Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2. Issue 3 (19th February 2013)

• Record Type: Journal Article
• Authors: 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, Hans‐Christian
• Is Part Of: Annals of neurology. Volume 73:Issue 3(2013:Mar.)
• Page Start: 419
• Page End: 429
• Publication Date: 2013-02-19
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.23814
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana23814-sec-0001" sec-type="section"> <title>Objective</title> <p>The outbreak of hemolytic–uremic syndrome and diarrhea caused by Shiga toxin–producing <italic>Escherichia coli</italic> 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.</p> </sec> <sec id="ana23814-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="ana23814-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="ana23814-sec-0004" sec-type="section"> <title>Interpretation</title> <p>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</p> </sec> </abstract>