Neuropathology of epilepsy

Epilepsy is one of the most common neurologic disorders, affecting about 50 million people worldwide. The disease is characterized by recurrent seizures, which are due to aberrant neuronal networks resulting in synchronous discharges. The term epilepsy encompasses a large spectrum of syndromes and diseases with different etiopathogenesis. The recent development of imaging and epilepsy surgery techniques is now enabling the identification of structural abnormalities that are part of the epileptic network, and the removal of these lesions may result in control of seizures. Access of this clinically well-characterized neurosurgical material has provided neuropathologists with the opportunity to study a variety of structural brain abnormalities associated with epilepsy, by combining traditional routine histopathologic methods with molecular genetics and functional analysis of the resected tissue. This approach has contributed greatly to a better diagnosis and classification of these structural lesions, and has provided important new insights into their pathogenesis and epileptogenesis. The present chapter provides a detailed description of the large spectrum of histopathologic findings encountered in epilepsy surgery patients, addressing in particular the nonneoplastic pathologies, including hippocampal sclerosis, malformations of cortical development, Sturge-Weber syndrome, and Rasmussen encephalitis, and reviews current knowledge regarding the underlying molecular pathomechanisms and cellular mechanisms mediating hyperexcitability.