scholarly journals Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261373
Author(s):  
Giuseppe Lanza ◽  
Francesco Fisicaro ◽  
Carmela Cinzia D’Agate ◽  
Raffaele Ferri ◽  
Mariagiovanna Cantone ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
De Novo ◽  
Systemic Disease ◽  
Conduction Time ◽  
Healthy Controls ◽  
Resting Motor Threshold ◽  
Significant Difference ◽  
Interstimulus Intervals

Background Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level. Methods Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured. Results The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals. Conclusions Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called “gluten encephalopathy”, which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed.

scholarly journals Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1530
Author(s):  
Francesco Fisicaro ◽  
Giuseppe Lanza ◽  
Carmela Cinzia D’Agate ◽  
Raffaele Ferri ◽  
Mariagiovanna Cantone ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Rating Scale ◽  
De Novo ◽  
Motor Evoked Potentials ◽  
Silent Period ◽  
Cross Sectional ◽  
Transcallosal Inhibition ◽  
Resting Motor Threshold

Background: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. Methods: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). Results: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. Conclusions: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.

scholarly journals Preserved Transcallosal Inhibition to Transcranial Magnetic Stimulation in Nondemented Elderly Patients with Leukoaraiosis

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Giuseppe Lanza ◽  
Rita Bella ◽  
Salvatore Giuffrida ◽  
Mariagiovanna Cantone ◽  
Giovanni Pennisi ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Elderly Patients ◽  
Magnetic Stimulation ◽  
Motor Evoked Potentials ◽  
Early Stage ◽  
Brain Magnetic Resonance Imaging ◽  
Single Pulse ◽  
Neuropsychological Profile ◽  
Resting Motor Threshold ◽  
Significant Difference

Structural corpus callosum (CC) changes in patients with leukoaraiosis (LA) are significantly associated with cognitive and motor impairment. The aim of this study is to investigate the transcallosal fibers functioning by means of transcranial magnetic stimulation (TMS) in elderly patients with LA. The resting motor threshold (rMT), the motor-evoked potentials (MEPs), and the controlateral (cSP) and ipsilateral silent periods (iSP) were determined using single-pulse TMS in 15 patients and 15 age-matched controls. The neuropsychological profile and the vascular burden at brain magnetic resonance imaging (MRI) were concomitantly explored. Patients reported abnormal scores at tests evaluating executive control functions. No significant difference was found in TMS measures of intra- and intercortical excitability. No CC lesion was evident at MRI. Transcallosal inhibitory mechanisms to TMS seem to be spared in LA patients, a finding which is in line with neuroimaging features and suggests a functional integrity of the CC despite the ischemic interruption of corticosubcortical loops implicated in cognition and behavior. The observed neurophysiological finding differs from that reported in degenerative dementia, even in the preclinical or early stage. In our group of patients, the pure extent of LA is more related to impairment of frontal lobe abilities rather than functional callosal changes.

scholarly journals Altered corticospinal microstructure and motor cortex excitability in gliomas: an advanced tractography and transcranial magnetic stimulation study

2020 ◽  
pp. 1-9
Author(s):  
Ayesha Sunil Mirchandani ◽  
Ahmad Beyh ◽  
José Pedro Lavrador ◽  
Henrietta Howells ◽  
Flavio Dell’Acqua ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Single Shot ◽  
Precentral Gyrus ◽  
Healthy Controls ◽  
Diffusion Weighted Images ◽  
Motor Cortex Excitability ◽  
Resting Motor Threshold

