Outcome Of Deep Brain Stimulation Research Articles

Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.

Parkinson’s disease may be caused by a single pathogenic variant (monogenic) in 5–10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson’s disease genes include autosomal dominant forms (SNCA, LRRK2, and VPS35) and autosomal recessive forms (PRKN, PINK1 and DJ1). Furthermore, mutations in the GBA gene are a key risk factor for Parkinson’s disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as ATP13A2, DCTN1, DNAJC6, FBXO7, PLA2G6, and SYNJ1. Furthermore, numerous genes have recently been implicated in Parkinson’s disease, such as CHCHD2, LRP10, TMEM230, UQCRC1, and VPS13C. Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson’s disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson’s disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.

818 Association Between Intraoperative LFP, Lead Location, and Outcomes in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

INTRODUCTION: Imaging-based, LFP-based and empirical programming strategies can be used to determine the optimal therapeutic contact for deep brain stimulation, but the most efficient strategy is unclear. METHODS: In this prospective, IRB-approved study, 10 awake patients were implanted with bilateral STN DBS using both an electrophysiologically- and imaged-confirmed technique. Once the DBS lead had been secured, LFP signals were recorded with a Grapevine Neural Amplifier (Ripple Neuro, UT) at 30 KHz and 16-bit A/D resolution, and LFPs were down-sampled to 2 KHz before further processing. Stereotactic CTs acquired two weeks postoperatively were fused to the pre-operative 3T, T2 weighted MRI and processed using the SureTune platform (Medtronic, MN). Therapeutic DBS programming parameters were obtained 6 months post-implantation, along with pre- and post-operative UPDRS Part III scores. RESULTS: There was a 54% reduction in the UPDRS score when comparing the preoperative OFF score, to the 6 month postoperative OFF Meds/ON Stimulation Score. 50% of the chosen contacts were in the STN only, 10% in the ZI only, and 35% in both. One lead was found to be outside the segmented STN and ZI; this patient did not experience clinical improvement based on their Part III UPDRS score. Beta (8-30Hz) power was 4.1 times higher for electrodes within the STN versus out, 1.4 times for ZI versus out, and 5.9 times higher for both versus neither. The average beta power was 15% higher in the chosen therapeutic contacts over those contacts not used. Lastly, we found that the number of electrodes within the STN correlated with the decrease in the UPDRS score (r=0.27). CONCLUSIONS: There is a strong correlation between image-based electrode localization, LFP characteristics, and clinical outcomes in patients undergoing STN DBS for Parkinson Disease. Focused programming strategies based on either imaging or LFP data can facilitate identification of the optimal therapeutic contact.

Seed-Based Connectivity Prediction of Initial Outcome of Subthalamic Nuclei Deep Brain Stimulation.

Subthalamic nuclei deep brain stimulation (STN-DBS) is a well-established treatment for Parkinson's disease (PD). Some studies have confirmed the long-term efficacy is associated with brain connectivity; however, whether the initial outcome is associated with brain connectivity and efficacy of prediction based on these factors has not been well investigated. In the present study, a total of 98 patients were divided into a training set (n = 78) and a test set (n = 20). The stimulation and medication responses were calculated based on the motor performance. The functional and structural connectomes were established based on a public database and used to measure the association between stimulation response and brain connectivity. The prediction of initial outcome was achieved via a machine learning algorithm-support vector machine based on the model established with the training set. It was found that the initial outcome of STN-DBS was associated with functional/structural connectivities between the volume of tissue activated and multiple brain regions, including the supplementary motor area, precentral and frontal areas, cingulum, temporal cortex, and striatum. These factors could be used to predict the initial outcome, with an r value of 0.4978 (P = 0.0255). Our study demonstrates a correlation between a specific connectivity pattern and initial outcome of STN-DBS, which could be used to predict the initial outcome of DBS.

Optimization of fast gray matter acquisition T1 inversion recovery (FGATIR) on 7T MRI for deep brain stimulation targeting

