BackgroundMonoclonal antibodies targeting CD20-expressing B cells constitute effective therapies for people with multiple sclerosis (pwMS) and can be administered intravenously (i.v.) or subcutaneously (s.c.). However, little is known about the differences in immunomodulatory effects of distinct B-cell depletion therapies.MethodsWe performed detailed characterizations of the immune cell composition in blood samples of pwMS treated with either i.v. [ocrelizumab (Ocre); n = 25] or s.c. [ofatumumab (Ofa); n = 25 or Ocre n = 25] administered anti-CD20 therapy compared to healthy controls (HC, n = 20). In addition, blood samples from n = 25 pwMS who switched their anti-CD20 therapy from i.v. Ocre to s.c. Ofa injection were analyzed before therapy change and after 4 and 8 weeks. We performed flow cytometry analysis of whole blood samples and purified peripheral blood mononuclear cells for intracellular cytokine staining.ResultsBoth anti-CD20 mAbs resulted in a depletion of CD19+ B cells [median (IQR) HC: 16.5 (10.1–22.2), Ocre i.v.: 0.4 (0.1–0.9), Ocre s.c.: 0.8 (0.4–1.2), Ofa s.c.: 1.7 (0.8–2.2)] and CD20+ T cells [median (IQR) HC: 9.1 (6.6–16), Ocre i.v.: 0.6 (0.1–1), Ocre s.c.: 0.3 (0.2–0.5), Ofa s.c.: 0.1 (0.1–0.4)] in peripheral blood. More in-depth characterization of the patients’ remaining B cells indicated higher percentages of memory B cells in Ocre and Ofa s.c. compared to Ocre i.v. treated pwMS [median (IQR) Ocre i.v.: 6.6 (0–13), Ocre s.c.: 18.4 (4–26.8), Ofa s.c.: 26.4 (21.1–30)]. In pwMS who switched from i.v. Ocre to s.c. Ofa therapy, the percentage of memory B cells increased over time [median (IQR) baseline: 14.6 (6.4–20.8), 4 weeks after switch: 12.1 (6–23.4), 8 weeks after switch: 22.8 (16.7–29.5)]. I.v. Ocre treatment led to significantly lower serum IgG levels in pwMS compared to HC.DiscussionOur data add to the knowledge on distinct antibody-specific properties and differential effects of s.c. versus i.v. administered B-cell depletion in pwMS. We identified a higher percentage of memory B cells in s.c. Ocre and Ofa B cell-depleted pwMS and pwMS who switched their anti-CD20 therapy from i.v. Ocre to s.c. Ofa injection. Further analysis will be needed to investigate how these observations link to safety and efficacy profiles of the different anti-CD20 therapies.

BACKGROUND AND OBJECTIVES:Disability trajectories in aquaporin-4 immunoglobulin G-seropositive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are primarily driven by attack-related damage. Confirmed disability worsening (CDW) independent of attacks has been described but occurs infrequently in AQP4-IgG+ NMOSD and MOGAD. Confirmed disability improvement (CDI) has not been evaluated in large cohorts. We determined the frequency of CDI and CDW independent of attacks and identified clinical factors associated with these outcomes in AQP4-IgG+ NMOSD and MOGAD. METHODS:This retrospective, multicenter cohort study analyzed data from the German Neuromyelitis Optica Study Group (NEMOS) registry. Adult patients with AQP4-IgG+ NMOSD or MOGAD and longitudinal Expanded Disability Status Scale (EDSS) assessments were included. EDSS episodes were defined as periods with ≥3 EDSS assessments without attacks, obtained ≥90 days after attack. CDW and CDI were defined as sustained EDSS increase or decrease (≥1.5 for baseline EDSS 0; ≥1.0 for EDSS 1.0-5.5; ≥0.5 for EDSS ≥6.0) confirmed after at least 6 months. The primary outcomes were annualized CDI and CDW rates. Risk factors were assessed using multivariable Anderson-Gill regression models. RESULTS:A total of 338 EDSS episodes of 307 patients (n: 202/105, median age at EDSS change: 56/41 years, 88/49% female, both p < 0.001; AQP4-IgG+ NMOSD/MOGAD) were included. Adjusted annualized CDI and CDW rates did not differ between AQP4-IgG+ NMOSD (CDI: 0.083, 95% CI 0.029-0.233; CDW: 0.025, 95% CI 0.007-0.092) and MOGAD (CDI: 0.057, 95% CI 0.012-0.277; CDW: 0.036, 95% CI 0.002-0.513). In AQP4-IgG+ NMOSD, a lower number of prior attacks was associated with higher CDI rates (hazard ratio [HR] 0.89, 95% CI 0.82-0.97). Younger age was associated with increased CDI rates in both AQP4-IgG+ NMOSD and MOGAD (HR 0.96, 95% CI 0.94-0.99, for both). DISCUSSION:CDI and CDW independent of attacks, although rare, occur in AQP4-IgG+ NMOSD and MOGAD. The association between fewer prior attacks and higher CDI rates in AQP4-IgG+ NMOSD underscores the importance of early attack prevention. Limitations include the retrospective design, and the limited number of CDI and CDW events.

