively, since 2005, the high frequency stimulation of subthalamic nucleus bilaterally. Patients underwent an evaluation protocol, before the intervention and annually after implantation, which included disease-specific scales, global and selective clinical monitoring (UPDRS), the structured assessment of cognitive skills, as well as verification of therapeutic window of stimulation parameters and the antiparkinsonian drug therapy. The following tests were used as a cognitive outcome measures: MiniMental State Exsamination (MMSE), Frontal Assessment Battery (FAB), Rey’s Test of Words, Corsi’s Test (CS), Digit span (DS), Raven Colored Progressive Matrices (RCPM), Attentive Matrix (AM), Trail Making A/B (TM A-B), Stroop Test (ST), Test Weigl (WT), copying designs (constructional praxis-CA), Test of overlapping figures ( VST-visuospatial tests), phonemic fluency (PF), semantic fluency (SF); The functional outcome was assessed by UPDRS part II (ADL).

Results. Thirty subjects were enrolled: mean age 60.0[SD6.4], years of disease 11.8[SD3.4], education 7.4[SD3.9], UPDRS Section II 15.9[SD5.6], LEDD 1055[SD 353]mg, MMSE  26.5[SD 3.2], FAB 15.1[SD 2.9].After 10 years of follow-up, on average, verbal and non-verbal memory remained unchanged; executive functions (ST, TMB) and fluency worsened significantly (p<.01): subjects lost 25% word at the SF test and the 19% at the PF. Ten patient (20%) showed a moderate-severe global cognitive impairment and reached a MMSE score lower than 20/30. UPDRS II showed, in the first 5 years after surgery, a significant improvement, which was gradually reducing until it disappeared and reversed at the tenth follow-up (Chi2 = 30.9, p <.0001). No direct relation was found between UPDRS II and MMSE after ten year of follow-up.

Conclusion. Subjects with STN-DBS for PD showed a prevalence of dementia similar to that of general PD population, as described in the literature. Also the evolution of the different monitored abilities confirm previous data. Cognitive condition did not emerged as predictor of disability.

Reference.

Capecci M, Ricciuti RA, Burini D, Bombace VG, Provinciali L, Iacoangeli M, Scerrati M, Ceravolo MG. Functional improvement after subthalamic stimulation in Parkinson's disease: a non-equivalent controlled study with 12-24 month follow up. J Neurol Neurosurg Psychiatry 2005;76(6):769-74

Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, Piano C, Piccininni C, Romito LM, Lopiano L, Albanese A. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: from the advanced phase towards the late stage of the disease? Parkinsonism Relat Disord. 2014;20(4):376-81

Merola A, Rizzi L, Artusi CA, Zibetti M, Rizzone MG, Romagnolo A, Bernardini A, Lanotte M, Lopiano L. Subthalamic deep brain stimulation: clinical and neuropsychological outcomes in mild cognitive impaired parkinsonian patients.  Neurol. 2014;261(9):1745-51.

Introduction:
Different neuromodulation methods are established to treat chronic headache and several reports indicate that sphenopalatin ganglion (SPG) stimulation offers advantages in Cluster headache over other other stimulation methods as occipital nerve stimulation. Limited evidence exists for both methods regarding both long-term efficacy and mechanism of action. We report on a patient suffering from chronic cluster headache with >20 attacks/months, who partially benefits from ONS and underwent additional SPG stimulation.

Methods:
The patients is a 47 y old male suffering from cluster headache therapy refractory to conventional medical treatment. He underwent ONS in another department via a midline approach at the C0/1 level with two octrodes connected with an IPG in the buttock (EonMini, St. Jude Medical). Reported initial reduction in headache days (from 25 to 4 days/months, VAS 10/10 to VAS 4/10) was lost after three months of treatment, when he consulted our department. A dislocation of one electrode was seen and a technically successful revision was performed. However, the patient reported stable conditions after 6 months with 20 headache days per months (VAS 8/10, required up to 60 triptane injections /month). As the patient still remained severely disabled and was unable to work we considered an additional SPG stimulation. 

Results:
A permanent SPG stimulation device (ATI) on the left side was implanted in collaboration with the ENT department, no adverse events occurred. Stimulation was switched on 4 weeks postoperatively. Using conventional stimulation parameters (120 Hz, 434µs, 1.6mA, 1+, 3-), pain relief was achieved with a significant decrease in cluster attacks (6 attacks/months). Additionally a reduction in triptane use to 8 injections per months was noted.

Conclusions:
This case report indicates that a combination of different neuromodulation methods to influence the trigemino-autonomic system is feasible, effective and safe. 

Background: Hypnosis can be described as a highly focused, absorbed attentional state that minimises competing thoughts and sensations. Hypnotic suggestibility is normally distributed in human populations and remains a stable individual trait. It is heritable as shown in classic twin studies. The genotype Val/Met variant of the Catechol-O-Metyltransferase (COMT) gene is more frequent in individuals with high hypnotic suggestibility. Interestingly, it is associated with prefrontal executive functions and working memory. Several neuroimaging studies have brought to light the neural basis of the hypnotic experience. Used as anesthetic since the early 1800's (first reported surgery in 1829), it was almost abandoned with the introduction of chemical anaesthesia. In recent years its application gained interest in neurosurgery.

Awake craniotomy with intraoperative neurophysiological monitoring is the emerging application field of hypnosis technique as a reliable method to control pain and discomfort during cortical and subcortical mapping of motor and language areas. A new promising field of interest of this technique is the DBS surgery, to avoid discomfort and enhance the reliability in detecting side effect during microstimulation in patients affected by PD and dystonia. Fully awaken procedures are proposed to young adult patients affected by dystonia in our center but not always accepted. Hypnosis may be the effecting and safe option in this cases. Difficulties in copying with the stress are often the only limitation to this method.

Objective: To describe a method for awake DBS surgery based on hypnosis.

Methods: We started proposing hypnosedation procedure to patients undergoing awake surgery for DBS from January 2015. One patient was enrolled: a 26 years-old woman affected by secondary dystonia due to ICP (pre-operative BFMDRS-M: 76/120). A tailored induction was performed, leading the patient to her safe place, giving different suggestions according with the sensations elicited by the surgery and considering the preferences of the patient. The patient underwent a bilateral DBS of Gpi with intraoperative microrecording and stimulation.

Results: The DBS conducted in hypnosis condition was successful. Burr hole and injection of anaesthetics were the procedures reported as unpleasant. During surgery, we were able to detect side effect, in particular visual disturbances, during microstimulation through different trajectories without discomfort or fear of our young patient. One year after DBS of bilateral Gpi with standard parameters, the improvement of dystonia was remarkable (post-op BFMDRS-M: 53/120; more important improvements were detected on mouth, speech, neck and trunk items).

Conclusion: The main findings are the effectiveness and reliability of the technique in performing DBS, the efficacy of hypnosis to reduce dystonic movements until a complete temporary resolution, and the positive psychological impact of the technique on this dystonic patient submitted to DBS.

Introduction: Angina pectoris and neuropathic pain disorders are highly prevalent. Spinal Cord Stimulation (SCS) may provide pain relief in these patients. During SCS treatment, paraesthesia is generally experienced by the patient. The significance of paraesthesia on treatment efficacy, the possible role of placebo effects, and the importance of electrode position are not well understood. However, a significant percentage of SCS patients (~20%) experiences long-term loss of effect (“non-responders”). We report on the effectiveness of a new paraesthesia-free SCS stimulation paradigm (Burst) for the treatment of angina pectoris (AP) refractory to tonic stimulation.

Materials/Methods:

A 60y male patient with a pre-existing 11 y history of severe coronary heart disease, diabetes mellitus, several myocardial infarctions, Bypass surgery, failed PTCA and PVD underwent conventional midline SCS. The tips of the two paramedian octrodes were placed at the Th2 level. After a successful trial period, the permanent stimulator was implanted in the right buttock. (EonMini™,SJM). Preoperatively, the patient suffered from 3-4 VAS 7/10 AP attacks daily. 

Results: At the 3 months follow-up we saw a partial effect on the continuous background pain with tonic stimulation (50Hz, PW 412 µs, amplitude Perception at 5.10 mA, Comfort at 6.80mA, continuous stimulation) but not on the peak attacks (stimulation left 0 0 + + - - - +, right 3+, 4+, 5-, 6-, 7-, 8+). Since this settings failed to improve quality of life, we decided to test BURST stimulation. A single-blinded allocation for a period of 1 week each was tested: Tonic 30 Hz Stimulation, Burst Stimulation with 500Hz 1000μs, and placebo (off) stimulation (burst Frequency 500Hz,  40 bursts per second,  PW 1000µs, BurstActive 5 (Pulses), Target 70% of 3, cyclic stimulation : 3600 sec. on / 15sec. off). The patient reported immediate pain relief under burst stimulation (VAS 1/10), no pain relief in placebo and tonic setting was reported. Pain relief was stable at 6 months follow-up. No stimulation induced side-effects were observed.

Discussion: Two key findings are presented in this study: 1) SCS produces reproducible and reversible pain relief in patients suffering from AP refractory to conventional treatment and 2) paresthesia is not mandatory for effective treatment. SCS is effective both in suprathreshold tonic and high frequency burst stimulation. Burst stimulation might be an alternative for AP cases refractory to tonic stimulation. Further non-inferiority designed studies are ongoing to proof this concept.

Conclusions: Overall, paraesthesia-free Burst Stimulation resulted in better pain relief in this AP patient. These encouraging results form the basis for further investigations.

Introduction

Deep Brain Stimulation is an established treatment modality in various movement disorders including dystonia. Due to the close proximity of the most common target point (GPi) to critical functional structures as the optic tract and the internal capsule, therapeutic yield might be limited by side effects.

Recently, segmented DBS leads have been made available. This technique comes with the promise of increased efficacy and side effect reduction. We hereby report on the first case of dystonia treated with directional lead deep brain stimulation.

Methods

A 31 year old female presented with a 20 year history of generalized dystonia. The severe additional

ataxic component left her wheelchair bound and she suffered from severe dysarthria.

The neurological complex was thought to be caused by a proven isolated Vitamin E deficiency

syndrome. MRI revealed structural changes of the basal ganglia anatomy with anatomical

distortions pronounced on the left (Image 1). Standard coordinates did not match the individual

anatomy of the patient. She therefore underwent bilateral GPi DBS surgery using direct

targeting of the left GPI. Directional leads were implanted in both hemispheres. 

Results

After calculation of standard AC-PC coordinates (3.5 mm anterior, 22.0 mm lateral and 4.0 mm below MCP) the trajectory was adapted guided by MRI anatomy to the lateral border of the optic tract. The posterior communicating artery took a atypical course above the optical tract further limiting the approach. Targeting was guided by three micro electrode recording tracts and a directional lead system (Vercise DBS, Boston Scientific) was implanted in an all-in-one GA setting. Conventional stimulation caused a fast worsening of the dysarthria and painful stimulation induced side effects. The segmented contacts were intensively tested at 90µs and 130 Hz in the postoperative course. Distinct effect/side-effect patterns for each contact were observed. 

Conclusion

Segmented leads allowing current steering offer new perspectives for DBS and will likely result in increased treatment efficacy while reducing side effect at the same time. While this is true for well known disorders and their targets (PD, generalized dystonia) this technique also yields the potential to treat disorders currently not amendable to DBS as no good benefit/side-effect ratio could be achieved with conventional DBS. This includes diseases as described here with complex and basically unknown changes in basal ganglia functionality and structure.

Introduction: A multitude of evidence supporting the beneficial effects of spinal cord stimulation (SCS) in patients suffering from chronic pain syndromes following spinal surgery has been published in the last decade.  Evidence is scarce however for the use of high frequency SCS (HFSCS) in the treatment of surgery naïve patients suffering from lower back pain (LBP). 

Methods: From June 2014 to April 2015 we prospectively enrolled patients suffering from LBP alone or in conjunction with leg pain in a trial of HFSCS.  None of the patients had undergone surgical procedures of the thoracic, lumbar or sacral spine.  Patients suffered medically intractable LBP and were deemed ineligible for spine surgery due to mismatches in imaging findings and clinical symptoms, or were medically unfit to undergo extensive surgical procedures.  All patients underwent trial stimulation for at least one week.  IPG implantation was conducted only following successful trials.  Pain levels were assessed daily during initial stay, 4 weeks later and then every 3 months.  Different pre-programmed modes of HFSCS were changed if pain persisted or increased during trial or post-implant follow-up. 

Results: A total of 8 patients (4 male, 4 female) underwent HFSCS trials.  Mean age was 60 ±4.8 years.  Mean VAS baseline intensity for back pain was 8.9 ±0.23 and 8.1 ±0.6 for leg pain.  All patients achieved meaningful reductions in pain intensities and underwent IPG implantation at a mean interval of 13 ±1.3 days.  Mean follow-up was 306 ±48 days in February 2016.  Mean back pain VAS reduction from baseline at last follow-up was -4.13 ±0.85, and -6.2 ±1.03 for leg pain.  Two patients showed skin irritations and localized pain at the IPG site.  Both patients underwent surgery to replant the IPG.  No infections were seen in any of the 8 patients enrolled.

Conclusions: In this prospective cohort of surgery naïve patients we were able to show good efficacy of HFSCS for both back and leg pain.  Reductions were long-lasting with a mean follow-up of nearly 10 months in our cohort, and a mean VAS reduction at last follow-up of 4.13 and 6.2 for back and leg pain, respectively.

Background

The Pudendal Nerve Neuralgia is a cause of chronic pelvis pain in both male and female. This pain is distributed in the pudendal nerve territory and can affect all function of this nerve (sensory, motor and autonomic).  The causes are classified in primary or secondary (in this case is related with history of trauma, abdominopelvic surgery, radiotherapy, etc.)  The diagnosis and treatment of this condition is a challenger, due the variety of clinical presentation, the delay in the diagnosis and the lack of evidence in which is the best treatment options, attempt directly in the cure of this syndrome.

Objective

The aim of the study is to analyze the outcome of the pulsed radiofrequency in our patients with Pundendal Syndrome and determine possible factors related with the best following treatment election.

Materials and Methods

Retrospective analysis involving patients with pudendal neuralgia treated with pulsed radiofrequency by the Department of Neurosurgery, Italian Hospital de Buenos Aires, since June 2015 to December 2015.  The radiofrequency was performed to all patients as first step for diagnosis and treatment. Previously, the patients had to fill Pelvic Pain and Sphincters Disorders Form, performed by the Center Pelvic Pain and Sphincters Disorders of the Italian Hospital in concordance by the International Pelvic Pain Society. These guide assesses all aspects of this kind of syndrome (pain aspects and Sphincters function). Then relevant data were collected and analyze. We excluded all patients that not accomplish the Nantes ´s Criteria. We used de Visual Analogue Scale (VAS) to assess the pain.

