INTRODUCTION

The effectiveness and safety of the use of Deep Brain Stimulation (DBS) to reduce motor complications of subjects with Parkinson's disease (PD) has been substantiated by several randomized controlled trials (Deuschl et al., 2006, Weaver et al., 2009, Okun et al., 2012, Scheupbach et al., 2013). Motor improvement following DBS is sustained for up to 10 years as reported by Castrioto et al. An in-depth evaluation of real-world outcomes following DBS will add to the existing database of knowledge and prove to be a useful tool for physicians. We present the outcomes of a large scale clinical registry that compiles the effectiveness and safety-related real-world outcomes of a multiple-source, constant-current DBS System in the treatment of levodopa-responsive PD.

METHODS

The Vercise DBS Registry is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific Corporation. The Vercise DBS system (Boston Scientific) is a CE-marked, multiple-source, constant-current system with a rechargeable battery. Subjects will be followed up at 3, 6,12 months and up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms will be evaluated. Clinical endpoints will be evaluated at baseline and during study follow up that include Unified Parkinson's Disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. The registry also utilizes the newly developed MDS UPDRS for the evaluation of motor symptoms and includes the evaluation of non-motor symptoms of PD (Non-Motor Symptom Assessment Scale) following DBS. Adverse events are also collected.

RESULTS

This report will provide the safety and effectiveness outcomes of the first cohort of subjects implanted with the Vercise DBS System analyzed at 6 months post-implantation as compared with baseline.

DISCUSSION

The Vercise DBS registry study represents the first comprehensive, large scale collection of real-world outcomes and evaluation of the safety and effectiveness of the Vercise DBS System. This report will provide such data from the first cohort of subjects analyzed at 6 months post-implantation as compared with baseline.

REFERENCES

Background: Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed surgical treatment for patients with Parkinson’s disease. The goal of the surgery is to place an electrode in the motor region of the STN while avoiding non-motor regions. However, distinguishing the motor region from the neighboring associative and limbic areas in individual patients using imaging modalities was until recently not possible. Here, we have performed a patient-specific dissection of the subdivisions of the STN using ultra-high field MR imaging to allow for individualized surgical planning.

Methods: We have acquired 7T diffusion-weighted images of seventeen patients with Parkinson’s disease scheduled for deep brain stimulation surgery.  Using a previously established protocol, the STN’s connections to the motor, limbic, and associative cortical areas were used to map the individual subdivisions of the nucleus.

Findings: A reproducible patient-specific parcellation of the STN into a posterolateral motor and gradually overlapping central associative area in all STNs, taking up on average 55·3 % and 55·6 % of the total nucleus volume. The limbic area was found in the anteromedial part of the nucleus.

Interpretation: Our results demonstrate that ultra-high field MR imaging can be used to perform an individualized and highly specific planning of deep brain stimulation surgery of the STN.

Introduction: Implant infection in DBS surgery is one feared complication. The growing number of DBS surgeries performed and use in a broader number of pathologies, may lead to a rising number of infections. There are no globally accepted guidelines for preventing this complication.

Methods: A cohort study was perfomed including all patients submitted to DBS surgery for Parkinson’s disease during the time period ranging from 2006 to 2016. Our group adopted in 2010 a two-step surgery, dividing the long DBS surgery procedure into two shorter ones. Data was divided into early infections (occurring in the first 90 days) and late infections (after 90 days). Our primary outcome was the infection rate in both groups and secondary outcomes were early infection rate (≤90 days), late infection rate (>90 days), time-to-infection, infection per year, infection site and involved microorganism.

Results: Total population included 190 patients (61.58% (n=117) males, 38.42% (n=73) females), 40,5% (n=77) in the 1-procedure group and 59,47% (n=113) in the 2-procedure group. Considering our primary outcome, 8 infections were diagnosed in the 1-procedure group (infection rate of 8.2%) and 1 in the two-procedure group (infections rate of 0.54%) – p value=0.041. Early infections were detected only in the 1-procedure group (2.1% - n=4 - versus 0%, p-value=0.033).

Conclusions: A standardized definition of surgical site infection and treatment guidelines are required. Our results indicate that splitting DBS surgery for Parkinson’s into a two-phase surgery may actually decrease the rate of infection, as opposed to the classic procedure practiced in most centers.

