Postmortem MRI reveals distinct structural features in sudden unexpected death in epilepsy

Magnetic resonance imaging (MRI) abnormalities have been reported in individuals who later die from sudden unexpected death in epilepsy (SUDEP), but their specificity and predictive value remain uncertain. Postmortem MRI (PM-MRI) offers a unique opportunity to distinguish structural features associated with SUDEP from changes related to epilepsy, comorbid illness, or the postmortem interval. We performed PM-MRI in nine individuals: five with suspected SUDEP, two with epilepsy who died from non-seizure-related causes, and two without epilepsy who died from sudden cardiac death. Hippocampal, amygdala, and subcortical volumes were quantified using validated segmentation methods and compared with 70 healthy in vivo controls. Compared with non-SUDEP cases, SUDEP cases showed significantly larger hippocampal (p = 0.014) and amygdala (p = 0.023) volumes, with most exceeding the healthy control mean, whereas non-SUDEP cases consistently demonstrated volume reductions. These findings parallel in vivo MRI observations in individuals at high risk of SUDEP and are consistent with transient peri- or postictal structural changes. In the context of recent large-scale studies showing few validated clinical SUDEP biomarkers beyond frequent generalized tonic-clonic seizures and sleeping alone, PM-MRI may provide an objective approach to positively identifying individuals who died from SUDEP. PLAIN LANGUAGE SUMMARY: We used magnetic resonance imaging (MRI) scans taken after death to study brain changes in people who died from sudden unexpected death in epilepsy (SUDEP). We found that certain brain areas involved in seizure control and automatic body functions, such as breathing and heart rate, were larger in people who died from SUDEP than in people who died from other causes. These changes were similar to those previously seen on brain scans of people with epilepsy who are known to be at higher risk of SUDEP while they were still alive. Our findings suggest that postmortem MRI may help identify brain changes linked to SUDEP.