OBJECTIVEThis prospective case-control study was conducted to examine whether spherical deconvolution (SD) can unveil microstructural abnormalities in the corticospinal tract (CST) caused by IDH-mutant gliomas. To determine the significance of abnormal microstructure, the authors investigated the correlation between diffusion parameters and neurophysiological data collected with navigated transcranial magnetic stimulation (nTMS).METHODSTwenty participants (10 patients and 10 healthy controls) were recruited. Diffusion-weighted images were acquired on a 3-T MRI scanner using a cardiac-gated single-shot spin echo echo-planar imaging multiband sequence (TE 80 msec, TR 4000 msec) along 90 diffusion directions with a b-value of 2500 sec/mm2 (FOV 256 × 256 mm). Diffusion tensor imaging tractography and SD tractography were performed with deterministic tracking. The anterior portion of the ipsilateral superior peduncle and the precentral gyrus were used as regions of interest to delineate the CST. Diffusion indices were extracted and analyzed for significant differences between hemispheres in patients and between patient and control groups. A navigated brain stimulation system was used to deliver TMS pulses at hotspots at which motor evoked potentials (MEPs) for the abductor pollicis brevis, first digital interosseous, and abductor digiti minimi muscles are best elicited in patients and healthy controls. Functional measurements such as resting motor threshold (rMT), amplitude of MEPs, and latency of MEPs were noted. Significant differences between hemispheres in patients and between patients and controls were statistically analyzed. The Spearman rank correlation was used to investigate correlations between diffusion indices and functional measurements.RESULTSThe hindrance modulated orientational anisotropy (HMOA), measured with SD tractography, is lower in the hemisphere ipsilateral to glioma (p = 0.028). The rMT in the hemisphere ipsilateral to a glioma is significantly greater than that in the contralateral hemisphere (p = 0.038). All measurements contralateral to the glioma, except for the mean amplitude of MEPs (p = 0.001), are similar to those of healthy controls. Mean diffusivity and axial diffusivity from SD tractography are positively correlated with rMT in the hemisphere ipsilateral to glioma (p = 0.02 and 0.006, respectively). The interhemispheric difference in HMOA and rMT is correlated in glioma patients (p = 0.007).CONCLUSIONSSD tractography can demonstrate microstructural abnormality within the CST of patients with IDH1-mutant gliomas that correlates to the functional abnormality measured with nTMS.

Transcallosal motor disinhibition to transcranial magnetic stimulation in de novo patients with Celiac disease

2021 ◽  
Vol 429 ◽  
pp. 118559
Author(s):  
Francesco Fisicaro ◽  
Giuseppe Lanza ◽  
Carmela D'Agate ◽  
Raffaele Ferri ◽  
Mariagiovanna Cantone ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
De Novo

scholarly journals Transcranial Magnetic Stimulation in Succinic Semialdehyde Dehydrogenase Deficiency: A Measure of Maturational Trajectory of Cortical Excitability

2021 ◽  
pp. 088307382110087
Author(s):  
Melissa Tsuboyama ◽  
Jingjing Liu ◽  
Harper Kaye ◽  
Melissa DiBacco ◽  
Phillip L Pearl ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Focal Epilepsy ◽  
Silent Period ◽  
Succinic Semialdehyde ◽  
Healthy Controls ◽  
Motor Threshold ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Resting Motor Threshold

Background: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a disorder of GABA degradation with use-dependent downregulation of postsynaptic GABAA/B receptors. We aim to measure the resulting cortical excitation: inhibition ratio using transcranial magnetic stimulation. Methods: In this single-center observational study, 18 subjects with SSADHD and 8 healthy controls underwent transcranial magnetic stimulation. Resting motor threshold, cortical silent period, and long-interval intracortical inhibition were measured in both groups. Resting motor threshold in focal epilepsy patients from an institutional transcranial magnetic stimulation database were also included. Results: SSADHD subjects had higher resting motor threshold than healthy controls but lower relative to focal epilepsy patients. Resting motor threshold decreased with age in all groups. Cortical silent period was longer in SSADHD subjects than in healthy controls. No difference was detected in long-interval intracortical inhibition between the 2 groups. Conclusion: Findings suggest abnormal corticospinal tract physiology in SSADHD, but with preserved developmental trajectory for corticospinal tract maturation. Defining features of these transcranial magnetic stimulation metrics in SSADHD will be better elucidated through this ongoing longitudinal study.

Associations between clinical outcome and tractography based on navigated transcranial magnetic stimulation in patients with language-eloquent brain lesions

2020 ◽  
Vol 132 (4) ◽  
pp. 1033-1042 ◽  
Author(s):  
Nico Sollmann ◽  
Alessia Fratini ◽  
Haosu Zhang ◽  
Claus Zimmer ◽  
Bernhard Meyer ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Brain Tumors ◽  
Risk Stratification ◽  
Magnetic Stimulation ◽  
Diffusion Tensor ◽  
Tumor Resection ◽  
Navigated Transcranial Magnetic Stimulation ◽  
Language Mapping ◽  
Significant Difference ◽  
Related Pathway

OBJECTIVENavigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.METHODSFifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).RESULTSA significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.CONCLUSIONSnTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.