Results

A total of twenty patients were treated in this period, thirteen were woman (65%) and seven were men (35%). The average age was 51,6, with a range between 31 to 74 years. The clinical history background is different between sex: urological background with 61.53% in women (interstitial cystitis, urethroplasty, reiterative urinary infection) and 85,71% in men (chronic prostatic infection, prostate resection, radiotherapy); coloproctological with 38.4% in woman (rectal prolapse, colostomy, enterocele); and gynecological 46.15 % (utheropexy, structural pelvic pathology, etc.). The average time between the onset to symptoms and the first consult was 28 months, with a range between 5 to 120 months. All patients complained for pelvic pain according Nantes Criteria in the first consult, except one that the syndrome was Sphinteric pure at the onset (affecting the defecation) and then appeared the pain aspects. The average VAS previous (VASpr) the treatment was 8,52, with a range 3 to 10.  The pain was associated with sphinteric dysfunction in 8 patients (40%), characterized with combined affections in 50% (urologic and coloproctological) and isolated urinary or coloproctological symptoms both with 25%. The outcome was assessed with VAS: in the first cycle of radiofrequency, the VASpr decrease in 41%. In the second cycle (VAS2), the VAS decrease in 60.1% and 43% if it is compare with the VASpr and the VAS post first radiofrequency respectively. Finally, the VAS in the third cycle decrease in 34% and 35% if it is compared with de VASpr and VAS2. The sphincter function improved in 6 of 8 patients, more frequently in urinary symptoms.

Conclusion

The pulsed radiofrequency is a very efficient treatment of the symptoms derived of pudendal neuralgia. In consequence of the lack of information in the literature related with the effectivity, is recommended a series from 2 to 4 procedure in every patient despite the partial improvement, separated with 2 o 3 months between it. In our series we notice that the best improvement was in the second cycle compared with the others. Some features of the clinical history of the patient like the background of trauma, the isolated pain in the penis, the time from the symptoms onset until the first consult more than four years, the poor response to opioids, could be special factors to consider in the election of the amount of radiofrequency cycles and the necessity to pass to the next step in the treatment protocols.

Axial tremor is detected in 40% to 60% of patients affected by Essential Tremor (ET).  Head tremor, when present, severely affects the social aspects and it is recognized as strongly enabling. In respect to tremor of extremity, axial tremor shows lower response to medical treatments and also Deep Brain Stimulation (DBS) of the Ventral Intermedius Thalamus (VIM), even when bilateral, gives inconsistent results. Here we report our preliminary experience in two cases of head tremor successfully treated with MRI-guided focalized ultrasounds  (MRgFUS). In April 2016, two men of respectively 35 and 52 years, affected by ET with head tremor underwent unilateral thalamotomy with MRgFUS at our Institution. A previous  multidisciplinar (neurological, neurosurgical, psychiatric and anestesiological) evaluation  was performed. Screening CT and MRI brain scan with opportune protocols for the visualization of basal ganglia and of the thalamus gave the elegibility to the treatment. The entity of tremor and the relative psychological impact were quantified by la Fahn-Tolosa-Marin Tremor Rating Scale (FTM)  and  Quality of Life in Essential Tremor (QUEST). The baseline FTM score was 38 and 44 respectively. FTM score for head tremor was 4 and 2. The thalamus treated corresponded to the drive side (the more affected one)  that was the left for the first patient and the right for the latter. Both patients  showed immediate benefit from the procedure, without any side effect. A brain MRI scan with contrast medium excluded complications related to the treatment. Surprisingly, together with the expected disappearance of the extremity tremor, we also observed a strongly  relief in axial head tremor that passed to a score of respectively   1 and 0 after the treatment. Unilateral thalamotomy with MRgFUS is efficacious not only to abolish contralateral extremity tremor but it has also a significant impact in ameliorating the axial tremor when the drive side is treated. Even with preliminary observations with limited follow up, this non invasive and high precision technique seems to offer other new perspectives also for other clinical variants of ET, highly enabling and, up to now, not responsive to the traditional therapeutic tools.     

Introduction: Twiddler syndrome (TS) is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices (1,2). The predisposing factors for development of TS include advanced age with more loose subcutaneous tissue, adipose patients with thick tissue layer precluding proper immobilization of internal pulse generator (IPG), creation of excessively large pocket or obsessive-compulsive behavior (3,4).  Additional factor related to the construction of the implanted hardware itself may be the number of anchoring holes in the IPG.

Methods: A prospectively collected database of all hardware related complications for patients operated on at the Neurosurgical Department of Postgraduate Medical Center of Warsaw was performed. In a total number of 347 leads implanted in 211 patients since 1999 we have identified 3 patients diagnosed with TS. All 3 patients with TS in our series were implanted with the IPG harboring one anchoring hole. This complication did not occurred in patients with the IPG harboring two anchoring holes.

Results: All 3 patients underwent revision surgery. During reoperations all IPGs were replaced and sutured with one additional silk suture through the plastic housing of the IPG to immobilize it properly in subcutaneous pocket. There were no recurrences of TS in our patients. All patients gained the previously derived benefit from STN DBS.   

Conclusions: Our case series suggests that a predisposing factor of TS may also be the construction of IPG itself (one anchoring hole intended for fixation) which naturally represents less fixation of the IPG to the fascia or muscle in the subcutaneous pocket. This preliminary report may favor the IPG with two anchoring holes which is less prone for development of TS. Placing additional silk suture that pass through a plastic housing of the IPG may help better immobilize the IPG and reduce the occurrence of TS.

[1] Bayliss CE, Beanlands DS, Baird RJ: The pacemaker-twiddler's syndrome: a new complication of implantable transvenous pacemakers. Can Med Assoc J  1968; 371-373.

[2] Geissinger G, Neal JH: Spontaneous twiddler's syndrome in a patient with a deep brain stimulator. Surg Neurol  2007;68:454-456.

 [3] Burdick AP, Okun MS, Haq IU, Ward HE, Bova F, Jacobson CE, Bowers D, Zeilman P, Foote KD: Prevalence of Twiddler's syndrome as a cause of deep brain stimulation hardware failure. Stereotact Funct Neurosurg 2010;88:353-359.

[4] Machado AG, Hiremath GK, Salazar F, Rezai AR: Fracture of subthalamic nucleus deep brain stimulation hardware as a result of compulsive manipulation: case report. 2005;57:E1318.

Introduction: Meige syndrome (MS) is characterized by blepharospasm, facial, oromandibular, and cervical dystonia. The medical treatment of this condition is challenging and unsuccessful over long time. Recent case reports and small clinical series showed that bilateral deep brain stimulation (DBS) of globus pallidus pars interna (GPi) improves dystonic features of MS validated by Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS) (1-5). 

Methods: We report on our experience in using bilateral GPi DBS in 5 cases of MS. We present short-term (3 months) follow-up as well long-term (from 24 months to 48 months) results. Preoperative and postoperative BFMDRS assessments were performed on each patient. The postoperative BFMDRS scores was done when both stimulators were switched on and compared to baseline scores.

Results: Bilateral GPi DBS reduced the BFMDRS total movement score by 75 % at short-term follow-up, and by 87 % at long-term follow-up when compared to baseline scores.  The BFMDRS total disability score was reduced by 46 % at short-term follow-up, and by 56 % at long-term follow-up when compared to baseline scores. 

Conclusions: Our results showed that bilateral GPi DBS in MS is effective and safe, if conservative treatment options failed. The benefit is not only observed at short and at long-term follow-up ranging from 24 to 48 months.

[1] Capelle HH, Weigel R, Krauss JK. Bilateral pallidal stimulation for blepherospasm-oromandibular dystonia (Meige syndrome). Neurology 2003;60: 2017- 2018.

[2] Markaki E, Kefalopoulou Z, Georgiopoulous M, Paschali A, Constantoyannis C.  Meige syndrome: a cranial dystonia treated with bilateral pallidal deep brain stimulation. Clin Neurol Neurosurg 2010;112: 344-346.

[3] Lyons MK, Birch BD, Hillman RA, Boucher OK, Evidente VG. Long-term follow-up of deep brain stimulation for Meige syndrome. Neurosurg Focus. 2010 Aug; 29(2):1-5.

[4] Ostrem JL, Marks WJ, Volz MM, Heath SL, Starr Ph. Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome)  Mov Disord. 2007; 22:1885-1891.

[5] Reese R, Gruber D, Schoenecker T, Bäzner H, Blahak C, Capelle HH, Falk D, Herzog J, Pinsker MO, Schneider GH, Schrader C, Deuschl G, Mehdorn HM, Kupsch A, Volkmann J, Krauss JK. Long-term clinical outcome in Meige syndrome treated with internal pallidum deep brain stimulation. Mov Disord. 2011;26:691-698. 

Introduction: Tardive dystonia (TD) represents a side effect of prolonged intake of neuroleptic drugs.  TD can be a disabling movement disorder persisting despite available medical treatment. Deep brain stimulation (DBS) has been reported successful in this condition although the number of treated patients with TD is still limited to small clinical studies or case reports (1-5). In this study, we present 3 additional cases of patients with results of bilateral globus pallidus internus (GPi) stimulation.

Methods: The formal assessment included the Burke-Fahn-Dystonia Rating Scale (BFMDRS). The preoperative and postoperative functional and motor parts of BFMDRS were compared in each patient.

Results: Three patients underwent successful bilateral GPi DBS for TD. The postoperative BFMDRS motor score improved by mean of 71% at the last follow-up.  There were no surgical or hardware-related complications over follow-up period.

Conclusion: Our experience indicates that bilateral GPi DBS can be an effective treatment for disabling TD.  The response of TD to bilateral GPi DBS is very rapid and occurs within days after the procedure.  

[3] Trottenberg T, Paul G, Meissner W, Maier-Hauff K, Taschner C, Kupsch A. Pallidal and thalamic neurostimulation in severe tardive dystonia. J Neurol Neurosurg Psychiatry 2001;70:557-559.

[4]. Trottenberg T, Volkmann J, Deuschl G, Kühn AA, Schneider GH, Müller J, Alesch F, Kupsch A. Treatment of severe tardive dystonia with pallidal deep brain stimulation. Neurology 2005;64:344–346.

[6]. Cohen OS, Hassin-Baer S, Spiegelmann R. Deep brain stimulation of the internal globus pallidus for refractory tardive dystonia. Parkinsonism Relat Disord. 2007;13:541–544.

The globus pallidus internus (GPi) is the final output relay of the basal ganglia for the control of movements but has also been shown to belong to a second pathway projecting to the lateral habenula. This latter pathway is related to reward processing. This prompted us to record, in eight  patients receiving deep brain stimulation of the GPI for the alleviation of movement disorders, local field potentials while these patients performed a lottery task. The task entailed choosing between a higher and a lower number, which changed their color after the patient’s choice with red (green) signaling a loss (win, in Euro cents) corresponding to the chosen number. Surface recordings showed a feedback related negativity from a frontal midline site, while time domain averages in the GPI showed differential modulation depending on the valence of the stimulus with polarity inversion indicating that this reward-modulated activity was indeed generated locally. Furthermore, wavelet decomposition of the LFP showed a reward-related response in the high beta / low gamma range. We conclude that human GPI is involved in reward processing, possibly in relation to the lateral habenula.

Deep brain stimulation (DBS) has become an accepted treatment for primary generalized and segmental as well as secondary dystonia. Growing evidence of sustained clinical benefit of DBS in dystonia has been reported in long-term studies >10 years. Detailed analysis of reappearance of dystonic symptoms after switch-off has shown rapid restoration of phasic elements within seconds whereas tonic symptoms re-emerged with some delay. It remains unclear, however, whether dystonia will recur in a similar fashion upon longterm DBS.

We report on a 32-year-old patient with generalized secondary dystonia with choreatiform movements due to perinatal asphyxia. The pre-operative Burke-Fahn-Marsden Scale motor score (BFM) was 80.5, disability score (DS) 19. Six months later, implantation of quadripolar stimulation electrodes (Model 3387; Medtronic Inc., Minneapolis) was performed bilaterally in the ventral intermediate nucleus (Vim) of the thalamus as well as the posteroventral lateral GPi with CT-guided stereotactic surgery and microelectrode recording. Post-operatively, the patient showed sustained improvement of the dystonic tremor and fine motor skills, he was able to grip objects and could guide the glass to his mouth by himself. Furthermore his speech improved (BFM 67.5, DS 15 at 17 months postoperatively).

Eventually, at 76 months, our patient presented for his routine follow-up and reported, that his DBS might have switched off.IPG check revealed a battery at end of life and analysis of DBS activity displayed an off-switch 5 weeks ago. Clinical examination was stable (BFM 69, DS 15).

Our patient had sustained clinical benefit as reflected by stable BFM score, which goes beyond the observations of improved symptoms after DBS discontinuation compared to the pre-OP situation. In parallel to previous reports he was under DBS for long time. To our knowledge, this is the first case of sustained therapeutic effect of DBS in dystonia after battery depletion in secondary dystonia. Systematic studies need to be performed to assess such neuromodulatory effects.

INTRODUCTION

Historically, DBS systems have delivered stimulation using cylindrical electrodes, which stimulate neurons around the entire circumference of the lead. In this study, we will test a directional DBS lead, which includes radially segmented electrodes designed for selective stimulation in directions orthogonal to the lead trajectory, in addition to standard cylindrical electrodes. Bilateral directional DBS leads will be connected to the Boston Scientific Vercise PC pulse generator, which provides an independent current source for each of its 16 contacts. This system, therefore, is capable of current steering to shape stimulation in the plane orthogonal to the long axis of the lead (directional stimulation), as well as providing Ring Mode (omnidirectional) stimulation equivalent to historical leads. We aim to characterize the effects of directional stimulation in subjects implanted with this system.

METHODS

DIRECT DBS is a prospective, randomized, multi-center, double-blind study employing a crossover design. Subjects (N = 10 to 12, adaptive) will be enrolled per center standard of care and implanted with a directional lead (Cartesia, Boston Scientific) included as part of a directional Vercise PC system for bilateral STN-DBS. Study visits occur in 3 major periods– during implant, at 3 months, and at 1 year. Programming is restricted during the first 3 months post-implant to Ring Mode. At 3 months, multiple single-day programming visits will be undertaken to optimize directional programming. Patients are then randomized to one of two arms (4 weeks per arm) for a double-blind crossover comparison between Ring Mode and unrestricted (e.g. directional) programming. After the crossover phase, subjects enter an open-label phase of the study, with follow-up at 1 year.

RESULTS

This exploratory study will have no prospective statistical hypothesis, but will collect data such as side effect threshold, therapeutic window, UPDRS scores, and quantitative accelerometer-based measures of bradykinesia and tremor.

DISCUSSION

DIRECT DBS is an exploratory study which will investigate the effects of subthalamic deep brain stimulation (DBS) using directional DBS leads with current steering in patients with Parkinson's disease. The DIRECT DBS trial will compare the effects of directional stimulation and omnidirectional stimulation over the first year post-implant. Results will inform future studies.

Objective. One of the most important problems of today's neurosurgery and neurology practice is strict patient selection for spinal cord neurostimulation. For this purpose it is very important to define the character and the power of pain and the level of the muscle tone, to analize the results of stimulation electromyography and to implant the trial system before operation.

