Seizures and epilepsy in older adults: Etiology, clinical presentation, and diagnosis

INTRODUCTION — 

Seizures and epilepsy are common in older adults. Nearly one-half of new-onset seizures occur in individuals over the age of 65 years [1,2]; however, recognizing seizures in this population is challenging because of the paroxysmal nature of the condition and the clinically subtle presentation of seizures in the majority of cases. Treatment decisions are also more complex; older patients are more susceptible to medication side effects and carry a greater burden of medical comorbidities.

Seizures are episodes of transient neurologic change due to hypersynchronous, hyperexcited neuronal activity. Seizures are divided into two categories: provoked and unprovoked. Provoked seizures, also known as acute symptomatic seizures, occur with an identifiable proximate cause and are not expected to recur in the absence of that particular cause or trigger (eg, hypoglycemia, alcohol withdrawal). Unprovoked seizures occur without an identifiable proximate cause, and epilepsy is defined as a condition of recurrent unprovoked seizures. In epilepsy, the seizures appear to occur spontaneously and are expected to recur in the absence of treatment.

This topic will cover the clinical presentation, differential diagnosis, and etiology of seizures and epilepsy in older patients. The treatment of seizures and epilepsy in older patients is discussed separately. (See "Seizures and epilepsy in older adults: Treatment and prognosis".)

EPIDEMIOLOGY

●Seizures and epilepsy increase in patients ≥60 years – Age has been shown to be an independent risk factor for developing seizures and epilepsy [3]. Acute symptomatic seizures are common in older patients. The incidence of acute symptomatic seizures in patients older than age 60 years is estimated at 0.55 to 1 per 1000 person-years, with linear increases every decade after age 30 years (figure 1) [4-6].

The incidence and prevalence of epilepsy (recurrent unprovoked seizures) also increase with age in adulthood and are highest in patients over 75 years of age [7-9].

●Incidence – In population-based studies, the incidence rate of new-onset epilepsy in older adults ranges from 1 to 3 per 1000 person-years [3-5,10-15] and is estimated to be two to six times higher than in younger adults [1]. Among United States Medicare beneficiaries age 65 years and older, the average annual incidence of epilepsy for the years 2001 to 2005 was highest for Black beneficiaries (4.1 per 1000), intermediate for White beneficiaries (2.3 per 1000), and lowest for Asian and Native American beneficiaries (1.6 and 1.1 per 1000) [13]. This trend has been confirmed in other studies [15].

●Prevalence – The prevalence of epilepsy in older adults is approximately 2 to 6 percent [13,15], three to four times higher than in younger adults.

CAUSES AND RISK FACTORS — 

Both acute symptomatic seizures and epilepsy occur as a consequence of diseases and conditions that more commonly affect older rather than younger adults [16].

Acute symptomatic seizures (provoked or triggered seizures) — Acute symptomatic seizures have an identifiable proximate cause; they occur at the time of a systemic illness or in close temporal association with a new brain insult (eg, within one week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; during the active phase of a central nervous system infection; or within 24 hours of a severe metabolic derangement) [17]. They are not expected to recur in the absence of the inciting cause or trigger.

Causes of acute symptomatic seizures are wide-ranging; virtually any acute insult to the brain can cause a seizure (table 1).

●Acute stroke – In older adults, acute stroke is the most common cause of acute symptomatic seizures, accounting for up to one-half of cases [4,6,18]. Seizures occur in <1 to 3 percent of adults with acute cerebrovascular events [19,20]; all stroke subtypes, including (rarely) transient ischemic attacks (TIAs), are associated with seizure [19-21].

Risk factors for acute poststroke seizures include hemorrhage, particularly lobar hemorrhage; large size of stroke; cortical involvement of ischemic stroke; and hyperglycemia [19,21,22]. Most acute seizures occur within 48 hours of ischemic stroke onset; in subarachnoid hemorrhage, seizures generally occur within hours [23,24]. Acute symptomatic seizures are also a risk factor for the eventual development of poststroke epilepsy. (See 'Epilepsy (unprovoked seizures)' below.)

●Trauma and other causes of acute intracranial lesions – Seizures may also be seen in association with acute head trauma, active intracranial infection, subdural hematoma, hypoxic-ischemic brain injury, and hypertensive encephalopathy. Trauma is the underlying cause of 4 to 17 percent of acute symptomatic seizures [4,6,18]. While older patients are susceptible to head trauma, they may be less likely to suffer acute seizures as a result than are younger patients [3,25]. Seizures associated with intracranial infections represent less than 3 percent of acute seizures in the older adult population [4,6,18].