Deep brain stimulation (DBS) is an increasingly utilized treatment for multiple neurological disorders. Continued improvements in DBS outcome are, in part, related to increasing ability to directly visualize stimulation targets by MRI. However, it is challenging to image DBS targets with conventional MRI techniques due to limited contrast. Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) is a commonly used MRI sequence that improves visualization of several key DBS targets by suppressing white matter (WM) signal to better reveal deep-brain gray matter (GM) structures. Due to increased signal level at high field strength, application of FGATIR on 7T MRI may allow higher spatial resolution and better DBS targeting accuracy. However, successful utilization of FGATIR requires meticulous sequence optimization involving multiple parameters to maximize GM signal while suppressing WM. This is further complicated by the transmit RF field (B1+) inhomogeneity on 7T, which can cause severe contrast degradation. In this work, we introduce a systematic approach to optimize FGATIR and to improve visualization of thalamic DBS targets on 7T. FGATIR optimization is cast into a constrained optimization problem whose objective function and constraints are designed to maximize the GM-WM contrast-to-noise ratio (CNR) while accounting for B1+ inhomogeneity. This approach allows a systematic search for optimal parameters across the multi-dimensional parametric space while limiting the negative effect of B1+ variation. Bloch equation simulations were performed to solve the proposed optimization problem and to compare the sequence derived from this method against the sequence optimized without considering B1+ inhomogeneity. The results showed that this approach can improve GM-WM CNR in the presence of B1+ inhomogeneity, especially in some high relative B1+ areas where several key thalamic DBS targets are located. Additionally, in vivo images were acquired on a clinical 7T MRI to further validate this approach. Severe contrast degradation in the thalamus was observed when B1+ effect was not considered in sequence optimization, while the proposed approach yielded improved image contrast in the thalamus with key DBS targets well-defined. These results demonstrated that the proposed method allowed optimization of FGATIR on 7T to better visualize thalamic DBS targets, which may lead to improved DBS targeting accuracy as well as treatment outcome.

Psychopathological and neuropsychological outcomes of deep brain stimulation for severe- treatment-resistant obsessive-compulsive disorder: An open-label case series

ObjectiveDeep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive–compulsive disorder (OCD). The present study describes the outcomes of the first DBS procedures for OCD in Iran. MethodsFour women patients (age range, 25–35 years) with severe OCD meeting stringent criteria for refractoriness to treatment were selected by Psychosurgery Review Board. DBS electrodes were bilaterally implanted in the internal capsule and nucleus accumbens (NAc). Clinical and neuropsychological assessments were undertaken before and after implantation. The outcomes included Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), neuropsychological assessments including the Wisconsin Card Sorting Test, Wechsler Memory Scale, and adverse events. ResultsThe baseline mean score of the Y-BOCS and HAM-A was 32 ± 6 and 23 ± 14 respectively and decreased to 26 ± 8 and 17 ± 9 after one-year implantation, showing a 19% improvement. Two patients were responders and showed a notable improvement. One patient's score declined 28%, who was not satisfied with DBS results, and one patient worsened under-stimulation. Improvements in the severity of anxiety and cognitive performance were consistent with OCD improvement, and the successfully treated patients showed improvement in anxiety and cognitive performance. No significant cognitive declines were seen. Two patients' suicidal ideation appeared after DBS as an important adverse event. ConclusionBilateral DBS of the internal capsule/NAc may be an effective and safe treatment for treatment-refractory OCD. However, there is a need to consider accessibility, high cost, cost-effectiveness, and standardized methodology in future research.

Axial Impairment Following Deep Brain Stimulation in Parkinson's Disease: A Surgicogenomic Approach.

Background: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed “surgicogenomics”.Objective: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson’s disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome.Methods: Retrospective clinical data was extracted from 150 patient’s charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score.Results:NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2.Conclusion:Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.

Long-term Outcome of Deep Brain Stimulation in Intralaminar Thalamus for Refractory Tourette Syndrome: A Case Report

BACKGROUND: Tourette syndrome (TS) is a neurobehavioral disease that has onset at an early age around 5–7 years old. This disease affects 0.3–0.8% of young age population. With criteria diagnosis at least one vocal and two motor tics beginning before 18 years old. The symptoms of tics remain unusual from a social point of view, thus making it difficult for patients to evolve their professional life and education level. We present a case report of a young male patient with refractory TS with a Yale Global Tic Severity Scale (YGTSS) score of 88 out of 100; he has experienced remarkable improvement after undergoing a deep brain stimulation (DBS) procedure. CASE REPORT: A 23-year-old male came to our neurosurgery outpatient clinic who had had a history of TS since 8 years ago. He had facial and jumping-type tics. Lately, his jumping movements cannot be controlled, with increasing frequency and intensity. The maximum tic-free interval is only 30 min. On 1st-time evaluation in the neurosurgery outpatient clinic, he scored 88 out 0f 100 on the YGTSS even after medication treatment, repetitive transcranial magnetic stimulation, and behavioral therapies. The DBS procedure was carried out in November 2018 with targets on the bilateral intralaminar nuclei of thalamus (centromedian nucleus). The result is convincing, with decrease of YGTSS score until 14 after 3 years evaluation postsurgery. CONCLUSION: After performing DBS targeting the bilateral thalamus (central thalamus nucleus), the severity of tic was dramatically reduced. The result is pleasing to the patient as they can resume activity in public and return to college. Case reports regarding the treatment of refractory TS with DBS are still rare in Indonesia. To the best of our knowledge, this is the first such report with long-term follow-up in South East Asia.

