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Background: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain. Methods: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥ 3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥ 4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias. Results: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42–2.16]; P <0.001), the coarsened exact matching (n=332–524, using multiple imputations of missing values; OR, 1.60 [1.08–2.36]; P =0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20–2.15]; P =0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59–4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30–3.75]), dependency or death (OR, 1.42 [0.91–2.23]), or mortality (OR, 1.65 [0.94–2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76–5.04]), dependency or death (OR, 1.49 [1.07–2.07]), and mortality (OR, 1.65 [1.11–2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73–4.29]). Conclusions: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Background Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. Case presentation A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient’s symptoms resolved without any sequelae. Conclusion In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.

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Background and ObjectiveDepleting CD20+B cells is the primary mechanism by which ocrelizumab (OCRE) is efficient in persons with multiple sclerosis (pwMS). However, the exact role of OCRE on other immune cell subsets directly or indirectly remains elusive. The purpose of this study is to characterize the dynamics of peripheral immune cells of pwMS on OCRE.MethodsWe collected blood samples from 38 pwMS before OCRE onset (T0) and at 6 and 12 months (T6, T12) after initiation. To cover the immune cell diversity, using mass cytometry time of flight, we designed a 38-parameter panel to analyze B, T, and innate immune cell markers and CNS migratory markers. In parallel, viral-specific CD8+T-cell responses were assessed by the quantification of interferon-γ secretion using the enzyme-linked immunospot assay on cytomegalovirus, Epstein-Barr virus, and influenza stimulations.ResultsBeside B-cell depletion, we observed a loss in memory CD8+CD20+and central memory CD8+T cells but not in CD4+CD20+T cells already at T6 and T12 (p< 0.001). The loss of memory CD8+T cells correlated with a lower CXCR3 expression (p< 0.001) and CNS-related LFA-1 integrin expression (p< 0.001) as well as a reduced antiviral cellular immune response observed at both time points (p< 0.001). Of note, we did not observe major changes in the phenotype of the other cell types studied. Seven of 38 (18.4%) patients in our cohort presented with infections while on OCRE; 4 of which were switched from dimethyl fumarate. Finally, using a mixed linear model on mass cytometry data, we demonstrated that the immunomodulation induced by previous disease-modifying therapies (DMTs) was prolonged over the period of the study.DiscussionIn addition to its well-known role on B cells, our data suggest that OCRE also acts on CD8+T cells by depleting the memory compartment. These changes in CD8+T cells may be an asset in the action of OCRE on MS course but might also contribute to explain the increased occurrence of infections in these patients. Finally, although more data are needed to confirm this observation, it suggests that clinicians should pay a special attention to an increased infection risk in pwMS switched from other DMTs to OCRE.

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Alemtuzumab is highly effective in relapsing remitting multiple sclerosis (RRMS), but autoimmune adverse events are of concern. In contrast to rare cases of immune-mediated cutaneous vasculitis, systemic vasculitis after alemtuzumab has not yet been described. We report the case of a 29-year-old man with RRMS who developed fever, auricular chondritis, cutaneous vasculitis and life-threatening diffuse alveolar haemorrhage, 12 months after alemtuzumab. Antibodies to myeloperoxidase appeared 9 months after alemtuzumab and were extremely high at the time of vasculitis. Outcome was favourable after glucocorticoids, plasma exchanges and rituximab. Thus, alemtuzumab may induce life-threatening vasculitis in patients treated for RRMS.