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Pathophysiology of seizures and epilepsy

INTRODUCTION

An epileptic seizure is an episode of neurologic dysfunction in which abnormal neuronal firing is manifest clinically by changes in motor control, sensory perception, behavior, and/or autonomic function. Epilepsy is the condition of recurrent spontaneous seizures arising from aberrant electrical activity within the brain. While anyone can experience a seizure under the appropriate pathophysiological conditions, epilepsy suggests an enduring alteration of brain function that facilitates abnormal neuronal firing.

The aberrant electrical activity that underlies epilepsy is the result of biochemical processes at the cellular level promoting neuronal hyperexcitability and neuronal hypersynchrony. However, a single neuron, discharging abnormally, is insufficient to produce a clinical seizure, which occurs only in the context of large neuronal networks. Cortical and several key subcortical structures are involved in generating a seizure.

This topic will review the cellular basis for focal and generalized seizure activity, with specific attention to ion channels, the essential currency of neuronal excitability. The pharmacology of antiepileptic drugs and issues related to the assessment and management of patients with epilepsy is discussed separately. (See "Pharmacology of antiepileptic drugs" and "Overview of the management of epilepsy in adults".)

CLASSIFICATION OF SEIZURES

Epilepsy is not a singular disease, but is heterogeneous in terms of clinical expression, underlying etiologies, and pathophysiology (table 1). As such, specific mechanisms and pathways underlying specific seizure types may vary. Epileptic seizures are broadly classified according to their site of origin and pattern of spread (figure 1).

  • Focal or partial seizures arise from a localized region of the brain and have clinical manifestations that reflect that area of brain. Focal discharges can remain localized or they can spread to nearby cortical areas, to subcortical structures and/or transmit through commissural pathways to involve the whole cortex. The latter sequence describes the secondary generalization of focal seizures. As an example, a seizure arising from the left motor cortex may cause jerking movements of the right upper extremity. If epileptiform discharges spread to adjacent areas and then the entire brain, a secondary generalized tonic-clonic seizure ensues.
  • Primary generalized seizures begin with abnormal electrical discharges in both hemispheres simultaneously. Generalized seizures involve reciprocal connections between the thalamus and neocortex. The manifestations of such widespread epileptiform activity can range from brief impairment of consciousness (as in an absence seizure) to generalized motor activity accompanied by loss of consciousness (generalized tonic-clonic seizure).
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