Alzheimer's disease (AD) is not ordinarily thought to be associated with seizures. As AD progresses, the incidence of seizures increases, and, late in the course, about 20% of patients develop seizures.³ It is important to recognize that even brief seizures can further impair function in a patient already compromised by AD. Moreover, it is not always apparent that occasional complex partial seizures characterized by behavioral change are any different from the usual fluctuations in mental status in the dementias. In fact, fluctuating confusional states or inattention are common to both conditions. (To suspect partial seizures, look for stereotypy, for example, repetitive staring for brief periods, increased confusion lasting for minutes [usually not hours], or observable automatisms, such as orofacial movements or repetitive purposeless movements of the hands or feet that accompany a confusional state. It is not always possible to make a clear differentiation. This is why EEG studies in suspected cases are essential. If there is any evidence of epileptiform activity [eg, spikes], then seizure activity should be suspected. Such patients may benefit from prolonged EEG/ Video monitoring.) This probably is the reason that patients in long-term care facilities may not be diagnosed as having seizures unless they develop generalized convulsions, which are not the most common seizure type in this population.⁴

An important clinical note: A variety of toxic-metabolic disorders may be complicated by seizures. By definition, these are not classified as epilepsy. Examples include hypoglycemia, hypocalcemia, hyponatremia, renal failure, and use of various medications, mainly psychotropic compounds. The seizures associated with these conditions are no less harmful than seizures as manifestations of epilepsy. The main consideration is treatment. Such seizures are usually treated acutely with antiepileptic drugs, but chronic AED treatment after the underlying disorder is corrected, is not indicated.

Morbidities resulting from seizures

A variety of problems—often serious, disabling, and life threatening—may result from the occurrence of seizures in geriatric patients. Fractures and dislocations are not uncommon and may lead to distress and impaired function. The liability in this population is more pronounced due to the high prevalence of osteoporosis.

All patients found on the floor who are unconscious or confused come into consideration for seizures as a possible etiology. Unless the cause of a fall is clear (and it often is not), a seizure is a possibility. Also in the differential are stroke, head injury secondary to the fall, and metabolic disorders. An EEG in all of these instances is indicated. If indeed there is epileptiform activity in the record, a seizure is a likely consideration. MRI of the brain, appropriate laboratory studies are also indicated.

More serious are head injuries, resulting in concussion and confusion, prolonged loss of consciousness, and even intracranial bleeding. The latter likely would present as subdural hematoma, although intraparenchymal hemorrhage is also possible. Physicians must be alert for new onset symptoms, such as headache, dizziness, or gait difficulty. The symptoms may be mild in degree but require an imaging study to search for intracranial blood. Even with relatively minor head injuries, an older patient may develop increased memory deficits or difficulties with concentration, often for a prolonged period. Other problems, less serious but nonetheless worrisome, are lacerations, bruises, and a bitten tongue, not to mention psychological traumata of embarrassment or fear.

Morbidities interfering with effective treatment of seizures

Co-morbidities not only contribute to the causation and consequences of seizures, but they also interfere with effective treatment. Common illness that leads to disability in late life can lead to poor medication adherences.⁵ For example, failing eyesight from senile macular degeneration or cataracts can cause confusion concerning which tablet or capsule to take at a particular time. The problem is compounded by the fact that older adults usually take multiple medications, many of which have a similar appearance (shape, color, size). If the individual has trouble with fine finger movements, perhaps secondary to a stroke, there is difficulty manipulating the dosage form, some of which are very small. Changes in mental status, such as concentration, confusion, or memory deficits, require that a caregiver be available to administer medications. If supervision is inadequate, the result will be poor adherence with predictable consequences. Other morbidities that pose difficulties for the older person with epilepsy include untoward results of cerebrovascular disease, such as dysphasia, dysphagia, diplopia, and any other dysfunction that impedes the person's ability to comply with treatment.

Morbidities that worsen the consequences of seizures

As noted, seizures in an older individual can lead to serious consequences. However, when there are coexisting deficits, such as the consequences of stroke (eg, hemiparesis, aphasia) or dementia (eg, Alzheimer's disease or multi-infarct dementia), post-ictal function may deteriorate further with delayed return to baseline over days, or even weeks. For example, a mild dysphasia may progress to a frank aphasia with inability to express one's self or comprehend what is said. A mild hemiparesis may convert to a hemiplegia with inability to move the previously mildly impaired limbs. In the patient with cognitive impairment, a seizure may result in worsening of memory, inability to concentrate, or confusion with a marked effect on an already impaired quality of life. Co-existing psychiatric conditions, especially depression, may worsen as a result of intercurrent seizures. Increased depression, in and of itself, is debilitating, but broader consequences include adverse effects on adherence with the resultant possibility of increased seizures.

For all these reasons, safe and effective treatment of seizures in the elderly is essential to preserve optimal functioning and quality of life.⁶

Co-morbidities secondary to adverse effects of AEDs

Antiepileptic drugs (AEDs) may interfere with optimal functioning due to adverse effects that may be exaggerated or more severe in older adults compared with younger patients.^7,8 In particular, the older, long established AEDs are more likely to lead to disability in older adults than the newer generation of antiepileptic compounds. Common adverse effects that physicians must take into consideration in older adults include ataxia, peripheral neuropathy, tremor, hyponatremia, soft-tissue changes, and organ system toxicity.

As a prototype of the established drugs, phenytoin is still widely used in the geriatric population. Its adverse effects can be categorized as hypersensitivity, dose-related, and chronic. There is no evidence that hypersensitivity due to phenytoin is more frequent or severe in older patients compared with younger patients. Dose-related side effects, while of similar incidence in all age groups, do have greater consequences in older adults.⁹ One of the most common is ataxia, which may occur at lower serum levels in older adults than younger subjects.¹⁰ Older adults often have gait problems due to a variety of causes (eg, stroke, Parkinson's disease, neuropathy); thus, even mild ataxia or gait unsteadiness secondary to AEDs can lead to a marked increase in underlying gait difficulties with an attendant risk of falling.

