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Vitamin D is known for its role in modulating calcium and phosphate homeostasis and is implicated both in bone mineralization and immune system regulation. The immune-modulatory role of vitamin D and its impact on multiple sclerosis (MS) courses are still debated. The aim of this review was to check the effect of vitamin D supplementation on cytokine profile regulation in people with MS. A significant increase in serum concentrations of interleukin (IL)-10 and Transforming growth factor (TGF)-β1 after vitamin D supplementation was demonstrated in most studies, with some of them reporting a reduction in disability scores after vitamin D supplementation and an inverse correlation between IL-10 levels and disability. The effect of vitamin D on the serum levels of IL-17 and IL-6 was controversial; different results across studies could be explained by a variability in the treatment duration, route, and frequency of administration, as well as the dosage of vitamin D supplementation, responses to vitamin D treatment and the serum levels reached with supplementation, including the methods used for cytokine analysis and the different cell types investigated, the MS phenotype, the disease phase (active vs. non-active) and duration, and concomitant treatment with disease-modifying therapies. Nevertheless, the significant increase in the serum concentrations of IL-10 and TGF-β1, demonstrated in most studies, suggests an anti-inflammatory effect of vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Urinary, bowel, and sexual dysfunctions are the most frequent and disabling pelvic floor (PF) disorders in patients with multiple sclerosis (MS). PF dysfunction negatively impacts the performance of daily living activities, walking, and the physical dimension of quality of life (QoL) in people with MS. Patient-reported outcomes on sphincteric functioning could be useful to detect PF disorders and their impact on patients' lives. PF rehabilitation proposed by Kegel is based on a series of regularly repeated exercises for "the functional restoration of the perineal muscles". Over time, various therapeutic modalities have been added to PF muscles exercises, through the application of physical or instrumental techniques, such as intravaginal neuromuscular electrical stimulation, electromyographic biofeedback, transcutaneous tibial nerve stimulation. PF rehabilitation has been applied in MS treatment, with improvements of lower urinary tract symptoms severity, QoL, level of anxiety and depression, and sexual dysfunction. This review aims to examine the different PF disorders in MS to evaluate the application of PF rehabilitation in MS and to highlight its advantages and limits, suggesting a multidisciplinary management of PF disorders, with a well-deserved space reserved for PF rehabilitation. [ABSTRACT FROM AUTHOR]

Background and purpose: The COVID‐19 emergency may cause post‐traumatic stress disorder (PTSD), and with regard to people with MS (pwMS) chronic exposure to a wide range of challenging life events has been shown to be correlated with worsening of neurological symptoms, increased lesion burden on brain magnetic resonance imaging and relapses. The aim was to investigate perceived stress, depression, perceived social support, habits and behaviour changes in pwMS through COVID‐19 in comparison to a control group. Methods: A web‐based survey was posted on SMsocialnetwork.com to investigate perceived stress (using the Perceived Stress Scale), depression (with Patient Health Questionnaire 2) and perceived social support (using Social Provision Scale 10 item) in pwMS and a control group through the COVID‐19 pandemic. A secondary group of people with migraine was investigated. Results: In all, 1286 answers from 612 pwMS and 674 control people were included in the final analysis. The answers from 318 people with migraine were included for a secondary analysis. A higher proportion of pwMS were depressed (43.1% vs. 23.1%; p < 0.001), had a high level of perceived stress (58% vs. 39.8%; p < 0.001) and felt significantly less social support (median 33 vs. 35; Q1–Q3 28–36 vs. 32–37; p < 0.001) compared to the control group. A higher percentage of people with migraine were depressed (50% vs. 43%, p = 0.04) compared to pwMS. Conclusions: Considering the negative impact that prolonged stress may have on clinical and radiological disease activity of pwMS, and bearing in mind that a beneficial effect has been demonstrated and achieved with stress management, it is suggested to promote stress control in these patients during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Background: The management of Multiple Sclerosis (MS) has undergone transformative evolution with the introduction of high-efficacy disease-modifying therapies (DMTs), specifically anti-CD20 monoclonal antibodies, such as ocrelizumab (OCR) and ofatumumab (OFA). Materials and methods: This is an independent retrospective cohort study in Relapsing MS (RMS) patients followed at eight Italian MS centers who initiated treatment with OCR or OFA in the participating centers and with at least 12 months on therapy. A generalized linear regression model inverse probability of treatment weight (IPTW) PS-adjusted was performed to evaluate the relationship between annualized relapse rate (ARR) and treatment groups. No evidence of disease activity-NEDA-3 at 12-month score was also collected. Safety profile of the investigated DMTs was recorded. Results: A total cohort of 396 RMS patients fulfilled the required criteria and were enrolled in the study. Out of them, 216 had a prescription of OCR and 180 of OFA. The mean follow-up was 13.2 ± 1.9 months. The estimated means for ARR did not show differences between the two groups, 0.059 for patients on OCR and 0.038 for patients on OFA (p = 0.185). The generalized regression model IPTW PS-adjusted did not reveal differences between patients on OCR and OFA (ExpBOFA 0.974, 95%CI 934–1.015, p = 0.207). NEDA-3 at 12 months was experienced by 199(92.1%) patients on OCR and 170(94.4%) patients on OFA (p = 0.368). Generally, both therapies exhibit good tolerability. Conclusions: The treatment with OCR and OFA resulted in comparable control of disease activity with good safety profile. Our results need further validation in larger multicentre studies with long-term follow-up. [ABSTRACT FROM AUTHOR]

Basically, they argue against the hypothesis that AI will change MS care within the next 10 years, highlighting several technical issues; the main issue is that running AI algorithms requires large data set sizes. A self-administered, artificial intelligence (AI) platform for cognitive assessment in multiple sclerosis (MS). [Extracted from the article]

We propose a possible approach for the remote monitoring of infection risk in people with multiple sclerosis, especially those on immunosuppressant drugs, during COVID-19 pandemic. We developed a digital triage tool to be sent to patients to quickly identify people with high risk of COVID-19 infection. This tool will also limit unnecessary accesses to the MS centers reducing the risk of spreading the infection. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS. [ABSTRACT FROM AUTHOR]

