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BACKGROUND: Fibromyalgia pain and related symptoms are poorly managed by approved pharmacological and alternative interventions. This trial aimed to evaluate the effects of the EXOPULSE Mollii Suit-a multisite transcutaneous electrical nerve stimulation device-on fibromyalgia pain, fatigue, affective symptoms, disease impact, and quality of life. METHODS: Adult patients with fibromyalgia were enrolled. Phase 1 implied a randomized, sham-controlled, cross-over, double-blind trial, applying daily 1 h sessions of active or sham intervention, over 2 weeks (2-week washout). In the open-label phase 2, all patients received daily active intervention for 4 weeks. Comparisons on pain, fatigue, disease impact, affective symptoms, quality of life, clinical impression, and comfort ratings were performed using Friedman, Wilcoxon signed rank, and Chi2 tests. RESULTS: Thirty-three patients completed the study (93.9% female, mean age: 51.3 years). Pain (primary endpoint assessed via a visual analog scale) was significantly reduced after the active (pre-active: 6.9 ± 1.4, post-active: 5.9 ± 1.8, pre-sham: 6.8 ± 1.4, post-sham: 6.6 ± 1.5) versus the sham intervention (X2 = 10.60, p = 0.014). This was also the case of other secondary endpoints (i.e., fatigue, anxiety, and disease impact), except depression and quality of life. The Clinical Global Impression of Change (CGI-C) was significantly different between the active and sham intervention periods (X2 p = 0.035), and the different proportions of categories were as follows: 'worsening' (sham: 18.2% vs. active: 0.0%), 'improvement' (sham: 48.5% vs. active 63.6%) or 'no change (sham: 33.3% vs. active 36.4%) respectively. After phase 2, significant positive effects were observed for most of the outcomes, and 78.8% of patients reported improvement according to CGI-C. CONCLUSIONS: This study suggests the clinical benefits of the EXOPULSE Mollii Suit in alleviating pain and fibromyalgia-related fatigue, emotional symptoms, and disease impact. It is worth noting that the study has several limitations related to the low number of participants, the short-term analysis of effects in the first blinded and controlled phase, and the open-label nature of phase 2. Future studies with a larger cohort and longer protocol treatment are needed, to further confirm the current results, and evaluate the long-term effects of this technique. SIGNIFICANCE: Patients with fibromyalgia suffer from pain as well as fatigue, sleep impairment, emotional disturbances, and altered quality of life. Transcutaneous electrical nerve stimulation might help manage those symptoms, but the available systems are limited by the fact that they could be applied at best over two sites. This randomized controlled study is the first to apply a multi-site transcutaneous electrical nerve stimulation device, the EXOPULSE Mollii Suit, with significant effects on fibromyalgia pain and related symptoms.

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This scientific commentary refers to 'Understanding the mechanisms of fatigue in multiple sclerosis: linking interoception, metacognition and white matter dysconnectivity', by Danciut et al. (https://doi.org/10.1093/braincomms/fcae292).

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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.

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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.

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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.

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(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.

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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.

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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.

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

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Background: Tarlov or perineural cysts are dilations of nerve roots resulting from a pathologically increased cerebrospinal fluid pressure. Although it is very common in the general population, most of these cysts remain asymptomatic. In some cases, they can evolve and exert pressure on neural elements, independently from their initial size. Case report: In this paper, we describe the case of a 33-year-old female known to have asymptomatic multiple and large radicular and pelvic Tarlov cysts. One cyst located in the right pelvic space progressed acutely after delivery, inducing a painful sciatica without neurological deficit. The intracystic bleeding can be a direct consequence of the delivery, leading to an acute and mechanical local compression of the right S1 root. A CT-guided puncture and aspiration allowed a complete recovery. This case report was completed by a review of the literature of these rare intracystic Tarlov bleedings. Conclusions: Intracystic hemorrhage is a rare complication of Tarlov cysts. Delivery-induced cyst bleeding was not described before. Patients known to have large and multiple Tarlov cysts should be monitored in post-partum, as their presence is considered a risk factor. Percutaneous cyst aspiration seems to be an effective and safe treatment to relieve symptoms.

