Abstracts

Although the heritability of epilepsy may be up to 70%, the complexity of genetic interactions has meant that gene association studies have been so far unrevealing. Finding intermediate biological markers or endophenotypes has the potential to provide important predisposing genetic information.
QMRI-based assessment of brain structures, such as volumetric and surface area analysis can provide endophenotypic information as a quantitative trait and can thus enhance the yield from gene association studies. In particular QMRI can provide structural information from brains that otherwise appear qualitatively normal.
The aim of this work was to demonstrate a suite of QMRI measures which may be used to provide endophenotypic analysis in epilepsy., Forty patients with temporal lobe epilepsy (TLE) who have attended the epilepsy service at Beaumont Hospital, Dublin and whose qualitative brain MRI is normal, were included in this study. QMRI data of twenty control subjects with no neurological deficit provided normative ranges for the study.
Using stereology, a mathematically unbiased and time efficient technique, the following MRI-based measurements were made for each subject: hippocampal volume, entorhinal cortex volume, cerebral volume and surface area, intra-cranial volume, cortical grey matter volume and cerebral white matter volume. From these measures, ratios were used to assess the degree of atrophy of structures as well as the degree of cortical folding., After correction for sex and head size, results revealed sixty percent of patients had cerebral atrophy, and thirty percent had cerebellar atrophy. Thrity percent of patients had an abnormal ratio of grey to white matter (cerebrum and cerebellum). For the mesial temporal structures, forty percent of patients had hippocampal atrophy (left and right), and twenty percent had entorhinal cortex atrophy (left and right). Twenty percent of patients had a reduced cerebral surface area, and twenty percent had an abnormal index of cerebral folding., Quantitative analysis of cerebral structures can enhance the yield of MR brain imaging by providing endophenotypic structural information as quantitative traits. Such information has the potential to be extremely valuable for improving the yield from gene association studies in epilepsy., (Supported by Royal College of Surgeons in Ireland Research Committee, Health Research Board and the Higher Education Authority of Ireland.)