Objective: To report for the first time an Italian epidemiological analysis of the prevalence of multiple sclerosis (MS) in patients with endometriosis (EMS), through the study of the endometriosis population of our referral center; to analyze the clinical profile and perform a laboratory analysis to examine the immune profile and the possible correlation to other autoimmune diseases of the enrolled patients. Methods: We evaluated 1652 women registered with EMS in the University of Naples Federico II and retrospectively searched patients with a co-diagnosis of MS. Clinical features of both conditions were recorded. Serum autoantibody and immune profiles were analyzed. Results: 9 out of 1652 patients presented a co-diagnosis of EMS and MS (9/1652 = 0.005%). Clinically, EMS and MS presented in mild forms. Hashimoto's thyroiditis was found in two patients (2/9). Even if not statistically significant, a trend of variation in CD4- CD8 T lymphocytes and of B cells were found. Conclusion: Our findings suggest an increased risk of MS in women with EMS. However, large-scale prospective studies are needed. [ABSTRACT FROM AUTHOR]

Resting State fMRI (RS-fMRI) represents an emerging and powerful tool to explore brain functional connectivity (FC) changes associated with neurologic disorders. Compared to activation/task-related fMRI, RS-fMRI has the advantages that (i) BOLD fMRI signals are self-generated and independent of subject's performance during the task and (ii) a single dataset is sufficient to extract a set of RS networks (RSNs) that allows to explore whole brain FC. According to these features RS-fMRI appears particularly suitable for the study of FC changes related tomultiple sclerosis (MS). In the present review we will first give a brief description of RS-fMRI methodology and then an overview of most relevant studies conducted so far in MS by using this approach.The most interesting results, in particular, regard the default-mode network (DMN), whose FC changes have been correlated with cognitive status of MS patients, and the visual RSN (V-RSN) whose FC changes have been correlated with visual recovery after optic neuritis. The executive control network (ECN), the lateralized frontoparietal network (FPN), and the sensory motor network (SMN) have also been investigated in MS, showing significant FC rearrangements. All together, RS-fMRI studies conducted so far in MS suggest that prominent RS-FC changes can be detected in many RSNs and correlate with clinical and/or structural MRI measures. Future RS-fMRI studies will further clarify the dynamics and clinical impact of RSNs changes in MS. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article onMRI abnormalities in OCDMS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. [ABSTRACT FROM AUTHOR]

Background: The default-mode network (DMN) has been increasingly recognized as relevant to cognitive status.Objectives: To explore DMN changes in patients with relapsing—remitting (RR) multiple sclerosis (MS) and to relate these to the cognitive status.Methods: Eighteen cognitively impaired (CI) and eighteen cognitively preserved (CP) RRMS patients and eighteen healthy controls (HCs), matched for age, sex and education, underwent neuropsychological evaluation and anatomical and resting-state functional MRI (rs-fMRI). DMN functional connectivity was evaluated from rs-fMRI data via independent component analysis. T2 lesion load (LL) was computed by a semi-automatic method and global and local atrophy was estimated by SIENAX and SPM8 voxel-based morphometry analyses from 3D-T1 images.Results: When the whole group of RRMS patients was compared with HCs, DMN connectivity was significantly weaker in the anterior cingulate cortex, whereas it was significantly weaker in the core but stronger at the periphery of the posterior cingulate cortex. These findings were more evident in CP than CI patients. Observed DMN changes did not correlate with global atrophy or T2-LL, but were locally associated with regional grey matter loss.Conclusion: Relapsing—remitting multiple sclerosis patients show a consistent dysfunction of DMN at the level of the anterior node. DMN distribution changes in the posterior node may reflect a possible compensatory effect on cognitive performance. [ABSTRACT FROM PUBLISHER]

Mucolipidosis IV is an autosomal recessive disorder caused by mutations in MCOLN1, which codes for mucolipin, a transient receptor potential protein. In order to investigate brain metabolic abnormalities in mucolipidosis IV, we studied 14 patients (11 children, 3 adults) by proton magnetic resonance spectroscopic imaging. The ratios of N-acetylaspartate/ creatine-phosphocreatine and N-acetylaspartate/choline-containing compounds in patients with mucolipidosis IV were significantly reduced in all regions of interest except the parietal gray matter and thalamus. The ratios of choline-containing compounds/creatine-phosphocreatine was not significantly reduced in patients compared with controls. The ratio of N-acetylaspartate/creatine-phosphocreatine were significantly lower (P = .005) in the more neurologically impaired patients compared with the least impaired. For every region of interest, except for parietal gray matter, the ratio of N-acetylaspartate/creatine-phosphocreatine was lower in the more motorically impaired patient group. There was no difference for the ratio of N-acetylaspartate/creatine-phosphocreatine between younger and older patients. These findings suggest that mucolipidosis IV is largely a static developmental encephalopathy associated with diffuse neuronal and axonal damage or dysfunction. Mucolipin deficiency impairs motor more than sensory central nervous system pathways. (J Child Neurol 2003; 18:443-449). [ABSTRACT FROM AUTHOR]

Introduction: People with multiple sclerosis (PwMS) exhibit a spectrum of needs that extend beyond solely disease-related determinants. Investigating unmet needs from the patient perspective may address daily difficulties and optimize care. Our aim was to identify patterns of unmet needs among PwMS and their determinants. Methods: We conducted a cross-sectional multicentre study. Data were collected through an anonymous, self-administered online form. To cluster PwMS according to their main unmet needs, we performed agglomerative hierarchical clustering algorithm. Principal component analysis (PCA) was applied to visualize cluster distribution. Pairwise comparisons were used to evaluate demographics and clinical distribution among clusters. Results: Out of 1764 mailed questionnaires, we received 690 responses. Access to primary care was the main contributor to the overall unmet need burden. Four patterns were identified: cluster C1, 'information-seekers with few unmet needs'; cluster C2, 'high unmet needs'; cluster C3, 'socially and assistance-dependent'; cluster C4, 'self-sufficient with few unmet needs'. PCA identified two main components in determining the patterns: the 'public sphere' (access to information and care) and the 'private sphere' (need for assistance and social life). Older age, lower education, longer disease duration and higher disability characterized clusters with more unmet needs in the private sphere. However, demographic and clinical factors failed in explaining the four identified patterns. Conclusion: Our study identified four unmet need patterns among PwMS, emphasizing the importance of personalized care. While clinical and demographic factors provide some insight, additional variables warrant further investigation to fully understand unmet needs in PwMS. [ABSTRACT FROM AUTHOR]

