Background: Tourette syndrome (TS) is a chronic neuropsychiatric disorder that presents with a combination of vocal and motor tics. Since 1999, deep brain stimulation (DBS) can be considered a therapeutic option for patients with treatment-refractory TS. The aim of this study is to evaluate long-term (>5 years) follow-up in TS patient treated with DBS. Methods: We retrospectively assessed all TS patients treated with DBS within a 10-year time period between 2009 and 2019. Demographic data, stimulation parameters, response of tics to chronic DBS and quality of life were evaluated. Clinical outcome was assessed using self-assessment scales (i.e.YGTSS). Results: A total of 22 TS patients (5 female, 17 male) were implanted for the treatment of severe tics. One patient received GPi DBS, while the targets for all remaining patients were located in the thalamus, predominantly in the centromedian nucleus/nucleus ventro-oralis internus (CM/V oi). The average age at the time of the initial implantation was 31.9 (SD = 11.2). 21 patients (95%) were available for long-term follow-up. The mean time interval since the initial implantation was 9.9 years (SD = 3.0). Of the 21 patients, 17 (81%) were responders with active stimulation. Three patients turned off the stimulation – one patient did not benefit, one patient's tics improved significantly even without stimulation and one patient's vocal tics disappeared completely, while motor tics showed little response to stimulation. In self-assessment, tics decreased on average by 73% under stimulation compared to the preoperative condition, while the premonitory urge diminished by 57%, and the quality of life improved by 77%.The Yale Global Tic Severity Scale (YGTSS), a gold standard for assessing tics in TS, was available for twelve patients during the long-term follow-up. The average YGTSS score decreased from 79.7 (SD = 16.4) preoperatively to 36.0 (SD = 24.3) after 12 months, and 24.2 (SD = 14.5) in the long-term follow-up, demonstrating persistent and even increasing significant improvement (p < 0.001). Complications leading to surgical revisions occurred in five patients. There were two instances of a short circuit due to a defect in the extension, one case of electrode dislocation following a fall during an epileptic seizure, and two cases of infection, each requiring the explantation of the entire DBS system, with reimplantation done in one instance. Conclusions: DBS for TS patients remains a highly effective therapy over many years after the implantation with a further tendency for improvement in the long-term.

Introduction: Over the past decade there has been increased use of laser interstitial thermal therapy (LITT) for stereotactic laser ablation (SLA) as an alternative to open resective procedures including anterior temporal lobectomy (ATL). Retrospective studies evaluating SLA for the treatment of mesial temporal lobe epilepsy (MTLE) have been promising, demonstrating slightly lower seizure freedom rates but fewer side effects and improved patient recovery. Here we report primary results from the SLATE trial, the first large prospective study to evaluate the safety and efficacy of the Visualase System in subjects with MTLE due to mesial temporal sclerosis (MTS). Methods: Prospective, single-arm, observational, multicenter study with outcomes compared against known effects of ATL. Pre-surgical evaluation consisted of a central review of each subject’s epilepsy history, MRI, EEG and any additional testing results available (e.g., PET, SPECT, invasive EEG or MEG) to confirm study qualification for treatment of their MTLE. Eligible subjects underwent unilateral MRI-guided SLA of their amygdala and hippocampus with the Visualase System (fig. 1) and were followed for 12 months. Results: In this study, 167 subjects were enrolled across 21 sites in the United States. 114 subjects received treatment across 18 sites and 107 subjects successfully completed the study (without a retreatment). One subject was retreated in the study between 3 and 6 months. The mean age of treated subjects was 44.2 ± 13.9 years (58.8% female). The average years from epilepsy diagnosis was 24.0 ± 17.2 years, and the average monthly seizure frequency of all seizure types over the 12 months prior to enrollment was 11.5 ± 15.4 seizures (median 4.5 seizures). Five subjects (4.4%) had a vagus nerve stimulator. Seventy-four patients (64.9%) had left sided SLA. At 12 months, 56.0% (95% LCI: 46.2%) of subjects had an Engel I outcome and were free of disabling seizures (Engel IA/IB). No subjects reported generalized convulsions with ASM discontinuation (Engel ID). The average change from baseline in the QOLIE-31 overall score was 9.4 ± 9.8 (N=93), with 38 (40.9%) subjects experiencing a clinically significant increase (≥ 11.8). The greatest improvement in quality of life (QOL) was in Engel I subjects. Performance