Category: DBS

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Altered brain network centrality in Parkinson’s disease patients after deep brain stimulation: a functional MRI study using a voxel-wise degree centrality approach

J Neurosurg 138:1712–1719, 2023

After deep brain stimulation (DBS), patients with Parkinson’s disease (PD) show improved motor symptoms and decreased verbal fluency, an effect that occurs before the initiation of DBS in the subthalamic nucleus. However, the underlying mechanism remains unclear. This study aimed to evaluate the effects of DBS on whole-brain degree centrality (DC) and seed-based functional connectivity (FC) in PD patients.

METHODS The authors obtained resting-state functional MRI data of 28 PD patients before and after DBS surgery. All patients underwent MRI scans in the off-stimulation state. The DC method was used to evaluate the effects of DBS on whole-brain FC at the voxel level. Seed-based FC analysis was used to examine network function changes after DBS.

RESULTS After DBS surgery, PD patients showed significantly weaker DC values in the left middle temporal gyrus, left supramarginal gyrus, and left middle frontal gyrus, but significantly stronger DC values in the midbrain, left precuneus, and right precentral gyrus. FC analysis revealed decreased FC values within the default mode network (DMN).

CONCLUSIONS This study demonstrated that the DC of DMN-related brain regions decreased in PD patients after DBS surgery, whereas the DC of the motor cortex increased. These findings provide new evidence for the neural effects of DBS on voxel-based whole-brain networks in PD patients.

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Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson’s Disease: 10 Years and Beyond

Neurosurgery 91:726–733, 2022

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson’s disease (PD), but little is known about the long-term benefit.

OBJECTIVE: To investigate the survival rate and long-term outcome of DBS.

METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed.

RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson’s Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation.

CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

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Radiological identification of the globus pallidus motor subregion in Parkinson’s disease

J Neurosurg 137:175–183, 2022

Globus pallidus (GP) lesioning improves motor symptoms of Parkinson’s disease (PD) and is occasionally associated with nonmotor side effects. Although these variable clinical effects were shown to be site-specific within the GP, the motor and nonmotor subregions have not been distinguished radiologically in patients with PD. The GP was recently found to have a distinct radiological signature on diffusion MRI (dMRI), potentially related to its unique cellular content and organization (or tissue architecture). In this study, the authors hypothesize that the magnitude of water diffusivity, a surrogate for tissue architecture, will radiologically distinguish motor from nonmotor GP subregions in patients with PD. They also hypothesize that the therapeutic focused ultrasound pallidotomy lesions will preferentially overlap the motor subregion.

METHODS Diffusion MRI from healthy subjects (n = 45, test-retest S1200 cohort) and PD patients (n = 33) was parcellated based on the magnitude of water diffusivity in the GP, as measured orientation distribution function (ODF). A clustering algorithm was used to identify GP parcels with distinct ODF magnitude. The individual parcels were used as seeds for tractography to distinguish motor from nonmotor subregions. The locations of focused ultrasound lesions relative to the GP parcels were also analyzed in 11 patients with PD.

RESULTS Radiologically, three distinct parcels were identified within the GP in healthy controls and PD patients: posterior, central, and anterior. The posterior and central parcels comprised the motor subregion and the anterior parcel was classified as a nonmotor subregion based on their tractography connections. The focused ultrasound lesions preferentially overlapped with the motor subregion (posterior more than central). The hotspots for motor improvement were localized in the posterior GP parcel.

CONCLUSIONS Using a data-driven approach of ODF-based parcellation, the authors radiologically distinguished GP motor subregions in patients with PD. This method can aid stereotactic targeting in patients with PD undergoing surgical treatments, especially focused ultrasound ablation.

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Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor

J Neurosurg 136:662–671, 2022

The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density–weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting.

METHODS Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author’s institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure–posterior commissure line).

RESULTS Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention.

CONCLUSIONS Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.

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Perioperative complications of deep brain stimulation among patients with advanced age

J Neurosurg 135:1421–1428, 2021

Deep brain stimulation (DBS) is an elective procedure that can dramatically enhance quality of life. Because DBS is not considered lifesaving, it is important that providers produce consistently good outcomes, and one factor they usually consider is patient age. While older age may be a relative contraindication for some elective surgeries, the progressive nature of movement disorders treated with DBS may suggest that older patients stand to benefit substantially from surgery. To better understand the risks of treating patients of advanced age with DBS, this study compares perioperative complication rates in patients ≥ 75 to those < 75 years old.