Cognitive impairment (CI) occurs in about 40–65% of people with multiple sclerosis (MS) during the disease course. Cognitive rehabilitation has produced non-univocal results in MS patients. Objective: The present study aimed to evaluate whether an Integrated Cognitive Rehabilitation Program (ICRP) in MS patients might significantly improve CI. Methods: Forty patients with three phenotypes of MS were randomly assigned into two groups: the experimental group (EG, n = 20), which participated in the ICRP for 10 weeks of training; and the control group (CG, n = 20). All participants' cognitive functions were assessed at three timepoints (baseline, post-treatment, and 3-month follow-up) with the California Verbal Learning (CVLT), Brief Visuospatial Memory (BVMTR), Numerical Stroop, and Wisconsin tests. Results: When compared to CG patients, EG patients showed significant improvements in several measures of cognitive performance after ICRP, including verbal learning, visuospatial memory, attention, and executive functions. Conclusions: Home-based ICRP can improve cognitive functions and prevent the deterioration of patients' cognitive deficits. As an integrated cognitive rehabilitation program aimed at potentiation of restorative and compensatory mechanisms, this approach might suggest an effective role in preserving neuronal flexibility as well as limiting the progression of cognitive dysfunction in MS. [ABSTRACT FROM AUTHOR]

• Gender influences MS prognosis. • Sex hormones changes affect MS clinical course. • Puberty, pregnancy, puerperium and climateric influence MS course. • Oral Contraceptives and assisted reproductive techniques modify immune system. Multiple Sclerosis is a multifactorial chronic autoimmune disease, affecting predominantly females in the fertile age. Sex hormones changes during a woman's life, from puberty to menopause, including pregnancy and puerperium, may influence the onset and course of Multiple Sclerosis. The effect of estrogen levels on immune, clinical and radiological aspects of Multiple Sclerosis, also stimulated investigation on the effect of sexual hormones therapies, such as oral contraceptives and assisted reproductive technique, on the Multiple Sclerosis course. A literature search for original articles and reviews was conducted in the databases, including PubMed, Scopus, and ClinicalTrials.gov of the U.S. National Library of Medicine site from 1988 to 2020. This review reports the effects of the physiological and iatrogenic hormonal changes either on immune or clinical or paraclinical features in the different life stages of women affected by Multiple Sclerosis. [ABSTRACT FROM AUTHOR]

• Breakthrough disease activity has been reported after fingolimod withdrawal. • Disease activity seems to be driven by dysregulated egress of lymphocytes from lymph-nodes. • The best therapeutic strategy after fingolimod withdrawal is still unknown. • Cladribine depletes circulating lymphocytes within 4 weeks. • We report 3 patients who were treated with cladribine as rescue therapy after fingolimod. • All patients exhibited persistent high disease activity after cladribine start. • Cladribine should be used with caution as a rescue strategy after fingolimod failure. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the JC papovavirus, and is a well known complication in patients with lymphoproliferative diseases (LPDs) during chemotherapy. We report the case of a 59-year-old woman affected by B-cell LPD who underwent three cycles of chemotherapy with fludarabine and rituximab and developed atypical PML six months after the last cycle of chemotherapy. Our patient showed the following peculiarities: chemotherapy regimen was neither heavy nor prolonged; the onset of neurological symptoms was unexpectedly late; the MRI lesion was atypical for non-HIV-related PML, being monofocal and infratentorial with early gadolinium (Gd) enhancement and mass effect; survival was rather prolonged despite the lack of treatment. These data suggest that in patients with LPDs, the occurrence of progressive neurological deficits should induce the suspicion of PML even when clinical onset is late (with respect to chemotherapy) and in the presence of a single infratentorial lesion, with Gd enhancement and mass effect. [ABSTRACT FROM AUTHOR]

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion. [ABSTRACT FROM AUTHOR]

Introduction: Migraine shows a significantly higher prevalence in women, especially during reproductive age when menstrual-related hormonal fluctuations represent the most common migraine trigger. Indeed, over 50% of patients report a higher occurrence of migraine attacks during the perimenstrual window. Menstrual migraine attacks are consistently referred to as more disabling, less responsive to symptomatic treatments, longer in duration, and more prone to relapse than non-menstrual migraine attacks. Evidence strongly suggests that estrogen fluctuations are involved in migraine attacks worsening during the perimenstrual window through several mechanisms directly or indirectly involving the CGRP pathway. We aimed to evaluate whether mAbs blocking CGRP-ligand or receptor (CGRP-mAbs) could represent an effective and safe preventive treatment for menstrual migraine attacks in patients with menstrual-related migraine (MRM) with previous treatment failures. Methods: Forty patients with MRM with at least three previous treatment failures received monthly CGRP-mAbs. At the baseline and after six CGRP-mAbs administrations, patients underwent to extensive interviews to assess frequency, duration, intensity, and responsiveness to painkiller intake of migraine attacks occurring during the perimenstrual window. Results: After six administrations of CGRP-mAbs we observed a reduction of median menstrual migraine frequency (from 5 to 2 days per month), pain intensity (from 8/10 to 6/10), and attacks duration (from 24 to 8 h) (p < 0.001). Nevertheless, a significant increase in the percentage of responding to migraine painkillers was observed from 42.5% at baseline to 95% at T1 (p < 0.001). Conclusions: CGRP-mAbs could represent a safe and effective preventive therapeutic strategy able to reduce the disabling burden of menstrual migraine attack frequency, duration, intensity, and significantly improve the response to painkillers. These findings could be related to and further indirectly prove the greater influence of CGRP-mediated mechanisms in the pathophysiology of menstrual migraine attacks. [ABSTRACT FROM AUTHOR]

