Deep Brain Stimulation Research Articles

Vestibular Neurostimulation for Parkinson's Disease: A Novel Device-Aided Non-Invasive Therapeutic Option.

Dopaminergic replacement therapy remains the mainstay of symptomatic treatment for Parkinson's disease (PD), but many unmet needs and gaps remain. Device-based treatments or device-aided non-oral therapies are typically used in the advanced stages of PD, ranging from stereotactic deep brain stimulation to levodopa or apomorphine infusion therapies. But there are concerns associated with these late-stage therapies due to a number of procedural, hardware, or long-term treatment-related side effects of these treatments, and their limited nonmotor benefit in PD. Therefore, there is an urgent unmet need for low-risk adjuvants or standalone therapies which can address the range of burdensome motor and nonmotor symptoms that occur in PD. Recent studies suggest that non-invasive neurostimulation of the vestibular system may be able to address these gaps through the stimulation of the vestibular brainstem sensory network which extensively innervates brain regions, regulating both motor and a range of nonmotor functions. Therapeutic non-invasive vestibular stimulation is a relatively modern concept that may potentially improve a broad range of motor and nonmotor symptoms of PD, even at early stages of the disease. Here, we review previous studies supporting the therapeutic potential of vestibular stimulation for the treatment of PD and discuss ongoing clinical trials and potential areas for future investigations.

Deep Brain Stimulation for Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views on Candidacy Factors

Introduction Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS. Objectives To explore mental health clinicians’ views on what clinical and psychosocial factors they would consider when determining which children with OCD would be good DBS candidates. Materials and Methods In depth, semi-structured interviews were conducted with n = 25 mental health clinicians who treat pediatric patients with OCD. The interviews were transcribed, coded, and analyzed using thematic content analysis. Three questions focused on key, clinical, and psychosocial factors for assessing candidacy were analyzed to explore respondent views on candidacy factors. Our analysis details nine overarching themes expressed by clinicians, namely the patient’s previous OCD treatment, OCD severity, motivation to commit to treatment, presence of comorbid conditions, family environment, education on DBS, quality of life, accessibility to treatment, and patient age and maturity. Conclusions Clinicians generally saw considering DBS treatment in youth as a last resort and only for very specific cases. DBS referral was predominantly viewed as acceptable for children with severe TR-OCD who have undertaken intensive, appropriate treatment without success, whose OCD has significantly reduced their quality of life, and who exhibit strong motivation to continue treatment given the right environment. Appropriate safeguards, eligibility criteria, and procedures should be discussed and identified before DBS for childhood TR-OCD becomes practice.

Targeting Oligodendrocyte Dynamics and Remyelination: Emerging Therapies and Personalized Approaches in Multiple Sclerosis Management.

Multiple sclerosis [MS] is a progressive autoimmune condition that primarily affects young people and is characterized by demyelination and neurodegeneration of the central nervous system [CNS]. This in-depth review explores the complex involvement of oligodendrocytes, the primary myelin- producing cells in the CNS, in the pathophysiology of MS. It discusses the biochemical processes and signalling pathways required for oligodendrocytes to function and remain alive, as well as how they might fail and cause demyelination to occur. We investigate developing therapeutic options that target remyelination, a fundamental component of MS treatment. Remyelination approaches promote the survival and differentiation of oligodendrocyte precursor cells [OPCs], restoring myelin sheaths. This improves nerve fibre function and may prevent MS from worsening. We examine crucial parameters influencing remyelination success, such as OPC density, ageing, and signalling pathway regulation [e.g., Retinoid X receptor, LINGO-1, Notch]. The review also examines existing neuroprotective and antiinflammatory medications being studied to see if they can assist oligodendrocytes in surviving and reducing the severity of MS symptoms. The review focuses on medicines that target the myelin metabolism in oligodendrocytes. Altering oligodendrocyte metabolism has been linked to reversing demyelination and improving MS patient outcomes through various mechanisms. We also explore potential breakthroughs, including innovative antisense technologies, deep brain stimulation, and the impact of gut health and exercise on MS development. The article discusses the possibility of personalized medicine in MS therapy, emphasizing the importance of specific medicines based on individual molecular profiles. The study emphasizes the need for reliable biomarkers and improved imaging tools for monitoring disease progression and therapy response. Finally, this review focuses on the importance of oligodendrocytes in MS and the potential for remyelination therapy. It also underlines the importance of continued research to develop more effective treatment regimens, taking into account the complexities of MS pathology and the different factors that influence disease progression and treatment.