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Fatigue is the most commonly reported symptom in patients with multiple sclerosis (MS). It is a worrisome, frequent, and debilitating manifestation that could occur at any time during the course of MS and in all its subtypes. It could engender professional, familial, and socioeconomic consequences and could severely compromise the patients' quality of life. Clinically, the symptom exhibits motor, cognitive, and psychosocial facets. It is also important to differentiate between perceived or subjective self-reported fatigue and fatigability which is an objective measure of decrement in the performance of cognitive or motor tasks. The pathophysiology of MS fatigue is complex, and its management remains a challenge, despite the existing body of literature on this matter. Hence, unraveling its neural mechanisms and developing treatment options that target the latter might constitute a promising field to explore. A PubMed/Medline/Scopus search was conducted to perform this review which aims (a) to reappraise the available electrophysiological studies that explored fatigue in patients with MS with a particular focus on corticospinal excitability measures obtained using transcranial magnetic stimulation and (b) to assess the potential utility of employing neuromodulation (i.e., non-invasive brain stimulation techniques) in this context. A special focus will be put on the role of transcranial direct current stimulation and transcranial magnetic stimulation. We have provided some suggestions that will help overcome the current limitations in upcoming research.

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INTRODUCTION: A significant number of patients with a peripheral neuropathy have IgM monoclonal gammopathy (IgM-MG). In this work, we encompassed the spectrum and outcome of IgM-related neuropathies (IgM-NP) in a large monocentric cohort of patients with IgM-MG. METHODS: We retrospectively reviewed the neurological and hematological findings and the course of neuropathy in all patients with IgM-MG over a five-year period in our center (Henri Mondor hospital, Assistance Publique Hôpitaux de Paris (APHP), France). RESULTS: Among 550 patients with IgM-MG, 83 patients (15%) had IgM-NP (55 males, mean age 67 y.o.). The median serum level of IgM-MG was 3.4 g/L, mostly kappa light chain component. The hematological diagnosis was Monoclonal Gammopathy of Undetermined Significance (MGUS) in 62 patients. Anti-MAG antibodies were detected in 38 patients with heterogeneous clinical and neurophysiological features. Four patients had neurolymphomatosis presenting as a non-length dependent predominantly motor neuropathy, which occurred long after the finding of IgM-MG and was responsive to hematological treatment. Five patients had an AL amyloid neuropathy revealed by a small fiber neuropathy. Finally, 30 patients were classified as "Neuropathy of Uncertain Relationship with the IgM" (NURIM) with characteristics close to those of an anti-MAG-NP at the time of diagnosis, except for the neurophysiological features with a predominant axonal pattern. CONCLUSION: This study emphasizes the wide spectrum of IgM-NP associated with a variety of hematological diagnoses. In particular, the course and prognosis vary considerably. In this setting, further studies are needed to unravel the group of patients classified as NURIM.

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OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by the accumulation of demyelinating lesions and axonal loss over its course. This study aimed to increase current knowledge of motor preparation in this condition, by assessing the two components of the Bereitschaftspotential (BP1 and BP2), also known as the readiness potential. METHODS: Twelve patients with MS and ten age- and gender-matched healthy controls (HC) were included. Patients' demographic and clinical data were collected. Participants were asked to perform two different tasks, a simple index extension and a Luria sequence. BP1 and BP2 values were obtained from 18 central electroencephalography electrodes and were compared between the two groups. RESULTS: Compared to HC, patients with MS showed earlier BP1 onset (i.e., longer latency) in almost all the analyzed scalp regions during index extension. This was also observed during the Luria sequence, but only in the centro-parietal regions. As for BP2 latency, no significant difference was noted between groups during either task. With regard to amplitudes, patients with MS had larger BP1 amplitudes in the right fronto-central area during index extension and greater BP1 and BP2 amplitudes in bilateral centro-parietal and left central regions during the Luria task. BP1 latency was also found to be significantly correlated with disease duration and performance on executive function tests (Trail Making Test). CONCLUSIONS: This study showed, for the first time, changes in the Bereitschaftspotential in patients with MS. These data reflect prolonged movement preparation in this population and may suggest global alteration of the premotor scheme.