Background: In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with multiple sclerosis (MS), but there are no data about maternal and fetal outcomes. Objectives: In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection. Methods: We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020–2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score–based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders. Results: In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32–3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations. Conclusion: Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes. [ABSTRACT FROM AUTHOR]

Background: Telemedicine has proven successful in relieving the burden of chronic neurological disorders from the national health care systems by ensuring a highly customized and effective management plan. Although many studies focus on assessing telemedicine effectiveness, little is known about the economic implications of telemedicine applications in chronic neurological diseases (CNDs). This issue could account for a lack of widespread implementation. Objective: Our study attempted to fill this gap by systematically reviewing scientific literature on the economic evaluation of telemedicine compared with traditional care in the management of CNDs. Methods: We performed a literature search on PubMed, Google Scholar, Scopus, Embase, and Medline. The inclusion criteria were as follows: (1) studies with a full cost-analysis; (2) randomized controlled trials; (3) studies comparing telemedicine interventions with traditional care; (4) articles focusing only on CNDs. Conversely, the exclusion criteria were as follows: (1) studies focusing on acute neurological conditions or other diseases and (2) study protocols, case report, duplicate articles, abstract only, books, letters to editors, and review articles. Results: Ten articles met the inclusion criteria. Three different approaches of telemedicine intervention could be identified: digital cognitive-behavioral therapy (CBT), motor telerehabilitation, and home monitoring and assessment devices. Conclusion: Cost-analysis showed an overall benefit in terms of both cost and effectiveness from the application of telemedicine instead of in-presence management in CNDs. Among the identified interventions, digital CBT proved to be the most cost-saving. However, promising results were also found in monitoring and assessment devices and in telerehabilitation. Definitely, however, more thorough, comprehensive, and high-quality economic evaluation studies are needed. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is characterized by a large spectrum of symptoms, involving all functional systems. Psychiatric symptoms are common in people with MS (pwMS) having an important impact on quality of life and on some features of MS (fatigue, sleep, disability, adherence to disease-modifying drugs). The main psychiatric disturbances in MS are depressive, bipolar, anxiety, schizophrenic and obsessive–compulsive syndromes. Methods: Literature search for original articles and review in the databases, including PubMed and Scopus from 1959 to 2019. Results and conclusion: Studies answering the aim of this review were selected and reported. Epidemiological and clinical aspects of psychiatric syndromes (PS) in MS as well as self-report diagnostic scales and radiological correlates of PS in MS are described. Moreover, some radiological studies about primary psychiatric disorders (PD) are reported to underline how gray matter atrophy, white matter abnormalities and corpus callosum involvement in these diseases, as features in common with MS, may explain the more frequent occurrence of PD in MS than in the general population. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique also used as a non-pharmacological intervention against cognitive impairment. The purpose of the present review was to summarize what is currently known about the effectiveness of rTMS intervention on different cognitive domains in patients with mild cognitive impairment (MCI) and to address potential neuromodulation approaches in combination with electroencephalography (EEG) and neuroimaging, especially functional magnetic resonance imaging (fMRI). In this systematic review, we consulted three main databases (PubMed, Science Direct, and Scopus), and Google Scholar was selected for the gray literature search. The PRISMA flowchart drove the studies' inclusion. The selection process ensured that only high-quality studies were included; after removing duplicate papers, explicit ratings were given based on the quality classification as high (A), moderate (B), or low (C), considering factors such as risks of bias, inaccuracies, inconsistencies, lack of direction, and publication bias. Seven full-text articles fulfilled the stated inclusion, reporting five double-blind, randomized, sham-controlled studies, a case study, and a randomized crossover trial. The results of the reviewed studies suggested that rTMS in MCI patients is safe and effective for enhancing cognitive functions, thus making it a potential therapeutic approach for MCI patients. Changes in functional connectivity within the default mode network (DMN) after targeted rTMS could represent a valuable indicator of treatment response. Finally, high-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has been shown to significantly enhance cognitive functions, such as executive performance, together with the increase of functional connectivity within frontoparietal networks. The main limitations were the number of included studies and the exclusion of studies using intermittent theta-burst stimulation, used in studies on Alzheimer's disease. Therefore, neuroimaging techniques in combination with rTMS have been shown to be useful for future network-based, fMRI-guided therapeutic approaches. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure. [ABSTRACT FROM AUTHOR]

Ocrelizumab is a humanized monoclonal antibody designed to bind to the CD20 molecule, resulting in a rapid depletion of B-cells; however, it has been shown that lymphocyte subpopulations other than B-cells are affected by the drug. To review the effects of ocrelizumab on circulating lymphocytes and identify candidate biomarkers to predict and monitor treatment response. A literature search for the most relevant articles from 2006 to 2022 was conducted in PubMed and Scopus. The effect of ocrelizumab on the peripheral immune system goes beyond B-cells; it also depletes T CD20 + lymphocytes. Further, ocrelizumab reshapes the T-cell response toward a low inflammatory profile and induces an increase in T CD8 + regulatory cell percentage. A higher Body Mass Index and higher B-cell count at baseline have been associated with early B-cell reappearance. Serum neurofilament light chain reduction has been associated with treatment response. Ocrelizumab treatment exerts a broad immunomodulatory effect and may be tailored based on patients' clinical and biological profiles. [ABSTRACT FROM AUTHOR]

Due to the COVID-19 pandemic, most memory clinics have had to suspend their activities. On the other hand, international dementia experts have recommended to provide urgently worldwide support for people living with dementia. This situation urges to play out new strategies to guarantee adequate care. Telemedicine and digital technology (DT) devices, such as smartphones, can be very helpful in remote monitoring and care. Technological devices such as videoconference or smartphone apps might be used for follow-up visits and support to patients and caregivers and to acquire digital markers of clinical progression. Hopefully, this dramatic situation would facilitate the process of progressive familiarization of neurologists with telemedicine and DT approach. [ABSTRACT FROM AUTHOR]

