Neurological Manifestations of Hemolytic Uremic Syndrome: A Comprehensive Review

Abstract

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications.

Keywords: STEC-HUS; atypical HUS; biomarkers; hemolytic uremic syndrome; nephrology; neuroimaging; pediatric neurology; thrombotic microangiopathy.

Figure 1

Shiga toxin-induced endothelial injury leading to cerebral microvascular thrombosis and ischemia. Created in BioRender online application, available at https://app.biorender.com/ (accessed on 10 June 2025).

Figure 2

Diagnostic workup in HUS with neurological manifestations. A stepwise algorithm outlining the evaluation of HUS patients with neurological symptoms, including clinical assessment, laboratory testing, neuroimaging, complement studies, genetic analysis, and final diagnostic differentiation between STEC-HUS and aHUS. Created in BioRender online application, available at https://app.biorender.com/ (accessed on 10 June 2025).