METHODS Patients undergoing DBS surgery for various indications by a single surgeon (May 2013–July 2019) were stratified into elderly (age ≥ 75 years) and younger (age < 75 years) cohorts. The risks of common perioperative complications and various outcome measures were compared between the two age groups using risk ratios (RRs) and 95% confidence intervals (CIs).

RESULTS A total of 861 patients were available for analysis: 179 (21%) were ≥ 75 years old and 682 (79%) were < 75 years old (p < 0.001). Patients ≥ 75 years old, compared with those < 75 years old, did not have significantly different RRs (95% CIs) of seizure (RR 0.4, 95% CI 0.1–3.3), cerebrovascular accident (RR 1.9, 95% CI 0.4–10.3), readmission within 90 days of discharge (RR 1.22, 95% CI 0.8–1.8), explantation due to infection (RR 2.5, 95% CI 0.4–15.1), or surgical revision (for lead, RR 2.5, 95% CI 0.4–15.1; for internal pulse generator, RR 3.8, 95% CI 0.2–61.7). Although the risk of postoperative intracranial bleeding was higher in the elderly group (6.1%) than in the younger group (3.1%), this difference was not statistically significant (p = 0.06). However, patients ≥ 75 years old did have significantly increased risk of altered mental status (RR 2.5, 95% CI 1.6–4.0), experiencing more than a 1-night stay (RR 1.7, 95% CI 1.4–2.0), and urinary retention (RR 2.3, 95% CI 1.2–4.2; p = 0.009).

CONCLUSIONS Although elderly patients had higher risks of certain outcome measures than younger patients, this study showed that elderly patients undergoing DBS for movement disorders did not have an increased risk of more serious complications, such as intracranial hemorrhage, infection, or readmission. Advanced age alone should not be considered a contraindication for DBS.

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Fields of Forel Brain Stimulation Improves Levodopa-Unresponsive Gait and Balance Disorders in Parkinson’s Disease

Neurosurgery 89:450–459, 2021

Gait and balance disturbance are challenging symptoms in advanced Parkinson’s disease (PD). Anatomic and clinical data suggest that the fields of Forel may be a potential surgical target to treat these symptoms.

OBJECTIVE: To test whether bilateral stimulation centered at the fields of Forel improves levodopa unresponsive freezing of gait (FOG), balance problems, postural instability, and falls in PD.

METHODS: A total of 13 patients with levodopa-unresponsive gait disturbance (Hoehn and Yahr stage ≥3) were included. Patients were evaluated before (on-medication condition) and 1 yr after surgery (on-medication-on-stimulation condition). Motor symptoms and quality of life were assessed with the Unified Parkinson’s Disease Rating scale (UPDRS III) and Quality of Life scale (PDQ-39). Clinical and instrumented analyses assessed gait, balance, postural instability, and falls.

RESULTS: Surgery improved balance by 43% (95% confidence interval [CI]: 21.2-36.4 to 35.2-47.1; P = .0012), reduced FOG by 35% (95% CI: 15.1-20.3 to 8.1-15.3; P = .0021), and the monthly number of falls by 82.2% (95% CI: 2.2-6.9 to −0.2-1.7; P = .0039). Anticipatory postural adjustments, velocity to turn, and postural sway measurements also improved 1 yr after deep brain stimulation (DBS). UPDRS III motor scores were reduced by 27.2% postoperatively (95% CI: 42.6-54.3 to 30.2-40.5; P < .0001). Quality of life improved 27.5% (95% CI: 34.6-48.8 to 22.4-37.9; P = .0100).

CONCLUSION: Our results suggest that DBS of the fields of Forel improved motor symptoms in PD, as well as the FOG, falls, balance, postural instability, and quality of life.

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What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center

J Neurosurg 135:619–628, 2021

In the absence of a standard or guideline for the treatment of epilepsy patients with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT), systematic single-center investigations are essential to establish effective approaches. Here, the authors report on the long-term results of one of the largest single-center ANT DBS cohorts.

