[Alexithymia in Multiple Sclerosis - Narrative Review]. / Alexithymie bei Multipler Sklerose ­ eine narrative Übersicht.

Alexithymia is a multidimensional construct of personality implicating difficulties in identifying and describing another's feelings, and externally oriented thinking. It is broadly reported in psychiatric patients but has gained little attention regarding its occurrence and pathophysiology in multiple sclerosis (MS). This narrative review aims to address prevalence, etiology, neurobiological, and clinical findings of alexithymia. The prevalence of alexithymia in MS ranges from 10 to 53%. There seems to be an association with anxiety, depression, fatigue, and some aspects of social cognition, while the relationship with clinical and classical cognitive variables was rarely evaluated. Only a few studies referred to its pathophysiology assuming an aberrant interhemispheric transfer or regional cerebral abnormalities. The prevalence of alexithymia in MS and the potential negative impact on quality of life and interpersonal communication could severely impact clinical MS management and a screnning for these factors should be mandatory. Thus, further evaluation is needed concerning its relationship with clinical, emotional, and cognitive confounders. Large-scale studies employing neuroimaging techniques are needed for a better understanding of the neural underpinnings of this MS feature.

Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat neuropathic pain but the quality of evidence remains low. We aimed to assess the efficacy and safety of neuronavigated rTMS to the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in neuropathic pain over 25 weeks. We carried out a randomized double-blind, placebo-controlled trial at four outpatient clinics in France. Patients aged 18-75 years with peripheral neuropathic pain were randomly assigned at a 1:1 ratio to M1 or DLPFC-rTMS and rerandomized at a 2:1 ratio to active or sham-rTMS (10 Hz, 3000 pulses/session, 15 sessions over 22 weeks). Patients and investigators were blind to treatment allocation. The primary end point was the comparison between active M1-rTMS, active DLPCF-rTMS and sham-rTMS for the change over the course of 25 weeks (Group × Time interaction) in average pain intensity (from 0 no pain to 10 maximal pain) on the Brief Pain Inventory, using a mixed model repeated measures analysis in patients who received at least one rTMS session (modified intention-to-treat population). Secondary outcomes included other measures of pain intensity and relief, sensory and affective dimensions of pain, quality of pain, self-reported pain intensity and fatigue (patients diary), Patient and Clinician Global Impression of Change (PGIC, CGIC), quality of life, sleep, mood and catastrophizing. This study is registered with ClinicalTrials.gov NCT02010281. A total of 152 patients were randomized and 149 received treatment (49 for M1; 52 for DLPFC; 48 for sham). M1-rTMS reduced pain intensity versus sham-rTMS (estimate for Group × Session interaction: -0.048 ± 0.02; 95% CI: -0.09 to -0.01; P = 0.01). DLPFC-rTMS was not better than sham (estimate: -0.003 ± 0.01; 95% CI: -0.04 to 0.03, P = 0.9). M1-rRMS, but not DLPFC-rTMS, was also superior to sham-rTMS on pain relief, sensory dimension of pain, self-reported pain intensity and fatigue, PGIC and CGIC. There were no effects on quality of pain, mood, sleep and quality of life as all groups improved similarly over time. Headache was the most common side effect and occurred in 17 (34.7%), 23 (44.2%) and 13 (27.1%) patients from M1, DLPFC and sham groups, respectively (P = 0.2). Our results support the clinical relevance of M1-rTMS, but not of DLPFC-rTMS, for peripheral neuropathic pain with an excellent safety profile.

Neurofeedback therapy for the management of multiple sclerosis symptoms: current knowledge and future perspectives.