Background. 

Recent advances in ultrasound transducer technology have allowed ultrasound to be transmitted with precision through the human skull.   Pilot studies suggest that MR guided focused ultrasound can be used to successfully generate stereotactic thalamic lesions.  We present the one year results of a double-blinded, randomized, controlled trial of FUS thalamotomy for essential tremor.  

Methods.

Seventy-six patients with medication-refractory essential tremor were randomized 3:1 to receive a unilateral focused ultrasound thalamotomy or a sham procedure.    Tremor (CRST) and quality of life (QUEST) measures were obtained at baseline, 3, 6, and 12 months.  Safety was determined adverse event monitoring throughout the study.   All tremor assessments were videotaped and then rated by an independent core lab of neurologists who not involved in the procedures. 

Results.

Contralateral hand tremor, the primary endpoint, was improved by 49% at 3 months (p<0.001) with the treatment (18.09 +4.81 to 9.55 + 5.06) compared to sham procedures (16.00 + 4.42 to 15.75 + 4.90) and the effect was durable at one year (10.89+4.86). 

Similarly, functional measures of disability and quality of life were statistically improved whereas there was no change in the sham cohort.                    

The most common side effects were paresthesia and gait disturbances, and remained at 12 months in 14% and 9%, respectively.   

Conclusion.

Focused ultrasound can be delivered effectively through the intact skull to make precise ablations deep in the brain.  MR guided focused ultrasound thalamotomy improves hand tremor and quality of life in ET with an acceptable safety profile.   

Objective:  Prelemniscal radiations (Raprl) have been reported as a safe and effective target to treat the symptomatic triade of Parkinson’s disease. However, little is known about the anatomical connectivity of its fibers and the mechanism of action of DBS in this area. The present report studies the fiber composition of Raprl through high resolution tractography and the effect of DBS on PET/CT metabolic activity of Regions of Interest (ROIs) derived from tractography.

Material and Methods. Twenty patients with prominent unilateral motor symptoms of PD were scanned with 3T MRI, in which diffusion weighted images (DWI) were acquired and constrained spherical deconvolution (CSD) identified diffusion profile in different directions. In five patients DBS electrodes were implanted in Raprl contralateral to most prominent symptoms and¹⁸Fluor-Deoxy- glucose (FDG) PET/CT performed preoperatively and after DBS was optimized. Metabolic changes induced by DBS on Regions of Interest (ROIs) derived from tractography, were determined by Statistical Parametric Mapping (SPM8). Non-stimulated hemisphere served as control for pre and post DBS PET/CT studies.

Results. In all cases tractography identified three major components: 1. Cerebellar-Thalamic-Cortical component, that at the level of the thalamus and cortex segregated in a posterior subset connecting with Vim and Primary Motor Cortex (PMC), and anterior subset connecting with the Vop and Supplementary Motor Cortex (SMC). 2. A component connecting Gpi through ansa lenticularis with the sub thalamus, were it divided into a superior subset to overlap cerebellar fibers in Vop and a subset continuing through Raprl to the dorsal brain stem between medial lemniscus and brachium conjunctivum, probably PPN 3. Fibers connecting orbital and dorsolateral frontal cortices with the mesencephalic tegmentum. On the other hand, Raprl-DBS induced an improvement >80% of symptoms, which correlated with a highly significant decrease of metabolic activity in PMC, SMA, Raprl, VL Thalamus, and both cerebellar hemispheres.

Conclusion. Raprl connectivity explains the effect of DBS on PD motor symptoms. Contrary to the current hypothesis of PD physiopathology, DBS induced a significant inhibition of Raprl that extends downstream to VL thalamus, motor cortices and cerebellum, associated with significant improvement of motor symptoms of PD.

Introduction: Spinal cord stimulation is an established method for treatment of chronic pain in FBSS patients. In the last decades only tonic stimulation patterns were used to modulate the pain. There were several reports that indicate that burst stimulation offers other opportunities and advantages. The goal of this study was to evaluate the pain level during placebo stimulation, burst stimulation, 500 Hz tonic stimulation with tonic 40-50 Hz stimulation as a baseline and to show long-term outcome among this population.

