Exploring adverse effects of deep brain stimulation: the need for personalized care and long-term monitoring.

Deep Brain Stimulation (DBS), an FDA-approved treatment for movement disorders such as Parkinson's Disease (PD), is increasingly used for various neurological and neuropsychiatric conditions. A recent systematic review and meta-analysis by Bahadori et al. highlighted a significant increase in Body Mass Index (BMI) among patients post-DBS, with most participants having PD. The study, however, noted moderate heterogeneity (I² = 67.566%) without thoroughly addressing its potential causes or proposing strategies to mitigate it. The review's limited patient diversity and short follow-up period also challenge its generalizability and long-term implications. In addition to BMI changes, DBS has been linked to motor, cognitive, and psychiatric side effects. Patients undergoing subthalamic nucleus (STN) stimulation, for example, face risks of motor complications, including speech and gait issues, while cognitive declines, particularly in verbal fluency and executive function, are also concerning. Psychiatric side effects such as depression, anxiety, and psychosis further complicate treatment outcomes. These findings underscore the importance of personalized treatment strategies, preoperative assessments, and ongoing patient education to minimize adverse effects and optimize the therapeutic potential of DBS.

Machine learning for the localization of Subthalamic Nucleus during deep brain stimulation surgery: a systematic review and Meta-analysis.

INTRODUCTION: Delineating subthalamic nucleus (STN) boundaries using microelectrode recordings (MER) and trajectory history is a valuable resource for neurosurgeons, aiding in the accurate and efficient positioning of deep brain stimulation (DBS) electrodes within the STN. Here, we aimed to assess the application of artificial intelligence, specifically Hidden Markov Models (HMM), in the context of STN localization. METHODS: A comprehensive search strategy was employed, encompassing electronic databases, including PubMed, EuroPMC, and MEDLINE. This search strategy entailed a combination of controlled vocabulary (e.g., MeSH terms) and free-text keywords pertaining to "artificial intelligence," "machine learning," "deep learning," and "deep brain stimulation." Inclusion criteria were applied to studies reporting the utilization of HMM for predicting outcomes in DBS, based on structured patient-level health data, and published in the English language. RESULTS: This systematic review incorporated a total of 14 studies. Various machine learning compared wavelet feature to proposed features in diagnosing the STN, with the HMM yielding a diagnostic odds ratio (DOR) of 838.677 (95% CI: 203.309-3459.645). Similarly, the K-Nearest Neighbors (KNN) model produced parameter estimates, including a diagnostic odds ratio of 25.151 (95% CI: 12.270-51.555). Meanwhile, the support vector machine (SVM) model exhibited parameter estimates, with a DOR of 13.959 (95% CI: 10.436-18.671). CONCLUSIONS: MER data demonstrates significant variability in neural activity, with studies employing a wide range of methodologies. Machine learning plays a crucial role in aiding STN diagnosis, though its accuracy varies across different approaches.

Letter to the Editor: "Efficacy of subthalamic deep brain stimulation programming strategies for gait disorders in Parkinson's disease: A systematic review and meta-analysis".

This letter provides valuable insights on the recently published article titled "Efficacy of Subthalamic Deep Brain Stimulation Programming Strategies for Gait Disorders in Parkinson's Disease: A Systematic Review and Meta-Analysis." While commending the authors comprehensive review, I suggest future research focus on standardizing gait disorder classifications, conducting long-term studies to assess the durability of DBS effects and exploring adaptive DBS systems for dynamic real-time programming. Additionally, integrating advanced neuroimaging techniques could enhance our understanding of neural connectivity changes post-DBS. These recommendations could significantly improve tailored interventions and outcomes for Parkinson's disease patients with gait disturbances.

Deep brain stimulation for Tourette's syndrome.

