Abstracts

Rationale: The thalamus plays an important role in the modulation and propagation of seizure activity. Recent neuroimaging studies have found reduced thalamus volume in juvenile myoclonic epilepsy (JME). However, the spatial pattern of this atrophy has not been reported and the goal of the current study is to characterize the distribution of thalamic atrophy in recent-onset JME. Using three-dimensional shape analysis, the study aims to test two alternative hypotheses: 1) If the overall pattern of volume reduction in JME is nonspecific, then the distribution of thalamic atrophy should be spread throughout the structure. 2) If thalamic atrophy patterns reflect disruption of specific fronto-thalamic-striatal circuits, then atrophy should be localized to specific regions of the thalamus. Methods: T1 weighted SPGR images were obtained on a 1.5 Telsa GE Sigma scanner (TR 24 ms, TE 5 ms, slice thickness 1.5 mm) in 21 individuals with recent-onset JME (age = 15.8 /- 3.0 years; epilepsy duration = 8.5 /- 3.7 months) and 54 healthy controls (HC, age = 13.3 /- 3 years). Automated segmentation of the thalamus was performed using FIRST (part of FSL, http://www.fmrib.ox.ac.uk/fsl), which is a model-based segmentation tool that searches through linear combinations of shape modes of variation for the most likely shape, based on T1 image intensity. The automated segmentation process produces binarized masks of each subject s thalamus. Total thalamus volumes from each subject were calculated from these masks and then normalized to total intracranial volume (ICV). Second, the automated segmentation also generates a deformable mesh of vertices composed of a set of triangles. The relative position of each corresponding vertex is then compared between JME subjects and healthy controls in order to determine the specific regions of atrophy. Thalamus three-dimensional shape analysis was carried out using F-statistics and multiple comparisons were corrected with false discovery rate. Results: Thalamus volume was analyzed by ANCOVA (ICV as covariate). There was a significant difference between groups (F = 8.616, p = 0.005) with the JME group exhibiting significantly smaller thalamic volume (mean = 15027.4 cm3, sd= 1641.2) compared to the controls (mean= 15795.2 cm3, sd= 1291.2). Three-dimensional shape analyses (see figure)showed the thalamus to be affected bilaterally in the regions of the anterior nuclei, mediodorsal nuclei, and pulvinar. Unilateral effects were observed in the right ventrolateral and ventroanterior nuclei. Conclusions: This study demonstrates that thalamic atrophy in JME is selective in nature, affecting the anterior nuclei, mediodorsal nuclei, and pulvinar bilaterally, with unilateral effects in the right ventrolateral and ventroanterior nuclei. Disturbances in thalamic circuitry are evident in this group of JME patients early in the course of their epilepsy. The specific neurobehavioral consequences of this disrupted circuitry remain to be determined. Supported by NIH 2RO1-44351