Subthalamic deep brain stimulation in Parkinson's disease with SNCA mutations: Based on the follow-up to 10years.

BackgroundsAlthough the short‐term efficacy of bilateral subthalamic deep brain stimulation (DBS) has been reported in a limited number of Parkinson's disease (PD) patients with SNCA mutations, there are no data for long‐term outcome.MethodsThis multicenter retrospective study investigated previously reported PD patients with SNCA mutations, implanted with bilateral subthalamic DBS. We compared demographic and clinical data at baseline and last follow‐up. Clinical data of motor and nonmotor symptoms and motor fluctuation were collected up to 10 years from DBS surgery.ResultsAmong four subjects, three had SNCA duplication and one had c.158C.A (p.A53E) mutation. The mean post‐implantation follow‐up duration was 5.4 ± 3.7 years. All patients with SNCA duplication showed favorable outcome, although one died from breast cancer 1.5 years after DBS. The patient with the missense mutation became wheelchair‐bound due to progressed axial, cognitive and psychiatric symptoms after 3.5 years from DBS despite the benefit on motor fluctuation.ConclusionBased on findings in our small cohort, subthalamic DBS could be beneficial for motor fluctuation in PD patients with SNCA mutations, especially those with SNCA duplication, and cognitive and psychiatric symptoms are important for the long‐term outcome of subthalamic DBS.

Changes in pallidal neural activity following long-term symptom improvement from botulinum toxin treatment in DYT6 dystonia: a case report

BackgroundThe globus pallidus internus is the main target for the treatment of dystonia by deep brain stimulation. Unfortunately, for some genetic etiologies, the therapeutic outcome of dystonia is less predictable. In particular, therapeutic outcomes for deep brain stimulation in craniocervical and orolaryngeal dystonia in DYT6-positive patients are poor. Little is known about the neurophysiology of the globus pallidus internus in DYT6-positive dystonia, and how symptomatic treatment affects the neural activity of this region.Case presentationWe present here the case of a 55-year-old Caucasian female DYT6-dystonic patient with blepharospasm, spasmodic dysphonia, and oromandibular dystonia where single-unit and local field potential activity was recorded from the globus pallidus internus during two deep brain stimulation revision surgeries 4 years apart with no symptomatic improvement. Botulinum toxin injections consistently improved dysphonia, while some of the other symptoms were only inconsistently or marginally improved. Neural activity in the globus pallidus internus during both revision surgeries were compared with previously published results from an idiopathic dystonic cohort. Single-cell firing characteristics and local field potential from the first revision surgery showed no differences with our control group. However, during the second revision surgery, the mean firing rate of single units and local field potential power in the gamma range were lower than those present during the first revision surgery or the control group.ConclusionsSymptoms related to facial movements were greatly improved by botulinum toxin treatment between revision surgeries, which coincided with lower discharge rate and changes in gamma local field oscillations.

Deep Brain Stimulation and Treatment Outcomes of Young- and Late-Onset (≤55 Years) Parkinson's Disease: A Population-Based Study.