●Metabolic encephalopathy – Metabolic disturbances cause approximately 6 to 30 percent of acute symptomatic seizures in older adults [4,6,18]. Metabolic disturbances can precipitate seizures at any age, and older adults are at higher risk because of the increased prevalence of multiple medical conditions, polypharmacy, and complications. Hypoglycemia, hyperglycemia, hyponatremia, and uremic and hepatic encephalopathy are all causes of acute symptomatic seizures [26,27].

●Drugs and alcohol – Drugs and drug withdrawal may be responsible for up to 10 percent of acute symptomatic seizures [4,6,18]. A number of medications have been implicated as a cause of acute seizures in late life (table 2) [28,29]. Older adults are likely to be particularly susceptible to seizures as a consequence of drugs because of a high prevalence of polypharmacy, impaired drug clearance, and a heightened sensitivity to the proconvulsant effects of medications [1]. Seizures can occur with alcohol, benzodiazepine, or barbiturate withdrawal [30].

●Autoimmune encephalitis – Acute symptomatic seizures are common in the acute phase of autoimmune encephalitis, which typically presents with rapidly progressive (less than three months) cognitive, behavioral, and psychiatric symptoms and/or movement disorders [7,31]. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

●Pulmonary embolism – Pulmonary embolism can rarely present with seizures [32,33]. Because of the high mortality associated with delayed diagnosis, pulmonary embolism should be considered in individuals presenting with acute symptomatic seizures who have hemodynamic instability and in those who have a history of cardiopulmonary symptoms prior to seizure [34].

Epilepsy (unprovoked seizures) — Unprovoked seizures occur without an identifiable proximate cause, and epilepsy is defined as a condition of recurrent unprovoked seizures. In epilepsy, the seizures appear to occur spontaneously and are expected to recur in the absence of treatment.

The causes of epilepsy are broadly categorized as genetic, structural, metabolic, immune, infectious, and unknown [35]. Major causes of epilepsy in older adults include cerebrovascular disease, neurodegenerative dementia, intracranial tumors, and trauma; a significant portion are of unknown etiology (table 1) [4,5,10,18]. For all etiologies, the risk of developing epilepsy is highest in the initial one to two years after the onset of the precipitating factor [36].

●Subacute and chronic stroke – Cerebrovascular disease is the most common known cause of epilepsy in older adults, responsible for one-third to one-half of cases of new-onset epilepsy in older patients [1,5,7,15,18]. Risk factors for poststroke epilepsy (hemorrhage, cortical involvement, stroke size) are similar to those for acute symptomatic seizures [22]. Acute symptomatic seizures and recurrent stroke are also risk factors for poststroke epilepsy [37]. Approximately 35 percent of individuals with acute symptomatic seizures at the time of stroke will develop poststroke epilepsy, compared with an overall 3 percent risk of poststroke epilepsy [9,37-41]. The risk of unprovoked seizures is highest in the first year after a stroke but remains substantially elevated for at least seven years [42].

●Late-onset unexplained epilepsy – The cause of new-onset epilepsy remains unexplained in approximately 13 to 50 percent of older adults [7]. Potential mechanisms and/or risk factors include small vessel cerebrovascular disease, sleep apnea with lower nocturnal oxygen saturation, and accumulation of amyloid beta and hyperphosphorylated tau [43,44].

●Neurodegenerative dementia – Alzheimer disease (AD) is a significant risk factor for epilepsy. Between 10 and 20 percent of patients with AD will develop seizures, a rate up to 10 times higher than expected [45-50]. A premorbid diagnosis of either AD or non-Alzheimer dementia are more common in patients presenting with a first unprovoked seizure compared with age-matched hospitalized controls (odds ratio [OR] 6 and 8, respectively) [51]. In prospective cohort studies, younger age at onset and more severe dementia have been identified as independent risk factors for incident epilepsy [51-53]. Likewise, comorbid epilepsy has been associated with earlier onset of cognitive decline in patients with amnestic mild cognitive impairment and AD [53,54].

Dementia is present in 8 to 18 percent of older adults with epilepsy [55]. In a population-based study that identified over 1000 older adults with incident epilepsy, dementia at baseline was much more likely compared with older adults without epilepsy (hazard ratio 7.39, 95% CI 5.21-10.50) [56]. Dementia may coexist and possibly interact with other causes of epilepsy. In a prospective study, preexisting dementia increased the risk of poststroke epilepsy [57]. In another retrospective case series, 40 percent of patients with dementia and seizures had another potential structural cause (usually stroke) for their seizures [58].

