Epilepsy in the Elderly: Why is it Different? Brenda Y. Wu, M.D., Ph.D.

Incidence of New Diagnosis of Epilepsy > 60y/o, ~25% Epilepsy was once thought to be a disorder of childhood Growing management challenge in the elderly Increase awareness among MDs that Sz is a significant helth problem in the elderly Incidence is much higher than previously thought Elderly are the fastest growing segment of population afflicted with epilepsy Epilepsy is the 3rd most frequently identified neurologic condition seen in the elderly. Pohlmann-Eden B, Acta Neurol Scand 2005(suppl);181:40-46

Etiology in Patients  age 60 Ramsay, et al. Neurology 2004; 62 (5 suppl 2).

Causes of Epilepsy Annegers JF. The epidemiology of epilepsy. In: Wyllie E, ed. The treatment of epilepsy: principles and practice.3rd Ed, 2001:165-72

Seizure Precipitants  Metabolic and electrolyte imbalance  Stimulant/other pro-convulsant intoxication: cocaine, anticholinergics, dopamine blockers, clozapine, immuno-suppressants, antibiotics, certain narcotics (e.g. Dilaudid)  Sedative or ethanol withdrawal  Severe sleep deprivation  Antiepileptic medication reduction or inadequate AED treatment  Hormonal variations or immunocompromise (e.g. platelets)  Stress  Fever or systemic infection  Concussion and/or closed head injury One or more precipitating factors can contribute to the patient’s seizure. The discovery of a precipitant does not obviate the need to search for intracranial pathology or a genetic predisposition toward seizures, but may lead to a non-epilepsy diagnosis (e.g., alcohol withdrawal seizure), and is very useful in counseling the patient. Common precipitants include metabolic and electrolyte imbalance (such as low blood glucose, low sodium, low calcium or low magnesium), antiepileptic medication reduction or inadequate AED treatment, hormonal variations, stress, infection, severe sleep deprivation, withdrawal from alcohol or other sedative agents, and administration of drugs with proconvulsant properties, such as central nervous system stimulants including cocaine, anticholinergics (including over-the-counter antihistamines), almost all dopamine blocking agents, newer antipsychotics (particularly clozapine), antidepressants (especially buproprion), immune suppressants such as cyclosporine, and antibiotics such as quinolones or imipenem-cilastatin.

Seizure Types in Patients  age 60 Seizures in older persons are more often extratemporal, usually confined to the frontal lobe. Most elderly Pt present with staring spells, only 35-40% have convulsions. In contrast, 70% of younger patients with epilepsy present with convulsion. Ramsay, R. E. et al. Neurology 2004;62:24-29S

Under-diagnosed Epilepsy in Elderly Obscured by multiple medical problems ‘Atypical’ symptoms from commonly discussed seizure types, often interpreted as caused by aging or depression Living alone, not being closely observed Half of delays—Patient did not seek for help. After 1st seizure, < 50% diagnosed (GTC—usually immediately versus only 20% for CPS) Only < 73% ultimately diagnosed by primary care physicians The mean time to the correct diagnosis was 1.7 years (median 2.5 months). ‘Atypical’ symptoms from commonly discussed seizure types, often mimic cardiac events or TIA

Typical Seizures for All Age Groups Generalized: absence, tonic-clonic, atonic Staring, shaking, incontinence, tongue bite, unresponsive Partial-onset epilepsy: simple or complex Aura Confusion, incoherent speech Oral or manual automatism Head turning

Symptoms in Late-onset Epilepsy Auras are less common Often non-specific auras: e.g. dizziness Less automatism Prolonged post-ictal confusion Common initial presentations (1 or more): altered mental status (41.8%), blackout/syncope/recurrent falls (29.3%), memory impairment (17.2%), dizziness (10.3%) & dementia (6.9%) New onset sleep walking/sleep talking; vivid dreams with arousal (Night terror ? REM behavior sleep disorder? frontal lobe epilepsy); jerks in sleep

Diagnosis Detailed history Clinical symptoms; Circumstances of event Past medical, neurological & psychiatric history, medications Physical Exam, lateralizing neurological signs, cognitive function Lab & Diagnostic studies: ECG Laboratory tests: immediately after events, supportive only Routine EEG (short) –low yield Long-term Video EEG monitoring—especially helpful, “gold-standard”

Epileptiform Activities on EEG First routine (short) EEGs (> age 60): Only seen in 35% with pre-existing epilepsy Only seen in 26% with late-onset epilepsy (onset after age 60) Past medical, neurological & psychiatric history, medications Long-term video EEG: More than 50% in patient with vague or non-specific clinical symptoms whose routine EEGs are normal or inconclusive if episodes are not captured. Low yiel Drury I. et al. Epilepsia. 1999; 40

Challenges Clinical Impact on quality of life More severe injuries More prolonged postictal confusion Impact on quality of life Less impact on employment Driving Competency of living independently Treatment: more intolerance issues Treatment Age-related pharmacokinetics: clearance, sensitivity, low tolerance,  dose-related adverse effects  drug-interactions

Nonlinear pharmacokinetics of Phenytion 1. The therapeutic window for some AEDs is narrow or non-existent in elderly patients. 2. Sometimes it is difficult to distinguish btw AED toxicity and age- or disease-related factors. 3. The basis of change in the therapeutic window is due to age-related changes in absorption, distribution, and elimination (renal and hepatic), and increased sensitivity to pharmacodynamic effects of AEDs. 4. With AEDs that are highly protein bound (PHT, VPA), lower initial doses may be needed in some elderly Pt due to age-related hypoalbuminemia, malnutrition or renal failure 5. AEDs primarily excreted via kidney Birnbaum A., et al. Neurology. 2003; 60.

Treatment of Epilepsy in Elderly Medication(s) make me sick? Is it the symptoms of the disease? Lower doses of high-protein bound AEDs in hypoalbuminemia Age-related Malnutrition Renal failure Lower doses of AEDs in patients with renal failure Excretion 1o via kidney (gabapentin, levetiracetam) Renal and liver (OXC, PB, TPM, ZNS) Treatment Age-related pharmacokinetics: clearance, drug sensitivity, low tolerance,  dose-related adverse effects  drug-interactions More sensitive to fluctuations in AED blood levels

Treatment of Epilepsy in Elderly Drug of choice Drug interaction Adverse effect: imbalance, mood swing, sedation, sleep pattern; weight changes; Co-existing medical problems: liver, kidney failure; Dosage Speech impairment from AED adverse effect versus uncontrolled seizures Compliance Management of precipitating factors: Sleep disorder (OSA etc), conditions affecting sleep quality, stress management, chronic infections, hormonal and electrolyte disturbance

Summary Epilepsy in elderly: high incidence but under-diagnosed Epileptic symptoms may be ‘atypical’ in elderly patients. Detailed history and descriptions will be helpful for diagnosis. Routine (short) EEG usually has low yield. Long term video EEG is more helpful to confirm the diagnosis. Pharmacological treatment plan should be individualized for better tolerance and compliance.