Faculty Bibliography

BACKGROUND:Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS:We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS:Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION/CONCLUSIONS:The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

BACKGROUND AND PURPOSE/OBJECTIVE:The basal forebrain contains multiple structures of great interest to emerging functional neurosurgery applications, yet many neuroradiologists are unfamiliar with this neuroanatomy because it is not resolved with current clinical MR imaging. MATERIALS AND METHODS/METHODS:= 13) to demonstrate and characterize the detailed anatomy of the basal forebrain using a clinical 3T MR imaging scanner. We measured the size of selected internal myelinated pathways and measured subthalamic nucleus size, oblique orientation, and position relative to the intercommissural point. RESULTS:= .084 and .047, respectively). Individual variability for the subthalamic nucleus was greatest for angulation within the sagittal plane (range, 15°-37°), transverse dimension (range, 2-6.7 mm), and most inferior border (range, 4-7 mm below the intercommissural plane). CONCLUSIONS:Direct identification of basal forebrain structures in multiple planes using the TSE T2 sequence makes this challenging neuroanatomy more accessible to practicing neuroradiologists. This protocol can be used to better define individual variations relevant to functional neurosurgical targeting and validate/complement advanced MR imaging methods being developed for direct visualization of these structures in living patients.

Decisions are made through the integration of external and internal inputs until a threshold is reached, triggering a response. The subthalamic nucleus (STN) has been implicated in adjusting the decision bound to prevent impulsivity during difficult decisions. We combine model-based and model-free approaches to test the theory that the STN raises the decision bound, a process impaired by deep brain stimulation (DBS). Eight male and female human subjects receiving treatment for Parkinson's disease with bilateral DBS of the STN performed an auditory two-alternative forced choice task. By ending trials unpredictably, we collected reaction time (RT) trials in which subjects reached their decision bound and non-RT trials in which subjects were forced to make a decision with less evidence. A decreased decision bound would cause worse performance on RT trials, and we found this to be the case on left-sided RT trials. Drift diffusion modeling showed a negative drift rate. This implies that in the absence of new evidence, the amount of evidence accumulated tends to drift toward zero. If evidence is accumulated at a constant rate this results in the evidence accumulated reaching an asymptote, the distance of which from the bound was decreased by DBS (p = 0.0079, random shuffle test), preventing subjects from controlling impulsivity. Subjects were more impulsive to bursts of stimuli associated with conflict (p < 0.001, cluster mass test). In addition, DBS lowered the decision bound specifically after error trials, decreasing the probability of switching to a non-RT trial after an error compared to correct response (28% vs. 38%, p = 0.005, Fisher exact test). The STN appears to function in decision-making by modulating the decision bound and drift rate to allow the suppression of impulsive responses.

Objectives: Patient satisfaction is one determinant of quality health care (Kondziolka et al. 2013). The performance of surgical procedures on conscious patients dictates unique considerations of patient comfort, experience, and satisfaction. In this study, we sought to better understand patients' experience during each stage of deep brain stimulation (

Objectives: STN stimulation is an effective treatment for Parkinson's disease but has been implicated in increasing impulsivity in patients. We sought to identify single unit and local field potential signatures associated with the correction of preplanned movement sequences in response to external stimuli.
Method(s): 6 patients with Parkinson's disease undergoing

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.

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: Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. METHODS: Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4-6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. FINDINGS: Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. INTERPRETATION: This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. FUNDING: Abbott (previously St Jude Medical).

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.