BackgroundMechanical thrombectomy (MT) is highly effective in large vessel occlusion (LVO) stroke. In north-east Germany, many rural hospitals do not have continuous neurological expertise onsite and secondary transport to MT capable comprehensive stroke centers (CSC) is necessary. In metropolitan areas, small hospitals often have neurology departments, but cannot perform MT. Thus, interhospital transport to CSCs is also required. Here, we compare time-to-care metrics and outcomes in patients receiving MT after interhospital transfer from primary stroke centers (PCSs) to CSCs in rural vs. metropolitan areas.MethodsPatients from ten rural telestroke centers (RTCs) and nine CSCs participated in this study under the quality assurance registry for thrombectomies of the Acute Neurological care in North-east Germany with TeleMedicine (ANNOTeM) telestroke network. For the metropolitan area, we included patients admitted to 13 hospitals without thrombectomy capabilities (metropolitan primary stroke centers, MPSCs) and transferred to two CSCs. We compared groups regarding baseline variables, time-to-care metrics, clinical, and technical outcomes.ResultsBetween October 2018 and June 2022, 50 patients were transferred from RTCs within the ANNOTeM network and 42 from MPSCs within the Berlin metropolitan area. RTC patients were older (77 vs. 72 yrs, p = 0.05) and had more severe strokes (NIHSS 17 vs. 10 pts., p < 0.01). In patients with intravenous thrombolysis (IVT; 34.0 and 40.5%, respectively), time from arrival at the primary stroke center to start of IVT was longer in RTCs (65 vs. 37 min, p < 0.01). However, RTC patients significantly quicker underwent groin puncture at CSCs (door-to-groin time: 42 vs. 60 min, p < 0.01). Despite longer transport distances from RTCs to CSCs (55 vs. 22 km, p < 0.001), there was no significant difference of times between arrival at the PSC and groin puncture (210 vs. 208 min, p = 0.96). In adjusted analyses, there was no significant difference in clinical and technical outcomes.ConclusionDespite considerable differences in the setting of stroke treatment in rural and metropolitan areas, overall time-to-care metrics were similar. Targets of process improvement should be door-to-needle times in RTCs, transfer organization, and door-to-groin times in CSCs wherever such process times are above best-practice models.

Das Kontinuum der Wachheitsgrade reicht von Wachheit über Somnolenz, Sopor bis zum Koma; abzugrenzen ist der Zustand des Stupors. Diese Bewusstseinsstörungen kommen bei intensivmedizinischen Patienten häufig vor. Ursächlich können unter anderem strukturelle Erkankungen des Gehirns, metabolische Entgleisung und Intoxikationen sein. Dieses Kapitel beschreibt die Pathogenese, die Diagnostik (u. a. Glasgow Coma Scale, Laboruntersuchungen, bildgebende Verfahren) sowie die Therapie. Bei hinreichend schwerwiegender Ursache kann nach Eintritt des Komas innerhalb von einigen Stunden ein akuter und irreversibler Hirnfunktionsausfall entstehen. Die Kriterien für dessen Festellung vor dem Hintergrund einer möglichen Organspende sind hier definiert und beschrieben. (in früheren Auflagen unter Mitarbeit von F. Weber, München, und H. Prange, Göttingen)

OBJECTIVE:Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.METHODS:Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.RESULTS:Four patients were identified as having a "possible" history of MS, and 7 patients as "definite" cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.CONCLUSION:There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.

Background and purpose: Interferon beta (IFNβ) preparations have some effect on the progressive phase of multiple sclerosis (MS). This limited effect might be partially because of a certain number of IFNβ non‐responders. Myxovirus resistance protein A (MxA) – a marker of IFNβ bioactivity – was correlated with the clinical response during an uncontrolled trial, investigating the safety of IFNβ‐1b in primary progressive (PPMS) patients.Methods: Twenty PPMS were treated with IFNβ‐1b (s.c.) for 1 year. Blood samples were taken before and 1, 2, 3, 6, 9, 12, and 15 months after treatment initiation and MxA protein levels were measured. Patients were clinically evaluated by EDSS and the more sensitive Incapacity Status Scale (ISS) and stratified in a stable and a progressing group.Results: Using ISS criteria, 11 patients remained stable and nine patients progressed during treatment. The mean area under the curve of log MxA levels during treatment were significantly higher in stable than in progressing patients (10.87 vs. 5.99; P = 0.002).Conclusion: A good biological response to IFNβ might be associated with a better clinical effect of this drug and could be helpful in future clinical studies for early identification of treatment responders.