Materials/Methods: The study was designed as a double blind, randomized, prospective, cross over study. 20 patients were enrolled and completed the study at the investigational site. The patients were randomized to one of six treatment sequences. Twenty patients with FBSS and a pre-existing SCS system each received 3 treatment allocations in random order for a period of 1 week: Tonic 500 Hz Stimulation, Burst Stimulation, and Placebo Stimulation.

Results: The primary outcome measure was overall pain intensity measured on a numerical rating scale (NRS), 6.9 (baseline) vs. 4.2 (tonic)(p<0.001), tonic vs. 2.08 (burst) (p<0.001). Secondary outcome measures were pain quality measured using the Short Form McGill Pain Questionnaire (SFMPQ). Additional data were collected relating to pain related disability measured using the Oswestry Disability Index (ODI). Mean overall NRS and SFMPQ scores were not significantly different between Tonic 500 Hz Stimulation and Placebo Stimulation. Although the lowest mean ODI score was observed under Burst Stimulation, no significant differences were found between the ODI categories. No adverse events occurred, and Burst Stimulation was significantly preferred by 17 patients (80%). Positive results sustained during the long-term follow up. After two years mean VAS score under burst stimulation was 3 (range 0-6) (p<0.001), 1 pat. died, 1 was lost for FU, 1 suffered from stroke and was switched off.

Conclusions: The lowest mean NRS and SFMPQ scores were observed under Burst Stimulation. For the Burst Stimulation treatment group, mean NRS and SFMPQ scores were significantly decreased compared with the other treatment groups. Overall, Burst Stimulation resulted in significantly better constant pain relief and improved pain quality during the 2y follow-up. 

Few options exit to treat medically refractory upper limb neuropathic pain. Chronically implanted peripheral nerve stimulation (PNS) may be a solution in cases of topographically limited pain due to a peripheral nerve lesion, when spinal cord stimulation is not possible or inefficient.

We report the outcome of a consecutive series of 26 patients suffering from chronic refractory upper limb neuropathic pain treated by brachial plexus nerve root stimulation o or suprascapular nerve stimulation. The technique consisted in the percutaneous, ultrasound-guided, implantation of one electrode (Pisces Quad, Medtronic) close to the suprascapular nerve or the cervical nerve roots within the brachial plexus. All the patients underwent a trial stimulation using externalized lead during 10-15 days. In case of positive trial, the electrode was then connected to a subcutaneous stimulator (Itrel 3 or 4, Medtronic). Chronic stimulation parameters were: mean pulse width 168 microseconds (range 90-210), mean frequency 56 Hz (range 20-85), mean voltage 1,13 Volt (range 0,3-2,1V). The stimulation voltage was set below the threshold inducing muscle contractions or paresthesia.

In this study, 24 patients could be evaluated and 2 patients were lost immediately after surgery. After one year of stimulation, 65% of the patients were improved ≥50%, including 12 patients (46%) improved ≥70%. At last follow-up (mean follow-up 28 months), the mean pain relief was 68%. Out of 20 patients still using the stimulation, 12 were very satisfied, 6 were satisfied, and 2 were poorly satisfied. Four patients were explanted due to loss of efficacy or complications. Medications related to chronic pain were completely stopped in 6 out of 20 patients after the surgery, reduced in 9 and unchanged in 5. Complications were: shock-like sensations (2 cases), superficial infection (1), electrode fracture (2) and electrode migration (2).

In this pilot study, suprascapular nerve or brachial plexus roots PNS provided a relatively safe, durable and effective option to control upper limb neuropathic pain.

Objective: Glossopharyngeal neuralgia (GPN) is a very rare pathology (0.7-0.8/100.000). Patients usually describe short episodes of paroxysmal pain, beginning at the base of the tongue and pharynx and irradiating towards the neck and the internal ear. We aim at reviewing our bicentric experience (Marseille and Lausanne University Hospital) in patients treated with Gamma Knife surgery (GKS) for idiopathic GPN.

