Abstracts

Rationale: Initially described almost two decades ago, familial mesial temporal lobe epilepsy provided the first strong evidence for genetics playing an important role in the etiology of temporal lobe epilepsy, traditionally regarded as a predominantly acquired disorder. Whilst genes for the rarer autosomal-dominant lateral temporal lobe epilepsy have been identified, the causes of familial mesial temporal lobe epilepsy remain largely unknown. It is also uncertain how common this syndrome is amongst patients presenting with mesial temporal lobe epilepsy. Here, we investigated its frequency in a cohort of patients with newly diagnosed mesial temporal lobe epilepsy.Methods: We performed a prospective study of consecutive consenting patients receiving a diagnosis of non-lesional mesial temporal lobe epilepsy at the Austin Health First Seizure Clinic between January 2005 and January 2012. Probands were required to have no epileptogenic lesion on brain MRI, except for hippocampal sclerosis. All available first-degree relatives of enrolled patients underwent a structured interview using a validated epilepsy questionnaire, irrespective of whether epilepsy was suspected. Efforts were made to obtain previous EEG and neuroimaging investigations, as well as physician letters and hospital records.Results: Thirty-six probands were enrolled [23 women; median age (range): 35 (18-73) years]. Thirty-three probands had no epileptogenic lesion on brain MRI, and three had hippocampal sclerosis. Six probands (17%; none with hippocampal sclerosis) had a family history of mesial temporal lobe epilepsy in first-degree relatives. Of these, five had one affected first-degree relative and one patient had two. Notably, prior to study enrolment, only one patient had reported a family history of mesial temporal lobe epilepsy in first-degree relatives. Two patients had reported first-degree relatives with “epilepsy”, and three were unaware of their family history. The seizure semiology in the affected relatives of the three probands who were unaware of their family history consisted of experiential phenomena, such as intense déjà vu, fear and dream-like state, and/or viscerosensory symptoms, at times progressing to brief loss of awareness without witnessed convulsion. There were an additional nine cases (25%) with a family history of other forms of epilepsy, single seizures or febrile seizures.Conclusions: Familial mesial temporal lobe epilepsy is a common genetic syndrome, affecting approximately one in six patients with newly diagnosed mesial temporal lobe epilepsy. It is also largely undiagnosed, possibly due to its mild nature, emphasizing the need to obtain a detailed epilepsy history directly from other family members.