Basics
Description
- A seizure is defined as an abrupt alteration in behavior or perception and is often a symptom of underlying CNS or metabolic dysfunction.
- Epilepsy is a disease characterized by recurrent, unprovoked seizures (2 or more).
Epidemiology
Incidence
- Seizures:
- Epilepsy:
- Average: 45/100,000
- Highest incidence under age 10 and over age 60 (>70 cases per 100,000)
- Cumulative lifetime incidence: 3.1% by age 80
Prevalence
- Seizures:
- Epilepsy:
- Point prevalence: 0.5 " 1.0% (highest in underdeveloped countries)
Risk Factors
History of any of the following:
- Perinatal or gestational insults including prematurity
- Febrile seizures
- Family history of epilepsy
- Encephalitis or meningitis
- Stroke or subarachnoid hemorrhage
- Head trauma involving loss of consciousness
- CNS tumor
- Dementia
Genetics
- Contribution of genetics unknown in most epilepsy syndromes
- Some idiopathic epilepsy syndromes linked to defects in ion channels via mendelian or complex inheritance
General Prevention
Avoid conditions that lower seizure threshold:
- Sleep deprivation
- Alcohol intoxication or withdrawal
- Illicit drugs: Cocaine, amphetamines
- Prescription drugs: Antipsychoticstricyclic antidepressants, bupropion, SSRIs, demerol, penicillins
Pathophysiology
- Prolonged depolarization of neuronal cell membranes
- Many possible mechanisms:
- Dysfunction of excitatory (glutamate) or inhibitory (GABA) neurotransmitters
- Defective ion channels
Etiology
- Idiopathic: 65.5%
- Vascular: 10.9%
- Congenital: 8.0%
- Trauma: 5.5%
- Neoplastic: 4.1%
- Degenerative: 3.5%
- CNS infection: 2.5%
- Underlying etiology varies by age. Most common identified etiology:
- <15 years: Congenital abnormalities
- 5 " 24 years: Head trauma
- 25 " 44 years: Brain tumor
- >45 years: Stroke
Diagnosis
History
- Assess for underlying risk factors
- Inquire about seizure frequency and duration
- Ask about catamenial pattern:
- Increased seizures in periovulatory and perimenstrual period seen in up to1/3 of women
- Signs and symptoms:
- Preceding the seizure (aura):
- Dej vu
- Rising epigastric sensation
- Olfactory hallucinations
- During the seizure (ictal):
- Automatisms: Lip smacking, picking
- Unresponsiveness or aphasia
- Focal or generalized clonic movements
- Oral laceration
- Urinary incontinence
- After the seizure (postictal):
- Confusion, agitation, psychosis
- Amnesia of the event
Physical Exam
- Focal neurological findings may provide clues to underlying CNS etiology.
- Postictal period: Todd 's paralysis, positive Babinski, dilated pupils
- Nystagmus and ataxia often seen with toxicity from anticonvulsant medications
Tests
Lab
Initial or acute onset seizures:
- Blood glucose
- Electrolytes: Sodium, calcium, magnesium, phosphate
- CBC
- Urine drug screen
Imaging
Initial or acute onset seizures:
- Head CT without contrast to exclude conditions requiring urgent intervention (hemorrhage, tumor)
- Brain MRI, performed in follow-up as outpatient to exclude more subtle structural lesions
Surgery
- EEG:
- Aids in classification of seizure type and localization of seizure onset
- Initial EEG normal in up to 50%
- Normal EEG does not exclude epilepsy.
- Lumbar puncture:
- All HIV+ patients with new onset seizure(s)
- Any patient with fever, elevated WBC, or suspicion of infection
Differential Diagnosis
- Physiological:
- Syncope
- Transient ischemic attack (TIA)
- Complicated migraine
- Sleep disorder
- Movement disorder: Tremor, tics
- Transient metabolic disturbance
- Psychiatric:
- Conversion disorder
- Panic attacks
- Attention deficit hyperactivity disorder (ADHD)
Treatment
Medication
- Traditional antiepileptic drugs (AEDs)
- Carbamazepine, phenobarbital, phenytoin, primidone, valproate
- Advantages
- Once daily dosing available with most preparations (except carbamazepine)
- Can be rapidly titrated or loaded intravenously (except carbamazepine)
- Inexpensive/generic available
- Disadvantages
- Drug interactions
- CNS side effects
- Teratogenicity
- Long-term effects
- Serum monitoring required
- Second-generation AEDs
- Gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, zonisamide
- Advantages
- Few drug interactions due to predominantly nonhepatic metabolism and low protein binding
- Fewer side effects
- Broad-spectrum coverage of all seizure types (lamotrigine, levetiracetam, topiramate, zonisamide)
- Generic formulations available for most
- Disadvantages
- Slow titration rate (except lacosamide, levetiracetam, gabapentin)
- Only levetiracetam and lacosamide available in IV formulation
- Degree of teratogenic risk unknown except for lamotrigine (see below)
Additional Treatment
General Measures
2/3 of patients can be controlled with medications
Issues for Referral
Refer to neurologist or epileptologist if:
- Refractory to 1st or 2nd medication trial
- Suspicion of pseudoseizures
- Pregnant or considering pregnancy
Complementary and Alternative Medicine
- Vagus nerve stimulation
- For patients refractory to medications and not surgical candidates
- Stimulator implanted subcutaneously in the chest with electrode to the left vagus nerve
- Provides seizure reduction and shortened seizure duration but rarely complete seizure control
- Maternal risk
- Moderately increased risk of cesarean delivery (1)[B]
- No clear evidence that seizure frequency increases during pregnancy (1)[B]
- Declining AED levels due to altered pharmacokinetics (lamotrigine, phenytoin and carbamazepine) (2)[B]
- Fetal risk
- Major malformations in 4 " 8% (twice the general population) of pregnant women taking AEDs
- Risks of maternal seizures include injury to fetus, abruption, or miscarriage secondary to maternal trauma.
