Epidemiology, Etiology, and Diagnosis

Epidemiology. The elderly are the segment of the population who are currently experiencing more seizures than any other. [24] Although epilepsy
is more common in children than young adults, in seniors age 70 the incidence of epilepsy is nearly twice that of children, and in those over 80, it
is more than 3 times that of children (Figure 1).[27]

Figure 1. Epilepsy in the elderly.

Elderly patients with risk factors for seizures who have a seizure have an 80% chance of experiencing another one. [40]In a recent epidemiologic
study of the nursing home population, 4.5% of patients were taking AEDs on admission for seizures or epilepsy. [41] An additional .5% of patients
began AEDs for seizures or epilepsy within the first 3 months after admission. [41] Seizures are of particular importance in the elderly because of the
increased incidence and mortality of status epilepticus. [27]
Etiology. Cerebrovascular disease is the most commonly identified cause of epilepsy in the elderly, accounting for up to 40% of cases.
[27]

Approximately one third of patients who had seizures within 2 weeks of a stroke go on to develop further seizures. [42] Hemorrhagic infarctions

are more likely to induce seizures than bland infarcts. [27]

Of interest, the hazard of stroke nearly triples in the years following seizure onset in people 60 years or older as compared with controls without
seizures, which suggests that underlying cerebrovascular disease may be responsible for the epilepsy. [43] Consequently, elderly patients with new
onset seizures should be screened for vascular risk factors and treated when indicated. [43]
The second most important identifiable cause of seizures in the elderly is dementia, responsible for 11% to 16% of cases. [27] Less frequent causes
of epilepsy in the elderly include brain tumors (4% to 6%) and trauma (1% to 3%). It is essential that elderly patients with new onset seizures have
high-quality imaging studies to identify the presence of hemorrhage, infection, or tumors, which may require neurosurgical intervention. As in other
age groups, attempts to identify the etiology of chronic epilepsy in the elderly may be frustrating, with up to 50% of cases remaining idiopathic or
cryptogenic. [27]
Similar seizure types occur in the elderly as in younger adults with the same type of epilepsy. According to one author, seizures with auras,
automatisms, loss of awareness, and lateralizing signs occur with equal frequency, whereas focal motor seizures and convulsions may be less
frequent in the elderly.[26] However, another source observed that auras and automatisms are less common, and postictal confusion may last
longer.[40]
Diagnosis. Diagnosis of epilepsy in the elderly may be more difficult because interictal EEGs are less likely to reveal interictal epileptic activity.
[44]

A retrospective review of 70 patients (40 men, 30 women; mean age, 70 years) with seizure onset at age 60 revealed that only 18 (26%) of

the patients had interictal epileptic activity on their first EEG. [44] Extended-duration EEGs may significantly increase the yield of epileptiform
activity. Unlike younger adults, complex partial seizures in the elderly are more likely to be extratemporal than temporal. [40] Seizures may be
responsible for episodes of altered mental status, confusion, memory loss, or syncope, which may be mistakenly attributed to comorbid diseases,
such as cardiac disease, dementia, hypertension, or transient ischemic attacks. [40]
Despite the high incidence of new onset epilepsy in the elderly, the time to diagnosis is often delayed. [45] In a study of 159 elderly veterans, the
mean time to diagnosis was 1.7 years; 50% of patients with generalized tonic-clonic seizures were immediately diagnosed, as compared with only
20.9% with complex partial seizures.[45]