Methods: Between 2003 and 2015, 21 patients were treated with 25 procedures. Eleven were women and 10 were men. All cases fulfilled the pharmaco-resistance criteria. Were analyzed patients with at least 6 months follow-up. GKS using a Gamma Knife (model B or C or Perfexion) was performed, based on both MRI and computer tomography targeting. A single 4-mm isocenter was positioned in the cisternal portion of the glossopharyngeal nerve at a mean distance of 14.6 +/- 3mm (range 9.3-23.5) anteriorly to the emergence of the nerve. The target was placed in the cisternal part for 2 and close to the glossopharyngeal meatus in 23 procedures. The mean maximal dose was 81.4+/-6.7 Gy (range 60-90). Three cases have had previous microvascular decompression (MVD), which was effective for 2, 8 and 13 years, respectively.

Results: The mean follow-up period was 5.2 +/- 3 years (range 0.9-12.1). At 3 months follow-up, 91.6% of the cases were pain free (BNI classes I to IIIA). At one year, 81.8% were still pain free (BNI classes I to IIIA), with 60% of them being BNI class IA. Recurrence appeared in 59.1%, in a mean time of 13.6 +/-10.4 months (range 3.1-36.6). Of them, 35% were controlled with medication and 25% (3 cases, 4 procedures) underwent a new radiosurgical procedure after 7, 17, 19 and 30 months, respectivelly. From these cases, two needed another open surgical procedure, with one undergoing a termocoagulation and another a neurotomy. At last follow-up, 16 cases (80%) were still pain free (BNI I-IIIA, 60% BNI IA). No complication was reported.

Conclusion: As in all cranial neuralgias, the reference technique remains MVD, as it addresses the cause (e.g. the neurovascular conflict). Radiosurgery is a valuable alternative, less invasive, with a very high rate of efficacy, in the absence of complications. The most important aspect is that the fifth nerve is easily identifiable, while the ninth nerve remains more challenging, so as its targeting. A multidisciplinary approach including a neurologist and neuroradiologist might be necessary, both for diagnosis and imaging purposes.

Despite the increasing number of pain relieving therapies, and the progresses made in headache treatment, about 20% of Chronic Cluster Headache suffering patients are still resistant to drugs. This form of Trigeminal Autonomic Cephalalgia is one of the cruelest pains ever described, consisting of extremely severe unilateral pain attacks in the orbitotemporal region accompanied by ipsilateral autonomic symptoms. Deep Brain stimulation (DBS) of the posterior hypothalamus (pHyp) was the first surgical technique introduced to prevent attacks, followed by Occipital Nerve Stimulation (ONS) and Sphenopalatine Ganglion stimulation (SPG). Open studies on pHyp stimulation have shown some efficiency, although the mechanism of its efficacy is still not clear. One of the most attractive hypothetic effects is the modulation of the mesencephalic grey substance or of its neighboring third ventricle’s floor structures. We already described an alternative technique consisting in intraventricular stimulation of the floor of the third ventricle. We report here the results at long term follow-up of the whole series of patients operated at Grenoble University.

Eleven patients diagnosed with intractable Chronic Cluster Headache, aged from 24 to 60 years, were enrolled in a prospective open study. Four out of 11 failed Occipital Nerve Stimulation (ONS). One patient received ONS 76 months after hypothalamic DBS. A single electrode was laid on the floor of the third ventricle. The number of attacks was collected at baseline and at 3, 6, 12 months postoperatively, then at long term (9-113 months). In addition to physical and laboratory monitoring, patients’ mood was regularly assessed.

Besides establishing the feasibility and safety of the technique, this study reports the long term efficacy of third ventricle stimulation in reducing the number of headache attacks : 3/11 patients are pain free or have >80% improvement, 5/11 have >50% improvement, 1/11 show lesser improvement, while 2/11 have no significant improvement. Anxiety and Depression scores are also significantly ameliorated. No severe adverse events have been reported so far.

This technique could be a surgical alternative when all techniques have failed to treat iCCH. It has shown efficacy, although it appears to progressively dampen its impact in some patients.

Introduction

As brain implants such as electrodes to record and stimulate neural tissue in laboratory animals are becoming more and more sophisticated, implant tip localization methods have not evolved over the last century. Even nowadays, histology and copying to stereotactic atlases remains not only the gold standard but also the most commonly used method for implant tip localization, despite huge advances in laboratory animal imaging technology. We aim to compare various modalities for electrode tip localization in terms of accuracy, time and costs.

