Search

The impact of distinct disease‐modifying therapies (DMTs) on severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccination efficacy in patients with multiple sclerosis (MS) is still enigmatic. In this prospective comparative study, we investigated humoral and cellular immune‐responses in patients with MS receiving interferon beta, natalizumab, and ocrelizumab pre‐vaccination and 6 weeks post second SARS‐CoV‐2 vaccination. Healthy individuals and interferon beta‐treated patients generated robust humoral and cellular immune‐responses. Although humoral immune responses were diminished in ocrelizumab‐treated patients, cellular immune‐responses were reduced in natalizumab‐treated patients. Thus, both humoral and cellular immune responses should be closely monitored in patients on DMTs. Whereas patients with a poor cellular immune‐response may benefit from additional vaccination cycles, patients with a diminished humoral immune‐response may benefit from a treatment with SARS‐CoV‐2 antibodies in case of an infection. [ABSTRACT FROM AUTHOR]

Objective: Direct pathogenic effects of autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in autoimmune limbic encephalitis (LE) have been questioned due to its intracellular localization. We therefore hypothesized a pathogenic role for T cells. Methods: We assessed magnet resonance imaging, neuropsychological and peripheral blood, and CSF flow cytometry data of 10 patients with long‐standing GAD65‐LE compared to controls in a cross‐sectional manner. These data were related to each other within the GAD65‐LE group and linked to neuropathological findings in selective hippocampectomy specimen from another two patients. In addition, full‐resolution human leukocyte antigen (HLA) genotyping of all patients was performed. Results: Compared to controls, no alteration in hippocampal volume but impaired memory function and elevated fractions of activated HLADR+ CD4+ and CD8+ T cells in peripheral blood and cerebrospinal fluid were found. Intrathecal fractions of CD8+ T cells negatively correlated with hippocampal volume and memory function, whereas the opposite was true for CD4+ T cells. Consistently, antigen‐experienced CD8+ T cells expressed increased levels of the cytotoxic effector molecule perforin in peripheral blood, and perforin‐expressing CD8+ T cells were found attached mainly to small interneurons but also to large principal neurons together with wide‐spread hippocampal neurodegeneration. 6/10 LE patients harbored the HLA‐A*02:01 allele known to present the immunodominant GAD65114–123 peptide in humans. Interpretation: Our data suggest a pathogenic effect of CD8+ T cells and a regulatory effect of CD4+ T cells in patients with long‐standing GAD65‐LE. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to characterize patients with ischemic stroke due to bacterial meningitis. Methods: In a single‐center retrospective study, we analyzed 102 patients with bacterial meningitis of which 19 had an ischemic stroke. Clinical characteristics, cerebrospinal fluid (CSF) analyses, and spatiotemporal distribution of infarcts were assessed. In addition, we searched PubMed from database inception to August 2021 for observational studies on ischemic stroke in patients with bacterial meningitis, and performed a meta‐analysis to investigate the frequency and timing of stroke as well as its effect on mortality. Results: In our cohort, 15 (78.9%) patients with stroke had an modified Rankin scale (mRS) ≥ 3 at discharge compared to 33 (39.8%) in patients without stroke (p < 0.01). Of 1,692 patients with bacterial meningitis from 15 cohort studies included in our meta‐analysis, cerebral infarcts were found in 332 (16%, 95% confidence interval [CI] = 0.13–0.20) patients. The occurrence of stroke was strongly associated with a higher mortality (odds ratio [OR] = 2.38, 95% CI = 1.70–3.34, p < 0.0001). There was no association of any specific causative pathogen with the occurrence of stroke. Infarcts were mainly distributed in territories of arteries located in the vicinity to the infection focus and peaked at 3 to –7 days and at 2 weeks after onset of meningitis. In patients with ischemic stroke, vasculopathy was found in 63.2% and additional intracerebral hemorrhage in 15.8%. Interpretation: This study found that ischemic stroke due to bacterial meningitis is caused by cerebral vasculopathy located in the vicinity of the infection focus, and that the time course of infarctions might enable a therapeutic intervention. ANN NEUROL 2023;93:1094–1105 [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement.Methods: In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n = 17), and with intracranial atherosclerosis (n = 25) served as controls.Results: Erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with and in 16 patients (100%) without intracranial involvement (p = 0.02). Headache was complained by 15 patients (50.0%) with and 13 patients (76.5%) without intracranial involvement (p = 0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, in contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at follow-up in these patients was 4 (interquartile range [IQR] = 2.0-6.0) and 4 patients (36.4%) died. Vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course.Interpretation: Typical characteristics of GCA, headache, and an elevated ESR, are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets. ANN NEUROL 2021;90:118-129. [ABSTRACT FROM AUTHOR]