Pediatric stroke in inborn errors of metabolism: clinical characteristics, neuroimaging features, and short-term outcomes
TL;DR
IEM represent an important and potentially treatable cause of pediatric stroke, particularly in populations with high consanguinity, and recognition of characteristic clinical features, distinctive MRI patterns, and supportive EEG findings can facilitate early diagnosis.
Abstract
Introduction Pediatric stroke has a broad etiological spectrum, with inborn errors of metabolism (IEM) increasingly recognized as an important and potentially treatable cause. This study aimed to characterize the clinical, radiological, and electroencephalographic features of IEM-related pediatric stroke and to evaluate short-term functional outcomes. Methods This prospective cohort study was conducted at The Children’s Hospital Lahore, Pakistan, and Sultan Qaboos University Hospital, Muscat, Oman (January 2024–December 2025). Children with confirmed stroke secondary to IEM were enrolled. Functional outcome was assessed at 3 months using the modified Rankin Scale (mRS), with scores 0–3 defined as favorable and 4–6 as unfavorable. Results Forty-four patients were included (59.1% male), with a mean age of 4.6 ± 4.2 years. Focal neurological deficits and encephalopathy were the most frequent presentations. Mitochondrial disorders and homocystinuria were the leading etiologies. MRI demonstrated heterogeneous patterns, most commonly focal ischemic lesions and brainstem–striatal involvement. Management included mitochondrial cocktails, vitamin therapy, and targeted metabolic treatments. Poorer outcomes (mRS 4–6) were associated with generalized epileptiform discharges with diffuse slowing on EEG, whereas favorable outcomes correlated with focal epileptiform discharges or normal EEG findings (p = 0.00018). Outcomes also varied by etiology, with homocystinuria and mitochondrial complex I deficiency associated with better recovery and Leigh disease and glutaric aciduria with worse prognosis (p = 0.041). Conclusion IEM represent an important and potentially treatable cause of pediatric stroke, particularly in populations with high consanguinity. Recognition of characteristic clinical features, distinctive MRI patterns, and supportive EEG findings can facilitate early diagnosis. Prompt metabolic and genetic evaluation is essential to guide targeted therapy and improve outcomes.