Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

Objective This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID‐19) in people with multiple sclerosis (PwMS). Methods We retrospectively collected data of PwMS with suspected or confirmed COVID‐19. All the patients had complete follow‐up to death or recovery. Severe COVID‐19 was defined by a 3‐level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID‐19 by multivariate and propensity score (PS)‐weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID‐19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty‐eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti‐CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID‐19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS‐weighted analysis and by all the sensitivity analyses. Interpretation This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID‐19 pandemic persists. ANN NEUROL 2021;89:780–789

In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.

In childhood and juvenile cases, multiple sclerosis (MS) is associated with cognitive impairment and low IQ scores, the latter related to younger age at onset. These aspects are of critical importance in helping children and adolescents with MS to manage their difficulties and psychosocial challenges.

Lateral premotor cortex (PM) in the macaque monkey can be segregated into structurally and functionally distinct subregions, including a major division between dorsal (PMd) and ventral (PMv) parts, which have distinct cytoarchitecture, function, and patterns of connectivity with both frontal and parietal cortical areas. The borders of their subregions are less well defined in the human brain. Here we use diffusion tractography to identify a reproducible border between dorsal and ventral subregions of human precentral gyrus. We derive connectivity fingerprints for the two subregions and demonstrate that each has a distinctive pattern of connectivity with frontal cortex and lateral parietal cortex, suggesting that these areas correspond to human PMd and PMv. Although putative human PMd has a high probability of connection with the superior parietal lobule, dorsal prefrontal cortex, and cingulate cortex, human PMv has a higher probability of connection with the anterior inferior parietal lobule and ventral prefrontal cortex. Finally, we assess the correspondence between our PMd/PMv border and local sulcal and functional anatomy. The location of the border falls at the level of the gyral branch that divides the inferior precentral sulcus from the superior precentral sulcus and corresponded closely to the location of a functional border defined using previous functional magnetic resonance imaging studies.

Our findings confirm the importance of systematic assessment of cognitive and psychosocial issues in children and teens with MS. The progressive nature of the cognitive difficulties emphasizes the need for developing effective treatment strategies.

The cerebral blood flow, oxygen extraction and oxygen utilization has been measured regionally in 22 dements, and 14 aged normal volunteers. Ten demented patients were studied twice at a six-month interval from initial measurements. The use of a steady-state 15O technique and positron tomography for measuring regional cerebral blood flow, regional oxygen extraction fraction and mean cerebral oxygen utilization is discussed. The limitations of measurements are reviewed in the light of the present results and the current state of technological development in positron emission tomography is discussed. A decline in cerebral blood flow and mean cerebral oxygen utilization was correlated with increasing severity of dementia in both degenerative and vascular dements. The decline was coupled, both for the cerebral hemisphere as a whole and regionally. There was no increase in oxygen extraction ratio globally, and therefore no evidence to support the existence of a chronic ischaemic brain syndrome. Focal abnormalities in oxygen utilization were observed for both vascular and degenerative groups. In the vascular group, parietal defects were the most pronounced. Individual derangements of the regional pattern varied, reflecting the different unique patterns of ischaemic damage in these patients. In the degenerative group, parietal and temporal defects were seen in the less severe group, but a profound depression in the frontal regions with relative sparing of occipital area characterized the severe degenerative dements.