Matirial. Methods.SamaraRegionalHospital neurosergery department use spinal cord stimulation systems implanting in the posterior epiduralspaceto patients with pain and spasticity (muscle spasm, spastic limbs) as a part of a complex therapy. 41 patients have been operated: 12 women and 29 men with there age ranging from 22 to 63 years. In 12 cases there was an injury of cervical region, in 23 cases - thoracic region and in 6 cases – lumbar region of the vertebral column. The electrode was implanted in the posterior epidural space on the lumbar level by a standard procedure.

Results. The result of neurostimulation is improvement of the quality of life of the patients (using the SF-36 survey): pain relief for 55-60%, muscle tone decreasing – from 2,85 to 1,35 points, what is confirmed by the results of stimulation electromyography.

Conclusion. The results of spinal cord stimulation depend on strict patient selection. After operation patients with chronic pain and spasticity find that neurostimulation positively impacts the quality of their lives: they achieve reduction in pain and decreasing of muscle spasm in limbs. Patients find that they can decrease or stop taking painkillers or other pain medications, they return to a more normal lifestyle and normal activities, aphysical therapy program recommended for them becomes more various.

Deep Brain Stimulation (DBS) is an established treatment in neurological diseases, e.g. Parkinson's disease or essential tremor (ET), while its underlying biological mechanisms are still have to be elucidated. DBS consists of delivering electrical pulses to a target in the brain through implanted electrodes.  It is believed that maximal therapeutic outcome is achieved when  the target  is completely stimulated while the stimulation beyond it is kept as small as possible, thus minimizing the risk of side effects. To facilitate this goal, recent developments in DBS leads enable asymmetrical stimulation with segmented contacts. The field produced by the lead can then be shaped more accurately, limiting the spill to adjacent areas.

Due to the limitations of in vivo studies, mathematical models aiming at a better understanding of DBS have been developed in the past years. In order to correctly predict the stimulation spread, the model has to take into consideration the patient-specific brain anatomy. In particular, white matter, grey matter, and cerebrospinal fluid possess different electrical properties. This can be taken into account by using Magnetic Resonance Imaging (MRI). Then, a Finite Element model individualized to the patient can be created. The stimulation field spread is optimized so that it completely covers a certain target that is manually segmented from MRI. In this case, the criterion for distinguishing between stimulated and non-stimulated domains is an electric field threshold of 200 V/m.

However, when individualizing the model, two uncertainties exist: the actual position of the lead and the reaction of the brain tissue to the implanted electrode.  The lead position is estimated from an image obtained by post-operative Computer Tomography. However, the estimate accuracy  is comparable to the size of the target, i.e. a few millimeters, and has to be accounted for in the stimuli optimization. Animal studies suggest that an encapsulation layer is formed around the lead after the surgery. In vivo impedance measurements in the human as well signalize this possibility.

The developed model has been applied to a clinical case of stimulating the caudal Zona Incerta in an ET patient with a segmented lead, see Fig. 1. The obtained stimuli optimization results agree well with symptoms observation.

The mathematical model of DBS is expected to be useful in e.g., shortening the programming time and/or reducing possible discomfort to the patient. In addition, potential gains of using alternative lead designs can be tested in silico in an inexpensive and prompt way.

Introduction:

Ultrasonic vocalizations (USV) are used by rats in a context and state dependent manner and can considered as an index of their psychological state as calls within specific frequency ranges are associated with distinct affective categories such as fear and anxiety (negative emotions, 20-30 kHz band), or playfulness and mating (positive emotions, 40-60 kHz band). The current study examined post-natal vocalization in the Flinders Sensitive Line (FSL) rodent model of depression, including the value of early vocalization in predicting subsequent behavioral deficits. Follow-up studies will investigate the behavioral and biological impact of Medial Forebrain Bundle High Frequency Stimulation in this model.  

Methods:

Flinders Sensitive Line (FSL) and age and gender matched Sprague-Dawley (SD) control rats derived from the breeding colony in the animal facility of the Freiburg University Medical Center were used. A total of 31 FSL and 39 SD pups were tested from 4 FSL and 3 SD dams, respectively. Behavioral assessment started on post-natal day 3 and continued until the age of 13 weeks. The pups were weaned at day 28 and perfused at age of 14 weeks.

Results:

Pre-weaning FSL pups (post-natal days 3-21) emitted significantly fewer calls compared to control rats. Following weaning (from week 4), FSL continued to vocalize less until week 8, and the reduced number of calls affected specifically the 40-60 kHz band. The young adult FSL rats also showed increased depressive-like behavior in the Forced Swim Test.

Conclusions:

FSL pups have depressive phenotype already during the first few weeks post-natally, as manifested by the overall reduced vocalization, and particularly in the positive affect spectrum. The pre-natal developmental/ biological factors and the environmental ones - such as reduced maternal attention during the post-natal period, need additional investigation. 

Introduction

The evidence regarding the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on language and cognitive abilities of individuals with Parkinson’s disease (PD) is contradictory. Moreover, the bulk of the evidence is based on English, a morphologically poor language. STN-DBS has recently been found to compromise the rule-based past tense formation in English.

Methods

Language tasks tapping rule-based past tense formation and comprehension of relative clauses and cognitive tasks tapping short-term memory, verbal working memory, set-shifting, and inhibition were administered to eight non-demented PD speakers of Greek, a morphologically rich language. Three participants were assessed before and after STN-DBS (Testing Type 1), and five participants with the stimulator on and off (Testing Type 2).

Results

No indication of deterioration in any of the language and cognitive abilities was detected after DBS or during stimulation. On the contrary, in Testing Type 1, one participant benefitted from STN-DBS in comprehending one type of structurally complex sentences and in inhibition, and another one benefitted in inhibition and set-shifting. In Testing Type 2, all tasks elicited similar performances across stimulation conditions both at the individual and group levels.

Conclusion

The results suggest that STN-DBS does not affect cognitive and language abilities of Greek-speaking PD individuals. (The sporadic benefits observed in Testing Type 1 can be considered a pre-surgery stress-related artifact.) Language-specific properties, such as morphological/inflectional richness, may determine the impact of STN-DBS on morphosyntactic processes. Rule-based past tense formation, for example, may not be affected in highly inflected languages.

Introduction:

Major Depressive Disorder (MDD) is a heterogeneous psychiatric disorder with broad symptomatic manifestations impacting on many facets of the sufferers’ life. Typically it is associated with anhedonia, loss of interest in most activities, feeling of despair, pervasive pessimism about the future, suicidal tendency, and anosmia. The current study examined state of olfactory memory and discrimination in the Flinders Sensitive Line rodent model of depression. Follow-up studies will investigate the behavioral and biological impact of Medial Forebrain Bundle High Frequency Stimulation in this model.  

Methods:

Male Flinders Sensitive Line (FSL) rats and Sprague-Dawley (SD) controls were trained on an Olfactory Discrimination test and a Social Interaction test to permit the evaluation of olfactory memory and discrimination, but also the drive to explore novel scents. 

Results:

On the Olfactory Discrimination test, the FSL and the control animals performed similarly at the shortest inter-trial interval (5 min) confirming that FSLs can learn and discriminated between known and novel odors. However, with extended delay of 30 min, the FSLs had a robust recall and odor discrimination deficit. At the longest delay (60 min) both groups performed equally poorly. The Social Interaction test further confirmed that the FSLs are less likely to explore and interact with an unfamiliar rodent.   

Conclusions:

The FSL rats, compared to the controls, showed a robust deficit in olfactory discrimination suggesting an impairment in olfactory memory and recall. FSL were also less likely to socialize with novel rats. Taken together, the data suggests that the FSL animals might have an impaired olfactory information processing capacity, or less motivated to explore novelty, both indicating potentially a dysfunctional limbic system.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has developed into a standard therapy for treating refractory stages of Parkinson’s disease (PD). DBS systems nowadays represent open loop technology. DBS is applied to the target area, without taking into account the motor state of the patient. Despite being a widely accepted approach, continuous and chronic DBS (cDBS) is suspected to cause side-effects such as speech impairment or tolerance to treatment, and has disadvantages with regard to energy efficiency and battery life [1, 2]. It would be desirable to have adaptive DBS (aDBS) systems, which provide stimulation on-demand only and which reduce or stop stimulation during sleep or other periods of inactivity. To realize the closed loop control of a patient’s motor symptoms by an aDBS approach, information about the motor state of the patient is required. Besides recordings of the actual motor output, such information may be provided by neural markers [1, 3, 4]. The power of LFP oscillatory components in the beta range (12-30 Hz) recorded from basal ganglia is considered the most informative neural marker. However, even lower frequent oscillations have been reported informative about dyskinetic symptoms [5]. As brain processes are highly non-stationary, the dynamics the neural markers and dynamic effects that DBS has on them should be considered [6] in the context of aDBS. In the present work, investigate dynamics of the theta power upon DBS.

Materials, Methods, and Results: Intraoperatively micro-electrode recordings (MER) were acquired as part of the implantation procedure for DBS of four PD patients (S1-S4). In each hemisphere, three electrodes were lowered into the target region STN simultaneously (anterior, central, lateral) over a Ben’s gun approach (FHC, USA). Stimulating on a singular macro-tip of the telescopic FHC electrode (FHC, USA) with increasing currents allowed to record signals with 5kHz sampling rate from two other MER positions (Leadpoint, Medtronic, USA). Starting with stimulation off, stimulation intensity was ramped up in steps of 0.2mA and 0.5 mA. Each intensity was delivered for 10 s at a rate of 130 Hz with interleaved pauses of 20 s duration to allow a washout of the DBS effects. During the ramp-up tests, patients were asked to neither move nor speak in order to avoid artifacts and spurious effects.

For S1, analysis of the left-hemisphere data had to be omitted due to acquisition issues. For the offline analysis of the remaining data, the first 15 s of the interleaved pauses (stimulation-off intervals within the ramp-up sequence) were extracted after bandpass filtering the data between 2 Hz and 8 Hz. Subsequently, the envelopes of the band-filtered signals were extracted by computing the real part of the Hilbert transformation of the data. Results are reported per subject and hemisphere. Within each hemisphere, the effects are average over all the stimulation-off intervals of a ramp-up sequence.

For at least five out of the seven analyzed data sets we observed a desynchronization within the first 5 seconds after stim off in at least one of the two recorded electrodes. Observed envelope effects are not necessarily comparable between hemispheres of a subject, probably because the exact location of the recording electrodes within the STN areas varies.

Conclusions: Beta-band oscillations are referred to as the most important neural marker for assessing effects of DBS in PD-patients. We have shown that other neural oscillations also react upon DBS, specifically theta-rhythms [2-8] Hz. Our data suggests, that the time dynamics should be considered if theta activity is exploited in aDBS approaches.

This work was (partly) supported by BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, grant number EXC 1086)

References:

[1] Carron, R., Chaillet, A., Anton, F., Pasillas-Lépine, W., & Hammond, C. (2013). Frontiers in systems neuroscience, 7(112), 1-18.

[2] Little, S., Pogosyan, A., Neal, S., Zavala, B., Zrinzo, L., Hariz, M., et al. (2013). Annals of neurology, 74(3), 449-457.

[3] Priori, A. (2015). Movement Disorders, 30(9), 1206-1212.

[4] Beudel, M., & Brown, P. (2016). Parkinsonism & related disorders, 22, S123-S126.

[5] Blumenfeld, Z., & Brontë-Stewart, H. (2015). Neuropsychology review, 25(4), 384-397.

[6] Borghini, G., Astolfi, L., Vecchiato, G., Mattia, D., & Babiloni, F. (2014). Neuroscience & Biobehavioral Reviews, 44, 58-75.

Introduction

Deep Brain Stimulation is an established treatment modality in various movement disorders. Targets are usually located within the basal ganglia. Due to the proximity of the target points to critical functional structures as the internal capsule, therapeutic yield might be limited by side effects. Furthermore energy consumption is potentially higher in conventional monopolar stimulation. Recently, segmented DBS leads have been made available. This technique comes with the promise of increased efficacy and side effect reduction. We therefore compared our preliminary data with segmented leads with the data from the Libra study conducted 4 years ago.

Methods:

The purpose of the Libra study was to evaluate the effects of a new Deep Brain Stimulation System for reducing symptoms of advanced, Parkinson’s disease Also the Activities of Daily Living, UPDRS scores, Quality of life of subject, device parameters including active contact in relation to efficacy, frequency, type and severity of therapy related AE’s events were evaluated. 3 months data from patients with segmented leads (Infinity) 6 patients  will be compared to the Libra data (6 patients).

Results

DBS Targeting was guided by three micro electrode recording tracts and a directional lead system (Infinity DBS, SJM) was implanted in an all-in-one GA setting in 6 patients. The segmented contacts were intensively tested at 90µs and 130 Hz in the postoperative course. Distinct effect/side-effect patterns for each contact were observed. Comparison of Parkinson’s symptoms as demonstrated by the UPDRS motor scores in the medication “off” state at Baseline compared to the medication “off” with stimulation “on” 3 months after device implantation. No differences in efficacy where seen between Libra and Infinity data amoing those 6 patients. However compared to the Libra data, no stimulation dependent side effects occurred in the Infinity group. Amplitude and frequency did not differ, however lower pulse width was used in 2 patients.

Conclusion

Segmented leads allowing current steering offer new perspectives for DBS and will likely result in increased treatment efficacy while reducing side effect at the same time. While this is true for DBS in general, there are cases with no good benefit/side-effect ratio could be achieved with conventional DBS. Since the threshold for side effects is higher in segmented leads, they are more adaptable to the individual patients needs and potentially resulting in a longer battery life.

Introduction

DBS has been etsablished for the treatment of movement disorders and many other diseases within the past 2 decades. One of the most popular target areas for DBS in Parkinson's disease (PD) is the area of the subthalamic nucleus. Whereas the overall effects of conventional DBS lead to significant improvement of the cardinal smyptoms of PD, there may be some limits, especially , if the electrodes are too close to some of the neigbouring structures, such as the internal capsule. The stimulation parameters sometimes may have to be reduced because of side effects in these cases, such like dysarthria, spasticity and similar ones.

Methods

Very recently, a new system had been relaesed for DBS in PD patients with the possibility to direct the current in certain directions, while suppressing others. This is beeing achieved by a segmentation of the electrodes. We report about our first, still limited experiences with this type of Deep Brain Stimulation device in 6 patients with PD. all patients underwent conventional preoperative testings according to the brain bank criteria and also the planning and targeting, as well as the intraoperative testing was performed in the conventional way; awake surgery with intraoperative microrecording and macrotesting. CT / MRI matching for the planning of the procedure.

Results

All patients were bilaterally implanted and had a significant success due to the DBS implantation. While intraoperatively sufficiently tested, 2/5 patients required adaptations of their stimulation parameters postoperativeley leading to capsular side effects with conventional stimulator settings.

In both patients, through the activation of the electrode segmentation, leading to directional steering of the stimulation current, allowed us to increase the stimulation current without capsular side effects. Both patients improved afterwards due to their PD symptoms. Videos with different stimulation parameters (with/out) directional current steering will be shown. 

Discussion

Directional current steering provides new and potentially helpful options for DBS treatments. However, the indications for this special kind of DBS may vary due to different indications and different target ares.

