Deep Brain Stimulation Treatment Research Articles

Assessing Cardiovascular Disease Risk Factors in Parkinson’s Disease by Treatment: Levodopa Alone versus Deep Brain Stimulation with Levodopa (P12-047-19)

ObjectivesCardiovascular disease (CVD) risk factors include obesity, hypertension (HTN), diabetes (DM), dyslipidemia, and hyperhomocysteinemia. They are associated with accelerated cognitive decline in persons with Parkinson’s disease (PwPD). Levodopa is the primary medication to manage PD but can increase homocysteine. However, PwPD taking levodopa have a lower prevalence of DM and HTN than PwPD not taking levodopa. Deep brain stimulation (DBS) is a newer PD treatment. DBS may lower levodopa dose, reducing homocysteine, but PwPD with DBS can experience weight gain. This case study will compare CVD risk factors of PwPD treated with levodopa alone versus DBS with levodopa. MethodsFour male participants with PD (2 taking levodopa (LD1, LD2) and 2 with DBS (DBS1, DBS2) were assessed for CVD risk at ≥7 evaluations within 3y. CVD risk factors assessed: 1) body mass index (BMI) ≥25 kg/m2; 2) diastolic blood pressure (DBP) > 80 mmHg; 3) high density lipoprotein cholesterol (HDL-C) < 40 mg/dL; 4) low density lipoprotein cholesterol (LDL-C) > 100 mg/dL; 5) total cholesterol to HDL-C (TC/HDL-C) ratio > 4; 6) the Dietary Screening Tool (DST); 7) Framingham’s CVD 10y risk score. At baseline LD1 (62 y) was on medication for PD, HTN and dyslipidemia and had a myocardial infarction. He was following a heart healthy diet and overtime reported eating smaller portions. At baseline LD2 (70 y) was on medication for PD and to lower LDL-C. LD2 experienced decreased appetite and food intake. At baseline, DBS1 (62 y) was on medication for PD, HTN and dyslipidemia. He eats a balanced diet but is at nutritional risk. DBS2 (68 y) was taking PD, HTN medication. He self-reported swallowing and chewing issues. ResultsDBS1/2 TC/HDL-C ratios categorized them at risk at all time points, while LD1/2 ratios were ideal. DBS1/2 experienced high LDL-C. HDL-C values were at risk level for DBS1/2, while LD1/2 were not. All were overweight to obese, but DBS1/2 consistently had high BMI scores. DBS1/2 DST scores were at nutritional risk, while LD1/2 DST scores were at possible risk or no risk. LD1/2 had elevated DBP, while DBS1/2 had normal values. ConclusionsWhile all PWPD exhibit CVD risk factors, DBS treated patients may be more likely to have a greater number of risk factors after treatment. Further studies should look into risk factors before and after treatment of DBS. Funding SourcesUniversity of Rhode Island’s Enhancement of Graduate Research Award and SPARK Award.

Cortico-subthalamic Coherence in a Patient With Dystonia Induced by Chorea-Acanthocytosis: A Case Report.

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatment in Parkinson’s disease (PD) but much less frequently targeted for other disorders. Here we report the results of simultaneous local field potential (LFP) recordings and magnetoencephalography (MEG) in a single patient who was implanted bilaterally in the STN for the treatment of dystonia induced by chorea-acanthocytosis. Consistent with the previous results in PD, the dystonia patient showed significant subthalamo-cortical coherence in the high beta band (28–35 Hz) on both sides localized to the mesial sensorimotor areas. In addition, on the right side, significant coherence was found in the theta-alpha band (4–12 Hz) that localized to the medial prefrontal cortex with the peak in the anterior cingulate gyrus. Comparison of STN power spectra with a previously reported PD cohort showed increased power in the theta and alpha bands and decreased power in the low beta band in dystonia which is consistent with most of the previous studies. The present report extends the range of disorders for which cortico-subthalamic oscillatory connectivity has been characterized. Our results strengthen the evidence that at least some of the subthalamo-cortical oscillatory coherent networks are a feature of the healthy brain, although we do not rule out that coherence magnitude could be affected by disease.

Finding the Sweet Spot: Fine-Tuning DBS Parameters to Cure Seizures While Avoiding Psychiatric Complications.