●Other static or progressive intracranial lesions – Intracranial lesions including brain tumors, vascular malformations, and head trauma also cause epilepsy in older adults. The tumors most frequently associated with epilepsy are gliomas, meningiomas, and metastases [59]. While these are more common in older than younger patients, seizures are less likely to be the presenting symptom in older adults [60].

Head trauma is the most likely cause of epilepsy in 2 to 21 percent of cases [4,10,18]. Older patients are particularly susceptible to head trauma, which may cause epilepsy as well as acute seizures [25,61].

Arteriovenous malformations usually manifest in younger adults; when first diagnosed in an older patient, seizures are much less likely to be the presenting symptom [62].

●Autoimmune-associated epilepsy – Autoimmune-associated epilepsies encompass a range of autoimmune and paraneoplastic syndromes characterized by seizures that persist and become chronic despite resolution of the active phase of encephalitis [7,31,35]. Although the various causes of autoimmune-associated encephalitis and epilepsy mainly affect children and young adults, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-like 2 (CASPR2) antibodies predominantly affect patients older than 50 years of age. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

●Psychiatric conditions – Emerging data suggest that preexisting psychiatric disorders are independently associated with new onset of epilepsy in older adults [63,64]. In a study of Medicare beneficiaries, prior history of substance abuse had the strongest significant association with new-onset epilepsy in older adults (adjusted OR 2.5), followed by psychosis (adjusted OR 2.3), bipolar disorder (adjusted OR 2.0), schizophrenia (adjusted OR 1.7), and depression (adjusted OR 1.5) [64].

PRESENTATION, SEIZURE TYPE, AND SEMIOLOGY

Presentations in older adults — A hallmark of seizures is their paroxysmal and episodic presentation. Seizures are typically episodic, brief, stereotyped, paroxysmal events that cause sudden transient motor, sensory, experiential, or behavioral symptoms or signs. Most seizures, whether focal or generalized, have a clear and abrupt clinical onset and rapid progression of symptoms over the course of seconds. However, the clinical presentation of seizures in older adults is frequently different from that of younger adults.

Features that suggest seizure in older adults:

●Confusion, behavioral change, or unresponsiveness

●Sudden falls with no recall or warning

●Recurrent events occurring in various positions or circumstances

●Arousal from sleep with confusion or disorientation

Seizures in older adults are often difficult to recognize for the following reasons:

●Lack of aura or preceding warning

●Lack of motor features

●Comorbid dementia

●Misdiagnosis as delirium

Older patients typically do not describe an aura or warning, and if they do, the symptoms may be nonspecific (dizziness or confusion). Seizures are also less likely to be convulsive or have motor features. In a randomized trial that enrolled nearly 600 older adults with new-onset epilepsy, focal seizure with impairment of awareness was the most common seizure type, affecting 38 percent of patients [65].

Focal seizures in older adults are often featureless and lack automatic behaviors (eg, lip smacking, repetitive hand movements), which are frequently observed in younger patients with epilepsy. Family members or caregivers of older adults may describe episodic confusion, unresponsiveness, or sudden sleepiness, and these fluctuating symptoms may be difficult to distinguish from delirium [66,67].

Features associated with specific etiologies

●Neurodegenerative disease – Rarely, seizures in individuals with neurodegenerative conditions can present with clusters of myoclonus (brief lightning-like movements) and/or tonic seizures (brief stiffening of the muscles), which can be difficult to differentiate from movement disorders [68,69]. An underrecognized syndrome of late-onset massive myoclonus with falls affects older patients with Down syndrome and is important to identify, particularly as survival with Down syndrome has improved [70]. (See "Down syndrome: Clinical features and diagnosis".)

●Autoimmune encephalitis – Patients with seizures due to autoimmune encephalitis may present with characteristic features, including sudden onset of frequent drug-resistant seizures, cognitive or behavioral change, and specific seizure types or movement disorders (eg, faciobrachial dystonic seizures associated with anti-leucine-rich glioma-inactivated 1 [LGI1] encephalitis, delayed-onset dyskinesia associated with anti-N-methyl-D-aspartate [NMDA] receptor encephalitis, and myoclonus seen with anti-glycine receptor [GlyR] encephalitis) [7]. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

●Transient epileptic amnesia – A rare syndrome termed transient epileptic amnesia (TEA) typically presents on awakening and is characterized by a self-limited but dense anterograde and/or retrograde amnesia [71]. Most spells last less than one hour, but TEA can manifest with multiple stereotypical attacks, and spells can last hours to days.