Background: No studies have reported the rate of motor complications (MC) and response to medical and surgical treatment in a population-based cohort of young-onset Parkinson's Disease (YOPD) patients and a cohort of sex-matched late-onset Parkinson's Disease (LOPD).Objective: To assess the outcomes of dopaminergic treatment in YOPD and LOPD, explore treatment-induced MC, medical adjustment, and rate of deep brain stimulation (DBS).Methods: We used the expanded Rochester Epidemiology Project (eREP) to investigate a population-based cohort of YOPD between 2010 and 2015 in 7 counties in Minnesota. Cases with onset ≤55 years of age were included as YOPD. An additional sex-matched cohort of LOPD (onset at ≥56 years of age) was included for comparison. All medical records were reviewed to confirm the diagnoses.Results: In the seven counties 2010–15, there were 28 YOPD patients, which were matched with a LOPD cohort. Sixteen (57%) YOPD had MC, as compared to 9 (32%) LOPD. In YOPD, 9 had motor fluctuations (MF) and Levodopa-induced dyskinesia (LID) together, whereas 3 had LID only and 4 MF only. In LOPD, 3 had MF and LID, 3 MF only, and 3 LID only. Following medical treatment for MC, 6/16 YOPD (38%) and 3/9 (33%) LOPD had symptoms resolution. In YOPD, 11/16 (69%) were considered for DBS implantation, in LOPD they were 2/9 (22%), but only 7 (6 YOPD and 1 LOPD) underwent the procedure. YOPD had significantly higher rates in both DBS candidacy and DBS surgery (respectively, p = 0.03 and p = 0.04). Among DBS-YOPD, 5/6 (83%) had positive motor response to the surgery; the LOPD case had a poor response. We report the population-based incidence of both YOPD with motor complications and YOPD undergoing DBS, which were 1.17 and 0.44 cases per 100,000 person-years, respectively.Conclusion: Fifty-seven percent of our YOPD patients and 32% of the LOPD had motor complications. Roughly half of both YOPD and LOPD were treatment resistant. YOPD had higher rates of DBS candidacy and surgery. Six YOPD and 1 LOPD underwent DBS implantation and most of them had a positive motor response after the surgery.

Effect of Deep Brain Stimulation on Female Parkinsonian Patients with Lower Urinary Tract Symptoms.

PurposeThis study aimed to investigate the characteristics of urodynamics in female parkinsonian patients with lower urinary tract symptoms (LUTS) and evaluate the outcomes of deep brain stimulation (DBS) based on overactive bladder (OAB) scores and quality of life (QOL) scores.Patients and MethodsUrodynamic assessment was performed in 20 female parkinsonian patients with LUTS. OAB scores and QOL scores were collected before and 6 months after DBS treatment (The target of DBS is STN). We evaluated the related factors affecting QOL score and also the changes in QOL score after DBS treatment.ResultsThe mean age of 20 patients was 60.6±6.3 years, with 65% of patients identified with OAB in urodynamic studies. The mean OAB total score and QOL score at baseline were 7.3±3.7 and 5.0±1.1, respectively. Four items in the OAB score were found to be independent factors and they influenced the baseline QOL scores. Six months after DBS treatment, the OAB total score and the QOL score were significantly decreased (3.7±3.2 (p = 0.002) and 3.4±1.4 (p < 0.001), respectively). Improvements in OAB item 2 (nocturia) and item 3 (urgency) scores were found to be independent factors, which had an influence on the improvement in QOL scores from multivariate analysis. Improvement of OAB item 2 (nocturia) exhibited the greatest influence on improvement in the QOL score. After DBS treatment, 40% of the patients showed significant improvement in urination symptoms (≥2 points reduction in QOL score), 30% of the patients showed mild improvement (1 point reduction in QOL score), and 30% patients showed no improvement (no change in QOL score). No patients exhibited worsening urination symptoms.ConclusionMost parkinsonian female patients with lower urinary tract symptoms were diagnosed with OAB. DBS treatment improved OAB symptoms. Improvement of nocturia and urgency positively impacts the QOL of female parkinsonian patients.

Long-Term Results of Deep Brain Stimulation for Treatment-Resistant Depression: Outcome Analysis and Correlation With Lead Position and Electrical Parameters.

Long-term efficacy and mechanisms of action of deep brain stimulation (DBS) for treatment-resistant depression (TRD) are under investigation. To compare long-term outcomes with active electrode's coordinates and its electrical parameters in patients with TRD treated with DBS in the subgenual cingulate gyrus (SCG-DBS). Seventeen patients with TRD underwent SCG-DBS. Demographic and baseline characteristics were recorded. The 17-item Hamilton Depression Rating Scale was used to measure the response to the therapy. The anterior commissure-posterior commissure coordinates of the active contacts and the total electrical energy delivered were calculated and correlated with clinical outcomes. Patient-specific tractographic analysis was performed to identify the modulated pathways in responders. Twelve women (70.6%) and 5 men (29.4%) with a median age of 48 yr (34-70 years) were included. Along the 5-year follow-up, 3 main clinical trajectories were observed according to symptom's improvement: great responders (≥80%), medium responders (≥50%-79%), and poor responders (<50%). Active contacts' coordinates and total electrical energy delivered showed no correlation with clinical outcomes. Brodmann area 10 medial was the most frequently stimulated area and the forceps minor, the most frequently modulated tract. SCG-DBS for TRD is clearly effective in some patients. Active contacts' coordinates were highly variable within the region and, like electrical parameters, did not seem to correlate with clinical outcomes. In the current series, Brodmann area 10 medial and the forceps minor were the most frequently targeted area and modulated pathway, respectively.

