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Background and Purpose: The COVID‐19 pandemic has significantly impacted health systems worldwide. Here, we assessed the pandemic's impact on clinical service, curricular training, and financial burden from a neurological viewpoint during the enforced lockdown periods and the assumed recovery by 2023. Methods: An online 18‐item survey was conducted by the European Academy of Neurology (EAN) NeuroCOVID‐19 Task Force among the EAN community. The survey was online between February and March 2023. Questions related to general, demographic, clinical, work, education, and economic aspects. Results: We collected 430 responses from 79 countries. Most health care professionals were aged 35–44 years, with >15 years of work experience. The key findings of their observations were as follows. (i) Clinical services were cut back in all neurological subspecialties during the most restrictive COVID‐19 lockdown period. The most affected neurological subspecialties were services for patients with dementia, and neuromuscular and movement disorders. The levels of reduction and the pace of recovery were distinct for acute emergencies and in‐ and outpatient care. Recovery was slow for sleep medicine, autonomic nervous system disorders, neurorehabilitation, and dementia care. (ii) Student and residency rotations and grand rounds were reorganized, and congresses were converted into a virtual format. Conferences are partly maintained in a hybrid format. (iii) Affordability of neurological care and medication shortage are emerging issues. Conclusions: Recovery of neurological services up to spring 2023 has been incomplete following substantial disruption of neurological care, medical education, and health economics in the wake of the COVID‐19 pandemic. The continued limitations for the delivery of neurological care threaten brain health and call for action on a global scale. [ABSTRACT FROM AUTHOR]

Background and purpose: Health risks associated with SARS‐CoV‐2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID‐19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID‐19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID‐19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID‐19 course. Methods: In this position paper, the NeuroCOVID‐19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID‐19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. Results: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS‐CoV‐2 vaccination. The prevailing concerns included the chance of worsening the pre‐existing neurological condition, vaccination‐related adverse events, and drug interaction. Conclusions: The EAN NeuroCOVID‐19 Task Force reinforces the key role of neurologists as advocates of COVID‐19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID‐19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals. [ABSTRACT FROM AUTHOR]

Background and purpose: Multiple sclerosis (MS) susceptibility is influenced by genetics; however, little is known about genetic determinants of disease expression. We aimed at assessing genetic factors influencing quantitative neuroimaging measures in two cohorts of progressive MS (PMS) and relapsing–remitting MS (RRMS) patients. Methods: Ninety‐nine PMS and 214 RRMS patients underwent a 3‐T brain magnetic resonance imaging (MRI) scan, with the measurement of five MRI metrics including T2 lesion volumes and measures of white matter, grey matter, deep grey matter, and hippocampal volumes. A candidate pathway strategy was adopted; gene set analysis was carried out to estimate cumulative contribution of genes to MRI phenotypes, adjusting for relevant confounders, followed by single nucleotide polymorphism (SNP) regression analysis. Results: Seventeen Kyoto Encyclopedia of Genes and Genomes pathways and 42 Gene Ontology (GO) terms were tested. We additionally included in the analysis genes with enriched expression in brain cells. Gene set analysis revealed a differential pattern of association across the two cohorts, with processes related to sodium homeostasis being associated with grey matter volume in PMS (p = 0.002), whereas inflammatory‐related GO terms such as adaptive immune response and regulation of inflammatory response appeared to be associated with T2 lesion volume in RRMS (p = 0.004 and p = 0.008, respectively). As for SNPs, the rs7104613T mapping to SPON1 gene was associated with reduced deep grey matter volume (β = −0.731, p = 3.2*10−7) in PMS, whereas we found evidence of association between white matter volume and rs740948A mapping to SEMA3A gene (β = 22.04, p = 5.5*10−6) in RRMS. Conclusions: Our data suggest a different pattern of associations between MRI metrics and functional processes across MS disease courses, suggesting different phenomena implicated in MS. [ABSTRACT FROM AUTHOR]

Objective: Primary progressive multiple sclerosis (PPMS) causes accumulation of neurological disability from disease onset without clinical attacks typical of relapsing multiple sclerosis (RMS). However, whether genetic variation influences the disease course remains unclear. We aimed to determine whether mutations causative of neurological disorders that share features with multiple sclerosis (MS) contribute to risk for developing PPMS.Methods: We examined whole-genome sequencing (WGS) data from 38 PPMS and 81 healthy subjects of European ancestry. We selected pathogenic variants exclusively found in PPMS patients that cause monogenic neurological disorders and performed two rounds of replication genotyping in 746 PPMS, 3,049 RMS, and 1,000 healthy subjects. To refine our findings, we examined the burden of rare, potentially pathogenic mutations in 41 genes that cause hereditary spastic paraplegias (HSPs) in PPMS (n = 314), secondary progressive multiple sclerosis (SPMS; n = 587), RMS (n = 2,248), and healthy subjects (n = 987) genotyped using the MS replication chip.Results: WGS and replication studies identified three pathogenic variants in PPMS patients that cause neurological disorders sharing features with MS: KIF5A p.Ala361Val in spastic paraplegia 10; MLC1 p.Pro92Ser in megalencephalic leukodystrophy with subcortical cysts, and REEP1 c.606 + 43G>T in Spastic Paraplegia 31. Moreover, we detected a significant enrichment of HSP-related mutations in PPMS patients compared to controls (risk ratio [RR] = 1.95; 95% confidence interval [CI], 1.27-2.98; p = 0.002), as well as in SPMS patients compared to controls (RR = 1.57; 95% CI, 1.18-2.10; p = 0.002). Importantly, this enrichment was not detected in RMS.Interpretation: This study provides evidence to support the hypothesis that rare Mendelian genetic variants contribute to the risk for developing progressive forms of MS. Ann Neurol 2018;83:51-63. [ABSTRACT FROM AUTHOR]