Fatigue is a frequent and debilitating symptom in patients with multiple sclerosis (MS). Affective manifestations are also of high prevalence in this population and can drastically impact the patients' functioning. A considerable proportion of patients with MS suffer from cognitive deficits affecting general and social cognitive domains. In addition, pain in MS is commonly observed in neurology wards, could be of different types, and may result from or be exacerbated by other MS comorbidities. These complaints tend to cluster together in some patients and seem to have a complex pathophysiology and a challenging management. Exploring the effects of new interventions could improve these outcomes and ameliorate the patients' quality of life. Neurofeedback (NFB) might have its place in this context by enhancing or reducing the activity of some regions in specific electroencephalographic bands (i.e., theta, alpha, beta, sensorimotor rhythm). This work briefly revisits the principles of NFB and its application. The published data are scarce and heterogeneous yet suggest preliminary evidence on the potential utility of NFB in patients with MS (i.e., depression, fatigue, cognitive deficits and pain). NFB is simple to adapt and easy to coach, and its place in the management of MS symptoms merits further investigations. Comparing different NFB protocols (i.e., cortical target, specific rhythm, session duration and number) and performing a comprehensive evaluation could help developing and optimizing interventions targeting specific symptoms. These aspects could also open the way for the association of this technique with other approaches (i.e., brain stimulation, cognitive rehabilitation, exercise training, psychotherapies) that have proved their worth in some MS domains.

Bifrontal transcranial direct current stimulation modulates fatigue in multiple sclerosis: a randomized sham-controlled study.

Fatigue is a frequent and debilitating symptom in patients with central nervous system diseases. Up to 90% of patients with multiple sclerosis (MS) suffer from fatigue that drastically affects the quality of life. MS patients also complain of anxiety and depressive symptoms and these three manifestations tend to cluster together in this clinical population. The objective of this work was to assess the effects of transcranial direct stimulation (tDCS), a noninvasive brain stimulation technique, on fatigue as well as anxiety and depressive symptoms. Eleven fatigued MS patients randomly received two blocks (active and sham tDCS) of five consecutive daily sessions of bifrontal tDCS (anode/cathode over the left/right prefrontal cortices, respectively) in a crossover manner, separated by a 3-week washout interval. Evaluation took place at day 1, day 5 (right after each block) and 1 week later. Active but not sham tDCS resulted in a significant improvement of fatigue at day 5 (p < 0.05), an effect that seems to last at least 1 week following the stimulation (p = 0.05). Active tDCS also significantly improved anxiety symptoms, but the effect emerged 1 week later (p < 0.05). No significant effects were obtained regarding depression (p > 0.05). Bifrontal tDCS seems to modulate fatigue in PwMS. The observed anxiolytic effects could constitute delayed after effects of tDCS or might be mediated by fatigue improvement. These findings merit to be addressed in large-scale controlled trials.

Phosphorus magnetic resonance spectroscopy and fatigue in multiple sclerosis.

Fatigue stands among the most debilitating multiple sclerosis (MS) manifestations. Several pathophysiological mechanisms have been proposed at its origin. However, unmet needs still exist, and further investigations are required to better understand and manage this complaint. A new imaging modality-the phosphorous magnetic resonance spectroscopy (31P-MRS)-might help studying fatigue by allowing the measurement of energy metabolites of various cerebral regions. Therefore, this work aimed to explore the association between fatigue and brain energy status. Thirty MS patients with progressive disease forms completed the study. Their sociodemographic and clinical data including fatigue and disability scores [i.e., Fatigue Severity Scale (FSS) and Expanded Disability Status Scale (EDSS)] were collected. 31P-MRS spectra of (1) bilateral frontoparietal area and (2) centrum semiovale normal appearing white matter (NAWM) were obtained. Percentages of phosphocratine and ß-adenosine triphosphate (ß-ATP) were calculated. FSS scores were found to be directly correlated with the frontoparietal ß-ATP % (p < 0.05). However, there were no significant correlations between FSS scores and NAWM energy metabolites or clinical data (i.e., age, EDSS scores or disease duration). These findings point toward the existence of a link between fatigue severity and the amount of cerebral ATP metabolites. Such a link might reflect either a high production or low utilization of ATP, both of which were paralleled with increased fatigue perception. While the former would be due to a redistribution of ion channels along demyelinated axons and subsequent changes in mitochondrial activity; the latter could be interpreted in the light of neuronal loss which would lead to a decrease in ATP utilization and accumulation of its metabolites.

