Concomitant Fractional Anisotropy and Volumetric Abnormalities in Temporal Lobe Epilepsy: Cross-Sectional Evidence for Progressive Neurologic Injury

Abstract

BackgroundIn patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI).Methodology/Principal FindingsFor 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures.Conclusions/SignificanceChronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.

Quantitative relaxometry and diffusion MRI for lateralization in MTS and non-MTS temporal lobe epilepsy

“…Asymmetry in DTI findings was also found in other recent studies (Shon et al, 2010, Kemmotsu et al, 2011, Keller et al, 2012, with both MTS and non-MTS patients with left seizure onset having more significant and more widespread abnormalities, including atrophy, than right-onset patients.…”

“…These differences between LTLE and RTLE have been speculated to be due to greater vulnerability of the left hemisphere to early injury and the progressive effects of seizures (Kemmotsu et al, 2011), or a combination of architectural, connectivity, physiological and developmental differences between the hemispheres (Keller et al, 2012), however, further studies are required to investigate the cause of this asymmetry.…”

A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy

“…In 18 of the latter (47.4%), 14,16,[20][21][22]24,30,[33][34][35][36][37][38]40,42,[50][51][52] no statistical approaches were implemented to correct for the effects of age. Although the remaining studies addressed aging, no consistent method was chosen: 3 reported no significant effects of age on morphometric measures in controls, 15,32,48 3 found no effect of age or no effect of age at epilepsy onset in patients, 19,29,53 2 corrected for age at onset, 18,28 5 corrected for age in patients, 17,26,47,49,54 4 utilized MRI measures adjusted for age 13,31,39,46 (based on regression models derived from controls), 1 calculated epilepsy duration/age ratios, 23 2 statistically compared chronological age effects between patients and controls. 41,45 Among the longitudinal studies, 3 were singlecohort studies of patients without controls (interscan interval ranging from 2.3 to 3.4 years 27,41,44 ).…”

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes

“…This is a new finding and suggests that left TLE may be associated with a bihemispheric hippocampal subfield alterations in these particular regions compared with right TLE, who showed evidence of reduced volumes in the contralateral hippocampal tail relative to patients with left TLE. There is an inconsistent literature on the effects of TLE laterality on the distribution of brain damage, with some indicating increasingly bilateral changes in left TLE,36, 37 in right TLE35, 38 and some studies suggesting equivalence 39. Just one of these studies39 has entered the hippocampal asymmetry (right>left) found in healthy controls14 as a confounding factor during statistical analysis.…”

“…In the absence of longitudinal data, cross‐sectional studies have correlated brain compartment volume with duration of epilepsy as a surrogate marker of progressive damage due to seizure chronicity. There is inconsistency in the literature with respect to relationships between hippocampal and extrahippocampal volume loss and duration of TLE 7, 10, 11, 36. Given that duration of epilepsy and chronological age are related, it is important to correct clinical correlations for patient age to determine whether brain atrophy is driven by epilepsy‐related factors or normal age‐related maturation.…”