Overview of the management of epilepsy in adults

INTRODUCTION AND APPROACH TO TREATMENT — 

The management of patients with epilepsy is focused on three main goals: controlling seizures, avoiding treatment adverse effects, and maintaining or restoring quality of life. Clinicians should assist in empowering patients with epilepsy to lead lifestyles consistent with their capabilities [1,2].

The optimal treatment plan is derived from an accurate diagnosis of the patient's seizure type(s), an objective measure of the intensity and frequency of the seizures, awareness of medication adverse effects, and an evaluation of disease-related psychosocial problems. A working knowledge of available antiseizure medications (ASMs), including their mechanisms of action, pharmacokinetics, drug-drug interactions, and adverse effects, is essential.

It is usually appropriate to refer the patient to a neurologist when establishing a diagnosis and formulating a course of treatment. Referral to an epilepsy specialist may be necessary if there is doubt about the diagnosis and/or if the patient continues to have seizures.

The overall approach to management of a patient with seizures is reviewed here. Evaluation of the patient who has had a first seizure and the pharmacology of specific ASMs are discussed separately:

●(See "Evaluation and management of the first seizure in adults".)

●(See "Initial treatment of epilepsy in adults".)

●(See "Antiseizure medication maintenance therapy and drug monitoring".)

●(See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

CLASSIFICATION — 

The first step in designing a treatment plan is to classify the patient's seizure type(s) using the framework of the International League Against Epilepsy [3-6]. (See "ILAE classification of seizures and epilepsy".)

There are two broad categories of seizures: focal (or partial) and generalized (table 1).

●Focal seizures involve only a portion of the brain, typically part of one lobe of one hemisphere. A focal seizure can be associated with impairment of awareness (previously called complex partial seizure) or no impairment of awareness (previously called simple partial seizures) and a variety of behaviors, as listed in the table (table 2). A focal seizure can evolve over seconds into a bilateral tonic-clonic seizure, also referred to as a secondarily generalized seizure. (See "Evaluation and management of the first seizure in adults", section on 'Types of seizures'.)

●Generalized seizures arise from both sides of the brain simultaneously. Generalized tonic-clonic seizures (also called grand mal seizures, major motor seizures, or convulsions) are the most common type of generalized seizures. Other types of generalized seizures are absence seizures (more often seen in childhood in association with generalized epilepsy syndromes) and clonic, myoclonic, tonic, and atonic seizures.

Seizure types and epilepsy syndromes are classified primarily upon clinical grounds, assisted by laboratory, neurophysiologic, and radiographic studies. Seizure type has important implications in the choice of antiseizure medications (ASMs). Accurate classification requires a full history from the patient and reports from observers who have witnessed actual seizures. Pointed questions may be necessary to reveal behaviors or environmental factors that contribute to the incidence of seizures. These "seizure triggers," such as sleep deprivation, alcohol intake, and stress, may be modifiable. Thus, taking steps that limit exposure to these triggers usually enhances the benefits of ASM therapy. (See "Evaluation and management of the first seizure in adults", section on 'History'.)

Patients may be better able to describe their seizure symptoms after reading published seizure descriptions, which in turn may improve the clinician's ability to categorize the seizure type and to plan a successful therapeutic approach [7]. Many patients experience more than one type of seizure (eg, focal seizures and focal to bilateral tonic-clonic seizures, previously called secondarily generalized seizures).

ANTISEIZURE MEDICATION THERAPY

When to start antiseizure medication therapy — Immediate antiseizure medication (ASM) therapy is usually not necessary in individuals after a single seizure, particularly if a first seizure is an acute symptomatic seizure (provoked) due to factors that resolve (algorithm 1). (See "Evaluation and management of the first seizure in adults", section on 'Acute symptomatic (provoked) seizure'.)

ASM therapy should be started in patients who are at significant risk for recurrent seizures, such as those with remote symptomatic (unprovoked) seizures. ASM treatment is generally started after two or more unprovoked seizures, because the recurrence proves that the patient has a substantially increased risk for repeated seizures, well above 50 percent. ASM treatment may also be considered for patients with a first unprovoked seizure who have factors associated with a high risk of seizure recurrence (algorithm 2). (See "Evaluation and management of the first seizure in adults", section on 'Unprovoked seizure'.)