TEA predominantly affects older men. Episodes of amnesia that are epileptic in origin will often be associated with olfactory hallucinations and motor manifestations and may be associated with diminished responsiveness and/or abnormal behaviors, features that are absent in transient global amnesia (TGA) [72]. However, these symptoms may not be volunteered and should be specifically elicited. Differentiating TEA from TGA can be different, but a hallmark of TEA is the recurrence of multiple stereotyped events and response to antiseizure medications (ASMs). (See "Transient global amnesia", section on 'Differential diagnosis'.)

Postictal manifestations — Older patients with secondarily generalized seizures may have prolonged postictal confusion and sleepiness that persists for up to several days to a week, particularly if there is underlying brain dysfunction or neoplasm [73].

Manifestations of the postictal period typically include confusion and suppressed alertness. Focal neurologic deficits may also be present, often referred to as Todd paralysis or postictal paresis. The postictal state may last from seconds to minutes to hours to days, depending upon several factors including location of seizure, the amount of cortex involved, the duration of the seizure, medications received, and age.

Convulsive status epilepticus — Status epilepticus (SE) is not infrequent in older patients; in one hospital-based study, 30 percent of first seizures in an older population presented as SE [36,74]. The incidence of SE in the older adult population (90 per 100,000) is two to four times higher compared with younger adults [75-77].

Convulsive SE is a clinical diagnosis, confirmed in most cases by the presence of sustained and generalized tonic and/or rhythmic clonic motor activity lasting for longer than five minutes or repetitive convulsive seizures without a return to baseline consciousness between seizures.

Stroke, either acute or remote, is the most frequent underlying etiology (in approximately one-third of patients) of convulsive SE in older patients [78]; other associated conditions include a history of epilepsy, dementia, and electrolyte imbalance [79]. Associated mortality is higher in older patients; a 2017 meta-analysis found that the pooled case fatality rate for older patients with SE was approximately 28 percent, compared with approximately 15 percent for all included patients [80]. Mortality is associated with the duration of the seizure activity, and also with the number of medical comorbidities [79].

Convulsive SE is reviewed in greater detail separately. (See "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis" and "Convulsive status epilepticus in adults: Management".)

Nonconvulsive status epilepticus — Nonconvulsive status epilepticus (NCSE) is a challenging diagnosis, particularly in the older patient. It typically manifests as an altered mental status with confusion, psychosis, lethargy, or coma [81-85]. Occasionally, NCSE may present as a more focal cognitive disturbance with aphasia or a neglect syndrome, even in the absence of underlying structural pathology [81,83,86,87]. In a series of 236 patients of all ages (38 percent were age ≥60 years) without overt seizure activity who received an electroencephalography (EEG) as part of a coma evaluation, 8 percent had NCSE [88].

More than half of NCSE cases occur in the setting of acute medical conditions, such as organ failure, drug toxicity, alcohol and benzodiazepine withdrawal, and other metabolic disturbances [89-92]. Less commonly, NCSE complicates a known diagnosis of epilepsy or occurs as a first presentation of epilepsy [84,90,92,93]. NCSE may also occur in the aftermath of convulsive SE. Every cause of acute symptomatic seizures and epileptic seizures has been associated with NCSE.

In one series of NCSE in critically ill older patients, most patients had underlying brain pathology (defined by history or neuroimaging), but only 2 of 38 had a previous diagnosis of epilepsy [90]. Mortality is high (27 to 52 percent) in this setting [83,90,92,93]. Aggressive treatment of NCSE may actually play a role in morbidity and mortality through induced hypotension, cardiac arrhythmias, and prolonged sedation [83,90,94].

A more detailed discussion of NCSE is presented elsewhere. (See "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis" and "Nonconvulsive status epilepticus: Treatment and prognosis".)

EVALUATION AND DIAGNOSIS

Goals of evaluation — The main goals of the diagnostic evaluation are to:

●Consider diagnoses other than seizure (see 'Differential diagnosis' below) such as syncope, delirium, or transient ischemic attack.

●Establish whether the patient has had one or more provoked or unprovoked seizures (see 'Causes and risk factors' above) and, if so:

●Determine the etiology of the seizures and/or epilepsy, which will guide management. The cause of a provoked seizure will likely require independent treatment (eg, acute stroke, metabolic derangement, intracranial infection) and may require short-term treatment with antiseizure medication (ASM), while something that causes an ongoing predisposition to seizures (epilepsy) will likely require long-term treatment with ASM.

For older adult patients with suspected seizures or epilepsy, the evaluation should include a detailed history of the event, a physical and neurologic examination, laboratory tests, an electrocardiogram (ECG), EEG for select patients to identify epileptiform activity, a neuroimaging study for all patients to detect a structural brain lesion.

