Abstracts

Rationale: Epileptic seizures can alter autonomic regulation, eliciting changes in blood pressure or cardiac rhythm, particularly when seizures propagate to autonomic regulatory areas such as the insula or cingulate cortex. Generalized Tonic-Clonic seizures (GTCs) are a consistent risk factor for Sudden Unexpected Death in Epilepsy (SUDEP), possibly arising from exaggerated autonomic changes, leading to outcomes such as impaired baroreflex sensitivity following the GTC, interfering with recovery from post-ictal hypotension, or eliciting of fatal arrhythmia. We examined, using MRI-based texture analysis regions for altered tissue homogeneity/entropy, with decreased values indicative of neuronal swelling and typically inflammatory processes, and increased values commonly associated with injury in GTC patients relative to healthy controls. Methods: Subjects were 53 patients with GTCs (from sites at Case Western Reserve, University College London, and University of California at Los Angeles) and 53 age- and gender-matched healthy controls (University of California at Los Angeles). High resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner, and images were bias-corrected. Entropy maps were calculated, normalized to a common space, smoothed, and compared between GTC and healthy control groups using ANCOVA (SPM12, family-wise error correction for multiple comparison, p < 0.01, covariates: age & sex). Results: Decreased entropy values, indicative of increased tissue homogeneity and neuronal swelling, appeared bilaterally throughout mid- and posterior- insular cortex and posterior cingulate. However, anterior insular gyri did not show signs of neuronal swelling, nor did the anterior cingulate, to which it is functionally connected. Bilaterally symmetrical increases in tissue homogeneity appeared in other autonomic regulatory areas, such as the ventromedial prefrontal cortex, caudal medulla, and deep cerebellar nuclei. Conclusions: The bilaterally symmetrical sparing of presumably inflammatory action on anterior insular and cingulate regions, sites which are significantly involved in autonomic regulation, and especially baroreceptor gain, was remarkable, considering the significant changes in other autonomic regions; the remaining autonomic regions (ventromedial frontal cortex, cerebellum, medullary sites) showed pronounced changes. Both the posterior insula and cingulate also showed decreased entropy; the posterior insula is especially involved in oxygen and somatosensory integration. The paucity of acute changes in the anterior insula and anterior cingulate suggests that more-posterior areas of these two structures, interacting with critical frontal cortex, cerebellar, and medullary regions underlie potential autonomic alterations in GTC. Funding: Supported by the National Institute of Neurological Disorders and Stroke NS090407.