White matter in temporal lobe epilepsy: clinico-pathological correlates of water diffusion abnormalities

Using magnetic resonance imaging, it is possible to measure the behavior of diffusing water molecules, and the metrics derived can be used as indirect markers of tissue micro-architectural properties. Numerous reports have demonstrated that patients with temporal lobe epilepsy (TLE) have water diffusion abnormalities in several white matter structures located within and beyond the epileptogenic temporal lobe, showing that TLE is not a focal disorder, but rather a brain network disease. Differences in severity and spatial extent between patients with or without mesial temporal sclerosis (MTS), as well as differences related to hemispheric seizure onset, are suggestive of different pathophysiological mechanisms behind different forms of TLE, which in turn result in specific cognitive disabilities. The biological interpretation of diffusion abnormalities is based on a wealth of information from animal models of white matter damage, and is supported by recent reports that directly correlate diffusion metrics with histological characteristics of surgical specimens of TLE patients. Thus, there is now more evidence showing that the increased mean diffusivity (MD) and concomitant reductions of diffusion anisotropy that are frequently observed in several white matter bundles in TLE patients reflect reduced axonal density (increased extra-axonal space) due to smaller-caliber axons, and abnormalities in the myelin sheaths of the remaining axons. Whether these histological and diffusion features are a predisposing factor for epilepsy or secondary to seizures is still uncertain; some reports suggest the latter. This article summarizes recent findings in this field and provides a synopsis of the histological features seen most frequently in post-surgical specimens of TLE patients in an effort to aid the interpretation of white matter diffusion abnormalities.