• Common causes
• Strokes
• Seizure presentation
• Causes of Episodic Neurologic Dysfunction
• Evaluation of first seizure
• First seizure treatment
• Choosing AEDs for seniors
• Pharmacokinetics
• Prognosis and quality of life
• Long-term management
• Surgery
• Status epilepticus
• References

Most metabolic conditions become more common with aging, as does the use of multiple prescription medications.1 Offending drugs(see Table: Drugs That May Lower Seizure Threshold) include theophylline and neuroleptics, as well as a variety of antidepressants.2 Sedative and alcohol withdrawal are also significant causes.

Although metabolic conditions and medication side effects may be recurrent, they are at least potentially preventable and, therefore, would not lead to a diagnosis of epilepsy.

Causes of epilepsy

On the other hand, acute neurologic conditions such as stroke or trauma may produce structural damage to the brain. Even functionally minor damage can permanently alter neuronal excitability and synchronization, resulting in a tendency toward recurrent unprovoked seizures—that is, epilepsy.

Because recovery from central nervous system injury, at least on a cellular level, is usually incomplete, the accumulation of brain insults over time would lead to increased incidence and prevalence of epilepsy with aging.

It is important to recognize, however, that even in patients with structural lesions that could potentially cause epilepsy, seizures can have a toxic-metabolic or other preventable cause. These should be ruled out before assuming that epilepsy has developed.

Nearly every study of epilepsy in the elderly has found vascular disease (either acute or remote) to be responsible for the largest proportion of cases, in general the majority of those for which a cause is known.Table: Etiology of Seizures and Epilepsy

Brain tumor (either metastatic or primary) is the next most common cause of epilepsy, reported in up to 28% of new-onset cases.

Other structural causes of epilepsy include:

• trauma, which may not be recalled by the patient
• degenerative disease, particularly senile dementia of the Alzheimer’s type
• infectious causes, such as meningitis or encephalitis.

Alzheimer’s disease, associated with seizures in perhaps 10% of cases,3,4 will be an increasingly important cause of epilepsy in the future unless effective methods of prevention or treatment are found.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Strokes may be divided into ischemic and hemorrhagic strokes. Ischemic strokes can be further subdivided into embolic, thrombotic, and small vessel (“lacunar”) strokes. Hemorrhagic strokes may be categorized by location and etiology.7 Seizures are most likely to result from strokes that directly affect cortex.

All causes of ischemic strokes and most causes of hemorrhagic strokes show marked increases with aging. Some (but not all) studies have shown that the embolic type of ischemic stroke has the greatest tendency to produce both acute seizures and epilepsy,8 perhaps because it is the most likely to involve cortex directly. Also, embolic strokes often include at least a small hemorrhagic component. In experimental models, the direct application of iron increases cortical irritability.

Overall, 4% to 14% of infarcts are associated with early seizures, usually defined as occurring within 1 to 2 weeks of the insult, whereas 3% to 10% are associated with later seizures.8-13

Early seizures are a risk factor for late seizures.14 Late seizures developed in 10 out of 31 patients with early seizures, in contrast to 3 out of 31 matched stroke patients without early seizures.

The longer the interval between the insult and the first seizure, the more likely it is that the seizure represents a permanent change in neuronal connectivity predictive of further seizures if untreated. The occurrence of seizures within a week or two after stroke does not necessarily indicate that epilepsy will develop, however.

The risk of seizures after hemorrhagic stroke is more strongly linked to mechanism and location than for ischemic stroke:

• 17% of hemorrhages in one study, typically with cortical extension, were accompanied by seizures, all occurring at the onset of hemorrhage.15
• Hypertensive hemorrhage is most often subcortical, decreasing the likelihood that seizures or epilepsy will result.16
• Lobar hemorrhage and basal ganglia hemorrhage involving the caudate are associated with a significant risk of acute seizures.17

In a sense, seizures may represent a marker for cerebrovascular disease in older patients:

• New-onset seizures are associated with hypertension, presumably a marker for cerebrovascular disease, even in the absence of clinical or neuroimaging evidence of stroke.18
• Transient ischemic attacks (TIAs) lasting less than 24 hours have in some series been found to presage epilepsy.
• Seniors presenting with seizures were found to have an increased incidence of vascular disease compared with a control population.19
• A trend of declining incidence of idiopathic seizures in seniors parallels the decline in cerebrovascular disease over the years from 1935 to 1984.20

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Information about specific seizures in seniors varies among studies. Partial seizures, particularly if defined as in the International League Against Epilepsy classification to include secondarily generalized seizures, are much more common than primarily generalized seizures, which usually have their onset in childhood or adolescence and often remit with maturity.

