Abstracts

Rationale: Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF), is caused by mutations in the LG1 gene, believed to be involved in neuronal migration, in approximately 50% of families. Ictal events include auditory phenomena, such as formed or unformed sounds, distortions, and sensory aphasia, and complex partial and secondary generalized tonic-clonic seizures, suggesting dominant temporal lobe pathology. We used functional magnetic resonance imaging to investigate auditory and verbal processing in ADPEAF. Methods: We studied eight patients from seven families with ADPEAF and 15 unrelated controls, using a GE Signa 3T scanner, with a gradient echo-planar sequence. Each subject had 3D fast SPGR anatomical images. All subjects were right-handed. Monitored activation paradigms included an auditory description decision task (ADDT), and a rising/falling musical tone discrimination task. Control conditions were reverse speech for auditory description decision, and silent rest for tone discrimination. Images were realigned, normalized, smoothed to 8 mm and analyzed with SPM2. Results were examined at p< 0.05 corrected for multiple comparisons, and at p< 0.001 uncorrected. Results: Controls showed bilateral fronto-temporal activation during tone discrimination, and predominantly left temporal and inferior frontal activation on ADDT. Patients had decreased activation compared to normal controls on both tasks, although the effect was more marked on the auditory description decision task, where normal left posterior temporal activation was not seen, even at reduced statistical thresholds. In individual patients, activation was reduced, or displaced from control localizations. Structural MRI showed no abnormalities. Patient’s seizures were well-controlled on a variety of antiepileptic drugs (AEDs). Conclusions: Our data suggest that patients with ADPEAF have disturbed functional anatomy for auditory processing. Possible AED effects cannot be excluded, but are not seen in other TLE populations. However, the LGI1 mutation may lead to cortical dysfunction in the absence of structural changes.