Explore the vast range of titles available.

Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.

The use of high-efficacy disease-modifying therapies (DMTs) early in the course of multiple sclerosis (MS) has been shown to improve clinical outcomes and is becoming an increasingly popular treatment strategy. As a result, monoclonal antibodies, including natalizumab, alemtuzumab, ocrelizumab, ofatumumab, and ublituximab, are frequently used for the treatment of MS in women of childbearing age. To date, only limited evidence is available on the use of these DMTs in pregnancy. We aim to provide an updated overview of the mechanisms of action, risks of exposure and treatment withdrawal, and pre-conception counseling and management during pregnancy and post-partum of monoclonal antibodies in women with MS. Discussing treatment options and family planning with women of childbearing age is essential before commencing a DMT in order to make the most suitable choice for each individual patient.

Clinical syndromes associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) are now recognized as a distinct neurological disease entity, and are gaining increasing attention. The pathogenic mechanisms underlying MOG-antibody disease (MOGAD) remain incompletely understood. Case series, facilitated by registries, and observational studies over the past few years have shed increasing light on the clinical aspects and therapeutic approaches of MOGAD. MOGAD may manifest with a variety of clinical syndromes, including acute disseminated encephalomyelitis (ADEM), autoimmune encephalitis, optic neuritis (ON) and transverse myelitis (TM). MOGAD can be either monophasic or relapsing. This review aims to provide a comprehensive updated description of the clinical spectrum, paraclinical features, and prognosis of MOG-antibody disease, as well as summarize its therapeutic considerations. Randomized clinical trials, standardized diagnostic criteria and treatment guidelines are the steps forward.

Background: Galcanezumab, along with three other monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, represents the latest disease-specific and mechanism-based treatment for the prophylaxis of migraine. Galcanezumab shares data also for the prophylaxis of cluster headache. Objective: To provide a pooled safety and efficacy analysis of all phase III randomized controlled trials of galcanezumab in the preventive therapy of migraine. Methods: A computer-based literature search was conducted on MEDLINE and the US National Institutes of Health Clinical Trials Registry for phase III randomized controlled trials of galcanezumab in migraine prevention. The primary outcome was the mean change in monthly migraine days (MMDs). The proportions of patients who reported at least one adverse event (AE), at least one serious adverse event (SAE) or withdrew from the study were used as safety outcomes. Results: Two trials were included in the efficacy meta-analysis and three in the safety meta-analysis. Migraine preventive treatment with subcutaneous galcanezumab, at both 120 mg and 240 mg dosages, was associated with a significantly greater reduction in the mean number of MMDs versus placebo (120 mg, MD = –1.98, 95% CI = –2.33 to –1.63; p < 0.0001) or (240 mg, MD = –1.86, 95% CI = –2.20 to –1.53; p < 0.0001). Galcanezumab was found to be more efficacious in all key secondary outcomes as well. Regarding safety, most of the adverse events were mild to moderate, while drop-out rates and serious adverse events were low. Conclusions: Galcanezumab is an efficacious and well-tolerated preventive treatment for migraine. Larger clinical trials with longer follow-up periods need to be conducted in order to provide more safety data of the above-mentioned drug.

Chronic pain is an underestimated and undertreated yet highly prevalent symptom in people with multiple sclerosis (pwMS), significantly impairing quality of life and functional outcomes. Its prevalence ranges from 23% to 90% across studies, reflecting methodological differences and discrepancies in the definition and recognition of chronic pain. In this article, we aim to provide an updated review of the pathophysiological mechanisms of chronic pain in MS, including the effect and interaction between neuropathic, nociceptive and nociplastic mechanisms, and propose a mechanism-based classification. Furthermore, we explore different therapeutic approaches, including both pharmacological and non-pharmacological interventions, tailored to each patient according to the mechanism involved. A deeper understanding of the distinct chronic pain mechanisms and phenotypes can provide more effective and personalized treatment strategies and lead to improved patient outcomes and quality of life.

ObjectiveOur study aimed to estimate the incidence of neoplasms in clinical trials of DMTs for MS and to test the hypothesis that DMTs increase the risk of neoplasms in the duration of MS randomized controlled trials (RCTs).MethodsData were extracted from 42 RCTs of DMTs published between 1991 and 2020. The incidence rate (IR) of neoplasms was estimated by pooling the neoplasms in the active and placebo-treatment arm per patient-year. The neoplasm incidence rate ratio (IRR) of active over placebo-treatment arms was used as measure of the effect of DMTs on the risk of developing neoplasms.ResultsThe meta-analysis included 10,638 placebo and 16,360 active-treatment arm patients. A non-significant pooled neoplasm incidence rate ratio (IRR: 1.0797; 95% CI: 0.8281 to 1.4077; P = 0.5711) with no heterogeneity (I2 = 0%) was observed in active over placebo-treatment groups from 1991 to 2020. We found a significant association between the incidence of neoplasms and the year of publication in both active and placebo arms of RCTs. Trials of sequestrating and depletive DMTs were associated with significantly higher incidence of neoplasms in both active and placebo-treated arms compared to immunomodulatory treatment trials.ConclusionsOur study indicates that treatment with DMTs has not modified the risk of neoplasms in MS clinical trials from 1991 to 2020, which may reflect a low carcinogenic potential of DMTs and/or that the neoplasia latencies far exceed the typical MS trial observation periods.

