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Source: Nguyen VHV, Baca CB, Chen JJ, Rogers SJ. Epilepsy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. Accessed May 16, 2017.


  • Seizure disorder.


  • (1) Occurrence of at least two unprovoked seizures with or without convulsions separated by at least 24 hours, (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; or (3) diagnosis of an epilepsy syndrome.


  • Categories of identified etiologies.

    • Genetic.

    • Structural.

    • Infectious.

    • Metabolic.

    • Immune.

    • Unknown.

  • Seizure onset in elderly may be associated with strokes, neurodegenerative disorders (eg, Alzheimer’s disease), and other conditions.

  • Unprovoked seizures without identifiable cause are called idiopathic or cryptogenic epilepsy.


  • Seizure results from excessive discharge of cortical neurons.

  • Mechanisms contributing to neuronal hyperexcitability may include:

    • Alterations of ion channels in neuronal membranes.

    • Biochemical modifications of receptors.

    • Modulation of second messaging systems and gene expression.

    • Changes in extracellular ion concentrations.

    • Alterations in neurotransmitter uptake and metabolism in glial cells.

    • Modification in ratio and function of inhibitory circuits.

    • Local imbalances between main neurotransmitters (eg, glutamate, γ-aminobutyric acid [GABA]) and neuromodulators (eg, acetylcholine, norepinephrine, and serotonin).


  • Epilepsy is the fourth most common neurologic disorder globally and in the United States following stroke, migraine, and Alzheimer’s disease.

  • Incidence: 44 per 100,000 person-years.

  • Approximately 125,000 new epilepsy cases occur in United States each year.

    • Only 30% in people younger than 18 years at time of diagnosis.

    • Bimodal distribution in occurrence of first seizure, with one peak in newborn and young children and second peak in patients older than 65 years.


  • Premature birth with small gestational weight, perinatal injuries (eg, anoxia), history of alcohol withdrawal seizures, history of febrile seizures, family history of seizures.

  • Seizures can be precipitated by:

    • Hyperventilation.

    • Photostimulation.

    • Sleep deprivation.

    • Sensory stimuli.

    • Emotional stress.

    • Hormonal changes with menses, puberty, or pregnancy.

  • Drugs that may provoke seizures include:

    • Theophylline.

    • Alcohol.

    • Phenothiazines.

    • Antidepressants (especially maprotiline or bupropion)

    • Street drugs.


  • Obtaining accurate history and description of event (including time course) from third party important because clinician often not in a position to witness seizures.

    • Questions to ask:

      • Was there any warning that something was going to happen? What were the warning signs?

      • Were there any abnormal movements or shaking?

      • Was there loss of bowel or bladder function?

      • Did you bite your tongue?

      • Was there any post-event confusion?

      • How much of the event do you remember?

      • How long did the event last?

      • How ...

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