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 New-onset seizures in the elderly patientThe medical consequences of uncontrolled seizures in an older person can be serious. PAs should know how to make this difficult diagnosis, as well as how best to treat elderly patients who have this serious condition.Kara A. Sutton, PA-C, MPASThe author is a physician assistant at Urgent Medical & Family Care in Greensboro, North Carolina. She has indicated no relationships to disclose relating to the content of this article.The incidence of seizures in older adults is often underestimated. A recent Veterans Administration study showed that for elderly patients who ultimately received a diagnosis of epilepsy, only 73.3% of primary care physicians or internists considered a seizure disorder in their initial differential diagnosis.1 Seizures are less likely to be witnessed in the elderly, who frequently live alone and may have limited social interactions.2 They are more likely to suffer debilitating fractures, subdural hematomas,3 and prolonged postictal states than are younger people with a seizure disorder.4 Psychologically, seniors with epilepsy may lose confidence and independence,5 and they are at increased risk for depression,6 already a problem in that population. 
The highest incidence of epilepsy occurs in adults who are older than 65 years.7 Nationwide, approximately 300,000 seniors have the disease,8 and by the year 2030 people older than 65 years will comprise nearly 20% of the US population.9 Elderly patients have an increased risk of stroke, more metabolic derangement, and a higher rate of comorbid illness, all of which may explain the higher prevalence of epilepsy in this population.10 Older patients are also at an increased risk for adverse drug effects. Both advanced age and the use of multiple medications make these patients more susceptible to drug toxicities.4,11 Seniors who are already experiencing compromised cognitive function can be significantly impaired by even brief seizures.12 Neurologic disabilities such as hemiparesis and aphasia may be exacerbated during prolonged postictal states.13 Having uncontrolled seizures also puts people at risk for falls, burns, intracerebral hemorrhage, subdural hematoma, postictal confusion, and decreased cognitive function.12,13 PathophysiologyA seizure is a series of aberrant, hypersynchronous electrical discharges of a group of cortical neurons that result in abnormal behaviors or sensory experiences. These electrical impulses are caused by dysregulation of excitatory and inhibitory neuronal effects, resulting in an excess of excitatory activity.14 Seizures appear in many different forms. An elderly patient having seizures may present with episodes of confusion, memory loss, or delirium.7 Family members or other caregivers may report periods of staring or disorientation. Table 1 lists classifications and descriptions for various seizure types. Partial seizures, the most common type in older adults, arise from focal, unilateral electrical discharges, while generalized seizures originate through diffuse, bilateral electrical discharges. The pathogenesis of partial seizures reflects focal areas of neuron damage secondary to cerebrovascular disease. Indeed, the most commonly identified comorbidities in a recent study of new-onset epilepsy in the elderly are strongly associated with cerebrovascular disease: hypertension, stroke, cardiac disease, and diabetes.15 
Complex partial seizures are the most common seizure type in adults of all ages. These often have activity centered in the frontal or parietal lobes, resulting in complaints such as dizziness, paresthesias, and memory disturbances.1,16 Diagnosis is usually easy in patients who present with generalized tonic-clonic seizures, but the manifestations of simple partial and complex partial seizures are often subtle and easily overlooked. Frequencies of the various seizure types in the elderly are shown in Table 21. History and physical examinationObtaining an accurate history of the paroxysmal event from the patient may be difficult or impossible. Thus, it is critical to obtain a reliable firsthand observer’s complete account of the events leading up to, during, and following the seizure. Ask about initial changes in speech or behavior, whether the onset was sudden or gradual, about the existence of pallor or cyanosis, and about abnormal motor activity, urinary incontinence, tongue-biting, lateralization of symptoms, or alteration in the patient’s level of consciousness.17 Historical features of the spell that are suggestive of syncope include episodes that are precipitated by pain, anxiety, or a change in position, are associated with diaphoresis and pallor, and involve a rapid recovery of neurologic function after the event.7 Prodromal neurologic symptoms (unusual tastes, smell, thoughts), postevent focal motor weakness or focal sensory deficits (Todd’s phenomenon), or a prolonged postictal period suggest seizure as the probable diagnosis.18 Ask the patient or the family about any systemic illnesses, current medications (including nutritional supplements or herbal compounds), recent stress or illnesses, sleep problems, history of head trauma, and family history of neurologic disorders. Table 3 (page 40) lists drugs that are commonly implicated in provoked seizure. Table 4 (page 40) lists other known triggers of seizures.
