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Seizure Management and Determining Potentially Misdiagnosed Seizures in Older Adults
Many older adults taking antiseizure medication have a diagnosis of seizure disorders that are not supported by objective diagnostic evidence. These “seizure disorders” are the result of years of misdiagnosis and a belief that the benefits of medication outweigh the potential for a seizure event. However, as the adverse effects of antiseizure medications increase with age and raise the risk of debilitating injury, re-evaluation of patients should be performed to ensure appropriate management. This article provides a foundation for geriatrics providers to appropriately manage misdiagnosed seizures as well as true seizures in older adults. Specific considerations for professionals working in long-term care are included.
Key words: seizures, antiseizure medication, misdiagnosis, geriatrics seizures
There is a direct correlation between seizure incidence and age; seizures are most common in patients older than age 65.1 After age 30, there is a linear increase every decade, with an incidence of 0.55 to 1 per 1000 people in individuals older than 60 years.2 Data also suggest acute symptomatic seizures are more common in older adults.
With data showing that by the year 2020 the diagnosis of half of all newly developed seizures will occur in patients older than 65 years, the subject has large bearing for long-term care (LTC) providers.3 Approximately 10% of nursing home residents in the United States take an antiepileptic drug.4 Consequently, it is vital to monitor for new seizure activity and to appropriately manage seizures in LTC settings. The management of seizures in older adults is complex, however. Physicians may be more concerned with undertreatment rather than continued treatment in patients without actual seizures. This article reviews current data on seizure management and diagnosis to assist geriatrics providers in appropriately managing misdiagnosed seizures as well as true seizures in older adults, with a specific focus on older adults residing in LTC facilities.
Potential Causes of Seizure
An acute symptomatic seizure is a seizure that occurs at the time of a systemic insult or in close temporal association with a documented brain insult.2 The most prevalent causes of acute symptomatic seizures are acute stroke, metabolic encephalopathy, drug intoxication, trauma, and infection.2 Acute strokes alone account for half of the cases of new-onset seizures.2 The leading causes of epilepsy in older adults are cerebrovascular disease, dementia, and trauma, rather than acute symptomatic seizures.5 However, one-third of epilepsy cases in older adults originates from an unknown etiology.5 Cerebrovascular disease causes up to half of all cases of epilepsy in older adults.2 Unprovoked seizure risk increases the first year after a stroke and remains substantially elevated for 7 years.6 This is concerning in a large population of patients receiving LTC after stroke.
Assessing Patient History
In the LTC setting, patient history may be better gathered through providers in the immediate settings where residents reside and through chronic supervision, as well as through the patient’s family. Although the actual seizure event may be difficult for most patients to recall, the sequence of events and circumstances that led up to the actual event is important for clinicians to investigate. Risk factors for epileptic seizure that should be assessed include recent head injury, abnormal early neurologic development or intellectual disability, stroke, Alzheimer disease, history of intracranial infection, alcohol and drug abuse, immunosuppression, history of cancer, rheumatologic disorders such as systemic lupus erythematosus, sickle cell disease, porphyria, and antiphospholipid syndrome.7 Certain medications also decrease the seizure threshold and thus increase a patient’s risk for seizures (Table 1).
Family history of seizure disorder is a positive risk factor for epilepsy. Both absence and myoclonic seizures have a genetic predisposition of inheritance. Recent studies show that seizure history among siblings is fairly well-documented, but parental history of seizures and epilepsy is generally underreported.8
Diagnostic Assessment
Some “seizure” diagnoses in LTC may only be based on the fact that the patient is currently taking an antiseizure medication. The presence of previous diagnoses may prevent those providing care in LTC settings from further investigating or discontinuing current medications. A seizure diagnosis should be based on objective documentation or evidence from diagnostic studies.
The diagnostic work-up for an older adult with a seizure disorder diagnosis should begin with a physical examination. Laboratory investigations are vital to exclude metabolic abnormalities that may have precipitated seizure activity in patients with and without epilepsy. In patients with acute seizures, providers should screen for electrolyte disturbances, confirm euglycemia, and monitor nitrogenous waste products (ie, blood urea nitrogen and creatinine), calcium, magnesium, and liver function. These diagnostics are easier to perform in a controlled LTC environment.
In patients with seizure history that have altered mental status, an electroencephalogram (EEG) can be used to exclude or identify seizure activity. Interictal EEG in older adults may be of limited use with relatively low sensitivity or specificity for confirmation of diagnosis. Between 12% and 38% of older individuals without seizures will have intermittent focal slowing on EEG.9 However, recent studies show the utility of video and ambulatory EEG in combination with electrocardiogram monitoring. These studies suggest that the combination helped in making nonepileptic diagnoses such as syncope, cerebrovascular events, obstructive sleep apnea and other sleep disorders, hypotension, and psychogenic events.10
Deprescribing
Seizure management requires ongoing assessment and reassessment because the risks of both seizures and adverse effects of medications are dynamic over time. Among the most important decisions a physician will make is when to deprescribe and when to continue antiepileptic medications. Deprescribing should be considered when the costs of adverse effects from antiseizure medications exceed the perceived benefits. These costs of antiseizure medications include adverse effects of the drugs, polypharmacy, and financial burden (Table 2).