Reversible Psychiatric Adverse Effects Related to Deep Brain Stimulation of the Anterior Thalamus in Patients With Refractory Epilepsy Järvenpää S, Peltola J, Rainesalo S, et al. Epilepsy Behav. 2018;88:373-379. doi:10.1016/j.yebeh.2018.09.006Objective:Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is becoming a more common treatment for drug-resistant epilepsy. Epilepsy and depression display a bidirectional association. Anterior nucleus of thalamus has connections to anterior cingulate cortex and orbitomedial prefrontal cortex, hence, a possible role in emotional and executive functions, and thus, ANT DBS might exert psychiatric adverse effects. Our aim was to evaluate previous and current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery and assess the predictability of psychiatric adverse effects. Programming-related psychiatric adverse effects are also reported.Method:Twenty-two patients with ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of depressive and other psychiatric symptoms was performed with Montgomery-Åsberg Depression Rating Scale, Beck Depression Inventory, and Symptom Checklist prior to surgery, concentrating on former and current psychiatric symptoms and medications. The follow-up visit was 1 year after surgery.Results:At the group level, no changes in mood were observed during ANT DBS treatment. Two patients with former histories of depression experienced sudden depressive symptoms related to DBS programming settings; these were quickly alleviated after changing the stimulation parameters. In addition, 2 patients with no previous histories of psychosis gradually developed clear paranoid and anxiety symptoms that also relieved slowly after changing the programming settings.Conclusion:The majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes.

Impact of Deep Brain Stimulation of the Subthalamic Nucleus on Neuropsychological Outcomes and Voxel‐Based‐Morphometric‐Analyses in Parkinson's Disease Patients

Parkinson's Disease (PD) is a movement disorder that is characterized by tremor, rigidity, and bradykinesia, due to significant cell‐death of the dopaminergic neurons in the substantia nigra. Deep brain stimulation (DBS) is a surgical intervention used to treat PD patients in which stimulating electrodes are placed bilaterally, most often in the subthalamic nucleus (STN). STN‐DBS is restricted to those who respond sufficiently well to a dopaminergic medication regimen. This procedure alleviates the motor symptoms associated with PD. Historically, the majority of clinical research on STN‐DBS has focused on motor outcomes. Until recently, few studies had explored the effect of STN‐DBS on post‐surgical cognitive and memory outcomes. Moreover, the relationship between cognitive outcomes and neuroanatomical changes in PD patients with STN‐DBS is largely unknown. The goal of this study was to correlate pre‐ and post‐ surgical memory and cognitive neuropsychological outcomes with volumetric changes in relevant neuroanatomical structures before and after DBS intervention. Thus far, 11 PD patients met inclusion criteria for this Colorado Multiple Institutional Review Board (COMIRB) approved study (COMIRB 16‐1060). Voxel‐based‐morphometry of cortical and subcortical brain regions were used to assess structural changes in T1‐weighted MR. Analyzed neuropsychological measures include those from the second edition of the California Verbal Language Test (CVLT‐II). Preliminary neuropsychological analyses suggest that Standard CVLT‐II Long Delayed Free recall of List Learning decreases post surgically. Further neuropsychological and neuroanatomical analyses are ongoing. This study is relevant because it will better characterize neuroanatomical and neurofunctional changes that occur with STN‐DBS so that physicians are better prepared to support their patients after STN‐DBS. Eventually, studies like this one may lead to predictive measures which allow physicians to better screen for patients who will benefit most from DBS surgery based on neuropsychological pre‐testing.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Longitudinal assessment of the neuroanatomical consequences of deep brain stimulation: Application of fornical DBS in an Alzheimer’s mouse model

