Pathophysiology of epilepsy

This work reviews the current knowledge on epileptogenesis and pathophysiology of epilepsy. Recently, gene defects underlying four monogenic epilepsies (generalized epilepsy with febrile seizures, autosomal dominant nocturnal frontal lobe epilepsy, benign familial neonatal convulsions and episodic ataxia type 1 with partial seizures) have been identified, shedding new light on the pathophysiology of epilepsy as these diseases are caused by ion channel mutations. Although epileptic syndromes differ pathophysiologically, common ictogenesis-related characteristics as increased neuronal excitability and synchronicity are shared as well as mechanisms involved in interictal-ictal transition. Emerging insights point to alterations of synaptic functions and intrinsic properties of neurons as common mechanisms underlying hyperexcitability. This work also reviews the neurochemical mechanisms of epilepsy. An imbalance between glutamate and gamma-aminobutyric acid neurotransmitter systems can lead to hyperexcitability but catecholaminergic neurotransmitter systems and opioid peptides were shown to play a role in epileptogenesis as well. An overview of currently available anti-epileptic drugs and their presumed mechanisms of action is given as an illustration of the neurochemistry of epileptogenesis. Most anti-epileptic drugs exert their anti-epileptic properties through only a few neurochemical mechanisms that are meanwhile basic pathophysiological mechanisms thought to cause seizures.