Voxel-based morphometry (VBM) in unilateral mesial temporal lobe epilepsy (mTLE): Volume loss beyond the seizure onset zone and neuropsychological implications

Recent studies in mTLE showed by means of EEG, MRI and FDG-PET structural or functional abnormalities outside the seizure onset-zone. Recent voxel-based morphometry (VBM)-studies were able to show hippocampal degeneration in mesial temporal lobe epilepsy (mTLE) patients, however, there was also marked extrahippocampal loss of brain volume. This VBM-study aimed to depict volume loss outside the seizure focus and to correlate neuropsychological deficits.

Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from two groups were performed. We applied an optimized VBM protocol on high resolution T1 weighted MR-images of 25 patients (m:w=16:9; mean age=41±13 a, l:r=15:10) with unilateral TLE in comparison to 50 age and gender matched healthy controls. Age at onset was 14±12 a. 10 had a history of febrile seizures. Diagnosis for unilateral TLE was confirmed by video-EEG-monitoring, MRI, interictal FDG-PET, and neuropsychology. The only structural abnormality in MRI was unilateral hippocampal atrophy and sclerosis.

Most prominent atrophy was found ipsilateral in the hippocampus. In left TLE additional volume loss was found ipsilateral in the parahippocampal gyrus, the cingulate gyrus, the thalamus, and some frontoconvex areas. Bilateral volume loss was evident in the thalamus and frontomesial. In right TLE we found aditional ipsilateral volume loss in the parahippocampal gyrus and cingulate gyrus. Bilateral volume loss was found in the thalamus, the cerebellar hemispheres, frontomesial and frontobasal. For certain regions we were able to find a correlation between duration of disease and degree of atrophy. Furthermore, for left TLE patients we could correlate neuropsychological deficits to certain locations of atrophy.

Our study confirms a widespread structural change in unilateral mTLE ipsilateral and contralateral to the side of seizure onset, which is far beyond the primary lesion and may reflect acquired neuronal damage due to repetitive seizure activity. Since there is no significant difference in clinical data between left and right mTLE the side of seizure onset might be relevant for volume loss additional to that at the onset zone. Further investigations are needed to clarify if the seizure type influences the distribution of volume loss, and how neurolopsychological deficits reflect a consequence of volume loss. However, this results show that mTLE is – in a chronic state – a widespread rather than a focal disease.