Abstracts

Rationale: Endophenotypes are heritable traits with a simpler genetic basis than a full disorder and may be present in family members who do not have the disease.(1) Endophenotypes can help increase our understanding of the pathophysiology of complex genetic disorders, including idiopathic epilepsy syndromes. Patients with idiopathic generalised epilepsy (IGE) have been shown to have subtle bilateral subcortical abnormalities, particularly of thalamus,(2, 3) which may be related to the generation of spike-and-wave discharges.(4) In order to identify a potential neuroanatomical endophenotype in IGE, we sought to investigate whether asymptomatic first-degree relatives show evidence of a similar topology of subcortical atrophy as patients with IGE compared to unrelated healthy controls using MRI techniques.Methods: We recruited 30 patients with IGE (mean age 30.6 yrs), 36 of their asymptomatic first-degree relatives (mean age 35.2 yrs) and 40 (mean age 30.8 yrs) healthy controls for MR imaging. 3D T1-weighted (IR-SPGR) images acquired on a 3 Tesla GE Signa HDx MR system were analysed using FSL FIRST tools, which (i) automatically segmented the thalamus, putamen, caudate and hippocampus in both cerebral hemispheres, (ii) parameterised volumetric labels (meshes) from the deformable surfaces of structures, and (iii) permitted vertex-wise shape analyses along the surface of the segmented structures. Comparisons were made between patients with IGE and controls, relatives and controls, and patients with IGE and their relatives separately.Results: Compared to controls, patients and relatives had significant deflation - a proxy for atrophy - encompassing a strikingly common topology across dorsal and ventral thalamic and putamenal regions in both hemispheres (Fig 1). No differences were observed in the caudate or hippocampus. No significant differences were observed when patients and relatives were compared directly, and there was no regional deflation observed in controls compared to patients and relatives.Conclusions: Both patients with IGE and their asymptomatic first-degree relatives show evidence of a similar topology of subcortical atrophy compared to healthy controls. This atrophy occurs bilaterally - in keeping with the generalised nature of IGE - and of structures thought to be crucial for bihemispheric accentuated epileptiform discharges, the modulation of seizure activity and the propagation of seizures throughout the brain.(5, 6) References 1.Gottesman, II. The American journal of psychiatry. 2003;160:636. 2.Kim JH. Neuroimage. 2007;37:1132. 3.Kim JH. Journal of neurology. 2013. 4.Tyvaert L. Neurology. 2009;73:2018. 5.Dreifuss S. Neurology. 2001;57:1636. 6.Du H. J Magn Reson Imaging. 2011;33:817.