The Marburg variant of multiple sclerosis (MvMS) is a rare, rapidly progressive demyelinating disorder characterized by an acute, monophasic onset with early, severe disability or death within weeks to months. In this systematic review, we aimed to: (I) describe patient characteristics and therapies used; (II) categorize outcomes; and (III) synthesize therapy-outcome relationships to guide practical management. We performed a PRISMA-guided systematic review of published MvMS cases reporting treatment and outcomes, and present an illustrative pediatric case from our center. Across databases, 144 records were identified (PubMed 34; Scopus 74; WoS 36), out of which 22 articles met inclusion criteria. Among the 23 patients synthesized (22 published cases plus our pediatric case), median age was 32 years (range 14-63), with a female predominance (78 %). Nearly all patients received high-dose corticosteroids (22/23; 96 %). Additional therapies were common and variably combined: plasma exchange (14/23; 61 %), IVIg (8/23; 35 %), cyclophosphamide (10/23; 43 %), mitoxantrone (7/23; 30 %), any cytotoxic (cyclophosphamide and/or mitoxantrone) (15/23; 65 %), B-cell-depleting therapy (rituximab/ocrelizumab) (4/23; 17 %), alemtuzumab (1/23; 4 %), and natalizumab (1/23; 4 %); doses were inconsistently reported across studies, and order/timing of therapies varied widely. Overall outcomes were death in 6/23 (26 %), stable deficit in 4/23 (17 %), improvement in 9/23 (39 %), and near-complete recovery in 4/23 (17 %). We also propose a set of pragmatic, evidence-based diagnostic criteria. These criteria classify cases as Definite, Probable, or Possible Marburg variant MS based on fulminant clinical course, characteristic MRI patterns, CSF/serologic exclusion of mimics, and-when available-pathological confirmation. While no single regimen was uniformly effective, our three-group analysis suggests a stepwise strategy: steroids ± plasma exchange alone were often insufficient; adding a cytotoxic agent with dual B- and T-cell activity (cyclophosphamide or mitoxantrone) was associated with more frequent improvement; and the highest proportion of improvement occurred when dual-arm cytotoxic therapy was combined with a B-cell-directed/lymphocyte-depleting agent.

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. 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. 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). 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.

The Marburg variant of multiple sclerosis (MS), first described in 1906 by Otto Marburg, an Austrian neurologist, is characterized by a fulminant monophasic course with rapid disease progression, often leading to death within weeks or months. Due to its rarity, no established treatment guidelines exist. A 34-year-old man was diagnosed with MS after presenting with acute-onset numbness and weakness in the right lower limb. Magnetic resonance imaging (MRI) revealed a significant burden of numerous supra- and infratentorial white matter plaques. The patient was treated with steroid pulse therapy. However, the patient's condition continued to deteriorate clinically and radiologically despite receiving intravenous immunoglobulin and plasma exchange. An extensive workup was performed to exclude other differential diagnoses that were significant for the presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF). A diagnosis of Marburg variant MS was considered, and high-dose cyclophosphamide (HiCy) (50 mg/kg/d IV) was initiated on alternate days for 4 days. Twenty-six days after treatment completion, the patient exhibited significant clinical improvement, with an Expanded Disability Status Scale (EDSS) score of 5. This case contributes to the growing evidence that cyclophosphamide may be an effective therapeutic option for patients with Marburg variants of MS who do not achieve satisfactory clinical improvement with conventional acute treatments.

Marburg disease (malignant multiple sclerosis, MS) is a rare, acute MS variant, predominantly occurring among young adults. Because it is characterized by rarity, high morbidity and mortality rates, the disease needs to be further characterized, and the experience of the physicians play a role in treatment regimens. We report the case of a 15-years-old female presenting with progressive weakness over the limbs, hyperreflexia and loss of sensation by physical examination, lab tests and radiological investigations (MRI). After treatment, nonimprovement was recognized by symptoms review after IV corticosteroids, Gabapentin and Clonazepam intake during a clinical visit. IV corticosteroids, Gabapentin and Clonazepam are not sufficient treatment for Marburg's variant of multiple sclerosis disease. Therefore, aggressive therapies can be used to further suppress the inflammatory process to prevent further neurological damage.

Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990-2021. We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. In 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6-7·8] deaths; 10·7% [9·8-11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8-171·6] DALYs; 5·6% [5·0-6·1] of all DALYs). In 2021, there were 93·8 million (89·0-99·3) prevalent and 11·9 million (10·7-13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4-67·7), intracerebral haemorrhage constituted 28·8% (28·3-28·8), and subarachnoid haemorrhage constituted 5·8% (5·7-6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4-117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7-38·1]), diet high in sugar-sweetened beverages (23·4% [12·7-35·7]), low physical activity (11·3% [1·8-34·9]), high systolic blood pressure (6·7% [2·5-11·6]), lead exposure (6·5% [4·5-11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5-10·5]). Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden. Bill & Melinda Gates Foundation.