A Scope of the Social Brain in Multiple Sclerosis: Insights From Neuroimaging Studies.

Multiple sclerosis (MS) is the most common inflammatory neurologic disease in young adults. Its pathological mechanisms include demyelination, neurodegeneration, and synaptopathy. Cognitive deficits occur in up to 65% of individuals with MS and affect both nonsocial (eg, information processing speed, memory, and executive functions) and social (ie, emotion recognition, theory of mind, and empathy) cognitive domains. In the last 3 decades, there has been a growing interest in social cognition and its relationship with neuropsychological, sociodemographic, and disease characteristics in individuals with MS. Uncovering the neuropathological correlates of social cognitive deficits is now a crucial aim that would also help us better understand the underlying mechanisms of social cognition. We reviewed 11 neuroimaging studies to investigate social cognition in MS. These studies focused mainly on facial emotion recognition and theory of mind, with the findings suggesting that a disrupted cortico-subcortical network forms the basis of social deficits involving both domains. We then interpreted these results in the context of multiple disconnection syndrome, which occurs as a result of axonal demyelination and degeneration within the connexome of several neural hubs devoted to social cognition. Heterogeneity in social cognitive performance, observed among our study participants, is discussed with reference to the cognitive reserve and brain reserve hypotheses. These reserves may explain why individuals with comparable clinical characteristics of MS may exhibit different cognitive profiles. Further research is required to generalize these findings to the MS population and to inform the development of effective interventions to improve psychosocial functioning in individuals with MS.

Longitudinal Extensive Transverse Myelitis in an Immunocompetent Older Individual-A Rare Complication of Varicella-Zoster Virus Reactivation.

Varicella-zoster virus (VZV) is a human neurotropic herpes virus that causes chickenpox in children. After becoming latent in dorsal root ganglia, it can reactivate to cause dermatological manifestations, the most common one being shingles or herpes zoster. Severe neurologic dysfunctions can occur in immunocompromised patients such as encephalitis, meningitis, myelitis and neuropathy. Longitudinal extensive transverse myelitis (LETM) is an unusual neurological complication mainly described in immunocompromised patients, with very few cases described in immunocompetent ones. We hereby report a case of VZV-induced LETM in an immunocompetent older adult-a situation rarely described in the literature. LETM is a rare complication of VZV and its pathogenesis; therapeutic interventions and prognosis are far from being fully clarified. However, a prompt diagnosis is needed to allow a rapid initialization of treatment and ensure a better outcome. Although the therapeutic lines are not clear, immunosuppressive agents may have their place in cases of unsuccessful results and/or relapses following acyclovir coupled with a well conducted methylprednisolone therapy. Further studies are highly needed to improve the current understanding of the disease course and mechanisms, and to optimize therapeutic strategies.

Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial.

INTRODUCTION: Polyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis ), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial. METHODS: We assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis ) and its subscores and correlation with disability and health scores. RESULTS: The mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests. CONCLUSIONS: Specially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis , broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901-911, 2017.

Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system, representing the primary cause of non-traumatic disability in young adults. Cognitive dysfunction can affect patients at any time during the disease process and might alter the six core functional domains. Social cognition is a multi-component construct that includes the theory of mind, empathy and social perception of emotions from facial, bodily and vocal cues. Deficits in this cognitive faculty might have a drastic impact on interpersonal relationships and quality of life (QoL). Although exhaustive data exist for non-social cognitive functions in MS, only a little attention has been paid for social cognition. The objectives of the present work are to reappraise the definition and anatomy of social cognition and evaluate the integrity of this domain across MS studies. We will put special emphasis on neuropsychological and neuroimaging studies concerning social cognitive performance in MS. METHODS: Studies were selected in conformity with PRISMA guidelines. We looked for computerized databases (PubMed, Medline, and Scopus) that index peer-reviewed journals to identify published reports in English and French languages that mention social cognition and multiple sclerosis, regardless of publication year. We combined keywords as follows: (facial emotion or facial expression or emotional facial expressions or theory of mind or social cognition or empathy or affective prosody) AND multiple sclerosis AND (MRI or functional MRI or positron emission tomography or functional imaging or structural imaging). We also scanned references from articles aiming to get additional relevant studies. RESULTS: In total, 26 studies matched the abovementioned criteria (26 neuropsychological studies including five neuroimaging studies). Available data support the presence of social cognitive deficits even at early stages of MS. The increase in disease burden along with the "multiple disconnection syndrome" resulting from gray and white matters pathology might exceed the "threshold for cerebral tolerance" and can manifest as deficits in social cognition. Admitting the impact of the latter on patients' social functioning, a thorough screening for such deficits is crucial to improving patients' QoL. (JINS, 2017, 23, 266-286).

