Stimulation Of Nucleus Research Articles

The impact on speech with different deep brain stimulation settings in Parkinson's disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by the progressive degeneration of the nigrostriatal dopaminergic pathway which affects movement initiation and maintenance, causing hypokinetic dysarthria in PD. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used to manage rigidity, bradykinesias and drug-induced dyskinesias. While STN DBS successfully manages many symptoms of PD, speech response has been widely reported as “no or negative impact”. The High-Frequency Setting (HFS) is more focused within the STN which is known to control appendicular symptoms. However, the unintentional HFS current spreading to adjacent brain areas, such as the corticospinal and corticobulbar tracts, was thought to contribute to the deterioration of axial symptoms, including speech. The Low-Frequency Setting (LFS) extends more dorsally and ventrally towards surrounding structures, hence does not show the same negative impact and may reduce the negative impact on the axial functions including speech. This double-blind, randomized perception study assesses the impact of two deep brain stimulation (DBS) settings (high-frequency stimulation and interleave-interlink dual-frequency paradigm) on speech produced by 20 patients with PD. The impact of the two testing conditions was different for different Syllable Types with significant negative correlation between the articulatory rate and articulatory accuracy.

PO027 / #1009 ANODIC VERSUS CATHODIC GENERATION OF SUBTHALAMIC NUCLEUS AND CORTICAL EVOKED POTENTIALS USING NON-SYMMETRICAL MONOPOLAR STIMULATION IN PARKINSON'S DISEASE PATIENTS: E-POSTER VIEWING

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard of care treatment for moderate to severe Parkinson’s disease. However, optimizing the therapeutic benefit of DBS can, in some cases, be complicated by the occurrence of side effects that are attributed to current spread outside of the target region. Modeling studies have suggested non-symmetric waveforms may result in preferential activation of neural elements and potentially increase DBS’ therapeutic window [1]. To date, however, data demonstrating the physiological effects of alternative waveform morphologies in human patients has been limited.

PO258 / #814 DEEP BRAIN STIMULATION IN DISORDERS OF CONSCIOUSNESS: A 10 YEAR INSTITUTIONAL EXPERIENCE: E-POSTER VIEWING

Disorders of consciousness, namely vegetative state (VS) and minimally conscious state (MCS), represent serious conditions with mayor consequences for patients and their families. Several studies have described regaining of consciousness in such patients using deep brain stimulation (DBS) of brain or brainstem nuclei. The aim of our study is to present results of 10 years’ experience in using DBS as a therapy for VS/ MCS patients.

O133 / #499 ANTERIOR THALAMIC NUCLEUS DEEP BRAIN STIMULATION IN REFRACTORY EPILEPSY. ANATOMICAL HOTSPOT FOR STABLE THERAPY RESPONDERS: TRACK 2: NEUROMODULATION FOR EPILEPSY

The SANTE trial documented the efficacy of Deep Brain Stimulation of the Anterior Nucleus of the Thalamus (ANT-DBS) in drug resistant epilepsy (DRE) patients.1 The Medtronic Registry for Epilepsy (MORE) is an observational open label study aiming to collect clinical data about ANT-DBS therapy efficacy. This study aims to detect objective evidence of anatomical hotspots for therapy effective ANT-DBS. Such hotspots may be used by Neurosurgeons as a guideline for DBS targeting in de-novo DBS for epilepsy patients.

Effect of Fastigial Nucleus Stimulation on Serum Inflammatory Factors in Patients with Coronary Heart Disease

Objective: To observe the effect of Fastigial Nucleus Stimulation (FNS) on serum inflammatory factors in patients with coronary heart disease. Methods: 144 patients with coronary heart disease were randomly divided into the experimental group (n = 72) and the control group (n = 72). The control group received conventional medication for coronary heart disease. The experimental group was given the cerebellar nucleus electrical stimulation on the basis of routine medication. High-sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor α (TNF-α), Lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured before and after treatment in both groups. Results: There were no significant differences in serum hs-CRP, TNF-α, IL-6 and Lp-PLA2 between the two groups before treatment (p > 0.05). After treatment, serum hs-CRP, TNF-α, IL-6 and Lp-PLA2 were significantly lower in the two groups than before treatment (p < 0.01). The levels of serum hs-CRP, TNF- α , IL-6 and Lp-PLA2 in the experimental group were significantly lower than those in the control group (p < 0.05). Conclusion: FNS can effectively reduce the level of serum inflammatory factors in patients with coronary heart disease. (Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT04121715).

