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Background and aimMonoclonal antibodies acting on the calcitonin gene-related peptide or on its receptor are new drugs to prevent migraine. Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene-related peptide (eptinezumab, fremanezumab, and galcanezumab). The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based guideline on the use of the monoclonal antibodies acting on the calcitonin gene-related peptide for migraine prevention.MethodsThe guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic review and analysis of the literature, assessed the quality of available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.ResultsWe found low to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in patients with episodic migraine and medium to high quality of evidence to recommend erenumab, fremanezumab, and galcanezumab in patients with chronic migraine. For several clinical questions, there was not enough evidence to provide recommendations using the GRADE approach and recommendations relied on experts’ opinion.ConclusionMonoclonal antibodies acting on the calcitonin gene-related peptide are new drugs which can be recommended for migraine prevention. Real life data will be useful to improve the use of those drugs in clinical practice.

BackgroundA previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments.MethodsThe guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.ResultsWe found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts’ opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives.ConclusionMonoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.

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.

BackgroundMultiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can share similar features, posing diagnostic challenges. In this study, we identified sets of conventional MRI lesion distribution criteria proposed for disease differentiation and investigated their clinical utility.MethodsWe searched five electronic databases for English-written and peer-reviewed diagnostic accuracy studies that included brain MRI at least. Hierarchical and univariate random-effects logistic regression models were employed for diagnostic accuracy meta-analysis. Heterogeneity was explored with subgroup analyses. Certainty of evidence was assessed using the GRADEpro tool.ResultsThree sets of criteria (‘Matthews’, ‘Cacciaguerra’, ‘MS lesion checklist’) were investigated in 11 studies (2008 patients; MS, n=1037; NMOSD, n=842; MOGAD, n=129), with low applicability concerns. Overall pooled sensitivity and specificity of the Matthews brain MRI criteria (MS vs seropositive-NMOSD differentiation) were 0.92 (0.86 to 0.96) and 0.85 (0.79 to 0.90), respectively, with higher diagnostic values in non-Caucasian populations and during follow-up. Pooled sensitivity and specificity of the Cacciaguerra brain-spinal cord criteria (seropositive-NMOSD vs MS differentiation) were 0.96 (0.76 to 0.99) and 0.83 (0.71 to 0.90), respectively. The MS lesion checklist (MS vs NMOSD/MOGAD differentiation) had lower diagnostic accuracy measures (sensitivity, specificity: 0.74, 0.79, respectively). The Matthews criteria provided the strongest moderate certainty evidence and also showed high pooled diagnostic accuracy for MS versus seronegative-NMOSD (sensitivity: 0.93 (0.84 to 0.97)); specificity: 0.90 (0.80 to 0.95)) and for MS versus MOGAD differentiation (sensitivity: 0.86 (0.81 to 0.90); specificity: 0.87 (0.76 to 0.93)).ConclusionsLesion distribution criteria can accurately discriminate between MS, NMOSD and MOGAD. Further optimised validation studies, and revisions or extensions may support sustained implementation.PROSPERO registration numberCRD42023472178.

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives. As migraine prevalence is high in women of reproductive age, it is common to face the issue of migraine and hormonal contraceptive use in clinical practice. In this document, we systematically reviewed data about the association between migraine, ischemic stroke and hormonal contraceptive use. Thereafter a consensus procedure among international experts was done to develop statements to support clinical decision making, in terms of cardiovascular safety, for prescription of hormonal contraceptives to women with migraine. Overall, quality of current evidence regarding the risk of ischemic stroke in migraineurs associated with the use of hormonal contraceptives is low. Available data suggest that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura. Thus, our current statements privilege safety and provide several suggestions to try to avoid possible risks. As the quality of available data is poor further research is needed on this topic to increase safe use of hormonal contraceptives in women with migraine.

Background The likelihood to help or harm (LHH) is an absolute measure of the benefit versus risk profile of a medication, which can be used to assess the potential for benefit versus harm of different disease-modifying treatments (DMTs) for relapsing multiple sclerosis (R-MS) and facilitate clinical decision-making. Objective The objective of this study was to assess absolute differences in benefit:risk ratios of oral DMTs for R-MS, using LHH analysis with no evidence of disease activity (NEDA) as beneficial outcome. Design/Methods The number needed to treat for a paient to achieve NEDA (NNTB NEDA ) was used as an effect size metric of efficacy and the number needed to treat for a patient  to experience  an adverse event (NNTH AE ), a serious adverse event (NNTH SAE ), or treatment discontinuation due to an adverse event (NNTH AE-D ) were used as measures of risk. The LHH—which is the ratio of NNTH:NNTB—values were calculated from published phase III trial data for oral DMTs. Results The values for likelihood to achieve NEDA than experience any AE ratio (LHH (AE/NEDA) ) were 3.9, 6.8, 12.5 and 3.7, the likelihood to achieve NEDA than experience a SAE ratio (LHH (SAE/NEDA) ) values were 3.5, 15, 23.5 and 2.8, and the likelihood to achieve NEDA versus discontinue treatment (LHH (AE-D/NEDA) ) values were 20.3, 4.3, 3.9 and 3.1 for cladribine, dimethyl-fumarate, fingolimod, and teriflunomide, respectively. Conclusions With all of the oral DMTs examined, R-MS patients are more likely to achieve NEDA than experience any adverse event.