Neurosyphilis is a severe disease which can manifest with various clinical signs. The diagnosis can be challenging. Patients with positive syphilis serology and neurological or psychiatric symptoms should undergo cerebrospinal fluid (CSF) examination. The definite diagnosis is based on CSF findings, including evidence of inflammation, intrathecal production of treponemal antibodies (plus reactive non-treponema specific tests in the CSF). However, these criteria are not always fulfilled and a diagnosis of probable neurosyphilis may be established using less stringent diagnostic criteria. Treatment with intravenous penicillin or ceftriaxone is recommended for neurosyphilis. Here, a short version of the recommendations of the German guidelines on neurosyphilis that were published in 2026 is presented.

Atypical neurological graft-versus-host disease (cGVHD) is a rare complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In addition to central nervous system (CNS) involvement, patients with cGVHD may also exhibit pathology of the peripheral nerves, muscles or neuromuscular junction. In this report, we propose more detailed diagnostic criteria for these manifestations and apply them in a case series of peripheral nervous system and muscles (PNSM) involvement of cGVHD. Based on an interdisciplinary evaluation applying the recent provisional criteria for atypical manifestations of cGVHD, we propose a scoring system to diagnose and classify the four distinct forms of atypical cGVHD affecting the PNSM: immune-mediated inflammatory polyneuropathy, small-fiber polyneuropathy, neuromuscular junction disorder, and myositis. The proposed scoring system was retrospectively applied to all patients who underwent allo-HSCT at the University Hospital of Regensburg between 2007 and 2022 and presented with suspected cGVHD involving the PNSM. The objective was to advance the understanding of neurological manifestations associated with cGVHD by systematically evaluating neurological symptoms, diagnostic findings, and the clinical trajectories of affected patients. Out of 770 patients who underwent allo-HSCT, 15 (1.9%) were identified with cGVHD affecting the PNSM. According to the proposed scoring system, six patients were classified as possible and nine patients as probable atypical cGVHD of the PNSM. 1st-line treatment comprised intravenous immunoglobulin for most cases (10/15). A clinical response to 1st-line therapy was observed in 11 patients. In total, 12 patients showed response to immunosuppressive treatment (IST) while two patients did not respond to IST and one patient did not receive IST, but was successfully treated with pyridostigmine. Nine patients suffered from long-term neurologic sequelae. The 6-months and 1-year overall survival following PNSM-cGVHD onset was 12/15 and 9/15 patients, respectively. Cause of death was at least partly attributed to PNSM-cGVHD in three patients; up to last follow-up, non-relapse related mortality was 6/15 patients and relapse-related mortality 2/15 patients. With an incidence of 1.9%, PNSM-cGVHD is a rare but serious complication after allo-HSCT associated with long-term neurologic sequelae; early diagnosis and IST are mandatory. We propose a modified scoring system to diagnose this entity as a basis for larger multicenter studies.

