title: Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Physiology I, Department of Neurology, University Hospital Münster, Westphalian Wilhelms University, Münster, Germany. sven.meuth@ukmuenster.de
authors: Sven G
authors: SG
authors: Meuth
authors: Kerstin
authors: K
authors: Göbel
authors: Tatyana
authors: T
authors: Kanyshkova
authors: Petra
authors: P
authors: Ehling
authors: Martin A
authors: MA
authors: Ritter
authors: Wolfram
authors: W
authors: Schwindt
authors: Martina
authors: M
authors: Bielaszewska
authors: Pia
authors: P
authors: Lebiedz
authors: Philippe
authors: P
authors: Coulon
authors: Alexander M
authors: AM
authors: Herrmann
authors: Wiebke
authors: W
authors: Storck
authors: Denise
authors: D
authors: Kohmann
authors: Johannes
authors: J
authors: Müthing
authors: Hermann
authors: H
authors: Pavenstädt
authors: Tanja
authors: T
authors: Kuhlmann
authors: Helge
authors: H
authors: Karch
authors: Georg
authors: G
authors: Peters
authors: Thomas
authors: T
authors: Budde
authors: Heinz
authors: H
authors: Wiendl
authors: Hans-Christian
authors: HC
authors: Pape
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004569:Electroencephalography; D004927:Escherichia coli Infections / Q000134:cerebrospinal fluid / Q000150:complications*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008564:Membrane Potentials / Q000187:drug effects; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics; D022641:Shiga Toxin 2 / Q000633:toxicity*; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology; D014281:Trihexosylceramides / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D022641:Shiga Toxin 2; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D002118:Calcium