Abstracts

Rationale: The symptoms in witnessed Sudden Unexplained Death in Epilepsy (SUDEP) suggest a breakdown of the central autonomic control. A previous MR study found evidence for structural damage in the mesencephalon in focal epilepsy that was more severe and extended into the lower brainstem in two patients who later died of SUDEP. Mesencephalon and medulla oblongata are both involved in autonomic control. The purpose of this study was 1. to expand the previous study by demonstrating an association between brainstem damage in focal epilepsy and reduced heart rate variability (HRV) as a proxy of autonomic control. 2. to replicate the findings of more extensive brainstem damage in a larger population of SUDEP patients. Methods: Two populations were studied: 1. Autonomic population (18 patients with focal epilepsy, 11 controls) with HRV measurements and standardized 3T MR exams. 2. SUDEP population (27 SUDEP epilepsy patients) with clinical MRI 1-10 years before SUDEP. Deformation-based morphometry of the brainstem was used to generate profile similarity maps from the resulting Jacobian determinant maps that were further characterized by graph analysis to identify regions with excessive expansion (sigExcROIs). Results: The total sigExcROIs counts in the autonomic population were negatively correlated with HRV (r=-0.37, p=0.03), sigExcROis counts in periventricular gray/medulla oblongata autonomic nuclei explained most of the HRV associated variation (r/r2=-0.82/0.67, p2=-0.60/0.35,p=0.001). Conclusions: These findings confirm those of the previous study and suggest that MRI can detect potentially life threatening brainstem damage years before SUDEP and thus might be used as biomarker to identify patients at risk of SUDEP due to epilepsy-associated brainstem m damage. Funding: Supported by U01NS090406-02 to AMG and UCSF REAC and Epilepsy Foundation award 325981 to SGM