Search

Objectives: Target 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 (MEP) with emphasis on the reduction of capsular side effects., Material and Methods: Micro-macroelectrode recordings were performed intraoperatively on 20 patients that underwent DBS treatment of the GPi (GPi-DBS). MEP were elicited intraoperatively by microelectrode stimulation during stereotactic DBS surgery. We studied the relationship between MEP thresholds and the internal capsule (IC) proximity., Results: We found a significant correlation between intraoperative MEP thresholds and IC proximity., Conclusions: We 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., Competing Interests: Declaration of competing interest CT reports no conflict of interest. PN received travel expenses from Abbott Medical and Boston Scientific, manufacturers of DBS devices. PJS received speaker honoraria and travel reimbursement from Abbott Medical. JV received consultant fees and/or travel grants and/or research grants from Abbott, Boston Scientific, Medtronic, UniQure. AS reports grants from German Research Council; personal fees from Medtronic Inc., Boston Scientific, Abbott Medical, UCB, and Teva Pharma. SJG received honoraria and/or travel expenses from Abbott Medical, Boston Scientific, Inomed and Medtronic., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cortical plasticity induced by quadripulse stimulation (QPS) has been shown to correlate with cognitive functions in patients with relapsing-remitting multiple sclerosis (RRMS) and to not be reduced compared to healthy controls (HCs)., Objective: This study aimed to compare the degree of QPS-induced plasticity between different subtypes of multiple sclerosis (MS) and HCs and to investigate the association of the degree of plasticity with motor and cognitive functions. We expected lower levels of plasticity in patients with progressive MS (PMS) but not RRMS compared to HCs. Furthermore, we expected to find positive correlations with cognitive and motor performance in patients with MS., Methods: QPS-induced plasticity was compared between 34 patients with PMS, 30 patients with RRMS, and 30 HCs using linear mixed-effects models. The degree of QPS-induced cortical plasticity was correlated with various motor and cognitive outcomes., Results: There were no differences regarding the degree of QPS-induced cortical plasticity between HCs and patients with RRMS ( p = 0.86) and PMS ( p = 0.18). However, we only found correlations between the level of induced plasticity and both motor and cognitive functions in patients with intact corticospinal tract integrity. Exploratory analysis revealed significantly reduced QPS-induced plasticity in patients with damage compared to intact corticospinal tract integrity ( p < 0.001)., Conclusion: Our study supports the notion of pyramidal tract integrity being of more relevance for QPS-induced cortical plasticity in MS and related functional significance than the type of disease., Competing Interests: PA received compensation for serving on Scientific Advisory Boards for Allergan, Celgene, Janssen Cilag, Ipsen, Merck, Merz Pharmaceuticals, Novartis, and Biogen; he received speaker honoraria and travel support from Novartis, Teva, Biogen, Celgene, Merz Pharmaceuticals, Ipsen, Allergan, Bayer Healthcare, Esai, UCB; Roche; he received research support from Novartis, Allergan, Biogen, Celgene, Teva, Merz Pharmaceuticals, Ipsen, and Roche. CH has been serving as a consultant for Univar and has received honoraria for lecturing and travel expenses/speaking honoraria from Abbott and Alexion, and research support from Abbott. SM has received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, SanofiAventis, Chugai Pharma, QuintilesIMS, and Teva, and research funding from the German Ministry for Education and Research (BMBF), the Deutsche Forschungsgemeinschaft, the Else Kröner Fresenius Foundation, the German Academic Exchange Service, the Hertie Foundation, the Interdisciplinary Center for Clinical Studies (IZKF) Muenster, the German Foundation for Neurology, Almirall, Amicus Therapeutics, Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. AS has received lecture fees from Abbott, Novartis, and Kyowa Kirin, and has been serving as a consultant for Abbott, Zambon, and Medtronic Inc. He received royalties from Georg Thieme Verlag. He is a government employee and receives through his institution funding for his research from the German Research Council, Abbott, and the Brunhilde Moll Foundation. I-KP received honoraria for speaking at scientific meetings, serving at scientific advisory boards, and consulting activities from Almirall, Bayer Pharma, Biogen, BMS, Celgene, Sanofi-Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She received research support from the German MS Society, Celgene, Novartis, Roche, and Teva. SG received honoraria and/or travel expenses from Abbott Medical, Abbvie, Boston Scientific, Medtronic, Rogue Research, and UCB, consulting fees from Zambon, and research support from Abbott and Hilde-Ulrichs Stiftung. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Balloff, Albrecht, Stucke, Scala, Novello, Hartmann, Meuth, Schnitzler, Penner and Groiss.)