Material and Methods

In 289g male Wistar (SD 7.8g; n=12) and 424g male Sprague-Dawley (SD 6.2; n=12) rats, preoperative CT imaging was followed by stereotactic implantation of 2 electrodes (one in each hemisphere). Next, after in vivo postoperative CT imaging (CTinvivo), unilateral electrolytic marking of the electrode tip position and euthanasia was performed. Now, an ex vivo postoperative CT with the skull and electrodes in place (CTexvivo) was followed by a 14-day iodine immersion and a new CT with and without skull and electrodes in place (CTiodine+skull; CTiodine-skull, respectively) in half of the specimens. Finally, all specimens underwent BlockFace, which is a 3D reconstruction of photographic images acquired with a digital camera facing the remainder of the paraffin block on the microtome, and histology. Six different researchers with different levels of experience picked the electrode tips either directly (when the electrode was directly visible) or indirectly via different definitions (when only the electrode track was visible).

For co-registration of the images to the Johnson-Paxinos MR-atlas, we first constructed a CT atlas based on the preoperative images of the Wistar rats. The postoperative CTs with bony anatomy were co-registered to this CT-atlas and via this atlas to the MR-atlas, while the modalities without bony anatomy were co-registered directly to the MR-atlas.

Results

All CT modalities and BlockFace allowed for electrode tip localization, with modality-specific advantages and disadvantages as compared to histology. While CTinvivo, CTexvivo and CTiodine+skull permit direct electrode visualization, CTioine-skull, BlockFace and histology only show the electrode track, that can be wider and deeper than the final electrode tip position. Depending on the target, histology and CTiodine-skull can show internal brain structures surrounding the electrode tip/trace, whereas the other modalities cannot and consequently heavily rely on the co-registration quality. Clearly, all but CTinvivo only permit localization after euthanasia, hereby only allowing subject exclusion due to erroneous implantation after completion of all tests.

Electrode tips could be reliably localized both in rats identical to and different from those used to create atlases (289g male Wistar rats and 424g male Sprague-Dawley rats, respectively).

Average time needed for localization of 2 electrodes in 1 rat brain (anesthesia, acquisition, preparation of chemicals, euthanasia and perfusion, brain extraction, paraffin embedding, slicing, staining, imaging post processing, tip picking) ranged from 27 minutes (CTinvivo) to 94 minutes (histology).

Average costs, as charged in our institution, for localization of 2 electrodes in 1 rat brain (anesthesia, CT use, chemicals and consumables, histological processing, microtome use) ranged from 5.50 euro (CTexvivo) to 21,24 euro (histology).

Conclusion

We conclude that CT imaging techniques and BlockFace are valuable alternatives to histology for electrode tip localization, and are both faster and cheaper as compared to histology.

The most severe complication in stereotactic deep brain stimulation (DBS) surgery is intracerebral bleeding. Therefor planning of the target site and trajectory is of out most importance. At many clinics intraoperative measurements as microelectrode recording (MER) are common complements to the image based surgical planning. However, MER has a tendence to increase the bleeding incident [1] expecially if several trajectories are chosen. We have developed an optical navigation tool which uses an insertion guide designed with forward looking optical fibres. The guide-probe is designed to fit Leksell^® Stereotactic System (Elekta instrument AB, Sweden) i.e. the same dimensions as a radio-frequency lesioning and impedance probe. Connection of the optical fibers to a LDF (Peliflux 5000, Perimed AB, Sweden) can be used to record the cerebral microcirculation and backscattered light reflecting the tissue greyness in front of the guide. The system has been used during more than 120 DBS implantations and typical “bar-codes“ i.e. grey-white matter changes along the insertion path have previously been defined for trajectories towards STN and VIM [2]. Ongoing work focuses on the “bar-code” for a combined VIM-Zi trajectory.

