Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2.

Meuth SG, Göbel K, Kanyshkova T, Ehling P, Ritter MA, Schwindt W, Bielaszewska M, Lebiedz P, Coulon P, Herrmann AM, Storck W, Kohmann D, Müthing J, Pavenstädt H, Kuhlmann T, Karch H, Peters G, Budde T, Wiendl H, Pape HC

Research article (journal) | Peer reviewed

Abstract

The outbreak of hemolytic-uremic syndrome and diarrhea caused by Shiga toxin-producing Escherichia coli O104:H4 in Germany during May to July 2011 involved severe and characteristic neurologic manifestations with a strong female preponderance. Owing to these observations, we designed a series of experimental studies to evaluate the underlying mechanism of action of this clinical picture.A magnetic resonance imaging and electroencephalographic study of patients was performed to evaluate the clinical picture in detail. Thereafter, combinations of different experimental settings, including electrophysiological and histological analyses, as well as calcium imaging in brain slices of rats, were conducted.We report on 7 female patients with neurologic symptoms and signs including bilateral thalamic lesions and encephalopathic changes indicative of a predominant involvement of the thalamus. Experimental studies in rats revealed an enhanced expression of the Shiga toxin receptor globotriaosylceramide on thalamic neurons in female rats as compared to other brain regions in the same rats and to male animals. Incubation of brain slices with Shiga toxin 2 evoked a strong membrane depolarization and intracellular calcium accumulation in neurons, associated with neuronal apoptosis, predominantly in the thalamic area.These findings suggest that the direct cytotoxic effect of Shiga toxin 2 in the thalamus might contribute to the pathophysiology of neuronal complications in hemolytic-uremic syndrome. ANN NEUROL 2013;73:419-429.

Details about the publication

JournalAnnals of Neurology
Volume73
Issue3
Page range419-429
StatusPublished
Release year2013
Language in which the publication is writtenEnglish
DOI10.1002/ana.23814
Link to the full texthttps://onlinelibrary.wiley.com/doi/full/10.1002/ana.23814

Authors from the University of Münster

Budde, Thomas
Institute of Physiology I (Neurophysiology)
Hundehege, Petra
Department of Neurology [closed]
Karch, Helge
Institute of Hygiene
Meuth, Sven
Department for Neurology
Müthing, Johannes
Institute of Hygiene
Pavenstädt, Hermann-Joseph
Medical Clinic of Internal Medicine D (Nephrology and Rheumatology) (Med D)
Peters, Georg
Institute of Medical Microbiology
Schwindt, Wolfram
Clinic of Radiology
Wiendl, Heinz Siegfried
Department of Neurology [closed]