Preoperative cognitive profile predictive of cognitive decline after subthalamic deep brain stimulation in Parkinson's disease.

Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD=2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.

Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease.

Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting electrodes into specific areas of the brain to treat a variety of medical conditions, including Parkinson's disease. Doubts and questions from patients prior to or following surgery should be addressed in line with the most recent scientific and clinical practice. ChatGPT emerges as an example of how artificial intelligence can be used, with its ability to comprehend and answer medical questions in an understandable way, accessible to everyone. However, the risks of these resources still need to be fully understood.ChatGPT models 3.5 and 4 responses to 40 questions in English and Portuguese were independently graded by two experienced specialists in functional neurosurgery and neurological movement disorders and resolved by a third reviewer. ChatGPT 3.5 and 4 demonstrated a good level of accuracy in responding to 80 questions in both English and Portuguese, related to DBS surgery for Parkinson's disease. The proportion of responses graded as correct was 57.5% and 83.8% for GPT 3.5 and GPT 4, respectively. GPT 3.5 provided potentially harmful answers for 6.3% (5/80) of its responses. No responses from GPT 4 were graded as harmful. In general, ChatGPT 3.5 and 4 demonstrated good performance in terms of quality and reliability across two different languages. Nonetheless, harmful responses should not be scorned, and it's crucial to consider this aspect when addressing patients using these resources. Considering the current safety concerns, it's not advisable for patients to use such models for DBS surgery guidance. Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease.

A Meta-Analysis of Medication Reduction and Motor Outcomes After Awake Versus Asleep Deep Brain Stimulation for Parkinson Disease.

There remains significant debate regarding the performance of deep brain stimulation (DBS) procedures for Parkinson disease (PD) under local or general anesthesia. The aim of this meta-analysis was to compare the clinical outcomes between "asleep" DBS (general anesthesia) and "awake" DBS (local anesthesia) for PD. We conducted a comprehensive literature review of all published studies on DBS for PD following PRISMA guideline on PubMed and Cochrane library from January 2004 to April 2023. Inclusion criteria included cohort ≥15 patients, clinical outcomes data which included Unified Parkinson's Disease Rating Scale (UPDRS) score and levodopa equivalent daily dosage (LEDD), and ≥3 months of follow-up. Analysis was conducted using Stata software. There were 18 articles that met inclusion criteria. On meta-analysis, there were no significant differences between awake or asleep DBS with regard to percent change in UPDRS III "off" med/"on" DBS condition (P = .6) and LEDD score (P = .99). On subgroup analysis, we found that the choice of target had no significant effect on improvement of UPDRS III (P = 1.0) or LEDD (P = .99) change for the asleep vs awake operative approach. There were also no statistically significant differences between microelectrode recording (MER) use and no MER use in postoperative UPDRS III (P = 1.0) or LEDD improvement (P = .90) between awake and asleep surgery. There was no significant difference in the primary motor outcomes and LEDD improvement between asleep vs awake DBS. The variables of target selection and MER use had no statistically significant impact on outcome. We find that asleep techniques are both safe and effective compared with the awake technique.

Exploring White Matter Microstructure with Symptom Severity and Outcomes Following Deep Brain Stimulation in Tremor Syndromes.

Essential tremor (ET) and dystonic tremor (DT) are movement disorders that cause debilitating symptoms, significantly impacting daily activities and quality of life. A poor understanding of their pathophysiology, as well as the mediators of clinical outcomes following deep brain stimulation (DBS), highlights the need for biomarkers to accurately characterise and optimally treat patients. We assessed the white matter microstructure of pathways implicated in the pathophysiology and therapeutic intervention in a retrospective cohort of patients with DT (n = 17) and ET (n = 19). We aimed to identity associations between white matter microstructure, upper limb tremor severity, and tremor improvement following DBS. A fixel-based analysis pipeline was implemented to investigate white matter microstructural metrics in the whole brain, cerebello-thalamic pathways and tracts connected to stimulation volumes following DBS. Associations with preoperative and postoperative severity were analysed within each disorder group and across combined disorder groups. DBS led to significant improvements in both groups. No group differences in stimulation positions were identified. When white matter microstructural data was aligned according to the maximally affected upper limb, increased fiber density, and combined fiber density & cross-section of fixels in the left cerebellum were associated with greater tremor severity across DT and ET patients. White matter microstructure did not show associations with postoperative changes in cerebello-thalamic pathways, or tracts connected to stimulation volumes. Diffusion changes of the cerebellum are associated with the severity of upper limb tremor and appear to overlap in essential or dystonic tremor disorders.