Complex partial seizures are the most common seizure type in seniors. In some cases, these represent the continuation into old age of refractory mesial temporal lobe epilepsy (TLE) that began in childhood, adolescence, or early adulthood. The prevalence of “typical” mesial TLE in seniors is uncertain.21 Similar limbic seizures can certainly begin late in life as a result of appropriately placed lesions.

Retrospective studies have been inconsistent in their identification or classification of secondarily generalized seizures and have considered only one-third to two-thirds to be partial.21-24 Electroencephalographic (EEG) data, when available, frequently show focal abnormalities.24,25

Anecdotally, manifestations of partial seizures in seniors are more varied than those in younger adults. In seniors, partial seizures largely follow vascular and neoplastic insults, which can occur in many areas of the brain. In young adults, on the other hand, most partial seizures are of mesial temporal origin.

Partial seizures with prominent motor manifestations, reflecting the low threshold of motor cortex to seizure generation,26 are often seen after stroke, although it is not clear that these seizures are more common in older than in younger persons.27 Reporting bias may affect these data because motor seizures are more likely to be recognized and diagnosed in patients who may have diminished communicative skills than are seizures with only subjective manifestations. Visceral, visual, and somatosensory auras preceding complex partial or secondarily generalized seizures are probably not rare but must be carefully sought.27,28

Classification of epilepsy syndromes in seniors leans strongly toward the localization-related, symptomatic group. Idiopathic syndromes would represent long-standing cases that have not remitted. Juvenile myoclonic epilepsy, for example, typically persists into adulthood. Since it is often misdiagnosed, it may occasionally “present” in old age. Since most of these idiopathic syndromes are defined in part by age of onset, however, their identification may be obscured in atypically older patients.21

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254. With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Whenever an older patient experiences a transient confusional state, unexplained loss of consciousness, or a fall without a clear environmental or medical explanation, the possibility of seizures must be considered.29,30 Episodic neurologic dysfunction has a wide differential diagnosis, however, with certain conditions being much more common in seniors.

Disorders that are sometimes difficult to distinguish from seizures include:31

• syncope
• TIAs
• migraine
• sleep disorders
• paroxysmal toxic-metabolic abnormalities
• movement disorders
• psychiatric conditions

Syncope

Potential causes
Syncope in seniors is particularly important to recognize because it becomes both more common and more potentially ominous with aging. Typically, the mean blood pressure must drop suddenly and significantly, usually to less than 50 mm Hg.32 Mechanisms that can cause a sufficient decrease in cerebral perfusion to produce the loss of consciousness and postural tone that characterizes syncope include:33

• an inappropriate reflex-mediated decrease in heart rate, vascular tone, or both
• arrhythmias producing decreased cardiac output
• decreased cardiac output from other causes

The most common manifestation of reflex-mediated syncope is simple vasovagal fainting. It usually follows a strong emotional stimulus and often (but not always) has a strong postural component. Vasovagal fainting is the most common cause of syncope in young people but it may account for only 1% to 5% of cases in seniors.32 Other reflex-mediated causes include carotid sinus syncope, micturition and defecation syncope, and syncope during and after eating.

It is essential to rule out cardiac arrhythmias because they can lead to sudden death if untreated. Both bradycardias and tachycardias may result in syncope. They often coexist in older people.33 Occasionally, however, arrhythmias that occur with altered consciousness may be seizure-induced.34,35

Other potential causes of syncope include medications that result in hypovolemia (e.g., diuretics), decreased venous tone (e.g., nitrates), or decreased systemic resistance (e.g., vasodilators and other antihypertensives). Nondrug causes of these phenomena, including fluid loss and autonomic neuropathy, are also common in seniors.