Neurological manifestations of coronavirus disease 2019 (COVID-19) have been frequently described. In this prospective study of hospitalized COVID-19 patients without a history of neurological conditions, we aimed to analyze their prevalence and prognostic value based on established, standardized and objective methods. Patients were investigated using a multimodal electrophysiological approach, accompanied by neuropsychological and neurological examinations. Prevalence rates of central (CNS) and peripheral (PNS) nervous system affections were calculated and the relationship between neurological affections and mortality was analyzed using Firth logistic regression models. 184 patients without a history of neurological diseases could be enrolled. High rates of PNS affections were observed (66% of 138 patients receiving electrophysiological PNS examination). CNS affections were less common but still highly prevalent (33% of 139 examined patients). 63% of patients who underwent neuropsychological testing (n = 155) presented cognitive impairment. Logistic regression models revealed pathology in somatosensory evoked potentials as an independent risk factor of mortality (Odds Ratio: 6.10 [1.01-65.13], p = 0.049). We conclude that hospitalized patients with moderate to severe COVID-19 display high rates of PNS and CNS affection, which can be objectively assessed by electrophysiological examination. Electrophysiological assessment may have a prognostic value and could thus be helpful to identify patients at risk for deterioration., (© 2023. The Author(s).)

Objective: To investigate the degree of synaptic plasticity in Multiple Sclerosis (MS) patients during acute relapses compared to stable MS patients and healthy controls (HCs) and to analyze its functional relevance., Methods: Facilitatory quadripulse stimulation (QPS) was applied to the primary motor cortex in 18 acute relapsing and 18 stable MS patients, as well as 18 HCs. The degree of synaptic plasticity was measured by the change in motor evoked potential amplitude following QPS. Symptom recovery was assessed three months after relapse., Results: Synaptic plasticity was induced in all groups. The degree of induced plasticity did not differ between acute relapsing patients, HCs, and stable MS patients. Plasticity was significantly higher in relapsing patients with motor disability compared to relapsing patients without motor disability. In most patients (n = 9, 50%) symptoms had at least partially recovered three months after the relapse, impeding meaningful analysis of the functional relevance of baseline synaptic plasticity., Conclusions: QPS-induced synaptic plasticity is retained during acute MS relapses. Subgroup analyses suggest that stabilizing metaplastic mechanisms may be more important to prevent motor disability but its functional relevance needs to be verified in larger, longitudinal studies., Significance: New insights into synaptic plasticity during MS relapses are provided., Competing Interests: Conflict of Interest Statement C. Balloff reports no disclosures relevant to the manuscript. S. Novello reports no disclosures relevant to the manuscript. A-S. Stucke reports no disclosures relevant to the manuscript. L.K. Janssen has received an individual funding granted by the Research Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf for her doctoral thesis (October 2021 - March 2022). E. Heinen reports no disclosures relevant to the manuscript. C.J. Hartmann reports no disclosures relevant to the manuscript. S.G. Meuth has received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, SanofiAventis, Chugai Pharma, QuintilesIMS and Teva, and research funding from the German Ministry for Education and Research (BMBF), the Deutsche Forschungsgemeinschaft, the Else Kröner Fresenius Foundation, the German Academic Exchange Service, the Hertie Foundation, the Interdisciplinary Center for Clinical Studies (IZKF) Muenster, the German Foundation for Neurology, Almirall, Amicus Therapeutics, Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche and Teva. A. Schnitzler has received lecture fees from Abbott, Novartis, Kyowa Kirin, and has been serving as a consultant for Abbott, Zambon, Medtronic Inc. He received royalties from the Georg Thieme Verlag. He is a government employee and receives through his institution funding for his research from the German Research Council, Abbott, and the Brunhilde Moll Foundation. I.-K. Penner received honoraria for speaking at scientific meetings, serving at scientific advisory boards and consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, Celgene, Sanofi-Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She received research support from the German MS Society, Celgene, Novartis, Roche, and Teva. S.J. Groiss received honoraria and/or travel expenses from Abbott Medical, Abbvie, Bial, Boston Scientific, Inomed, Medtronic, Rogue Research, UCB, consulting fees from Bial, Zambon and research support from Abbott and Hilde-Ulrichs Stiftung. P. Albrecht received compensation for serving on Scientific Advisory Boards for Allergan, Celgene, Janssen Cilag, Ipsen, Merck, Merz Pharmaceuticals, Novartis, Biogen; he received speaker honoraria and travel support from Novartis, Teva, Biogen, Celgene, Merz Pharmaceuticals, Ipsen, Allergan, Bayer Healthcare, Esai, UCB; Roche; he received research support from Novartis, Allergan, Biogen, Celgene, Teva, Merz Pharmaceuticals, Ipsen, and Roche., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: One of the main challenges posed