Deep brain stimulation of hippocampus in treatment of refractory temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious.

What can neuroimaging of neuromodulation reveal about the basis of circuit therapies for psychiatry?

Neuromodulation is increasingly becoming a therapeutic option for treatment resistant psychiatric disorders. These non-invasive and invasive therapies are still being refined but are clinically effective and, in some cases, provide sustained symptom reduction. Neuromodulation relies on changing activity within a specific brain region or circuit, but the precise mechanisms of action of these therapies, is unclear. Here we review work in both humans and animals that has provided insight into how therapies such as deep brain and transcranial magnetic stimulation alter neural activity across the brain. We focus on studies that have combined neuromodulation with neuroimaging such as PET and MRI as these measures provide detailed information about the distributed networks that are modulated and thus insight into both the mechanisms of action of neuromodulation but also potentially the basis of psychiatric disorders. Further we highlight work in nonhuman primates that has revealed how neuromodulation changes neural activity at different scales from single neuron activity to functional connectivity, providing key insight into how neuromodulation influences the brain. Ultimately, these studies highlight the value of combining neuromodulation with neuroimaging to reveal the mechanisms through which these treatments influence the brain, knowledge vital for refining targeted neuromodulation therapies for psychiatric disorders.

Interrogating basal ganglia circuit function in people with Parkinson's disease and dystonia.

The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials. GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression. We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses. This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

Interrogating basal ganglia circuit function in people with Parkinson’s disease and dystonia

Background:The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.Methods:Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials.Results:GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression.Conclusions:We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.Funding:This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

The Rate and Risk Factors of Deep Brain Stimulation-Associated Complications: A Single-Center Experience.

Deep brain stimulation (DBS) is an established neurosurgical treatment of a variety of neurological disorders. DBS is considered a safe and effective neurosurgical procedure; however, surgical complications are inevitable, and clinical outcomes may vary. The aim of this study was to describe DBS complications at a large clinical center in the United States and to investigate the relationship between patients' baseline characteristics, surgical technique, and operative complications. We identified all patients who underwent DBS lead implantation at our center between 1st January 2012 and 1st January 2020. We extracted relevant information regarding patient demographics, surgical details, clinical complications, and clinical outcomes from the electronic medical records. A total of 859 leads were implanted in 481 patients (153 men, 328 women). The mean patient age at the time of the surgery was 65 years, with the mean disease duration of 13.3 years. There were no mortalities and 57 readmissions within 30 days (mean = 14.2 days). The most common complications included pneumocephalus (n = 661), edema (n = 78), altered mental state (n = 35), implantable pulse generator discomfort (n = 34), hemorrhage (n = 26), and infection (n = 23). Most notably, the use of general anesthesia, hypertension, heart disease, and depression were associated with significantly longer postoperative stay. High preoperative body mass index was associated with higher rates of surgery-related infections and lead revision/explantation. The intraoperative mean arterial pressure, anesthesia type, and frame apparatus were all important predictors of postoperative pneumocephalus. In this report, we described the rates and types of complications associated with DBS surgery at a large neurosurgical center in the United States. The novel insights highlighted in this study present an opportunity to further improve the clinical outcomes and patient selection in DBS surgery.

Ethics of deep brain stimulation for neuropsychiatric disorders.

