para>Epilepsy is the third most common disease of the brain in the elderly, after stroke and dementia.
Diagnosing epileptic seizures in the elderly may prove difficult, as symptoms such as auras and generalized tonic " “clonic seizures are rarer, but status epilepticus is more common.
Elderly are more sensitive to side effects from antiepileptic drugs (AEDs); therefore, target dose should be half of dosing for younger population (1).
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Pediatric Considerations
Breastfeeding is not contraindicated. Sedation of the infant should be monitored.
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Pregnancy Considerations
Monitor serum levels of AEDs.
There is a 2-fold increase in congenital malformations in children born to mothers taking certain anticonvulsants. Some expectant mothers can stop taking anticonvulsants safely for the 1st trimester or initial 6-week period (organogenesis). Avoid valproate and lamotrigine. Epileptic patients should notify their neurologist before conception, if possible.
Recommend against use of Category C or D AEDs during pregnancy/nursing. Levetiracetam and topiramate are alternatives for women of childbearing potential (2).
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EPIDEMIOLOGY
Incidence
- 200,000 new cases of epilepsy are diagnosed in the United States annually, with 45,000 new cases in children <15 years of age.
- Pediatric (<2 years of age) and older adults (>65 years of age) more commonly present with new-onset seizures.
- Predominant sex: male = female
Prevalence
- 2.7 million with seizure disorder
- 4 million people have had ≥1 seizures.
- 326,000 children ( ≤14 years of age) and 600,000 adults (>65 years of age) have a seizure disorder.
ETIOLOGY AND PATHOPHYSIOLOGY
- Synchronous and excessive firing of neurons, resulting in impairment of normal control of CNS
- Seizures may be triggered by metabolic/medical conditions, but such seizures do not necessarily define the presence of a seizure.
- CNS infection
- Hyperthyroidism
- Hypoglycemia or hyperglycemia
- Hyponatremia
- Uremia
- Porphyria
- Hypoxia
- Confusional migraine
- Transient ischemic attack
- Narcolepsy/sleep disorder
- Toxins (e.g., lead, picrotoxin, strychnine)
- Brain tumor
- Stroke/cardiovascular accident
- Drug/alcohol overdose/withdrawal
- Eclampsia
- Head injury
- Heat stroke
Genetics
Family history increases risk 3-fold. ‚
RISK FACTORS
Children delivered breech have a prevalence rate of 3.8% compared with 2.2% in vertex deliveries. ‚
GENERAL PREVENTION
Take measures to prevent head injuries. Reduce exposure to lead-containing products. ‚
COMMONLY ASSOCIATED CONDITIONS
Infections, tumors, drug abuse, alcohol and drug withdrawal, trauma, metabolic disorders ‚
DIAGNOSIS
- Physiologic seizures are true cortical events and may require acute intervention.
- Conventional classification of seizures
- Generalized seizures
- Tonic " “clonic: tonic phase: sudden loss of consciousness; clonic phase: sustained contraction followed by rhythmic contractions of all four extremities; postictal phase: headache, confusion, fatigue; clinically hypertensive, tachycardic, and otherwise hypersympathetic
- Absence: impaired awareness and responsiveness
- Atonic: abrupt loss of muscle tone
- Myoclonic: repetitive muscle contractions
- Febrile seizures
- Usually ≤6 years
- Fever without evidence of any other defined cause of seizures
- Recurrent febrile seizures probably do not increase the risk of epilepsy.
- Symptomatic focal epilepsies
- Complex partial seizures
- Simple partial seizures
- Nonconvulsive status epilepticus: most commonly seen in ICU patients; no tonic " “clonic activity seen so must diagnose with bedside EEG
- Status epilepticus: repetitive generalized seizures without recovery between seizures; considered a neurologic emergency
HISTORY
- Eyewitness descriptions of event; patient impressions of what occurred before, during, and after the event
- Screen for etiologies, including provoking/ameliorating factors for the event, such as sleep deprivation.
- Ask about bowel/bladder incontinence, tongue biting, other injury, automatisms, or prior seizure activity.
PHYSICAL EXAM
Thorough neurologic exam ‚
DIFFERENTIAL DIAGNOSIS
- Idiopathic
- Hippocampal sclerosis and other neurodevelopmental abnormalities of the brain
- Acute infection (meningitis, abscess, encephalitis)
- Metabolic and endocrine disorders
- Trauma
- Drug and alcohol withdrawal
- Tumor
- Vascular disease, including vasculitis
- Familial/genetic, infantile, and pediatric seizure syndromes (e.g., Lennox-Gastaut, benign familial, myoclonic epilepsy of infancy)
- Other etiologies (by age of onset)
- Infancy (0 to 2 years)
- Hypoxic-ischemic encephalopathy/other injury to cerebral cortex
- Metabolic: hypoglycemia, hypocalcemia, hypomagnesemia, vitamin B6 deficiency, phenylketonuria
- Childhood (2 to 10 years): absence or febrile (usually <6 years) seizure
- Adolescent (10 to 18 years): arteriovenous malformation
- Late adulthood (>60 years)
- Degenerative disease, including dementia
- Metabolic: hypoglycemia, uremia, hepatic failure, electrolyte abnormality
DIAGNOSTIC TESTS & INTERPRETATION
A negative EEG does not rule out a seizure disorder. Interictal EEG sensitivity may be as low as 20%; multiple EEGs may increase sensitivity to 80%. ‚
- Sleep deprivation may be helpful prior to EEG, and hyperventilation and photic stimulation during recording may increase sensitivity.
