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

Abstract

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.

Recovery of thalamic microstructural damage after Shiga toxin 2-associated hemolytic–uremic syndrome

“…It comprises acute kidney injury, thrombocytopenia (platelet count b 150.000 cells/mm 3 ), and microangiopathic hemolytic anemia [2]. HUS is the most common cause of acute renal failure in childhood [3][4][5][6][7] and occurs predominantly in children younger than five years [2,[6][7][8][9][10][11]. Between May and July 2011, the world's largest reported HUS outbreak affected northern Germany [8,12,13].…”

“…Additionally, the following pathomechanisms have also been proposed: metabolic (azotaemia, hyponatremia with consequent osmotic derangements, and demyelination) [16], inflammatory [10,18], mixed toxic-inflammatory [11,14], mixed toxic-metabolic [8,19,20], and direct toxic effects [16]. However, the possibility that Stx may have a direct influence on neurons has not been systematically analyzed [9]. Recently, based on combinations of different experiments in Long-Evans rats, Meuth et al found an enhanced expression of Gb3 receptors on thalamic neurons of female rats compared to other brain regions and to male animals.…”

“…Using acutely prepared brain slices in this study, it was suggested that binding of Stx2 to the Gb3 receptor could directly induce neuronal and astrocytic apoptosis. Together with MRI findings and electroencephalogram (EEG) results of seven female patients suffering from neurological complications due to Stx2-associated HUS, the authors proposed that a direct cytotoxic effect of Stx2 in the thalamus contributes to the pathophysiology of neuronal complication following HUS [9].…”

“…However, inconsistent results were achieved by this method [7,10,11,16,19]. A few studies succeeded to identify the thalamus as "main target structure" in patients with neurological complications due to Stx2-associated HUS [8,9,13,14,16,19]. Thus convMRI including DWI of seven patients of the study of Meuth et al [9] revealed -despite severe neurological deficits -only slight thalamic hyperintensities in T2 weighted (T2w)/FLAIR images and mildly reduced ADC values in the thalamus, whereas T1 weighted (T1w) images were inconspicuous.…”

“…Here we use diffusion tensor imaging (DTI) in three of seven patients of the study of Meuth et al [9] to address the following objectives: (i) Can DTI better monitor thalamic alterations in individual patients suffering from severe neurological deficits due to Stx2-caused HUS than convMRI? (ii) Do thalamic changes captured by DTI better correlate with neurological symptoms and more precisely reflect the disease course than those detected by convMRI?…”