Following its success in the treatment of refractory movement disorders, deep brain stimulation (DBS) is currently under clinical investigation as a possible treatment for several neuropsychiatric disorders, including Alzheimer’s disease (AD). DBS’s mechanism of action, delivery regimen, optimal brain target, and timeline of behavioural and neuroanatomical outcomes are all open fields of investigation. There is a critical need to develop methodologies that allow us to examine the time course of both behavioural changes and neuroanatomical remodelling in response to DBS. Here we present a proof-of-concept methodology for DBS experiments which incorporates both brain imaging and behaviour in a longitudinal fashion.We implanted triple transgenic AD mouse models (expressing mutations for both amyloid and tau) with custom magnetic resonance imaging (MRI)-compatible, carbon based electrodes. Mice received DBS or sham stimulation to the fornix (a critical white matter node in the brain's memory circuit) for 1 h (100 Hz, 100 μs pulses, 100 μA). Treatment was followed with an adapted Morris water maze (to test learning and memory; performed weekly) and structural MRI (to assess neuroanatomy; 3 days before and 3 days after DBS with a 6 week follow-up). The acute DBS treatment improved learning and long term memory in a delayed, sex specific, and transient manner relative to sham-stimulated controls. Significant, persistent, volumetric changes were seen in diverse brains structures, also heavily mediated by sex. We believe this methodology may be used as a template for DBS-related experimentation and will encourage preclinical studies to use longitudinal designs.

Post mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most commonly used surgical treatment for Parkinson's disease (PD). The disease-modifying aspects of DBS at a cellular level are not fully understood, and the key question of the effect of DBS on the degeneration of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) remains to be answered. A major technical hurdle in determining any neuroprotective effect by DBS is its use in mid- to late-stage patients with PD when a majority of the DA neurons have been lost. In this work, we hypothesized that the long-term clinical benefits of DBS are, at least in part, due to a neuromodulatory effect on the SNpc neurons. These changes would affect cellular energetics and mitochondrial metabolism. We examined the number and volume of mitochondria as well as their vicinity to the DA presynaptic terminals postmortem caudate and putamen of 3 healthy individuals, 4 PD cases, and 3 DBS-treated patients. PD seems to have caused an increase in the mean distance between mitochondria and presynaptic terminals as well as a decrease in mean mitochondrial volume and numbers in DA projections. Although there was no difference in distance between mitochondria and presynaptic terminals of SNpc neurons in PD brains vs. DBS-treated brains, DBS treatment seemed to have inhibited or reversed the reduction in mitochondrial volume and numbers caused by PD. These results suggest enhanced metabolic plasticity leading to neuroprotection in the SNpc as a result of STN-DBS.-Mallach, A., Weinert, M., Arthur, J., Gveric, D., Tierney, T. S., Alavian, K. N. Post mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.

A systematic review of deep brain stimulation for the treatment of drug-resistant epilepsy in childhood.

OBJECTIVE Drug-resistant epilepsy (DRE) presents a therapeutic challenge in children, necessitating the consideration of multiple treatment options. Although deep brain stimulation (DBS) has been studied in adults with DRE, little evidence is available to guide clinicians regarding the application of this potentially valuable tool in children. Here, the authors present the first systematic review aimed at understanding the safety and efficacy of DBS for DRE in pediatric populations, emphasizing patient selection, device placement and programming, and seizure outcomes. METHODS The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations. Relevant articles were identified from 3 electronic databases (MEDLINE, Embase, and Cochrane CENTRAL) from their inception to November 17, 2017. Inclusion criteria of individual studies were 1) diagnosis of DRE; 2) treatment with DBS; 3) inclusion of at least 1 pediatric patient (age ≤ 18 years); and 4) patient-specific data. Exclusion criteria for the systematic review included 1) missing data for age, DBS target, or seizure freedom; 2) nonhuman subjects; and 3) editorials, abstracts, review articles, and dissertations. RESULTS This review identified 21 studies and 40 unique pediatric patients (ages 4–18 years) who received DBS treatment for epilepsy. There were 18 patients with electrodes placed in the bilateral or unilateral centromedian nucleus of the thalamus (CM) electrodes, 8 patients with bilateral anterior thalamic nucleus (ATN) electrodes, 5 patients with bilateral and unilateral hippocampal electrodes, 3 patients with bilateral subthalamic nucleus (STN) and 1 patient with unilateral STN electrodes, 2 patients with bilateral posteromedial hypothalamus electrodes, 2 patients with unilateral mammillothalamic tract electrodes, and 1 patient with caudal zona incerta electrode placement. Overall, 5 of the 40 (12.5%) patients had an International League Against Epilepsy class I (i.e., seizure-free) outcome, and 34 of the 40 (85%) patients had seizure reduction with DBS stimulation. CONCLUSIONS DBS is an alternative or adjuvant treatment for children with DRE. Prospective registries and future clinical trials are needed to identify the optimal DBS target, although favorable outcomes are reported with both CM and ATN in children. ABBREVIATIONS ATN = anterior thalamic nucleus; CM = centromedian nucleus of the thalamus; DBS = deep brain stimulation; DRE = drug-resistant epilepsy; RNS = responsive neurostimulation; STN = subthalamic nucleus; VNS = vagus nerve stimulation.

