Target For Deep Brain Stimulation Research Articles

CM-Pf deep brain stimulation in polyneuromodulation for epilepsy.

Neuromodulation is a viable option for patients with drug-resistant epilepsies. We reviewed the management of patients with two deep brain neurostimulators. In addition, patients implanted with a device targeting the centromedian-parafascicular (CM-Pf) nuclear complex supplements this report to provide an illustrative case to implantation and programming a patient with three active devices. A narrative review using PubMed and Embase identified patients with drug-resistant epilepsy implanted with more than one neurostimulator was performed. Combinations of vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) were identified. We provide a background of a newly reported case of an adult with a triple implant eventually responding to CM-Pf DBS as the third implant following suboptimal benefit from VNS and RNS. In review of the literature, dual-device therapy is increasing in reports of use with combinations of VNS, RNS, and DBS to treat patients with drug-resistant epilepsy. We review dual-device implants with thalamic DBS device combinations, functional neural networks, and programming patients with dual devices. CM-Pf is a new target for DBS and has shown a variable response in focal epilepsy. We report the unique case of 28-year-old male with drug-resistant focal epilepsy who experienced a 75% seizure reduction with CM-Pf DBS as his third device after suboptimal responses to VNS and RNS. After 9 months, he also experienced seizure freedom from recurrent focal to bilateral tonic-clonic seizures. No medical or surgical complications or safety issues were encountered. We demonstrate safety and feasibility in an adult combining active VNS, RNS, and CM-Pf DBS. Patients with dual-device therapy who experience a suboptimal response to initial device use at optimized settings should not be considered a neuromodulation "failure." Strategies to combine devices require a working knowledge of brain networks.

Research hotspots and frontiers of essential tremor from 2013 to 2023: a visualization analysis based on CiteSpace.

ET, one of the most prevalent neurological disorders, presents a significant challenge in terms of disability. Despite the growing focus on ET in recent years, comprehensive bibliometric analysis has been lacking. This study delves into essential tremor research covering the period from 2013 to 2023, utilizing the Web of Science (WOS) database. Employing CiteSpace for quantitative analysis, it examines an array of metrics including annual publication trends, contributions from countries and institutions, authorship patterns, key terminologies, and patterns of reference co-citation. The primary objective is to use CiteSpace for a detailed visual exploration of the literature over the last decade, pinpointing the evolving landscape and key areas of focus in essential tremor research, and thus providing a foundation for future investigative endeavors. There were 2,224 literary works included in all. The amount of published works has been steadily rising in recent years. Of them, the majority originate from the United States, Louis, Elan D. is the publisher of the most publications (161 articles), and Movement Disorders is the journal that receives the most citations. The key words contribution and co-cited literatures suggest that the main research hotspots in recent years are the physiological and pathological mechanism of essential tremor, the determination of optimal targets for deep brain stimulation (DBS) and surgery transcranial magnetic resonance-guided focused ultrasound (MRgFUS) in the surgical management of essential tremor and the innovative research of botulinum toxin administration method.

Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.

Validation of the hotspot for dorsolateral subthalamic nucleus targeting in deep brain stimulation surgery for Parkinson’s disease: a post hoc analysis of a randomised controlled trial

BackgroundVisualisation of the dorsolateral subthalamic nucleus (STN) remains challenging on 1.5 and 3Tesla T2-weighted MRI. Our previously defined hotspot, relative to the well-visualised medial STN border, serves as an MRI...

Robot-assisted deep brain stimulation

Deep brain stimulation (DBS) is recognised as a safe and effective treatment for several movement disorders, namely essential tremor, Parkinson's disease, and dystonia, as well as for obsessive–compulsive disorder and refractory epilepsy. The main anatomical target of DBS is the basal ganglia. The DBS system comprises a pulse generator and surgically implanted electrodes. Lead placements must be accurate because the effects of DBS rely on the spatial restriction of the stimulation. Neurosurgical centres have started adopting robot-assisted DBS surgery. The results so far have been promising, with lead placement accuracy comparable to that of frame-based procedures. Additionally, robot-assisted procedures are shorter and less demanding on patients. Robot-assisted DBS can be used on patients who are fully awake or under general anaesthesia, as well as on children.