Objective:

Since a few years rechargeable pacemaker technology is available in deep brain stimulation. This technical innovation becomes more and more important in our clinical practise, particularly for patients with high amplitude and accordingly high wattage. But due to the requirements in handling the rechargeable device, this kind of pacemaker is not eligable for every patient.

Methods:

Over a period of ten years around 360 patients underwent deep brain stimulation for several indication in our department. Rechargeable pacemaker are often used for replacement after battery depletion or sometimes for first implantation. Within this time for two patients we had to change the rechargeable pacemaker against a non-rechargeable one before its actual expiration of term because of difficulties with the application.

Results:

First patient is 73 years old with Parkinson's disease, underwent bilateral deep brain stimulation in the internal globus pallidus in 2006. Pacemaker has been changed against non-rechargable ones because of battery depletion in 2008 and 2010. In 2012 it has been decided to implant a rechargeable device because of the comparatively more frequently need of pacemaker-replacments. At the request of the patient in 2014 the pacemakes has been changed against a non-rechargeable one again because of increasing problems with the handling of the recharger and inconvenience with the daily monitoring of the battery level.

Second patient is 62 years old and underwent bilateral deep brain stimulation in the Nucelus accumbens because of an addictive disorder in 2009. The pacemaker has been changed in 2013 against a rechargeable device. In 2015 the pacemaker needed to be replaced by a non-rechargeable on again. The patient had rising difficulties in coping with the recharging process.

Conclusions:

Rechargeable pacemaker are a step forward in providing medical treatment in standard of technical innovation. Many patients stand to benefit from rechargeable pacemakers, smaller devices and less operations. But with the new technology we have new requirements in the technical capabilities and compliance of our patients aswell. Some of them seem not to be up to it or to prefer the simpleness of a non-rechargeable pacemaker.

Tonic dopamine levels modulate the power of beta oscillations in the subthalamic nucleus. The physiological role of this relationship, however, remains unclear. Phasic changes in dopamine may be caused by rewards. Here, we investigated whether beta activity might therefore be related to reward processing. We recorded local field potentials (LFPs) from the subthalamic nuclei of 19 patients with Parkinson’s disease who performed a computer-based reinforcement-learning task. Afterwards, we correlated the magnitudes of patients’ obtained rewards with task-related power changes in their LFP oscillations. During reward presentation, beta activity was positively correlated with reward magnitudes. During responding, moreover, alpha and low beta activities were negatively correlated with previous reward magnitudes, while the likelihood of repeating the previous response correlated positively. Our results thereby suggest a role of beta activity in the processing of rewards, while alpha and low beta activity might be involved in reward-based response adaptation.

A 71-year-old male has been diagnosed with drug-resistant essential tremor (ET), in a familial context, with symptoms that started in childhood, at the age of 11. Tremor was predominant in the right upper limb, in a right-handed patient, provoking dramatic functional impairment.

Due to a relative contra-indication to DBS (anticoagulation treatment for pulmonary embolism), an initial Gamma Knife (GK) thalamotomy of the left ventro-intermediate nucleus (Vim) was performed. After progressive and dramatic clinical alleviation, which persisted up to two years, the tremor relapsed. Magnetic resonance imaging (MRI) showed the presence of a small contrast-enhancement (CE) surrounding a hypodense T1 necrotic core which, after co-registration with the dosimetry palnning in the Leksell GammaPlan, corresponded to the GK targeting. Additionally, the DWI data made possible the semi-automated segmentation of 7 clusters of thalamic nuclei, with the ventro-lateral ventral (VLV, nomenclature as from Morel et al.) cluster containing the contrast-enhancement area, as corresponding to the GKS target and in a ventral position, having anatomical relevance.

A deep-brain stimulation (DBS) procedure was decided after multidisciplinary discussion. Due to the fact that the patient had bilateral tremor, and DBS could offer bilateral implantation without additional risks, it has been decided to treat both sides. For the left previously treated by GK, we aimed at stimulating the vicinity of the preexisting lesion. On this side, intraoperative microrecording showed that the center of the CE visualized lesion on MRI was silent (with no cells) and was surrounded by an area of normally active neurons; however, there was a clear difference in terms of potentials of action between the left (with previous GK) and the right (with no previous GK), raising the question whether new or surviving cells were present on the left. Additional data while comparing left and right tracks showed that neuronal noise, single unit amplitude and frequency were significantly higher on the non-GK treated side, suggesting that the cells on the previously treated left GK side were surviving and not new ones, different than those on the right. The patient had immediate and complete clinical alleviation after DBS.

However, three days after the DBS procedure, he presented with dysarthria and left hemisyndrome. A CT scan and angio-CT showed right sylvian hypoperfusion, with right carotid artery thrombus. An MRI performed at 1.5T revealed an ischemia on the territory of the right anterior choroidal artery and progression of the carotid thrombus. The patient has been putted under anticoagulation treatment, with further disappearance of symptoms. Additionally, tremor on the left side remained suppressed after the stroke, with no need for stimulation on that specific side. Eighteen months latter, this important alleviation persisted bilaterally, by unilateral stimulation.

Electrophysiological findings suggest functional reorganization at the periphery of the necrotic core visualized on the follow-up MRI after GK. Consequently, this peripheral area containing neuronal activity is most probably the one responding to DBS, although the former is not identhical on both sides, but with a final identhical clinical efect. Deep-brain stimulation after GK thalamotomy, aiming at a target closed to the previous lesion is possible and can lead to tremor suppression with durable effect. The analysis of the electrophysiological findings in this unique case helps to better understand the functional neuronal reorganization after GK thalamotomy.

Objective: The globus pallidus internus (GPi) is regarded as an established and safe target for deep brain stimulation (DBS) in dystonia. Recent reports on the occurrence of bradykinetic symptoms like freezing, postural instability and micrographia after chronic DBS of the GPi in patients with dystonia however stimulated a discussion on alternative targets. Here, we report on the unusual occurrence of dyskinesias upon chronic pallidal stimulation.

Methods: A 74-year-old man with segmental dystonia including blepharospasm, orofacial dystonia and aerophagia underwent bilateral stereotactic implantation of DBS electrodes in the GPi. Eleven years later during effective chronic DBS for dystonia he experienced gradual onset of hyperkinetic involuntary movements mainly concerning his arms but also his trunk. 

Results: Detailed assessment in various conditions showed that off DBS resulted in an increase of both choreatic hyperkinesias and dystonia. High frequency and low amplitude DBS improved both dystonia and hyperkinesias, while high voltage DBS resulted in further improvement of dystonia but also in increased hyperkinesias. As a compromise between optimal stimulation for dystonia and hyperkinesias we finally choose a bipolar intermediate amplitude stimulation mode.

Conclusion: Chronic pallidal DBS might be accompanied not only by bradykinetic symptoms but also in the rare case by hyperkinesias. Such an occurrence requires complex reassessment of stimulation programming.

Objective: Deep brain stimulation (DBS) has been shown to be efficacious in the treatment of primary dystonia. There is less experience in secondary dystonia. Since patients with secondary dystonia, who are often more disabled, may be more vulnerable to postoperative complications we aimed to investigate the 30-day morbidity in a large cohort of patients with secondary dystonia operated over a period of 19 years.

Methods: From 1997 until 2016, a total of 49 patients (27 women and 22 men; mean age 43,5 years (range 13-77)) with secondary dystonia underwent DBS with electrodes implanted either in the Thalamus or the posteroventral lateral globus pallidus internus (GPi). Most frequent cause of for dystonia was cerebral palsy in 17 patients.

Results: There were no intraoperative or directly postoperative complications related to surgery. The electrode location was corrected in 2 instances. Two patients developed a wound infection, one patient had subdural hematoma and subcutaneous collection of cerebrospinal fluid (CSF). Three weeks after DBS a subdural hematoma and CSF resolved.

Conclusion: The 30-day morbidity rate in DBS for secondary dystonia is comparable to that in primary dystonia. 

Objective: Pallidal deep brain stimulation (DBS) has been established as a treatment option in patients with medically refractory dystonia. Mohr-Tranebjaerg syndrome (MTS) or Dystonia-Deafness-Syndrome is a rare genetic disorder characterized by deafness, dystonia and neurological abnormalities like impaired vision, dementia and cortical blindness. So far little is known about the efficacy of DBS in MTS.

Methods: A 44-year- old man with a history of generalized dystonia, deafness, visual blindness, ataxia and tremor was diagnosed with MTS which was confirmed by genetic analysis. He underwent bilateral stereotactic implantation of DBS electrodes in the posteroventral lateral globus pallidus internus (GPi). Electrode location was confirmed by postoperative stereotactic CT.

Results: Bilateral pallidal stimulation yielded modest improvement of dystonia at 6-months follow-up. During the next four months there was an increase of tremor and ataxia. The initial benefit was lost within the next two years. Extensive reprogramming did not yield additional improvement. After three years of chronic stimulation it was decided to switch off the pacemaker because of loss of efficacy.

INTRODUCTION

Holmes' tremor (HT) combines resting, postural and action tremor. The two treatment options are pharmacotherapy and deep brain stimulation (DBS). Pharmacotherapy is usually insufficient. The best surgical target is the ventral intermediate thalamic nucleus (VIM). In the absence of a satisfactory response or if the effects of stimulation diminish with time, alternative targets exist. We report on a young patient with HT who underwent unilateral VIM and globus pallidum internus (GPI) stimulation.

CASE REPORT

In 2012, a 26 years old male patient known for a midbrain arteriovenous malformation (AVM) was diagnosed with HT. The AVM had been treated by embolization and radiosurgery in 2001. A second haemorrhage in 2009 resulted in left hemiparesis including the lower face, left internuclear ophtalmoplegia, and dysarthria. HT thus developed three years later, beginning in the left arm, and progressed to the rest of the left side of the body except the head. Brain magnetic resonance imaging (MRI) in 2012 showed traces of the haematoma located strictly on the right side in the mesencephalon including the area containing the central tegmental tract, as well as the lower thalamus, and bilateral hypertrophic olivary degeneration in the medulla oblangata. After failure of pharmacotherapy, the patient underwent DBS of the right VIM. The initial significant improvement of HT worsened after three months of stability, despite multiple stimulation adjustments. Nine months after the initial implantation, we added DBS of the right GPI which re-established therapeutic efficiency without side effects. This effect was stable at last follow-up (30 months), and the patient was neurologically autonomous.

CONCLUSION

VIM stimulation alone is an affective treatment to decrease various types of tremor. The complex physiopathology of HT, however, certainly involves dysfunction of at least two different systems: the dopaminergic nigrostriatal and cerebellothalamic pathways. Simultaneous stimulation of VIM and GPI for HT has previously been reported as successful; results of additional stimulation of the ventralis oralis anterior nucleus (VOA) are mixed. The present case confirms that targeting of two areas of the brain may be necessary: VIM stimulation proved insufficient but subsequent GPI stimulation resulted in significant lonf term improvement of HT. 

The efficacy of DBS in basal ganglia depends upon the effective stimulation of target nuclei: moreover, it results from a careful anatomical reperage, a sure intraoperative neurophysiology and a conscientious postoperative reglage. Light errors in surgical positioning, individual anatomy and variables in local electrical fields may decrease the efficacy of DBS. Tayloring the electric field may overcome some of these constrains. Recently, the main Companies involved in DBS technology developed directional leads, able to configure anisotropical electric fields, as to cover variable tissue volumes, according to clinical evidence.

The aim of this investigation is to verify the efficacy of directional leads in patients undergoing DBS for movement disorders.

10 patients (6M-4F, mean age 52 – mean disease duration 9 yrs) suffering from movement disorders (8 PD, 1 Generalized dystonia, 1 cerebellar tremor), underwent DBS (7 Stn, 2 Gpi, 1 RaPl)  with stereotactic approach, obtained after anatomical reperage in volumetric Mri - normalized upon S&W atlas - with the aid of intraoperative MERs; three exploring traces were performed in mean on each side and the stimulating directional leads were positioned  after confirmation from semi-microstimulation along the best trace. Intraoperative evidence of the correct electrodes' positioning and orientation was obtained by means of plain fluoroscopy.  Pre and postoperative clinical evaluation followed validated scores (UPDRS – BFMDRS - TRS). Mean FU is 6 months: for each patient were considered: clinical outcome,  stimulus parameters, electrode configurations and orientation and possible adverse events.

9 patients are actually on FU; 1 drop out for infection of the IPG. Active leads are 17 as a whole; 15 leads in directional configuration and 2 in “ring” configuration; in all the cases DBS is performed with monopolar stimulation; current is delivered through two directional contacts, with total current splitted respectively 25% and 75%, PW 60 microsec, Fr 130 Hz; mean delivered current is 2.3 mA, mean voltage is 2.2 V. The final configurations resulted after many sessions of reglage, during which the activation of the directional contacts obtained better clinical results than the activation in "ring" mode. Last FU reported decrease of UPDRS III 50%, UPDRS II 70%, BFMDRS 60%, TRS 85%. Mean LEDD decrease was 50%. No collateral effects were recorded.

In conclusion, directional leads allowed us to obtain taylored electric fields in 15 sides out of 17, suggesting clinical effects more consistent than in “ring” mode. No significant collateral effects were observed. Moreover, larger cohort of patients and longer FU are necessary to confirm these preliminary data.

Deep brain stimulation (DBS) is now widely used in the treatment of Parkinson's disease, tremor, and dystonia. In Parkinson's disease, recent work has demonstrated that early DBS may have a significant benefit on quality of life and motor symptoms while permitting a decrease in levodopa equivalent dosage. DBS is usually preferred in Parkinsonian patients who initially benefit from dopaminergic treatment and lose its effectiveness during disease progress. In this study, we retrospectively evaluated DBS side effects in patients with Parkinson disease.
62 Idiopathic Parkinson patients treated with DBS and followed during 2008-2014 were involved in our study. Four Condition Test was used in the in the assessment of treatment response, stimulus related side effects and the effect of DBS on symptoms during off medication / on DBS ,on medication / on DBS, off medication / off DBS, on medication / off DBS. During follow-up, therapeutic and electrode impedance was controlled and parameters effective in symptom control and side effects were noted. When no pathology was detected, reimaging with cranial MR and CT was performed to define if there was a pathology on the localization of DBS target.
30 patients were women and 32 of them were men. Subthalamic nucleus was the target in 49 patients, globus pallidus internus was in 11 and ventrointermedial nucleus of thalamus was the target of DBS in 2 patients. Complications related to surgery, instrumentation and stimulation were defined.
With the results of our study, we want to share common complications of DBS during Parkinsonian patients follow-up. Clinicians should take care of these complications for the benefit of patients.

INTRODUCTION: Robotic systems have been introduced in stereotactic neurosurgery to meliorate the accuracy in performing surgery, to reduce the operative risk and to improve the diagnostic yield. The project RONNA (Robotic Neuronavigation) includes research and development of innovative and competitive robotic system for use in neurosurgery through the cooperation of public university and the business sector.

