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The potential impact of disease-modifying therapies (DMTs) for multiple sclerosis (MS) on COVID-19 vaccination is poorly understood. According to recent observations, the humoral immune response could be impaired in patients treated with ocrelizumab or fingolimod. Our study evaluated the immunogenicity and safety of mRNA COVID-19 vaccines in a convenience sample of 140 MS patients treated with different DMTs, undergoing vaccination between April and June 2021. Humoral immune response was tested 1 month after the second dose, using a chemiluminescent microparticle immunoassay to detect IgG against SARS-CoV-2 nucleoprotein. We explored the potential correlation between the IgG titer and DMTs. All patients in treatment with first-line DMTs, natalizumab, cladribine, and alemtuzumab, developed a measurable humoral response. In patients treated with ocrelizumab and fingolimod, the IgG level was significantly lower, but only some patients (22.2% for fingolimod and 66% for ocrelizumab) failed to develop a measurable humoral response. In the ocrelizumab group, the IgG level was positively correlated with the time from last infusion. No SARS-CoV-2 infections were reported after vaccination. The most reported side effects were pain at the injection site (57.1%) and fatigue (37.9%). No patient experienced severe side effects requiring hospitalization. Our study confirms that COVID-19 vaccination is safe and well-tolerated in MS patients and should be recommended to all patients regardless of their current DMTs. Since fingolimod and ocrelizumab could reduce the humoral immune response, in patients treated with these drugs, detecting SARS-CoV-2 antibodies could be helpful to monitor the immune response after vaccination.

Over the past decades, among all the non-invasive brain stimulation (NIBS) techniques, those aiming for neuromodulatory protocols have gained special attention. The traditional neurophysiological outcome to estimate the neuromodulatory effect is the motor evoked potential (MEP), the impact of NIBS techniques is commonly estimated as the change in MEP amplitude. This approach has several limitations: first, the use of MEP limits the evaluation of stimulation to the motor cortex excluding all the other brain areas. Second, MEP is an indirect measure of brain activity and is influenced by several factors. To overcome these limitations several studies have used new outcomes to measure brain changes after neuromodulation techniques with the concurrent use of transcranial magnetic stimulation (TMS) and electroencephalogram (EEG). In the present review, we examine studies that use TMS-EEG before and after a single session of neuromodulatory TMS. Then, we focused our literature research on the description of the different metrics derived from TMS-EEG to measure the effect of neuromodulation.

Non-invasive brain stimulation (NIBS) techniques—including repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS)—have emerged as valuable tools for modulating neural activity and promoting plasticity. Traditionally, their effects have been interpreted within a binary framework of long-term potentiation (LTP)-like and long-term depression (LTD)-like plasticity, largely inferred from changes in motor evoked potentials (MEPs). However, existing models do not fully capture the complexity of the biological processes engaged by these techniques and despite extensive clinical application, the cellular and molecular mechanisms underlying NIBS remain only partially understood. This systematic review, conducted in accordance with the PRISMA 2020 guidelines, synthesizes evidence from in vivo, in vitro, and ex vivo studies to delineate how NIBS influences neurotransmission through intracellular signaling, gene expression, and protein synthesis at the cellular level. Emphasis is placed on the roles of classical synaptic models, grounded in Ca2+-dependent glutamatergic signaling and receptor phosphorylation dynamics, as well as broader forms of plasticity involving BDNF–TrkB signaling, epigenetic modifications, neuroimmune and glial interactions, anti-inflammatory pathways, and apoptosis- and survival-related cascades. By integrating findings in humans with those in animal and cellular models, we identify both shared and technique-specific molecular mechanisms underlying NIBS-induced effects, highlighting emerging evidence for multi-pathway, non-binary plasticity mechanisms. Understanding these convergent pathways provides a mechanistic foundation for refining stimulation paradigms and improving their translational relevance for treatment of neurological and psychiatric disorders.

PurposeMultiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.ParticipantsPOINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6–12 (re-baseline), 18–24, 30–36, 42–48 and 54–60 months after DMT initiation.Findings to date748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing–remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm3, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (−0.16 (−0.22 to –0.09)), driven by the deep grey matter (−0.47 (−0.55 to –0.40)), and of the whole white matter (−0.18 (−0.28 to –0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm2. When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (−0.15 (−0.24 to –0.10)).Future plansModelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.

Electroencephalographic (EEG) signals evoked by transcranial magnetic stimulation (TMS) are usually recorded with passive electrodes (PE). Active electrode (AE) systems have recently become widely available; compared to PE, they allow for easier electrode preparation and a higher-quality signal, due to the preamplification at the electrode stage, which reduces electrical line noise. The performance between the AE and PE can differ, especially with fast EEG voltage changes, which can easily occur with TMS-EEG; however, a systematic comparison in the TMS-EEG setting has not been made. Therefore, we recorded TMS-evoked EEG potentials (TEPs) in a group of healthy subjects in two sessions, one using PE and the other using AE. We stimulated the left primary motor cortex and right medial prefrontal cortex and used two different approaches to remove early TMS artefacts, Independent Component Analysis and Signal Space Projection—Source Informed Recovery. We assessed statistical differences in amplitude and topography of TEPs, and their similarity, by means of the concordance correlation coefficient (CCC). We also tested the capability of each system to approximate the final TEP waveform with a reduced number of trials. The results showed that TEPs recorded with AE and PE do not differ in amplitude and topography, and only few electrodes showed a lower-than-expected CCC between the two methods of amplification. We conclude that AE are a viable solution for TMS-EEG recording.