Precision targeting in the globus pallidus interna: insights from the multicenter, prospective, blinded VA/NINDS CSP 468 study.

Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson's disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets. In this study, the authors analyzed the anatomical lead location and 6-month postsurgical, double-blinded outcome measures of 86 patients who underwent bilateral GPi DBS. These patients were selected from the multicenter Veterans Affairs (VA)/National Institutes of Neurological Disorders and Stroke (NINDS) Cooperative Studies Program (CSP) 468 study to identify the optimal target zones ("sweet spots") for the control of overall motor (United Parkinson's Disease Rating Scale [UPDRS]-III), axial, tremor, rigidity, and bradykinesia symptoms. Lead coordinates were normalized to Montreal Neurological Institute space and the optimal target zones were identified and validated using a leave-one-patient-out approach. The authors' findings revealed statistically significant optimal target zones for UPDRS-III (R = 0.37, p < 0.001), axial (R = 0.22, p = 0.042), rigidity (R = 0.20, p = 0.021), and bradykinesia (R = 0.23, p = 0.004) symptoms. These zones were localized within the primary motor and premotor subdivisions of the GPi. Interestingly, these zones extended beyond the GPi lateral border into the GPi-globus pallidus externa (GPe) lamina and into the GPe, but they did not reach the GPi ventral border, challenging traditional surgical approaches based on pallidotomies. Drawing upon a robust dataset, this research effectively delineates specific optimal target zones for not only overall motor improvement but also symptom subscores. These insights hold the potential to enhance the precision of targeting in subsequent bilateral GPi DBS surgical procedures.

Deep Brain Stimulation of the Subthalamic Nucleus vs. Globus Pallidus Internus in the Treatment of Parkinson’s Disease: A Systematic Review

Abstract Background Parkinson’s disease (PD) is a very common debilitating disease especially in the elderly population. Bilateral stimulation of the subthalamic nucleus or the globus pallidus internus provides significant motor benefits for patients with advanced Parkinson’s disease, while reducing dyskinesia and motor fluctuation. High frequency stimulation of the STN and the GPi is relatively safe. The effects are stable even after 1 year of stimulation. Aim of the Work The primary goal of the current review is to compare the efficacy of using the Subthalamic Nucleus (STN) vs. the Globus Pallidus Internus (GPi) as the primary target for Deep Brain Stimulation (DBS) in the treatment of Parkinson disease (PD); in terms of improved motor function measured using the Unified Parkinson's Disease Rating Scale (UPDRS), psychiatric symptoms, rate of reduction of medication, and complications. This will be done through a systematic review of literature addressing this research question. Patients and Methods In this Review, the authors are aiming at the analysis of the collective outcomes from studies comparing bilateral deep brain stimulation of the Subthalamic Nucleus and the Globus Pallidus Internus in the management of idiopathic Parkinson’s disease. The following electronic databases were searched for included articles: PubMed, Google Scholar, EMBASE, Science Direct, Cochrane database of systematic reviews, using the keywords “Parkinson’s disease – treatment – management – deep brain stimulation – subthalamic – globus pallidus internus” in different combinations. Also, manual search were conducted for reference lists of included articles. Limiting the search in English. The information sources previously mentioned were searched from 2000 to 2021. Results A total of 594 patients underwent STN-DBS, with a mean change in total UPDRSIII score of 3.26 on medication and 25.04 off medication. A total of 446 patients underwent GPi-DBS, with a mean change in total UPDRSIII score of 4.75 on medication and 19.31 off medication. There was a higher change for GPi on medication that was statistically significant with a p value (˂0.001), while off medication STN caused a higher change that was also statistically significant with a p value (˂0.001). We observed a statistically significant higher average improvement in ADLs after STN-DBS than GPi, however, non- motor function improvements were greater after GPi DBS than STN DBS. Conclusion Based on our systematic review and other available data in the literature, the STN may be the preferred target for DBS in consideration of motor function improvement, medication reduction, and economic efficiency, although GPI stimulation has some advantages in terms of mood and cognition. Treatment decisions should be individualized and based on patients’ specific symptoms and expectations. Additional well-designed multicenter clinical trials that can minimize bias are needed, especially for evaluation of the long-term outcomes of the two stimulation targets.

