Abstracts

Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a form of idiopathic lateral temporal lobe epilepsy frequently caused by mutations in the leucine-rich, glioma inactivated 1 ([italic]LGI1[/italic]) gene. Subjects with epilepsy in families with [italic]LGI1[/italic] mutations have not generally been found to have mesial temporal sclerosis or other structural brain abnormalities detected on MRI. However, in one previously reported family with an [italic]LGI1 [/italic]mutation, a lateral temporal malformation was identified in 10 individuals. This result was important because it strongly supported the concept that [italic]LGI1[/italic] influences risk through a neurodevelopmental mechanism. We attempted to replicate these findings in other families., We studied 15 subjects (10 affected, 2 clinically unaffected mutation carriers, 3 unaffected non-carriers) from six ADPEAF families, each of which had a different [italic]LGI1 [/italic]mutation. Subjects underwent high-resolution structural MRI on a Philips 3-tesla scanner, including MPRAGe, FLAIR, t1 and t2 sequences, and neuropsychological testing with a special emphasis on language measures. MRIs were analyzed by radiologists blinded to clinical and genetic data., Subjects ranged in age from 20-81 years; nine were male and six female; and education ranged from 13-21 years. These factors were similar in affected and unaffected subjects. We found no evidence of mesial temporal sclerosis, malformations of cortical development, or abnormal gyral patterns in any of the 15 subjects. One affected individual (age 63) had bilateral T2 increases, and two unaffected subjects, neither of whom carried a mutation, had incidental findings thought to be unrelated to epilepsy (a bifrontal white matter abnormality, and marginally lower right temporal neocortical volume). Verbal IQ scores were significantly lower in subjects with epilepsy than in those without epilepsy (ave. 108 vs. 124, p=0.012). Among subjects without epilepsy, however, verbal IQ was similar in subjects who carried a mutation (ave.=124) and those who did not (ave.=125), suggesting that the difference in verbal IQ was more likely to be due to epilepsy or its treatment than to the mutation [italic]per se[/italic]. In contrast, average scores for the oral word association test were lower both in subjects with epilepsy (94) and clinically unaffected mutation carriers (95) than in noncarriers (120) (p=0.048)., The results of this study do not support the previously reported association of [italic]LGI1 [/italic]mutations with a structural brain abnormality detectable on high-resolution MRI. Although the number of subjects tested is small, findings from the oral word association test may reflect an impact of mutations on language function., (Supported by NIH R01 NS36319 and the NINDS Division of Intramural Research.)