Total intravenous anesthesia with remimazolam in a patient with epilepsy who underwent deep brain stimulation: a case report

Drugs administered for anesthesia can trigger seizure attacks in patients with epilepsy. Benzodiazepines have been consistently reported to be anticonvulsants, and a novel benzodiazepine, remimazolam, was recently introduced. We report a case of total intravenous anesthesia maintained with remimazolam in a patient with epilepsy who underwent deep brain stimulation of both anterior thalamic nuclei. Despite the administration of multiple anti-epileptic drugs, no tolerance to remimazolam was observed. Perioperative seizures were also not observed. Remimazolam can be considered the anesthetic of choice in patients with epilepsy.

Mapping the neural circuits responding to deep brain stimulation of the anterior nucleus of the thalamus in the rat brain

Clinical studies have demonstrated that deep brain stimulation of the anterior nucleus of the thalamus (ANT) is a safe and effective treatment for focal epilepsy and drug-resistant epilepsy. However, the mechanism of action of ANT deep brain stimulation, especially in terms of neuromodulatory circuits, is not fully understood. In this study, we evaluated the anatomical and functional connectivity of the ANT in rats. For anatomical connectivity, herpes simplex virus (HSV) and pseudorabies virus (PRV; Bartha stain) were focally injected into the ANT of rats to label the connected brain structures in the retrograde and anterograde directions, respectively. For functional connectivity, we used c-Fos mapping in conjunction with electrical stimulation of the ANT to map the brain structures functionally connected to the ANT. Circuit connectivity mapping revealed that the ANT was connected to the hippocampus, the nucleus accumbens, the dorsal part of the lateral septal nucleus (LSD), the amygdala, the secondary motor cortex (M2), the cingulate cortex, the substantia nigra, the hypothalamus, and other regions. The ipsilateral connections were stronger than the contralateral connections. Deep brain stimulation of the ANT resulted in c-fos expression in the cortex, hippocampus, amygdala, striatum and hypothalamus, with the strongest activation in the hippocampus. These results suggest that the ANT has a wide range of structural and functional connections, which may underlie the effectiveness of deep brain stimulation in treating epilepsy. Data Availability StatementThe datasets generated for this study are available on request to the corresponding author.

Deep brain stimulation of the subthalamic nucleus for epilepsy.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a promising palliative option for patients with refractory epilepsy. However, crucial questions remain unanswered: Which patients are the optimal candidates? How, where, and when to stimulate the STN? And what is the mechanism of STN-DBS action on epilepsy? Thus, we reviewed the clinical evidence on the antiepileptic effects of STN-DBS and its possible mechanisms on drug-resistant epilepsy, its safety, and the factors influencing stimulation outcomes. This information may guide clinical decision-making. In addition, based on the current knowledge on the effect of STN-DBS on epilepsy, we suggest research that needs to be carried out in the future.

Microendoscopic transventricular deep brain stimulation of the anterior nucleus of the thalamus as a safe treatment in intractable epilepsy: A feasibility study

IntroductionDeep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is proposed in patients with severe intractable epilepsy. When used, the transventricular approach increases the risk of bleeding due the anatomy around the entry point in the thalamus. To avoid such a complication, we used a transventricular microendoscopic technique. MethodsWe performed a retrospective study of nine adult patients who were surgically treated for refractory epilepsy between 2010 and 2019 by DBS of the anterior thalamic nucleus. ResultsEndoscopy provides a direct visual control of the entry point of the lead in the thalamus through the ventricle by avoiding ependymal vessels. No hemorrhage was recorded and accuracy was systematically checked by intraoperative stereotactic MRI. We reported a responder rate improvement in 88.9% of patients at 1 year and in 87.5% at 2 years. We showed a significant decrease in global seizure count per month one year after DBS (68.1%; P=0.013) leading to an overall improvement in quality of life. No major adverse effect was recorded during the follow-up. ANT DBS showed a prominent significant effect with a decrease of the number of generalized seizures. ConclusionWe aimed at a better ANT/lead collimation using a vertical transventricular approach under microendoscopic monitoring. This technique permitted to demonstrate the safety and the accuracy of the procedure.