Provoked seizures are usually generalized tonic-clonic seizures.19 A comprehensive review of systems may elicit history of nocturnal enuresis, encopresis, tongue-biting, or any sudden cognitive decline, suggesting seizures.20 The physical examination concentrates on evaluating any injuries sustained during the spell and finding evidence of focal neurologic deficits or signs of systemic illness, with special attention to physical findings suggestive of cerebrovascular or atherosclerotic disease. Injuries due to a fall onto an outstretched hand are a sign of initial preservation of consciousness, which is unlikely with a seizure.21 Orthostatic vital signs coupled with a history of dimming vision preceding the attack are more consistent with a diagnosis of syncope, as opposed to seizure.22 TestingIn general, the imaging modality of choice for evaluating suspected seizures is MRI because of its sensitivity for finding subtle or small lesions. Emergent CT is required when any of the following are present: new focal neurologic deficits, persistently altered mental status, a recent history of trauma, persistent headache, anticoagulant use, immunocompromised status, or fever.23 Routine laboratory evaluation in an elderly person with suspected seizures should include a CBC; tests to measure electrolytes, calcium, magnesium, phosphorus, BUN, creatinine, and glucose; liver function tests; and toxicology screening.7,20 Lumbar puncture is indicated when encephalitis, meningitis, or cancer is suspected.7 EEG is essential, but results should be interpreted with care as older patients often have nonspecific abnormalities consistent with diffuse atherosclerotic changes. They also have a lower incidence of interictal epileptiform activity than is seen in persons with epilepsy overall, which further decreases the utility of EEG.24 One-time EEG has a relatively low sensitivity (50%); performing multiple tests increase the diagnostic yield.25 The gold standard of EEG diagnosis is the actual recording of a seizure, but this can be difficult without relatively frequent seizure activity. Prolonged video EEG or ambulatory EEG monitoring may clarify the diagnosis in patients with repeated periods of altered mental status, dizziness, or paroxysmal movements.2,16
Differential diagnosisThe differential diagnosis of seizures in the elderly is listed in Table 5. Once seizures are diagnosed, you must determine whether the seizures are provoked (unlikely to recur without the provoking stimulus) or unprovoked (usually symptomatic and likely to recur without treatment).