Tourette's syndrome is a neuropsychiatric disorder characterized by formidable motor and vocal tics. Many individuals also present with comorbid neuropsychiatric conditions. Though patients often benefit from pharmacological and behavioral therapies, a subset of individuals develop severe, treatment-resistant symptoms that might necessitate more invasive interventions, such as Deep Brain Stimulation (DBS). DBS, particularly targeting regions like the globus pallidus internus (GPi) and the centromedian-parafascicular complex (CM-Pf) of the thalamus, has demonstrated effectiveness in reducing tic severity and improving quality of life. This review outlines the mechanism, clinical efficacy, and long-term outcome of DBS in TS. Results from clinical studies reveal significant reductions in tics. However, success with DBS is variable depending on a number of factors, including target selection and electrode placement. The use of DBS has ethical considerations, which include risks to the surgical procedure, the need for full and complete informed consent, and questions about the implications of such treatment on cognitive and emotional growth. Long-term follow-up will be required to ensure appropriate patient outcomes and complication management. Additional research and ethical debate will be needed with advancing DBS technology to ensure responsible and equitable treatment. This paper narratively summarizes the surgical options available for TS, with a focus on the current status of DBS in the management of the disease.

Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Deep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists. METHODS AND ANALYSIS: This is a randomised, double-blind, controlled clinical trial involving 64 patients who had their first stroke at least 6 months ago and are experiencing poststroke limb dysfunction. These patients must receive necessary support at home and consent to participate. The aim is to evaluate the effectiveness and safety of DBS and VNS therapies. Patients are excluded if they have implantable devices that are sensitive to electrical currents, severe abnormalities in their lower limbs or are unable to comply with the trial procedures. The study has two parallel, distinct treatment arms: the Stimulation Group and the Sham Group. Initially, the Stimulation Group will undergo immediate electrical stimulation postsurgery, while the Sham Group will receive non-stimulation 1 month later. After 3 months, these groups will swap treatments, with the Stimulation Group discontinuing stimulation and the Sham Group initiating stimulation. Six months later, both groups will resume active stimulation. Our primary outcomes will meticulously assess motor function improvements, using the Fugl-Meyer Assessment, and safety, monitored by tracking adverse reaction rates. Furthermore, we will gain a comprehensive view of patient outcomes by evaluating secondary measures, including clinical improvement (National Institutes of Health Stroke Scale), surgical complications/side effects, quality of life (36-item Short Form Questionnaire) and mental health status (Hamilton Anxiety Rating Scale/Hamilton Depression Rating Scale). To ensure a thorough understanding of the long-term effects, we will conduct follow-ups at 9 and 12 months postsurgery, with additional long-term assessments at 15 and 18 months. These follow-ups will assess the sustained performance and durability of the treatment effects. The statistical analysis will uncover the optimal treatment strategy for poststroke hemiplegia, providing valuable insights for clinicians and patients alike. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Ethical Committee of Chinese PLA General Hospital (S2022-789-01). The findings will be submitted for publication in peer-reviewed journals with online accessibility, ensuring adherence to the conventional scientific publishing process while clarifying how the research outcomes will be disseminated and accessed. TRIAL REGISTRATION NUMBER: NCT06121947.

Olfactory bulb stimulation mitigates Alzheimer's-like disease progression.

BACKGROUND: Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits. AIMS: Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aß) AD model rats. METHODS: Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by the evaluations of histological, behavioral, and local field potential signal processing. RESULTS: OB stimulation counteracted Aß plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task. CONCLUSION: This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.

Brain Stimulation in Alzheimer's Disease Trials.