Making the diagnosis — The diagnosis of seizure is primarily based on clinical history and is supported when the clinical features are most consistent with seizure rather than alternative diagnoses. Seizures are typically episodic, brief, stereotyped, paroxysmal events that cause sudden transient motor, sensory, experiential, or behavioral symptoms or signs.

Findings from neuroimaging, EEG, and laboratory studies may provide supportive evidence for the diagnosis and are particularly important when the diagnosis or etiology remains uncertain after the initial evaluation. In some cases, the diagnosis may be tentative despite a thorough evaluation.

Clinicians should maintain a high level of suspicion for possible seizures in older patients presenting with intermittent or fluctuating confusional states. In cases where typical seizure manifestations are absent and patients present with nonspecific clinical symptoms and signs (eg, patients with confusion, behavioral change, or unresponsiveness), as is more common in older adults, confirming the diagnosis of new-onset seizures or epilepsy may depend upon evidence of epileptiform activity on routine EEG or continuous video-EEG monitoring. (See 'Presentations in older adults' above and 'Electroencephalography' below.)

Patient history — There is no diagnostic test that can substitute for a detailed history. The goals of the history taking are to characterize the events, rule out alternative diagnoses, determine whether similar events have happened in the past, and, if the events are convincing for seizures, evaluate for underlying etiology. (See "Evaluation and management of the first seizure in adults", section on 'History'.)

Obtaining eyewitness reports is imperative. Older adult patients often have comorbid cognitive impairment and may have difficulty giving an accurate history [95]. They can also be unaware of their seizures. Patients should be evaluated with a screening test such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) if there is concern for cognitive impairment. (See "Evaluation of cognitive impairment and dementia".)

●Description of the event – The most important part of the evaluation is the taking of the history and obtaining a reliable, detailed description of events from the patient, eyewitnesses, and caregivers. This assessment should include a detailed description of the circumstances leading up to the seizure and the patient's behavior before, during, and after the event. Reviewing home videos of events can also be instructive.

●Medications and substances – Alcohol intoxication or withdrawal and drugs of abuse are potential causes of seizures. A number of prescription and over-the-counter medications have also been associated with iatrogenic seizures (table 2). For most drugs, the magnitude of risk is likely low unless the drug is taken at supratherapeutic doses, or in combination with other drugs that inhibit its metabolism, or in the setting of underlying liver or renal dysfunction. Focal-onset seizures are less likely to be drug-induced compared with generalized tonic-clonic seizures.

●Past medical history – Other risk factors for seizures should be addressed, including head injury, stroke, dementia, intracranial tumor or infection, immunosuppression, cancer, rheumatologic disorders, and hematologic disorders.

Examination — The neurologic examination should evaluate for lateralizing abnormalities, such as weakness, hyperreflexia, or a positive Babinski sign, which may point to a contralateral structural brain lesion. (See "Evaluation and management of the first seizure in adults", section on 'Examination'.)

Laboratory evaluation

●Basic studies – Because metabolic abnormalities can precipitate seizures in patients with and without epilepsy, patients with acute seizures should have blood analyzed for levels of electrolytes, blood urea nitrogen, creatinine, glucose, calcium, magnesium, and liver function tests.

Complete blood count, differential, and platelets should also be performed in anticipation of initiating ASMs.

●Toxicology screen – For patients with suspected toxin exposure or substance abuse, or those with unexplained seizures, a toxicology screen of urine and blood for alcohol and drugs is indicated since certain drugs and drug or alcohol withdrawal can cause acute symptomatic seizures.

●Lumbar puncture – Lumbar puncture for cerebrospinal fluid (CSF) cell count, protein, glucose, and stains with cultures should be performed whenever there is suspicion of meningitis or encephalitis.

●Autoantibodies – For patients who present with explosive-onset epilepsy, characterized by new, sudden onset of frequent seizures, the evaluation should include testing of serum and CSF for autoantibodies associated with autoimmune and paraneoplastic encephalitis [7,31], particularly leucine-rich glioma-inactivated 1 (LGI1) antibodies and contactin-associated protein-like 2 (CASPR2) antibodies, which mainly affect older adults [7,96]. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis".)

Electrocardiogram — An ECG should be performed in all patients with loss of consciousness or unexplained falls. The ECG can identify features that may suggest cardiac arrhythmia as a cause of syncope, including acquired or congenital long QT syndromes.

