Tourette Syndrome Treatment Updates: a Review and Discussion of the Current and Upcoming Literature.

PURPOSE OF REVIEW: This study aims to examine the treatments currently available for Tourette syndrome (TS) and to discuss evolving therapies, spanning behavioral, pharmacologic, complementary and alternative medicine, and neuromodulation approaches. RECENT FINDINGS: Behavioral therapies have undergone several modifications to improve accessibility, including transitioning to a virtual format which is particularly important in the current pandemic. There are several recent or ongoing pharmacologic studies that have shown promise including the selective D1 receptor antagonist ecopipam and various cannabinoid compounds. Adaptive DBS may enable the physiologic markers of tics to determine stimulation parameters and improve tic outcomes related to neuromodulation. In recent years, there has been a wealth of research across multiple treatment domains in the TS field. This review highlights exciting and new potential options for the future treatment of patients with TS.

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

Importance: Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. Objective: To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. Design, Setting, and Participants: The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. Exposures: Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). Main Outcomes and Measures: Scores on the Yale Global Tic Severity Scale and adverse events. Results: The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]). Conclusions and Relevance: Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

Hypertensive urgency: an important aetiology of rebound hypertension.

A 46-year-old African-American man with a history of hypertension, end-stage kidney disease (on haemodialysis) and previous cocaine misuse presented to the emergency room with a sudden onset of severe headache and diaphoresis without other neurological or cardiovascular signs/symptoms. He checked his blood pressure at home and found it to be 230/130. It did not improve despite taking two serial doses of oral clonidine 0.3 mg. Evaluation with head CT and lumbar puncture demonstrated no acute intracranial process, such as subarachnoid haemorrhage. These symptoms started after he took Libido-Max, an over-the-counter supplement for erectile dysfunction. This supplement includes yohimbine, an α-2 antagonist, which counteracts the effects of oral clonidine, one of his routine antihypertensive medications. This led to rebound hypertension and made his hypertensive urgency resistant to oral clonidine. He was successfully treated with intravenous labetalol and his symptoms quickly resolved after lowering of his blood pressure.

A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms.

OBJECTIVE: To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. DESIGN: We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. SETTING: A university movement disorders center. PATIENTS: Five patients with implanted DBS. MAIN OUTCOME MEASURE: A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. CONCLUSIONS: This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01329198.

DBS candidates that fall short on a levodopa challenge test: alternative and important indications.

INTRODUCTION: Candidacy for deep brain stimulation (DBS) in Parkinson disease (PD) is typically assessed by the preoperative motor response to levodopa along with an interdisciplinary evaluation. However, recent cases treated at our institution have achieved good outcomes with DBS despite a sub-30% improvement in motor scores. The aim of this study was to examine the outcomes of DBS in a subset of patients who failed to reach the 30% motor improvement threshold. METHODS: A review of all DBS patients treated at the University of Florida Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS database. All patients with sub-30% improvement in Unified Parkinson Disease Rating Scale Part III after dopaminergic medication administration were included. RESULTS: Nine patients were identified; DBS was performed for severe dyskinesia (n=5), "on/off motor" fluctuations (n=1) and medication-refractory tremor (n=3). The target symptoms were improved in all patients. Postoperatively, scores on the Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson disease questionnaire-39 improved (P<0.05). CONCLUSIONS: Although motor response to levodopa remains the primary selection criteria for DBS candidacy in Parkinson disease, patients who do not meet the 30% threshold and have disabling symptoms may still benefit from DBS. Select patients with severe dyskinesia, "on/off" motor fluctuations, and/or medication-refractory tremor may experience significant benefits from DBS and should be considered on a case by case basis through an interdisciplinary team evaluation.