A reproducible pipeline for parcellation of the anterior limb of the internal capsule

The anterior limb of the internal capsule (ALIC) is a white matter structure connecting the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation (DBS) for obsessive-compulsive disorder. There is strong interest in improving DBS targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. Following algorithm development and refinement, we analyzed 43 control subjects each with 2 sets of 3T MRI data and a subset of 5 controls with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on prefrontal PFC regions of interest, and we analyzed the relationships among bundles. We successfully reproduced the topographies established by prior anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intra-subject variability relative to inter-subject variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. Our dMRI algorithm reliably generates biologically validated ALIC white matter reconstructions, allowing for more precise modelling of fibers for neuromodulation therapies.

Intraoperative DBS targeting of the globus pallidus internus by using motor evoked potentials

ObjectivesTarget localization for deep brain stimulation (DBS) is a crucial step that influences the clinical benefit of the DBS procedure together with the reduction of side effects. In this work, we address the feasibility of DBS target localization in the globus pallidus internus (GPi) aided by intraoperative motor-evoked potentials with emphasis on the reduction of capsular side effects. Material and methodsMicro-macroelectrode recordings were performed intraoperatively on 20 patients that underwent DBS treatment of the GPi (GPi-DBS). Motor evoked potentials (MEP) were elicited intraoperatively by micro- and macroelectrode stimulation during stereotactic DBS surgery. We studied the relationship between MEP thresholds and the internal capsule (IC) proximity. ResultsWe found a significant correlation between intraoperative MEP thresholds and IC proximity for microelectrode stimulation. ConclusionsWe provide further evidence of the role of MEPs for DBS target localization in the GPi, which extends and confirms the usefulness of MEPs as previously reported by DBS target localization studies dealing with the subthalamic and thalamic nuclei. Our approach is advantageous in that it provides criteria to determine the DBS target without the need to rely on a patient's response while avoiding capsular effects.

The comparison of DBS and RNS for adult drug-resistant epilepsy: a systematic review and meta-analysis.

Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE. PubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis. A total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50-62%, p > 0.05) and 61% (95% CI 54-68%, p > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58-76%, p > 0.05) and 71% (95% CI 64-78%, p > 0.05). Different targets of DBS did not show significant effect on seizure reduction (p > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p < 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS (p > 0.05). Both DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.

Basal ganglia theta power indexes trait anxiety in people with Parkinson's disease.

Neuropsychiatric symptoms are common and disabling in Parkinson's disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments.In this study, we assessed the intracranial neurophysiological correlates of anxiety in PD patients treated with deep brain stimulation (DBS) in the laboratory and at home. We hypothesized that low-frequency (theta-alpha) activity would be associated with anxiety. We recorded local field potentials (LFP) from the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi) DBS implants in three PD cohorts: 1) patients with recordings (STN) performed in hospital at rest via perioperatively externalized leads, without active stimulation, both ON or OFF dopaminergic medication; 2) patients with recordings (STN or GPi) performed at home while resting, via a chronically implanted commercially available sensing-enabled neurostimulator (Medtronic Percept™ device), ON dopaminergic medication, with stimulation both ON or OFF; 3) patients with recordings performed at home while engaging in a behavioral task via STN and GPi leads and electrocorticography paddles (ECoG) over premotor cortex connected to an investigational sensing-enabled neurostimulator, ON dopaminergic medication, with stimulation both ON or OFF.Trait anxiety was measured with validated clinical scales in all participants, and state anxiety was measured with momentary assessment scales at multiple time points in the two at-home cohorts. Power in theta (4-8 Hz) and alpha (8-12 Hz) ranges were extracted from the LFP recordings, and their relation with anxiety ratings was assessed using linear mixed-effects models. In total, 33 PD patients (59 hemispheres) were included. Across three independent cohorts, with stimulation OFF, basal ganglia theta power was positively related to trait anxiety (all p<0.05). Also in a naturalistic setting, with individuals at home at rest with stimulation and medication ON, basal ganglia theta power was positively related to trait anxiety (p<0.05). This relationship held regardless of the hemisphere and DBS target. There was no correlation between trait anxiety and premotor cortical theta-alpha power. There was no within-patient association between basal ganglia theta-alpha power and state anxiety. We showed that basal ganglia theta activity indexes trait anxiety in PD. Our data suggest that theta could be a possible physiomarker of neuropsychiatric symptoms and specifically of anxiety in PD, potentially suitable for guiding advanced DBS treatment tailored to the individual patient's needs, including non-motor symptoms.