Neuroimaging — A brain imaging study should be obtained in all older individuals who present with possible seizures or epilepsy, given the higher frequency with age of stroke and other structural brain disease as possible etiologies. In general, magnetic resonance imaging (MRI) of the brain is the preferred imaging modality because it is more sensitive than computed tomography (CT), especially if there are focal symptoms, abnormal neurologic examination findings, or abnormal EEG patterns. Contrast-enhanced imaging increases the ability to identify tumors, inflammatory disease, and abscesses, but may not be required if these conditions are not specifically suspected.

In the Veterans Aging Cohort Study (VACS) of new-onset seizures in 593 older patients (age ≥60 years), only 18 percent of patients were found to have normal CT scans [1]. Stroke was seen in 43 percent, encephalomalacia in 9 percent, and tumors in 2 percent. Other nonspecific abnormalities (atrophy, small vessel disease, hydrocephalus) were identified in the remaining and were probably incidental.

Electroencephalography — For older patients who are in the hospital for altered mental status of unclear etiology, EEG is a useful tool to exclude or identify seizure activity, especially nonconvulsive status epilepticus (NCSE), as a contributor to the encephalopathy. By contrast, a routine interictal EEG has limited diagnostic utility for older patients with unclear events when the history is more suggestive of syncope [95]. In the outpatient setting, if the clinical suspicion is high for seizures, a routine EEG can provide objective evidence to support a diagnosis of seizures and epilepsy; however, it is important not to interpret a negative EEG as evidence to disprove or exclude the diagnosis.

●Utility of EEG monitoring – Elective video or ambulatory EEG monitoring can be invaluable in the evaluation of possible epilepsy in older adults, particularly when combined with ECG monitoring. However, video-EEG monitoring is not widely available outside of specialized centers. Several retrospective case series have found a high yield with events recorded in 55 to 83 percent of older patients who were selected for video-EEG monitoring, presumably because of clinical suspicion for seizures [97-100]. In one of the larger studies, 46 of 94 patients who had video-EEG monitoring had documented epileptic events and 27 documented nonepileptic events [97]. Nonepileptic diagnoses made in this setting include syncope, cerebrovascular events, obstructive sleep apnea and other sleep disorders, hypotension, and psychogenic events. (See "Video and ambulatory EEG monitoring in the diagnosis of seizures and epilepsy" and 'Differential diagnosis' below.)

Selection of appropriate patients for this test should be undertaken thoughtfully and should include an understanding of the frequency of events. Only individuals with events occurring at least weekly and who can tolerate hospital confinement should be considered for prolonged video-EEG monitoring. For individuals with rare events, continuous monitoring (ambulatory or video-EEG) will likely be nondiagnostic because interictal (between seizure) EEG in the older person may be of limited utility, with relatively low sensitivity and specificity for the diagnosis of epilepsy (see "Electroencephalography (EEG) in the diagnosis of seizures and epilepsy"). Additionally, older patients are more susceptible to hospital complications such as deep venous thrombosis, deconditioning, delirium, and falls.

●EEG findings – Nonspecific EEG abnormalities such as intermittent focal slowing are seen in 12 to 38 percent of older individuals without seizures [97,101]. Usually, these abnormalities make up a small portion (1 or 2 percent) of the tracing; more intrusive and more epileptiform abnormalities increase the likelihood of associated epilepsy [102].

A normal EEG does not rule out the possibility of seizures or epilepsy, and it is seen in approximately two-thirds of patients with epilepsy [103,104]. Activation procedures (hyperventilation and photic stimulation) and repeated evaluations add little to the diagnostic yield of the test in this age group [104]. More frequent seizures and EEG recording within 24 hours of an event increase the likelihood of an abnormal interictal EEG [105].

DIFFERENTIAL DIAGNOSIS

Diagnostic challenges and pitfalls — Differentiating seizures from other paroxysmal disorders can be challenging in the older adult for many of the same reasons that diagnosing seizures can be difficult; because of the "atypical" symptomatology, seizures in older patients are frequently misdiagnosed, or the diagnosis is delayed.

Older patients are more likely to have other medical conditions and take multiple medications; therefore, it is imperative to consider other paroxysmal conditions (table 3), including syncope due to cardiac arrhythmias or orthostatic hypotension, delirium and confusional states (table 4), fluctuating behavioral disturbances and abnormal movements due to neurodegenerative conditions, metabolic disturbances, and transient ischemic attacks (TIAs). Most seizures end spontaneously within two to three minutes. However, in the older adult, seizures can cause prolonged postseizure confusion and sleepiness. As a result, it can be difficult to ascertain if there is a paroxysmal and/or episodic quality to the events.