METHODS The outcome data of 23 consecutive patients with transventricularly implanted electrodes were retrospectively analyzed with regard to adverse events, lead placement, stimulation-related side effects, and changes in seizure frequency. Depression and quality-of-life scores were collected in a subgroup of 9 patients.

RESULTS All but 2 patients initially underwent bilateral implantation, and 84.4% of all DBS leads were successfully located within the ANT. The mean follow-up time was 46.57 ± 23.20 months. A seizure reduction > 50% was documented in 73.9% of patients, and 34.6% achieved an Engel class I outcome. In 3 patients, clinical response was achieved by switching the electrode contact or changing from the monopolar to bipolar stimulation mode. Unilateral implantation seemed ineffective, whereas bilateral stimulation with successful ANT implantation only on one side led to a clinical response. Double stimulation with additional vagus nerve stimulation was safe. Changes in cycling mode or stimulation amplitude influenced therapy tolerability and, only to a lesser extent, seizure frequency. Side effects were rare and typically vanished by lowering the stimulation amplitude or changing the active electrode contact. Furthermore, depression and aspects of quality of life significantly improved with ANT DBS treatment.

CONCLUSIONS The transventricular approach as well as double stimulation proved safe. The anteroventral ANT appeared to be the most efficacious stimulation site. This systematic investigation with reluctant medication changes allowed for the development of a better idea of the association between parameter changes and outcome in ANT DBS patients, but larger samples are still needed to assess the potential of bipolar stimulation and distinct cycling frequencies. Furthermore, more multifaceted and objective assessments of treatment outcome are needed to fully assess the effects of ANT DBS treatment.

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A Novel Framework for Network-Targeted Neuropsychiatric Deep Brain Stimulation

Neurosurgery 89:E116–E121, 2021

Deep brain stimulation (DBS) has emerged as a promising therapy for neuropsychiatric illnesses, including depression and obsessive-compulsive disorder, but has shown inconsistent results in prior clinical trials. We propose a shift away from the empirical paradigm for developing new DBS applications, traditionally based on testing brain targets with conventional stimulation paradigms. Instead, we propose a multimodal approach centered on an individualized intracranial investigation adapted from the epilepsy monitoring experience, which integrates comprehensive behavioral assessment, such as the Research Domain Criteria proposed by the National Institutes of Mental Health. In this paradigm-shifting approach, we combine readouts obtained from neurophysiology, behavioral assessments, and self-report during broad exploration of stimulation parameters and behavioral tasks to inform the selection of ideal DBS parameters. Such an approach not only provides a foundational understanding of dysfunctional circuits underlying symptom domains in neuropsychiatric conditions but also aims to identify generalizable principles that can ultimately enable individualization and optimization of therapy without intracranial monitoring.

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Deep brain stimulation for aggressiveness: long-term follow-up and tractography study of the stimulated brain areas

J Neurosurg 134:366–375, 2021

Initial studies applying deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) to patients with pathological aggressiveness have yielded encouraging results. However, the anatomical structures involved in its therapeutic effect have not been precisely identified. The authors’ objective was to describe the long-term outcome in their 7-patient series, and the tractography analysis of the volumes of tissue activated in 2 of the responders.

METHODS This was a retrospective study of 7 subjects with pathological aggressiveness. The findings on MRI with diffusion tensor imaging (DTI) in 2 of the responders were analyzed. The authors generated volumes of tissue activated according to the parameters used, and selected those volumes as regions of interest to delineate the tracts affected by stimulation.

RESULTS The series consisted of 5 men and 2 women. Of the 7 patients, 5 significantly improved with stimulation. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be involved in the stimulation field.

CONCLUSIONS In this series, 5 of 7 medication-resistant patients with severe aggressiveness who were treated with bilateral PMH DBS showed a significant long-lasting improvement. The PMH, ventral tegmental area, dorsal longitudinal fasciculus, and medial forebrain bundle seem to be in the stimulation field and might be responsible for the therapeutic effect of DBS.

 

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Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?

Neurosurgery DOI:10.1093/neuros/nyaa141

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.

OBJECTIVE: To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.

METHODS: The relationship between seizure control and the location of the active contacts to the ANT-MTT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps. RESULTS: After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r 2 = 0.24, P = .01) and is ∼30% smaller (P = .015) in responders than in non-responders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot. C

CONCLUSION: Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.

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