Development of a miniature device for emerging deep brain stimulation paradigms.

Deep brain stimulation (DBS) is a neuromodulatory approach for treatment of several neurological and psychiatric disorders. A new focus on optimising the waveforms used for stimulation is emerging regarding the mechanism of DBS treatment. Many existing DBS devices offer only a limited set of predefined waveforms, mainly rectangular, and hence are inapt for exploring the emerging paradigm. Advances in clinical DBS are moving towards incorporating new stimulation parameters, yet we remain limited in our capacity to test these in animal models, arguably a critical first step. Accordingly, there is a need for the development of new miniature, low-power devices to enable investigation into the new DBS paradigms in preclinical settings. The ideal device would allow for flexibility in the stimulation waveforms, while remaining suitable for chronic, tetherless, biphasic deep brain stimulation. In this work, we elucidate several key parameters in a DBS system, identify gaps in existing solutions, and propose a new device to support preclinical DBS. The device allows for a high degree of flexibility in the output waveform with easily altered shape, frequency, pulse-width and amplitude. The device is suitable for both traditional and modern stimulation schemes, including those using non-rectangular waveforms, as well as delayed feedback schemes. The device incorporates active charge balancing to ensure safe operation, and allows for simple production of custom biphasic waveforms. This custom waveform output is unique in the field of preclinical DBS devices, and could be advantageous in performing future DBS studies investigating new treatment paradigms. This tetherless device can be easily and comfortably carried by an animal in a back-mountable configuration. The results of in-vitro tests are presented and discussed.

Robust Clinical Benefit of Multi-Lead Deep Brain Stimulation for Treatment of Gilles de la Tourette Syndrome and its Comorbidities

Robust Clinical Benefit of Multi-Lead Deep Brain Stimulation for Treatment of Gilles de la Tourette Syndrome and its Comorbidities

Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome

Background/Aim: The prevalence of cognitive symptoms in recently diagnosed Parkinson’s disease (PD) patients may be as high as 60%. We report a novel deep brain stimulation (DBS) strategy targeting both motor and cognitive symptoms. Methods: A PD patient diagnosed with mild cognitive impairment underwent DBS surgery targeting the globus pallidus interna (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere. Results: Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation. Conclusion: This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead.

Continuous subcutaneous apomorphine in advanced Parkinson's disease patients treated with deep brain stimulation.

Deep brain stimulation (DBS) is an effective therapy for patients with advanced Parkinson's disease (PD). However, sometimes, it is not sufficient to adequately control motor symptoms. We describe our experience with continuous subcutaneous apomorphine infusion (APO) in patients with DBS. We undertook a retrospective analysis of all patients treated with DBS and APO at our centre over 12years. Subjects were allocated to four groups: (1) APO temporarily before DBS, (2) APO after DBS complications before a new DBS, (3) APO after definitive DBS removal, and (4) APO in patients with DBS and declining response. Motor state and other parameters were analysed and compared for the different treatments. Data for 71 patients were evaluated. Group 1: (n = 18) patients improved their motor function significantly with both APO and DBS (off-hours before APO 5.4 ± 1.4; after APO 1.4 ± 1.2, p > 0.001; after DBS 0.7 ± 0.8, p < 0.001). Group 2: (n = 11) patients were found to have mild but significant worsening of motor state between the first DBS treatment (off-hours 0.7 ± 1.0) and APO (2.2 ± 1.5, p = 0.02), and improvement between APO and the second DBS treatment (off-hours 0.6 ± 0.8, p = 0.03). Group 3: (n = 12) patients had mild but significant worsening of motor function between DBS (off-hours 1.1 ± 1.0) and APO (2.0 ± 0.9, p = 0.03). Group 4: (n = 13) significant improvement in motor function was observed between DBS alone (off-hours 3.9 ± 2.6) and DBS combined with APO (2.2 ± 1.3, p = 0.03). In advanced PD, DBS may be not sufficient or may fail to control motor symptoms adequately. In these cases, APO, whether alone or in combination with DBS, is a good choice to improve the disease control.