Adenosine Triphosphate Metabolism Measured by Phosphorus Magnetic Resonance Spectroscopy: A Potential Biomarker for Multiple Sclerosis Severity.

BACKGROUND/AIMS: Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously shown abnormal changes in energy metabolites in the brain of multiple sclerosis (MS) patients. However, the relationship between these energy metabolites - particularly adenosine triphosphate (ATP) - and the disease severity remains unclear. The objective of this study was to determine whether measuring ATP metabolites can help to predict disease severity in MS patients. METHODS: 31P-MRS at 3 tesla was performed in 9 relapsing remitting (RRMS), 9 secondary progressive MS patients (SPMS), and 10 age-matched healthy controls. ATP metabolites (expressed as %) in normally appearing white matter of the centrum semiovale were compared between patients and healthy controls. The relationship between Expanded Disability Status Scale (EDSS) and ATP metabolites was evaluated. RESULTS: RRMS and SPMS patients had higher phosphocreatine (PCr) and lower phosphodiesters than healthy controls. In addition, RRMS patients had higher ß-ATP% than SPMS patients. ß-ATP% was negatively correlated with EDSS in all patients. CONCLUSION: Our findings suggest a defective PCr metabolism in both patient groups, and a higher state of energy production in RRMS that might reflect a compensatory mechanism in face of the increased needs. The correlation of ß-ATP with EDSS makes it a candidate biomarker for assessing MS disease severity.

[Facial emotion recognition, theory of mind and empathy in multiple sclerosis]. / Emotionserkennung, Theory of Mind und Empathie bei Multipler Sklerose.

Multiple sclerosis (MS), a chronic progressive inflammatory disease of the central nervous system, causes frequent disability, mood disorders, fatigue, and cognitive dysfunction. As a part of the last, social cognition is frequently disturbed in MS patients. It comprises empathy and social perception of emotions from facial, bodily and vocal cues. Social cognitive deficits worsen affect decoding, interpersonal relationship, and quality of life. Despite the impact of these deficits on global functioning, only a small number of studies have investigated its correlations and overlaps with MS symptoms. This review focuses on the definition and anatomy of social cognition and draws attention to findings of neuropsychological and neuroimaging studies on social cognitive performance in MS.Results of the available studies show that social cognitive deficits are already measurable in early stages of MS. Over time course of the disease, neuropsychological and neuroimaging studies show an increase of disease burden and social and non-social cognitive impairment following the hypothesis of a disconnection syndrome resulting from gray and white matters lesions. These structural changes might exceed a threshold of compensatory restorative and neuroplasticity mechanisms and finally lead to deficits in social cognition. Considering this burden in social functioning, a further assessment of sociocognitive deficits in MS is urgently needed to provide specific therapeutic approaches and to improve quality of life.

[Multiple sclerosis fatigue, its neural correlates, and its modulation with tDCS]. / Fatigue bei Multipler Sklerose: Neuronale Korrelate und Möglichkeiten nicht-invasiver Hirnstimulation mit tDCS.