Background: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare but potentially reversible autoimmune encephalopathy. The most frequent neuroimaging correlates are normal brain MRI or non-specific white matter hyperintensities. Methods: We present the first description of conus medullaris involvement, also providing an extensive review of MRI patterns described so far. Results: Our results show that in less than 30% of cases, it is possible to find focal SREAT neuroanatomical correlates. Among these, T2w/FLAIR temporal hyperintensities are the most frequent, followed by basal ganglia/thalamic and brainstem involvement, respectively. Conclusions: Unfortunately, spinal cord investigation is an uncommon practice in the diagnostic approach of encephalopathies, thus neglecting potential pathological lesions of the medulla spinalis. In our opinion, the extension of the MRI study to the cervical, thoracic, and lumbosacral regions may allow finding new, and hopefully specific, anatomical correlates. [ABSTRACT FROM AUTHOR]

Despite being a common issue in people with multiple sclerosis (pwMS), sexual dysfunction is still underinvestigated. This work aims to assess the potential determinants of sexual dysfunction in pwMS by considering its relationship with disease severity (in terms of global disability), illness perception, and depressive symptoms. In this multicenter study, 1010 pwMS responded to an online survey. A serial mediation model considering negative illness perception and depressive symptoms as mediators of the relationship between disease severity and sexual dysfunction was conducted using the SPSS PROCESS Macro with bias-corrected bootstrapping (5000 samples). Disease severity exerts an indirect effect on sexual dysfunction via illness perception, both independently and through depressive symptoms. However, the results indicated that illness perception plays a more crucial role in sexual dysfunction in pwMS with mild disability than in pwMS with moderate-severe disability. This study suggests that higher disability increases its magnitude by enhancing negative illness perception, that, in turn, affects sexual dysfunction both directly and through depressive symptoms, especially in pwMS with mild disability. Modulating the effect of illness perception by favoring adaptive coping strategies might represent a valid approach to mitigate sexual dysfunction symptoms in MS. [ABSTRACT FROM AUTHOR]

Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. Results: we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9–3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Discussion and conclusions: Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia. [ABSTRACT FROM AUTHOR]

Background: Many factors are believed to be positively associated with the incidence of relapses in people with multiple sclerosis (MS), including infections. However, their role is still controversial. We aimed to investigate whether symptomatic infections in people with MS increase the risk of relapse in the short, medium, or long term. Materials and Methods: We enrolled consecutive patients with relapsing MS (RMS) from October to December 2018. From enrolment up to September 2020, an online questionnaire investigating the occurrence of infections was sent via WhatsApp® monthly to the enrolled patients, while in-person visits were performed every six months. When patients complained of symptoms compatible with relapses, they attended an extra in-person visit. Results: We enrolled 155 patients with RMS, and 88.38% of patients were treated with disease-modifying therapies. In the dataset, 126,381 total patient days, 78 relapses, and 1202 infections were recorded over a period of about 2 years. No increased risk of relapse after clinically manifest infections was found in the short-, medium-, or long-term period. No correlation was found between all infections and the number of relapses (p = 0.212). The main analyses were repeated considering only those infections that had at least two of the following characteristics: duration of infection ≥ 4 days, body temperature > 37° Celsius, and the use of drugs (antibiotics and/or antivirals), and no significant associations were observed. Conclusions: No associations between infections and relapses were observed, likely suggesting that disease-modifying therapies may protect against the risk of relapse potentially triggered by infections. [ABSTRACT FROM AUTHOR]

Objective: Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing–remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability. The identification of signs, symptoms, markers of progression, and strategies to manage MS patients is mandatory to allow early identification of those at higher risk of conversion to SPMS, for prompt intervention to cope with the progression of the disease. Methods: A panel of Italian experts from Southern Italy have reviewed the current knowledge on MS and its management and identified the crucial tools for SPMS recognition. Results: More effective communication between patients and clinicians should be established, with the support of digital tools. Moreover, the improvement in the clinical use of biomarkers for progression (cellular structures and tissue organization, such as neurofilaments and chitinase 3-like 1, axonal and neurons density) and of instrumental analyses for recognition of whole-brain atrophy, chronic active lesions, spinal cord lesions and atrophy, and the improvement the combination of the Expanded Disability Status Scale and the evaluation of cognitive dysfunction are discussed. Conclusion: Given the availability of a pharmacological option, adequate education both for patients, regarding the evolution of the disease and the specific treatment, and for professionals, to allow more effective and sensitive communication and the best use of diagnostic and management tools, could represent a strategy to improve patient management and their quality of life. [ABSTRACT FROM AUTHOR]

Ocrelizumab is a humanized monoclonal anti-CD20 antibody, approved for the treatment of relapsing and primary-progressive multiple sclerosis. We reported a case of pericarditis in an RRMS patient treated with ocrelizumab, who presented with chest pain, high body temperature and laboratory findings of systemic inflammation, with a favorable clinical outcome. [ABSTRACT FROM AUTHOR]

Patients afflicted by multiple sclerosis experience a relapsing-remitting course in about 85% of the cases. Furthermore, after a 10/15-year period their situation tends to worse, resulting in what is considered the second phase of multiple sclerosis. While treatments are now available to reduce the symptoms and slow down the progression of the disease, the administration of drugs must be adapted to the course of the disease, and predicting relapsing periods and the worsening of the symptoms can greatly improve the outcome of the treatment. For this reason, indicators such as the patient-reported outcome measures (PROMs) have been largely used to support early diagnosis and prediction of future relapsing periods in patients affected by multiple sclerosis. However, such indicators are insufficient, as the prediction they provide is often not accurate enough. In this paper, machine learning techniques have been applied to data obtained from clinical trial, in order to improve the prediction capabilities and provide doctors with an additional instrument to evaluate the clinical situation of patients. After the application of correlation indicators and the use of principal component analysis for the reduction of the dimensionality of the feature space, classification algorithms have been applied and compared, in order to identify the best suiting one for our purposes. After the application of re-balance algorithms, the accuracy of the machine learning-based prediction system reaches 79%, demonstrating the capability of the framework to correctly predict future progression of disability. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Results: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75–4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02). Conclusions: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab. [ABSTRACT FROM AUTHOR]