The issues to be considered in deciding when to start ASM therapy are discussed in detail separately. (See "Initial treatment of epilepsy in adults", section on 'When to start antiseizure medication therapy'.)

ASM therapy is not necessarily lifelong. (See "Approach to the discontinuation of antiseizure medications".)

Choosing an antiseizure medication — Approximately half of patients with a new diagnosis of epilepsy will become seizure-free with the first ASM prescribed [8,9]. Tolerability of adverse effects is as important as efficacy in determining the overall effectiveness of treatment. No single ASM is optimal for every patient. The selection of a specific ASM for treating seizures must be individualized considering:

●Drug effectiveness for the seizure type or types (table 3 and table 4) [10]

●Potential adverse effects of the drug (see 'Adverse effects of therapy' below)

●Interactions with other medications

●Comorbid medical conditions, especially, but not limited to, hepatic and renal disease

●Age and sex, including childbearing plans

●Lifestyle and patient preferences

●Cost

In general, enzyme-inducing ASMs (eg, phenytoin, carbamazepine, phenobarbital, primidone, and less so, oxcarbazepine and topiramate) are the most problematic for drug interactions with warfarin and oral contraceptive therapy, as well as certain anticancer and anti-infective drugs (table 5). Specific interactions of ASMs with other medications may be determined using the drug interactions program.

Issues to consider in selecting a specific ASM are discussed in detail separately. (See "Initial treatment of epilepsy in adults", section on 'Selection of an antiseizure medication'.)

Adverse effects of therapy — During the first six months of ASM treatment, adverse events due to systemic toxicity and neurotoxicity cause ASM failure to the same degree as lack of efficacy against seizures (table 6 and table 7). Serum levels that are associated with neurotoxicity vary from patient to patient, and toxicity can occur even when measured levels are considered to be within the appropriate therapeutic range. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'ASM levels'.)

The usual strategy in patients experiencing peak-level adverse effects from a specific drug is to alter the medication regimen or treatment schedule to minimize adverse effects; one alteration may be to spread the medication over more doses throughout the day. The clinician should attempt to correlate serum drug concentrations with the patient's adverse effects before abandoning that medication. Specifically, obtaining levels when a patient is experiencing adverse effects and comparing them with levels obtained when the patient is free from symptoms can be helpful in the management of some patients.

It can also be useful to refer to the patient's seizure calendar in planning the timing of drug levels in an attempt to prove a cause-and-effect relationship between peak levels and adverse effects (see "Antiseizure medication maintenance therapy and drug monitoring", section on 'Seizure calendar'). As an example, in a patient who experiences seizures only at night but who has adverse effects in the afternoon from their morning dose of ASMs, shifting part of the morning dose to the bedtime dose may eliminate these adverse effects while improving seizure control.

Many adverse effects of ASMs specific to individual medications are reviewed in detail separately (see "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects"). Some severe reactions that are common to more than one medication include the following:

●Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) – These are rare but severe idiosyncratic reactions characterized by fever and mucocutaneous lesions, which have been associated with the use of carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, zonisamide, lamotrigine, and (less commonly) other ASMs. SJS, TEN, and DRESS are reviewed in detail elsewhere:

•(See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Rare but potentially serious adverse effects'.)

•(See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)

•(See "Drug reaction with eosinophilia and systemic symptoms (DRESS)".)

●Suicidal ideation and behavior – People with epilepsy are at increased risk for depression and suicidality. ASMs may (possibly) increase the risk, as discussed separately. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Rare but potentially serious adverse effects'.)

Therefore, clinicians prescribing ASMs should identify a current or past history of depression, anxiety, and suicidal ideation or behavior in their patients. Patients taking ASMs should be monitored for emergence or worsening of suicidal ideation, behavior, or depression. Patients, families, and caregivers should be encouraged to call their clinician if they observe any symptoms of depression, and clinicians should be extra attentive to warning signs during medication changes. (See "Comorbidities and complications of epilepsy in adults", section on 'Screening'.)