PATIENTS AND METHODS: I.J. (60 y) was admitted to the University Hospital Dubrava due to sudden onset of confusion and weakness of the left limbs. Within neuroradiological imaging we performed contrast enhanced brain MSCT, which showed central necrotic expansive lesion with ring enhancement, surrounding edema, located in the right frontal lobe. The first robot-guided stereotactic biopsy in Croatia was done on the 10 th of March  2016 . In local anesthesia using RONNA and commercial neuronavigation system, which served as a confirmation,  location of biopsy was defined. We took 4 samples for pathohistological analysis and evacuated 45 ml of liquid cystic content.

RESULTS: There were no operative and postoperative complications. After surgery patient was transferred to the Department, without neurological deficits. Postoperative CT and MRI reveiled no signs of acute bleeding or ischemia and confirmed that samples were taken from the planned sites. The definitive pathohistological finding confirmed diagnosis of glioblastoma.

CONCLUSION: In our humble experience robot significantly increases the accuracy and helps the surgeon by giving him additional conformation ,all of which increases patients safety. We hope that  further clinical use will reduce duration of the surgery and expand the use of robots in neurosurgery.

Introduction:

Percutaneous cannulation of the foramen ovale to reach the gasserian ganglion has been extensively discussed, starting with Hartel`s free hand approach to intraoperative imaging (i.e. by CT or fluoroscopy), stereotaxy and neuronavigation techniques. In this abstract, we will describe a technical note to approach the foramen ovale by real time fluoroscopy using Hartel`s entry point to achieve maximal accuracy and efficient radiofrequency lesioning of the Trigeminal ganglion.

Methods:

The patient lies supine on a fluoroscopic table with interscapular pad, and moderate head rotation towards the contralateral side of the target thus minimizing the C-arm rotation in both caudo-cranial and lateral direction. This also facilitates the surgeon`s position near the head of the patient during the procedure. (Fig.1a) The Hartel`s entry point is then marked with a needle tip. A submental view of the skull is then obtained. The foramen ovale is easily identified by its location at the anterior border of the petrous bone 1-2cm lateral to its apex. Then locate the foramen medial to the mandibular ramus and lateral to the maxillary air sinus (Fig.2). You need to align the foramen with the metal pointer so you can cannulate the foramen in tunnel view. The needle is then directed towards the superomedial wall of the foramen. (Fig1b) Lateral view is then obtained by aligning both auditory meatus together. Then the cannula is slowly advanced to the target trigeminal division. Then, we obtain AP view matching the petrous upper border with the middle of orbital cavity to visualize the trigeminal impression and the relation of the needle to it. Confirm needle location functionally by measuring impedance (usually from 200-400ohm) and do sensory and motor stimulation at 50Hz and 2Hz successively. Finally, do conventional lesioning at 65-70 degree for 60 seconds for 3 cycles and assess pinprick sensation after each cycle to confirm adequate lesioning.

Results:

We performed 29 cases from 2013 to 2015 with follow up period ranged from 6 months to 3 years, 27 showed over 75% reduction in VAS score and were classified as excellent response, 4 patient had undergone V1 lesioning, 2 patients of them developed corneal anesthesia with no evidence of keratitis at 1 year follow up. 3 patients had residual area of pain which were managed by repeating the procedure within one week to achieve complete coverage. 2 patients developed motor weakness in mastication, which improved within 6 months, the mean cannulation time was 11.9 min ±6.5, mean threshold painful stimulation was 0.39 V ±0.23, and mean impedance was 288 Ohm ±47.

Conclusions:

Real time fluoroscopy using Hartel`s entry point provides safe and accurate method to locate and approach the trigeminal ganglion in a relatively short time.

Introduction

Trigeminal neuralgia (TN) is reportedly one of the most excruciating orofacial pain syndromes. In most cases, the cause is idiopathic.  The goal of microvascular decompression (MVD) is to decompress the trigeminal root from offending vessels, aiming at a permanent cure with no or little sensory deficit.

Methods

102 patients submitted to MVD to treat trigeminal were selected, retrospectively, from the data of the Neurosurgery department in Centro Hospitalar e Universitário de Coimbra.

A telephone questionnaire was performed to inquire patients about their experiences after surgery.

Outcome was evaluated by the Barrow Neurological Institute scale.

SPSS was used for statistical treatment and statistical significance was considered as a p-value <0.05.

Results

A total of 102 patients were enrolled, with a mean age of 61,68 at time of surgery. 55,9% were women, and 44,1% were men.

95% of the cases had a typical presentation, with a right side involvement in 60,8%.

V2-V3 was the pain territory most often encountered, representing 33,3% of the cases, followed by V1-V2 territory (24,5%) and V2 (19,6%).

89,7% had some kind of vascular compression, confirmed at surgery, 69,1% of which was of arterial nature. 

AICA was the most frequently involved artery, in 53% of the cases.

Gore Tex was the more often used prosthesis, in 79%, followed by Teflon in 18%, Dacron in 2% and Silastic in 1%.

There was a 17,7% complication rate, with hipostesia of one of the V pair branches being the most frequent one (47,6%).

Symptomatic relief was achieved in 91%, with total pain relief in 67%.  Only 4% continued with uncontrolled pain after surgery. 27% had recurrence of symptoms. 

There was a significant statistical difference (p=0.005, Pearson Qui-Square) in the outcome between the different kind of vessels involved. In fact, severe uncontrollable pain was associated with compression by the ACS artery and better results were noticed in cases with compression by the AICA artery.

The type of prosthetic material used, influenced the clinical recurrence (p =0.016, Pearson Qui-Square), and patients with Gore-Tex prosthetics had a larger recurrence rate. There was also a significant statistical difference between the type of prosthetics and the complication rate (p= 0.022, Pearson Qui-Square), Gore Tex being implicated in more cases of complications.

The territory of involvement had influence in the kind of complication associated (p-value 0.032, Pearson- Qui Square).

Conclusion

MVD is a safe and effective procedure to relieve typical TN and our series demonstrated good surgical results, similar to other series in the literature.

Preoperative identification of neurovascular compression, surgical planning and choice of prosthetic material have important implications in the clinical outcome.

Authors:

Samih Hassan MBBS MRCS 1, Susie Lagrata 2,  Sarah Miller 2, Manjit Matharu PhD FRCP* 2, Ludvic Zrinzo MD PhD FRCS (Neuro.Surg)* 1,3

* Both senior authors have contributed equally to the paper

Affiliations:

1-    Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK

2-    Headache Group, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK 

3-    Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK

Key words :

Neuromodulation, microvascular decompression (MVD),  short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).

Objectives: To assess the relative effectiveness of neuromodulation and trigeminal microvascular decompression (MVD) in patients with medically intractable short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).

Methods: We present two patients with medically refractory SUNCT who underwent MVD following beneficial but incomplete response to neuromodulation. One of them had occipital nerve stimulator and the other had deep brain stimulator.  Brain MRI was performed and confirmed neurovascular conflict with the ipsilateral trigeminal nerve in both patients.

Result: Although neuromodulation provided significant benefit in both patients, it did not deliver complete relief from pain and management required numerous postoperative visits with adjustment of medication and stimulation parameters. Conversely, MVD was successful in eliminating symptoms of SUNCT in both patients with no need for further medical treatment or neuromodulation.

Conclusion: Surgical treatment of medically intractable SUNCT is challenging because of the severity and rarity of the condition combined with the paucity of reports in the literature. Over the last decade, peripheral and central neuromodulation as well as trigeminal microvascular decompression have emerged as efficacious treatments. The aim of this report is to highlight that microvascular decompression may be preferable to neuromodulation in the subset of SUNCT patients with ipsilateral neurovascular conflict. Neuromodulation should probably be reserved for those patients without conflict or for those who fail to respond to MVD.

Background

The efficacy of epidural spinal cord stimulation on chronic neuropathic pain due to failed back surgery syndrome or nerve root lesions is well reported. There is even literature reporting the effects of spinal cord stimulation in controlling peripheral vascular lesions as in peripheral arteriopathies or diabetic neuropathies and in Complex Regional Pain Syndrome type II. This is probably due to an effect of epidural spinal cord stimulation mainly on the parasympathetic nervous system.

Case Description

A 14 years old boy affected, since birth, by a quickly growing widespread lymphangioma at the pelvis and right thigh, was submitted to repetitive surgical procedures to try to reduce its extension. Recurrence always occurred. Due to a massive swelling of his right lower limb and a wide painful area all over the pelvis and right lower limb, the patient lately lost his autonomy being almost bedridden or wheelchaired. On January 2015 the patient was submitted to the implant of a low dorsal epidural eight leads MR compatible electrode connected to an MR compatible stimulator. The patient, one month after the implant, completely recovered his autonomy with a marked shrinkage of his right lower limb and nearly disappearance of pain. He returned to a normal daily activity. A hip-MR showed partial reduction of the lesion, one year later. The patient is still nearly free from pain.

Conclusion

This is the first case report of severe chronic pain syndrome due to a widespread lymphangioma successfully treated by means of epidural spinal cord stimulation.

Background/Aims

Sphenopalatine ganglion stimulation has been proposed as a novel approach to treat chronic cluster headache. To achieve a therapeutic effect, the surgical lead placement in the pterygopalatine fossa is a crucial step. The present study analyses the role of both neuronavigation and the 3D O-arm® platform in improving the precision of the sphenopalatine ganglion microstimulator implantation.

Methods

Two patients with refractory chronic cluster headache underwent sphenopalatine ganglion microstimulation. Based on a preoperative 3D CT-scan, a neuronavigation system was used to plan the trajectory towards the pterygopalatine fossa. Intraoperatively the microstimulator was implanted using neuronavigation and anatomical landmarks from 2D acquisitions. At the end of surgery a 3D O-arm® data set was acquired to localize the implanted device and to confirm an optimal final position in the pterygopalatine fossa. The O-arm® data set was then analyzed and compared with a postoperative CT image series.  

Results

Neuronavigation helped in performing the dissection towards the pterygopalatine fossa, however was not accurate for the implantation of the device. The O-arm® was found to be a precise and reliable control tool providing the same information with respect to the device localization as the CT-scan images obtained postoperatively.

Conclusion

Neuronavigation has a limited role during the positioning of sphenopalatine ganglion microstimulator but remains useful in the surgical approach to the pterygopalatine fossa. Newer surgical instruments that can be used in correlation with the neuronavigation system should be developed. O-arm® could advantageously replace the postoperative CT to accurately check the position of the microstimulator, without an increase in surgical duration. We hypothesize that the intraoperative use of the O-Arm® could avoid potential second look surgeries for device misplacement.

Introduction: Trigeminal neuralgia and neuropathy are characterized by pain in the face, originating from the trigeminal nerve. The trigeminal neuralgia has a paroxysmal profile and the neuropathy a permanent burning sensation.

The thermocoagulation of the Ganglion Gasseri was the first effective minimal invasive functional neurosurgery therapy in the treatment of trigeminal neuralgia. On the other side the trigeminal neuropathy has always been very difficult to treat with most of the patients having serious problems controlling the symptoms despite elaborate medication. Over the last 8 years the evolution of stimulation protocols (Burst, HD, Whisper, 10K) as well as the development of new products (IPGs and electrodes) has revolutionized our treatment options especially in the treatment of trigeminal neuropathy.

In our department we are using the complete portfolio of functional neurosurgery to treat these two conditions for more than 35 years now.

Materials and Methods: The aim aof the study is to retrospectively analyse the patients with trigeminal neuralgia and neuropathy we treated from 2007 to 2015 using the complette portfolio of functional neurosurgery.

Results:

From 2007 to 2015 we treated 262 patients with trigeminal neuralgia for a sum of 424 Thermocoagulations of the Ganglion Gasseri. 57% were women and 43% men.

In the same period we also treated forty-six patients with a neuropathic facial pain.

The retrospective analysis of the patients with neuralgia showed that:

• Women with MS had an adequate pain relief for 22 months, men for 16 months.

• Women and men with recurrent idiopathic neuralgia 16 months

• Women with microvascular compression with MVD 41 months, men 46 months.

• MS patients had a recurrence rate of 48.8%

• Patients with microvascular compression of the trigeminal nerve had an overall recurrence rate of 32%.

• Patients with idiopathic neuralgia had a recurrence rate of 24,4%.

  The complication rate was under 1.5%, with neuropathy being the main postoperative complication.

   

  The patients with V2 and V3 neuropathy were treated with a PNS System in the Ganglion Gasseri itself. The patients with the V1 and V2 neuropathy were treated with a PNFS System in area of the pain itself. All patients were stimulated with various protocols (Tonic, HD/ Whisper, Burst). Both groups of patients showed a reduction of the VAS Score of more than 50%. Both groups achieved a reduction of the pain medication of more than 30%.

  Conclusion and discussion:

  Trigeminal neuralgia and neuropathy are two sides of the same coin when it comes to treating them. The evolution of neuromodulation products and stimulation protocols add an extra arsenal in the existing options with the ability to adapt the treatment to the patient and achieve definitive control over the symptoms. In conclusion functional neurosurgery, in its full spectrum and portfolio, offers all around treatments with safe, efficient, minimal invasive and long lasting effects.

Introduction: More than 100 cases for hiccup have been described in literature. In case of intractable hiccup the surgery can improve this disorder. The complete denervation of phrenic nerve seemed to be highly risky so the neuromodulative techniques appear to be justified. We reviev the Literature about Vagal Nerve Stimulation (VNS) in hiccup and add a case report.

Material and Methods: The Literature search found three cases of VNS performed for intractable hiccup. We report a further case of a 68-year-old male presented with continuous, intractable hiccup. His disorder had developed after a partial stomach resection for gastric ulcer performed in 2005 and is characterized by 60 hiccups/minute all day along. After chronic VNS stimulation the hiccup decreased of 50% and the patient improved the sleep. At last follow-up (3 months ago) the benefit is unchanged.

Results: The VNS output current was 2- 2.5 Mamph OFF 5' ON 30''. At present only four cases of VNS in intractable hiccup has been reported with complete benefit in two patients and partial benefit in other two at follow-up

Conclusions: The VNS on persistent hiccup has been reported in few cases after drugs failure administration and no long term benefit from phrenic nerve block. This technique should be standardized in the treatment of intractable hiccups and an uniform score evaluation of the results should be introduced.

Aims. Angina pectoris (AP) and peripheral vascular disease (PVD) is a chronic pain conditions caused by coronary and peripheral artery diseases, which can’t be relieved by the vascular surgery treatment. Spinal cord stimulation (SCS) is a neuromodulation therapy that appears to be an effective and safe treatment for these patients.

Methods. We had applied SCS in 14 patients with AP and 36 patients with PVD (n=50). The leads were inserted in the epidural space at the Th₁-Th₂ (for AP) and Th₁₂-L₁ (for PVD) levels. Myocardium perfusion scintigraphy (MPS) in AP patients and transcutaneous oximetry (TCO) in PVD patients were performed on admission, on the 7^th day and in 1 year after procedure. The visual analogue scale (VAS) was used to assess the degree of pain both in rest and physical activity in all patients.

Results. The patients showed 8,21±0,89 marks according VAS before the procedure and pain relief to 1,78±0,98 marks (p<0,01) after 1 year of procedure in group of AP patients. In group of PVD patients pain impairment was from 9,43±1,25 to 1,03±0,1 marks according VAS. All the patients demonstrated the rise of tolerance to the physical activity. MPS detected the increase in coronary reserve from 9 to 3 prearranged units, TCO showed oxygen saturation’s increase from 7 to 70 mm Hg on the shin. There were no any procedural complications.

