Factors in seizure occurrence

Seizures are always a symptom of brain dysfunction. They usually reflect some degree of interaction between intrinsic factors (seizure threshold) and extrinsic factors (physiological or environmental stressors). Thus, drugs (whether medicinal, botanical, or recreational) can increase the risk of seizures by lowering a patient's seizure threshold below some critical level. Many extrinsic factors (e.g., alcohol, street drugs, and anesthetics) are transient or reversible. Others, especially those that cause permanent cerebral injury, are not.

Both patient factors and medication factors can contribute to seizure occurrence:

  • Patient factors
    • Inherited seizure predisposition
    • Brain injury (chronic or acute)
    • Breakdown of blood-brain barrier
    • Hypoalbuminemia, hypoxia
    • Hypomagnesemia
    • Renal or hepatic failure
    • Illicit drug or alcohol abuse
  • Medication factors
    • Drug lowers seizure threshold (see Table: Drugs that may lower seizure threshold)
    • Drug causes hyponatremia
    • Rapid increase, accidental or deliberate
    • Overdose of epileptogenic (toxic) drug
    • Drug induces metabolism of anticonvulsant
    • Drug inhibits metabolism of toxic drug
    • Drug shares protein binding with anticonvulsant or epileptogenic drug

Physicians should evaluate new-onset seizures in the context of an affected person's overall health and lifestyle. Among the factors to consider are:

  • concurrent illnesses
  • medications (prescribed, herbal, and over-the-counter)
  • recent anesthesia
  • use of alcohol, cigarettes, or illicit substances

Seizures related to these factors may not be manifestations of epilepsy, a chronic disorder in which seizures recur unpredictably and usually without demonstrable triggers.

Managing drug treatment

Drugs and drug interactions may exacerbate epilepsy and contribute to intractability. Patients with epilepsy who require antiepileptic drugs (AEDs) must be warned of possible adverse interactions from drugs used for other illnesses, whether over-the-counter nostrums taken for common ailments or treatments prescribed by a physician for serious diseases. The effects of medications used intermittently, such as analgesics, antibiotics, and decongestants, can be especially difficult to manage.

Decisions about treatment of new-onset seizures depend on obtaining accurate information about the circumstances under which the seizure(s) occurred: Are they sufficient to explain the seizures? Are they remediable? Acute symptomatic seizures usually do not require treatment with AEDs if the precipitants can be eliminated or avoided. If AEDs must be prescribed, it is important to recognize the effect they may have on other aspects of the patient's treatment.

The pages that follow review the most common ways in which drugs affect seizure susceptibility, and the drug interactions most commonly encountered in practice. They also touch on the effects of chronic illnesses or procedures on antiepileptic drugs (AEDs) and their effect on seizure risk.

Adapted from: Koppel BS. Contribution of drugs and drug interactions (prescribed, over the counter, and illicit) to seizures and epilepsy. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;155-173. With permission from Elsevier (www.elsevier.com).

Authored by: Barbara S. Koppel MD
Reviewed by: Steven C. Schachter MD on 3/2004
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