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.
Other diagnostic studies
Brain imaging, preferably magnetic resonance imaging with contrast, should be done in every patient with possible epilepsy due to stroke, traumatic brain injury, or other structural brain disease.51
Electrocardiography helps exclude cardiac causes such as arrhythmia.
Blood testing. Metabolically provoked seizure can be distinguished by blood analysis for electrolytes, blood urea nitrogen, creatinine, glucose, calcium, magnesium, liver enzymes, and drug levels (eg, ethanol). A complete blood cell count with differential and platelets should also be done in anticipation of starting antiepileptic drug therapy.
Lumbar puncture for cell count, protein, glucose, stains, and cultures should be performed whenever meningitis or encephalitis is suspected.
A sleep study with concurrent video-EEG monitoring may be required to distinguish epileptic seizures from sleep disorders.
Neuropsychological testing may help account for the degree of cognitive impairment present.
Risk factors for stroke should be assessed in every elderly person who has new-onset seizures, because the risk of stroke is high.17
Figure 1 shows the workup for an elderly patient with suspected new-onset epilepsy.
TREATING EPILEPSY IN THE ELDERLY
Therapeutic challenges
Age-associated changes in drug absorption, protein binding, and distribution in body compartments require adjustments in drug selection and dosage. The causes and manifestations of these changes are typically multifactorial, mainly related to altered metabolism, declining plasma albumin concentrations, and increasing competition for protein binding by concomitantly used drugs.
The differences in the pharmacokinetics and pharmacodynamics of antiepileptic drugs depend on the patient’s physical status, relevant comorbidities, and concomitant medications.52 Renal and hepatic function may decline in an elderly patient; accordingly, precaution is needed in the prescribing and dosing of antiepileptic drugs.
Adverse effects from seizure medications are twice as common in elderly patients compared with younger patients. Ataxia, tremor, visual disturbance, and sedation are the most common.1 Antiepileptic drugs are also harmful to bone; induced abnormalities in bone metabolism include hypocalcemia, hypophosphatemia, decreased levels of active vitamin D metabolites, and hyperparathyroidism.53
Elderly patients tend to take multiple drugs, and some drugs can lower the seizure threshold, particularly antidepressants, anti-psychotics, and antibiotics.32 The herbal remedy ginkgo biloba can also precipitate seizure in this population.54
Antiepileptic drugs such as phenobarbital, primidone (Mysoline), phenytoin (Dilantin), and carbamazepine (Tegretol) can be broad-spectrum enzyme-inducers, increasing the metabolism of many drugs, including warfarin (Coumadin), cytotoxic agents, statins, cardiac antiarrhythmics, antihypertensives, corticosteroids, and other immunosuppressants.55 For example, carbamazepine can alter the metabolism of several hepatically metabolized drugs and cause significant hyponatremia. This is problematic in patients already taking sodium-depleting antihypertensives. Age-related cognitive decline can worsen the situation, often leading to misdiagnosis or patient noncompliance.
Table 3 profiles the interactions of commonly used antiepileptic drugs.
The ideal pharmacotherapy
No single drug is ideal for elderly patients with new-onset epilepsy. The choice mostly depends on the type of seizure and the patient’s comorbidities. The ideal antiepileptic drug would have minimal enzyme interaction, little protein binding, linear kinetics, a long half-life, a good safety profile, and a high therapeutic index. The goal of management should be to maintain the patient’s normal lifestyle with complete control of seizures and with minimal side effects.
The only randomized controlled trial in new-onset geriatric epilepsy concluded that gabapentin (Neurontin) and lamotrigine (Lamictal) should be the initial therapy in such patients.56 Trials indicate extended-release carbamazepine or levetiracetam (Keppra) can also be tried.57
The prescribing strategy includes lower initial dose, slower titration, and a lower target dose than for younger patients. Intense monitoring of dosing and drug levels is necessary to avoid toxicity. If the first drug is not tolerated well, another should be substituted. If seizures persist despite increasing dosage, a drug with a different mechanism of action should be tried.58 A patient with drug-resistant epilepsy (failure to respond to two adequate and appropriate antiepileptic drug trials59) should be referred to an epilepsy surgical center for reevaluation and consideration of epilepsy surgery.
Patient and caregiver support is an essential component of management. New-onset epilepsy in the elderly has a significant effect on quality of life, more so if the patient is already cognitively impaired. It erodes self-confidence, survival becomes difficult, and the condition is worse for patients who live alone. Driving restrictions further limit independence and increase isolation. Hence, psychological support programs can significantly boost the self-esteem and morale of such patients and their caregivers.
SPECIAL CONSIDERATION: EPILEPSY IN THE NURSING HOME
Certain points apply to the growing proportion of elderly who reside in nursing homes:
- Several studies in the United States and in Europe60–62 suggest that this subgroup is at higher risk of polypharmacy and more likely to be treated with older antiepileptic drugs.
- Only a minority of these patients (as low as 42% in one study60) received adequate monitoring of antiepileptic drug levels.
- The clinical characteristics and epileptic etiologies of these patients are less well defined.
Together, these observations highlight a particularly vulnerable population, at risk for medication toxicity as well as for undertreatment.
OUR KNOWLEDGE IS STILL GROWING
New-onset epilepsy, although common in the elderly, is difficult to diagnose because of its atypical presentation, concomitant cognitive impairment, and nonspecific abnormalities in routine investigations. But knowledge of its common causes and differential diagnoses makes the task easier. A high suspicion warrants referral to a neurologist or epileptologist.
Challenges to the management of seizures in the elderly include deranged physiologic processes, multiple comorbidities, and polypharmacy. No single drug is ideal for antiepileptic therapy in the elderly; the choice of drug is usually dictated by seizure type, comorbidities, and tolerance level. The treatment regimen in the elderly is more conservative, and the target dosage is lower than for younger adults. Emotional support of patient and caregivers should be an important aspect of management.
Our knowledge about new-onset epilepsy in the elderly is still growing, and future research should explore its diagnosis, treatment strategies, and care-delivery models.