Siponimod, a selective modulator of sphingosine 1-phosphate receptors 1 (S1P1) and 5 (S1P5), has recently been marketed for patients with Secondary Progressive Multiple Sclerosis (SPMS). Herein, we report three SPMS patients presenting disease reactivation in the first three months after switching from fingolimod to siponimod. Fingolimod binds to S1P1, S1P3, S1P4 and S1P5 receptors. S1P3 holds a central role in eliciting central proinflammatory responses, thus it has been hypothesized that upregulation of S1P3 may be the mechanism behind relapses after switching from fingolimod to siponimod. Further studies are needed to investigate the safety and efficacy of this treatment sequencing. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence has shed light on the role of the hemostatic pathway and its components in the pathogenesis of multiple sclerosis (MS), particularly in enhancing and sustaining neuroinflammation. Objective: To review the clinical, experimental, and neuroimaging evidence supporting the role of different components of the hemostatic pathway in the pathogenesis of neuroinflammation in MS and discuss their translational potential as disease biomarkers and therapeutic targets. Methods: A literature search for most relevant articles from 1956 to 2020 was conducted in PubMed and Scopus. Results: Hemostasis components appear to be involved in different key events of neuroinflammation in MS including mononuclear cell diapedesis, microglia activation, and neuronal damage. Conclusion: The findings on the interplay between hemostatic and thrombotic molecular pathways in the pathogenesis of neuroinflammation in MS open new opportunities for developing novel biomarkers for disease monitoring and prognosis, as well as novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: Cladribine administration has been approved for the treatment of relapsing–remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging. Methods: We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models. Results: Of the 243 subjects included in the study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 ± 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41–0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1–2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04–3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1–4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997–0.999, p = 0.01). Conclusion: In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions.316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired about a previous diagnosis of PsO. Demographic and MS history data were retrospectively gathered for two groups: MS patients without and with PsO. Information about MS phenotype, Expanded Disability Status Scale (EDSS) score at the diagnosis and at last follow-up, disease modifying therapy (DMT) were collected retrospectively from our MS data set. PsO diagnosis was confirmed by an experienced dermatologist and severity was assessed with the Psoriasis Area and Severity Index (PASI).Among 253 respondents, 5.85% reported a PsO diagnosis that was confirmed after the dermatological evaluation Among patients with psoriasis 66.67% had progressive course of MS (p = 0.032) and the onset of PsO typically occurred after MS diagnosis. 9 out 15 patients had a PASI score of 0 and 6 are currently undergoing treatment with an anti-CD20 therapy. Notably, a subset of our patients were on anti-CD20 therapy and did not experience a worsening of dermatological symptoms.The prevalence of PsO in our outpatient MS population aligns with previous studies. Treatment approaches should be tailored to individual patient needs, emphasizing collaboration between neurologists and dermatologists. Medications like dimethyl fumarate, effective in both conditions, could be considered. The data from our study also suggest that anti-CD20 therapy may be a viable option for some patients with concurrent MS and mild PsO, without a significant worsening of dermatological symptoms. Further research is needed to elucidate the complex relationship between MS and PsO and to develop more effective therapeutic strategies for patients with both conditions.Methods: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions.316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired about a previous diagnosis of PsO. Demographic and MS history data were retrospectively gathered for two groups: MS patients without and with PsO. Information about MS phenotype, Expanded Disability Status Scale (EDSS) score at the diagnosis and at last follow-up, disease modifying therapy (DMT) were collected retrospectively from our MS data set. PsO diagnosis was confirmed by an experienced dermatologist and severity was assessed with the Psoriasis Area and Severity Index (PASI).Among 253 respondents, 5.85% reported a PsO diagnosis that was confirmed after the dermatological evaluation Among patients with psoriasis 66.67% had progressive course of MS (p = 0.032) and the onset of PsO typically occurred after MS diagnosis. 9 out 15 patients had a PASI score of 0 and 6 are currently undergoing treatment with an anti-CD20 therapy. Notably, a subset of our patients were on anti-CD20 therapy and did not experience a worsening of dermatological symptoms.The prevalence of PsO in our outpatient MS population aligns with previous studies. Treatment approaches should be tailored to individual patient needs, emphasizing collaboration between neurologists and dermatologists. Medications like dimethyl fumarate, effective in both conditions, could be considered. The data from our study also suggest that anti-CD20 therapy may be a viable option for some patients with concurrent MS and mild PsO, without a significant worsening of dermatological symptoms. Further research is needed to elucidate the complex relationship between MS and PsO and to develop more effective therapeutic strategies for patients with both conditions.Results: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions.316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired about a previous diagnosis of PsO. Demographic and MS history data were retrospectively gathered for two groups: MS patients without and with PsO. Information about MS phenotype, Expanded Disability Status Scale (EDSS) score at the diagnosis and at last follow-up, disease modifying therapy (DMT) were collected retrospectively from our MS data set. PsO diagnosis was confirmed by an experienced dermatologist and severity was assessed with the Psoriasis Area and Severity Index (PASI).Among 253 respondents, 5.85% reported a PsO diagnosis that was confirmed after the dermatological evaluation Among patients with psoriasis 66.67% had progressive course of MS (p = 0.032) and the onset of PsO typically occurred after MS diagnosis. 9 out 15 patients had a PASI score of 0 and 6 are currently undergoing treatment with an anti-CD20 therapy. Notably, a subset of our patients were on anti-CD20 therapy and did not experience a worsening of dermatological symptoms.The prevalence of PsO in our outpatient MS population aligns with previous studies. Treatment approaches should be tailored to individual patient needs, emphasizing collaboration between neurologists and dermatologists. Medications like dimethyl fumarate, effective in both conditions, could be considered. The data from our study also suggest that anti-CD20 therapy may be a viable option for some patients with concurrent MS and mild PsO, without a significant worsening of dermatological symptoms. Further research is needed to elucidate the complex relationship between MS and PsO and to develop more effective therapeutic strategies for patients with both conditions.Discussion and conclusion: Multiple sclerosis (MS) and psoriasis (PsO) are distinct chronic autoimmune conditions with varying impacts on patients' lives. While the co-occurrence of MS and PsO has been reported, the underlying pathogenic link remains unclear. This study aimed to investigate the prevalence of PsO in a MS outpatient clinic population and explore the potential interplay between these conditions.316 MS patients who had at least one visit at our MS center in the last year, were selected from our outpatient MS Clinic electronic database and were e-mailed in August 2023 and inquired about a previous diagnosis of PsO. Demographic and MS history data were retrospectively gathered for two groups: MS patients without and with PsO. Information about MS phenotype, Expanded Disability Status Scale (EDSS) score at the diagnosis and at last follow-up, disease modifying therapy (DMT) were collected retrospectively from our MS data set. PsO diagnosis was confirmed by an experienced dermatologist and severity was assessed with the Psoriasis Area and Severity Index (PASI).Among 253 respondents, 5.85% reported a PsO diagnosis that was confirmed after the dermatological evaluation Among patients with psoriasis 66.67% had progressive course of MS (p = 0.032) and the onset of PsO typically occurred after MS diagnosis. 9 out 15 patients had a PASI score of 0 and 6 are currently undergoing treatment with an anti-CD20 therapy. Notably, a subset of our patients were on anti-CD20 therapy and did not experience a worsening of dermatological symptoms.The prevalence of PsO in our outpatient MS population aligns with previous studies. Treatment approaches should be tailored to individual patient needs, emphasizing collaboration between neurologists and dermatologists. Medications like dimethyl fumarate, effective in both conditions, could be considered. The data from our study also suggest that anti-CD20 therapy may be a viable option for some patients with concurrent MS and mild PsO, without a significant worsening of dermatological symptoms. Further research is needed to elucidate the complex relationship between MS and PsO and to develop more effective therapeutic strategies for patients with both conditions. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple sclerosis (MS) are considered at higher risk of COVID-19 infection due to treatment with immune modulators and immune-suppressive agents. The exact risk factors are not clear. So, we aimed to conduct a study to determine the predictors of catching COVID-19 infection during the pandemic stage in patients with multiple sclerosis (MS). Methods: We conducted a multicenter screening study and developed an online questionnaire to collect patients' self-reported demographic features along with MS-related and COVID-19-related information. The online questionnaire link was released by the Iran Multiple Sclerosis Society (IMSS) social media channel, accessible for 4160 MS patients totally and also was sent by WhatsApp for nonmember cases. Results: Totally, 1448 MS patients participated in our study. Twenty-five (1.7%) patients were diagnosed with COVID-19, from which 4 were hospitalized, 4 were treated with medical therapy, and 17 patients had home-quarantine. The patients with COVID-19 diagnosis were more frequently treated with rituximab (28% vs 24%, P = 0.001) than others, and cardiovascular comorbidity was more frequent in this group (8% vs 1.6%, P = 0.01). Regression analysis showed that cardiovascular disease was a significant positive predictor of COVID-19 infection (OR = 5.2, 95% CI: 1.1-23.7). Conclusions: Patients with MS who have cardiovascular disease should be more monitored for COVID-19 infection as they are at higher risk of infection. [ABSTRACT FROM AUTHOR]

