Microstructural white matter abnormality and frontal cognitive dysfunctions in juvenile myoclonic epilepsy

Previous neuroimaging studies provide growing evidence that patients with juvenile myoclonic epilepsy (JME) have both structural and functional abnormalities of the thalamus and frontal lobe gray matter. However, limited data are available regarding the issue of white matter (WM) involvement, making the microstructural WM changes in JME largely unknown. In the present study we investigated changes of WM integrity in patients with JME, and their relationships with cognitive functions and epilepsy-specific clinical factors.

We performed diffusion tensor imaging (DTI) and neuropsychological assessment in 25 patients with JME and 30 control subjects matched for age, gender, and education level. Between-group comparisons of fractional anisotropy (FA) and mean diffusivity (MD) were carried out in a whole-brain voxel-wise manner by using tract-based spatial statistics (TBSS). In addition, both FA and MD were correlated with cognitive performance and epilepsy-specific clinical variables to investigate the influence of these clinical and cognitive factors on WM integrity changes.

Neuropsychological evaluation revealed that patients with JME had poorer performance than control subjects on most of the frontal function tests. TBSS demonstrated that, compared to controls, patients with JME had significantly reduced FA and increased MD in bilateral anterior and superior corona radiata, genu and body of corpus callosum, and multiple frontal WM tracts. Disease severity, as assessed by the number of generalized tonic-clonic seizures in given years, was negatively correlated with FA and positively correlated with MD extracted from regions of significant differences between patients and controls in TBSS.

Our findings of widespread disturbance of microstructural WM integrity in the frontal lobe and corpus callosum that interconnects frontal cortices could further support the pathophysiologic hypothesis of thalamofrontal network abnormality in JME. These WM abnormalities may implicate frontal cognitive dysfunctions and disease progression in JME.