Background and purpose The Rio score ( RS) and the modified Rio score ( MRS) are two scoring systems that can identify the early predictive factors of disability progression in relapsing−remitting multiple sclerosis ( RRMS) patients treated with interferon-β ( IFN-β). The objective of the study was to validate the usefulness of the RS and MRS in a large cohort of multiple sclerosis patients treated with IFN-β in daily clinical practice. Methods The analysis included a cohort of RRMS patients treated with different formulations of IFN-β for at least 1 year. The RS and MRS were used to classify the patients after 1 year of treatment. Multivariate analysis was performed to identify predictive variables of suboptimal response at 5 years, defined as Expanded Disability Status Scale confirmed progression or switching to a second-line therapy. Results Sixty-nine of 416 included patients were considered as suboptimal responders at 5-year evaluation. The possible score range was 0-3. A higher risk of suboptimal response was found for RS and MRS in the presence of ≥2 scores (hazard ratio 3.0, P = 0.002, and hazard ratio 5.0, P < 0.0001, respectively). Conclusions Our study confirmed, in a daily clinical setting, that MRS had a better specificity and accuracy than RS in identifying the patients who will have a poor response to long-term IFN-β treatment. [ABSTRACT FROM AUTHOR]

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess 'mirror' properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech. Hum Brain Mapp 36:1010-1027, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusion In October 2020, the European Academy of Neurology (EAN) consensus statement for management of patients with neurological diseases during the coronavirus disease 2019 (COVID‐19) pandemic was published. Due to important changes and developments that have happened since then, the need has arisen to critically reassess the original recommendations and address new challenges.In step 1, the original items were critically reviewed by the EAN COVID‐19 Task Force. In addition, new recommendations were defined. In step 2, an online survey with the recommendations forged in step 1 was sent to the Managing Groups of all Scientific and Coordinating Panels of EAN. In step 3, the final set of recommendations was made.In step 1, out of the original 36 recommendations, 18 were judged still relevant. They were edited to reflect the advances in knowledge and practice. In addition, 21 new recommendations were formulated to address the new knowledge and challenges. In step 2, out of the 39 recommendations sent for the survey, nine were approved as they were, whilst suggestions for improvement were given for the rest. In step 3, the recommendations were further edited, and some new items were formed to accommodate the participants' suggestions, resulting in a final set of 41 recommendations.This revision of the 2020 EAN Statement provides updated comprehensive and structured guidance on good clinical practice in people with neurological disease faced with SARS‐CoV‐2 infection. It now covers the issues from the more recent domains of COVID‐19‐related care, vaccine complications and post‐COVID‐19 conditions. [ABSTRACT FROM AUTHOR]

Background Method Results Conclusions The COVID‐19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID‐19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID‐19‐related neurological issues.Activities carried out during and after the pandemic by the EAN NeuroCOVID‐19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics.During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro‐covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID‐19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated “COVID‐19 Breaking News” section in EANpages.The EAN NeuroCOVID‐19 Task Force was immediately engaged in various activities to participate in the fight against COVID‐19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Cannabinoid receptor and N-acyl phosphatidylethanolamine phospholipase D-Evidence for altered expression in multiple sclerosis," by D.A. Hilton and colleagues in the 2011 issue.

Objective: Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course., Materials and Methods: This single-centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first-line disease-modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001-December 2005, and January 2006-September 2011., Results: A total of 1068 relapsing-remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P < 0.0001), started more frequent treatment with high-dose interferon beta or glatiramer acetate (P < 0.0001), and had experienced a more frequent treatment escalation strategy (P = 0.004) than patients in other cohorts. The multivariate analysis adjusted for baseline characteristics showed that pwMS of the last cohort had a high probability of showing no evidence of disease activity (NEDA3) at 4 years (OR 3.22, 95% CIs 1.89-5.47; P < 0.0001). These results were confirmed in a propensity score analysis., Conclusions: Our study showed an improvement over the last 15 years in the treatment response; this observation can be associated to a paradigm shift in MS treatment strategies., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)