In the large Veterans Affairs trial, 73 percent of patients ultimately diagnosed with epilepsy had a different referral diagnosis [1,65]. These included altered mental status, confusion, blackout spells, memory disturbance, syncope, dizziness, and dementia. In another series, TIA, depression, and metabolic or psychiatric disorders were among the initial misdiagnoses [81]. Misdiagnosis is more common in patients with focal seizures than with generalized tonic-clonic seizures. Despite the known association of seizures and cerebrovascular disease, a history of stroke or TIA was associated with a 1.7-year delay in diagnosing seizures [106]. Similarly, comorbid dementia can obscure the recognition of seizures.

Syncope — Cardiogenic syncope is common in the older population and associated with high morbidity and mortality. Cardiogenic syncope can occur when the patient is supine; can be accompanied by incontinence; and can result in a prolonged recovery period, particularly if the patient remains hypotensive, mimicking a postictal state. In addition, abnormal motor movements (brief jerky movements) may accompany syncope, further confusing the observer.

Cardiogenic syncope can present as sudden falls without prodromal symptoms and result in serious self-injury. Orthostatic hypotension leading to syncope can also present as sudden falls because older patients may not recognize prodromal lightheadedness or dizziness due to cognitive impairment. Differentiating syncope from seizure is discussed in more detail separately. (See "Nonepileptic paroxysmal disorders in adolescents and adults", section on 'Syncope'.)

Delirium and confusional states — Delirium and acute toxic-metabolic encephalopathy may be difficult to distinguish from focal seizures with impairment of consciousness or awareness and nonconvulsive status epilepticus (NCSE), particularly in a patient with baseline neurologic impairment [107]. Episodic, dramatic changes in mental status with a return to normal or baseline cognition strongly suggest seizures, but the presentation may be more subtle.

When present, stereotyped motor movements or automatisms suggest seizure. However, tremor, asterixis, and myoclonus can accompany delirium. Hallucinations may be a feature of either condition. Causes of delirium (table 4) and seizures overlap, and delirium and seizures can coexist. Continuous video-EEG can identify or exclude seizures in this setting. (See "Diagnosis of delirium and confusional states".)

In the setting of severe medical illness, NCSE presents a particularly difficult diagnostic and treatment challenge (see 'Nonconvulsive status epilepticus' above). It manifests as an altered mental status with confusion, psychosis, lethargy, or coma. This nonspecific presentation can be associated with a delay to diagnosis, up to five days in one series of older patients [81]. A high index of suspicion for the diagnosis is required, as the underlying illness may often be deemed a sufficient explanation for altered sensorium. (See "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis".)

Transient ischemic attacks — TIAs may be mistaken for seizures, and in rare circumstances, they may also induce seizures. (See 'Acute symptomatic seizures (provoked or triggered seizures)' above.)

The diagnosis of TIAs becomes much less likely if the history indicates multiple stereotyped episodes over an extended time without permanent neurologic sequelae. Repeated episodes of ischemia involving the same vascular territory would likely result in sustained or fixed neurologic deficits.

Typically, brain ischemia presents as "negative" symptoms such as hemiparesis or hemisensory loss. By contrast, seizures usually cause "positive" symptoms (involuntary shaking or movements) from neural hyperexcitability. One exception is the condition "limb-shaking" TIAs, which represent a source of diagnostic confusion. In this rare condition, cerebral ischemia occurring in the setting of high-grade carotid stenosis causes intermittent weakness in a single limb, which can mimic the clonic jerky movements of a focal motor seizure [108,109].

Certain symptoms, such as speech arrest or language dysfunction (aphasia), can occur in a TIA or a seizure. Sudden, isolated aphasia (sudden language dysfunction without other manifestations) is more likely to be a TIA but can occur with seizures. Evolving symptoms would be more suggestive of seizure. Associated confusion/disorientation and/or amnesia for the event would also favor the seizure diagnosis.

Transient global amnesia — Transient global amnesia (TGA) occurs in older individuals and is characterized by striking amnesia with preservation of other cognitive domains (patients remain awake, alert, and attentive). TGA episodes last much longer than most seizures (usually several hours) and are without lethargy or motor manifestations. Differentiating transient epileptic amnesia (TEA) from TGA can be difficult, but a hallmark of TEA is the recurrence of multiple stereotyped events and response to antiseizure medications. (See "Transient global amnesia".)

Sudden unexplained falls/drop attacks — These are events characterized by a sudden fall to the ground without warning. Although seizures can present in this fashion in older patients, cardiogenic syncope and vestibular pathologies are more likely potential causes. (See "Syncope in adults: Epidemiology, pathogenesis, and etiologies", section on 'Causes of syncope' and "Evaluation of the patient with vertigo", section on 'Drop attacks'.)

