Neurological Involvement in Pediatric Hemolytic Uremic Syndrome: A Symptom-Oriented Analysis

Şahin, Sevim; Özdoğan, Elif Bahat; Kaya, Gülay; Özgün, Nezir; Cansu, Ali; Kalyoncu, Mukaddes; Dilber, Embiya

doi:10.1055/s-0037-1603643

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…The actions of Stxs on the microvasculature of the spinal column and the brain are thought to be a major cause of CNS disease. Numerous clinical case reports show that some pediatric patients with D+HUS develop severe neurological manifestations associated with Stx-mediated renal damage [164,184,185,186,187]. STEC O104:H4-infected D+HUS patients developed neurological manifestations, including lethargy and impaired visual function with complete blindness, supporting ocular involvement in D+HUS pathogenesis [164,188].…”

Section: Roles Of Stxs In Cns Immunopathogenesismentioning

confidence: 99%

Roles of Shiga Toxins in Immunopathology

Lee

Tesh

2019

Toxins

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Shigella species and Shiga toxin-producing Escherichia coli (STEC) are agents of bloody diarrhea that may progress to potentially lethal complications such as diarrhea-associated hemolytic uremic syndrome (D+HUS) and neurological disorders. The bacteria share the ability to produce virulence factors called Shiga toxins (Stxs). Research over the past two decades has identified Stxs as multifunctional toxins capable of inducing cell stress responses in addition to their canonical ribotoxic function inhibiting protein synthesis. Notably, Stxs are not only potent inducers of cell death, but also activate innate immune responses that may lead to inflammation, and these effects may increase the severity of organ injury in patients infected with Stx-producing bacteria. In the intestines, kidneys, and central nervous system, excessive or uncontrolled host innate and cellular immune responses triggered by Stxs may result in sensitization of cells to toxin mediated damage, leading to immunopathology and increased morbidity and mortality in animal models (including primates) and human patients. Here, we review studies describing Stx-induced innate immune responses that may be associated with tissue damage, inflammation, and complement activation. We speculate on how these processes may contribute to immunopathological responses to the toxins.

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Section: Roles Of Stxs In Cns Immunopathogenesismentioning

confidence: 99%

Roles of Shiga Toxins in Immunopathology

Lee

Tesh

2019

Toxins

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“…The Stxs produced by Shigella dysenteriae serotype 1 and select serotypes of E. coli are the most potent known virulence factors involved in the pathogenesis of hemorrhagic colitis, which can progress to potentially fatal systemic complications such as acute renal failure [6] and neurological abnormalities [7,8]. Although multiple studies have defined the pathologic host responses to Stx1 and Stx2 in multiple cell types, sensors capable of detecting Stxs in susceptible cells following intoxication have also been recognized as critical tools (reviewed in [9,10]).…”

Section: Introductionmentioning

confidence: 99%

A portable and high-sensitivity optical sensing system for detecting fluorescently labeled enterohaemorrhagic Escherichia coli Shiga toxin 2B-subunit

Kim

Park

et al. 2020

PLoS ONE

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We developed a stand-alone, real-time optical detection device capable of reading fluorescence intensities from cell samples with high sensitivity and precision, for use as a portable fluorescent sensor for sensing fluorescently labeled enterohemorrhagic Escherichia coli (EHEC) Shiga toxins (Stxs). In general, the signal intensity from the fluorescently labeled Stxs was weak due to the small number of molecules bound to each cell. To address this technical challenge, we used a highly sensitive light detector (photomultiplier tube: PMT) to measure fluorescence, and designed a portable optical housing to align optical parts precisely; the housing itself was fabricated on a 3D printer. In addition, an electric circuit that amplified PMT output was designed and integrated into the system. The system shows the toxin concentration in the sample on a liquid crystal display (LCD), and a microcontroller circuit is used to read PMT output, process data, and display results. In contrast to other portable fluorescent detectors, the system works alone, without any peripheral computer or additional apparatus; its total size is about 17 × 13 × 9 cm 3 , and it weighs about 770 g. The detection limit was 0.01 ppm of Alexa Fluor 488 in PBS, which is ten thousand times lower than those of other smartphone-based systems and sufficiently sensitive for use with a portable optical detector. We used the portable real-time optical sensing system to detect Alexa Fluor 488-tagged Stx2B-subunits bound to monocytic THP-1 cells expressing the toxin receptor globotriaosylceramide (Gb3). The device did not detect a signal from Gb3-negative PD36 cells, indicating that it was capable of specifically detecting Stxs bound to cells expressing the toxin receptor. Following the development of a rapid and autonomous method for fluorescently tagging cells in food samples, the optical detection system described here could be used for direct detection of Shiga toxins in food in the field.

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Cerebral microstructural changes in children suffering from hemolytic uremic syndrome

et al. 2023

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To evaluate microstructural cerebral changes in children suffering from typical hemolytic uremic syndrome (HUS) based on apparent diffusion coefficient (ADC) maps. For 12 pediatric HUS patients (0.8 - 14.6 years of age) conventional magnetic resonance imaging (cMRI) at 1.5 T was retrospectively analyzed. ADC values were measured in 35 different brain regions and compared with age-related, previously published ADC reference values from a healthy pediatric control group. The HUS cohort was divided into 2 subgroups depending on clinical outcome. Subgroup A showed poor neurological outcome whereas subgroup B demonstrated improvement without lasting neurological deficits. Qualitative analysis revealed lesions by diffusion-weighted imaging (DWI) with hypointense correlate on the ADC map in basal ganglia and/or thalami and corresponding T2 hyperintensities in the majority of patients in Subgroup A (80%). Those in Subgroup B did not show qualitative DWI alterations with ADC correlate even when T2 hyperintense lesions were detected in basal ganglia and/or thalami. Quantitative analysis demonstrated abnormal ADC values in all HUS patients with a trend to a greater number of affected regions in Subgroup A compared to Subgroup B (16 versus 11 median number of regions respectively, p = 0.56). Conclusion: Using DWI qualitative and quantitative differences were found between HUS patients showing poor neurological outcome and those without neurological deficits at discharge. While ADC values indicated more extensive cerebral changes than conventional qualitative findings, both may provide early prognostic indicators for neurological outcome in pediatric HUS patients. What is Known:• In patients with STEC-HUS and neurological symptoms, MRI may show hyperintense signals on T2 and altered diffusivity mostly affecting basal ganglia, thalami and periventricular white matter. What is New:• In such patients, early MRI including quantitative ADC measurements over different brain regions may allow for detection of signal alterations possibly reflecting microstructural changes in such patients.

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Neurological Involvement in Pediatric Hemolytic Uremic Syndrome: A Symptom-Oriented Analysis

Cited by 4 publications

References 30 publications

Roles of Shiga Toxins in Immunopathology

Roles of Shiga Toxins in Immunopathology

A portable and high-sensitivity optical sensing system for detecting fluorescently labeled enterohaemorrhagic Escherichia coli Shiga toxin 2B-subunit

Cerebral microstructural changes in children suffering from hemolytic uremic syndrome

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