Pathophysiology of seizures and epilepsy
- Carl E Stafstrom, MD, PhD
Carl E Stafstrom, MD, PhD
- Professor of Neurology and Pediatrics
- Johns Hopkins University
- Jong M Rho, MD
Jong M Rho, MD
- Professor of Paediatrics, Clinical Neurosciences, Physiology, and Pharmacology
- Dr. Robert Haslam Chair in Child Neurology
- University of Calgary
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, 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 seizure recurrence. Epileptogenesis is the process by which the normal brain becomes prone to epilepsy .
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. Several key cortical and subcortical structures are involved in generating a seizure.
This topic reviews the cellular basis for focal and generalized seizure activity, with specific attention to ion channels, the essential currency of neuronal excitability, and the hippocampus, one of the most seizure-prone areas of the brain. The pharmacology of anti-seizure drugs and issues related to the assessment and management of patients with epilepsy are discussed separately. (See "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects" 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 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, it is called a secondarily generalized tonic-clonic seizure.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- CLASSIFICATION OF SEIZURES
- CELLULAR PHYSIOLOGY
- Ion channels
- Voltage-dependent conductances
- - Depolarizing conductances
- - Hyperpolarizing conductances
- Synaptic transmission
- - Excitatory transmission
- - Inhibitory transmission
- Role of glia
- PATHOPHYSIOLOGY OF EPILEPSY
- Focal epilepsy: Mesial temporal lobe epilepsy
- - Paroxysmal depolarization shift
- - Synchronizing mechanisms
- - Consequences of repeated seizures
- Primary generalized epilepsy: Absence epilepsy
- Susceptibility of the immature brain