Brain distortions in patients with primarily generalized tonic-clonic seizures

A precondition for the diagnosis of primarily generalized epilepsy with tonic-clonic seizures (GTCS) is absence of brain pathology. This definition, based on normal findings on computed tomography (CT) and magnetic resonance imaging (MRI) is challenged however, by observation of microscopic migrational disturbances in patients with GTCS. In the present study, we examined whether hitherto undiscovered gross manifestations of the reported migrational disturbances may be detected by analysis of CT and MRI scans with a computerized anatomic brain atlas.

The atlas program permitted group comparisons of size, intrinsic proportion, and shape of the brain. Healthy men (n = 20), patients with partial seizures (n = 8), secondarily generalized partial seizures (n = 8), and patients with GTCS (n = 10) were studied. The contours of the brain of the computerized atlas were first transformed and adjusted to the contours, central structures, and ventricles of each subject's MRI scans. During this process, the specific parameters for the shape, size, and proportion of the brain were determined, resulting in a set of values for each subject. These values were then applied for comparisons between the four investigated groups.

In relation to the controls, patients with GTCS had brains significantly flattened in the craniocaudal direction (p = 0.002), with a disproportionally small caudal part. The anterior portion of their brain was also, relatively elongated as compared with the posterior portion (p = 0.04). Similar systematic abnormalities were not observed in patients with partial epilepsy.

The observed deformations are compatible with previously reported findings of Purkinje cell degeneration and frontal lobe microdysgenesis in GTCS. The study suggests a new approach to identify effects of morphologic abnormalities in the brain when results of conventional structural neuroimaging are normal.