scholarly journals Study of the role of the transcranial magnetic stimulation on language progress in autism spectrum disorder

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Mohamed E. Darwish ◽  
Heba W. El-Beshlawy ◽  
Ehab S. Ramadan ◽  
Shimaa M. Serag
Keyword(s):  
Autism Spectrum Disorder ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Autism Spectrum ◽  
Language Therapy ◽  
Children With Asd ◽  
Group I ◽  
Mild Improvement ◽  
Significant Difference

Abstract Background Children with autism spectrum disorder (ASD) are almost universally delayed in the acquisition of spoken language as primary means of communication so they tend to have restricted outcomes in terms of independence and integration. Transcranial magnetic stimulation (TMS) is a promising, emerging tool for the study (study and modulate excitability and plasticity, applied in single pulses to investigate corticospinal excitability, pairs of pulses to study intracortical inhibition and facilitation) and potential treatment of ASD. The purpose of this study is to evaluate the role of repetitive TMS in language progress in children with ASD. Results There was a statistically significant clinical improvement in patients receiving active TMS (group I) comparing baseline Childhood Autism Rating Scale (CARS) assessment and after treatment (P ≤ 0.05). There was mild improvement with no significant difference between the patients receiving active TMS (group I) and those of sham TMS (group II), and both groups received language therapy as regard post-treatment CARS. There was significant difference in improvement between the two groups according to eye contact (P ≤ 0.05). There was significant improvement in response to examiner (P ≤ 0.05). There was mild improvement with no statistically significant difference in attention between the two groups. There was significant difference in improvement between the two groups according to active expressive language. There was no statistically significant difference in passive vocabulary between the two groups. Conclusion Repetitive transcranial magnetic stimulation (rTMS) over left inferior frontal gyrus may be a safe and effective way of improving language of ASD. The joint application of rTMS and standard language therapy may lead to more rapid improvement in the language progress of children with ASD.

scholarly journals Motor disability in patients with multiple sclerosis: transcranial magnetic stimulation study

2020 ◽  
Vol 56 (1) ◽  
Author(s):  
Anssam Bassem Mohy ◽  
Aqeel Kareem Hatem ◽  
Hussein Ghani Kadoori ◽  
Farqad Bader Hamdan
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Lower Limb ◽  
Magnetic Stimulation ◽  
Motor Evoked Potential ◽  
Invasive Procedure ◽  
Single Pulse ◽  
Lower Limbs ◽  
Control Group ◽  
Conduction Time ◽  
Motor Disability

Abstract Background Transcranial magnetic stimulation (TMS) is a non-invasive procedure used in a small targeted region of the brain via electromagnetic induction and used diagnostically to measure the connection between the central nervous system (CNS) and skeletal muscle to evaluate the damage that occurs in MS. Objectives The study aims to investigate whether single-pulse TMS measures differ between patients with MS and healthy controls and to consider if these measures are associated with clinical disability. Patients and methods Single-pulse TMS was performed in 26 patients with MS who hand an Expanded Disability Status Scale (EDSS) score between 0 and 9.5 and in 26 normal subjects. Different TMS parameters from upper and lower limbs were investigated. Results TMS disclosed no difference in all MEP parameters between the right and left side of the upper and lower limbs in patients with MS and controls. In all patients, TMS parameters were different from the control group. Upper limb central motor conduction time (CMCT) was prolonged in MS patients with pyramidal signs. Upper and lower limb CMCT and CMCT-f wave (CMCT-f) were prolonged in patients with ataxia. Moreover, CMCT and CMCT-f were prolonged in MS patients with EDSS of 5–9.5 as compared to those with a score of 0–4.5. EDSS correlated with upper and lower limb cortical latency (CL), CMCT, and CMCT-f whereas motor evoked potential (MEP) amplitude not. Conclusion TMS yields objective data to evaluate clinical disability and its parameters correlated well with EDSS.

scholarly journals Antidepressant effect of repetitive transcranial magnetic stimulation is not impaired by intake of lithium or antiepileptic drugs

2021 ◽  
Author(s):  
T. Hebel ◽  
M. A. Abdelnaim ◽  
M. Deppe ◽  
P. M. Kreuzer ◽  
A. Mohonko ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Transcranial Magnetic Stimulation ◽  
Antiepileptic Drugs ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Factor Group ◽  
Mood Stabilizers ◽  
Motor Threshold ◽  
Chi Square ◽  
Resting Motor Threshold