The impact of pulse timing on cortical and subthalamic nucleus deep brain stimulation evoked potentials.

The impact of pulse timing is an important factor in our understanding of how to effectively modulate the basal ganglia thalamocortical (BGTC) circuit. Single pulse low-frequency DBS-evoked potentials generated through electrical stimulation of the subthalamic nucleus (STN) provide insight into circuit activation, but how the long-latency components change as a function of pulse timing is not well-understood. We investigated how timing between stimulation pulses delivered in the STN region influence the neural activity in the STN and cortex. DBS leads implanted in the STN of five patients with Parkinson's disease were temporarily externalized, allowing for the delivery of paired pulses with inter-pulse intervals (IPIs) ranging from 0.2 to 10 ms. Neural activation was measured through local field potential (LFP) recordings from the DBS lead and scalp EEG. DBS-evoked potentials were computed using contacts positioned in dorsolateral STN as determined through co-registered post-operative imaging. We quantified the degree to which distinct IPIs influenced the amplitude of evoked responses across frequencies and time using the wavelet transform and power spectral density curves. The beta frequency content of the DBS evoked responses in the STN and scalp EEG increased as a function of pulse-interval timing. Pulse intervals <1.0 ms apart were associated with minimal to no change in the evoked response. IPIs from 1.5 to 3.0 ms yielded a significant increase in the evoked response, while those >4 ms produced modest, but non-significant growth. Beta frequency activity in the scalp EEG and STN LFP response was maximal when IPIs were between 1.5 and 4.0 ms. These results demonstrate that long-latency components of DBS-evoked responses are pre-dominantly in the beta frequency range and that pulse interval timing impacts the level of BGTC circuit activation.

Deep brain stimulation of the anterior nuclei of the thalamus in focal epilepsy

ObjectiveTo review the therapeutic effects of deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) and the predictors of its effectiveness, safety, and adverse effects. MethodsA comprehensive search of the medical literature (PubMed) was conducted to identify relevant articles investigating ANT-DBS therapy for epilepsy. Out of 332 references, 77 focused on focal epilepsies were reviewed. ResultsThe DBS effect is probably due to decreased synchronization of epileptic activity in the cortex. The potential mechanisms from cellular to brain network levels are presented. The ANT might participate actively in the network elaborating focal seizures. The effects of ANT-DBS differed in various studies; ANT-DBS was linked with a 41% seizure frequency reduction at 1 year, 69% at 5 years, and 75% at 7 years. The most frequently reported adverse effects, depression and memory impairment, were considered non-serious in the long-term follow-up view. ANT-DBS also has been used in a few cases to treat status epilepticus. ConclusionsWe reviewed the clinical literature and identified several factors that may predict seizure outcome following DBS therapy. More large-scale trials are required since there is a need to explore stimulation settings, apply patient-tailored therapy, and identify the presurgical predictors of patient response. SignificanceA critical review of the published literature on ANT-DBS in focal epilepsy is presented. ANT-DBS mechanisms are not fully understood; possible explanations are provided. Biomarkers of ANT-DBS effectiveness may lead to patient-tailored therapy.