The aim of the present investigation was to evaluate the LDFs potential as “vessel alarm”, and patient safety during DBS implantations in 50 patients (83 trajectories) at Linköping University Hospital (LiU M182-04, T54-09). Medical record and postoperative radiology were reviewed together with the optical data collected during surgery. All patients were on systemic anticoagulation therapy and undervent a postoperative CT. Recordings were done at 2471 tissue sites. Of these positions 170 (6.9%) spots showed a doubled microvascular blood flow compared to the surrounding. Seventy three (4.3%) of these showed more than five time higher blood flow than the surrounding tissue. High blood flow peaks were most common along VIM trajectories. All trajectories except one were recorded without adverse events. A small heamorrhage was detected with the help of the microvascular blood flow measurements along one preplanned VIM trajectory. In this case both the grey-white matter and blod flow “bar-codes” deviated from expected shapes. Post-operative evaluation showed that the frame system was dislocated and thus a deviating trajectory recorded [2].

The LDF system is highly sensitive and can detect small microvascular changes and grey-white matter differences on 0.5 mm measurement resolution along trajectories [3]. The LDF measurements can also visualize ventricular and sulci involvement, and thus warn if the blood flow starts to increase in sensitive regions. The microvascular recordings correlates well with the systemic heart frequency and can also display microvascular regulations such as vasomotion and local vessel peaks. With the LDF method's forward looking feature in combination with controlled insertion of the probe, it has a potential to act as a ”vessel alarm” and thus helps further minimizing the risks of bleedings. Future potential applications include vessel tracking in combination with MER and stereotactic optical biopsies for tumour diagnostics.

References

[1] L. Zrinzo, T. Foltynie, P. Limousin, and M. I. Hariz, "Reducing hemorrhagic complications in functional neurosurgery: a large case series and systematic literature review," J Neurosurg, vol. 116, pp. 84-94, Jan 2012.

[2] K. Wårdell, P. Zsigmond, J. Richter, and S. Hemm, "Relationship between laser Doppler signals and anatomy during deep brain stimulation electrode implantation toward the ventral intermediate nucleus and subthalamic nucleus," Neurosurgery, vol. 72, pp. ons127-40, Jun 2013.

[3] K. Wårdell, S. Hemm-Ode, P. Rejmstad, and P. Zsigmond, "High-Resolution Laser Doppler Measurements of Microcirculation in the Deep Brain Structures: A Method for Potential Vessel Tracking," Stereotact Funct Neurosurg, vol. 94, pp. 1-9, Jan 22 2016.

Object: Recently, high intensity ultrasound has been precisely focused through the intact human skull to perform thalamotomy.  Acoustic energy of lower intensities is capable of both exciting and inhibiting neural tissues without heat or tissue damage.  Thus, we investigated in a large brain animal model the potential for low intensity focused ultrasound  for noninvasive brain mapping. 

Methods: The swine sensory thalamus was stereotactically targeted with low intensity focused ultrasound, and somatosensory evoked potentials were recorded from an epidural grid electrode.  SSEP recordings were simultaneously obtained from trigeminal, median, and tibial stimulations during thalamic sonications.  Magnetic resonance thermography was used to monitor temperature at the acoustic focus and histology was used to assess for potential tissue injury. 

Results:  Low intensity focused ultrasound inhibited sensory evoked potentials with a spatial resolution ~2mm.  This method could be used to selectively inhibit thalamic nuclei. Specific trigeminal SSEP suppression occurred and was transient without affecting medial or tibial SSEP.  The converse was true when targeting the ventrolateral thalamic nucleus. There was no observed tissue heating during sonications and no histological evidence of tissue damage. 

Conclusions: Low intensity focused ultrasound can be safely used to reversibly modulate deep neuronal circuits in the central nervous system.  Noninvasive brain mapping with focused ultrasound is likely feasible in humans.

Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

Objective: Ablative procedures are still useful in the treatment of intractable pain despite the proliferation of neuromodulation techniques. Here we present the results of gamma knife thalamotomy (GT) in various pain syndromes.

