Preventing Shift from Pneumocephalus During Deep Brain Stimulation Surgery: Don't Give Up the 'Fork in the Brain'.

Clinical vignette: We present the case of a patient who developed intra-operative pneumocephalus during left globus pallidus internus deep brain stimulation (DBS) placement for Parkinson's disease (PD). Microelectrode recording (MER) revealed that we were anterior and lateral to the intended target. Clinical dilemma: Clinically, we suspected brain shift from pneumocephalus. Removal of the guide-tube for readjustment of the brain target would have resulted in the introduction of movement resulting from brain shift and from displacement from the planned trajectory. Clinical solution: We elected to leave the guide-tube cannula in place and to pass the final DBS lead into a channel that was located posterior-medially from the center microelectrode pass. Gap in knowledge: Surgical techniques which can be employed to minimize brain shift in the operating room setting are critical for reduction in variation of the final DBS lead placement. Pneumocephalus after dural opening is one potential cause of brain shift. The recognition that the removal of a guide-tube cannula could worsen brain shift creates an opportunity for an intraoperative team to maintain the advantage of the 'fork' in the brain provided by the initial procedure's requirement of guide-tube placement.

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.

Management of essential tremor deep brain stimulation-induced side effects.

Deep brain stimulation (DBS) is an effective surgical therapy for carefully selected patients with medication refractory essential tremor (ET). The most popular anatomical targets for ET DBS are the ventral intermedius nucleus (VIM) of the thalamus, the caudal zona incerta (cZI) and the posterior subthalamic area (PSA). Despite extensive knowledge in DBS programming for tremor suppression, it is not uncommon to experience stimulation induced side effects related to DBS therapy. Dysarthria, dysphagia, ataxia, and gait impairment are common stimulation induced side effects from modulation of brain tissue that surround the target of interest. In this review, we explore current evidence about the etiology of stimulation induced side effects in ET DBS and provide several evidence-based strategies to troubleshoot, reprogram and retain tremor suppression.

Neuromodulation for the treatment of Prader-Willi syndrome - A systematic review.

Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

U.S. Tax Credits to Promote Practical Proactive Preventative Care for Parkinson's Disease.

Persons with Parkinson's disease (PD) and society at large can profit from a strategic investment into a forward leaning, practical, preventative, and proactive multidisciplinary care policy. The American healthcare system is not easily bent to accommodate this type of care, and thus a tax benefit is an attractive option. An individual federal income tax benefit of $6200 each year for every person residing in the US with a diagnosis of PD, could among other offerings provide monthly access to a licensed clinical social worker and access to mental health services. The implementation of more coordinated care has the potential reduce the burden of depression, anxiety, and demoralization. Personal training would also be covered and directed by physical and occupational therapists. The combination of home-based and telemedicine services would have the added benefit of improving access. The tax benefit would also provide access to a dietician. This type of care strategy could be designed to proactively identify early signs of aspiration and urinary tract infections to 'head off' significant morbidity. A $6200/year individual tax benefit for those diagnosed with PD will thus translate into more fall prevention, more care in the home setting, less hospitalizations, less depression, less anxiety, less demoralization, better diets, and less persons placed in nursing facilities. Additionally, this tax benefit will provide the potential for billions of dollars in savings to the healthcare system. A tax benefit for PD is a practical preventative and proactive strategy which can serve to advantage both this generation and the next.

Deep brain stimulation for refractory major depressive disorder: a comprehensive review.

Deep brain stimulation (DBS) has emerged as a promising treatment for select patients with refractory major depressive disorder (MDD). The clinical effectiveness of DBS for MDD has been demonstrated in meta-analyses, open-label studies, and a few controlled studies. However, randomized controlled trials have yielded mixed outcomes, highlighting challenges that must be addressed prior to widespread adoption of DBS for MDD. These challenges include tracking MDD symptoms objectively to evaluate the clinical effectiveness of DBS with sensitivity and specificity, identifying the patient population that is most likely to benefit from DBS, selecting the optimal patient-specific surgical target and stimulation parameters, and understanding the mechanisms underpinning the therapeutic benefits of DBS in the context of MDD pathophysiology. In this review, we provide an overview of the latest clinical evidence of MDD DBS effectiveness and the recent technological advancements that could transform our understanding of MDD pathophysiology, improve the clinical outcomes for MDD DBS, and establish a path forward to develop more effective neuromodulation therapies to alleviate depressive symptoms.

Current perspectives on tractography-guided deep brain stimulation for the treatment of mood disorders.

INTRODUCTION: Deep brain stimulation (DBS) is an emerging therapy for mood disorders, particularly treatment-resistant depression (TRD). Different brain areas implicated in depression-related brain networks have been investigated as DBS targets and variable clinical outcomes highlight the importance of target identification. Tractography has provided insight into how DBS modulates disorder-related brain networks and is being increasingly used to guide DBS for psychiatric disorders. AREAS COVERED: In this perspective, an overview of the current state of DBS for TRD and the principles of tractography is provided. Next, a comprehensive review of DBS targets is presented with a focus on tractography. Finally, the challenges and future directions of tractography-guided DBS are discussed. EXPERT OPINION: Tractography-guided DBS is a promising tool for improving DBS outcomes for mood disorders. Tractography is particularly useful for targeting patient-specific white matter tracts that are not visible using conventional structural MRI. Developments in tractography methods will help refine DBS targeting for TRD and may facilitate symptom-specific precision neuromodulation. Ultimately, the standardization of tractography methods will be essential to transforming DBS into an established therapy for mood disorders.