Syncope can also be caused by a sudden obstruction of blood flow from a pulmonary embolus, or more chronic obstruction from aortic stenosis in the setting of increased demand.

Diagnosis
If the history of the episodes includes a postural component, that supports the diagnosis of syncope. (Even vasovagal syncope can occur in the supine position with sufficient emotional stimulus, however.)

Premonitory symptoms such as palpitations, warmth, diaphoresis, fading vision and hearing, nausea, and diffuse weakness also support a diagnosis of syncope, although all these symptoms also may occur during partial seizure auras. In syncope, they are often of more gradual onset, and the nausea associated with syncope does not typically have the rising component that is so common in seizures of mesial temporal origin. Pallor is more often noted with syncope but may also occur during limbic seizures.

Diffuse stiffening or frank clonic movements may occur with syncope, particularly if the person is maintained in the head-up position.36 With rare exceptions, convulsive syncope does not represent a cortical electrical seizure but occurs with cortical depression, usually manifested on the EEG by diffuse flattening.37 The release of brainstem mechanisms from cortical inhibition is the hypothesized mechanism.

Unlike a generalized tonic-clonic seizure, convulsive syncope is usually followed by little or no confusion or somnolence. Urinary incontinence and tongue biting are occur rarely.

Physical examination should emphasize cardiovascular features. Orthostatic vital signs are sometimes revealing. Ancillary tests worthy of consideration include:38

• ECG (electrocardiogram)
• ambulatory ECG (Holter) monitoring
• echocardiography
• tilt-table testing (in selected cases)
• cardiac electrophysiologic studies (in selected cases)

TIAs

TIAs (transient ischemic attacks) are important to recognize because of the impact that treatment can have on the risk of future stroke and myocardial infarction.39,40 Although ischemia generally produces “negative symptoms” such as weakness or visual loss rather than “positive symptoms” such as stiffening, shaking, or visual hallucinations, there are many exceptions.

Among the most dramatic are so-called limb-shaking TIAs associated with severe carotid disease contralateral to the involved leg, arm, or both.39,41 These are rarely bilateral. The face and cognition are spared. Their duration may be seconds to minutes, similar to that of seizures, but unlike motor seizures, these TIAs are consistently postural and respond to endarterectomy rather than antiepileptic drugs (AEDs).

Conversely, seizures manifested by motor inhibition, loss of vision, and aphasia with preserved consciousness are rare but well documented. It can be difficult to distinguish them from TIAs, but the EEG is invaluable in confirming their epileptic origin.42,43

Features of the history supporting a diagnosis of TIAs include:

• constellations of symptoms consistent with ischemia in either anterior or posterior circulations, or in a “lacunar” distribution
• prior vascular disease or known risk factors
• much slower resolution than for seizures (duration up to several hours)

Neurologic examination during symptoms usually confirms a vascular distribution. Bruits may be present.

Vascular and cardiac studies may confirm a suspected location or mechanism.

Neuroimaging studies can be extremely helpful in showing evidence of either prior vascular insults or an active lesion corresponding to the current symptoms. An appropriately placed infarct could also provide the substrate for seizures, however. EEG may be helpful and diagnostic if recorded ictally.

Migraine

Migraine can be difficult to distinguish from epilepsy, and the two processes can coexist. Migraine is more common in younger than in older adults, but migraine may more often occur without headache in seniors.44,45

Migraine auras such as scintillating scotomata, hemianopia, or monocular blindness may be confused more readily with TIAs than with seizures. “Basilar migraine” symptoms, however, can include altered consciousness as well as vertigo, ataxia, and visual disturbances.45 This can mimic a seizure or nonconvulsive status epilepticus.

Sleep disorders

Obstructive sleep apnea is common in seniors, affecting 5% to 10% or more of seniors.46 Nocturnal cardiac arrhythmias may increase the risk of cardiac or cerebral ischemia and of sudden death. The most common consequence of sleep apnea is excessive daytime somnolence, which may greatly affect functioning. Sleepiness can sometimes manifest as “microsleeps,” brief periods of unresponsiveness that can be confused with partial seizures. Rarely, intermittent confusion or even apparent dementia can result from excessive sleepiness.