on neuropsychological measures related to cognition and language, verbal learning and memory, and visual reproduction appeared stable between baseline and 1-year post-surgical evaluation at the group level, with none of the tests showing changes that would indicate a clinically meaningful decline. Mood assessments at 1-year showed mean reductions in depression (Beck Depression Inventory) and anxiety (Beck Anxiety Inventory) of -4.4 ± 7.9 (37.6%) and -4.7 ± 9.1 (43.4%), respectively. There were 157 adverse events (AEs) reported in 73 (64%) treated subjects through 12 months post-enrollment. For the primary safety endpoint, the incidence of qualifying device, procedure, or anesthesia related AEs through 12 months was 10 events in 9 treated subjects (7.9%) (95% UCI: 14.5%) and included the following: postoperative wound infection (1), soft tissue infection (1), upper respiratory tract infection (1), cognitive disorder (1), headache (3), partial seizures with secondary generalization (1), quadrantanopia (1), and confusional state (1). The most commonly reported visually related AEs post enrollment were quadrantanopia (21 subjects, 18.4%) and visual field defects (5 subjects, 4.4%), and were either mild (24) or moderate (2) in severity. One quadrantanopia event was classified as moderate and permanent, qualifying for the primary safety endpoint. No deaths or unanticipated adverse events were observed. Conclusions: The SLATE study passed both its primary safety and efficacy endpoints. The Engel I rate at 1 year was 56%, which is consistent with prior studies evaluating SLA in patients with MTS, but lower than an historical benchmark for open surgical resection (Engel I 64%). Notable clinical improvements in QOL were observed with no reports of SUDEP. Neuropsychological outcomes appeared to be superior to that of open resection procedures, which are known to result in significant post-surgical declines in language and memory for a large proportion of patients even when MTS is present. The results from the SLATE study demonstrate that SLA is an effective and well-tolerated therapy that may be used in place of open resective procedures for MTLE.

Essential tremor (ET) can be extremely disabling, may not respond to conservative therapy, and is often bilateral. Other than the phase three clinical trial data, experience with outcomes following bilateral MRgFUS thalamotomy is limited. We report on a single-institution cohort of ET patients who underwent staged bilateral MRgFUS thalamotomy from 2020 to 2024, with minimum three-months of follow-up after bilateral treatment. Follow-up occurred at three, six, 12, and 24+ months post-treatment. Upper extremity tremor was assessed using the Clinical Rating Scale for Tremor Part B (CRST-B) and normalized based on maximum score for dominant and non-dominant arms (nCRST-B). Patients were asked directly about six adverse effects (speech changes, sensory changes, gait disturbance, dysphagia, dysgeusia, and upper extremity ataxia) and their satisfaction with the decision to undergo bilateral treatment. Thirty patients underwent staged bilateral MRgFUS thalamotomy, mostly to treat their non-dominant arm (86.7%). Of the 30 patients, 25 (83%) have 6-month follow-up, 19 (63%) have 12-month follow-up, and 10 (33%) have 24+ months of follow-up. The median time between unilateral and staged-bilateral treatment was 11.6 months (IQR 9.7 – 13.8; Range 6.0 – 21.6). Tremor severity at baseline for the unilateral and bilateral sides was similar (nCRST-B 63.5% and 67.7% respectively), and was significantly improved bilaterally after MRgFUS, but not as greatly on the second treated side (nCRST-B of 17.0% for unilateral and 33.1% for bilateral sides at combined last follow up for patients with minimum six-months of data). Most patients reported at least one new adverse effect after bilateral treatment (86.7%), although these were largely mild (Figure 1). Notably, 70% reported speech changes at three-months, improving to 53% at 12-months; 50% reported sensory changes at three-months, improving to 26% at 12-months; 40% reported gait disturbance, improving to 21% at 12-months; 30% reported dysphagia at three-months, improving to 16% at 12-months; 23% reported dysgeusia at three-months, improving to 11% at 12-months; and 7% reported upper extremity ataxia at three-months, improving to 5% at 12-months. When asked whether they considered bilateral treatment worthwhile in retrospect, 83% patients reported “yes” at three- and six-months, but this declined to 71% at 12-months, and 60% at 24+ months. In this series, rates of patient-reported adverse effects were higher than expected after staged bilateral MRgFUS thalamotomy for ET. In combination with less complete tremor control, adverse effects appeared to contribute to lower patient satisfaction at 12-months and 24+ months after bilateral treatment.