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

Background: Neuropsychological deficits in patients with multiple sclerosis (MS) have been shown to be associated with the major pathological substrates of the disease, ie, inflammatory demyelination and neurodegeneration. Double inversion recovery sequences allow cortical lesions (CLs) to be detected in the brain of patients with MS. Modern postprocessing techniques allow cortical atrophy to be assessed reliably.Objective: To investigate the contribution of cortical gray matter lesions and tissue loss to cognitive impairment in patients with relapsing-remitting MS.

Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. Histological, immunological and neuroimaging studies have provided new insight in this rapidly expanding field, and form the basis of the most recent hypotheses on the pathogenesis of grey matter damage. DOI: https://doi.org/10.1038/nrn3900Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-111099 Accepted Version Originally published at: Calabrese, Massimiliano; Magliozzi, Roberta; Ciccarelli, Olga; Geurts, Jeroen J G; Reynolds, Richard; Martin, Roland (2015). Exploring the origins of grey matter damage in multiple sclerosis. Nature Reviews Neuroscience, 16 (3) AbstractMultiple sclerosis is characterised at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, in recent years it has become clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage has been suggested to have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unclear. This review will summarize and highlight important histological, immunological, and neuroimaging results from this rapidly expanding field and will address the most recent hypotheses on the pathogenesis of grey matter damage.

Background: A significant inflammatory pathologic disorder in the cortex of patients with multiple sclerosis (MS) has been demonstrated by ex vivo studies.

A common pattern of intrathecal (meninges and CSF) inflammatory profile strongly correlates with increased cortical pathology, both at the time of diagnosis and at death. These results suggest a role for detailed CSF analysis combined with MRI as a prognostic marker for more aggressive MS. Ann Neurol 2018 Ann Neurol 2018;83:739-755.