Faculty Bibliography

OBJECTIVE:The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the treatment of Parkinson disease (PD)-related tremor has been well established. However, the relative impact on arm, leg, and chin tremor has been less clearly elucidated. The authors evaluated the distribution of tremors in a PD cohort undergoing STN DBS and sought to evaluate the differential impact of DBS as a function of tremor location. METHODS:A retrospective study of patients with PD with tremor who underwent DBS surgery between 2012 and 2016 was performed to evaluate the impact of STN stimulation on overall and regional tremor scores. RESULTS:Across 66 patients the authors found an average of 78% overall reduction in tremor after 6 months. In this cohort, the authors found that tremor reduction was somewhat better for arm than for leg tremors, especially in instances of higher preoperative tremor (84% vs 71% reduction, respectively, for initial tremor scores ≥ 2). No significant difference in response was found between patients with medication-responsive versus medication-nonresponsive tremors. CONCLUSIONS:The authors found that although DBS improved tremor in all regions, the improvement was not uniform between chin, arm, and leg-even within the same patient. The reasons behind these differing responses are speculative but suggest that STN DBS may more reliably reduce arm tremors than leg tremors.

Introduction: Deep brain stimulation (

Importance/UNASSIGNED:Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. Objective/UNASSIGNED:To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. Design, Setting, and Participants/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:Scores on the Yale Global Tic Severity Scale and adverse events. Results/UNASSIGNED: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 12.97 (5.58) 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/UNASSIGNED: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.

OBJECTIVE Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS. METHODS The authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient's pre- and postoperative images. RESULTS Patients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up. CONCLUSIONS The authors' data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.

BACKGROUND: The development of cysts at the electrode lead is a rare complication of deep brain stimulation (DBS), with only 3 cases reported in the literature. A better understanding of the variable clinical presentations and courses of these cysts may help increase awareness of this potentially life-threatening complication. OBJECTIVE: To review the clinical presentation of patients with intraparenchymal cysts following DBS implantations. METHODS: We report 3 patients who developed a cyst along the course of the DBS lead. These patients received DBS for different indications and in different brain locations. RESULTS: Clinical courses differed considerably with 1 asymptomatic patient followed conservatively, 1 mildly symptomatic patient who had the DBS hardware removed for insidious worsening over months, and 1 who had it emergently removed for acute development of hydrocephalus. Serial imaging revealed spontaneous reduction in cyst size over time in the asymptomatic patient, and following removal in 1 of the symptomatic patients. CONCLUSION: This report highlights the variable clinical presentation and course of patients who develop cysts along the DBS lead. It suggests that some cases can be followed clinically without removal of hardware but that ongoing vigilance is required given the potential for serious adverse events.

Out of approximately 600 deep brain stimulation surgeries performed at our center over 10 years, 5 patients received "rescue"

BACKGROUND: Targeting the subthalamic nucleus (STN) for deep brain stimulation (DBS) using standard stereotactic coordinates in conjunction with high-resolution magnetic resonance imaging (MRI) generally results in effective symptomatic relief for the cardinal motor features of Parkinson's disease (PD). The angle of approach, however, influences the resultant field of stimulation and can lead to undesired side effects. METHODS: We review a case where symptomatic improvement was accompanied by significant side effects despite reasonable STN stereotactic base coordinates. Revision of the lead using similar base coordinates but a significantly different angle of approach greatly improved the outcome. RESULTS: Stimulation ventromedial to the STN improved tremors but brought about dysarthria and dystonia. Computer-based stimulation field modeling helped understand the regions associated with the side effects and illustrate the difference between pre- and post-revision stimulation fields. CONCLUSION: Lead angle can impact DBS outcome and should be taken into consideration.

Tourette Syndrome (TS) is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS), already widely utilized for Parkinson's disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with DBS worldwide, have delayed regulatory agency approval (e.g., FDA and equivalent agencies around the world). The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry.

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.