Is epilepsy a curable neurodegenerative disease?

This scientific commentary refers to ‘Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections’, by Tai et al. (doi:10.1093/brain/aww187) . Temporal lobe epilepsy (TLE) is the most frequent focal epilepsy in adults. The epileptogenic network responsible for seizures encompasses multiple limbic structures including the hippocampus and neighbouring cortices. The histomorphological hallmark of TLE is mesial temporal sclerosis, described originally in post-mortem studies as neuronal loss and gliosis in the hippocampus, entorhinal cortex and amygdala. About a third of patients do not respond to anti-epileptic medication despite continued development of new molecules. Drug-resistant TLE is a serious chronic condition associated with high risk for psychosocial impairment, cognitive decline and mortality. In these patients, surgery is currently the only therapeutic solution to reduce the seizure burden and, in many instances, cure the epilepsy. MRI has been instrumental in TLE surgery by allowing the in vivo detection of neuronal loss and gliosis as indexed by hippocampal atrophy on T1-weighted MRI and increased signal in T2-weighted images. In this issue of Brain , Tai and co-workers provide compelling evidence that long-standing epilepsy is associated with tauopathy, providing a basis for conceptualizing TLE, and possibly all epilepsies, as neurodegenerative disorders (Tai et al. , 2016). In the strictest sense, neurodegeneration refers to pathology affecting neuronal structure and consequently function. In practice, neurodegenerative diseases form an ensemble of conditions with heterogeneous pathological …