Multiple sclerosis (MS) is a neuro-inflammatory disease characterized by demyelination in the central nervous system (CNS). Although a substantial endogenous capacity for remyelination has been demonstrated, this process is frequently incomplete and exhibits marked intra- and inter-individual heterogeneity. Several factors influence the extent of spontaneous myelin regeneration, including age, sex, disease course, and lesion localization. Oligodendrocytes (OL), derived from oligodendrocyte progenitor cells (OPCs), are the principal myelinating cells of the CNS. The regenerative cascade involves several key stages, including OPC activation, recruitment, differentiation into oligodendrocytes (OL), and myelin deposition. This process is orchestrated in a spatiotemporal manner by a complex interplay of intracellular signaling pathways, genetic determinants, and dynamic microenvironmental cues, which together balance inhibitory and pro-remyelinating influences. Several lines of evidence indicate that chronically demyelinated axons are vulnerable to degeneration, whereas successful remyelination may confer neuroprotection. These observations underscore remyelination as a promising neuroprotective therapeutic target for preventing or slowing disability progression in MS, a condition in which gradual neuroaxonal degeneration is believed to underlie irreversible disability progression. In this review, we aim to bridge the gap between fundamental biological mechanisms of remyelination and their clinical relevance. We examine recent advances in in vivo techniques for assessing remyelination and discuss how these measures correlate with clinical and disability outcomes. In addition, we review recent clinical trials of remyelination-promoting therapies and analyze the challenges that have limited their advancement beyond phase II. Overall, we seek to provide a comprehensive overview of the remyelination process from bench to bedside, highlighting both the obstacles and the therapeutic potential of remyelination strategies in MS.

Background Tension-type headache (TTH) is the most prevalent primary headache disorder, affecting individuals of all ages and imposing a substantial global burden. While traditionally considered a peripheral skeletomuscular condition, current evidence suggests a prominent role for central mechanisms and neurotransmitter dysregulation. In this context, growing evidence highlights the noradrenergic system as a key contributor, both for the TTH genesis and maintenance. Methods A systematic literature search was performed according to PRISMA guidelines. A comprehensive search of PubMed/MEDLINE and EMBASE via Scopus up to March 2024 identified studies examining the relationship between TTH and the noradrenergic system. Results Forty-three eligible studies were included and categorized according to their focus on pathophysiology or treatment. Biochemical studies consistently reported reduced noradrenergic activity, including reduced plasma norepinephrine/epinephrine levels and dopamine-β-hydroxylase activity in TTH patients, often correlating with headache severity and chronicity. Neurophysiological and autonomic investigations further supported noradrenergic involvement, revealing altered reflex suppression, impaired sympathetic habituation, and reduced central autonomic responsiveness in TTH. Pharmacological studies indicated that medication enhancing noradrenergic transmission achieved superior clinical efficacy compared to those acting on the serotonergic system only. Discussion Overall, the body of evidence underscores the noradrenergic system’s integral role in TTH. The dysregulated noradrenergic system appears to contribute to central sensitization and impaired pain inhibition. These findings, along with the consistent efficacy of noradrenergic-targeting treatments, support a shift towards a more mechanistically specific and personalized approaches. Future research is needed to clarify the specific noradrenergic pathways implicated in TTH, in order to refine treatment strategies and enhance efficacy through precision medicine.

Background and objectivesThere is no data regarding validity and reliability of the Greek version of Neurogenic Bladder Symptom Score (NBSS) questionnaire. In this study we investigated these parameters using a sample of Greek patients with multiple sclerosis (MS).Materials and methodsPatients with different types and severity of multiple sclerosis were recruited from a single center in Greece prospectively. All patients completed the MusiQoL and NBSS questionnaires at baseline and 20 days later, without receiving any new treatment. Construct validity, internal consistency and test–retest reliability were tested. Internal consistency was investigated using Cronbach’s alpha coefficient, while test–retest reliability using Intraclass Correlation Coefficient (ICC). Construct validity was assessed by comparing NBSS quality of life question 24 with MusiQoL questionnaire.ResultsA total of 91 patients were evaluated. The dimensions of NBSS exhibited high internal consistency, both for overall questionnaire score (Cronbach’s alpha coefficient of 0.91) and for every subdomain separately (Cronbach’s alpha coefficient of 0.95 for incontinence, 0.88 for storage symptoms and 0.74 for consequences). Test–retest reliability was satisfactory both for overall score [ICC of 0.85, (0.35–0.94), p < 0.001] and for every subdomain separately (ICC of 0.90 for incontinence, 0.83 for storage symptoms and 0.90 for consequences). Pearson’s correlation coefficient of question number 24 of the NBSS questionnaire regarding quality of life with the MusiQoL questionnaire revealed a moderate correlation [r = 0.64, (0.48–0.80), p < 0.0001].ConclusionsThe Greek version of NBSS appears to be a valid and reliable instrument for assessing neurogenic bladder symptoms in Greek population suffering from multiple sclerosis.