Alzheimer's disease (AD) continues to lack definitive curative therapies, necessitating an urgent exploration of innovative approaches. This review provides a comprehensive analysis of recent clinical trials focusing on invasive and non-invasive brain stimulation techniques as potential interventions for AD. Deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are evaluated for their therapeutic efficacy, safety, and applicability. DBS, though invasive, has shown promising results in mitigating cognitive decline, but concerns over surgical risks and long-term effects persist. On the other hand, non-invasive methods like rTMS, tDCS, and tACS have demonstrated potential in enhancing cognitive performance and delaying disease progression, with minimal side effects, but with varied consistency. The evidence hints towards an individualized, patient-centric approach to brain stimulation, considering factors such as disease stage, genetic traits, and stimulation parameters. The review also highlights emerging technologies and potential future directions, emphasizing the need for larger, multi-center trials to confirm preliminary findings and establish robust clinical guidelines. In conclusion, while brain stimulation techniques present a promising avenue in AD therapy, further research is imperative for more comprehensive understanding and successful clinical implementation. Through this review, we aim to catalyze the scientific discourse and stimulate further investigation into these novel interventions for AD.

Harnessing the sensing and stimulation function of deep brain-machine interfaces: a new dawn for overcoming substance use disorders.

Substance use disorders (SUDs) imposes profound physical, psychological, and socioeconomic burdens on individuals, families, communities, and society as a whole, but the available treatment options remain limited. Deep brain-machine interfaces (DBMIs) provide an innovative approach by facilitating efficient interactions between external devices and deep brain structures, thereby enabling the meticulous monitoring and precise modulation of neural activity in these regions. This pioneering paradigm holds significant promise for revolutionizing the treatment landscape of addictive disorders. In this review, we carefully examine the potential of closed-loop DBMIs for addressing SUDs, with a specific emphasis on three fundamental aspects: addictive behaviors-related biomarkers, neuromodulation techniques, and control policies. Although direct empirical evidence is still somewhat limited, rapid advancements in cutting-edge technologies such as electrophysiological and neurochemical recordings, deep brain stimulation, optogenetics, microfluidics, and control theory offer fertile ground for exploring the transformative potential of closed-loop DBMIs for ameliorating symptoms and enhancing the overall well-being of individuals struggling with SUDs.

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Deep brain stimulation (DBS), including optical stimulation and electrical stimulation, has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders. Advances in DBS microsystems based on implantable microelectrode array (MEA) probes have opened up new opportunities for closed-loop DBS (CL-DBS) in situ. This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously. Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems, key challenges, including excessive wired communication, need to be urgently resolved. In this review, we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field. This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

Woodhouse-sakati syndrome with no reportable MRI findings: a case report.

BACKGROUND: Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive condition caused by biallelic pathogenic variants in the DCAF17 gene, with fewer than 200 cases reported in the literature. Symptoms first emerge in middle-late adolescence with a spectrum of hypogonadal and progressive neurological features. CASE PRESENTATION: We present a case of WSS with no reportable T2-weighted, apparent diffusion coefficient mapping and susceptibility weighted MRI findings. This differs from cases reported in the current literature. Our patient developed abnormal movements in both legs, clumsiness of the hands, dysarthria, and swallowing difficulties. Moreover, she presented with alopecia manifesting as frontal and temporal balding, severe dystonia with painful dystonic spasms primarily in the left upper limb, as well as primary amenorrhea. She was not independently ambulatory on presentation, requiring wheelchair assistance. Genetic testing, the crucial test for a definitive diagnosis, was undertaken in Qatar and confirmed WSS. Treatment provided includes botulinum toxin injections and deep brain stimulation, providing better dystonia control, with progress in walking and strength exercises, and overall remarkable improvement. Intensive neurorehabilitation regimes were also deployed from admission, including physiotherapy, occupational therapy and speech and language therapy. CONCLUSION: This case adds to the current literature on WSS manifestations, with all previously reported cases having positive MRI findings, unlike our case.

Real-world outcomes of Deep Brain Stimulation for dystonia treatment: Protocol for a prospective, multicenter, international registry.