Deep brain stimulation of the anterior nucleus of the thalamus for drug‐resistant epilepsy: Long‐term efficacy and outcomes from a prospective cohort

AbstractAimThe anterior nucleus of the thalamus (ANT) has been one of the deep brain stimulation (DBS) targets for drug‐resistant epilepsy. This study aims to investigate the control of seizures among patients with ANT DBS for epilepsy. We have pioneered DBS for epilepsy in Hong Kong since 2015 and this study aims to report the long‐term outcomes from a prospective cohort.MethodsThis is a prospective cohort study of ANT DBS for adult patients with drug‐resistant epilepsy, who are unsuitable for resective epilepsy surgery.ResultsSix patients (3 females and 3 males, mean age 31.3) received bilateral ANT DBS in a tertiary university hospital from 2015 to 2018 (one in 2015, two in 2017 and three in 2018). Both frontal transventricular and parietal approaches were used. The active contacts were selected based on the closest Euclidean distance to the mammillothalamic tract and ANT junction. Five of the six cases (83.3%) achieved greater than 50% reduction in seizures after the operations. The median percentage of reduction in seizures was 58.5% at 3 years after DBS (range, 32.7%–80%). Overall, there was a trend of improving seizure control rate from year 1 to year 6 after the ANT DBS operations.ConclusionsThis is the first report of ANT DBS for drug‐resistant epilepsy in Hong Kong. The results are encouraging. ANT DBS for drug‐resistant epilepsy is effective and sustained in long term. The treatment option of ANT DBS should be considered in suitable candidates with drug‐resistant epilepsy in our locality.

Post-mortem brain histological examination in the substantia nigra and subthalamic nucleus in Parkinson's disease following deep brain stimulation.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, pathologically hallmarked by the loss of dopamine neurons in the substantia nigra (SN) and alpha-synuclein aggregation. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a common target to treat the motor symptoms in PD. However, we have less understanding of the cellular changes in the STN during PD, and the impact of DBS on the STN and SN is limited. We examined cellular changes in the SN and STN in PD patients with and without STN-DBS treatment. Post-mortem brain tissues from 6 PD non-STN-DBS patients, 5 PD STN-DBS patients, and 6 age-matched controls were stained with markers for neurodegeneration (tyrosine hydroxylase, alpha-synuclein, and neuronal loss) and astrogliosis (glial fibrillary acidic protein). Changes were assessed using quantitative and semi-quantitative microscopy techniques. As expected, significant neuronal cell loss, alpha-synuclein pathology, and variable astrogliosis were observed in the SN in PD. No neuronal cell loss or astrogliosis was observed in the STN, although alpha-synuclein deposition was present in the STN in all PD cases. DBS did not alter neuronal loss, astrogliosis, or alpha-synuclein pathology in either the SN or STN. This study reports selective pathology in the STN with deposits of alpha-synuclein in the absence of significant neuronal cell loss or inflammation in PD. Despite being effective for the treatment of PD, this small post-mortem study suggests that DBS of the STN does not appear to modulate histological changes in astrogliosis or neuronal survival, suggesting that the therapeutic effects of DBS mechanism may transiently affect STN neural activity.

Bilateral deep brain stimulation of the subthalamic nucleus: Targeting differences between the first and second side

Introduction and objectivesDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is a recognized treatment for drug-refractory Parkinson's disease (PD). However, the therapeutic success depends on the accuracy of targeting. This study aimed to evaluate potential accuracy differences in the placement of the first and second electrodes implanted, by comparing chosen electrode trajectories, STN activity detected during microelectrode recording (MER), and the mismatch between the initially planned and final electrode positions on each side. Materials and methodsIn this retrospective cohort study, we analyzed data from 30 patients who underwent one-stage bilateral DBS. For most patients, three arrays of microelectrodes were used to determine the physiological location of the STN. Final target location depended also on the results of intraoperative stimulation. The choice of central versus non-central channels was compared. The Euclidean vector deviation was calculated using the initially planned coordinates and the final position of the tip of the electrode according to a CT scan taken at least a month after the surgery. ResultsThe central channel was chosen in 70% of cases on the first side and 40% of cases on the second side. The mean length of high-quality STN activity recorded in the central channel was longer on the first side than the second (3.07±1.85mm vs. 2.75±1.94mm), while in the anterior channel there were better MER recordings on the second side (1.59±2.07mm on the first side vs. 2.78±2.14mm on the second). Regarding the mismatch between planned versus final electrode position, electrodes on the first side were placed on average 0.178±0.917mm lateral, 0.126±1.10mm posterior and 1.48±1.64mm inferior to the planned target, while the electrodes placed on the second side were 0.251±1.08mm medial, 0.355±1.29mm anterior and 2.26±1.47mm inferior to the planned target. ConclusionThere was a tendency for the anterior trajectory to be chosen more frequently than the central on the second side. There was also a statistically significant deviation of the second electrodes in the anterior and inferior directions, when compared to the electrodes on the first side, suggesting that another cause other than brain shift may be responsible. We should therefore factor this during planning for the second implanted side. It might be useful to plan the second side more anteriorly, possibly reducing the number of MER trajectories tested and the duration of surgery.