Abstract Introduction The effect of concomitant medication on repetitive transcranial magnetic stimulation (rTMS) outcomes in depression remains understudied. Recent analyses show attenuation of rTMS effects by antipsychotic medication and benzodiazepines, but data on the effects of antiepileptic drugs and lithium used as mood stabilizers or augmenting agents are sparse despite clinical relevance. Preclinical electrophysiological studies suggest relevant impact of the medication on treatment, but this might not translate into clinical practice. We aimed to investigate the role of lithium (Li), lamotrigine (LTG) and valproic acid (VPA) by analyzing rTMS treatment outcomes in depressed patients. Methods 299 patients with uni- and bipolar depression treated with rTMS were selected for analysis in respect to intake of lithium, lamotrigine and valproic acid. The majority (n = 251) were treated with high-frequency (10–20 Hz) rTMS of the lDLPFC for an average of 17 treatment sessions with a figure-of-8 coil with a MagVenture system aiming for 110% resting motor threshold, and smaller groups of patients were being treated with other protocols including intermittent theta-burst stimulation and bilateral prefrontal and medial prefrontal protocols. For group comparisons, we used analysis of variance with the between-subjects factor group or Chi-Square Test of Independence depending on the scales of measurement. For post-hoc tests, we used least significant difference (LSD). For differences in treatment effects between groups, we used an ANOVA with the between-subjects factor group (groups: no mood stabilizer, Li, LTG, VPA, Li + LTG) the within-subjects factor treatment (pre vs. post treatment with rTMS) and also Chi-Square Tests of independence for response and remission. Results Overall, patients showed an amelioration of symptoms with no significant differences for the main effect of group and for the interaction effect treatment by group. Based on direct comparisons between the single groups taking mood stabilizers against the group taking no mood stabilizers, we see a superior effect of lamotrigine, valproic acid and combination of lithium and lamotrigine for the response and remission rates. Motor threshold was significantly and markedly higher for patients taking valproic acid. Conclusion Being treated with lithium, lamotrigine and valproic acid had no relevant influence on rTMS treatment outcome. The results suggest there is no reason for clinicians to withhold or withdraw these types of medication from patients who are about to undergo a course of rTMS. Prospective controlled work on the subject is encouraged.

scholarly journals Clinical, Neurophysiological, and MRI Markers of Fampridine Responsiveness in Multiple Sclerosis—An Explorative Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Sepehr Mamoei ◽  
Henrik Boye Jensen ◽  
Andreas Kristian Pedersen ◽  
Mikkel Karl Emil Nygaard ◽  
Simon Fristed Eskildsen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Longitudinal Study ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Motor Evoked Potentials ◽  
Step Test ◽  
Conduction Time ◽  
Lesion Load ◽  
Clinical Trial Registration ◽  
Peripheral Motor

Objective: Persons with multiple sclerosis (PwMS), already established as responders or non-responders to Fampridine treatment, were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and magnetic resonance imaging (MRI) outcomes in a 1-year explorative longitudinal study.Materials and Methods: Data from a 1-year longitudinal study were analyzed. Examinations consisted of the timed 25-foot walk test (T25FW), six spot step test (SSST), nine-hole peg test (9-HPT), five times sit-to-stand test (5-STS), symbol digit modalities test (SDMT), transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) examining central motor conduction times (CMCT), peripheral motor conduction times (PMCT) and their amplitudes, electroneuronography (ENG) of the lower extremities, and brain structural MRI measures.Results: Forty-one responders and eight non-responders to Fampridine treatment were examined. There were no intergroup differences except for the PMCT, where non-responders had prolonged conduction times compared to responders to Fampridine. Six spot step test was associated with CMCT throughout the study. After 1 year, CMCT was further prolonged and cortical MEP amplitudes decreased in both groups, while PMCT and ENG did not change. Throughout the study, CMCT was associated with the expanded disability status scale (EDSS) and 12-item multiple sclerosis walking scale (MSWS-12), while SDMT was associated with number of T2-weighted lesions, lesion load, and lesion load normalized to brain volume.Conclusions: Peripheral motor conduction time is prolonged in non-responders to Fampridine when compared to responders. Transcranial magnetic stimulation-elicited MEPs and SDMT can be used as markers of disability progression and lesion activity visualized by MRI, respectively.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03401307.

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