Seizure disorders A spate of new antiepileptics help rein in the brainstorms BY Kerri L. Schellenberg, MD and S. Nizam Ahmed, MD

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Epilepsy is a common neurologic disorder with significant medical and social consequences. The cumulative incidence is estimated at 33 per 100,000 person-years.1 A seizure is a paroxysmal hypersynchronous discharge of the cerebral neurons. Seizures can be provoked in some individuals by high fever (febrile seizures), sleep deprivation and metabolic derangements. An unprovoked seizure occurs in the absence of any acute inciting factor. Epilepsy is defined as a tendency for recurrent seizures in the absence of provoking stimuli. In clinical practice, a diagnosis of epilepsy can be made if a patient has two or more unprovoked seizures. A majority of patients with more than two unprovoked seizures will go on to have further episodes.2

What types of seizures exist?
The International League Against Epilepsy (ILAE) introduced a classification system in 1981 that's still widely used.3 Seizures are broadly classified as partial if electrical activity begins in a focal area of the brain, or generalized if the activity is widespread and symmetrical at onset. In 2001, ILAE revised the classification system.4 As a result, seizures are first determined to be either self-limiting or continuous, and then categorized as generalized or focal.

Partial seizures (focal seizures) usually originate from areas of the brain with focal pathology. Examples include strokes, brain tumours, or cerebral abscesses. If consciousness isn't altered during a seizure, it's classified as a simple partial seizure. It's termed a complex partial seizure if there's an alteration of awareness during the event. Partial seizures that spread to bilateral motor areas leading to tonic-clonic activity are called secondarily generalized seizures. In this way, a partial seizure may begin as a simple partial seizure and subsequently evolve into a complex partial and secondarily generalized seizure.

Generalized seizures don't originate from an identifiable focal area and tend to involve both hemispheres simultaneously. They can be classified as convulsive or non-convulsive. Tonic, clonic, tonic-clonic (formerly called grand mal), and myoclonic seizures are of the generalized convulsive type, whereas absence seizures (formerly called petit mal) are examples of non-convulsive seizures.

What's behind these seizures?
In developed countries, onset of epilepsy occurs in a bimodal distribution. Risk is high in the first year of life, while the second peak occurs in individuals over 75 years of age. Partial (focal) seizures are the most common presentation in the older population.5

The main risk factor for unprovoked generalized seizures is genetic susceptibility. Provoked generalized seizures, on the other hand, can result from withdrawal of alcohol and benzodiazepines, illicit drug use, excessively high fever and sleep deprivation, in addition to metabolic derangements, such as hyponatremia or hypoglycemia.

Partial seizures can follow any insult to the cerebral neurons. Examples include stroke, tumour, abscess, meningitis, trauma and congenital malformations. Keep in mind that patients who develop febrile seizures have a higher risk of developing epilepsy later in life.6

How do symptoms manifest?
The clinical presentation depends on the site of seizure onset within the brain, and whether the seizure is focal or generalized.

Simple partial seizures usually present with motor or sensory symptoms. Clonic activity may march from one site to a progressively larger area. Look for sensory symptoms, such as numbness, tingling, and special sensory systems that include the sense of smell. A Todd's paralysis refers to lateralized weakness that may follow a partial seizure in the involved limb. Autonomic and psychic symptoms are less common.