Deep Brain Stimulation Treating Dystonia: A Systematic Review of Targets, Body Distributions and Etiology Classifications.

Background: Deep brain stimulation (DBS) is a typical intervention treating drug-refractory dystonia. Currently, the selection of the better target, the GPi or STN, is debatable. The outcomes of DBS treating dystonia classified by body distribution and etiology is also a popular question.Objective: To comprehensively compare the efficacy, quality of life, mood, and adverse effects (AEs) of GPi-DBS vs. STN-DBS in dystonia as well as in specific types of dystonia classified by body distribution and etiology.Methods: PubMed, Embase, the Cochrane Library, and Google Scholar were searched to identify studies of GPi-DBS and STN-DBS in populations with dystonia. The efficacy, quality of life, mood, and adverse effects were quantitatively compared. Meta-regression analyses were also performed. This analysis has been registered in PROSPERO under the number CRD42020146145.Results: Thirty five studies were included in the main analysis, in which 319 patients underwent GPI-DBS and 113 patients underwent STN-DBS. The average follow-up duration was 12.48 months (range, 3–49 months). The GPI and STN groups were equivalent in terms of efficacy, quality of life, mood, and occurrence of AEs. The focal group demonstrated significantly better disability symptom improvement (P = 0.012) than the segmental and generalized groups but showed less SF-36 enhancement than the segmental group (P < 0.001). The primary groups exhibited significantly better movement and disability symptom improvements than the secondary non-hereditary group (P < 0.005), which demonstrated only disability symptom improvement compared with the secondary hereditary group (P < 0.005). The primary hereditary and idiopathic groups had a significantly lower frequency of AEs than the secondary non-hereditary group (P < 0.005). The correlation between disability symptom improvement and movement symptom improvement was also significant (P < 0.05).Conclusion: GPi-DBS and STN-DBS were both safe and resulted in excellent improvement in efficacy and quality of life in patients with dystonia. Compared with patients with segmental dystonia, patients with focal dystonia demonstrated better improvement in dystonia symptoms but less enhancement of quality of life. Those with primary dystonia had a better response to DBS in terms of efficacy than those with secondary dystonia. Patients who exhibit a significant improvement in movement symptoms might also exhibit excellent improvement in disability symptoms.

Predicting long term outcomes of deep brain stimulation in obsessive compulsive disorder, depression, and anorexia nervosa

Predicting long term outcomes of deep brain stimulation in obsessive compulsive disorder, depression, and anorexia nervosa

Retrospective Review of Clinical Effects, Tolerability and Outcomes of Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) in Patients Aged 23 and Younger

Retrospective Review of Clinical Effects, Tolerability and Outcomes of Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) in Patients Aged 23 and Younger

Patient-specific modeling of the volume of tissue activated (VTA) is associated with clinical outcome of DBS in patients with an obsessive-compulsive disorder.

Deep brain stimulation (DBS) promises to treat an increasing number of neurological and psychiatric disorders. DBS outcome is directly a factor of optimal targeting of the relevant brain structures. Computational models can help to interpret a patient's outcome by predicting the volume of tissue activated (VTA) around DBS electrode contacts. Here we report results of a preliminary study of DBS in two patients with obsessive-compulsive disorder and show that VTA predictions, which are based on patient-specific volume conductor models, correlate with clinical outcome. Our results suggest that patient specific VTA calculation can help inform device programing to maximize therapeutic effects and minimize side effects.Clinical Relevance- Patient-specific modeling of the volume of activated tissue can predict clinical outcomes and thus, can help to optimize DBS device programing to maximize therapeutic effects.

Prediction of Deep Brain Stimulation Outcome in Parkinson's Disease With Connectome Based on Hemispheric Asymmetry.

