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Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2
Author(s) -
Meuth Sven G.,
Göbel Kerstin,
Kanyshkova Tatyana,
Ehling Petra,
Ritter Martin A.,
Schwindt Wolfram,
Bielaszewska Martina,
Lebiedz Pia,
Coulon Philippe,
Herrmann Alexander M.,
Storck Wiebke,
Kohmann Denise,
Müthing Johannes,
Pavenstädt Hermann,
Kuhlmann Tanja,
Karch Helge,
Peters Georg,
Budde Thomas,
Wiendl Heinz,
Pape HansChristian
Publication year - 2013
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23814
Subject(s) - thalamus , shiga toxin , medicine , pathophysiology , toxin , pathology , neuroscience , biology , escherichia coli , microbiology and biotechnology , biochemistry , gene
Objective 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. Methods 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. Results 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. Interpretation 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