Other causes of poor nocturnal sleep, such as periodic limb movement syndrome, can have similar daytime manifestations.46 Occasionally, the limb movements themselves may be mistaken for seizure activity. Usually they are easy to distinguish because they occur as sustained 0.5- to 5-second movements at 20- to 60-second intervals rather than in a rapid, rhythmic pattern.

Somnambulism and night terrors, the classic parasomnias of slow-wave sleep, may be confused with seizures but are rare in old age.46,47

Nocturnal enuresis, raising the possibility of a nighttime convulsion, may occur in seniors because of a urinary tract infection or other urologic cause. Typically, however, daytime incontinence is also present.

The narcolepsy-cataplexy syndrome generally presents in early adulthood, although it may not be diagnosed until later. Obstructive sleep apnea, which may coexist with narcolepsy, is a much more common cause of daytime somnolence in seniors, however.

Attacks of “paroxysmal nocturnal dystonia” are likely to represent frontal lobe seizures.46

Rapid eye movement (REM) sleep behavior disorder is a recently recognized parasomnia that occurs most commonly in elderly men. It consists of sudden arousals from REM sleep that are immediately followed by complex and often violent behavior (at times appearing directed), although the patient is unresponsive and amnestic for these periods. There is a significant risk of injury to the patient or bed partner. These behaviors are often construed as defensive activity related to dreaming, with loss of the somatic atonia that is normally present during REM sleep and dreaming. These episodes are easily misinterpreted as complex partial seizures or postictal agitation.47

Polysomnography is essential for diagnosis of sleep apnea, periodic limb movements, and parasomnias. In most laboratories it is possible to perform more complete EEG recording than the minimum needed for sleep staging, and this should be done when nocturnal seizures are considered.

The multiple sleep latency test is a means of quantifying daytime sleepiness. It is essential in diagnosing narcolepsy and can be helpful in assessing the effects of other sleep disorders on daytime alertness.

Toxic-metabolic disturbances

Most toxic-metabolic disturbances produce a long-lasting confusional state that does not strongly suggest an isolated seizure, although nonconvulsive status epilepticus48-50 or a prolonged postictal state should be considered. The picture may be confused by myoclonus, which can occur in many electrolyte disturbances, intoxications, uremia, and sepsis.

The EEG may show sharp activity, although usually not frank spikes and not a dominant focus unless there is preexisting focal illness. The triphasic wave pattern, most strongly associated with hepatic encephalopathy, is also often seen in uremia. postanoxic coma, and other encephalopathies. At times, this pattern can be difficult to distinguish from the generalized sharp-slow or even frank spike-wave complexes of nonconvulsive generalized status epilepticus, which could clinically resemble a metabolic encephalopathy as well.51

In doubtful cases, benzodiazepine infusion can be helpful if both the EEG and the patient improve, although this test is not always easy to interpret in practice.

The clinical manifestations of glucose abnormalities, particularly hypoglycemia in patients who are taking insulin or hypoglycemic agents, may be brief. Typically, the patient exhibits anxiety, tremor, sweating, and tachycardia consistent with sympathetic nervous system activation, but at times loss of consciousness and even true convulsive seizures may occur. Nonketotic hyperglycemia can cause focal myoclonus and true focal or generalized seizures, as can uremia.

Movement disorders

Movement disorders may be mistaken for motor seizures. Characteristics of movement disorders include:

• preserved consciousness
• usually bilateral
• generally not episodic, although they may wax and wane

High doses of AEDs may actually produce movement disorders in some patients. For example, valproate commonly causes a dose-related tremor, and phenytoin rarely produces dystonia.

Psychiatric disorders

Although psychiatric disorders, particularly depression, are common in seniors, new-onset psychogenic nonepileptic seizures are probably rare. This has not been carefully studied, however.