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The objective of the different types of treatments for a spinal metastasis is to provide the best oncological and functional result with the least aggressive side effects. Initially created in 2010 to help clinicians in the management of vertebral metastases, the Spine Instability Neoplastic Score (SINS) has quickly found its place in the decision making and the treatment of patients with metastatic spinal disease. Here we conduct a review of the literature describing the different changes that occurred with the SINS score in the last ten years. After a brief presentation of the spinal metastases' distribution, with or without spinal cord compression, we present the utility of SINS in the radiological diagnosis and extension of the disease, in addition to its limits, especially for scores ranging between 7 and 12. We take this opportunity to expose the latest advances in surgery and radiotherapy concerning spinal metastases, as well as in palliative care and pain control. We also discuss the reliability of SINS amongst radiologists, radiation oncologists, spine surgeons and spine surgery trainees. Finally, we will present the new SINS-derived predictive scores, biomarkers and artificial intelligence algorithms that allow a multidisciplinary approach for the management of spinal metastases.

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BACKGROUND: Sleep complaints are commonly reported by patients with multiple sclerosis (PwMS). Several pharmacological and alternative interventions have been tried, but are usually faced by limited efficacy. Hence, exploring other methods such as transcranial direct current stimulation (tDCS), might be of interest. The aim of this study was to assess the effects of bifrontal tDCS on subjective (i.e., Epworth Sleepiness Scale (ESS)) and objective sleep measures (i.e., actigraphy). METHODS: Seven patients completed the study. Patients randomly received two blocks of five daily sessions each in a crossover design (active and sham, with a washout interval of three weeks). The anode and cathode were placed over the left and right dorsolateral prefrontal cortices, respectively. Sleep assessment included ESS, sleep onset latency, total sleep duration, time in bed, sleep efficiency, waking after sleep onset, and number of awakenings. RESULTS: Compared to baseline scores (11.14 ± 4.06), significant decrease in ESS was obtained after active intervention (7.86 ± 4.18; p = 0.011), but not after sham intervention (9.57 ± 5.62; p = 0.142). No significant changes were observed with regards to actigraphy measures. Sessions were well tolerated, and no serious side-effects were reported at any time. CONCLUSION: Bifrontal tDCS resulted in significant improvement in daytime sleepiness, but did not yield any effect on objective sleep measures in PwMS. This discrepency might be explained by the modest association that could exist between objective and subjective sleep measures. In addition, it could be assumed that modulating objective sleep measures would require a larger sample size, more stimulation sessions, or modulation of other cortical areas.

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Meningiomas arise from arachnoidal cap cells of the meninges, constituting the most common type of central nervous system tumors, and are considered benign tumors in most cases. Their incidence increases with age, and they mainly affect females, constituting 25-46% of primary spinal tumors. Spinal meningiomas could be detected incidentally or be unraveled by various neurological symptoms (e.g., back pain, sphincter dysfunction, sensorimotor deficits). The gold standard diagnostic modality for spinal meningiomas is Magnetic resonance imaging (MRI) which permits their classification into four categories based on their radiological appearance. According to the World Health Organization (WHO) classification, the majority of spinal meningiomas are grade 1. Nevertheless, they can be of higher grade (grades 2 and 3) with atypical or malignant histology and a more aggressive course. To date, surgery is the best treatment where the big majority of meningiomas can be cured. Advances in surgical techniques (ultrasonic dissection, microsurgery, intraoperative monitoring) increase the complete resection rate. Operated patients have a satisfactory prognosis, even in those with poor preoperative neurological status. Adjuvant therapy has a growing role in treating spinal meningiomas, mainly in the case of subtotal resection and tumor recurrence. The current paper reviews the fundamental epidemiological and clinical aspects of spinal meningiomas, their histological and genetic characteristics, and their management, including the various surgical novelties and techniques.

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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.

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Electrical or magnetic stimulation methods for brain or nerve modulation have been widely known for centuries, beginning with the Atlantic torpedo fish for the treatment of headaches in ancient Greece, followed by Luigi Galvani's experiments with frog legs in baroque Italy, and leading to the interventional use of brain stimulation methods across Europe in the 19th century [...].