Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Long-Term Experience with Occipital and Supraorbital Nerve Stimulation for the Various Headache Disorders-A Retrospective Institutional Case Series of 96 Patients.

OBJECTIVE: We have provided long-term data on clinically meaningful pain alleviation for drug-refractory headache disorders using occipital (ONS) and supraorbital nerve stimulation (SONS). METHODS: We performed a retrospective review of 96 patients with migraine, cervicogenic headache, cluster headache, neuropathic pain of the scalp, tension-type headache, and new daily persistent headache who had undergone ONS (61.5%), SONS (11.5%), or combined ONS plus SONS (27.1%) trial implantation and definitive implantation from 2007 to 2017. Changes in pain perception over time were monitored using the visual analog scale (VAS) for pain. RESULTS: The cohort consisted of 60.4% women and 39.6% men, with a mean age of 46.9 ± 11.5 years and pain duration of 14 ± 14.1 years. Of the 96 patients, 65 (67.7%) were treatment responders to a trial (≥30% amelioration in the average or maximum VAS score for pain and/or number of headache days) that had lasted 22.5 ± 8.8 days. The reduction in their average VAS score for pain was to 37% ± 24.4% of baseline compared with 99.1% ± 24.1% of baseline for those without a response (P < 0.01). Of the 56 patients who had undergone implantation and had long-term follow-up data available for ≤10 years, 32 (57.1%) reported a ≥50% reduction in their average VAS score for pain. Four patients (6.5%) had requested hardware explantation. Stage II complications included 1 infection (1.6%) and 6 electrode dislocations (9.7%). The study limitations included the retrospective nature, lack of controls receiving placebo intervention, and randomization. CONCLUSIONS: After careful patient selection according to a positive response to a trial of ONS and/or SONS, clinically meaningful long-term benefit was achieved in 57.1% of our patients with various chronic headache conditions.

Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients.

BACKGROUND: Benefits of dopaminergic therapy and deep brain stimulation are limited and unpredictable for axial symptoms in Parkinson's disease. Dorsal spinal cord stimulation may be a new therapeutic approach. The objective of this study was to investigate the therapeutic effect of spinal cord stimulation on gait including freezing of gait in advanced PD patients. METHODS: Five male PD participants with significant gait disturbances and freezing of gait underwent midthoracic spinal cord stimulation. Spinal cord stimulation combinations (200-500 µs/30-130 Hz) at suprathreshold intensity were tested over a 1- to 4-month period, and the effects of spinal cord stimulation were studied 6 months after spinal cord stimulation surgery. Protokinetics Walkway measured gait parameters. Z scores per gait variable established each participant's best spinal cord stimulation setting. Timed sit-to-stand and automated freezing-of-gait detection using foot pressures were analyzed. Freezing of Gait Questionnaire (FOG-Q), UPDRS motor items, and activities-specific balance confidence scale were completed at each study visit. RESULTS: Spinal cord stimulation setting combinations of 300-400 µs/30-130 Hz provided gait improvements. Although on-medication/on-stimulation at 6 months, mean step length, stride velocity, and sit-to-stand improved by 38.8%, 42.3%, and 50.3%, respectively, mean UPDRS, Freezing of Gait Questionnaire, and activities-specific balance confidence scale scores improved by 33.5%, 26.8%, and 71.4%, respectively. The mean number of freezing-of-gait episodes reduced significantly from 16 presurgery to 0 at 6 months while patients were on levodopa and off stimulation. CONCLUSIONS: By using objective measures to detect dynamic gait characteristics, the therapeutic potential of spinal cord stimulation was optimized to each participant's characteristics. This pilot study demonstrated the safety and significant therapeutic outcome of spinal cord stimulation in advanced PD patients, and thus a larger and longer clinical study will be conducted to replicate these results. © 2018 International Parkinson and Movement Disorder Society.

Stimulation of the Spinal Cord and Dorsal Nerve Roots for Chronic Groin, Pelvic, and Abdominal Pain.

BACKGROUND: Chronic neuropathic groin pain is a common problem. It can arise following surgery or trauma, or spontaneously as part of various pelvic pain syndromes. A number of different stimulation techniques have been reported in the literature to treat this area, but due to the complex anatomy of the region, it can be difficult to target effectively with paresthesias. OBJECTIVES: In this study we report our results treating patients with chronic neuropathic groin, pelvic, and abdominal pain, using spinal cord stimulation and dorsal nerve root stimulation. STUDY DESIGN: Open label, prospective study that includes all patients treated with a new trial stimulator system at a single center between July 1, 2011, and October 31, 2013. SETTING: Academic university neurosurgical pain center, Canada. METHODS: Thirty-two patients had trials of spinal cord stimulation and/or dorsal nerve root stimulation in the thoracic or lumbar spine. Patients were evaluated on visual analog scale pain scores, SF-36, and morphine equivalent daily dose. Data were recorded at the pre-implant visit, and 3, 6, and 12 months following permanent implant. RESULTS: The 15 patients who went on to permanent implants had, on average, significant pain reduction and improvements in quality of life at the 12 month follow-up. The majority of patients who were taking opioids at the initial assessment were able to reduce their dose with treatment. Three patients with successful trials were long-term non-responders, of whom 2 had the permanent device removed. LIMITATIONS: This study would benefit from a larger sample size that would have adequate power for comparisons between patient subgroups and stimulation techniques. CONCLUSION: Dorsal nerve root stimulation is an effective long-term treatment for neuropathic groin pain.