Before making this diagnosis, rule out physiologic nonepileptic events such as those described above. Use video-EEG monitoring to look for ictal or postictal EEG change.52 Verify that the events do not resemble seizure types during which a negative surface EEG recording is common, such as simple partial or frontal lobe seizures. Placebo induction may also have a place in diagnosis.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

In the acute setting, if full recovery does not follow promptly after the seizure apparently terminates, EEG is necessary to rule out ongoing nonconvulsive status epilepticus.53

The EEG usually need not be obtained immediately, but the yield of interictal epileptiform discharges and diagnostic postictal slowing is maximal if the test is done soon after the event. In some situations, such as if encephalitis is suspected, the EEG can be crucial to early diagnosis.54

Epileptiform findings on EEG—particularly periodic lateralized epileptiform discharges—are also highly predictive of the development of seizures after stroke even if no seizures have been observed.55

If diagnosis remains uncertain or frequent events are occurring despite treatment, long-term video-EEG monitoring, perhaps with additional ECG and polysomnography, is indicated.

The electroencephalographer must be familiar with the effects of normal aging on the EEG, particularly temporal slowing, which is often asymmetric (L>R), and with normal variants that could be mistaken for epileptiform abnormalities.54-56

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254. With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

First, a thorough evaluation should establish that the event was in fact a seizure. Reversible or avoidable seizure precipitants must be ruled out. Alcohol withdrawal, for example, is not rare in seniors. Acute treatment may be necessary to prevent status epilepticus in this situation, but AEDs are not used chronically except in those who have been shown to have seizures remote from heavy alcohol consumption.

The 2-year recurrence risk after a first seizure has been estimated at 23% to 71% in a meta-analysis of several studies.57 Risk is highest in those with abnormal neurologic status and in those with a remote brain insult.57-59 This would include most seniors who present with a seizure after prior stroke.

A randomized study has shown that treatment decreases recurrence risk by about 50%.60 It does not guarantee that no further seizures will occur, so activities such as driving must be limited until it is clear that the risk of injury is sufficiently low.

Patient activities, risk of injury with further seizures, coexisting illness, susceptibility to drug side effects, and attitudes toward taking medications must all be taken into account.61-63

Drug interactions are nearly inevitable for many seniors, who often take more than three—and sometimes 10 or more—prescription medications.64 The ability of many AEDs to induce or inhibit hepatic metabolizing enzymes makes pharmacokinetic interactions extremely likely. Although the possibility that a seizure could lead to a fall may drive the decision to treat, drug interactions or excessive AED dosing can cause ataxia and falling.

On the other hand, there have been rare reports of persistent worsening of stroke-related deficits after seizures, which would tend to favor treatment in this situation.65

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Table: Choosing antiepileptic drugs for elderly patients.

For partial seizures, the most commonly used drugs in the United States remain phenytoin (Dilantin, Phenytek) and carbamazepine (Tegretol, Carbatrol). Some studies support the contention that valproate (Depakote, Depakene) is equally effective and well tolerated,66 especially for partial seizures that secondarily generalize, but others dispute this finding.67

Valproate remains the preferred drug for primary generalized epilepsies, but these are much less likely to present in old age than partial epilepsies.

Newer AEDs such as gabapentin (Neurontin) and lamotrigine (Lamictal) have advantages, especially for seniors. Gabapentin has not been approved for monotherapy, which is preferred to polytherapy (especially in the elderly), but it may be useful for seniors because it appears to have minimal pharmacokinetic interactions with other drugs. Lamotrigine is approved for either adjunctive therapy or withdrawal to monotherapy for partial seizures, and has no major effects on other drugs, although enzyme inducers (see below) increase its metabolism, and enzyme inhibitors, particularly valproate, significantly slow its metabolism. Preliminary results from a multicenter, randomized, prospective Veterans' Administration study suggest that gabapentin and lamotrigine are better tolerated in elderly men than carbamazepine.96 Case series of elderly patients treated with with levetiracetam monotherapy, an AED thus far approved only for adjunctive therapy, also suggest a favorable safety and efficacy profile relative to older AEDs. 97

Enzyme induction by carbamazepine, phenytoin, or barbiturates may decrease the effects of other drugs. Warfarin is a particular problem: prothrombin time must be checked more often and the dose adjusted to avoid loss of anticoagulant effect. Enzyme-inducing AEDs typically also lower folate and vitamin D levels. Vitamin D is particularly important to elderly women, who are already prone to osteopenia and associated fracture.

Drugs whose effects are decreased by enzyme-inducing AEDs include:

• acetominophen
• cyclosporine A
• digoxin
• disopyramide
• furosemide
• neuroleptics
• propranolol
• quinidine
• steroids
• theophylline
• tricyclics
• warfarin

Withdrawal of an enzyme-inducing drug, or enzyme inhibition from other drugs, presents the opposite risk. Hemorrhage is a significant danger for patients taking warfarin.