Chapter 10 - Motor cortical circuits in Parkinson disease and dystonia

We review the motor cortical and basal ganglia involvement in two important movement disorders: Parkinson's disease (PD) and dystonia. Single and paired pulse transcranial magnetic stimulation studies showed altered excitability and cortical circuits in PD with decreased silent period, short interval intracortical inhibition, intracortical facilitation, long afferent inhibition, interhemispheric inhibition, and cerebellar inhibition, and increased long interval intracortical inhibition and short interval intracortical facilitation. In dystonia, there is decreased silent period, short interval intracortical inhibition, long afferent inhibition, interhemispheric inhibition, and increased intracortical facilitation. Plasticity induction protocols revealed deficient plasticity in PD and normal and exaggerated plasticity in dystonia. In the basal ganglia, there is increased β (14-30Hz) rhythm in PD and characteristic 5-18Hz band synchronization in dystonia. These motor cortical circuits, cortical plasticity, and oscillation profiles of the basal ganglia are altered with medications and deep brain stimulation treatment. There is considerable variability in these measures related to interindividual variations, different disease characteristics, and methodological considerations. Nevertheless, these pathophysiologic studies have expanded our knowledge of cortical excitability, plasticity, and oscillations in PD and dystonia, improved our understanding of disease pathophysiology, and helped to develop new treatments for these conditions.

Automatic Sleep Stage Classification Based on Subthalamic Local Field Potentials.

Deep brain stimulation (DBS) is an established treatment for patients with Parkinson's disease (PD). Sleep disorders are common complications of PD and affected by subthalamic DBS treatment. To achieve more precise neuromodulation, chronicsleepmonitoringand closed-loop DBS toward sleep-wake cycles could potentially be utilized. Local field potential (LFP) signals that are sensed by the DBS electrode could be processed as primary feedback signals. This is the first study to systematically investigate the sleep-stage classification based on LFPs in subthalamic nucleus (STN). With our newly developed recording and transmission system, STN-LFPs were collected from 12 PD patients during wakefulness and nocturnal polysomnography sleep monitoring at one month after DBS implantation. Automatic sleep-stage classificationmodels were built with robust and interpretable machine learning methods (support vector machine and decision tree). The accuracy, sensitivity, selectivity, and specificity of the classification reached high values (above90% at most measures) at group and individual levels. Features extracted in alpha (8-13 Hz), beta (13-35 Hz), and gamma (35-50 Hz) bandswere found to contribute the most to the classification. These results will directly guide the engineering development of implantable sleepmonitoring and closed-loopDBS and pave the way for a better understanding of the STN-LFP sleep patterns.

Role of GABAB receptors in proepileptic and antiepileptic effects of an applied electric field in rat hippocampus in vitro

The mechanisms underlying antiepileptic effects of deep brain stimulation (DBS) are complex and poorly understood. Studies on the effects of applied electric fields on epileptic nervous tissue could enable future advances in DBS treatments. Applied electric fields are known to inhibit or enhance epileptic activity in vitro through direct effects on local neurons, but it is unclear whether trans-synaptic effects participate in such actions. The present study investigates, in an epileptic brain slice model, the influence of GABAB receptor activation on excitatory and suppressive effects of a short-duration (10 ms) electric field in rat hippocampus. The results show that perfusion of the GABAB receptor antagonist, CGP 55845 (2 μM), could abolish applied-field induced suppression of orthodromic-stimulus evoked epileptiform afterdischarge activity in the CA1 region. GABAB receptor blockade was associated with an enhanced excitatory (proepileptic) effect of the applied field. However, the suppressive effect, observed in isolation using weak field stimuli, was left unchanged. The G-protein-activated inwardly rectifying K+ channel (GIRK) antagonist, tertiapin (30–50 nM), mimicked the effects of CGP 55845. The results suggest that the applied field activate (elements of) local interneurons to release GABA onto GABAB receptors. The resulting activation of postsynaptic GIRK channels inhibits neuronal activity thereby dampening the direct stimulatory effect of the applied field. The study indicates that local-stimulus induced GABAB receptor activation can serve a protective role under antiepileptic paradigms by preventing electrical stimulation from causing hyperexcitation.

