Types and Mechanisms of Epilepsy

Various types of seizure can be recognized on the basis of the nature and distribution of the abnormal discharge. Epileptic seizures are generally classified into focal (partial) and generalized, though there is some overlap and many varieties of each. Partial seizures are those in which the discharges begin locally and often remain localized. The clinical manifestation of focal seizures varies depending on the origin of epileptic discharges (so-called epileptic focus); the attack may involve motor, sensory, autonomic and psychic symptoms. They can be divided into two categories, simple (if consciousness is not lost) or complex (if consciousness is lost, due to the involvement of the reticular formation). The commonest form of focal epilepsies (50-60%) originates from the temporal lobe (TLE), on the basis of mesial temporal (hippocampal) sclerosis, associated with previous complex febrile seizures, or developmental abnormalities and dysembryoplastic neuroepithelioma. Generalized seizures involve the whole brain, including the reticular system, thus producing abnormal electrical activity throughout both hemispheres. Immediate loss of consciousness is characteristic of generalized seizures. Two important categories are tonic-clonic (grand mal) seizures and absence epilepsy. According to the casual aetiology, epilepsy is also classified into idiopathic and symptomatic (Browne and Holmes 2003; Engel 2004; Holmes 2004).

In general, excitation will naturally tend to spread throughout a network of interconnected neurons but is normally prevented from doing so by inhibitory mechanisms. Thus, epileptogenesis can arise if excitatory transmission is facilitated or inhibitory transmission is reduced. In certain respects epileptogenesis resembles long-term potentiation, and similar types of use-dependent synaptic plasticity may be involved (Kullmann et al. 2000). The highly interconnected networks of the mammalian forebrain can generate a wide variety of synchronized activities, including those underlying epileptic seizures, which often appear

Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary

G.Di Giovanni et al. (eds.), 5-HT2C Receptors in the Pathophysiology of CNS Disease, 429

The Receptors 22, DOI 10.1007/978-1-60761-941-3_22, © Springer Science + Business Media, LLC 2011

as a transformation of otherwise normal brain rhythms. The simplest form of epileptiform activity in these structures is the interictal spike, a synchronized burst of action potentials generated by recurrent excitation, followed by a period of hyperpolarization, in a localized pool of pyramidal neurons. Seizures can also be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges, either as clonic or spike wave activity, again mediated by both intrinsic membrane properties and synaptic interactions.

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