Atypical manifestations of chronic graft-versus-host disease (cGVHD) can affect both the central nervous system (CNS) and peripheral nervous systems presenting with diverse clinical and paraclinical features. These manifestations are often difficult to distinguish from other neurologic conditions, particularly those resulting from drug toxicity and opportunistic infections. To date, only rough diagnostic criteria for these rare manifestations have been proposed. The objective of this study was to contribute additional data to the existing literature and to develop more specific diagnostic criteria for cGVHD affecting the CNS. Based on the 2020 National Institutes of Health report on atypical cGVHD and an interdisciplinary approach, we propose 3 distinct forms of CNS-cGVHD: vasculitis-like, demyelinating, and meningoencephalitis. We have developed a scoring system to categorize the likelihood of CNS-cGVHD as unlikely, possible, or probable. The score was applied in a retrospective review of all patients who underwent allo-HSCT at the University Hospital of Regensburg between 2007 and 2022, focusing on those with suspected CNS-cGVHD by analyzing the neurologic symptoms, diagnostic findings, and clinical course of all patients. Out of 770 patients who underwent allo-HSCT, 19 (2.5%) were identified with possible (n = 6) or probable (n = 13) cGVHD affecting the CNS. These included 12 patients with meningoencephalitis, 4 patients with vasculitis-like, and 1 patient with demyelinating cGVHD; 2 patients presented with "mixed phenotype" showing symptoms of 2 entities. First-line treatment comprised corticosteroids for most cases (n = 18), with 8 patients receiving at least 2 agents concomitantly as part of the initial therapeutic regimen. A clinical response to first-line therapy was observed in 12 patients. A median of 2 lines of therapy were administered for treatment of CNS-cGVHD, with 14 patients showing a response to immunosuppressive therapy (IST), and 5 patients showing no response to IST. The 6-month and 1-year overall survival following CNS-cGVHD onset was 78% for both. The cause of death was attributed at least in part to CNS-cGVHD in 4 patients, extraneurologic cGVHD in 2 patients, cardiovascular disease in 1 patient, cerebral hemorrhage in 1 patient, and relapse of acute myeloid leukemia in 1 patient. Eight of the 19 patients experienced long-lasting (>6 months) neurologic sequelae. Diagnosing atypical cGVHD remains a significant challenge and necessitates interdisciplinary discussions between neurologists and hematologists on a case-by-case basis. We propose new diagnostic criteria aimed at standardizing the diagnostic process for CNS manifestations of cGVHD. With an incidence of 2.5%, CNS-cGVHD is a rare but serious complication after allo-HSCT, associated with long-term neurologic sequelae; early diagnosis and early IST may improve neurologic outcomes. Our modified scoring system is aimed at diagnosing this entity as a basis for larger, multicenter studies. © 20XX American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

BACKGROUND:Infections of the central nervous system (CNS) occur in up to 15 % of patients with hematological or oncological diseases (HOD), particularly in high-risk populations. The most common causative agents are viruses or fungi. Prompt initiation of adequate diagnostic procedures and anti-infective treatment is crucial, as treatment delays increase mortality. METHODS:We present an update of our previous guideline published in 2016 on the management of CNS infections in patients with HOD. The grading of recommendation strength and level of evidence followed the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) standards, based on a systematic literature review and a stepwise consensus process involving experts in internal medicine, hematology, oncology, infectious diseases, neurology, microbiology, and radiology. This process included several web-based meetings by the guideline panel, whereas the final recommendations were approved by the assembly of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology in September 2024. FINDINGS AND INTERPRETATION:Evidence-based recommendations on the diagnosis and treatment of CNS infections in adult patients with HOD are essential in daily clinical practice to improve outcomes for patients at high risk of morbidity and mortality.