Provoked seizures are usually of the generalized tonic-clonic type.19 If provocation has been ruled out but the patient is having generalized tonic-clonic seizures, the ictal events are probably partial seizures that secondarily generalize. New-onset idiopathic generalized tonic-clonic seizures in older adults are rare19 except in patients with Alzheimer’s disease, who usually have generalized seizures due to the global brain pathology of that disease. Epilepsy will develop in approximately 20% of patients with Alzheimer’s disease by their fifth year after diagnosis.26
Treatment and follow-upUp to 80% of older adults who have had a single seizure are likely to have another.1,27 Because of this high recurrence risk, some advise initiating antiepileptic drug (AED) treatment after only one symptomatic seizure when a cortical lesion has been identified via neuroimaging.19 When selecting the initial AED, consider seizure type, pharmacokinetic profile, possible drug interactions, other medical conditions, efficacy, expected adverse effects, and cost14 (see the table “Comparative characteristics of first- and second-generation antiepileptic drugs” on the Web). Counsel the patient about potential adverse effects that may be related to the medication and the likelihood of success with treatment. Long-term thinking is very important. New-onset seizures in elderly patients are often controlled with relatively modest dosages of whichever AED is first selected.19 Thus the primary consideration for successful treatment is tolerability,15,28 and clinicians should choose the initial drug with this in mind.4,29 Normal physiologic changes of aging alter the pharmacokinetic profiles of many AEDs. Older adults have lower circulating protein concentrations (leading to a higher proportion of active free drug at an equivalent serum drug level), decreased renal elimination, altered distribution volumes, impaired hepatic metabolism, and decreased enzyme inducibility.10,29 There are alterations in the GI absorption of highly insoluble AEDs such as phenytoin and carbamazepine.29 Common AED side effects such as dizziness, somnolence, increased tremor, and unsteadiness are especially troublesome in the elderly, who often have disequilibrium or gait problems at baseline. These problems are usually dose-dependent and can be minimized with slow titration, but note that the elderly tend to experience side effects at serum drug levels that are not considered high in other age groups.11 Soporific phenobarbital is a particularly unsuitable choice.30 Additional areas of concern for older patients are chronic adverse effects such as osteoporosis, peripheral neuropathy, and weight gain, common with the use of first-generation AEDs.12 These adverse effects have not been noted with second-generation AEDs.31 Cognitive or other neurologic deficits are also common in seniors,32,33 and formal cognitive function testing before initiating treatment is important.1 Lamotrigine, gabapentin, levetiracetam, pregabalin, and zonisamide are desirable first choices for treatment because of their most favorable cognitive profiles.29 The increased expense of this new generation of AEDs may well be offset by decreased costs due to adverse drug effects.29 Monotherapy is desirable in this population, as polypharmacy tends to increase the incidence of dose-related side effects. However, until fairly recently, none of the second-generation AEDs had FDA approval for initial monotherapy. To address this, in 2004 the American Academy of Neurology and the American Epilepsy Society published guidelines for using second-generation AEDs in treating new onset epilepsy.34 They recommended that gabapentin, lamotrigine, topiramate, and oxcarbazepine could be used for initial monotherapy in patients with newly diagnosed epilepsy. Another AED that is commonly used as initial monotherapy in elderly patients with new-onset epilepsy is levetiracetam.29 All patients who still have uncontrolled seizures after 3 months of treatment should be referred to a specialist.10 Also, patients should be counseled about possible seizure triggers, including sleep deprivation, use of alcohol or stimulants, and any known triggers for that person. Patient educationProviding patients and their families with information about epilepsy can help to minimize the negative psychological impact of the diagnosis. Misconceptions about the disease and its treatment are common and can frighten or confuse patients, especially regarding their ability to live and care for themselves independently.19 Driving One area of concern is whether patients with seizures can drive safely.35 All 50 states require people to refrain from driving after a seizure for a period of time, usually 6 to 12 months.7 California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania require clinicians to report patients who are having seizures to the Department of Motor Vehicles, and if a patient with epilepsy is involved in an accident, the clinician could be found negligent for a failure to report. The Epilepsy Foundation provides a helpful, concise listing of each state’s driving laws.
Adherence to treatment Seizures will be controlled only if the patient takes the AED regularly, as prescribed. Compliance can be a challenge for those who may already be taking a number of drugs for other conditions.15 Pills may look similar, dosing schedules may differ, and arthritic hands may have difficulty opening bottles and handling tiny pills. Clinicians must do their part to help patients adhere to treatment; diligent patient education and prescribing medications that require fewer daily doses help to increase compliance and the opportunity for the patient to remain seizure-free.17
ConclusionNew-onset seizures are relatively common in the elderly and often go unrecognized. Seizure characteristics in the older adult are different from those in younger people, and a high index of suspicion is necessary for proper evaluation and diagnosis. All elderly patients with new-onset seizures should have at least one EEG, an MRI of the brain, and an appropriate laboratory workup.7,20 AED therapy should be chosen to maximize tolerability; in most cases, this means prescribing one of the second-generation AEDs.
REFERENCES
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