Background Epilepsy is two to three times more common in patients with multiple sclerosis (pwMS) compared to the general population. Patients with MS and epilepsy without other identifiable causes (MS + E) show greater cortical damage than those without epilepsy (MS-E). However, it's unclear whether MS + E patients exhibit distinct cognitive and neuropsychological features requiring specific management. Methods In a cohort of pwMS from three MS centers, MS + E patients were identified and data on MS clinical features, epilepsy history, and treatments were collected. A matched group of MS-E patients was included. Assessments included cognitive and neuropsychiatric tests. Cognitive impairment (CI) was defined as scoring ≥1.5 standard deviations below normative values in ≥1 cognitive domain. Results CI was more prevalent in MS + E (n = 33) patients than in MS-E (n = 33). MS + E patients had lower processing speed (p < 0.01) and visuospatial memory (p = 0.03). MS + E was independently associated with CI (odds ratio 3.6, 95% confidence interval 1.21–12). Somatization, phobia, anxiety, and depression were the most affected neuropsychological domains in MS + E, with global psychological distress negatively correlating with processing speed (rho −0.36, p = 0.048). Conclusions MS + E is associated with higher CI, particularly in processing speed and visuospatial memory, alongside psychological distress, highlighting the need for targeted multidisciplinary care to improve outcomes and quality of life.

Background: SARS-CoV-2 infection has been associated with different neurological conditions such as Guillain-Barré, encephalitis and stroke. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease characterized by recurrent ischemic stroke, cognitive decline, migraine and mood disturbances. One of the mechanisms involved in CADASIL pathogenesis is endothelial dysfunction, which causes an increased risk of recurrent strokes. Since COVID-19 infection is also associated with coagulopathy and endothelial dysfunction, the risk of ischemic stroke might be even higher in this population. We describe the case of a CADASIL patient who developed an acute ischemic stroke after SARS-CoV-2 infection. In patients with diseases causing endothelial dysregulation, such as CADASIL, the hypercoagulability related to COVID-19 may contribute to the risk of stroke recurrence.

Transcranial magnetic stimulation coupled with electroencephalography (TMS-EEG) allows for the study of brain dynamics in health and disease. Cranial muscle activation can decrease the interpretability of TMS-EEG signals by masking genuine EEG responses and increasing the reliance on preprocessing methods but can be at least partly prevented by coil rotation coupled with the online monitoring of signals; however, the extent to which changing coil rotation may affect TMS-EEG signals is not fully understood. Our objective was to compare TMS-EEG data obtained with an optimal coil rotation to induce motor evoked potentials (M1standard) while rotating the coil to minimize cranial muscle activation (M1emg). TMS-evoked potentials (TEPs), TMS-related spectral perturbation (TRSP), and intertrial phase clustering (ITPC) were calculated in both conditions using two different preprocessing pipelines based on independent component analysis (ICA) or signal-space projection with source-informed reconstruction (SSP-SIR). Comparisons were performed with cluster-based correction. The concordance correlation coefficient was computed to measure the similarity between M1standard and M1emg TMS-EEG signals. TEPs, TRSP, and ITPC were significantly larger in M1standard than in M1emg conditions; a lower CCC than expected was also found. These results were similar across the preprocessing pipelines. While rotating the coil may be advantageous to reduce cranial muscle activation, it may result in changes in TMS-EEG signals; therefore, this solution should be tailored to the specific experimental context.

Malnutrition among children population of less developed countries is a major health problem. Inadequate food intake and infectious diseases are combined to increase further the prevalence. Malnourishment brings to muscle cells loss with development of cardiac complications, like arrhythmias, cardiomyopathy and sudden death. In developed countries, malnutrition has generally a different etiology, like chronic diseases. The aim of our study was to investigate the correlation between malnutrition and left ventricular mass in an African children population. 313 children were studied, in the region of Antsiranana, Madagascar, with age ranging from 4 to 16 years old (mean 7,8 ± 3 years). A clinical and echocardiographic evaluation was performed with annotation of anthropometric and left ventricle parameters. Malnutrition was defined as a body mass index (BMI) value age- and sex-specific of 16, 17 and 18,5 at the age of 18, or under the 15th percentile. Left ventricle mass was indexed by height2.7 (LVMI). We identified a very high prevalence of children malnutrition: 124 children, according to BMI values, and 100 children under the 15th percentile. LVMI values have shown to be increased in proportion to BMI percentiles ranging from 29,8 ± 10,8 g/m2.7 in the malnutrition group to 45 ± 15,1 g/m2.7 in >95th percentile group. LVMI values in children < 15th BMI percentile were significantly lower compared to normal nutritional status (29,8 ± 10,8 g/m2,7 vs. 32,9 ± 12,1 g/m2,7, p = 0.02). Also with BMI values evaluation, malnourished children showed statistically lower values of LVMI (29,3 ± 10,1 g/m2,7 vs. 33,6 ± 12,5 g/m2,7, p = 0.001). In African children population, the malnourishment status is correlated with cardiac muscle mass decrease, which appears to be reduced in proportion to the decrease in body size.

The eight-and-a-half syndrome is a rare neuro-ophthalmological condition caused by a structural lesion in the dorsal portion of the pons, involving critical areas of the brainstem, i.e., medial longitudinal fasciculus (MLF), abducens nucleus, facial genu, and colliculus. It is characterized by internuclear ophthalmoplegia with horizontal gaze palsy and peripheral facial palsy. Although the syndrome is most frequently caused by vascular or demyelinating diseases, several different underlying causes might occur. Herein, we describe a case of the eight-and-a-half syndrome caused by a lung adenocarcinoma metastasis localized in the lower pontine tegmentum. Then, we review the current literature on the underlying causes of the eight-and-a-half syndrome.