WarpDrive: Improving spatial normalization using manual refinements.

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together.

Meta-analysis of Association between Newer Glucose-Lowering Drugs and Risk of Parkinson's Disease.

Background: The association between newer classes of glucose-lowering drugs (GLDs) and the risk of Parkinson's disease (PD) remains unclear. Objective: The aim was to examine the effect of newer GLDs on the risk of PD through a meta-analysis of randomized outcome trials. Methods: The methods included randomized placebo-controlled outcome trials that reported PD events associated with three newer classes of GLDs (ie, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose co-transporter-2 inhibitors) in participants with or without type 2 diabetes. The pooled odds ratio (OR) and 95% confidence interval (CI) were estimated using Peto's method. Results: The study included 24 trials involving 33 PD cases among 185,305 participants during a median follow-up of 2.2 years. Newer GLDs were significantly associated with a lower PD risk (OR: 0.50; 95% CI: 0.25-0.98) than placebo. Conclusion: Newer GLDs may possibly be associated with a decreased risk of PD; however, larger datasets are required to confirm or refute this notion.

Identification and Management of Persistent Stimulation-Induced Dyskinesia Associated with STN DBS: The See-Saw Dilemma.

Clinical vignette: A 73-year-old woman with Parkinson's disease (PD) underwent implantation of bilateral subthalamic nucleus deep brain stimulators (STN-DBS) to address bilateral upper extremity medication-refractory tremor. Post-operatively, she experienced a "see-saw effect" where small increases in stimulation resulted in improvement in one symptom (tremor) with concurrent worsening in another (dyskinesia). Clinical dilemma: SID is usually considered a positive predictor of DBS outcome. However, there are cases where SID cannot be optimized. Lead location and pre-operative characteristics may contribute to this adverse effect. If the combination of programming and medication adjustments fails to resolve SID, what can be done to "rescue" the outcome? Clinical solution: Management of SID requires a gradual and steadfast programming approach. Post-operative lead localization can guide advanced programming and decision-making. Rescue surgical interventions may be considered. Gap in knowledge: In cases where SID is persistent despite deploying persistent optimization strategies, there is limited guidance on next steps.

Weight and survival after deep brain stimulation for Parkinson's disease.

BACKGROUND: Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear. OBJECTIVES: To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight. METHODS: This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses. RESULTS: There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0-12 months after the first or 0-36 months after the second surgery) was positively associated with survival (R2 = 0.14, p < 0.001). DISCUSSION: Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts.

Type, Timing, Frequency, and Durability of Outcome of Physical Therapy for Parkinson Disease: A Systematic Review and Meta-Analysis.

Importance: Parkinson disease (PD) is a neurodegenerative syndrome affecting approximately 1% of the population older than 60 years, and a major goal of treatment is preservation of physical function through physical therapy (PT). Although PT outcomes for PD are well documented, aggregate information on the parameters of PT are needed to guide implementation. Objective: To evaluate current evidence on the types, timing, frequency, duration, and outcomes of PT regimens applied for PD. Data Sources: PubMed, Embase, Medline, and the Web of Science Core Collection were searched for articles published from January 1, 2000, to August 10, 2022. Search terms included terms related to Parkinson disease, PT interventions, and PT-related outcomes. Study Selection: Included studies were peer-reviewed randomized clinical trials available in English of any PT intervention for patients with PD that included PT-related outcomes. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Data Extraction and Synthesis: Two reviewers extracted data and assessed quality using the Cochrane Risk of Bias Tool. Data were analyzed using a random-effects model. Main Outcomes and Measures: A meta-analysis compared outcomes of nonstandard PT vs standard PT and standard PT vs no intervention for Unified Parkinson's Disease Rating Scale (UPDRS) score and measures of gait and balance. Results: A total of 46 trials with 3905 patients were included (range of mean ages, 61-77 years). Ten trials (22%) compared 2 types of nonstandard PT interventions; 26 (57%), nonstandard PT vs standard PT; and 10 (22%), PT vs no intervention. The most common nonconventional PT intervention was aquatic physiotherapy (5 trials [11%]). Durations of PT regimen ranged from 2 to 12 weeks in 39 trials (85%), and PT was most commonly performed with frequencies of either twice or 3 times weekly (27 [59%]). In most trials (39 [85%]), PT session length ranged from 30 to 60 minutes. Across trials, PT outcomes were reported for gait (14 trials [30%]), balance (10 [22%]), quality of life (3 [9%]), and cognition (1 [2%]). Approximately half of the trials (22 [48%]) documented durability of some level of benefit after completion of the prescribed regimen. Meta-analysis showed no significant difference for PT vs no intervention in UPDRS scores (standardized mean difference [SMD], -1.09; 95% CI, -2.50 to 0.33) or for nonstandard PT vs standard PT in measures of gait (SMD, 0.03; 95% CI, -0.53 to 0.59), balance (SMD, 0.54; 95% CI, -0.03 to 1.12), and UPDRS score (SMD, -0.49; 95% CI, -1.04 to 0.06). Meta-analytic regression of moderators revealed no significant differences in outcomes by frequency of PT per week (SMD, 0.17; 95% CI, -0.03 to 0.36). Conclusions and Relevance: The findings suggest that although a wide range of types and regimens of PT for PD have been tested, comparative effectiveness of different models of care and implementation strategies as well as long-term durability of their outcomes remain undetermined.