Evaluating reflexive saccades and UDPRS as markers of Deep Brain Stimulation and Best Medical Treatment improvements in Parkinson's disease patients: a prospective controlled study.

To date, there has been no clear evidence regarding the evaluation of saccades as a monitoring tool of motor impairment in Parkinson's disease (PD) Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) patients. The aim of this study was to evaluate the long-term impact of STN-DBS and pharmacological treatment on reflexive saccades' (RS) parameters and UPDRS alterations. The DBS group consisted of 20 PD patients who underwent bilateral STN-DBS. The Postoperative (POP) group consisted of 14 post-DBS patients. The Best Medical Therapy (BMT) group consisted of 20 patients on pharmacotherapy only. RS parameters and the UPDRS scale were measured during three visits in four phases of treatment (i.e. BMT-ON/OFF, DBS-ON/OFF). The significant UPDRS III and UPDRS. Total improvements were observed in all three study groups (p < 0.05), but RS latency improvement was stated only in the DBS group in the DBS-ON phase (p < 0.05). A significant correlation between RS latency increase and UPDRS III score worsening was found in all study groups, with the most evident effect in the UPDRS III ON phase (p < 0.05). RS parameters correlated with UPDRS III outcomes during the postoperative period in DBS-STN patients. Therefore, saccadic evaluation may be a good biomarker of the patient's response to surgical and/or pharmacological treatment.

Assessment of Safety and Outcome of Lateral Hypothalamic Deep Brain Stimulation for Obesity in a Small Series of Patients With Prader-Willi Syndrome

Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. To test the safety and study the outcome of DBS in patients with PWS. This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.

Comparison of Short-Term Stimulation of the Globus Pallidus Interna and Subthalamic Nucleus for Treatment of Primary Dystonia

To compare the efficacy and side effects of bilateral globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) in the same patient with primary dystonia. Patients with primary dystonia from the department of functional neurosurgery in Beijing Tiantan Hospital were recruited for the study. Four electrodes were bilaterally implanted in the GPi and STN. A trial stimulation was applied to determine the preliminary therapeutic effects. Five evaluations were conducted: preoperative, postoperative (before stimulation), after sham stimulation, and after stimulation for 24 hours of GPi and STN using optimal parameters, judged by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS movement score decreased after both short-term GPi stimulation (from 15.3 ± 6.9 to 7.6 ± 4.2, P < 0.05) and short-term STN stimulation (from 15.3 ± 6.9 to 8.6 ± 5.0, P < 0.05). There were significant reductions in facial (eyes and mouth) movement scores after short-term GPi and STN DBS compared with baseline (P < 0.05), but not in cervical symptoms (P > 0.05). The cervical symptoms of tonic dystonia had an improvement after long-term DBS treatment (P < 0.05). There were more adverse events with STN DBS; however, most side effects could be ameliorated by adjusting stimulation parameters. Both short-term GPi and STN stimulation improved the motor symptoms of dystonia, but there was no significant difference between GPi DBS and STN DBS. There were more side effects associated with STN stimulation.

Simulation Study of Intermittent Axonal Block and Desynchronization Effect Induced by High-Frequency Stimulation of Electrical Pulses.

