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Review and Commentary on Epilepsy and the Elderly
They are our grandparents, our parents, neighbors and friends. They are Seniors—and they are at high risk for not just diseases like Alzheimer’s, heart disease and stroke, but for a more chronic and potentially more harmful disease- epilepsy.
According to the United States Census Bureau, “There is a projected percentage increase in the 65-and-over population between 2000 and 2050 of 147 percent. By comparison, the population as a whole would have increased by only 49 percent over the same period.” (1) What does this percentage increase mean? It means that as our life expectancy rate increases so too do the health risks we will face such as epilepsy. Until recently, epilepsy was believed to be predominantly a childhood disorder. Research now shows that the incidence of epilepsy in people age 75 and over is higher than in the first ten years of life. In fact, statistics have illustrated that approximately 7% of seniors have epilepsy.
A classic study by Alan Hauser, published in 1992, demonstrated that in people over the age of 60 living in Olmstead County, Minnesota, there is a sharp increase in the incidence of epilepsy.(2) The incidence in the 60+ year old age group was 127 per 100,000. This is in contrast to the incidence in 5-year olds, whose incidence rate is half that of the elderly. In all likelihood, the reason for this is probably due to the high prevalence rate of cerebrovascular disease in the elderly population. Hence, of the patients who suffer a stroke, approximately five to ten percent will later go on to develop epilepsy.
In fact, the most common cause of new-onset epilepsy in an elderly person is arteriosclerosis and the associated cerebrovascular disease. When I was in training 25 years ago, I was taught that the development of epilepsy in an older person meant a brain tumor. Newer data tells us that this is not the case. Only 5% of elderly patients who develop seizures have a brain tumor, whereas approximately 40% have underlying cerebrovascular disease. Another source of epilepsy in the elderly is Alzheimer’s disease. Although we think of Alzheimer’s as a problem of behavior and cognition, 10% of these people also develop epilepsy.
The clinical manifestations of epilepsy in the elderly are different than in younger adults and children. For example, in younger adults and children with epilepsy, approximately 60% present with generalized tonic-clonic seizures. In contrast, only 30% of elderly with epilepsy have generalized tonic-clonic seizures. In fact, the most common type of seizure in elderly patients with epilepsy is a complex partial seizure. Furthermore, another unique feature seizures in elderly patients is that the elderly often have more severe and prolonged post-ictal symptoms than younger individuals. In terms of epileptiform activity, when epilepsy begins in the elderly the yield of specific epileptiform activity via an EEG is less than half that of the younger adult population. Therefore, the concept of getting an EEG to rule out epilepsy is a conceptual error at any age, but it is even more of a problem in the elderly, and could lead to the misdiagnosis of epilepsy if the EEG is normal or shows non-specific abnormalities.
Veterans Administration Cooperative Study
In response to the lack of information regarding treatment of seizures in the elderly, the Veterans Administration Cooperative Study group (VA CSP) 428 recently completed a large multi-center study in which the primary purpose was to look at the treatment of epilepsy in veterans age 60 or older with new-onset partial seizures (3). The study was conducted in a double-blind fashion and compared three antiepileptic drugs: two newer, second-generation AEDs - gabapentin and lamotrigine - with a standard first-generation AED - carbamazepine.
Based on the results of the study, the researchers made several observations. First, there was a significant delay in treatment of epilepsy in the elderly. They found that only 24% of patients were initially diagnosed with epilepsy when they presented to their health care providers. Moreover, it took a mean of 19 months from the time the seizures began to the time epilepsy was correctly diagnosed. Confounding factors cited by the researchers included the presence of pre-existing known cerebrovascular disease or known cardiac disease in half of these patients. While these are valid confounding factors, I think the delay in treatment can be attributed to the way in which physicians are taught to diagnose. Essentially, physicians are taught to put all of the patient’s problems into a single diagnostic category. As was the case in this study, many of the patients in this study were initially incorrectly diagnosed because they were thought to have cardiac arrhythmia or “mini stroke” when the problem was actually epilepsy. Another clinical situation that was misdiagnosed in this study was episodic confusion that was due to a post-ictal phenomenon, and not confusion associated with senility or dementia. In fact, some of these patients were mistakenly treated for Alzheimer’s disease when in fact they were having seizures with prolonged post-ictal cognitive difficulties.
AEDs in the Elderly
There is now evidence (with more coming) that some of the newer anti-epileptic drugs are probably superior in this age group as compared to older traditional medicines. VA #428 for example, clearly demonstrated that the newer drugs, lamotrigine and gabapentin, were better tolerated than the first-generation drug carbamazepine. Currently, studies are underway to analyze other newer agents. For reasons that we don’t understand elderly-onset epilepsy is usually easier to control compared to epilepsy that begins in a younger age. Also, some of the second-generation AEDs seem to be more easily tolerated by the elderly versus the first-generation AEDs.
The question then arises, “If elderly patients with epilepsy tolerate some of the newer AEDs better why do physicians continue to prescribe first-generation AEDs?” One argument that some physicians use is that older anti-epileptic drugs are cheaper. While this may be true to a certain degree, studies suggest older AEDs are not as well tolerated compared to the newer agents. Moreover, recent pharmacoeconomic studies suggest the use of first-generation AEDs may actually be more expensive in terms of total health care costs than second generation AEDs.
In addition, first-generation medications have strong interactions with many other medications that seniors take, which does not occur with some of the newer AEDs. A specific drug-drug interaction that has been researched and is relevant to the elderly population with epilepsy is the effect of traditional AEDs on statins. The VA Cooperative study found that 80% of those patients were prescribed a statin. As stated earlier, arteriosclerosis is a major underlying cause of new-onset epilepsy in the elderly. The older traditional anti-epileptic drugs in contrast to the newer ones are potent hepatic inducers. In a recent study by Ucar (published in 2004) it was demonstrated that the serum concentrations of statins were lowered by 75% when taken with carbamazepine (4). Statins currently are the most expensive class of medicine in the VA pharmacy budget. By prescribing an older AED that is an inducer of hepatic metabolism to a patient also taking a statin drug, the physician must increase the dosage of the statin. Increasing the dosage also increases the number of times the patient will need to fill the prescription, thus defeating the physician’s original intention of helping the patient to save money.
Epilepsy in the elderly is much more common than once thought. In fact it is the most common time in life when epilepsy begins. It presents differently than epilepsy starting at a younger age and if one is looking only for generalized tonic-clonic seizures the diagnosis will be missed. The underlying cause seems to be most commonly arteriosclerosis, more specifically the sequelae of cerebrovascular disease and not neoplasm. Finally, there are both double blind controlled data as well as theoretical reasons that suggest that some of the newer anti-epileptic drugs may have advantages in this population over the old traditional medications, though more research is needed.
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