Abstracts

Rationale: The mammillary bodies (MBs) provide an important link between the hypothalamic paraventricular nucleus and medullary nuclei, which serve cardiovascular and respiratory regulation. Damage to the mammillary bodies could compromise cardiovascular and breathing control; both aspects are suspected of playing significant roles in Sudden Unexpected Death in Epilepsy (SUDEP). In addition, the MB also serve essential roles in memory and spatial orientation deficits often seen in patients with epilepsy, and interfere with quality of life. MB volume loss has been mostly described in patients with focal seizures, particularly in temporal lobe epilepsy. However, MB volume has not yet been examined in patients with generalized tonic clonic seizures (GTCs), who are at significantly greater risk for SUDEP. Here we investigate MB volume changes in patients with GTCs. Methods: Whole-brain high-resolution T1-weighted images were collected from 53 patients with GTCs and 53 age- and gender-matched control subjects using a 3.0-Tesla MRI scanner. Subjects were selected from a pool of patients with epilepsy undergoing assessment in the Epilepsy Monitoring Units at Ronald Reagan UCLA Medical Center, University College London, and the University Hospitals Cleveland Medical Center as part of an NINDS Center without Walls, Center for SUDEP Research. A single investigator, blinded to subject group assignment, manually traced left and right structures on image sections containing the MBs, oversampled to a resolution of 0.2 mm x 0.2 mm x 0.2 mm. MB volumes were corrected for overall brain size, and between-group differences were assessed using two-sample t-Tests. Results: When combined, male and female GTC patients showed no significant differences in MB volume over controls. However, male patients with GTCs showed a significant increase in MB volume relative to male controls (Left mean: GTC: 94.6mm3, CON: 71.4 mm3, p3, CON: 70.9 mm3, p < 0.004). The female GTC group showed only a non-significant trend of declines in MB volume over female controls. Conclusions: MB injury presumably results from the consequences of excitotoxic injury from intermittent or sustained hypoxia induced by apneic or ischemic events during seizures. Excessive excitation of the fornix fibers during ictal periods has the potential to elicit such MB injury and, after a period of time, loss of neurons and volume. However, the injurious process normally follows a path which includes initial glial swelling, and thus, increased volumes. Increased MB volumes may result from such glial swelling to hypoxia, a process susceptible to hormonal mechanisms. The findings indicate the importance of assessing injury in the context of gender, since an evaluation which focused only on combined male and female data did not reveal the outcomes here. In addition to possible protection offered by the female sex, the duration of hypoxia exposure likely provides a major factor in the MB neuronal injury time course, a significant concern with the increased risk for SUDEP with duration of GTCs. Funding: National Institute of Neurological Disorders and Stroke U01NS090407