A suggested approach to the assessment of suicidal ideation and behavior in adults is discussed separately. (See "Suicidal ideation and behavior in adults".)

●Bone disease – Bone loss has also been described in patients receiving long-term ASMs. The screening, treatment, and prevention of ASM-related bone disease is discussed separately. (See "Antiseizure medications and bone disease".)

Drug interactions — Certain ASMs, particularly older first-generation ASMs, have the potential for important drug-drug interactions:

●Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate are enzyme-inducing agents; these ASMs can increase the clearance and reduce the effect of numerous medications including concomitant ASMs, hormonal contraceptives, oral anticoagulants, antipsychotics, antibiotics, antivirals, immunosuppressives, chemotherapeutic agents, statins, and antidiabetic agents [11].

●Valproate, felbamate, and cenobamate can decrease the clearance and increase the levels of concomitant ASMs, anticoagulants, antipsychotics, and calcium channel blockers [11].

Comprehensive information on drug-drug interactions can be determined using the UpToDate drug interactions program. The drug interactions of specific ASMs are reviewed in detail separately. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

Maximizing the likelihood of a successful outcome

Patient education — The diagnosis of epilepsy can be distressing. Before starting treatment, clinicians should begin a dialogue with the patient, family, and caregivers to increase their understanding of epilepsy and their ability to report necessary and relevant information. The discussion should review the incidence and risk factors for sudden unexpected death in epilepsy (SUDEP), other epilepsy comorbidities, and expectations of the treatment plan, including the importance of adherence to ASM therapy. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Educating patients'.)

Titration and monitoring — We start treatment with a single ASM (monotherapy). The recommended initial dose for individual ASMs and a potential titration schedule are presented separately. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

Approximately 50 percent of patients will obtain seizure freedom with the first monotherapy. In general, the strategy is to "start low and go slow" by gradually titrating to the lowest effective dose that achieves seizure freedom while minimizing adverse effects. However, for patients who continue to have frequent or disabling seizures after epilepsy onset, a medication that can be safely titrated rapidly may be preferred. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Antiseizure medication titration'.)

Patients with epilepsy should have routine follow-up visits to record seizure frequency, inquire about medication adverse effects, and obtain any needed tests. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Follow-up visits'.)

Seizure calendar — We encourage the use of a seizure calendar to help track the patient's response to ASM therapy and identify possible adverse effects and seizure triggers. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Follow-up visits' and "Antiseizure medication maintenance therapy and drug monitoring", section on 'Seizure calendar'.)

Clinicians should recognize that patients are often unaware of their seizures and may therefore significantly underestimate the number of seizures that occur, especially those that occur during sleep or that disrupt consciousness [12]. Prolonged electroencephalography (EEG) recordings may be helpful in such patients to determine seizure frequency, either ambulatory or in a video-EEG monitoring unit. (See "Video and ambulatory EEG monitoring in the diagnosis of seizures and epilepsy".)

Generic substitution — Most generic medications are much less expensive than brand-name products. Bioequivalence of generic medications is defined by regulatory authorities. Although patient acceptance of (and adherence to) generic ASM therapy may be lower compared with brand-name ASMs, accumulating evidence suggests that the use of generic ASMs does not compromise efficacy. The role of generic ASMs in the treatment of epilepsy is reviewed in detail elsewhere. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Generic substitution'.)

Alcohol intake — Alcohol consumption in small amounts (one to two drinks per day) may not affect seizure frequency or serum levels of ASMs in patients with well-controlled epilepsy [13]. Heavier alcohol intake (three or more drinks per day) increases the risk of seizures, particularly during the withdrawal period (6 to 48 hours after drinking either stops or is significantly reduced), and this practice should be strongly discouraged [14]. (See "Alcohol withdrawal: Epidemiology, clinical manifestations, course, assessment, and diagnosis", section on 'Alcohol withdrawal seizures'.)