Background: Migraine affects more than a billion people all over the world and requires critical employment of healthcare resources. Telemedicine could be a reasonable tool to manage people suffering from headaches, and it received a big push from the COVID-19 pandemic. Objective: This review aims to propose a practical approach for the virtual management of these patients. Methods: To do this, we conducted a literature search, including 32 articles relevant to the topic treated in this review. Results: The most challenging step in telemedicine applied to practical neurology remains the clinical assessment, but through a careful headache history and a recently proposed entirely virtual neurological assessment, this hitch can be easily overcome. Electronic diary compilations and virtual administration of disability-measuring scales, conversely, are the key features of effective long-term follow-up although we do not have apps that met the criteria of scientific reliability. Furthermore, tele-rehabilitation seems to be effective and has demonstrated to be a solution to alternatively treat chronic patients at home, and can be considered part of the remote management of headache patients. Moreover, virtual management of headaches finds an application in specific communities of patients, as pediatric patients and for rural communities of low- and middle-income countries suffer from health disparities, with inadequate resources and knowledge gaps. Conclusion: Telemedicine could be promising for patients with no regular or convenient access to headache specialists and seems to be a priority in managing migraine patients to avoid non-urgent hospitalizations [ABSTRACT FROM AUTHOR]

Background: Stress is a potential trigger for clinical and radiological activity in Multiple Sclerosis (MS). COVID-19 pandemic has been a relevant source of mental distress in people with MS (pwMS) and deeply impacted on disease management. Objective: To investigate the association between stress, anxiety, depression, and risk of relapse during the COVID-19 pandemic. Methods: From an electronic database used for clinical practice, we extracted data of relapsing–remitting (RR) or relapsing-progressive (RP) MS patients and calculated the annualized relapse rate (ARR) during 2019 and 2020. From 01/12/2020 to 30/12/2020, enrolled patients were invited to fill in a Google Forms survey to investigate depression, anxiety, stress, and Post-Traumatic Stress Disorder (PTSD). Results: We selected 216 patients with RR or RP-MS to calculate ARR: compared to 2019, in 2020 there was a significant increase in ARR (p = 0.0142). Over 216 selected pwMS, 154 completed the survey. Matching the survey responses and incidence of relapses in 2020, there was a significant association between relapses and stress (p = 0.030) and relapses and depression (p = 0.011), but not between relapses and anxiety (p = 0.130) or PTSD (p = 0.279). Conclusions: Our results support the hypothesis that pandemic-related stress is associated to clinical exacerbations, both as a possible consequence of the COVID-19 impact on MS care. [ABSTRACT FROM AUTHOR]