BACKGROUND AND OBJECTIVES:Comorbidities greatly influence the course of many diseases. However, systematic data on comorbidities in patients with autoimmune encephalitis (AE) are scarce. We aimed to characterize comorbidities in patients with common AE variants and assess their influence on outcome and occurrence of infectious complications. METHODS:This multicenter, retrospective cohort study analyzed adult patients with definite anti-N-methyl-d-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated-1 (LGI1), anti-contactin-associated protein-like-2 (CASPR2), and anti-immunoglobulin-like cell adhesion molecule-5 (IgLON5) AE registered by the GErman NEtwork for REsearch on AuToimmune Encephalitis between June 2004 and July 2023. Preexisting conditions (PECs), secondary diagnoses, and infectious complications documented during hospitalization were analyzed. Outcome was evaluated using a modified Rankin Scale (mRS), with unfavorable outcome defined as mRS >2 after a minimum of 12 months of follow-up. RESULTS:Among 308 patients with AE (144 NMDAR-AE, 98 LGI1-AE, 47 CASPR2-AE, and 19 IgLON5-AE), nearly half had cardiovascular and metabolic/endocrine, one-third neurologic, and one-fifth psychiatric comorbidities. Accompanying autoimmunity was observed in 12.7%. Univariable analysis showed that the presence of ≥3 PECs (OR 2.80, 95% CI 1.57-4.92), especially cardiovascular (OR 1.93, 95% CI 1.09-3.30) and psychiatric PECs (OR 3.84, 95% CI 1.96-7.31), was associated with unfavorable outcome. Multivariable regression analysis confirmed psychiatric PECs as independent risk factors (OR 4.55, 95% CI 1.99-10.60). During hospitalization, 13.6% of patients developed severe infections, although these were not associated with unfavorable outcome (OR 1.94, 95% CI 0.97-3.89). AE disease severity (OR 5.41, 95% CI 1.38-27.67) and intensive care unit admission emerged as the only independent predictors of severe infections (OR 20.76, 95% CI 7.02-75.10). DISCUSSION:As premorbid psychiatric conditions are main factors associated with unfavorable outcomes, these patients would highly benefit from integrated interdisciplinary treatment centers, or at least heightened awareness of these factors. Concomitant autoimmunity affecting other organs is frequent and should be sought. The risk of severe infections during the acute phase of AE is moderate and, given their lack of effect on outcome, should not justify withholding appropriate immunotherapy, even in elderly patients with comorbidities. Future prognostic models should incorporate comorbidities, particularly psychiatric ones, to enhance risk assessment and guide personalized care strategies.

Objective:This study analyzed clinical characteristics, attack recovery and long-term disability accumulation in late-onset (LO ≥ 50 years at onset) versus early-onset (EO < 50 years) NMOSD. Methods:This multicenter cohort study included demographic and clinical data from 446 NMOSD patients collected from 35 German Neuromyelitis Optica Study Group (NEMOS) centers. Time to disability milestones was estimated through Kaplan-Meier analysis and Cox proportional hazard regression models adjusted for sex, year of onset, immunotherapy exposure and antibody status. Generalized estimating equations (GEE) were used to compare attack outcomes. Results:Of the 446 NMOSD patients analyzed (83.4% female, 85.4% AQP4-IgG-positive, median age at disease onset = 43 years), 153 had a late-onset (34.3%). AQP4-IgG+ prevalence was higher in LO- than in EO-NMOSD (94.1% vs. 80.9%, p<0.001). Optic neuritis at onset was more frequent in EO-NMOSD (27.4% vs. 42.6%, p<0.002), whereas myelitis was more common in LO-NMOSD (58.4% vs. 37.9%, p<0.001). Both groups had similar annualized attack rates (AAR, 0.51 vs. 0.54, p=0.352), but attack recovery was poorer (complete remission in 15.6% vs. 27.4%, p<0.001) and relapse-associated worsening (RAW) was higher in LO-NMOSD (RAW: 3 vs. 0.5, p<0.001). Long-term immunotherapy use was comparable. LO-NMOSD exhibited faster progression to disability endpoints (EDSS 4: HR = 2.64, 95% CI=1.81-3.84). Interpretation:LO-NMOSD patients presented more often with myelitis, experienced worse attack outcomes and faster disability accumulation, despite comparable AAR, acute attack treatment and long-term treatment regimens. Accordingly, therapeutic strategies for attack and prophylactic treatment in LO-NMOSD have to be improved.

