Abstracts

Rationale: The causes of SUDEP are still unknown but the respiratory and cardiac symptoms observed in witnessed cases suggest that a breakdown of the central autonomic control system plays an important role. The brainstem is one of the regions that is crucial for the central autonomic control. The objective of this study was therefore to investigate if temporal lobe epilepsy (TLE) is associated with structural damage in the brainstem and if damage involving autonomic brainstem centers can also be found in two TLE who died under circumstances suggestive of SUDEP. Methods: Whole brain T1 images covering the brainstem were obtained from 15 controls (mean age 37.7 11.9) and 28 TLE patients (19 with mesial-temporal-sclerosis (TLE-MTS) mean age 41.7 10.2, and 10 without (TLE-no) mean age 37.9 10.3) on a 4T MRI. Two additional patients (49 y old TLE-no and 39 y old TE-MTS) who died later under circumstances consistent with probable SUDEP had been studied with the same protocol. The brainstem region was extracted from each image by co-registering them to an atlas with a brainstem label. The images from the control group were used to build a brainstem population atlas onto which all images were warped using the DARTEL and the Jacobian determinants calculated from the resulting transformation matrices. SPM8 was used to compare the Jacobian determinant maps (JDM) between controls and each TLE group (FDR<0.05 at cluster level). The Jacobian determinant maps were corrected for ICV differences and converted into z-score maps for single subject analysis.Results: TLE-MTS had significant volume loss in the region of the superior and inferior colliculi and periaqueductal gray that extended into the inferior and medial thalamus. The volume loss in TLE-no did not reach significance. Four TLE-MTS and one TLE-no had evidence for severe brainstem atrophy (mean z-score -2) in those regions in the single subject analyses. The TLE-MTS SUDEP case had extensive volume loss in the ventrolateral medulla and in the parabrachial/K lliker-Fuse and periaqueductal regions. The TLE-no SUDEP patient had atrophy in the periaqueductal gray. Conclusions: The findings of this study show that TLE can be associated with volume loss in brainstem regions involved in autonomic control (periaqueductal gray). The two patients who died of SUDEP had atrophy in the same regions which indicates that brainstem atrophy might constitute a risk factor for SUDEP. Structural damage in brain stem regions involved in autonomic control might increase the risk of a fatal dysregulation during situations with increased demand to the autonomic system such as following severe seizures.