Septal stimulation attenuates hippocampal seizure with subregion specificity.

Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment. Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model. DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons. DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS. The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.

Evaluating functional connectivity differences between DBS ON/OFF states in essential tremor

Deep brain stimulation (DBS) targeting the ventral intermediate (Vim) nucleus of the thalamus is an effective treatment for essential tremor (ET). We studied 15 ​ET patients undergoing DBS to a major input/output tract of the Vim, the dentato-rubro-thalamic tract (DRTt), using resting state functional MRI (rsfMRI) to evaluate connectivity differences between DBS ON and OFF and elucidate significant regions most influential in impacting tremor control and/or concomitant gait ataxia. Anatomical/functional 1.5T MRIs were acquired and replicated for each DBS state. Tremor severity and gait ataxia severity were scored with DBS ON at optimal stimulation parameters and immediately upon DBS OFF. Whole brain analysis was performed using dual regression analysis followed by randomized permutation testing for multiple correction comparison. Regions of interest (ROI) analysis was also performed. All 15 patients had tremor improvement between DBS ON/OFF (p ​< ​0.001). Whole brain analysis revealed significant connectivity changes between states in the left pre-central gyrus and left supplemental motor area. Group analysis of ROIs revealed that, with threshold p ​< ​0.05, in DBS ON vs. OFF both tremor duration and tremor improvement were significantly correlated to changes in connectivity. A sub-group analysis of patients with greater ataxia had significantly decreased functional connectivity between multiple ROIs in the cortex and cerebellum when DBS was ON compared to OFF. Stimulation of the DRTt and concordant improvement of tremor resulted in connectivity changes seen in multiple regions outside the motor network; when combined with both structural and electrophysiologic connectivity, this may help to serve as a biomarker to improve DBS targeting and possibly predict outcome.

P.038 Exploring alternative deep brain stimulation targets for movement disorder in children – a systematic literature review

Background: Deep Brain Stimulation (DBS) has become increasingly prevalent in the management of paediatric movement disorders, with the globus pallidus interna (GPi) serving as the most utilized target. However, limitations exist, including variable responses in genetic versus acquired forms of movement disorder and structural damage in the GPi would preclude its use as a target. Given these limitations, there is a pressing need to explore alternative targets. We investigated the application of non-GPi targets in paediatrics through a systematic review. Methods: Individual data points were gathered from references identified through a systematic electronic search and analysed descriptively. We included paediatric patients (0-18 years) with movement disorders who underwent non-GPi-DBS. We excluded adults and other indications. Results: Preliminarily, 64 patients were identified from 40 references. Dystonia was the most common movement disorder type, followed by tremor and chorea. The subthalamic nucleus was the frequent DBS target for dystonia, yielding promising outcomes of improvement as measured on the Burke-Fahn-Marsden movement scale ranging from 43% to 95%. The ventral intermediate nucleus was the second most employed target, demonstrating favourable results. Conclusions: Non-pallidal DBS targets hold promise as potentially efficient and safe. However, to further validate their effectiveness and safety, larger multi-centre randomized studies are required.