- Potential harm of untreated seizure disorder to a pregnant woman and her fetus usually greater than risk of AED use
- Congenital malformations:
- Cleft lip/palate, congenital heart defects, neural tube defects, urogenital defects (3)[A]
- Most strongly associated with use of polytherapy and valproate (3)[A]
- Data regarding use of other newer agents lacking except lamotrigine associated with possible increased risk of cleft lip/palate
- Poor cognitive outcome associated with valproate, possibly phenytoin and phenobarbital (3)[B]
- Increased risk of small for gestational age (3)[B]
- Some AEDs are transferred into breast milk but no evidence to support adverse effects on newborn (2)[C]
- Recommendations
- Monotherapy at the lowest dose needed to control seizures (3)[B]
- Avoid polytherapy as well as monotherapy with valproate (3)[A]
- Folic acid supplementation: 1 " 4 mg/day (start prior to conception) (2)[B]
- Monthly serum drug levels for women taking lamotrigine, phenytoin, and carbamazepine after conception (2)[B]
- Breastfeeding is not contraindicated but should be monitored (2)[C].
- Prenatal testing
- Maternal serum alpha-fetoprotein at 15 " 20 weeks
- Level II (structural) ultrasound at 16 " 20 weeks
Surgery
- Focal brain resection in patients with partial onset seizures refractory to trials of 2 or more medications (alone or in combination)
- Most successful in patients with focal lesions seen on MRI and/or temporal lobe seizures
- Up to 70% seizure freedom rate
In-Patient Considerations
Admission Criteria
- Status epilepticus
- Continuous seizure activity >5 " 10 minutes or
- ≥2 seizures without return to baseline in between
- Prolonged postictal state
Ongoing Care
Follow-Up Recommendations
Patient Monitoring
- CBC and liver function tests
- All patients taking carbamazepine, phenobarbital, phenytoin, and valproate due to risk of agranulocytosis and hepatotoxicity
- Sodium
- Risk of hyponatremia in patients taking carbamazepine and oxcarbazepine, especially elderly and patients on salt-wasting diuretics
- Serum drug levels
- Available for all AEDs
- Aids in monitoring for toxicity, noncompliance
Prognosis
- Classification into appropriate epilepsy syndrome aids in prognosis
- Some generalized epilepsy syndromes will remit in childhood (childhood absence, benign rolandic).
- Juvenile myoclonic epilepsy and adult onset temporal lobe epilepsy least likely to remit
Complications
- Infertility
- Number of births decreased by 33 " 66%
- Anovulatory cycles increased
- Also occurs in women on no AEDs
- Decreased bone mineral density
- Reported with phenobarbital, mysoline, phenytoin, carbamazepine, and valproate
- Consider screening with DXA scan
- Supplement calcium and vitamin D to ensure adequate daily intake (vitamin D minimum 1,000 IU/day)
- Contraception
- AEDs that decrease the efficacy of hormonal contraception: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate (>200 mg/day)
- Oral contraceptives may decrease lamotrigine serum levels by up to 50%.
- Intrauterine devices should be considered to avoid these potentially serious drug interactions.
References
1Harden CL, Hopp J, Ting T. Management issues for women with epilepsy: Obstetrical complications and change in seizure frequency. Epilepsia. 2009;50(5):1229 " 1236. [View Abstract]2Harden CL, Pennell PB, Koppel BS. Management issues for women with epilepsy: Vitamin K, folic acid, blood levels and breast feeding. Epilepsia. 2009;50(5):1247 " 1255. [View Abstract]3Harden CL, Meador KJ, Pennell PB. Management issues for women with epilepsy: Teratogenesis and perinatal outcomes. Epilepsia. 2009;50(5):1237 " 1246. [View Abstract]
Additional Reading
1Crawford P. Managing epilepsy in women of child bearing age. Drug Safe. 2009;32(4):293 " 307. [View Abstract]2LaRoche SM. A new look at the second-generation antiepileptic drugs: A decade of experience. Neurologist. 2007;12(3):133 " 139.
Additional Reading see also
- Epilepsy Foundation. Website: www.efa.org
- North American Pregnancy Registry. Website: www.aedpregnancyregistry.org
Codes
ICD9
- 345.90 Epilepsy, unspecified, without mention of intractable epilepsy
- 649.40 Epilepsy complicating pregnancy, childbirth, or the puerperium, unspecified as to episode of care or not applicable
ICD10
- G40.909 Epilepsy, unsp, not intractable, without status epilepticus
- O99.350 Diseases of the nervous sys comp pregnancy, unsp trimester
SNOMED
- 84757009 epilepsy (disorder)
- 199297006 disease of nervous system complicating pregnancy, childbirth and puerperium (disorder)
Clinical Pearls
- Patients with a single seizure and risk factors for seizure recurrence should be considered for treatment.
- Second-generation anti-epileptic drugs have similar efficacy but are better tolerated than the traditional agents.
- Pre-conceptual counseling aids in optimizing treatment to reduce maternal and fetal complications.