Deep brain stimulation (DBS) has been successfully used in treating neural disorders in brain, such as Parkinson’s disease and epilepsy. However, the precise mechanisms of DBS remain unclear. Regular DBS therapy utilizes high-frequency stimulation (HFS) of electrical pulses. Among all of neuronal elements, axons are mostly inclined to be activated by electrical pulses. Therefore, the response of axons may play an important role in DBS treatment. To study the axonal responses during HFS, we developed a computational model of myelinated axon to simulate sequences of action potentials generated in single and multiple axons (an axon bundle) by stimulations. The stimulations are applied extracellularly by a point source of current pulses with a frequency of 50–200 Hz. Additionally, our model takes into account the accumulation of potassium ions in the peri-axonal spaces. Results show that the increase of extracellular potassium generates intermittent depolarization block in the axons during HFS. Under the state of alternate block and recovery, axons fire action potentials at a rate far lower than the frequency of stimulation pulses. In addition, the degree of axonal block is highly related to the distance between the axons and the stimulation point. The differences in the degree of block for individual axons in a bundle result in desynchronized firing among the axons. Stimulations with higher frequency and/or greater intensity can induce axonal block faster and increase the desynchronization effect on axonal firing. Presumably, the desynchronized axonal activity induced by HFS could generate asynchronous activity in the population of target neurons downstream thereby suppressing over-synchronized firing of neurons in pathological conditions. The desynchronization effect generated by intermittent activation of axons may be crucial for DBS therapy. The present study provides new insights into the mechanisms of DBS, which is significant for advancing the application of DBS.

White Matter Changes Along the Electrode Lead in Patients Treated With Deep Brain Stimulation.

Introduction: Deep brain stimulation (DBS) is an established treatment for various movement disorders. There is little data available about the potential damage to brain parenchyma through DBS treatment. The objective of this study was to investigate the occurrence of signal changes on magnetic resonance imaging (MRI) in patients treated with DBS.Methods: We retrospectively analyzed MRI scans of 30 DBS patients (21 patients with Parkinson's disease, 3 patients with dystonia and 6 patients with tremor) that had undergone additional MRI scans after DBS surgery (ranging from 2 months to 8 years). Axial T2 sequences were analyzed by two raters using a standardized lesion mapping procedure.Results: 26 out of 30 analyzed patients showed hyperintense white matter changes surrounding the DBS lead (mean volume = 2.43 ml). Lesions were prominent along the upper half of the electrode lead within the subcortical white matter, with no abnormalities along the lower lead. Their volume was significantly correlated to the time from surgery to MRI and to the number of microelectrodes used in surgery, but was independent from underlying disease (Parkinson's disease, dystonia, tremor), target structure (STN, GPi, VIM), demographical data, or cardiovascular risk factors.Discussion: White matter changes along the electrode leads in DBS patients are a frequent finding. These changes seem to evolve with certain latency after surgery and might be radiologically classified as a gliosis. Our findings identify the number of intraoperatively used microelectrodes as a risk factor in the formation of gliosis. Therefore, mechanical damage at the time of surgery and an individual tissue response might contribute to their evolution. Further studies are needed to define the exact mechanisms and their clinical impact.

Deep brain stimulation in pediatric dystonia: a systematic review.

While deep brain stimulation (DBS) treatment is relatively rare in children, it may have a role in dystonia to reduce motor symptoms and disability. Pediatric DBS studies are sparse and limited by small sample size, and thus, outcomes are poorly understood. Thus, we performed a systematic review of the literature including studies of DBS for pediatric (age < 21) dystonia. Patient demographics, disease causes and characteristics, motor scores, and disability scores were recorded at baseline and at last post-operative follow-up. We identified 19 studies reporting DBS outcomes in 76 children with dystonia. Age at surgery was 13.8 ± 3.9 (mean ± SD) years, and 58% of individuals were male. Post-operative follow-up duration was 2.8 ± 2.8years. Sixty-eight percent of patients had primary dystonia (PD), of whom 56% had a pathological mutation in DYT1 (DYT1+). Across all patients, regardless of dystonia type, 43.8 ± 36% improvement was seen in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (-M) scores after DBS, while 43.7 ± 31% improvement was observed in BFMDRS disability (-D) scores. Patients with PD were more likely to experience ≥ 50% improvement (56%) in BFMDRS-M scores compared to patients with secondary causes of dystonia (21%, p = 0.004). DYT1+ patients were more likely to achieve ≥ 50% improvement (65%) in BFMDRS-D than DTY1- individuals (29%, p = 0.02), although there was no difference in BFMDRS-M ≥ 50% improvement rates between DYT1+ (66%) or DYT1- (43%) children (p = 0.11). While DBS is less common in pediatric patients, individuals with severe dystonia may receive worthwhile benefit with neuromodulation treatment.