Conclusions. According to recommendations of Neuromodulation Appropriateness Consensus Committee (NACC) SCS can be recommended as evidence level 2a, degree of recommendation A, for the patients with refractory angina pectoris. And in case of peripheral vascular disease the NACC recommends SCS be utilized  prior to the irreversible approach of sympathectomy. Our experience confirmes that SCS is a minimally invasive technique to reduce the pain and improve quality of life with vascular reserve enhancement in AP and PVD patients.

Cluster headache (CH)  is the commonest of the trigeminal automonic cephalalgias (TAC), it occurs up to 56-400 cases/100.000 habitants and is characterized for repeated attacks of severe, unilateral pain in the orbital, supraorbital or temporal region, lasting  15-180  minutes and occurring from once every other day to 8 times/day. It is associated  with one or more autonomic symptoms: conjunctival injection and/or lacrimation, nasal congestion or rhinorrea, eyelid edema, forehead and facial sweating, miosis and/or ptosis, sense of restlessness and agitation .  The male/female ratio is reported as 2.5:1. The age of the onset is more frecuently between 32-38 years.  The  exact cause and pathofhysiology remain unknown, however some neuropeptides in trigeminal innervation have been related (CGRP, substance P and vasoactive intestinal peptide). The attacks are often produced at night time and follow episodic and circadian patterns.

The episodic form of CH affects 85% of cases and up to 10% are affected by the chronic form wich consists on attacks that occur for more than 1 year whithout remission or with remissions lasting less than a month. Only 4% of patients affected by the  chronic form of CH are refractary to medical management and therefore suitable for  surgical treatment.

The different surgical options include ablative therapies on sphenopalatine ganglion, ablative therapies on V cranial nerve, DBS of the posterior hypothalamus, neuromodulation of occipital nerve, microvascular decompression of sphenopalatine ganglion and microvascular decompression of V cranial nerve, all of them with variable and controversial results.

The microvascular decompression of trigeminal nerve is a non ablative therapie, wich avoids many secondary effects and has been described as an effective  surgical treatment. Lovely et al. reported good results with treatment of chronic CH through microvascular decompression of trigeminal nerve, alone or in combination with section and/or microvascular decompression of the intermediate nerve in 28 patients, including 2 with bilateral disease. However, although 22 of 30 procedures (77.3%) resulted in an excellent or good outcome in the immediate postoperative period, the success rate dropped to 46.6% with long-term follow up. Rowed et al, Solomon and Apfelbaum, Morgenlander and Wilkins reported similar results.  

We describe the experience in our center with 2 cases of microvascular decompression of V cranial nerve  for chronic, refractary cluster headache.

Introduction:

   Analgesics was used to control various pain syndrome for many years. The efficacy of pain control with new innovated pharmacotherapeutics is getting better gradually. However, for ischemic pain, the acceptable outcome of painkillers is not so impressive to free from symptoms. Ischemic pain is not only the unpleasant feeling, but it will progress to tissue damage on involved limb. As early stage of ischemic limb, patients ,usually, presented simply painful without skin lesion or vascular occlusion in imaging study. These symptoms will be confused to differentiate pain origin between lumbar root impingement and insufficient microcirculation on involved limb.

Method and Material:

In past 10 years, 420 cases failed back surgery syndrome were surveyed with plain dynamic X-ray, MRI and electrophysiologic studies to verify pain origin. One hundred and thirty-four cases( 32%) were no nerve impingement or instability on spine even presented significant lower limb pain . In these cases, painful area focuses on lower limb rather than on lumbar spine . Neither skin lesion nor vascular compromising was found on involved limb.

Stress myocardial Thallium-201 scintigraphy were instructed with supine position after an exercise SPECT imaging. The result showed an insufficient microcirculation of muscle at involved limb. The average pain score VAS is 7.11.

Of 134 cases, 62 patients received spinal cord stimulation(SCS) treatment. Stimulator ( Medtronic co.)were implanted at epidural space around T10-T11. Other patients prescribed with analgesics, physical therapy or hyperbaric oxygenation due to economic reason.  

Result:

   All cases were evaluated on OPD follow-up regularly. After 12 months of treatment, VAS in the group of SCS treatment improved with 7.27 vs 3.43, compared to the other group with 7.18 vs 6.84. The walking distance increased by an average 3.7-fold in SCS group. Fontaine stage and sleeping quality also had significant improvement.

Conclusion:

    Spinal cord stimulation was used to treat the intractable pain for many years. The majority of candidates were emphasized on neuropathic pain. In recent decays, many analgesics were developed for pain reduction instead of spinal cord stimulation. Nevertheless, the effect of pain control of ischemic limb is still limited. For those patients with atypical neuropathic pain, muscle perfusion scanning might be a possible way to find out the early stage of PAOD. Using the spinal cord stimulation to treat ischemic limb is not only pain disruption but also refill the micro-circulation in hypoperfused tissue. 

Introduction

DRG stimulation is a modern and effective neuromodulative method of treatment of chronic neuropathic pain with dermatomal distribution. The Freedom Stimulator is the smallest implanted stimulator system. Freedom stimulator (Stimwave, CA, USA) is implanted through a needle.

Aim of the study was to assess the efficacy and usefulness of this system in our department.

Material.

We evaluated the effects and sustainability of the analgesic effects of this type of stimulation in 3 patients with chronic neuropathic pain of foot in two cases  and in thigh in one case. Diagnoses were following: CRPS t.II in foot pain caused by cauda equine injury, idiopathic neuropathic peripheral pain located in foot and FBSS with distribution in right thigh.

Methods

In two patients electrode and stimulator leads were implanted into the intervertebral foramen of L5/S1 in two cases and L3/L4 in one case. Stimulator were charged with the use of the wearable antenna externally worn by patients

Results

In 3 patients after one month of stimulation we observed significant reduction of pain assessed in VAS score:  90% reduction of intensity of idiopathic neuropathic pain, 60% reduction of CRPS t.2 and 70% reduction in FBSS .

Conclusions

Stimulating system seems to be effective, minimally invasive and convenient for patients. 

Background and objectives. Chronic electrical motor cortex stimulation (MCS) is the youngest among the neuromodulation methods for the treatment of chronic neurogenic pain syndromes. Currently, the most common indications for MCS are central post-stroke pain, atypical facial pain, phantom pain. There are some contraindications: the lack of effect of rhythmic transcranial magnetic stimulation (rTMS), clinically significant mental disorders, cognitive disorders disallowing the patient to learn the skills of treatment with the stimulation system, severe somatic diseases. Despite relatively well-defined indications and patient selection criteria adequate analgesia in long-term follow-up cannot be achieved, even in the absence of technical and iatrogenic complications. In this regard, the question about the predictors of MCS efficacy is not still closed. Our study is aimed to evaluate potential psychological prognostic for MCS efficacy for the treatment of neurogenic pain.

Materials and methods.  The study includes patients with chronic neurogenic pain syndromes, long taking medication with lack of efficacy, having indications for MCS implantation. To date, we have retrospectively included and analyzed 11 patients (6 men and 5 women), who was treated in N.N. Burdenko Neurosurgery Institute between 2005 and 2010. The approximate age of the patients was 53.y.o. Two patients (1 male and 1 female) suffer from right-side trigeminal neuralgia, occurred due to multiple sclerosis. In two male patients there is a phantom pain of post-traumatic genesis. Two male and one female patients suffer from post-stroke central pain syndrome in one half of the body. In 3 patients (1 male and two female) have a complex regional pain syndrome, occurred after the injury of the right brachial plexus. One patient developed pain in his left hand after the removal of intradural extra medullary tumors of the spinal cord at the cervical level, subsequent DREZ-lesion was not effective. Before surgery all the patients had been neurologically examined and tested with following scales: 36-Item Short Form Survey (SF-36), Spielberger’s personal and situational anxiety, Beck’s depression questionnaire, The Pain Catastrophizing Scale and Chronic Pain Coping Inventory (CPCI). All patients have been being examined in 1-year or more follow-up after MCS implantation and then divided into 2 groups of treatment efficacy. The effectiveness criterion was 30% and more pain relief according to the visual analog scale (VAS).

Results. Pain relief due to MCS was more than 30% in 7 patients. In 4 patients pain relief was below 30%. The main quality of life parameters, namely General Health (GH), Vitality (VT), Social Functioning (SF) and Mental Health (MH) was higher in the group of high MCS efficiency, while Role-Emotional parameter was higher in low MCS efficiency group. There were no differences in other quality of life parameters between the groups. Levels of depression and reactive anxiety did not differ between the groups. Personal anxiety was higher in the group of low MCS efficiency. Expression of wellness-focused coping strategies (Coping Self-Statements, Task Persistence) and the strategy of Seeking Social Support was higher in the group of high effective MSC as compared with group of low effective MCS. Pain catastrophizing levels was higher in the group of high effective MSC.

Discussion. We can suggest, that personality and psychological characteristics of patients (such as chronic pain coping strategies, personal anxiety, pain catastrophizing) may influence on the efficacy of MCS for the treatment of chronic neurogenic pain syndromes. Furthermore, MCS can be assumed to affect the basic quality of life parameters. Further follow-up observation and further studies are necessary to determine predictors of MCS efficacy.

Introduction
Tourette Syndrome (TS) is thought to result from malfunctions in the cortico-basal ganglia (CBG) pathway. The striatum controls the output of the basal ganglia (BG) through two pathways: the direct pathway to the globus pallidus internus (GPi) and the indirect pathway to the GPi through the globus pallidus externus (GPe). Functional and animal models of the BG provide two models with potential mechanisms for hyper-behavioral disorders like TS. First, hyperkinetic symptoms may originate from abnormal focal activation of striatal neurons which inhibit the activity of a sub-population of GPi neurons, leading to a phasic disinhibition of their targets. Second, striatal disinhibition may lead to reduced tonic inhibition exerted by the GPi on its thalamo-cortical targets. Both theories suggest that this leads to a transient action expression, such as a tic. The emergence of deep brain stimulation (DBS) targeting the GPi in TS provides an opportunity to directly observe the neuronal activity in the BG.

Methods
We analyzed the neuronal activity in both the GPe and the GPi of seven awake TS patients (TSP) who underwent physiologic mapping for placement of bilateral DBS electrodes in the anterior GPi. Up to 5 microelectrodes were used to record the neuronal activity along the trajectory. Recording took place from 10 mm above target to 4 mm beneath target in 0.5–1.0 mm steps. Moreover, we evaluated possible similarities and differences with the neuronal activity recorded from the Non-Human Primate (NHP). We observed normal Non-Human Primates (NP) and the motor tic NHPs model (TMP) after implanting 2 chambers stereotaxically to allow bilateral access to the motor cortex and the BG. The tic model was observed following microinjections of GABA_A antagonist (bicuculline) into the motor region of the striatum. The animal's behavior was continuously monitored by video cameras and EMG recordings and multiple microelectrodes were used to simultaneously record neuronal activity from the GPe and GPi.

Results
A total of 199 single neurons were recorded from seven awake TSP and they were identified as GPe (n = 64) or GPi (n = 135) neurons based on their location and trajectory history, including border cells and reduced background activity. The mean firing rates were 48.25 ± 3.8 spikes/s and 47.17 ± 2.8 spikes/s for GPe and GPi, respectively. We compared these firing rates to the firing rates of neurons that were recorded from the NP and the TMP. A total of 136 neurons (72 GPe, 64 GPi) were recorded from two NPs, and 151 neurons (73 GPe, 78 GPi) were recorded from three TMPs.
A significant decrease was found in the baseline firing rate of both the GPe and GPi neurons during the tic state (both TSP and TMP), compared with the NP (two-sample t-test, p<0.01, figure 1A). For TSP, the firing rates positively skewed (0.99 and 1.06 for GPe and GPi, respectively, figure 1B) by a minority of high firing rate neurons. These results were in contrast to the distributions of the NHPs' neurons (NP: 0.08 and 0.25; TMP: 0.48 and 0.11, for GPe and GPi respectively). The skewness indicates that the firing rate of most TSP neurons is even lower, with a subpopulation of high frequency discharge neurons. While the firing rates were similar between GPe and GPi neurons, the firing patterns of the neurons in each nuclei were different. Both the coefficient of variation (CV) and the Fano factor (FF) were higher in GPe neurons, in line with their typical pauses, compared to GPi neurons. In the GPi, the CV and the FF were significantly higher during tics, in comparison to the normal state, reflecting increased bursting.

Conclusion
The combination of data from human patients and the NHP model of the disorder provides novel insights into the release of abnormal actions by the CBG pathway. Reduced baseline firing rate was found in both segments of the globus pallidus of the TSPs and the TMPs compared to the NPs. The two striatal cell populations contributing to the direct and indirect pathways of the BG are disinhibited and provide increased inhibition to both the GPe and GPi. This results in a tonic reduced inhibition on thalamic and cortical regions which is phasically modulated around the tic time.

INTRODUCTION

In deep brain stimulation (DBS), thin quadripolar electrodes connected to a neuropacemaker are implanted into subcortical central structures of the brain where pathological neuronal activity is modulated with electrical current. The method has revolutionized the treatment of Parkinson´s disease and other movement disorders and is under investigation for, among others, some psychiatric conditions.

DBS has in this group shown some promising results, but the material is limited and heterogeneous, consisting mainly of small non-randomized studies with electrodes implanted in many different brain target structures(1).

Here we present a patient with severe major depressive disorder (MDD) and co-morbid anorexia nervosa treated with DBS in the medial forebrain bundle (MFB) and subsequently in the bed nucleus of stria terminalis (BNST).

CASE PRESENTATION

 History

The patient, a 60-year woman, had childhood onset of anxiety and anorexia nervosa, with symptoms of anxiety connected to food intake, restricted eating and later on purging. The course of the eating order was remitting and relapsing with episodes at age 14, 28 and most recently at age 44. The last episode had a prolonged course and over time her depressive symptoms became more and more severe and since the age of 47 her main problem was MDD, with significant symptoms of anxiety. By the end her eating disorder had clear depressive components with thoughts of being a burden to relatives, not being worth to eat and suicidal ideations about starving to death. At the age of 54 the patient was committed to a closed psychiatric ward.

 Treatment

The patient had tried and failed psychotherapy, several different SSRI, SNRI, NaSSA, MAOIs, tricyclic antidepressants, mood stabilizers, neuroleptics and ketamine infusions, with little or no effect. The only treatment providing relief was ECT, and the patients had received since many years three sessions of ECT every fourth week. Unfortunately ECT resulted in a gradual loss of memory, finally removing most of her memories from before her 30 years of age. Attempts to reduce the frequency of ECT sessions failed since this resulted in several suicide attempts while being admitted.

Therefore after extensive screening and informed consent, the patient was included in an ongoing study of DBS for MDD. The MFB was chosen as target based on a recent report, which highlighted the acute and quick effect of this treatment(2).