INTRODUCTION: Deep Brain Stimulation (DBS) is an established therapeutic approach for the treatment of dystonia. However, to date, no large-scale or comprehensive DBS dystonia patient registry has been yet undertaken. Here, we describe the protocol for a world-wide registry of clinical outcomes in dystonia patients implanted with DBS. METHODS AND ANALYSIS: This protocol describes a multicenter, international clinical outcomes registry consisting of up to 200 prospectively enrolled participants at up to 40 different sites to be implanted with a constant-current, multiple independent current controlled (MICC) DBS device (Vercise DBS Systems, Boston Scientific) for treatment of dystonia. Key inclusion criteria for registry candidates include the following: understanding of study requirements and treatment procedures, a signed written informed consent form prior to participation, and meeting all criteria established in the locally applicable Instructions for Use (IFU) for the implanted DBS system. Key clinical endpoints include (but are not limited to) the evaluation of disease state (Burke-Fahn-Marsden Dystonia Rating Scale [BFMDRS], Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), quality of life (Short Form Health Survey-36, Short Form Health Survey-10), and treatment satisfaction (Clinical Global Impression of Change [CGI-Clinician; CGI-Subject; CGI-Caregiver]) at 6-months, 12-months, 2-years, and 3-years post-lead placement. Adverse events are documented and reported using structured questionnaires. PERSPECTIVES: Treatment of patients with dystonia using DBS has progressed considering recent technological advances. This international dystonia outcomes registry aims to collect and evaluate real-world clinical data derived from patients who have been implanted with a constant-current, MICC-equipped DBS system (with available directional capabilities), per standard of care.

Deep brain stimulation for obsessive compulsive disorder: the functional neurosurgeon armamentarium.

Deep brain stimulation (DBS) is a neurosurgical procedure that utilizes implanted electrodes and electrical stimulation for the treatment of neurological disorders. In cases where patients present with severe functional impairment while being refractory to less invasive treatment options, DBS is considered "gold standard." Still, DBS-related work is still widely under investigation, with ethical issues arising that may impact a patient's physical and psycho-social status. These include patient selection, informed consent, patient autonomy, pre-operation counseling and professional psycho-social preparation and follow-up support. Bioethicists and philosophers have increasingly worked together with in clinicians and researchers to identify, address and present ethical consideration in both clinical practice and research to balance the risk-benefit ratio in DBS treatment for obsessive-compulsive disorder.

Non-invasive temporal interference brain stimulation reduces preference on morphine-induced conditioned place preference in rats.

Long-term use of opioid drugs such as morphine can induce addiction in the central nervous system through dysregulation of the reward system of the brain. Deep brain stimulation (DBS) is a non-pharmacological technique capable of attenuating behavioral responses associated with opioid drug consumption and possesses the capability to selectively activate and target localized brain regions with a high spatial resolution. However, long-term implantation of electrodes in brain tissue may limit the effectiveness of DBS due to changes in impedance, position, and shape of the tip of the stimulation electrode and the risk of infection of nerve tissue around the implanted electrode. The main objective of the current study is to evaluate the effect of temporal interference (TI) brain stimulation on addictive behaviors of morphine-induced conditioned place preference (CPP) in rats. TI stimulation is a non-invasive technique used transcranially to modulate neural activity within targeted brain regions. It involves applying two high-frequency currents with slightly different frequencies, resulting in interference and targeted stimulation of different brain areas with the desired spatial resolution. The results indicated that TI stimulation with the amplitude of I 1 = I 2 = 0.5 mA, carrier frequency of 2 kHz, frequency difference of 25 Hz, ON-OFF stimulation frequency of 0.25 Hz, and total duration of 10 min in three consecutive days resulted in a significant reduction of morphine preference in the morphine-stimulation group in comparison with the morphine group (p < 0.001). These findings highlight the potential of TI stimulation as a modulatory intervention in mitigating the addictive properties of morphine and provide valuable insights into the therapeutic implications of this stimulation paradigm for treatment of opioid drugs in human subjects.