Psychogenic spells and/or behavioral spells — It is a myth that late-onset psychogenic spells are rare; therefore, nonepileptic spells should be considered when evaluating the older adult with episodic changes in behavior.

The clinical features of these nonepileptic events can be similar to spells seen in younger patients [110]. Nonepileptic spells in older patients can present with eye closure, staring, asynchronous limb movements, pelvic thrusting, and/or complex behaviors such as screaming or crying. Not all nonepileptic spells in older patients are psychogenic or somatoform in etiology. Episodic unresponsiveness or sudden episodes of decreased alertness can be seen in patients with Alzheimer disease and dementia with Lewy bodies and are not epileptic in etiology.

The main difference between late-onset psychogenic nonepileptic attacks and psychogenic events in younger patients is the associated trauma; in older patients, health-related traumatic events are more likely, while in younger patients, antecedent sexual abuse is more likely [111]. (See "Functional seizures: Etiology, clinical features, and diagnosis".)

Sleep disorders — Rapid eye movement (REM) sleep behavior disorder (RBD) can be mistaken for epilepsy. This is a parasomnia characterized by vivid dreams in REM sleep without the usual accompanying muscle atonia [36,37]. RBD causes individuals to "act out" their dreams, especially when they are vivid or frightening. Injuries to the patient and bed partner can result.

Patients are generally able to describe the dream, a feature that is helpful in distinguishing RBD from seizures. Episodes can recur during the night, and preferentially occur in the second half of sleep when there is the greatest preponderance of REM sleep.

While sometimes occurring as an isolated idiopathic condition in younger adults, RBD in older adults is most commonly associated with alpha-synuclein neurodegenerative disorders including dementia with Lewy bodies and Parkinson disease. It usually presents after the age of 50 years [59]. The diagnosis can be confirmed with polysomnography. (See "Rapid eye movement sleep behavior disorder".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Seizures (The Basics)")

●Beyond the Basics topics (see "Patient education: Seizures in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Acute symptomatic (provoked) seizures are common in older adults, and the prevalence of epilepsy (recurrent unprovoked seizures) increases with age, being highest in patients >75 years of age. (See 'Epidemiology' above.)

●Causes and risk factors – In older adults, acute symptomatic seizures are most often seen in the setting of acute stroke, intracranial lesions, and metabolic encephalopathy (table 1). Cerebrovascular disease and degenerative dementia are common causes of epilepsy in older patients, but one-third to one-half of cases are of unknown etiology. (See 'Causes and risk factors' above.)

●Presentation and semiology – The clinical presentation of seizures in the older population is often atypical and easily mistaken for other conditions such as delirium, transient ischemic attack, or syncope. Features that may suggest seizure in older adults include episodic confusion, behavioral change, or unresponsiveness, sudden falls with no recall or warning, and arousal from sleep with confusion or disorientation. In contrast with younger adults, older adults with seizures are less likely to have an aura, be convulsive, or have motor features. (See 'Presentation, seizure type, and semiology' above.)

●Evaluation and diagnosis – The main goals of the diagnostic evaluation are to establish whether the patient has had one or more provoked or unprovoked seizures and, if so, determine the etiology of the seizures and/or epilepsy. It is important to determine whether a first seizure is a provoked event that is not expected to recur in the absence of that trigger or if it is the first sign of new-onset epilepsy, a condition in which recurrent unprovoked seizures are expected in the absence of treatment.

•A reliable history and description of the event from an eyewitness are invaluable and superior to testing in the diagnosis of epileptic seizures. (See 'Patient history' above.)

•Because metabolic abnormalities can precipitate seizures, patients with acute seizures should have blood analyzed for electrolytes, blood urea nitrogen, creatinine, glucose, calcium, magnesium, and liver function tests. A toxicology screen, lumbar puncture, and/or autoantibody testing may be appropriate for select patients, as described above. (See 'Laboratory evaluation' above.)

•A brain imaging study should be obtained in all older patients due to the frequency of stroke or other structural disease as an etiology. (See 'Neuroimaging' above.)

•EEG monitoring, particularly video-EEG monitoring, can be helpful when the diagnosis or etiology remains uncertain after the initial evaluation. (See 'Electroencephalography' above.)

●Differential diagnosis – Considerations in the differential diagnosis of seizures in older patients include syncope, delirium and confusional states, transient cerebral ischemia, and other disorders (table 3). (See 'Differential diagnosis' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Hyunmi Choi, MD, MS, and Anil Mendiratta, MD, who contributed to an earlier version of this topic review.