Deep Brain Stimulation for Tourette's Syndrome and Challenging for Neuropsychiatric Disease

The efficacy of deep brain stimulation(DBS)for Tourette's syndrome is being well established. Herein, we performed DBS in 38 patients and confirmed that its efficacy was comparable with that reported internationally. Although many patients experience severe symptoms, the indications for surgery remain controversial. One reason for this is that Tourette syndrome has the potential for spontaneous remission, while DBS treatment results in the need for long-term management, which can be difficult for some patients. Furthermore, while several targets for DBS have been reported, no treatment guidelines have yet been established. The efficacy of DBS for neuropsychiatric disorders, such as obsessive-compulsive disorder, depression, and dementia, is gradually being reported. However, this use has many limitations in terms of expectations similar to those seen with Tourette's syndrome, leading to problems with expanding indications for these disorders. Indications for these disorders should be addressed in conjunction with ethical issues. It is expected that more data on this topic will be collected in the future.

503. Precision Deep Brain Stimulation Targeting for Obsessive-Compulsive Disorder Based on Tractography

503. Precision Deep Brain Stimulation Targeting for Obsessive-Compulsive Disorder Based on Tractography

Deep Brain Stimulation for Primary Refractory Tinnitus: A Systematic Review.

tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show promise. This systematic review focuses on the current evidence for the safety and efficacy of DBS for treatment of refractory tinnitus. a systematic search in PubMed and EMBASE was performed to identify peer-reviewed studies on DBS of non-cortical structures for the primary indication of tinnitus treatment. Three studies were identified as meeting these criteria, one of which had two related sub-studies. seven patients with available data who underwent DBS for tinnitus were identified. DBS targets included nucleus accumbens (NAc), ventral anterior limb of the internal capsule (vALIC), caudate nucleus, and the medial geniculate body (MGB) of the thalamus. All studies used the Tinnitus Functional Index (TFI) as a primary outcome measure. DBS of the caudate was most commonly reported (n = 5), with a mean TFI improvement of 23.3 points. Only one subject underwent DBS targeting the NAc/vALIC (extrapolated TFI improvement 46.8) and one subject underwent DBS targeting the MGB (TFI improvement 59 points). DBS is a promising treatment option for refractory subjective tinnitus, with early data, from small patient cohorts in multiple studies, suggesting its safety and efficacy. Further studies with a larger patient population are needed to support this safety and efficacy before implementing this treatment to daily practice.

Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

General anesthesia versus local anesthesia for deep brain stimulation targeting of STN in Parkinson's disease: A systematic review and meta-analysis.

Subthalamic nucleus deep brain stimulation (STN-DBS) is a viable therapeutic for advanced Parkinson's disease. However, the efficacy and safety of STN-DBS under local anesthesia (LA) versus general anesthesia (GA) remain controversial. This meta-analysis aims to compare them using an expanded sample size. The databases of Embase, Cochrane Library and Medline were systematically searched for eligible cohort studies published between 1967 and 2023. Clinical efficacy was assessed using either Unified Parkinson's Disease Rating Scale (UPDRS) section III scores or levodopa equivalent dosage requirements. Subgroup analyses were performed to assess complications (adverse effects related to stimulation, general neurological and surgical complications, and hardware-related complications). Fifteen studies, comprising of 13 retrospective cohort studies and 2 prospective cohort studies, involving a total of 943 patients were included in this meta-analysis. The results indicate that there were no significant differences between the 2 groups with regards to improvement in UPDRS III score or postoperative levodopa equivalent dosage requirement. However, subgroup analysis revealed that patients who underwent GA with intraoperative imaging had higher UPDRS III score improvement compared to those who received LA with microelectrode recording (MER) (P = .03). No significant difference was found in the improvement of UPDRS III scores between the GA group and LA group with MER. Additionally, there were no notable differences in the incidence rates of complications between these 2 groups. Our meta-analysis indicates that STN-DBS performed under GA or LA have similar clinical outcomes and complications. Therefore, GA may be a suitable option for patients with severe symptoms who cannot tolerate the procedure under LA. Additionally, the GA group with intraoperative imaging showed better clinical outcomes than the LA group with MER. A more compelling conclusion would require larger prospective cohort studies with a substantial patient population and extended long follow-up to validate.

The role of neuromodulation in the management of drug-resistant epilepsy.

Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies.This comprehensive review aims to provide valuable insights on present and future use of neuromodulation.