Structural connectivity modifications following deep brain stimulation of the subcallosal cingulate and nucleus accumbens in severe anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a mental health disorder characterized by significant weight loss and associated medical and psychological comorbidities. Conventional treatments for severe AN have shown limited effectiveness, leading to the exploration of novel interventional strategies, including deep brain stimulation (DBS). However, the neural mechanisms driving DBS interventions, particularly in psychiatric conditions, remain uncertain. This study aims to address this knowledge gap by examining changes in structural connectivity in patients with severe AN before and after DBS. METHODS: Sixteen participants, including eight patients with AN and eight controls, underwent baseline T1-weigthed and diffusion tensor imaging (DTI) acquisitions. Patients received DBS targeting either the subcallosal cingulate (DBS-SCC, N = 4) or the nucleus accumbens (DBS-NAcc, N = 4) based on psychiatric comorbidities and AN subtype. Post-DBS neuroimaging evaluation was conducted in four patients. Data analyses were performed to compare structural connectivity between patients and controls and to assess connectivity changes after DBS intervention. RESULTS: Baseline findings revealed that structural connectivity is significantly reduced in patients with AN compared to controls, mainly regarding callosal and subcallosal white matter (WM) tracts. Furthermore, pre- vs. post-DBS analyses in AN identified a specific increase after the intervention in two WM tracts: the anterior thalamic radiation and the superior longitudinal fasciculus-parietal bundle. CONCLUSIONS: This study supports that structural connectivity is highly compromised in severe AN. Moreover, this investigation preliminarily reveals that after DBS of the SCC and NAcc in severe AN, there are WM modifications. These microstructural plasticity adaptations may signify a mechanistic underpinning of DBS in this psychiatric disorder.

A Patient-Centered Perspective on Changes in Personal Characteristics After Deep Brain Stimulation.

Importance: Deep brain stimulation (DBS) results in improvements in motor function and quality of life in patients with Parkinson disease (PD), which might impact a patient's perception of valued personal characteristics. Prior studies investigating whether DBS causes unwanted changes to oneself or one's personality have methodological limitations that should be addressed. Objective: To determine whether DBS is associated with changes in characteristics that patients with PD identify as personally meaningful. Design, Setting, and Participants: This cohort study assessed changes in visual analog scale (VAS) ratings reflecting the extent to which patients with PD manifested individually identified personal characteristics before and 6 and 12 months after DBS at a large academic medical center from February 21, 2018, to December 9, 2021. The VAS findings were tailored to reflect the top 3 individually identified personal characteristics the patient most feared losing. The VASs were scored from 0 to 10, with 0 representing the least and 10 the most extreme manifestation of the trait. Change scores were examined at the individual level. Content analysis was used to code the qualitative data. Qualitative and quantitative analyses were performed from January 12, 2019 (initial qualitative coding), to December 15, 2023. Exposure: Deep brain stimulation. Main Outcomes and Measures: The primary outcome variable was the mean VAS score for the top 3 personal characteristics. The secondary outcome was the incidence of meaningful changes on the patients' top 3 characteristics at the individual level. Results: Fifty-two of 54 dyads of patients with PD and their care partners (96.3%) were recruited from a consecutive series approved for DBS (36 patients [69.2%] were male and 45 care partners [86.5%] were female; mean [SD] age of patients, 61.98 [8.55] years). Two patients and 1 care partner were lost to follow-up. Increases in the mean VAS score (indicative of greater manifestation of [ie, positive changes in] specific characteristics) were apparent following DBS for ratings of both the patients (Wald χ2 = 16.104; P < .001) and care partners (Wald χ2 = 6.746; P < .001) over time. The slopes of the changes for both the patient and care partners were correlated, indicating agreement in observed changes over time. The individual level analyses indicated that scores for most patients and care partners remained the same or increased. Conclusions and Relevance: In this cohort study, participants reported greater (more positive) manifestations of individually identified, valued characteristics after DBS. These findings may be relevant to informing decision-making for patients with advanced PD who are considering DBS.

Long-term outcomes of subthalamic nucleus deep brain stimulation for Parkinson's disease in Singapore.

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson's disease (PD), reducing dyskinesia and time spent in the "OFF" state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the "OFF" state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P<0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.