Some medications inhibit the metabolism of certain AEDs, requiring dosage adjustments to avoid toxicity. Affected AEDs include carbamazepine, phenytoin, lamotrigine, and barbiturates. Common drugs with this effect include:

• amiodarone
• chloramphenicol
• chlorpromazine
• cimetidine
• ranitidine
• erythromycin
• imipramine
• ketoconazole
• nifedipine
• trimethoprim
• isoniazid
• phenylbutazone
• verapamil

Gabapentin and levetiracetam are not metabolized through the hepatic P450 enzyme system, and are not subject to these interactions.

Drugs with a high protein binding fraction may displace and be displaced by other drugs that are highly bound, including such common medicines as aspirin. Typically, the displaced drug initially has a stronger effect as more free drug becomes available, and then an increased rate of metabolism tends to compensate. For example, if aspirin is added to phenytoin, transient toxicity may occur until metabolism “catches up” to the higher free level. Because the free fraction of phenytoin will be elevated as long as aspirin is taken, the patient’s “therapeutic range” for total level falls. Direct measurement of the free fraction may be helpful in this situation. Among the newer AEDs, only tiagabine is strongly protein bound, and therefore subject to this set of interactions.

Several potential adverse effects of AEDs may be of particular concern in seniors:

• sensitivity to sedation or paradoxical agitation from barbiturates and benzodiazepines.68-70
• ataxia from several drugs, with risk of falls
• risk of bradyarrhythmias from carbamazepine’s ability to slow atrioventricular nodal conduction (especially in patients with cardiac conduction defects)
• risk of hyponatremia with carbamazepine and oxcarbazepine
• thrombocytopenia or thrombocytopathy with valproate (rarely, but of concern in patients taking antiplatelet agents or anticoagulants)
• exacerbation of dose-related tremor with valproate, in those with preexisting essential tremor or parkinsonism
• parkinsonism, dementia, and hearing deficit, also reported with valproate.71

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Pharmacokinetics includes the processes of drug absorption, distribution, and elimination via metabolism and excretion. Drug pharmacokinetics change predictably with aging. These changes are of variable clinical significance for the use of antiepileptic drugs (AEDs):72-74

Table: Pharmacokinetics and aging

Absorption of AEDs remains complete, unless calcium-containing antacids are taken.

Drug distribution is affected by the decrease in lean body mass that occurs with aging, as well as by decreased albumin levels for drugs that are highly protein bound. These effects tend to oppose each other: lipophilic AEDs would be distributed to tissues other than brain more than in younger people, but there is also more free drug to distribute.

Drug elimination tends to be slower because of decreased hepatic enzyme activity and hepatic blood flow, as well as decreased renal clearance. The net result of these factors for most people and most drugs is to lower drug clearance.72,74,75 Seniors thus are often more sensitive to adverse effects and interactions, including sedation and ataxia. AEDs generally should be started at lower doses in seniors, titrated more slowly, and stabilized at lower doses and levels than in younger patients.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

In most seniors, seizures are readily controlled by a single antiepileptic drug (AED), according to most retrospective series.76 However, compliance problems related to cognitive, sensory, and motor deficits and social isolation may interfere with successful treatment.77,78

Excess mortality over that expected for age appears to be related primarily to underlying illness such as cancer or vascular disease.79 The incidence of sudden death in epilepsy (SUDEP) may increase with aging.80

Maximizing quality of life and, when possible, normalizing lifestyle are explicit goals of treatment for people with epilepsy. The obstacles to independent function presented by aging make fulfilling these goals even more challenging, but still paramount. Medical and psychosocial correlates of epilepsy in the elderly deserve careful attention, often through a multidisciplinary team including primary care providers, medical specialists, mental health professionals, social workers, and family members.77,78

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254. With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Underreporting of symptoms has been well documented in the elderly.81 Family members or visiting nurses should be enlisted to ensure adequate reporting. They also can be critical to ensuring that seniors comply with medication regimens, given possible problems with cognitive, sensory, and motor deficits and social isolation.