Double dissociation of selective recollection and familiarity impairments following two different surgical treatments for temporal-lobe epilepsy.

Research has firmly established that the integrity of the medial temporal lobe (MTL) is critical for recognition memory. This ability is supported by recollection, which involves recovery of contextual details of a past stimulus encounter, and familiarity assessment, which leads to awareness of prior occurrence without such recovery. Dual-process models of MTL organization posit that recollection and familiarity are supported by the hippocampus and perirhinal cortex, respectively. Alternatively, it has been argued that both structures support these recognition processes similarly as part of a more integrated declarative memory system; from this perspective, reported selective recollection impairments with circumscribed hippocampal lesions may reflect differential sensitivity to overall memory strength, rather than a deficit in a distinct recognition process. Findings from past neuropsychological research remain inconsistent and controversial, in part due to biases in patient selection, variability in clinical etiology, and limited lesion documentation. Here, we administered a verbal recognition-memory task in combination with remember-know judgements to 10 individuals who had undergone left- or right-sided stereotactic amygdalo-hippocampotomy as a surgical treatment for intractable temporal-lobe epilepsy. Comparisons with healthy control participants revealed isolated impairments in recollection with preserved familiarity, regardless of hemispheric site of lesion. In addition, we show that this impairment can be observed at a comparable level of memory strength (i.e., overall recognition performance) as the selective familiarity impairment we previously described in N.B.--an individual who underwent a tailored surgical resection of the left anterior temporal lobe with hippocampal sparing for treatment of temporal-lobe epilepsy. By revealing a double dissociation concerning temporal-lobe mechanisms for recollection and familiarity, this evidence argues against a unitary, strength-based account of MTL organization.

Bilateral hippocampal stimulation for intractable temporal lobe epilepsy: impact on seizures and memory.

The effect of continuous electrical stimulation of the hippocampus bilaterally on seizures and memory was assessed in two subjects with seizures from both mesial temporal lobes who were not candidates for resective epilepsy surgery. A double blind, randomized, controlled, cross-over trial design was utilized. Two electrodes with four contacts each were implanted along the axis of the hippocampus bilaterally. Simultaneous stimulation of all electrodes contacts was either on or off during each 3-month interval. Seizure frequency decreased by 33% in the two patients during stimulation and remained lower by 25% for the 3 months after stimulation was turned off before returning to baseline (p < 0.01). No consistent change in objective or subjective measures of memory occurred. No other adverse effects occurred. Seizure frequency is reduced both during and for a period after bilateral hippocampal stimulation, but the overall impact in this study is not as robust as has been previously reported.

Visualization and navigation system development and application for stereotactic deep-brain neurosurgeries.

We present the development of a visualization and navigation system and its application in pre-operative planning and intra-operative guidance of stereotactic deep-brain neurosurgical procedures for the treatment of Parkinson's disease, chronic pain, and essential tremor. This system incorporates a variety of standardized functional and anatomical information, and is capable of non-rigid registration, interactive manipulation, and processing of clinical image data. The integration of a digitized and segmented brain atlas, an electrophysiological database, and collections of final surgical targets from previous patients facilitates the delineation of surgical targets and surrounding structures, as well as functional borders. We conducted studies to compare the surgical target locations identified by an experienced stereotactic neurosurgeon using multiple electrophysiological exploratory trajectories with those located by a non-expert using this system on 70 thalamotomy, pallidotomy, thalamic deep-brain stimulation (DBS), and subthalamic nucleus (STN) DBS procedures. The average displacement between the surgical target locations in both groups was 1.95 +/- 0.86 mm, 1.83 +/- 1.07 mm, 1.88 +/- 0.89 mm and 1.61 +/- 0.67 mm for each category of surgeries, respectively, indicating the potential value of our system in stereotactic deep-brain neurosurgical procedures, and demonstrating its capability for accurate surgical target initiation.

Hemiparkinsonism-somatic hemiatrophy syndrome.

PURPOSE: This paper highlights the hemiparkinsonism-hemiatrophy (HPHA) syndrome as a unique presentation of the parkinsonian state. Clinically relevant diagnostic and treatment aspects are reviewed. METHOD: We report a case of HPHA, in a 21-year-old, otherwise healthy, woman. Clinical and radiographic features of our case are presented. We also review the current literature on the clinical, radiological and pathophysiological mechanisms of HPHA. RESULTS: In our case, despite the lack of benefit from anticholinergics and dopamine agonists (the patient declined treatment with levodopa), the patient showed a dramatic improvement with subthalamic nucleus stimulator (STN) implantation. There are no reported cases of use of STN stimulator in HPHA. CONCLUSION: Hemiparkinsonism-hemiatrophy is a distinct entity that may be clinically and pathogenetically different from idiopathic Parkinson's disease; hence, HPHA needs to be considered as a possible syndrome in patients that have persistent unilateral parkinsonism. As medications are reported to be unhelpful in HPHA cases, early surgical intervention may be an option, such as in our case.