Automatic localization of target point for subthalamic nucleus-deep brain stimulation via hierarchical attention-UNet based MRI segmentation.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease, the outcome of this surgery is highly dependent on the accurate placement of the electrode in the optimal target of STN. In this study, we aim to develop a target localization pipeline for DBS surgery, considering that the heart of this matter is to achieve the STN and red nucleus segmentation, a deep learning-based automatic segmentation approach is proposed to tackle this issue. To address the problems of ambiguous boundaries and variable shape of the segmentation targets, the hierarchical attention mechanism with two different attention strategies is integrated into an encoder-decoder network for mining both semantics and fine-grained details for segmentation. The hierarchical attention mechanism is utilized to suppress irrelevant regions in magnetic resonance (MR) images while build long-range dependency among segmentation targets. Specifically, the attention gate (AG) is integrated into low-level features to suppress irrelevant regions in an input image while highlighting the salient features useful for segmentation. Besides, the self-attention involved in the transformer block is integrated into high-level features to model the global context. Ninety-nine brain magnetic resonance imaging (MRI) studies were collected from 99 patients with Parkinson's disease undergoing STN-DBS surgery, among which 80 samples were randomly selected as the training datasets for deep learning training, and ground truths (segmentation masks) were manually generated by radiologists. We applied five-fold cross-validation on these data to train our model, the mean results on 19 test samples are used to conduct the comparison experiments, the Dice similarity coefficient (DSC), Jaccard (JA), sensitivity (SEN), and HD95 of the segmentation for STN are 88.20%, 80.32%, 90.13%, and 1.14mm, respectively, outperforming the state-of-the-art STN segmentation method with 2.82%, 4.52%, 2.56%, and 0.02mm respectively. The source code and trained models of this work have been released in the URL below: https://github.com/liuruiqiang/HAUNet/tree/master. In this study, we demonstrate the effectiveness of the hierarchical attention mechanism for building global dependency on high-level semantic features and enhancing the fine-grained details on low-level features, the experimental results show that our method has considerable superiority for STN and red nucleus segmentation, which can provide accurate target localization for STN-DBS.

Subthalamic high-beta oscillation informs the outcome of deep brain stimulation in patients with Parkinson's disease.

BackgroundThe therapeutic effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) is related to the modulation of pathological neural activities, particularly the synchronization in the β band (13–35 Hz). However, whether the local β activity in the STN region can directly predict the stimulation outcome remains unclear.ObjectiveWe tested the hypothesis that low-β (13–20 Hz) and/or high-β (20–35 Hz) band activities recorded from the STN region can predict DBS efficacy.MethodsLocal field potentials (LFPs) were recorded in 26 patients undergoing deep brain stimulation surgery in the subthalamic nucleus area. Recordings were made after the implantation of the DBS electrode prior to its connection to a stimulator. The maximum normalized powers in the theta (4–7 Hz), alpha (7–13 Hz), low-β (13–20 Hz), high-β (20–35 Hz), and low-γ (40–55 Hz) subbands in the postoperatively recorded LFP were correlated with the stimulation-induced improvement in contralateral tremor or bradykinesia–rigidity. The distance between the contact selected for stimulation and the contact with the maximum subband power was correlated with the stimulation efficacy. Following the identification of the potential predictors by the significant correlations, a multiple regression analysis was performed to evaluate their effect on the outcome.ResultsThe maximum high-β power was positively correlated with bradykinesia–rigidity improvement (rs = 0.549, p < 0.0001). The distance to the contact with maximum high-β power was negatively correlated with bradykinesia–rigidity improvement (rs = −0.452, p < 0.001). No significant correlation was observed with low-β power. The maximum high-β power and the distance to the contact with maximum high-β power were both significant predictors for bradykinesia–rigidity improvement in the multiple regression analysis, explaining 37.4% of the variance altogether. Tremor improvement was not significantly correlated with any frequency.ConclusionHigh-β oscillations, but not low-β oscillations, recorded from the STN region with the DBS lead can inform stimulation-induced improvement in contralateral bradykinesia–rigidity in patients with PD. High-β oscillations can help refine electrode targeting and inform contact selection for DBS therapy.

