New-onset epilepsy in the elderly: Challenges for the internist
ABSTRACTNew-onset epilepsy in the elderly is difficult to diagnose, owing to atypical presentation, concomitant cognitive impairment, similarities with other common disorders, and nonspecific changes on electroencephalography (EEG). Its management is also challenging because of its deranging physiology, comorbidities, and polypharmacy. Antiepileptic drugs must be carefully chosen and closely monitored. Support of the patient and caregiver is key.
KEY POINTS
- About 25% of new-onset seizures occur after the age of 65.
- Most new-onset cases of epilepsy in the elderly are secondary to cerebrovascular disease, metabolic disturbances, dementia, traumatic brain injury, tumor, or drug therapy.
- The diagnosis is challenging and can be confused with syncope, transient ischemic attack, cardiac arrhythmia, metabolic disturbances, transient global amnesia, neurodegenerative disease, rapid-eye-movement sleep behavior disorder, and psychogenic disorders.
- The clinical presentation of seizures in the elderly differs from that in younger patients.
- A detailed clinical history, blood tests, electrocardiography, magnetic resonance imaging, and EEG can be helpful in diagnosing.
- No single drug is ideal for new-onset epilepsy in the elderly; the choice depends mainly on the type of seizure and the comorbidities present.
Contrary to the popular belief that epilepsy is mainly a disease of youth, nearly 25% of new-onset seizures occur after age 65.1,2 The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.3 As our population ages, the burden of “elderly-onset” epilepsy will rise.
A seizure diagnosis carries significant implications in older people, who are already vulnerable to cognitive decline, loss of functional independence, driving restrictions, and risk of falls. Newly diagnosed epilepsy further worsens quality of life.4
The causes and clinical manifestations of seizures and epilepsy in the elderly differ from those in younger people.5 Hence, it is often difficult to make a diagnosis with certainty from a wide range of differential diagnoses. Older people are also more likely to have comorbidities, further complicating the situation.
Managing seizures in the elderly is also challenging, as age-associated physiologic changes can affect the pharmacokinetics and pharmacodynamics of antiepileptic drugs. Diagnosing and managing elderly-onset epilepsy can be challenging for a family physician, an internist, a geriatrician, or even a neurologist.
In this review, we emphasize the common causes of new-onset epilepsy in the elderly and the assessment of the clinical clues that are essential for making an accurate diagnosis. We also review the pharmacology of antiepileptic drugs used in old age and highlight the need for psychological support for patients and caregivers.
RISING PREVALENCE IN THE ELDERLY
In US Medicare beneficiaries age 65 and older, the average annual incidence rate of epilepsy in 2001 to 2005 was 10.8 per 1,000.6 A large study in Finland revealed falling incidence rates of epilepsy in childhood and middle age and rising trends in the elderly.7
In the United States, the rates are higher in African Americans (18.7 per 1,000) and lower in Asian Americans and Native Americans (5.5 and 7.7 per 1,000) than in whites (10.2 per 1,000).6 Incidence rates are slightly higher for women than for men and increase with age in both sexes and all racial groups.
Acute symptomatic seizure is also common in older patients. The incidence of acute seizures in patients over age 60 was estimated at 50 to 100 per 100,000 per year in one study.7 The rate was considerably higher in men than in women. The study also found a 3.6% risk of experiencing an acute symptomatic seizure in an 80-year lifespan, which approaches that of developing epilepsy.8 The major causes of acute symptomatic seizure were traumatic brain injury, cerebrovascular disease, drug withdrawal, and central nervous system infection.
CAUSES OF NEW-ONSET EPILEPSY IN THE ELDERLY
The most common causes of new-onset epilepsy in the elderly include cerebrovascular disease, metabolic disturbances, dementia, traumatic brain injury, tumors, and drugs.3,9–11
Cerebrovascular disease
In older adults, acute stroke is the most common cause, accounting for up to half of cases.5,12
Seizures occur in 4.4% to 8.9% of acute cerebrovascular events.13,14 The risk varies by stroke subtype, although all stroke subtypes, including transient ischemic attack, can be associated with seizure.15 For example, although 1% to 2% of patients experienced a seizure within 15 days of a transient ischemic attack or a lacunar infarct, this risk was 16.6% after an embolic stroke.15
Beyond this increased risk of “acute seizure” in the immediate poststroke period (usually defined as 1 week), the risk of epilepsy was also 20 times higher in the first year after a stroke.14 However, seizures tend to occur within the first 48 hours after the onset of ischemic stroke. In subarachnoid hemorrhage, seizures generally occur within hours.16
In a population-based study in Rochester, NY,17 epilepsy developed in two-thirds of patients with seizure related to acute stroke. Two factors that independently predicted the development of epilepsy were early seizure occurrence and recurrence of stroke.
Interestingly, the risk of stroke was three times higher in older patients who had new-onset seizure.18 Therefore, any elderly person with new-onset seizure should be assessed for cerebrovascular risk factors and treated accordingly for stroke prevention.
Metabolic disturbances
Acute metabolic disorders are common in elderly patients because of multiple comorbidities and polypharmacy. Hypoglycemia and hyponatremia need to be particularly considered in this population.19
Other well-documented metabolic causes of acute seizure, including nonketotic hyperglycemia, hypocalcemia, and uremic or hepatic encephalopathy, can all be considerations, albeit less specific to this age group.
Dementia
Primary neurodegenerative disorders associated with cognitive impairment, such as Alzheimer disease, are major risk factors for new-onset epilepsy in older patients.3,5 Seizures occur in about 10% of Alzheimer patients.20 Those who have brief periods of increased confusion may actually be experiencing unrecognized complex partial seizures.21
A case-control study discovered incidence rates of epilepsy almost 10 times higher in patients who had Alzheimer disease or vascular dementia than in nondemented patients.22 A prospective cohort study in patients with mild to moderate Alzheimer disease established that younger age, a greater degree of cognitive impairment, and a history of antipsychotic use were independent risk factors for new-onset seizures in the elderly.23 Preexisting dementia also increases the risk of poststroke epilepsy.24
Traumatic brain injury
The most common cause of brain trauma in the elderly is falls. Subdural hematoma, which can occur in the elderly with trivial trauma or sometimes even without it, needs to be considered. The risk of posttraumatic hemorrhage is especially relevant in patients taking anticoagulants.
Traumatic brain injury has a poorer prognosis in older people than in the young,25 and it accounts for up to 20% of cases of epilepsy in the elderly.26 Although no study has specifically addressed the longitudinal risk of epilepsy after traumatic brain injury in the elderly, a study in children and young adults revealed the risk was highest in the first year, with the increased risk persisting for more than 10 years.27