When evaluated before surgery at baseline the patient weighted 40 kg with a  body mass index (BMI)  of 16.6. She was deemed severely depressed. She scored 43 points on MADRS, 22 on HAM-D and 34 on HAM-A. She preferred lying alone in a dark room. She exhibited reduced facial mimic. She responded adequately to questions, but with short sentences and a monotonous voice.

At age 56, the patient underwent implantation of two DBS electrodes (Medtronic model 3389) in the MFB in the posteromedial hypothalamic area just anterior of the red nucleus (Figure 1). Stimulation was initiated two days after surgery. When the patient returned one week later the effect was perceived as dramatic. The patient considered herself to be “quite happy”. She had a normal facial mimic, spoke fluently and smiled occasionally.

Bipolar stimulation was delivered using three contacts on each side, at 130 Hz, and 60 uS. The voltage was gradually increased and after 4 months was 2.8 V on the left side and 3.0 V on the right. Further increase was not possible since it caused blurred vision. At 6 months MADRS was reduced to 26 points, HAM-D 22 and HAM-A 21.

Ten months after the procedure the patient complained of blurred vision. Numerous adjustments of stimulation and cessation of lamotrigin (due to possibility of the drug to attenuate visual side-effects) were tried in the following period without success. The symptom was partly stimulation induced, but even after the stimulation had been turned off for 2 weeks, some minor symptoms remained. The stimulation was restarted with a voltage reduced to a level where the side effects were tolerable, however, with a reduced effect on her psychiatric symptoms.

Two years after the first procedure the patient was therefore re-operated, with implantation of bilateral electrodes (Medtronic model 3387) in the BNST (Figure 1). The patient received monopolar stimulation through two contacts on each electrode and gradually increasing voltage. At 12 month the patient had 130 Hz, 120 uS and 4.3 V bilaterally. The stimulation in the MFB was simultaneously reduced and turned off without any signs of deterioration.

 Outcome and follow-up

The improvement seen after BNST DBS was more gradual but very profound. Nine months after surgery the patient was released from the psychiatric ward and returned to her home. Prior to this she had been subject to hospital care, initially due to her eating disorder and lastly due to severe MDD with suicidal ideation, for almost 4 years. She is now living fulltime at home with her family and participating in social gatherings and outdoor activities. She considers herself to be profoundly improved and at 12 months her MADRS was reduced to 13 points, HAM-D scored 6 and HAM-A 5 points.

During the whole postoperative periods, neither of the surgical procedures had any significant effect on her anorexia, in terms of BMI. However, following the second procedure all her anxiety for food and eating vanished. She has virtually stopped vomiting, her food intake is more stable and less prone to large variations, and tube feeding could be cessated. However, in the words of the patient, she continues out of habit to eat just enough to keep her weight stable, even in the absence of anxiety or obsessive thoughts. However, she is now motivated to start behavioral training to change this pattern.

 DISCUSSION

 According to WHO, depression is the most common cause of disability with a prevalence of 3-5%(3), and the STAR*D studies have demonstrated the limitations of conventional treatments(4). Not only is depression associated with a suffering for the patients, an often severe social handicap and a reduced quality of life, but also with a significant mortality. It is estimated that 90 % of the suicides are related to psychiatric diseases, the most common cause being depression, where the mortality due to suicide is around 10-15% (5).

Anorexia nervosa has one of the highest mortality rates of any psychiatric disorder and the presence of anxiety and mood disturbances portends a worse prognosis of the disorder (6). As for depression conventional treatment methods have demonstrated limitations. Pharmacological methods have been shown to be ineffective in anorexia nervosa (7). Even with psychotherapy and self-help programs, where effectiveness ranges from 60-70%, there remains a group of patients with intractable symptoms (8).

Even though the majority of patients will respond well to non-interventional therapy, there remains a significant group in both depression and anorexia nervosa, in whom conventional treatment will yield little or no relief of symptoms. In severely affected patients where therapy resistant symptoms have caused a high degree of suffering and handicap, interventional procedures in the form of stereotactic functional neurosurgery might be indicated. The experience of these experimental procedures remains, however, still limited.

A total of 100 patients treated with DBS for MDD in nine different studies and several brain targets have been published{Naesstrom, 2016 #141}(9).  The most common targets are the subcallosal cingulate gyrus (SCCG)⁹, the nucleus accumbens (NA) and the ventral caudate/ventral striatum (VC/VS)(10-12). The inferior thalamic peduncle and the lateral habenula were the target in two case reports(13, 14). The most recently published brain target for DBS in depression is the MFB, where results have been presented for seven patients(2). The results of DBS for depression have been generally promising, although recent blinded randomized multicenter studies in the US have failed to show benefit from active stimulation compared to sham stimulation(11). Concerning the BNST this target has only been published in one study of DBS for obsessive compulsive disorder (OCD), but not for MDD(15).

In our patient the MFB, connecting the amygdala, ventral tegmental area, NA, ventromedial and lateral nuclei of the hypothalamus, was initially chosen as target since the onset of effect has been reported to be rapid (2). A fast onset of effect was deemed essential considering the patients dependency on ECT and the fact that ECT may not be possible to do after DBS implantation. Blurred vision following this procedure has been described in the original publication(2), even though not in the way described here with late appearance and semi-reversibility.

When a second surgery was considered indicated the BNST, a part of the anxiety-regulating network between amygdala, hypothalamus, thalamus and orbitofrontal cortex(15), was chosen as target. This decision was based on our own experience of the effect of BNST DBS for concomitant depressive symptoms and anxiety in patients with OCD and generalized anxiety disorder (GAD) (unpublished data). Furthermore, studies have pointed out BNST as an important brain structure involved in anorexia nervosa and anxiety disorders (15-18).

Even though the indication for this procedure was MDD, it would not have been unreasonable to expect a positive effect on the patient’s concomitant anorexia. Effects of improved mood and anxiety could potentially disrupt important illness-maintaining factors. The improvement of this patients mood, anxiety and quality of life, even with remaining sign of underweight, is promising, in view of the well known poor response of underweight patients to conventional pharmacological and psychological therapies. In the literature DBS for anorexia has been performed on three different brain targets in 14 patients, several with concomitant MDD, OCD or GAD, published in five reports.  The SCCG was targeted in seven patients(19, 20), NA in six(21, 22) and the VC/VS in one(23). Most patients in this heterogenous material seem to have benefited to various extents from the procedures.

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15. Luyten L, Hendrickx S, Raymaekers S, Gabriels L, Nuttin B. Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder. Mol Psychiatry. 2015.

16. Ciccocioppo R, Biondini M, Antonelli L, Wichmann J, Jenck F, Massi M. Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198. Psychopharmacology (Berl). 2002;161(2):113-9.

17. Ciccocioppo R, Fedeli A, Economidou D, Policani F, Weiss F, Massi M. The bed nucleus is a neuroanatomical substrate for the anorectic effect of corticotropin-releasing factor and for its reversal by nociceptin/orphanin FQ. J Neurosci. 2003;23(28):9445-51.

18. Luyten L, Casteels C, Vansteenwegen D, van Kuyck K, Koole M, Van Laere K, et al. Micro-positron emission tomography imaging of rat brain metabolism during expression of contextual conditioning. J Neurosci. 2012;32(1):254-63.

19. Lipsman N, Woodside DB, Giacobbe P, Hamani C, Carter JC, Norwood SJ, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013;381(9875):1361-70.

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INTRODUCTION

 Obsessive-compulsive disorder (OCD) is a chronic disorder affecting approximately 2 % of the population. It is  characterized by persistent obsessive, intrusive thoughts generating anxiety, and related compulsions (tasks or "rituals") with the function of neutralizing the distress [1].  This disorder is one of the most disabling psychiatric disorders and it comes with a significant mortality. Alonso et al suggest that 10 - 27 % of the patients might attempt suicide during their lifetime [2]. Further, up to 10 % of patients with OCD continues to demonstrate severe therapy-refractory symptoms despite trying multiple available treatments [3  4]. New treatments are currently under evaluation, including deep brain stimulation (DBS), which modulates brain circuits hypothesized to be implicated in OCD. DBS is an established treatment for severe therapy-refractory Parkinson’s disease, dystonia and essential tremor [5] and is currently evaluated for a number psychiatric disorders. The most well studied of these psychiatric disorders is OCD, where data from more than 100 patients with severe OCD has been published. The majority of patients were evaluated within a large number of mostly small and non-randomized studies targeting different brain structures. However, the results have been promising with a symptom reduction typically about 50 % and minor side effects [6]. DBS for OCD is not an established therapy, but has received an FDA approval as a “humanitarian device exemption”[8], thus advancing further forward from experimental to clinical use.

DBS trials for psychiatric conditions require collaboration between multidisciplinary teams highly specialized in DBS, participating patients, primary psychiatric health care providers and often also involvement of other caretakers and family members. This invasive and (probably) life-long treatment, differs considerably from the established therapies, and was in one study ranked as the least preferred novel treatment among inpatients with OCD [7]. It is therefore of importance to get an understanding of the level of knowledge and existing concerns among both medical staff and patients regarding this novel therapy. Such data can be of value to both the professional and public debate, guidelines and policymaking concerning DBS for OCD.

A few publications have been presented regarding quality of life and experiences in OCD patients after treatment with DBS [9 10]. The authors are, however, unaware of any studies that have examined the knowledge and attitude of DBS in patients with OCD not enrolled in a DBS study. The same is also true regarding their medical mental-health care contacts; psychiatrists and psychotherapists. Therefore, the aim of this study was to identify level of knowledge and concerns, which might be relevant for future study designs and creation of information targeting healthcare professionals and patients.

The study was conducted through a web-based survey, specifically aimed to psychiatrist, cognitive behavioral therapy (CBT) psychotherapists and patients with OCD. Given the relatively small sample sizes, and the paucity of previous research in this area, the study was exploratory.

 MATERIALS AND METHOD

 Three web-based surveys were constructed for psychiatrist, patients with OCD and therapists with experience of CBT, respectively. The surveys contained questions regarding age, sex, previous knowledge of DBS, source of knowledge, attitudes and concerns towards the therapy. The patient survey included additional questions regarding self-assessed severity of the disorder and current treatment regime. The link to the web-survey was distributed among psychiatrist in the northern region of Sweden and a national CBT psychotherapist group. For patients with OCD, a link was published at the website of the national Swedish OCD patient-support group. The data was analyzed using the statistical tool SPSS, version 22. The project was approved by the Umeå University board of ethics.

RESULTS

 A total of 65 patients with OCD, 44 psychiatrists and 52 psychotherapists responded to the survey. 

 Patients

In response to the question how large an impairment OCD had on their social and professional life 3.1% answered no, 15.4% minor, 24.6% moderate, 41.5% major and 15.4% extreme impairment. Of the patients 38.5% had a combination of pharmacological therapy and psychotherapy, 35.4% only pharmacological therapy and 7.7% only psychotherapy, while 18.5% received no current treatment. 29.2% had knowledge of DBS for OCD prior to the survey. A majority; 94.7% listed media, such as internet or newspapers, as source for the information. Additionally, 15.7% had also received information about DBS from their physician and 10.5% from patient-support groups. 58.5% of the patients were positive to consider undergoing DBS for OCD. Males were more positive than females (p-value 0.05), but no differences were seen regarding age. A possible trend could suggest that patients with prior knowledge of DBS were more positive (p-value 0.167). The most common concerns regarding DBS were; adverse-effects of stimulation (61.5%), possibility of lack of effect on OCD symptoms (60%), change in personality (56.9%) and complications of anesthesia or surgery (56.9%). No significant correlation was seen between these four concerns.

 Psychiatrists

Of the responders 57% were certified psychiatrists and 43% under specialist-training in psychiatry. 93.2% had knowledge of DBS for OCD prior to the survey. A majority: 78% listed scientific sources, such as research journals, as source of information. Additionally, 58.5% had also received information about DBS from colleagues, 14.6% from media and 9.7% from patients. After being presented with a list of inclusion and exclusion criteria for DBS for OCD 50 % estimated that their clinic had 2-5 patients that could fulfill these criteria, 34 % 6-10 patients, 14 % >10 patients and 2 % no patients. 95 % were positive to refer patients for DBS for OCD. The most common concerns regarding DBS were; resistance from patients to undergo neurosurgical treatment (63.6%), complications of surgery or anesthesia (54.5%), difficulty to identify eligible patients (52.3%) and ethical concerns with neurosurgery (29.5%).

 CBT psychotherapists

All responders had experiences with CBT for OCD, 46% had a degree in psychology and the remainder had additional training in CBT. 40.4% had knowledge of DBS for OCD prior to the survey. A majority; 61.9% listed scientific sources as source of information. Additionally, 57.1% had also received information about DBS from colleagues, 28.5% from media and 3.8% from patients. After being presented with a list of inclusion and exclusion criteria for DBS in OCD 54% estimated that their clinic had no patients that could fulfill these criteria, 38% 2-5 patients, 4% 6-10 patients and 4% >10 patients. 94% were positive to DBS for OCD. The most common concerns regarding DBS were; complications of surgery or anesthesia (63.5%), change in personality (38.5%), ethical concerns with neurosurgery (34.6%) and possibility of lack of effect on symptoms (34.6%).

 Discussion

 Of the OCD patients 29% had knowledge of DBS prior to the survey. The majority had obtained this information through media and there was a non-significant trend suggesting that patients with previous knowledge of DBS were more positive to undergoing such treatment.

 It has previously been pointed out that patients educate themselves and build their hopes from uncritical media sources [14 15], which might be a problem since media cover on DBS tend be overly optimistic with minimal coverage of risks. Concern has also been raised for DBS gaining public popularity before a full evaluation of effectiveness and adverse-effects in psychiatric indications is undertaken [11-13].

 This highlights the importance of establishing a dialogue between experts and the general public to foster a better understanding of the possibilities and limitations of DBS. Ultimately, scientists and physicians in the field need to consider the public portrayal of DBS for OCD, to ensure realistic hopes.

In comparison the main source of information for psychiatrists and psychotherapists consisted scientific sources and colleagues. The waste majority of psychiatrists (93,1%) and almost half of the CBT therapists (40,3%) had previous knowledge of DBS. This could reflects the high interest for the field, which can be seen in the increasing number of publications related to DBS for psychiatric indications [16].

Considering the novelty and invasiveness of DBS in psychiatry, an unexpected majority of psychiatrists (95%), CBT psychotherapists (94%) and OCD patients (58.5%) were positive to DBS as a therapy for OCD. However, there is a risk for selection bias with primarily individuals with an interest in DBS participating in the study. That over half of the patients could consider treatment with DBS contrasts with a previous study from 2010 by Patel et al., where DBS was ranked as the least preferred investigational treatment among patients with OCD [7]. Similarly with Patel et al. we found that males were more positive towards DBS than females.

The positive attitude towards DBS among psychiatrists and CBT psychotherapists is reassuring considering the potential need for medical follow up for future DBS OCD patients in their own community. Two commonly mentioned concerns among psychiatrist were resistance to neurosurgery among potential patients and the difficulty to identify eligible candidates. This could represent a lack of knowledge of selection criteria for OCD trials and risks and possibilities of DBS. Strategies to communicate selection criteria for patient referral to psychiatrist and develop clear psychiatric postsurgical follow-up strategies for the patients’ primary psychiatric contacts will be needed in the future. It will further be of importance to optimize care and transfer of knowledge to local psychiatric health contacts for this novel patient group. Furthermore, CBT has been suggested as a promising augmentation of DBS in OCD [10 17]. This encourages an increased involvement of CBT psychotherapists.