Methods and Patients: Between 1996 and 2015, we performed unilateral GT in 18 patients (F:M=12:6; age range 53 – 89, mean 80 yrs) suffering from various severe pain syndromes (3 thalamic pain, 5 postherpetic trigeminal neuralgia [TN], 4 resistant classic TN, 3 secondary TN, 2 TN with multiple sclerosis, 1 phantom pain), in whom conservative treatment had failed. The median follow up was 22 months (range 12 –78 months). Invasive procedures for pain release preceded in 13 patients: gamma knife irradiation of the trigeminal nerve, balloon compression or glycerolysis in the cavum Meckeli. The Leksell Sterotactic Frame, GammaPlan Software (Elekta) and T1- and T2-weighted sequences acquired at 1.5 T (Siemens Avanto) were used for localization of the targeted medial thalamus – centrum medianum (CM). The CM was localized 4 – 6 mm lateral to the wall of the 3^rd ventricle, 8mm posterior to the mid-point and 3 mm superior to the intercommissural line. GT was performed by Leksell Gamma Knife with an applied dose ranging from 140 to 155 Gy; single shot, 4 mm collimator. Pain relief after radiation was evaluated. Decreased pain intensity to less than 50 % of the previous level was considered as successful.

Results: Initial successful results were achieved in 8 (44.4 %) of the patients, with complete pain relief in 1 these patients.  Relief was achieved after a median latency of 5 months (range 2 – 36 months). Pain recurred in 4 (50 %) of patients after a median latent interval of 24 months (22 – 30 months). No neurological deficits were observed.

Conclusions: Our results suggest that GT in patients suffering from severe pain syndromes is a relatively successful and safe method that can be used even in severely affected patients. The only risk of GT for our patients was failure of treatment, as we did not observe any clinical side effects.

Supported by MH CZ - DRO (Nemocnice Na Homolce –NNH, 00023884), IG151201

Background

Dorsal root entry zone lesioning (DREZ) lesioning as a treatment of intractable neuropathic pain after brachial pleexus avulsion injury has proven to have long lasting pain relief (1). However, the safety and success of this method depends on accurate localisation of the DREZ. Difficulties in accurately localising the DREZ due to the lack of normal anatomy motivated the development of a neurophysiological techinique to identify the DREZ.

Methods

A multimodal approach was developed over a consecutive series of 22 patients. The method comprised spinal cord somatosensory evoked potentials with peripheral nerve stimulation and spinal cord motor evoked potentials. In addition, the integrity of the ascending and descending pathways was monitord during thermocoagulation radiofrequency lesioning with transcranial motor evoked potentials and somatosensory evoked potentials.

Results

The corticospinal tract and dorsal columns were located reliably using these methods thereby allowing identification of the lesion site lying between these two functional columns. Postoperatively, 90% of patients reported complete pain relief. 10% (2 patients) had partial pain relied and both were at the start of the series whilst the technique was being developed. One has been reoperated and is now pain free. The median follow up period after surgery was 18 months. There were no long term complications but there were transient lower limb clumsiness and numbness reflecting mild dorsal column loss.

Conclusion

A multimodal neurophysiological approach improves the accuracy of localising the DREZ for thermocoagulation lesioning in the treatment of neuropathic deafferentiation pain after brachial plexus avulsion injuries. The results were excellent and long lasting with minor side effects. This continous monitoring provides the additional safety needed to create adequate leaiosn reflected by these good results.

Reference

(1) Microsurgical lesioning in the dorsal root entry zone for pain due to brachial plexus avulsion: a prospective series of 55 patients. Sindou MP, Blondet E, Emery E, Mertens P. J Neurosurg 2005 Jun;102(6):1018-28

Longterm follow-up of bifocal thalamic deep brain stimulation for treatment of chronic neuropathic pain

Mahmoud Abdallat, Andreas Wloch, Hans E. Heissler, Assel Saryyeva, Joachim K. Krauss

Klinik für Neurochirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover

Objective:

To assess long-term efficacy of deep brain stimulation (DBS) for chronic neuropathic pain in consecutive patient.

Methods:

Patients with chronic neuropathic pain which were refractory to medication underwent bifocal thalamic implantation of DBS electrodes. Targets were the centromedian parafascicular nucleus (CM-Pf) and somatosensory thalamus (either nucleus ventralis postereolateralis, VPL, or ventralis postereomedialis, VPM) Elektrodes were implanted by CT-stereotactic surgery and externalized for 4-14 days to assess the effect of the two targets and to decide whether chronic stimulation could be administrated. Therefore DBS electrodes were either removed or a pulse generator was implanted. Assesment of pain included VAS scores and patient self rating. Patients were follow-up regularly at annual visits on longterm.