Purpose: To investigate in multiple sclerosis (MS) patients, the relationship between pain and religiosity and to determine whether distinct dimensions of religiosity were associated with quality of life. Methods: MS patients during clinical follow-up filled out the visual analogue scale for pain (VAS), the Mc Gill questionnaire (McGQ), the 36-Item Short Form Health Survey (SF-36), and the religious attitude scale (RAS), and expanded disability status scale (EDSS) was assessed. Results: Ninety-two MS patients were enrolled, only two declined. There was a negative correlation between religious practice and faith and some domains of the SF-36 and a positive correlation between sensory, affective, and evaluative aspects of pain (at McGQ) and religious practices, and between evaluative aspects of pain (at McGQ) and faith. EDSS was significantly higher in practitioner believers compared to not practitioners. Conclusions: More disabled MS patients, with worse quality of life, also due to physical pain, find a source of comfort in faith and religious practices. Pain is not relieved by prayer; therefore, we may guess that in MS the poor beneficial effect of religiosity and practice on pain perception may be linked to a structural/functional damage of neural circuits involved in reducing pain during prayer. [ABSTRACT FROM AUTHOR]

Background: Friedreich's ataxia (FRDA) is an untreatable disease that negatively impacts patients' and caregivers' quality of life. Objectives: The aims were to improve the quality of the information for FRDA patients and caregivers and suggest a possible tool to spread this information. Material and methods: Thirty-four FRDA patients and 45 caregivers were interviewed separately using a structured self-administered survey about their information-seeking behavior, their level of expectation and satisfaction for the information received, and the need for further information. Results and conclusion: For patients and caregivers, the main source of information was the FRDA specialist and the media. The most searched items were "general information"; patients and particularly caregivers desired to get more information on existing and experimental therapies. Adequate information supply is part of good medical care; therefore, a deeper insight of clinicians in information-seeking behavior of FRDA patients and caregivers would provide tailored information and improve therapeutic alliance. [ABSTRACT FROM AUTHOR]

We have previously evidenced that Mindfulness Meditation (MM) in experienced meditators (EMs) is associated with long-lasting topological changes in resting state condition. However, what occurs during the meditative phase is still debated. Utilizing magnetoencephalography (MEG), the present study is aimed at comparing the topological features of the brain network in a group of EMs (n = 26) during the meditative phase with those of individuals who had no previous experience of any type of meditation (NM group, n = 29). A wide range of topological changes in the EM group as compared to the NM group has been shown. Specifically, in EMs, we have observed increased betweenness centrality in delta, alpha, and beta bands in both cortical (left medial orbital cortex, left postcentral area, and right visual primary cortex) and subcortical (left caudate nucleus and thalamus) areas. Furthermore, the degree of beta band in parietal and occipital areas of EMs was increased too. Our exploratory study suggests that the MM can change the functional brain network and provides an explanatory hypothesis on the brain circuits characterizing the meditative process. [ABSTRACT FROM AUTHOR]

Introduction: Blood coagulation constituents might exert immunomodulatory functions in the CNS and may trigger neuroinflammation and demyelination. We evaluated whether particular single-nucleotide polymorphisms (SNPs), thought to be involved in fibrinogen-mediated hemostatic pathways, are overrepresented in patients with MS compared with controls. Methods: The case–control study consisted of 119 MS patients recruited consecutively at our clinic, and 68 healthy controls. Afterwards, we created a cumulative genetic risk score (CGRS) which included the 5 selected hemostatic risk alleles (Beta-Fibrinogen 455G/A, Glycoprotein IIIa P1A2, Factor V Leiden, Factor V H2R, and Prothrombin 20210G/A). Multivariate ordinal logistic regression and multivariate multinomial logistic regression were applied to evaluate the effect of CGRS on MS susceptibility. Results: The FGB 455 G/A and Factor V H1299R variants might be associated with MS status, in the recessive and dominant model, respectively. A cumulative association of the five SNPs investigated with the disease was observed. Discussion: We found that MS patients carried more pro-hemostatic variants than healthy controls. An increasing number of unfavorable alleles might increase the likelihood of being in the MS group, in the cumulative analysis. Our findings encourage to evaluating these variants in a larger population-based cohort. [ABSTRACT FROM AUTHOR]

Background: Cerebral microbleeds (CMBs) are small round/oval lesions seen in MRI-specific sequences. They are divided in deep and lobar according to their location. Lobar CMBs (L-CMBs) are commonly associated with amyloid angiopathy. Although CMBs have been considered clinically silent for a long time, a growing body of evidence has shown that they could play a crucial role in cognitive functioning.Objective: The aim of this systematic review was to estimate the role of L-CMBs in cognitive performance.Methods: We selected, from the Cochrane Library, Embase, PubMed, and ScienceDirect databases, clinical studies, published from January 2000 to January 2020 and focused on the association between L-CMBs and cognitive functions. The inclusion criteria were: 1) participants grouped according to presence or absence of CMBs, 2) extensive neuropsychological examination, 3) CMBs differentiation according to topographical distribution, and 4) MRI-based CMB definition (< 10 mm and low signal in T2*/SWI). The impact of L-CMBs was separately assessed for executive functions, visuospatial skills, language, and memory.Results: Among 963 potentially eligible studies, six fulfilled the inclusion criteria. Four studies reported a greater reduction in executive performances in participants with L-CMB and two studies showed a statistically significant association between visuospatial dysfunction and L-CMBs. No association was found between hippocampal memory or language abilities and L-CMBs.Conclusion: Lobar CMBs are associated with a reduction of processing speed and visuospatial performances, thus suggesting the contribution of vascular amyloid deposition to this cognitive profile. This occurrence enables us to suspect an underlying Alzheimer's disease pathology even in absence of typical hippocampal memory impairment. [ABSTRACT FROM AUTHOR]