While the cost of medications for older adults on fixed incomes can cause economic burden, it should be noted that available generic medications have the potential for more variable chemical compositions compared with brand-name formulations. With older adults having such a narrow therapeutic window, there is concern for increased side effects with the generics. This must be weighed before starting, continuing, or discontinuing antiseizure medications.
Physiologic changes in older adults complicate the use of many antiseizure medications. With increased hepatic impairment and decreased enzyme inducibility, it is difficult to dose these medications appropriately (Table 3). Decreased renal elimination in older adults complicates the issue. Older adults also have noticeable decreases in concentration of plasma proteins, and albumin leads to decreased protein binding of medication, which leads to potentially toxic levels in the blood stream when theoretical therapeutic range is achieved. Drug distribution is also disrupted by changes in lean body mass and muscle tissue associated with aging. These issues are exacerbated when patients are already taking multiple medications for comorbid conditions. This leads to polypharmacy and increased chances for unwanted interactions.
Antiseizure medications tend to have high potential for drug interactions. The medications at highest potential for adverse drug interactions are enzyme-inducing medications such as phenobarbital, phenytoin, and carbamazepine.
Antiseizure medications also carry their own risk of side effects. Older adults in studies have demonstrated increased sensitivity to the side effects of these medications, even at lower doses.11 Frequent side effects include confusion, impaired gait, sedation, tremor, dizziness, visual disturbance, and mental decline.12 These medications are also highly associated with increases in osteoporosis and potentially debilitating fractures.
Older adults with a one-time seizure-like episode without abnormalities on EEG, symptomatic causes, abnormal neurological exam, or seizure occurring during sleep are at low risk for repeated seizure activity. Prescribers must make an individual judgment on whether the patient will benefit with continued therapy or whether medications should be discontinued. The decision could be shared between primary care physicians in collaboration with a neurologist. In older adults with only one documented seizure-like episode, it would be appropriate to consider discontinuing antiseizure medications until a recurrent seizure-like episode. Of course, the benefit of seizure prevention in older adults includes prevention of recurrent seizure activity. Not correctly managing the care of older adults with seizures creates an increased risk of events that may lead to permanent debilitation, including catastrophic falls. Patients who have 2 or more documented seizures with adequate objective information are likely to have recurrent symptomatic seizure episodes and would benefit from antiseizure medications. Data suggests patients who present initially with an unprovoked seizure have a 33% chance of having a recurrent seizure within 5 years.13 Patients who have an unprovoked seizure with epileptiform abnormality on EEG, symptomatic causes on imaging, or focal neurologic abnormalities, or a seizure that occurs during sleep, have at least a 60% chance of another seizure within 10 years.14 This population would benefit from antiseizure drug therapy.
It is appropriate to consider discontinuing antiseizure medications in patients who have remained seizure free for 2 to 4 years. Many studies have evaluated individual risk factors in the likelihood of seizure recurrence. A meta-analysis of 10 studies found several characteristics that were independent risk factors for seizure recurrence.15 The indicators most correlated with seizure risk were seizure-free interval on medication, age of onset of seizure activity, history of febrile seizures, number of total seizures, and epileptiform abnormality on EEG.15
The decision to discontinue medications should be based on clinical judgment with objective information to weigh risks and benefits. Patients must understand the options and be well informed so they can express their wishes to their physician. If a decision to discontinue medications is made, a withdrawal plan must follow. Sudden withdrawal of antiseizure medications such as carbamazepine and oxcarbazepine can provoke seizures and, therefore, must be tapered slowly.16 For patients who wish to continue antiseizure medication, it is important to frequently reevaluate the need in light of overall health. Patients continuing on medications that need to be monitored for therapeutic dosing should understand that dosing may need to change because of physiologic aging and possible worsening of comorbid conditions.
Special Considerations in the LTC Setting
As stated earlier, one of the most important prognostic factors to look at before deciding to discontinue medications is the seizure-free interval. If a patient has been seizure-free for a prolonged period with only a few total seizures, it would be reasonable to discuss ceasing antiseizure medication. In LTC settings, families and the power-of-attorney representative often make these types of decisions rather than patients. Informed consent is an appropriate topic of discussion, which should include the patient and all responsible parties. A stepwise approach is important. The first step is to review the case thoroughly and work with decision makers to come to consensus on what should be done. Staff is pivotal to monitor patients who discontinue antiepileptic medications. Having consistent basic neurologic examinations and increased supervision to detect possible seizure activity aids in future decisions on whether to stay off of a medication or resume antiepileptics. The most devastating injuries after a seizure episode involve falls, drowning, and burns. More frequent evaluation should also be performed by an on-site physician and nursing staff in the weeks immediately following cessation of antiepileptic medications.
Seizures in older adults in LTC can be difficult to manage due to poor medical histories, unclear patient or family expectations of palliative or end-of-life care for patients, and lack of objective documented data pertaining to the seizures.
Conclusion
The process of managing seizures in older adults can be difficult but is necessary in the pursuit of high-quality, person-centered care. Seizure management requires ongoing assessment and reassessment for all older individuals with a recent or past seizure diagnosis. Balancing the risks and benefits of continuing antiseizure medication is one of the most important parts of adequate seizure management.
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