by the surgical deep brain stimulation (DBS) procedure is the successful targeting of the structures of interest and avoidance of side effects, especially in asleep surgery. Here, intraoperative motor evoked potentials (MEPs) might serve as tool to identify the pyramidal tract. We hypothesized that intraoperative MEPs are useful to define the distance to the pyramidal tract and reduce the occurrence of postoperative capsular side effects., Materials and Methods: Motor potentials were evoked through both microelectrode and DBS-electrode stimulation during stereotactic DBS surgery on 25 subthalamic nuclei and 3 ventral intermediate thalamic nuclei. Internal capsule proximity was calculated for contacts on microelectrode trajectories, as well as for DBS-electrodes, and correlated with the corresponding MEP thresholds. Moreover, the predictivity of intraoperative MEP thresholds on the probability of postoperative capsular side effects was calculated., Results: Intraoperative MEPs thresholds correlated significantly with internal capsule proximity, regardless of the stimulation source. Furthermore, MEPs thresholds were highly accurate to exclude the occurrence of postoperative capsular side effects., Conclusions: Intraoperative MEPs provide additional targeting guidance, especially in asleep DBS surgery, where clinical value of microelectrode recordings and test stimulation may be limited. As this technique can exclude future capsular side effects, it can directly be translated into clinical practice., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease., Materials and Methods: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life., Results: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period., Conclusion: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Deep brain stimulation (DBS), an effective treatment for movement disorders, usually involves lead implantation while the patient is awake and sedated. Recently, there has been interest in performing the procedure under general anesthesia (asleep). This report of a consecutive cohort of DBS patients describes anesthesia protocols for both awake and asleep procedures., Methods: Consecutive patients with Parkinson's disease received subthalamic nucleus (STN) implants either moderately sedated or while intubated, using propofol and remifentanil. Microelectrode recordings were performed with up to five trajectories after discontinuing sedation in the awake group, or reducing sedation in the asleep group. Clinical outcome was compared between groups with the UPDRS III., Results: The awake group (n = 17) received 3.5 mg/kg/h propofol and 11.6 μg/kg/h remifentanil. During recording, all anesthesia was stopped. The asleep group (n = 63) initially received 6.9 mg/kg/h propofol and 31.3 μg/kg/h remifentanil. During recording, this was reduced to 3.1 mg/kg/h propofol and 10.8 μg/kg/h remifentanil. Without parkinsonian medications or stimulation, 3-month UPDRS III ratings (ns = 16 and 52) were 40.8 in the awake group and 41.4 in the asleep group. Without medications but with stimulation turned on, ratings improved to 26.5 in the awake group and 26.3 in the asleep group. With both medications and stimulation, ratings improved further to 17.6 in the awake group and 15.3 in the asleep group. All within-group improvements from the off/off condition were statistically significant (all ps < 0.01). The degree of improvement with stimulation, with or without medications, was not significantly different in the awake vs. asleep groups (ps > 0.05)., Conclusion: The above anesthesia protocols make possible an asleep implant procedure that can incorporate sufficient microelectrode recording. Together, this may increase patient comfort and improve clinical outcomes., (© 2022. The Author(s).)

Background: Cortical reorganization and plasticity may compensate for structural damage in Multiple Sclerosis (MS). It is important to establish sensitive methods to measure these compensatory mechanisms, as they may be of prognostic value., Objective: To investigate the association between the degree of cortical plasticity and cognitive performance and to compare plasticity between MS patients and healthy controls (HCs)., Methods: The amplitudes of the motor evoked potential (MEP) pre and post quadripulse stimulation (QPS) applied over the contralateral motor cortex served as measure of the degree of cortical plasticity in 63 patients with relapsing-remitting MS (RRMS) and 55 matched HCs. The main outcomes were the correlation coefficients between the difference of MEP amplitudes post and pre QPS and the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R), and the QPS x group interaction in a mixed model predicting the MEP amplitude., Results: SDMT and BVMT-R correlated significantly with QPS-induced cortical plasticity in RRMS patients. Plasticity was significantly reduced in patients with cognitive impairment compared to patients with preserved cognitive function and the degree of plasticity differentiated between both patient groups. Interestingly, the overall RRMS patient cohort did not show reduced plasticity compared to HCs., Conclusions: We provide first evidence that QPS-induced plasticity may inform about the global synaptic plasticity in RRMS which correlates with cognitive performance as well as clinical disability. Larger longitudinal studies on patients with MS are needed to investigate the relevance and prognostic value of this measure for disease progression and recovery., (Copyright © 2022. Published by Elsevier Inc.)