Background/Objectives: Over the past few decades, there has been increased scientific interest in the prevalence of headache disorders among people with MS (pwMS). Although the latest data suggest an association between migraine and multiple sclerosis, studies have been providing inconsistent results largely due to methodological differences, including small sample sizes, lack of control groups, absence of structured headache diaries, and variability in diagnostic criteria. This study aims to address the question of whether pwMS have a higher prevalence of primary headache disorders than healthy controls (HCs) and whether MS is associated with an increased risk of headaches. Methods: In this cross-sectional, case–control study, consecutive pwMS from Eginition University Hospital, Athens, Greece, along with matched HCs, were recruited. Both groups were assessed for headache disorders, over the past 3 months from the day of recruitment, using a semi-structured questionnaire and diagnosed according to the International Classification for Headache Disorders 3 (ICHD-3) criteria. A multivariable logistic regression model adjusted for age and sex evaluated the association between MS and headache disorders. Results: Ninety-six pwMS and ninety-six matched HCs met the inclusion criteria and were enrolled in the study. A higher prevalence of primary headache disorders in pwMS (71.9%) compared to HCs (43.8%) was observed. Specifically, 28.1% of pwMS had migraine, and 38.5% had tension-type headache (TTH). PwMS were significantly more likely to be diagnosed with any primary headache disorder (OR = 4.54; 95% CI: 2.28 to 9.04; p = 1.7), migraine (OR = 2.21 95% CI: 1.05 to 4.62; p < 0.05), and TTH (OR = 2.16 95% CI: 1.16 to 4; p < 0.05) compared to HCs. Conclusions: Our study suggests that primary headache disorders are more prevalent in pwMS in a cohort recruited from the MS outpatient clinic at Eginition University Hospital in Athens, Greece, compared to the general population and highlights the need for targeted headache management within this group. Prospective longitudinal studies are needed to draw more robust conclusions on a potential association and its underlying mechanisms.

Galcanezumab is a humanized monoclonal antibody blocking the calcitonin gene-related peptide (CGRP) pathway by targeting the CGRP. Data from four phase-3 randomized placebo-controlled clinical trials showed that galcanezumab is superior to placebo in reducing migraine headaches, migraine-specific quality of life, and headache-related disability. Most of the adverse events (AEs) were mild to moderate and did not affect trial completion rates significantly. Along with erenumab, fremanezumab, and eptinezumab, galcanezumab forms a novel class of anti-migraine preventative treatments that is disease-specific and mechanism-based, unlike the standard ones. In addition, galcanezumab has also been shown to be effective in cluster headache, though more clinical trials are required. Overall, galcanezumab is a promising emerging treatment in migraine prophylaxis. However, it needs to be tested in larger clinical trials focused on treatment-resistant migraine. Furthermore, its safety profile, especially its potential association with an increased cardiovascular risk, needs to be established through long-term, real-world data. This review aims to give an overview of its pharmacological properties as well as to report and discuss data from clinical trials and its potential place in headache therapeutics.

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, which was first identified in 2016, is an immune-mediated inflammatory disorder of the nervous system characterized by antibodies targeting GFAP. The exact pathogenic mechanisms, as well as the role of anti-GFAP antibodies, remain unclear; however, it seems that neuroinflammation is mediated by specific CD8+ T-cells and that neoplasms or viral infections can act as the initial trigger. Although the clinical spectrum of the disease is broad and heterogenous, GFAP astrocytopathy most commonly presents as meningoencephalitis with or without myelitis. Other symptoms include headache, visual disturbances, extrapyramidal or brainstem syndromes, and psychiatric manifestations including psychosis. The disease has a characteristically favorable response to steroid treatment while relapses occur in approximately 20–30% of the patients. Methods: We present two cases of GFAP astrocytopathy admitted to our hospital: a 43-year-old male with persistent headache and a 59-year-old female with acute dysarthria and swallowing difficulties followed by cognitive and behavioral symptoms. Results: Additionally, we conduct a comprehensive review of the literature to elucidate the role of anti-GFAP antibodies in disease pathogenesis and examine imaging characteristics, clinical manifestations, and treatment options for this recently described neuroimmunological condition. Conclusions: This review presents two unusual cases of GFAP-astrocytopathy and provides evidence for the pathogenesis, clinical presentation, imaging characteristics and treatment options of the disease.

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.