OBJECTIVES It is unknown whether the immunological effects of beta-interferon (IFN-beta) differ in primary progressive multiple sclerosis (PPMS) when compared with relapsing-remitting multiple sclerosis (RRMS). Therefore, we investigated the effects of IFN-beta1b treatment in PPMS on proliferation and cytokine pattern of peripheral blood mononuclear cells (PBMC) and interleukin-10 (IL-10) serum level. METHODS Eighteen patients were treated with IFN-beta1b for 12 months in an open-label trial. Serum and PBMC were collected longitudinally. RESULTS Interleukin-10 serum levels increased (P = 0.02) during treatment. Tumor necrosis factor-alpha was increased in anti CD3 (OKT3) antibody stimulated PBMC during treatment (P = 0.04), whereas secretion of IL-10 was decreased in OKT3 (P = 0.04), but increased in concavalin A stimulated PBMC (P = 0.02). CONCLUSIONS Interleukin-10 serum levels rose in IFN-beta1b-treated patients as has been observed in RRMS. The changes in cytokine patterns secreted by T-lymphocytes of PPMS patients, however, differ from effects observed in RRMS supporting the hypothesis that PPMS differs in some immunological aspects from RRMS.

Die Zahl der verfügbaren oder kurz vor der Zulassung stehenden Virustatika wächst kontinuierlich. Neben den antiretroviralen Präparaten zur Behandlung der HIV-Infektion liegt der Schwerpunkt auf Präparaten mit Aktivität gegen Mitglieder der Familie der Herpesviridae, insbesondere das Varicella-zoster-Virus und das Herpes-simplex-Virus. Die Studienlage bezüglich der antiviralen Behandlung viraler Infektionen des Nervensystems ist unbefriedigend. Einzig für die Therapie des Herpes zoster liegen mehrere kontrollierte Studien vor. Diese Studien deuten darauf hin, dass durch Einsatz neuer Virustatika wie des Famciclovir oder des Valaciclovir der akute Zosterschmerz schneller sistiert und die Rate an Post-zoster-Neuralgien sinkt. Für die Therapie der viralen Enzephalitiden existieren in der Regel nur Einzelfallberichte. Dennoch bietet das erweiterte Spektrum an antiviral wirksamen Substanzen auch bei der viralen Enzephalitis die Möglichkeit, im Einzelfall Präparate einzusetzen, die zumindest in vitro eine Aktivität gegen das kausale Pathogen entfalten. Bei der Herpes-simplex-Enzephalitis bleibt Aciclovir das Mittel der ersten Wahl.

Background: A pathological classification has been developed of early active multiple sclerosis ( MS) lesions that reveals four patterns of tissue injury: I - T cell/macrophage associated; II - antibody/ complement associated; III - distal oligodendrogliopathy, and IV - oligodendrocyte degeneration in the periplaque white matter. Mechanisms of demyelination in early MS may differ among the subgroups. Previous studies on biopsied MS have lacked clinicopathological correlation and follow up. Critics argue that observations are not generalisable to prototypic MS.Objective: To describe the clinicopathological characteristics of the MS Lesion Project biopsy cohort.Methods: Clinical characteristics and disability of patients with pathologically confirmed inflammatory demyelinating disease ( excluding ADEM) classified immunopathologically ( n = 91) and patients from the Olmsted County MS prevalence cohort ( n = 218) were determined.Results: Most patients who underwent biopsy and had pathologically proved demyelinating disease ultimately developed definite ( n = 70) or probable ( n = 12) MS ( median follow up 4.4 years). Most had a relapsing remitting course and 73% were ambulatory (EDSS <= 4) at last follow up. Nine patients remained classified as having an isolated demyelinating syndrome at last follow up. Patients with different immunopathological patterns had similar clinical characteristics. Although presenting symptoms and sex ratios differed, the clinical course in biopsy patients was similar to the prevalence cohort. Median EDSS was <4.0 in both cohorts when matched for disease duration, sex, and age.Conclusions: Most patients undergoing biopsy, who had pathologically confirmed demyelinating disease, were likely to develop MS and remain ambulatory after a median disease duration of 4.4 years. The immunopathological patterns lacked specific clinical correlations and were not related to the timing of the biopsy. These data suggest that pathogenic implications derived largely from MS biopsy studies may be extrapolated to the general MS population.

Early, active multiple sclerosis lesions show four immunopathological patterns of demyelination. Although these patterns differ between patients, multiple active lesions from a given patient have an identical pattern, which suggests pathogenic heterogeneity. Therapeutic plasma exchange (TPE) has been successfully used to treat fulminant demyelinating attacks unresponsive to steroids. We postulated that patients with pattern II would be more likely to improve after TPE than those with other patterns since pattern II lesions are distinguished by prominent immunoglobulin deposition and complement activation. We retrospectively studied 19 patients treated with TPE for an attack of fulminant CNS inflammatory demyelinating disease. All patients with pattern II (n=10), but none with pattern I (n=3) or pattern III (n=6), achieved moderate to substantial functional neurological improvement after TPE (p<0.0001). Patients with multiple sclerosis with pattern II pathology are more likely to respond favourably to TPE than are patients with patterns I or III.