Areas to be specifically questioned include:

• seizure frequency, including simple partial seizures
• compliance with antiepileptic drug (AED) regimens
• adverse drug effects
• new drugs that can potentially interact with AEDs
• newly diagnosed conditions such as cardiac, renal, or hepatic disease.

Periodic monitoring of blood chemistries and AED levels is probably more useful for this age group than for younger patients. Monitoring may detect long-term changes before they become symptomatic.

The possibility of adding or substituting one of the newer AEDs should be considered, although in general a change in therapy should be avoided if seizures are controlled without significant adverse drug effects.

Withdrawal of AEDs

If it can be verified that the patient has been free from seizures for at least 2 years, the possibility of drug withdrawal can be raised. A prospective study82 of the risk of seizure recurrence in this circumstance did not find advanced age to be a significant risk factor in a multivariate analysis. Under the best of circumstances, one-third to one-half of patients experience a relapse after drug withdrawal.

EEG testing has limited value in this decision. As at any age, an important issue is the risk of injury or social limitation (e.g., driving restriction) if a relapse occurs.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Of several thousand patients nationwide who have received surgical treatment for intractable epilepsy, probably only a handful have been older than age 50. Cascino et al83 reported at least worthwhile outcomes in every one of 8 patients aged 50 to 60 after temporal lobectomy, with 3 becoming seizure-free.

Many people with long-standing epilepsy have never been referred for evaluation for surgery and may be first identified as surgical candidates in old age. Increased risk of comorbidity and perioperative complications, as well as possibly decreased potential benefit from a successful outcome, should be considered. But despite these considerations, many patients may wish to pursue the possibility of living the rest of their lives with no or far fewer epileptic seizures.

When epilepsy is the result of an extratemporal lesion, the same issues apply. The likelihood of a progressive, histologically malignant lesion increases with age, however. In these cases the goal of resective surgery would be postponing disability and death rather than alleviating epilepsy.

Arguments about increased risk and decreased benefit are more salient when applied to extratemporal, nonlesional epilepsy. In most studies, the success rate for surgery has been lower than for temporal lobe epilepsy. A more demanding evaluation also is required, usually involving invasive monitoring.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Both the incidence and complications of status epilepticus increase with aging. Morbidity and mortality increase steadily with age after age 20, mortality rates being in excess of 50% in patients over age 80.84,85 To some extent this statistic both reflects and interacts with other mortality risk factors, including duration of status and, especially, etiology. (See more information on Complications and Prognosis.)

Causes

The highest mortality rates occur when status epilepticus is associated with anoxia, infection, metabolic dysfunction, trauma, tumor, and vascular disease, particularly hemorrhage.85

Status epilepticus brought on by the abrupt discontinuation of AED therapy, a major precipitant among patients with known epilepsy, continues to have a relatively good prognosis in older patients, if treated promptly.

Treatment

Prompt treatment is especially important in seniors, to avoid systemic complications86,87 such as:

• blood pressure lability
• hypoxemia
• acidosis
• rhabdomyolysis with renal failure

Seniors are more sensitive than younger people to the hypotensive and respiratory suppressant effects of intravenously administered AEDs, particularly phenytoin, barbiturates, and benzodiazepines. Vital signs must be carefully monitored and sometimes the rate of infusion must be slowed, despite the risk of prolonging status. Phenytoin, for example, should probably be infused at rates no greater than 25 mg/min.

An interesting alternative for second-line treatment is intravenous valproate, which, though not currently FDA-approved for the treatment of status epilepticus, can be safely loaded at a rapid rate without significant cardiorespiratory suppression. 94

The decision to use pentobarbital coma in refractory status is particularly difficult. Increased complications related to age beyond 40 and to multiple organ failure have been documented.88

Data are insufficient to determine whether midazolam infusion is safer. Anecdotal reports suggest that it may be.89 Propofol is another option for refractory status epilepticus. Retrospective studies do not conclusively distinguish among these three alternatives with respect to efficacy and safety.95

Other neurologic or medical conditions may mimic nonconvulsive generalized90,91 or partial92,93 status epilepticus. A thorough history, examination, and testing may prevent iatrogenic harm from inappropriate treatment.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

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