- Video EEG monitoring is used to differentiate psychomotor nonepileptic seizures (NES) from true cortical events.
Initial Tests (lab, imaging)
- Glucose, sodium, potassium, calcium, phosphorus, magnesium, BUN, ammonia; drug and toxin screens
- AED levels (if patient is taking antiepileptic medication)
- CBC and UA: Rule out infection.
- Imaging is recommended for new-onset seizures. MRI is preferred to CT.
- CT scan of brain: indicated routinely as initial evaluation, especially in the ER
- Brain MRI: superior in evaluation of the temporal lobes (e.g., mesial temporal sclerosis)
- Bone scan to determine bone mineral density (BMD): generally done if patients are taking older AEDs such as phenytoin and carbamazepine
Follow-Up Tests & Special Considerations
- Drugs that may alter lab results: AED therapy may affect the EEG results dramatically.
- Inadequate AED levels may be altered by many medications such as erythromycin, sulfonamides, warfarin, cimetidine, and alcohol.
- Disorders that may alter lab results: Pregnancy decreases serum concentration.
Diagnostic Procedures/Other
Lumbar puncture for spinal fluid analysis may be necessary to rule out meningitis if fever and/or impairment of consciousness are present. ‚
TREATMENT
- 50 " “60% presenting with an initial unprovoked seizure will not have a recurrence; 40 " “50% will have a recurrence within 2 years (3).
- Starting antiepileptic medications is likely to reduce recurrences of seizures but does not alter long-term outcomes or improve quality of life (4)[C].
- Evidence is conflicting whether or not to start AEDs routinely in patients on initial seizure with no focal abnormalities on exam or imaging. Many recommend deferring treatment until a second seizure has occurred (4)[C].
MEDICATION
- AED of choice: Select based on type of seizure, potential adverse effects/drug interactions, and cost.
- Monotherapy is preferred whenever possible. Treatment should begin with a single agent, and the dose titrated until seizures are controlled or side effects become problematic. Consider a different agent if the first choice is not effective versus adding a second agent.
First Line
Treatment options include the following: ‚
- Carbamazepine (Tegretol): 100 to 200 mg/day in 1 to 2 doses; therapeutic range, 4 to 12 mg/L
- Valproic acid (Depakene): 750 to 3,000 mg/day in 1 to 3 doses to begin at 15 mg/kg/day; therapeutic range, 50 to 150 mg/L. This is considered the drug of choice for generalized tonic " “clonic seizures (2)[B].
- Lamotrigine (Lamictal): 25 to 50 mg/day; adjust in 100-mg increments every 1 to 2 weeks to 300 to 500 mg/day in 2 doses
- Oxcarbazepine (Trileptal): 300 mg BID, increase to 300 mg every 3 days; maintenance, 1,200 mg/day.
- Levetiracetam (Keppra): 1,000 mg/day in 2 doses
- Ethosuximide (Zarontin) 750 to 1,250 mg/day divided BID
Second Line
- Phenytoin (Dilantin): 200 to 400 mg/day in 1 to 3 doses; therapeutic range, 10 to 20 mg/L
- Topiramate (Topamax): 50 mg/day; adjust weekly to effect; 400 mg/day in 2 doses, max 1,600 mg/day
- Gabapentin (Neurontin): 1,800 to 3,600 mg in 3 to 4 doses for adjunct therapy
- Pregabalin (Lyrica): 150 to 300 mg/day in 2 to 3 doses
- Lacosamide (Vimpat): Add-on therapy for refractory seizures; 200 to 300 mg/day in 2 doses
- Eslicarbazepine (Aptiom): 400 mg once/day initially, 800 to 1,200 mg once/day maintenance, adjunctive therapy
- Zonisamide (Zonegran): 100 to 400 mg in 1 to 2 doses
- Ezogabine (Potiga): 600 to 1,200 mg in 3 doses
- Perampanel (Fycompa): 4 to 12 mg daily
- Clonazepam (Klonopin): 1.5 to 8 mg in 2 to 3 doses
- Clobazam (Onfi): 20 to 40 mg in 1 to 2 doses
- Rufinamide (Banzel): 3,200 mg in 2 doses
- Alternative drugs: Other medications are available to treat seizures, but these are generally reserved for third-line treatment due to side effects (5).
- Phenobarbital: 50 to 100 mg BID " “TID; therapeutic range, 15 to 40 mg/L. Long-term use may impair cognition.
- Primidone (Mysoline): 100 to 125 mg at bedtime; adjust to max of 2,000 mg/day in 2 doses. Converted to phenobarbital
- Vigabatrin (Sabril): 3 g in 2 doses. Restricted distribution via the SHARE program.