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability.

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T>G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C>A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.

Neuromodulation in drug-resistant epilepsy: A review of current knowledge.

Nearly 1% of the global population suffers from epilepsy. Drug-resistant epilepsy (DRE) affects one-third of epileptic patients who are unable to treat their condition with existing drugs. For the treatment of DRE, neuromodulation offers a lot of potential. The background, mechanism, indication, application, efficacy, and safety of each technique are briefly described in this narrative review, with an emphasis on three approved neuromodulation therapies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation (RNS). Neuromodulatory approaches involving direct or induced electrical currents have been developed to lessen seizure frequency and duration in patients with DRE since the notion of electrical stimulation as a therapy for neurologic diseases originated in the early nineteenth century. Although few people have attained total seizure independence for more than 12 months using these treatments, more than half have benefitted from a 50% drop in seizure frequency over time. Although promising outcomes in adults and children with DRE have been achieved, challenges such as heterogeneity among epilepsy types and etiologies, optimization of stimulation parameters, a lack of biomarkers to predict response to neuromodulation therapies, high-level evidence to aid decision-making, and direct comparisons between neuromodulatory approaches remain. To solve these existing gaps, authorize new kinds of neuromodulation, and develop personalized closed-loop treatments, further research is needed. Finally, both invasive and non-invasive neuromodulation seems to be safe. Implantation-related adverse events for invasive stimulation primarily include infection and pain at the implant site. Intracranial hemorrhage is a frequent adverse event for DBS and RNS. Other stimulation-specific side-effects are mild with non-invasive stimulation.

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

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. To investigate the survival rate and long-term outcome of DBS. We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

Dexmedetomidine depresses neuronal activity in the subthalamic nucleus during deep brain stimulation electrode implantation surgery.

Micro-electrode recordings are often necessary during electrode implantation for deep brain stimulation of the subthalamic nucleus. Dexmedetomidine may be a useful sedative for these procedures, but there is limited information regarding its effect on neural activity in the subthalamic nucleus and on micro-electrode recording quality. We recorded neural activity in five patients undergoing deep brain stimulation implantation to the subthalamic nucleus. Activity was recorded after subthalamic nucleus identification while patients received dexmedetomidine sedation (loading - 1 μg kg-1 over 10-15 min, maintenance - 0.7 μg kg-1 h-1). We compared the root-mean square (RMS) and beta band (13-30 Hz) oscillation power of multi-unit activity recorded by microelectrode before, during and after recovery from dexmedetomidine sedation. RMS was normalised to values recorded in the white matter. Multi-unit activity decreased during sedation in all five patients. Mean normalised RMS decreased from 2.8 (1.5) to 1.6 (1.1) during sedation (43% drop, p = 0.056). Beta band power dropped by 48.4%, but this was not significant (p = 0.15). Normalised RMS values failed to return to baseline levels during the time allocated for the study (30 min). In this small sample, we demonstrate that dexmedetomidine decreases neuronal firing in the subthalamic nucleus as expressed in the RMS of the multi-unit activity. As multi-unit activity is a factor in determining the subthalamic nucleus borders during micro-electrode recordings, dexmedetomidine should be used with caution for sedation during these procedures. NCT01721460.