Epilepsy

SOURCE

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. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146062782. Accessed May 16, 2017.

CONDITION/DISORDER SYNONYM

• Seizure disorder.

DEFINITION

• (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.

ETIOLOGY

• 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.

PATHOPHYSIOLOGY

• 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).

EPIDEMIOLOGY

• 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.

RISK FACTORS

• 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.

CLINICAL PRESENTATION

• 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 often do you have these events?