Deep Brain Stimulation (DBS) has emerged as a revolutionary neurosurgical technique with significant implications for the treatment of various neuropsychiatric disorders. Initially developed for movement disorders like Parkinson's disease, DBS has expanded to psychiatric conditions such as obsessive-compulsive disorder, depression, anorexia nervosa, dystonia, essential tremor, and Tourette's syndrome. This paper explores the clinical efficacy and ethical considerations of DBS in treating these disorders. While DBS has shown substantial promise in alleviating symptoms and improving quality of life, it raises ethical challenges, including issues of informed consent, patient selection, long-term management, and equitable access to treatment. The irreversible nature of DBS, potential adverse effects, and the high cost of the procedure necessitate a rigorous ethical framework to guide its application. The ongoing evolution of neuromodulation requires continuous ethical analysis and the development of guidelines to ensure that DBS is used responsibly and equitably across different patient populations. This paper underscores the need for a balanced approach that integrates clinical efficacy with ethical considerations to optimize patient outcomes and ensure sustainable practice.

Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study.

If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS. We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson's disease patients and for those with motor fluctuations and dyskinesias. Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.

Cost-Effectiveness Analysis of Deep Brain Stimulation for the Treatment of Alcohol Use Disorder and Alcoholic Liver Disease.

Alcohol use disorder (AUD) is a major public health concern and cause of mortality and morbidity. Alcohol-associated liver disease (ALD) is a debilitating complication of AUD, mitigated by abstinence from alcohol use. Deep brain stimulation (DBS) is emerging as a potential treatment for AUD. However, its cost-effectiveness compared to the standard medical treatment is unclear. To estimate the cost-effectiveness of DBS compared to medical management for patients with AUD and ALD. We utilized a decision analytic model based on published literature to conduct a cost-effectiveness analysis of costs and health outcomes for DBS and medical management in patients with AUD and ALD. We also carried out a threshold analysis to determine the probability of success necessary for DBS to be cost-effective. Costs were measured in 2024 US dollars and effectiveness in quality-adjusted life years (QALYs). We used a time horizon of 1-2 years and adopted a societal perspective. Our results show that for AUD patients in general, DBS is not cost-effective at any DBS success rate. However, for advanced ALD patients, defined as fibrosis stage 3 or beyond DBS becomes cost-effective. For these patients, DBS is cost-effective over a two-year period at a $100,000 willingness-to-pay threshold at DBS success rates greater than 53%. For advanced decompensated ALD patients, DBS is cost-effective over a one-year period at DBS success rate greater than 35%. Should it prove efficacious, DBS may be cost-effective for patients with AUD and ALD. Thus, future randomized controlled trials to evaluate its efficacy are warranted.

Automated Sleep Detection in Movement Disorders Using Deep Brain Stimulation and Machine Learning.

Automated sleep detection in movement disorders may allow monitoring sleep, potentially guiding adaptive deep brain stimulation (DBS). The aims were to compare wake-versus-sleep status (WSS) local field potentials (LFP) in a home environment and develop biomarkers of WSS in Parkinson's disease (PD), essential tremor (ET), and Tourette's syndrome (TS) patients. Five PD, 2 ET, and 1 TS patient were implanted with Medtronic Percept (3 STN [subthalamic nucleus], 3 GPi [globus pallidus interna], and 2 ventral intermediate nucleus). Over five to seven nights, β-band (12.5-30 Hz) and/or α-band (7-12 Hz) LFP power spectral densities were recorded. Wearable actigraphs tracked sleep. From sleep to wake, PD LFP β-power increased in STN and decreased in GPi, and α-power increased in both. Machine learning classifiers were trained. For PD, the highest WSS accuracy was 93% (F1 = 0.93), 86% across all patients (F1 = 0.86). The maximum accuracy was 86% for ET and 89% for TS. Chronic intracranial narrowband recordings can accurately identify sleep in various movement disorders and targets in this proof-of-concept study. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

What Should be the Anatomical Target in Deep Brain Stimulatıon in an Essential Tremor Plus Rest Tremor Case? Technical Case Report of Deep Brain Stimulation

While Deep Brain Stimulation (DBS) of Subthalamic Nucleus (STN) is effective on resting tremors, but its effectiveness on postural and kinetic tremors is limited. DBS of the Ventral Intermediate Nucleus (VIM) is effective on many types of tremors, especially postural and kinetic tremors, but its effect is weak on motor symptoms in Parkinson’s disease (PD). Although there is a consensus in the literature about where the anatomical target should be in essential tremor (ET) and PD, there are only case reports about where the anatomical target should be in Essential Tremor Plus Rest Tremor (ET+RT) cases.In this article, we aimed to reveal the effectiveness of STN DBS in a case-diagnosed with ET+RT. The patient had action tremors in both upper extremities for 21 years and developed rest tremors in both upper and lower extremities for the last six years. Rest tremor was effectively controlled with bilateral STN DBS. Postural tremor in the right upper extremity was continued, although it decreased.STN may be an appropriate choice when choosing an anatomical target in DBS in cases of resting, postural, and kinetic tremor.