Multiple sclerosis (MS) is a chronic progressive and inflammatory disease of the central nervous system and causes high rates of non-traumatic disability in young adults. Fatigue is frequently reported by a major part of patients during the disease course and dramatically increases the burden of illness. Despite the high prevalence of fatigue and its enormous impact on quality of life, its pathophysiological mechanisms are still unclear. Its etiology is multifactorial and complex, and is usually classified into 'primary' fatigue resulting from the pathological brain changes versus 'secondary' fatigue following disease symptoms, sleep disturbances, mood disorders, and side effects of medication. Hypotheses concerning the pathophysiology of this symptom are based on radiological, physiological, and endocrine data. It has been suggested that fatigue refers to structural and functional changes in a variety of neuronal networks. Over the past years, non-invasive brain stimulation methods were used to modulate brain function, especially transcranial direct current stimulation (tDCS) has proven to impact neuronal connectivity; however evidence is still sparse due to the pilot character of the studies. In this review we aim at discussing the neuronal correlates of fatigue and the potential influence of tDCS in the modulation of the symptoms.

The Hand Motor Hotspot is not Always Located in the Hand Knob: A Neuronavigated Transcranial Magnetic Stimulation Study.

The hand motor hot spot (hMHS) is one of the most salient parameters in transcranial magnetic stimulation (TMS) practice, notably used for targeting. It is commonly accepted that the hMHS corresponds to the hand representation within the primary motor cortex (M1). Anatomical and imaging studies locate this representation in a region of the central sulcus called the "hand knob". The aim of this study was to determine if the hMHS location corresponds to its expected location at the hand knob. Twelve healthy volunteers and eleven patients with chronic neuropathic pain of various origins, but not related to a brain lesion, were enrolled. Morphological magnetic resonance imaging of the brain was normal in all participants. Both hemispheres were studied in all participants except four (two patients and two healthy subjects). Cortical mapping of the hand motor area was conducted using a TMS-dedicated navigation system and recording motor evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) muscle. We then determined the anatomical position of the hMHS, defined as the stimulation site providing the largest FDI-MEPs. In 45 % of hemispheres of normal subjects and 25 % of hemispheres of pain patients, the hMHS was located over the central sulcus, most frequently at the level of the hand knob. However, in the other cases, the hMHS was located outside M1, most frequently anteriorly over the precentral or middle frontal gyrus. This study shows that the hMHS does not always correspond to the hand knob and M1 location in healthy subjects or patients. Therefore, image-guided navigation is needed to improve the anatomical accuracy of TMS targeting, even for M1.

Reappraisal of the anatomical landmarks of motor and premotor cortical regions for image-guided brain navigation in TMS practice.

Image-guided navigation systems dedicated to transcranial magnetic stimulation (TMS) have been recently developed and offer the possibility to visualize directly the anatomical structure to be stimulated. Performing navigated TMS requires a perfect knowledge of cortical anatomy, which is very variable between subjects. This study aimed at providing a detailed description of sulcal and gyral anatomy of motor cortical regions with special interest to the inter-individual variability of sulci. We attempted to identify the most stable structures, which can serve as anatomical landmarks for motor cortex mapping in navigated TMS practice. We analyzed the 3D reconstruction of 50 consecutive healthy adult brains (100 hemispheres). Different variants were identified regarding sulcal morphology, but several anatomical structures were found to be remarkably stable (four on dorsoventral axis and five on rostrocaudal axis). These landmarks were used to define a grid of 12 squares, which covered motor cortical regions. This grid was used to perform motor cortical mapping with navigated TMS in 12 healthy subjects from our cohort. The stereotactic coordinates (x-y-z) of the center of each of the 12 squares of the mapping grid were expressed into the standard Talairach space to determine the corresponding functional areas. We found that the regions whose stimulation produced almost constantly motor evoked potentials mainly correspond to the primary motor cortex, with rostral extension to premotor cortex and caudal extension to posterior parietal cortex. Our anatomy-based approach should facilitate the expression and the comparison of the results obtained in motor mapping studies using navigated TMS.

The contribution of EEG to assess and treat motor disorders in multiple sclerosis.