- Felbamate (Felbatol): 2,400 to 3,600 mg in 3 to 4 doses. Significant risk for aplastic anemia
- Contraindications: Refer to manufacturer 's profile of each drug.
- Precautions: Doses should be based on individual 's response guided by drug levels.
- Consider cautioning about increased risk of suicide, but risk of untreated seizures is far greater than increased risk of suicide.
- Patients are susceptible to sudden unexpected death in epilepsy, possibly due to cardiac arrhythmia.
ISSUES FOR REFERRAL
Referral and follow-up frequency is based on severity and patient 's wishes. ‚
SURGERY/OTHER PROCEDURES
- Resection for seizures that fail traditional therapy
- Vagus nerve stimulation
COMPLEMENTARY & ALTERNATIVE MEDICINE
- No evidence suggests that any complementary medicines reduce seizures, but they may induce serious drug interactions with prescribed AEDs.
- Psychological therapies may be used in conjunction with AED therapy. Cognitive-behavioral therapy, relaxation, biofeedback, and yoga all may be helpful as adjunctive therapy (6)[C].
- Patients with NES should be referred for psychotherapy.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Outpatient therapy usually is sufficient, except for status epilepticus.
- Protect the airway and, if possible, protect the patient from physical harm; do not restrain. Administer acute AEDs.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Maintain adequate drug therapy; ensure compliance and/or access to medication. Drug therapy withdrawal may be considered after a seizure-free 2-year period. Expect a 33% relapse rate in the following 3 years. ‚
Patient Monitoring
- Monitor drug levels and seizure frequency.
- CBC and lab values (e.g., calcium, vitamin D) as indicated; BMD
- Monitor for side effects and adverse reactions.
- All patients currently taking any AED should be monitored closely for notable changes in behavior that could indicate the emergence/worsening of suicidal thoughts/behavior/depression.
DIET
Ketogenic diet may be beneficial in children in conjunction with AED therapy and refractory seizures. ‚
PATIENT EDUCATION
Stress the importance of medication compliance and the avoidance of alcohol and recreational drugs. ‚
- Individuals with uncontrolled seizures should be encouraged to avoid heights and swimming.
- State driving laws: http://www.epilepsy.org
PROGNOSIS
- Depends on type of seizure disorder: ~70% will become seizure-free with appropriate initial treatment, 30% will continue to have seizures. The number of seizures within 6 months after first presentation is a prognostic factor for remission.
- ~90% who are seen for a first unprovoked seizure attain a 1- to 2-year remission within 4 or 5 years of the initial event (3).
- Life expectancy is shortened in persons with epilepsy.
- The case fatality rate for status epilepticus may be as high as 20%.
REFERENCES
11 Werhahn ‚ KJ. Epilepsy in the elderly. Dtsch Arztebl Int. 2009;106(9):135 " “142.22 Perucca ‚ E, Tomson ‚ T. The pharmacological treatment of epilepsy in adults. Lancet Neurol. 2011;10(5):446 " “456.33 Berg ‚ AT. Risk of recurrence after a first unprovoked seizure. Epilepsia. 2008;49(Suppl 1):13 " “18.44 Krumholz ‚ A, Wiebe ‚ S, Gronseth ‚ GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults: report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84(16):1705 " “1713.55 The Medical ‚ Letter. Drugs for epilepsy. Treat Guidel Med Lett. 2013;11(126):9 " “18.66 Marson ‚ A, Ramaratnam ‚ S. Epilepsy. Clin Evid. 2005;(13):1588 " “1607.
ADDITIONAL READING
- Shih ‚ JJ, Ochoa ‚ JG. A systematic review of antiepileptic drug initiation and withdrawal. Neurologist. 2009;15(3):122 " “131.
- Wiebe ‚ S, Tellez-Zenteno ‚ JF, Shapiro ‚ M. An evidence-based approach to the first seizure. Epilepsia. 2008;49(Suppl 1):50 " “57.
SEE ALSO
Seizures, Febrile; Status Epilepticus ‚
CODES
ICD10
- R56.9 Unspecified convulsions
- P90 Convulsions of newborn
- G40.909 Epilepsy, unspecified, not intractable, without status epilepticus
- G40.309 Generalized idiopathic epilepsy and epileptic syndromes, not intractable, without status epilepticus
- G40.009 Local-rel idio epi w seiz of loc onst,not ntrct,w/o stat epi
ICD9
- 780.39 Other convulsions
- 779.0 Convulsions in newborn
- 345.90 Epilepsy, unspecified, without mention of intractable epilepsy
- 345.50 Localization-related (focal) (partial) epilepsy and epileptic syndromes with simple partial seizures, without mention of intractable epilepsy
SNOMED
- seizure disorder (disorder)
- Convulsions in the newborn
- Epilepsy (disorder)
- Generalized epilepsy (disorder)
- Localization-related epilepsy (disorder)
CLINICAL PEARLS
- Switching from brand to generic drug is safe. Monitor seizure activity after switch for 2 months.
- Encourage helmet usage to minimize head injuries.
- To consider driving, states require seizure-free period from 3 to 12 months.
- Drug initiation after a single seizure will decrease risk of early seizure recurrence but does not affect long-term prognosis of developing epilepsy.