Parkinson’s disease (PD) is a neurodegenerative disease that is associated with motor and non-motor symptoms and caused by lack of dopamine in the substantia nigra of the brain. Subthalamic nucleus deep brain stimulation (STN-DBS) is a widely accepted therapy of PD that mainly inserts electrodes into both sides of the brain. The effect of STN-DBS was mainly for motor function, so this study focused on the recovery of motor function for PD after DBS. Hemispherical asymmetry in the brain network is considered to be a potential indicator for diagnosing PD patients. This study investigated the value of hemispheric brain connection asymmetry in predicting the DBS surgery outcome in PD patients. Four types of brain connections, including left intra-hemispheric (LH) connection, right intra-hemispheric (RH) connection, inter-hemispheric homotopic (Ho) connection, and inter-hemispheric heterotopic (He) connection, were constructed based on the resting state functional magnetic resonance imaging (rs-fMRI) performed before the DBS surgery. We used random forest for selecting features and the Ridge model for predicting surgical outcome (i.e., improvement rate of motor function). The functional connectivity analysis showed that the brain has a right laterality: the RH networks has the best correlation (r = 0.37, p = 5.68E-03) between the predicted value and the true value among the above four connections. Moreover, the region-of-interest (ROI) analysis indicated that the medioventral occipital cortex (MVOcC)–superior temporal gyrus (STG) and thalamus (Tha)–precentral gyrus (PrG) contributed most to the outcome prediction model for DBS without medication. This result provides more support for PD patients to evaluate DBS before surgery.

Pressing ethical issues in considering pediatric deep brain stimulation for obsessive-compulsive disorder

BackgroundRefractory obsessive-compulsive disorder (OCD) among adults is the first psychiatric indication of deep brain stimulation (DBS) to receive an FDA Humanitarian Device Exemption (HDE). Given the HDE approval and encouraging evidence that has since emerged, exploration of DBS for OCD may expand to adolescents in the future. More than 100,000 adolescents in the U.S. suffer from refractory OCD, and there is already a precedent for the transition of DBS in adults to children in the case of dystonia. However, the risk-benefit analysis of pediatric DBS for OCD may be more complex and raise different ethical questions compared to pediatric DBS for dystonia. ObjectiveThis study aimed to gain insight into pressing ethical issues related to using DBS in adolescents with OCD. MethodsSemi-structured interviews were conducted with clinicians (n = 25) caring for pediatric patients with refractory OCD. Interview transcripts were coded with MAXQDA 2018 software and analyzed using thematic content analysis to identify emergent themes. ResultsFive central themes were identified in clinician responses, three of which were exacerbated in the pediatric DBS setting. Clinicians expressed concerns related to conditions of decision-making including adolescents' capacity to assent (80%), the lack of evidence about the outcomes and potential unknown effects of using DBS in adolescents with OCD (68%), and the importance of exhausting other treatment options before considering DBS (20%). ConclusionsStrategies to address clinician concerns include implementation of validated decision support tools and further research into the outcomes of pediatric DBS for OCD to establish clear guidelines for patient selection.

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up.

Objective: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant depression (TRD) that has shown variable efficacy. This report describes long-term outcomes of DBS for TRD.Methods: A consecutive series of 8 patients with TRD were implanted with ventral capsule/ventral striatum (VC/VS) DBS systems as part of the Reclaim clinical trial. Outcomes from 2009 to 2020 were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Demographic information, MADRS scores, and data on adverse events were collected via retrospective chart review. MADRS scores were integrated over time using an area-under-the-curve technique.Results: This cohort of patients had severe TRD-all had failed trials of ECT, and all had failed a minimum of 4 adequate medication trials. Mean ± SD follow-up for patients who continued to receive stimulation was 11.0 ± 0.4 years (7.8 ± 4.3 years for the entire cohort). At last follow-up, mean improvement in MADRS scores was 44.9% ± 42.7%. Response (≥ 50% improvement) and remission (MADRS score ≤ 10) rates at last follow-up were 50% and 25%, respectively. Two patients discontinued stimulation due to lack of efficacy, and another patient committed suicide after stimulation was discontinued due to recurrent mania. The majority of the cohort (63%) continued to receive stimulation through the end of the study.Conclusions: While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this small open-label study demonstrates that some patients achieve meaningful and sustained clinical benefit. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including patient selection, integrative outcome measures, and long-term observation is essential for future trial design.Trial Registration: ClinicalTrials.gov identifier: NCT00837486.

Preoperative REM Sleep Behavior Disorder and Subthalamic Nucleus Deep Brain Stimulation Outcome in Parkinson Disease 1 Year After Surgery.

To determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD. We analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBD-) probable RBD preoperatively. At preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Society-sponsored version of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] III "off": 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaire-39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBD- patients. Both pre-opRBD+ and pre-opRBD- patients had significant MDS-UPDRS IV score decrease (-37% and -33%, respectively), MDS-UPDRS III "med 'off'/stim 'on'" score decrease (-52% and -54%), and dopaminergic treatment decrease (-52% and -49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes. In patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery. NCT02360683. This study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery.