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BackgroundMP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS).MethodsMP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P1 receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro.ResultsFTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220+ B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs.ConclusionsThe data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0924-4) contains supplementary material, which is available to authorized users.

Objective: To analyse the characteristics of patients with neurological complaints seeking evaluation in an interdisciplinary emergency department (ED) during the rise of the COVID-19 pandemic in Germany. Methods: In this retrospective study, data on the number of ED presentations due to neurological complaints in weeks 1-15/2020 were collected. In addition, hospital chart data of patients referred for neurological evaluation during weeks 12-15/2020 when the pandemic began impacting on public life in Germany were analysed regarding demographic information, chief complaints, modes of presentation and disposition and ED discharge diagnosis. Both data sets were compared to respective periods from 2017. Results: During the surge of COVID-19, we found a significant decrease of the total number of neurological ED patients by 47.6%. Comparing weeks 12-15 of 2017 and 2020, we found a decrease in the number of patients of <30 years (p<0.001) and an increase of those � 70 years (p<0.001). A higher proportion of patients were admitted to escalated care (p=0.03), and fewer patients were discharged against medical advice (p<0.001). In addition, the ratio of less acute diagnoses (eg, benign headaches) declined significantly. Conclusion: Our findings suggest that the pandemic has contributed to a-potentially transient-reframing of laypeople's perception of urgency and necessity for emergency presentation. The establishment and promotion of health-care structures and services like telemedical consultations and the creation of safe ED environments will be essential to enable adequate delivery of care in potential future waves of the pandemic.