Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Studies in animal models of MS have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T cells is necessary for development of autoimmune CNS inflammation. This suggests that GM-CSF may have a pathogenic role in MS as well, and a clinical trial testing its blockade is ongoing. However, there have been few reports on GM-CSF production by T cells in MS. The objective of this study was to characterize GM-CSF production by T cells of MS patients, and to determine the effect of interferon-beta (IFN-β) therapy on its production. GM-CSF production by peripheral blood (PB) T cells and the effects of IFN-β were characterized in samples of untreated and IFN-β-treated MS patients vs. healthy subjects. GM-CSF production by T cells in MS brain lesions was analyzed by immunofluorescence. Untreated MS patients had significantly greater numbers of GM-CSF+ CD4+ and CD8+ T cells in PB compared to healthy controls and IFN-β-treated MS patients. IFN-β significantly suppressed GM-CSF production by T cells in vitro. A number of CD4+ and CD8+ T cells in MS brain lesions expressed GM-CSF. Elevated GM-CSF production by PB T cells in MS is indicative of aberrant hyperactivation of the immune system. Given its essential role in animal models, abundant GM-CSF production at the sites of CNS inflammation suggests that GM-CSF contributes to MS pathogenesis. Our findings also reveal a potential mechanism of IFN-β therapy, namely suppression of GM-CSF production.

Background: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services. Objectives: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic’s impact on healthcare delivery. Methods: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d’Hebron-Centre d’Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care. Results: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. Conclusion: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.

Passive lung insufflation can distend the lungs of patients with NMD significantly greater than air stacking, particularly when glottic and bulbar-innervated muscle dysfunction is severe. LIC, MIC, and VC measurements permit quantifiable assessment of glottic integrity and, therefore, bulbar-innervated muscle function for patients with NMD. The patients who benefit the most from insufflation therapy are those who have the lowest VC.

Objective Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. Methods We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. Results Grossly apparent thalamic discolorations in cm‐thick brain slices were T2/fluid‐attenuated inversion recovery (FLAIR) hyperintense, T1‐hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman’s rho = −0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). Interpretation Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81–92