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KEY CONCEPTS

KEY CONCEPTS

  • A seizure is a transient alteration in behavior or perception caused by abnormal synchronous firing of large ensembles of neurons in the brain. Epilepsy refers to a collection of diverse disorders that are characterized by an enduring predisposition to repeated seizures.

  • Epileptic activity in the brain can be detected by the electroencephalogram (EEG), a noninvasive test that records electrical activity from numerous surface electrodes on the scalp.

  • At onset, hypersynchronous neuronal activity in focal seizures remains confined largely to a specific brain region within one hemisphere of the brain. In contrast, generalized seizures refer to those that rapidly engage a bilateral network of numerous brain regions.

  • Seizures typically occur because of a focal or more generalized imbalance between excitatory and inhibitory synaptic processes in the brain. This change can be caused by any number of different developmental abnormalities as well as acquired brain insults, including tumors, strokes, head injury, and autoimmune processes.

  • An area of the brain that generates epileptic activity is called a seizure focus. Such epileptic activity can remain localized or spread and become generalized.

  • While many monogenic causes of epilepsy have been identified and characterized, in most patients, the inheritance of epilepsy is complex and polygenic.

  • Most anticonvulsants work by suppressing the function of Na+ or Ca2+ channels or by enhancing GABA–mediated inhibitory synaptic transmission.

  • Other known actions of a smaller number of anticonvulsants include potentiation of K+ channels or inhibition of glutamatergic transmission mediated through several mechanisms including decreased glutamate release via binding a synaptic vesicle–associated protein termed synaptic vesicle protein 2A (SV2A).

  • Other therapeutic targets not involving ion channels or glutamatergic and GABAergic neurotransmission include cannabidiol (CBD), which has been approved for the specific treatment of seizures in patients with Lennox–Gastaut syndrome and Dravet syndrome.

This chapter is devoted to epilepsy and its pharmacologic treatments. Epilepsy or “the epilepsies” refer to an etiologically heterogeneous group of neurologic disorders that are characterized by the enduring predisposition to develop seizures. Epileptic seizures are stereotyped and paroxysmal alterations in behavior or perceptions that feature excessive and hypersynchronous firing of sets of neurons in the brain. Seizures themselves are common: approximately 5% to 10% of people will experience at least one seizure in their lifetimes. In contrast, roughly 1 in 26 individuals will develop epilepsy. The treatment of epileptic seizures has steadily improved with the introduction of several new categories of medications with better side effect profiles. However, close to one-third of individuals with epilepsy are not fully treated with the range of medications available today and there is not yet a consensus as to whether the newer antiepileptic medications are more effective than older agents. There has also been the increased application of neurosurgical interventions for patients with medication–refractory illness.

SEIZURES AND EPILEPSY

As a first approximation, the precise behavioral or perceptual disturbances associated with a given seizure are directly related ...

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