Background and objectivesThe diagnosis of multiple sclerosis (MS) is based on the McDonald diagnostic criteria and the exclusion of relevant differential diagnoses. This study aimed to determine the relative frequencies of MS differential diagnoses and to identify which diagnostic measures are most effective in distinguishing those from one another.MethodsWe conducted a retrospective analysis of all cases treated in the neurology ward of the University Hospital Regensburg during the years 2019 and 2020. The inclusion criteria comprised cases presenting with subacute focal neurological symptoms accompanied by corresponding lesions on magnetic resonance imaging (MRI) that could not be primarily attributed to MS, tumor, hemorrhage, or ischemia, as well as cases with abnormal external MRI findings who were referred to our clinic for the evaluation or exclusion of multiple sclerosis.ResultsA total of 127 cases were included in the study. Differential diagnoses of MS were predominantly of inflammatory or vascular origins or non-specific white matter lesions. The primary diagnostic tools for distinguishing differential diagnoses of MS from one another were patient history (fever), cerebrospinal fluid analysis, and brain MRI, as well as a duplex ultrasound of the cranial vessels.DiscussionOur study demonstrates that cerebrospinal fluid analysis and brain MRI are essential not only for the diagnosis of MS but also for distinguishing among its various differential diagnoses. In particular, duplex ultrasound may assist in identifying vascular lesions, while the presence of fever may suggest an infectious cause.

Background Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) impose psychological burdens on patients. Chronic illnesses create challenges for both patients and their partners, who also play a crucial role in managing disease-related stress. Despite its relevance, little is known about the role of dyadic coping (DC) in these conditions. This study investigates DC in NMOSD and MOGAD, aiming to provide clinical recommendations.Methods The CoMMOnsense-Study is a cross-sectional, prospective study of 59 NMOSD and 50 MOGAD patients and their respective partners, recruited from 15 centres of the German Neuromyelitis Optica Study Group registry. Participants completed self-report questionnaires on DC, depression, anxiety and quality of relationship. Correlation analyses were performed to compare findings based on antibody status. Subsequently, multivariate regression analyses were conducted to identify relevant predictors of DC.Results Patients with NMOSD and MOGAD demonstrated higher levels of depressive symptoms (NMOSD: p=0.007; MOGAD: p=0.023) and stress communication scores (NMOSD: p=0.022; MOGAD: p=0.013) than their partners. Negative coping was low across all subgroups (Stanine 1). Despite high DC and relationship quality, discrepancies were observed in the coping perceptions between partners.Conclusions Coping is highly shared within partnerships affected by NMOSD and MOGAD, while discrepancies in coping perceptions and protective buffering suggest the presence of unfavourable coping mechanisms. Reducing protective buffering and illness-related distortions shows potential areas for enhancing DC.

BACKGROUND:Modulation of the gut microbiota composition has been suggested as a potential disease modifying therapy in immune-mediated diseases such as multiple sclerosis (MS). However, a conclusive mechanism linking gut microbiota modulation to peripheral immune responses has remained elusive so far. METHODS:In this exploratory cohort study, people with MS (pwMS) and healthy controls (HC) supplemented a lactobacilli-rich probiotic for two or six weeks and were additionally investigated six weeks after the last intake. Immune cell phenotyping was performed in blood samples, complemented by mRNA expression analysis, serum cytokine measurements, and Treg suppression assays. Besides gut microbiota composition analysis, metabolite production was investigated in stool and serum. Links between metabolites and peripheral immune system were investigated in in vitro T cell differentiation assays. FINDINGS:In peripheral blood, Treg cells increased in both groups, while Th1 cells were significantly reduced in pwMS. This promotion of a regulatory immunophenotype was complemented by increased concentrations of IL-10 in serum and higher expression of IL10 and CTLA4. Functional assays revealed an enhanced suppressive capacity of Treg cells due to the probiotic intervention. The tryptophan metabolite indole-3-acetate (IAA) increased in stool and serum samples of pwMS during the probiotic intake. In vitro, IAA specifically enhanced the formation of IL-10 secreting T cells together with CYP1a1 expression. This effect was blocked by addition of an aryl hydrocarbon receptor (AHR) inhibitor. INTERPRETATION:A lactobacilli-enriched probiotic promotes a regulatory immunophenotype in pwMS, probably by enhancing AHR agonists in the gut. It may be of interest as add-on therapy in immune-mediated diseases such as MS. FUNDING:This study has in part been funded by Novartis Pharma GmbH and BMBF grant no. 01EJ2202B.