Pallidal Versus Subthalamic Deep-Brain Stimulation for Generalized Isolated Dystonia: A Retrospective Study.

Objectives: Deep-brain stimulation (DBS) has been used for the treatment of medically refractory dystonia with excellent results. In this study, we compared in detail the therapeutic advantages of two DBS targets for generalized isolated dystonia. Methods: In this retrospective study, we recruited 29 patients with generalized isolated dystonia who had undergone DBS treatment targeting either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) in the Department of Functional Neurosurgery at Tiantan Hospital, Beijing, China, between January 2016 and December 2021. The movement and disability subscales of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) were used to assess the severity of their dystonic symptoms and their activities of daily living, respectively. SF-36 was used to evaluate the patients' health-related quality of life. Results: The percentage improvement in the BFMDRS-M score at 6 months relative to the baseline score was clearly higher in the STN group (63.91%) than in the GPi group (38.36%). At the 3-, 6-, and 12-month follow-ups, the percentage improvement in arm symptoms was significantly higher after DBS of the STN (70.64%, 80.66%, and 76.89%, respectively) than after stimulation of the GPi (36.75%, 34.21%, and 38.47%, respectively). At 12 months after surgery, patient quality of life had improved on all SF-36 subscales in both groups. Conclusions: STN-DBS may have more advantages than GPi-DBS in patients with obvious arm dystonia. STN-DBS had a better clinical effect than GPi-DBS within 6 months after surgery.

Dopaminergic progenitors generated by small molecule approach survived, integrated, and promoted functional recovery in (6-OHDA) mouse model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the loss of dopamine-producing neurons in the brain, causing motor symptoms like tremors and stiffness. Although current treatments like medication and deep brain stimulation can alleviate symptoms, they don't address the root cause of neuron loss. Therefore, cell replacement therapy emerges as a promising treatment strategy. However, the generation of engraftable dopaminergic (DA) cells in clinically relevant quantities is still a challenge. Recent advances in cell reprogramming technologies open up vast possibilities to produce patient-specific cells of a desired type in therapeutic quantities. The main cell reprogramming strategies involve the enforced expression of individual or sets of genes through viral transduction or transfection, or through small molecules, known as the chemical approach, which is a much easier and safer method. In our previous studies, using a small molecule approach (combinations of epigenetic modifiers and SMAD inhibitors such asDorsomorphin and SB431542), we have been able to generate DA progenitors from human mesenchymal stem cells (hMSCs). The aim of this study was to further improve the method for the generation of DA progenitors and to test their therapeutic effect in an animal model of Parkinson's. The results showed that the addition of an autophagy enhancer (AE) to our DA cell induction protocol further increased the yield of DA progenitor cells. The results also showed that DA progenitors transplanted into the mouse model of PD survived, integrated, and improved PD motor symptoms. These data suggest that chemically-produced DA cells can be very promising and safe cellular therapeutics for PD.

More than pacemakers and defibrillators: perioperative management of implantable devices for patient safety.

The use of implantable medical devices (IMDs) continues to increase with estimates that 10% of the American population will have an IMD in their lifetime. IMDs require special considerations for management in the perioperative period to ensure optimal patient care and patient safety. This review summarizes the current perioperative considerations for IMDs. This review summarizes perioperative recommendations for spinal cord stimulators, deep brain stimulators, peripheral nerve stimulators, vagus nerve stimulators, muscle stimulators, intrathecal drug delivery systems, implantable infusion pumps, artificial pancreas devices, continuous glucose monitors, and cochlear implants. There are multiple publications and guidelines regarding the perioperative considerations of cardiac implantable electronic devices; thus, this review excludes those devices. This review includes recommendations on management of the device perioperatively, the potential complications, and postoperative care of the device. There are very few guidelines regarding the perioperative management of IMDs. Given the significant impact that these devices have on patient care and safety, evidence-based guidelines should be established.