 Complications from surgery and anesthesia was a common concern in all three groups. This is similar to Leykin et al, where participants in a DBS-trial for treatment-resistant depression correctly identified the surgery itself as the riskiest part of the study [18]. As pointed out by Lipsman et al. “Although DBS is minimally invasive neurosurgery, it is the maximally invasive psychiatric treatment available” [19]. DBS in psychiatric disorders have the advantage of being able to build on 20 years of experience with DBS in movement disorders. The surgical procedure and the risk for complications does not differ greatly from its use in more well studied indications e.g. Parkinson’s disease [20].

Side-effects of the stimulation was a main concern in the patient group. Compared to the extensive data on surgical complications, there is limited knowledge about the potential stimulation related adverse effects of DBS in psychiatric disorders. Multiple different anatomical targets are under evaluation in OCD (nucleus accumbens, ventral capsule/ventral striatum, subthalamic nucleus, internal capsule, inferior thalamic peduncle, bed nucleus of stria terminalis) and they differ in probability and quality of stimulation induced side-effects [6]. Related to the issue with multiple targets under investigation is the concern from patients and CBT psychotherapists of the possibility of limited effect of DBS on symptoms. Thus, further research is needed to establish efficacy and safety of the different targets for OCD.

The use of DBS in OCD and psychiatric disorders faces a number of unique ethical challenges. It might therefore not be surprising that ethical issues with psychiatric neurosurgery were one of the main concerns among the psychiatrists. Hence, it is reassuring that the topic is often discussed in the literature [12 21-25].

 The possibility of DBS induced personality changes was the second most common concern among CBT psychotherapists and the third in the patient group. The concept of personality is a complex question and it is not possible from this survey to know what the groups would define as a change. However, the possibility of stimulation induced changes in personality is currently one of the most discussed clinical side effect and ethical concern for DBS in psychiatric indications [21 26 27]. Most of the authors suggest that positive changes of important elements of personality, such as mood and cognitive behavior, should rather be an intended outcome rather than an unwanted, coincidental side-effect. There are few reports of perceived positive and negative changes in personality after treatment with DBS in patients with Parkinson’s disease [28 29]. Concerning OCD a small study by Gabriels et al. found no adverse changes in personality when using self-rated personality inventory in three patients treated with DBS in the internal capsule [30]. However, empirical studies systematically looking at the effects of DBS on personality in psychiatric patients are still missing.

Considering eligibility of patients, over half of the psychotherapist reported that they had no OCD patients that would fulfill the presented inclusion criteria for DBS. This was in contrast to the psychiatrists, where only 2% estimated that they had no patients fulfilling the inclusion criteria. This discrepancy could be due to psychotherapists encountering patients motivated and eligible for CBT therapy, hence with a less severe form of the disorder, while psychiatrists might encounter a greater diversity of OCD patients, including some with severe symptoms. A study using data from a naturalistic clinical sample found that meeting the stringent criteria to qualify for DBS is rare among the general OCD population [31]. The question of the potential need for DBS in OCD and how to determine the candidates that will most likely benefit from the therapy has still to be determined.

CONCLUSION

 The interest and research for DBS in psychiatric disorders have surged the past decade since the first publication of Nuttin et al. 2003 and the therapy is hoped to have the potential to relief symptoms in some of the most disabling disorders known to humankind [32]. With the FDA approval for a “humanitarian device exemption” and the increasing number of worldwide implantations, DBS for OCD is already moving from experimental to clinical use [6 8]. Thus increasing the number of potential patients that will be in need of ongoing follow-up care by professionals in mental health care. This underlines the importance of proper education and information for potential DBS patients and their healthcare contacts. The current knowledge and experience of DBS in OCD mainly derives from small non-randomized studies. There are still plenty of challenges identified by the participants of this study: source and quality of information, efficacy, potential adverse effects and eligibility. For all of those, the current evidence base is very limited; therefore, a broad research agenda is needed for studies going forward.

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Background

Interpersonal dysfunction has long been recognised as a core component of depressive illness.  Some studies suggest that interpersonal difficulties may be persistent and recover more slowly than symptoms. Difficulties in interpersonal functioning may also reflect ongoing risks for relapse/reccurrence of depression. Understanding someone’s interpersonal functioning is an important role in monitoring recovery from illness.

There is little in the literature comparing pre- and post-operative measures of interpersonal functioning following psychiatric neurosurgery. Here we report outcomes following anterior cingulotomy for chronic, treatment-refractory depression.

Method

The Inventory of Interpersonal Problems – 64-item (IIP-64) is a self-report measure of difficulties that people repeatedly encounter in their relationships with others. The eight scales of the IIP64 assess interpersonal problems in eight domains: Domineering/Controlling; Intrusive/Needy; Self-Sacrificing; Overly Accommodating; Nonassertive; Socially Inhibited; Cold/Distant; Vindictive/Self-Centred. The total score reflects how much difficulty a person experiences in interpersonal relationships.

We use the IIP-64 routinely to assess interpersonal functioning over time. We now report the outcomes from 15 patients who underwent anterior cingulotomy for chronic, treatment-refractory depression. The IIP-64 was completed at baseline and at 12-months following surgery. Response at 12-months was defined as ≥50% improvement on the 17-item Hamilton Rating Scale for Depression (HRSD-17).

We compared changes in scores on the IIP-64 in relation to changes in symptom burden. Scores were ipsatised by subtracting the individual’s mean scores from each response on other items in the questionnaire in order to compensate for uniform response bias. Ipsatised scores on each of the IIP-64 domains were plotted pre- and post-surgery. Total T-scores at 12-months were compared between responders and non-responders. Finally, we attempted to relate change in depressive symptoms to changes in interpersonal functioning.

Results

Fifteen individuals (M:F ratio was 1:14) underwent thermal anterior cingulotomy. The mean ± SD age was 48.9 ± 8.3 years. The mean ± SD baseline HRSD-17 score was 28.5 ± 5.0. Five of the fifteen (33.3%) had previously failed to respond to a trial of Vagus Nerve Stimulation (VNS), but none had previously undergone ablative neurosurgery.

All individuals demonstrated impairments in interpersonal functioning at baseline, with mean total T-scores on the IIP-64 of 70.3 ± 7.9. As expected, depressed patients showed greatest difficulties in domains related to depression such as: Nonassertive; Socially Inhibited; and Cold/Distant.

In terms of response rate, 7/15 (46.7%) met criteria for response at 12-months. Those who responded showed a reduction in their IIP-64 Total T-score from 68.3 ± 7.4 to 56.3 ± 14.7. Non-responders showed no significant change in their scores: baseline 72.0 ± 8.3; 12-months 72.1 ± 8.3. Responders tended to show a ‘normalisation’ of scores in typically depressive domains, with improvements observed in domains relating to greater control and greater affiliation.

There was a robust relationship between magnitude of change on the HRSD-17 at 12-months and change on the IIP-64, with those showing greatest symptom improvement having the greatest improvement in interpersonal functioning (Pearson’s r=0.645; P=0.009).

Conclusions

Although the sample size is relatively small, there are clear relationships between improvements in depressive symptoms and changes in interpersonal functioning. Furthermore, there is a statistically-significant relationship between symptom change and improvement in interpersonal functioning. Importantly, there was no evidence of deterioration in interpersonal functioning; even in non-responders.

At the current time, it is not possible to determine if changes in interpersonal functioning pre-date improvements in mood. However, the relationship between symptoms and interpersonal difficulties would support the hypothesis that as symptoms improve, an individual’s interpersonal functioning improves.

Prospective monitoring of interpersonal functioning is, therefore, a useful tool in assessing outcome following neurosurgical treatment of depression.

Introduction:

We present three cases of patients with morbid obesity, treated by bilateral deep brain stimulation of the nucleus accumbens. In these cases, the starting point of illness was the operation of the craniopharyngioma with multihormonal hypothalamic pituitary deficiency.

Patients and methods:

First patient M. K. with a BMI of 52.64 (weight 150.7 kg). He was implanted stimulator for deep brain stimulation to both sides of the nucleus accumbens septum (nucleus accumbens - NACC). The procedure was performed on 06.07.2012. During hospitalization we not observed any negative consequences of stimulation, weight at the day of departure from hospital was lower by 3.5 kg.

The second patient N.Z. with severe obesity (weight 132 kg assuming the increase 168cm) - was implanted stimulator for deep brain stimulation to both sides of the nucleus accumbens septum (nucleus accumbens - NACC) on 02.21.2014. Surgery without complications. Good tolerance stimulation.

The third patient M.K. with severe obesity (weight 138 kg assuming the increase 164cm) - was implanted stimulator for deep brain stimulation to both sides of the nucleus accumbens septum (nucleus accumbens - NACC). Surgery without complications. Good tolerance stimulation.

Results:

 After a month M. K. body weight from baseline was lower by more than 7kg. We did not observe any complications and side effects during the period of stimulation. The neuropsychological study without deviating from the norm, especially without cognitive impairment. The patient feels well, thinking about food take sick about 20% of the daily activity - previously about 80%. In the course of treatment has been interrupted twice stimulation - the first time because of the stimulator off, the second time because of damage to the connecting cables. In both situations, the patient reported immediately to the consultation feeling strong deterioration.

 The second patient N.Z. feels good, thinking about food can control, not eating at night (before mandatory every 2 h). On the day of the quantity and quality of meals does not deviate from the norm, the patient no longer feels compulsion food.

The third patient N.Z. can fully control thinking about food, the patient no longer feels compulsion food.

Conclusions:

In our opinion, based on the results of the  patients described above, the treatment proved to be effective and safe procedure.

Objectives

Diffusion weighted imaging (DWI) is a valuable tool for localizing white matter fibres and measuring metrics of diffusivity. Conventional imaging methods are limited in their ability to distinguish white matter tracts from surrounding tissue. Diffusion imaging and tractography algorithms can be used to overcome this limitation by visually reconstructing anatomically accurate white matter fibres. While this technique has been successfully used in the CNS, DWI of peripheral nerve fibres has been very limited, but would prove to be of value in non-invasive treatment, including focused ultrasound (FUS), particularly since DWI allows for in vivo measurement of microstructural changes following FUS. In this study we report a method of anatomically accurate DWI reconstruction of the sciatic nerve in a piglet model, followed by measurement of diffusivity metrics before and after lesioning of the sciatic nerve with FUS. 

Methods

Bilateral sciatic nerves in two piglets (average weight 7.5 kg) were studied. T1 anatomical and DWI scans were acquired on a 3T MRI using a 32-channel cardiac-torso phased receive-only coil. The DWI scanning parameters included 128 diffusion directions, 1.6mm isotropic voxel resolution, and diffusion weighting of b=800 s/mm². Eddy current, motion, and fieldmap corrections were performed. A one-direction reverse phase-encoded sequence was also incorporated for correcting diffusion gradient-associated image distortions. The T1 and DWI scans were co-registered for accurate anatomical localization. Probabilistic streamline tractography was performed using MRTrix3 with the following parameters: step size 0.16 mm; stopping angle 30 deg; stopping and initial fibre orientation amplitude 0.1; generated tracks 1000. Fibre tracts were used to target the sciatic nerves in all subjects using an MR-guided FUS system. Targeted regions were sonicated once per nerve with the following parameters: treatment cell diameter 8mm; exposure time 27s; input power range 50-110 W. A region of interest (ROI) based analysis was performed in order to measure scalar diffusion metrics of fractional anisotropy (FA), radial (RD), axial (AD), and mean (MD) diffusivities. Five cross-sectional ROIs (3.2 x 3.2 x 1.6 mm³) were placed along the sciatic nerve covering the region targeted by the FUS beam. Comparisons were performed across nerve segments before and after treatment.

Results

The tracts of all sciatic nerves were successfully imaged both before and after treatment. Tracts extended from the spinal cord dorsal root ganglion past the distal head of the ipsilateral femur. Measurement of ROI diffusion metrics in the targeted segments demonstrated that, following treatment, there was a significant decrease in FA and significant increases in MD and AD (p<0.05). An increase in RD was also observed but it failed to reach statistical significance (p=0.055). Histological analysis confirmed FUS lesions covering the nerve as well as surrounding hamstring muscle.

Discussion

Using the described imaging protocol, we were able to consistently reconstruct the sciatic nerve in piglets both before and after treatment with FUS. The tracts of the sciatic nerve could be easily distinguished from surrounding blood vessels, fat, muscle, and other tissue which can otherwise obscure accurate target identification. Post-treatment subjects exhibited decreased FA and increased diffusivities at the treatment site. This is indicative of the thermal breakdown of axonal nerve fibres as the directionality of water diffusion becomes more isotropic following FUS sonication. DWI and tractography algorithms have thus been shown to be effective tools for visualizing white matter structures for FUS targeting and for assessing the microstructural changes that occur following FUS treatment.

Intrathecal Baclofen therapy is a well-recognized safe and effective treatment modality in selected patients with medical refractory spasticity. The medicine (β-[4-chlorophenyl]-GABA) is delivered through a programmable pump implanted subcutaneously and connected with a close system to the subarachnoid space. The pump is usually filled 2-4 times per year. Sudden under or over dosing of the Baclofen drug delivered to the intrathecal space may lead to serious and possibly fatal outcome. In this presentation the author will describe his experience in managing cases suffering serious complications of intrathecal baclofen therapy treated in his center. These include cases of Baclofen deprivement and overdosing. The presentation shall discuss issues of preventing, early recognition and management of these serious and can be fatal complications.

Objectives: Presentation of a case series of 3 patients suffering from intractable spasticity, treated with intrathecal baclofen therapy. A new “hybrid” pump (Siromedes 20ml, Tricumed) was implanted in all patients, during the period from November 2015 to January 2016.

Methods: a) A 30 year old female patient developed spastic right hemiplegia after a road traffic accident in 2004. She was treated with intrathecal baclofen therapy until the depletion of her programmable pump. In November 2015 she underwent surgical substitution of her previous pump with the new “hybrid” pump. b) A 68 year old male patient developed spastic right hemiparesis after several ischemic episodes. He was receiving intrathecal baclofen therapy with a programmable pump since 2009. His old pump was depleted and replaced with the new “hybrid” pump. c) A 17 year old male patient was suffering from severe spastic tetraparesis due to cerebral palsy. He underwent implantation of the new “hybrid” pump.

Results: The post-operative period was smooth for all three patients, with spasticity efficiently alleviated immediately after the initiation of baclofen therapy. The new baclofen pump represents a unique “hybrid” mode of function, since it can be programmable for at least 8 years and thereafter continues to operate for a long period as a constant flow pump.

Conclusions: The new “hybrid” pump appears to be a safe and efficient alternative for intrathecal baclofen therapy. All 3 patients had an uncomplicated follow up period of 5 months or more. Longer follow-up periods and a larger patients sample are necessary for conclusive results.