In recent years, early use of highly effective disease modifying immunotherapies in relapsing-remitting multiple sclerosis (RRMS) demonstrated superior efficacy in preventing disability progression. For this study, we investigated ocrelizumab as first line therapy of RRMS in a monocentric, retrospective study. In our outpatient clinic, ocrelizumab was administered as first-line therapy in 33 patients with an anticipated highly active disease course. Patients were re-evaluated clinically every 6 months and at least annually with cranial magnetic resonance imaging (MRI), with a mean follow-up period of 27 months. Subgroup analyses were conducted based on age, sex, disease duration, and disability as measured by EDSS at initiation of therapy. Ocrelizumab therapy was administered within the first year of diagnosis. The median EDSS at the time of ocrelizumab initiation was 2.5, with male patients showing higher disability compared to the females. The annualized relapse rate (ARR) decreased from 2.24 to 0.058 during the observation period. EDSS remained stable throughout the therapy period for the entire cohort. Starting treatment earlier and at a lower initial EDSS correlated with a better outcome. Gender and age had no impact on the therapeutic efficacy. The most common infusion related reactions included fatigue (25 %) and headaches (9 %). Mild infections occurred in 21 % of patients. These data highlight the role of ocrelizumab as an effective first-line therapeutic approach for patients with highly active RRMS.

BackgroundRecurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.MethodsThis longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS). We analysed unadjusted ARR and implemented survival analyses and Cox proportional hazard regression to assess efficiency and risk factors for subsequent attacks over time.ResultsRituximab and azathioprine are the most widely used immunotherapies in NMOSD as well as in MOGAD, with changes in distribution over the last decade. Immunotherapy demonstrated significant therapeutic effects in NMOSD but less pronounced effects in MOGAD. Risk factors for attacks included younger age and prior attacks under the same therapy. Efficacy varied among the different immunotherapies, with azathioprine, rituximab and eculizumab showing significant risk reductions in AQP4-IgG seropositive NMOSD.ConclusionsThis study provides insights into the evolving treatment landscape and effectiveness of immunotherapies in NMOSD and MOGAD. Established off-label therapies continue to play an important role, especially for patients with stable disease, with emerging evidence supporting newly approved therapies. Future studies are needed to refine treatment algorithms and address the ongoing uncertainties in MOGAD management.

Myasthenia gravis (MG) is a B-cell-mediated autoimmune disease and the most frequent disorder of the neuromuscular junction.Characteristic symptoms are muscle weakness, dysphagia, diplopia and fatigue that typically increase throughout continuous muscular activity [1,2].Diagnosis of MG typically involves clinical evaluation and diagnostic testing such as low-frequency repetitive nerve stimulation, blood tests to detect specific antibodies, and imaging studies of the thymus gland, which is often involved in the development of the disease.Treatment for MG includes the use of medications to improve muscle function and suppress the autoimmune response.Cholinesterase inhibitors and immunosuppressive medications are commonly used to manage MG symptoms.Living with MG can be challenging and within 2 years of the initial diagnosis, 15-20% of MG patients develop a potentially life-threatening myasthenic crisis (MC) [3].MC has been defined as respiratory failure requiring mechanical ventilation (MV) due to respiratory muscle weakness or bulbar dysfunction.The mortality, even in our times, is around 12% and prolonged MV (defined as more than 15 days) occurs in 44.7% of the MG patients [4].Analysis of invasive ventilated patients showed that in eligible patients, early tracheostomy can be associated with a shorter mechanical ventilation duration

BACKGROUND AND OBJECTIVES:Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care. METHODS:We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale {EDSS}]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics. RESULTS:Fifty-two patients (87% female, age 55.0 ± 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 - 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6-10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0-4) in the 2 years preceding ECU to 0 (range 0-0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score ≥ 7). The overall discontinuation rate was 19%. DISCUSSION:Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU-particularly in patients with comorbidities-must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.