Sudden unexpected death in autism (SUDA) represents a significant mortality risk in autism spectrum disorder (ASD), with a substantial proportion of cases remaining classified as undetermined despite comprehensive autopsy. Recent clinical evidence (2024-2025) documents thiamine deficiency presenting as cardiac arrest in ASD children with severe restrictive eating. We propose that chronic nutritional myelinopathy (CNM)-a distinct entity from acute central pontine myelinolysis-may contribute to a subset of these deaths through progressive brainstem demyelination.We conducted a systematic literature synthesis of clinical case reports of thiamine deficiency in ASD populations (2020-2025), autopsy studies of nutritional myelinopathy, neuropathological literature on thiamine-dependent myelination, and SUDA case characteristics. We developed diagnostic criteria distinguishing CNM from acute osmotic demyelination and proposed enhanced forensic investigation protocols.Recent clinical evidence documented critical thiamine deficiency in ASD children with severe ARFID, including cases presenting with cardiac arrest. Systematic reviews of 63 articles confirmed thiamine deficiency prevalence in autism populations with self-imposed dietary restrictions. Autopsy studies demonstrate that chronic thiamine deficiency produces diffuse brainstem myelin pallor with increased immature oligodendrocytes-distinct from the geographic demyelination of acute central pontine myelinolysis. We propose specific histopathological criteria (diffuse myelin pallor on Luxol Fast Blue, preserved axons, increased Olig2+ oligodendrocytes, minimal CD68+ macrophages) and clinical prodrome (gait abnormality, unexplained weight loss, autonomic instability).CNM may represent a previously underrecognized mechanism contributing to a subset of SUDA deaths in ASD individuals with severe restrictive eating. Enhanced brainstem histopathology using myelin-specific staining could identify CNM in a subset of currently undetermined cases, enabling preventive intervention in high-risk living patients.
Zamani Klass (Fri,) studied this question.