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Keywords:

  • classification;
  • mTOR;
  • neuronal precursor;
  • pathomechanisms.

Abstract

Structural abnormalities of the brain are increasingly recognized in patients that suffer from pharmacoresistant focal epilepsies by applying high-resolution imaging techniques. In many of these patients, epilepsy surgery results in control of seizures. Neuropathologically, a broad spectrum of malformations of cortical development (MCD) is observed in respective surgical brain samples. These samples provide a unique basis to further understand underlying pathomechanisms by molecular approaches and develop improved diagnostics and entirely new therapeutic perspectives. Here we provide a comprehensive description of neuropathological findings, available classification systems as well as molecular mechanisms of MCDs. We emphasize the recently published ILEA classification system for focal cortical dysplasias (FCDs), which are now histopathologically distinguished as types I to III. However, this revised classification system represents a major challenge for molecular neuropathologists, as the underlying pathomechanisms in virtually all FCD entities will need to be specified in detail. The fact that only recently, the mammalian target of rapamycin (mTOR)-antagonist Everolimus has been introduced as a treatment of epilepsies in the context of tuberous sclerosis-associated brain lesions is a striking example of a successful translational “bedside to bench and back” approach. Hopefully, the exciting clinico-pathological developments in the field of MCDs will in short term foster further therapeutic breakthroughs for the frequently associated medically refractory epilepsies.