OBJECTIVE: Electroencephalography (EEG) can highlight significant changes in spontaneous electrical activity of the brain produced by altered brain network connectivity linked to inflammatory demyelinating lesions and neuronal loss occurring in multiple sclerosis (MS). In this review, we describe the main EEG findings reported in the literature to characterize motor network alteration in term of local activity or functional connectivity changes in patients with MS (pwMS). METHODS: A comprehensive literature search was conducted to include articles with quantitative analyses of resting-state EEG recordings (spectrograms or advanced methods for assessing spatial and temporal dynamics, such as coherence, theory of graphs, recurrent quantification, microstates) or dynamic EEG recordings during a motor task, with or without connectivity analyses. RESULTS: In this systematic review, we identified 26 original articles using EEG in the evaluation of MS-related motor disorders. Various resting or dynamic EEG parameters could serve as diagnostic biomarkers of motor control impairment to differentiate pwMS from healthy subjects or be related to a specific clinical condition (fatigue) or neuroradiological aspects (lesion load). CONCLUSIONS: We highlight some key EEG patterns in pwMS at rest and during movement, both suggesting an alteration or disruption of brain connectivity, more specifically involving sensorimotor networks. SIGNIFICANCE: Some of these EEG biomarkers of motor disturbance could be used to design future therapeutic strategies in MS based on neuromodulation approaches, or to predict the effects of motor training and rehabilitation in pwMS.

Event-related desynchronization and synchronization in multiple sclerosis.

BACKGROUND: Motor preparation and execution can be impaired in patients with multiple sclerosis (pwMS). These neural processes can be assessed using electroencephalography (EEG). During a self-paced movement, EEG signal amplitude decreases before movement (event-related desynchronization, ERD) and increases after movement (event-related synchronization, ERS). OBJECTIVE: To reappraise ERD/ERS changes in pwMS compared to healthy controls (HC). METHODS: This single-center study included 13 pwMS and 10 sex/age-matched HC. 60-channel EEG was recorded during two self-paced movements of the right hand: a simple index finger extension task and a more complex finger tapping task. Clinical variables included MS type, sex, age, disease duration, disability, grip strength, fatigue and attentional performance. EEG variables included ERD and ERS onset latency, duration, and amplitude determined using two methods of signal analyses (based on visual or automated determination) in the alpha and beta frequency bands in five cortical regions: right and left frontocentral and centroparietal regions and a midline region. Neuroimaging variables included the volumes of four deep brain structures (thalamus, putamen, pallidum and caudate nucleus) and the relative lesion load. RESULTS: ERD/ERS changes in pwMS compared to HC were observed only in the beta band. In pwMS, beta-ERD had a delayed onset in the midline and right parietocentral regions and a shortened duration or increased amplitude in the parietocentral region; beta-ERS had a shorter duration, delayed onset, or reduced amplitude in the left parieto/frontocentral region. In addition, pwMS with a more delayed beta-ERD in the midline region had less impaired executive functions but increased caudate nuclei volume, while pwMS with a more delayed beta-ERS in the parietocentral region contralateral to the movement had less fatigue but increased thalami volume. CONCLUSION: This study confirms an alteration of movement preparation and execution in pwMS, mainly characterized by a delayed cortical activation (ERD) and a delayed and reduced post-movement inhibition (ERS) in the beta band. Compensatory mechanisms could be involved in these changes, associating more preserved clinical performance and overactivation of deep brain structures.

Motor function in multiple sclerosis assessed by navigated transcranial magnetic stimulation mapping.