RESULTS :

Over a period of 16 years, a total of forty patients (20 women, 20 men; mean age of surgery 53.8 years, range 24-73 years) underwent bifocal implantation of thalamic DBS electrodes. Impulse generator were implanted in 33/40 patients for chronic stimulation, while 7 patients did not a chieve adequate benefit during test stimulation. Three patients were lost to follow-up in longterm followup, and in five patients the neurostimulation system was explanted due to infection. On longterm 20/33 had chronic CM-Pf stimulation and 13/33 had VPL/VPM stimulation. In three patients, the target was changed through the years or both electrodes were stimulated in parallel. The properties of marked/ excellent vs moderate/ minor vs no improvement was similar with both targets in longterm follow-up according to patient self-rating.

Conclusions

Pain pathway pass through thalamic relay, it is quite unclear, however, which thalamic nuclei would be the optimal targets for chronic stimulation (paleo-/ neo-spinothalamic tracts).  Good improvement of pain after DBS in the both of targets and no significant difference between CM-Pf and VPL as a good target of DBS for pain. There is significant reduction of analgesics after DBS

Peripheral neuropathic pain (PNP) and Complex Regional Pain Syndrome (CRPS) can be effectively treated with peripheral nerve stimulation (PNS). In this case series report effectiveness of novel, miniature, wirelessly controlled microstimulator of tibial nerve (BlueWind, Israel) in PNP and CRPS was evaluated. In this pilot study the follow-up was 6 months in 6 patients, the average preoperative VAS was 7.5, after 1 month was 2.6 (p=0,03), after 3 months was  1.6 (p =0.03), and after 6 months average VAS score was 1.3 (p=0.02). Mean average score in 6 patients during a week preceding baseline visit was 7.96, preceding  1 month visit 3.32 (p=0,043), preceding 3 months visit 3.65 (p=0,045), preceding 6 moths visit was 2.49 (p=0,002). Average SF-McGill pain score before surgery was 23.8, after 1 month 11.0  (p=0,45), after 3 months was 6.3 (p=0.043), after 6 months 4.5 (p=0,01) . Applied therapy caused reduction of pain immediately after its application and therapeutic effect was observed in the 1^st and the 3^rd months till the 6^th month on similar level in all patients. No complications of the treatment were observed. Intermittent tibial nerve stimulation with the use of novel, miniature, wirelessly controlled device can be effective and feasible in PNP and CRPS. It is a safe, minimally invasive and convenient neuromodulative method.

Introduction: Venous compression is not considered a classical cause of trigeminal neuralgia. Outcome after decompression of such neurovascular conflicts has not been yet thoroughly studied. The objective of this study is to describe the clinical characteristics and outcome in a series of patients with classical TN due to venous compression.

Material and methods: All patient with suffering from TN treated by microvascular decompression (MVD) from 2005 to 2013 were included if a significant venous compression was found at the surgery. Patients were evaluated for clinical presentation, operative findings and the long-term outcome. Patients were considered as successfully treated for their trigeminal neuralgia if they were classed as BNI I or II.  Kaplan-Meier analysis was used to determine probability of success at ten years follow up.

Results: Out of 313 patients having been treated by MVD during the study period in 55 (17.5%) a vein was the main compressive vessel, in 26 (8.3%) it was the only compressive vessel.  Probability of relief with no need for medication at ten years was 70.6%. The patients with focal arachnoiditis had a poor long term outcome BNI III-V 71% compared to 14.5% without (p=0.0037 Fisher’s exact test). Degree of compression did not significantly influence outcome. No differences in outcome were found between patient presenting purely venous compression and mixed venous and arterial compression. Atypical trigeminal neuralgia and degree of compression were not prognostic factors in this series.

Conclusion: Venous neurovascular conflict as a cause of trigeminal neuralgia is far from rare. Microvascular decompression in cases with evident compression on imaging studies gives a good probability of pain relief encouraging to propose surgery for such patients.