Treatment Considerations
Compared with younger patients, elderly patients are more likely to be taking multiple medications, which increase the probability of drug-drug
interactions.[40] Age-related hepatic and renal dysfunction may require lower doses and increased dosing intervals. [27] Cognitive function may be
impaired due to Alzheimer's disease, Parkinson's disease, multiple cerebral infarcts, alcohol-related conditions, or other etiologies, which
potentially increase the sensitivity to adverse medication effects. Dose-dependent side effects, such as dizziness or imbalance, and drug-specific
adverse events, such as hyponatremia and tremor, may occur at lower AED serum levels than in younger patients. [40]Advanced age is a risk factor
for bone loss, which may be exacerbated by older AEDs, such as phenobarbital, phenytoin, and primidone. [46] AED polytherapy appears worse
than monotherapy in terms of facilitating the risk of osteopenia or osteoporosis. Fractures associated with bone disease may lead to loss of
independence, hospitalization, and death. The newer AEDs are not known to affect bone loss, but long-term term data on these agents are
limited.[46]
New AEDs in the elderly. Limited information is available regarding the use of new AEDs in the elderly. [27] A recent review of AED use by 21,435
Veterans Administration (VA) patients, ages 65 or older, revealed that 80% were treated with phenobarbital or phenytoin. [5] Both of these drugs
may sedate patients cause cognitive side effects, and potentially produce drug-drug interactions. [47] In addition, phenytoin can be difficult to dose
because of its nonlinear side effects (Physicians' Desk Reference [PDR]).
As elderly patients are likely to be taking multiple medications, [27] AEDs that lack drug-drug interactions offer a particular advantage. Of the new
AEDs, only gabapentin and levetiracetam fit this profile. [1] Both of these drugs are effective in partial seizures and are primarily renally excreted.
Consequently, dosage adjustments must be made for patients with impaired renal function. Somnolence may limit dosing for both gabapentin and
levetiracetam.[27]
A recently completed, 18-center, VA Cooperative study (VACS 428) compared carbamazepine (600 mg/day), gabapentin (1500 mg/day), and
lamotrigine (150 mg/day) for newly diagnosed epilepsy in 594 patients who were at least 60 years old (mean age, 72.3). [48] Twenty-five percent of
patients had only generalized tonic-clonic seizures and 43% had only partial complex seizures. At 3 months, 66% were seizure-free, which
declined to 58% at 6 months. The most common side effects were weight gain (55.3%), sedation (44.3%), gastrointestinal problems (29.5%),
change in mood/affect (29.1%), dizziness (28.7%), gait disturbance (28.4%), weight loss (27.6%), cognitive decline (27.2%), and hyponatremia
(7.1%).[48] A full report of the study's findings is pending.
A retrospective study that evaluated the effectiveness of zonisamide in 100 patients according to patient age found that patients > 60 years old (n
= 11) experienced an outcome as good if not better, than younger patients. None of the elderly patients discontinued the drug due to lack of
efficacy, whereas 27% discontinued due to side effects. [49]
A retrospective study that evaluated the effectiveness of levetiracetam in 171 patients according to patient age found that 4 (19%) of the 21
elderly patients became seizure-free, which was higher than the other age groups. [50] Adverse effects were similar in all age groups.[50] Another
retrospective study of 13 patients 60 treated with levetiracetam monotherapy for at least 6 months identified 8 (61.5%) who became seizure-free
at doses of 500-3000 mg/day (mean, 1839.2). [51]
A double-blind protocol comparing topiramate monotherapy at 50 mg/day vs 200 mg/day in patients 60 years or older has enrolled 39 patients
and is under way. Preliminary results suggest that side effects are similar in the elderly as in other age groups. [52]
In a cohort study of oxcarbazepine, the number of drug discontinuations due to adverse events was similar in 52 patients 65 years or older as
compared with 1574 adults ages 18-64. The study authors concluded that oxcarbazepine was safe to use in elderly patients. [53]
Adverse events. A number of factors render the elderly particularly susceptible to adverse events of AEDs: The large number of medications
typically taken by elderly people increases the likelihood of drug-drug interactions; [24] increased age renders older patients more susceptible to
AED neurotoxic effects, such as ataxia, sedation, tremor, and visual disturbances; [27] and underlying neurodegenerative or cerebrovascular
disease may worsen cognitive side effects. [24]Decreased serum plasma proteins and albumin reduce protein binding sites, leading to an increase
in unbound active drug, and decreased hepatic and renal function increases AED half-lives, augmenting the probability of drug toxicity if dosages
are not reduced and/or dosing intervals increased.[27] Traditional AEDs, such as carbamazepine, phenytoin, and valproate, are highly proteinbound and primarily metabolized by the liver (Table 3). Carbamazepine and phenytoin are also inducers of hepatic metabolism, which may result
in decreased effectiveness of other medications, including chemotherapeutic drugs, steroids, or warfarin. [27]
Older age is a risk factor for hyponatremia due to carbamazepine. [54] Hyponatremia may also occur with oxcarbazepine (Table 3). The addition of a
thiazide diuretic in a 60-year-old patient who had previously tolerated carbamazepine resulted in dizziness, lethargy, and somnolence associated
with hyponatremia.[54] Consequently, elderly patients taking carbamazepine or oxcarbazepine should be monitored for the development of
hyponatremia, particularly when combined with diuretic treatment.
New AEDs should be considered as first-line therapy for elderly patients with seizures, [40] and risks and benefits must be compared with older
AEDs (Table 3). AED-related side effects may be minimized in elderly patients by beginning treatment at a low dose and titrating slowly to
effectiveness.[40]