INTRODUCTION: Impaired motor function is a major cause of disability in multiple sclerosis (MS), involving various neuroplasticity processes typically assessed by neuroimaging. This study aimed to determine whether navigated transcranial magnetic stimulation (nTMS) could also provide biomarkers of motor cortex plasticity in patients with MS (pwMS). METHODS: nTMS motor mapping was performed for hand and leg muscles bilaterally. nTMS variables included the amplitude and latency of motor evoked potentials (MEPs), corticospinal excitability measures, and the size of cortical motor maps (CMMs). Clinical assessment included disability (Expanded Disability Status Scale, EDSS), strength (MRC scale, pinch and grip), and dexterity (9-hole Pegboard Test). RESULTS: nTMS motor mapping was performed in 68 pwMS. PwMS with high disability (EDSS ≥ 3) had enlarged CMMs with less dense distribution of MEPs and various MEP parameter changes compared to pwMS with low disability (EDSS < 3). Patients with progressive MS had also various MEP parameter changes compared to pwMS with relapsing remitting form. MRC score correlated positively with MEP amplitude and negatively with MEP latency, pinch strength correlated negatively with CMM volume and dexterity with MEP latency. CONCLUSIONS: This is the first study to perform 4-limb cortical motor mapping in pwMS using a dedicated nTMS procedure. By quantifying the cortical surface representation of a given muscle and the variability of MEP within this representation, nTMS can provide new biomarkers of motor function impairment in pwMS. Our study opens perspectives for the use of nTMS as an objective method for assessing pwMS disability in clinical practice.

Effects of the TENS device, Exopulse Mollii Suit, on pain related to fibromyalgia: An open-label study.

Fibromyalgia is characterized by diffuse and chronic pain, that is often only partially alleviated by the available pharmacological treatments. Therefore, nonpharmacological interventions such as transcutaneous electrical stimulation (TENS) are highly needed to improve the quality of life of this population. However, the classical TENS devices offer a limited number of electrodes and are not adapted to this diffuse painful condition. For these reasons, we aimed to assess the effects of a new TENS device, the Exopulse Mollii Suit, that can stimulate up to 40 muscle groups integrated into pants and jackets and connected to a control unit. We report the data of 50 patients who received one session of active stimulation (pulse intensity 2 mA, and pulse frequency 20 Hz). Pain intensity was evaluated by means of the visual analogue scale (VAS), before (T0) and after the session (T1), and 24 h later (T24). Compared to baseline scores, a significant decrease in VAS was observed after the session (p<0.001), and 24 h later (p<0.001). T1 scores were significantly lower than T24 scores (p<0.001). Therefore, this new system seems to exert analgesic effects whose mechanisms primarily evoke the theory of "gate control". The effects were transient and started to decrease the following day, highlighting the need for additional studies to better evaluate the long-term effects of this intervention on pain, mood, and quality of life.

Ramsay Hunt Syndrome in Asymptomatic COVID-19 Infection: A Case Report and a Literature Review.

(1) Background: COVID-19 infection has affected almost 6 million people worldwide. Geniculate Ganglion Zoster resulting in Ramsay Hunt Syndrome (RHS) has been rarely described in this context. (2) Methods: Here, a case of RHS in the context of asymptomatic COVID-19 infection is reported followed by a literature review of the previously published cases (PubMed research combining "COVID-19" and "Ramsay Hunt Syndrome" or their abbreviations/synonyms, searching for data published at any time till October 2023). (3) Results: Five cases have been previously published (age range: 25-67 years; n = 3 males). Three patients were known to be immunocompetent prior to infection, one was receiving corticotherapy for lung disease, and one had an unspecified immune status. RHS predominantly involved both facial and vestibulocochlear nerves, with one case exclusively involving the facial nerve as the presented case. Regarding facial nerve palsy, three were right-sided (like the current report) and two were left-sided. Two cases were asymptomatic to COVID-19 (like the present patient), one had mild fatigue, and two had classical COVID-19 symptoms preceding RHS symptoms. Workup included serological testing against Varicella Zoster Virus and PCR assays that can detect the viral DNA in saliva, blood, tears, exudates, and cerebrospinal fluid. The treatment combined antiviral and corticosteroid therapies which yielded heterogeneous outcomes that might be related to some demographic and clinical data. (4) Conclusions: RHS rarely occurs in the context of COVID-19. Early recognition is important. Management seems to be similar to the classical condition. Some data may help predict facial nerve recovery.

Brain Stimulation and Neuroplasticity-Series II.

Following the great success of the first series of the Special Issue "Brain Stimulation and Neuroplasticity" [...].