A chronic consequence of phenytoin treatment is development of a peripheral neuropathy, ie, progressive sensory (and sometimes) motor loss in the distal portions of the extremities. If mild, it is not a major issue. It can be more severe and interfere with function that perhaps is already compromised by another process. The neuropathy causes increasing gait unsteadiness over the years, and in combination with an already impaired gait due to an underlying neurological process, compounds the patient's disability.

Osteoporosis is an issue with compounds metabolized by the P450 system and is described with phenytoin and carbamazepine.

Other AED co-morbidities that are particularly problematic in older patients include tremor, likely to result from valproate or carbamazepine treatment.¹¹ Tremor, even when mild, can impair ability to manipulate medications and lead to difficulties with adherence. The tremor associated with valproate is serum concentration-dependent. Lowering the daily dose should lead to a decline in tremor intensity, but crossover to another drug will eliminate it.

Some AEDs, in particular carbamazepine and oxcarbazepine, are associated with hyponatremia.¹² Generally speaking the decline in serum sodium concentration is modest and thought to be a physiological consequence of treatment. Conversely, severe hyponatremia may occur, thus increasing seizure liability.

Soft-tissue changes have been associated with older AEDs, eg, gingival hypertrophy (phenytoin) and frozen shoulder (phenobarbital). While relatively minor, these conditions can cause disability–gingival bleeding, periodontal infection from gingival hypertrophy; pain and disability from frozen shoulder.

Certain AEDs are known to cause toxicity to major organ systems, eg, the liver and bone marrow. Although relatively rare, phenytoin may lead to altered liver function tests and, even more rarely, to liver failure. Carbamazepine is known to lower the white blood cell count without evidence of bone marrow depression. The count may fluctuate over time but usually does not dip below 3,000. Rarely, pancytopenia may occur.

Drug interactions

The older patient is typically on multiple medications for different medical and neurological problems. In our VA study on seizures in elderly, the average number of prescribed drugs was seven.² Thus, there is a high probability that medically significant drug interactions may occur.¹³ This is particularly problematic with the older enzyme-inducing (EI) AEDs. Reduced effectiveness of statins, calcium channel blockers, warfarin, and antidepressants have been described. These effects may result in worsening of existing medical problems. Thus selecting an AED without potential to induce or inhibit liver enzymes is preferable.

Conclusion

Epilepsy in the elderly population presents both diagnostic and therapeutic challenges not commonly found in younger age groups. Because correct diagnosis and rational treatment are essential to success, it is recommended that older patients with new onset seizures, or those with established seizure disorders who continue to have seizures or side effects of treatment, be referred to an epileptologist, or a neurologist with a special interest in seizure disorders for an opinion. A cooperative effort between the primary care physician and neurologist will ensure that the patient receives continuing effective management.

Dr. Rowan is professor, department of neurology, Mount Sinai School of Medicine, and chief of neurology, Bronx Veterans' Administration Medical Center, NY.

Disclosure: The author, peer reviewers, series editors, and editor (Janice T. Radak) report no relevant financial relationships. Dr. Sherman reports stock ownership in Pfizer.

This is the third and final article in a series on epilepsy and seizures in older adults developed in conjunction with the Epilepsy Foundation of America.

References

1. CDC/National Center for Health Statistics, 1995 National Health Interview Survey (unpublished data). Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/ss4808a2.htm. Accessed November 29, 2005.

2. Rowan AJ, Ramsay RE, Collins JF, et al; VA Cooperative Study 428 Group. New onset geriatric epilepsy: A randomized study of gabapentin, lamotrigine and carbamazepine. Neurology 2005; 64(11):1868–73.

3. Romanelli MF, Morris J, Askin K, Coben LA. Advanced Alzheimer's disease is a risk factor for late-onset seizures. Arch Neurol 1990; 47(8):847–50.

4. Hauser WA. Epidemiology of seizures and epilepsy in the elderly. In: Rowan AH, Ramsay RE (eds). Seizures and epilepsy in the elderly. Boston: Butterworth-Heinemann, 1997:7-20.

5. Cramer JA. Identifying and improving compliance patterns: a composite plan for health care providers. In: Cramer JA, Spilker B, Eds. Patient Compliance in Medical Practice and Clinical Trials. New York:Raven Press; 1991:387-392.

6. Rowe JW, Kahn RL. Successful Aging. New York, Pantheon Books, 1998.

7. Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313(3):145–151.

8. Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med 1992; 327(11):765–71.

9. Feely J, Coakley D. Altered pharmacodynamics in the elderly. Clin Geriatr Med 1990; 6(2):269–83.

10. Cloyd J. Commonly used antiepileptic drugs: Age-related pharmacokinetics. In: Rowan AJ, Ramsay RE. Seizures and Epilepsy in the Elderly. Boston: Butterworth-Heinemann, 1998, 219–28.

11. Rowan AJ. Valproate. In: Engel J Jr, Pedley TA, eds. Epilepsy, A Comprehensive Textbook. Philadelphia, Lippencott-Raven 1998,1599–1608.

12. Klenfeld M, Casimir M, Borra S. Hyponatremia as observed in a chronic disease facility. J Am Geriatr Soc 1979; 27(4):156–61.

13. Leppik IE, Wolff D. Drug interactions in the elderly with epilepsy. In: Rowan AJ, Ramsay RE. Seizures and Epilepsy in the Elderly. Boston: Butterworth-Heinemann, 1998, 291-302.