In an effort to enable people with epilepsy to live as normal a life as possible, it may be reasonable to advise that limited alcohol intake is acceptable, provided there is no history of alcohol or substance use disorder or a history of alcohol-related seizures. However, patients should be aware that the data are not definitive.

Patients who are otherwise medically cleared to drive should nevertheless avoid driving and other high-risk activities for 24 to 48 hours after heavy alcohol intake due to the higher risk of seizures.

Nonadherence — Rates of nonadherence with ASM therapy are high among people with epilepsy. The potential consequences include an increased risk of seizures, hospitalization, fractures, head injuries, and mortality. Factors associated with an increased risk of nonadherence include younger age, feeling depressed, ASM adverse effects, perceived lack of ASM efficacy, and belief that treatment was no longer needed.

Clinicians should suspect nonadherence if a patient denies the diagnosis of epilepsy (note that some patients may be unaware of their seizures), has limited financial means to pay for ASMs, has difficulty tolerating adverse effects, or forgets when or how to take medication because of memory impairment. An unexpected increase in the number or severity of seizures, or either subtherapeutic or supratherapeutic serum drug concentrations, also suggests nonadherence. However, serum levels can fluctuate due to a number of factors; thus, they should be interpreted with some caution.

Adherence diminishes when intervals between office visits grow longer and when medication regimens grow increasingly complex and expensive. Clinicians should be attuned to out-of-pocket costs and strive to use the simplest regimen possible, with generic substitutions when appropriate. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Nonadherence with ASM therapy' and "Patient education: Coping with high prescription drug prices in the United States (Beyond the Basics)".)

Nonadherence may also result from a failure of the clinician to effectively communicate. Written information about medications and changes in dosing should be provided in simple language. Improving the patient's understanding of their disorder and the need for regular intake of medications may also improve motivation and adherence.

In addition to patient education, the use of calendars, medication alarms, and medication dosette boxes may help improve adherence. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Nonadherence with ASM therapy'.)

Failure of initial therapy — For patients with breakthrough seizures or failure of initial ASM monotherapy that is adequately dosed and tolerated, adding a second ASM (combination therapy) is appropriate if the first ASM is well tolerated and improves but does not abolish seizures. Except in the case of a serious adverse event from the first ASM, the second medication is typically increased to therapeutic levels before the first agent is reduced to prevent a flurry of seizures or status epilepticus during the switch-over period. The second ASM is gradually titrated up to effect (control of seizures) or to toxicity (adverse effects). However, patients should expect a temporary increase in adverse effects during the overlap period that will likely abate when the first ASM is subsequently tapered off.

ASM substitution is appropriate if the first ASM is poorly tolerated at a lower dose or fails to improve seizure control.

Although data from randomized trials are limited, several studies have found that seizure outcomes are similar when comparing ASM monotherapy substitution versus adding a second ASM. (See "Antiseizure medication maintenance therapy and drug monitoring", section on 'Breakthrough seizures'.)

Discontinuing antiseizure medication therapy — After at least a two-year seizure-free interval, it is reasonable to begin a discussion about continued ASM therapy versus a trial of discontinuation. This decision must be individualized and weighs the risks of seizure recurrence against the possible benefits of drug withdrawal, all of which may vary significantly across patients. This is discussed in detail elsewhere. (See "Approach to the discontinuation of antiseizure medications".)

DRUG-RESISTANT EPILEPSY — 

Drug-resistant epilepsy (DRE) may be defined as failure of adequate trials of two tolerated and appropriately chosen and used antiseizure medication (ASM) schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom [15]. (See "Evaluation and management of drug-resistant epilepsy", section on 'Definition'.)

The diagnosis and classification of epilepsy should be reconsidered in patients whose seizures do not respond to ASM trials. In particular, video-EEG monitoring to confirm the epileptic nature of spells should be considered in anyone still having seizures after two ASM trials or more than one year of treatment. (See "Video and ambulatory EEG monitoring in the diagnosis of seizures and epilepsy".)

When possible, patients with apparent or true DRE should be referred for evaluation by an epilepsy specialist, ideally at a comprehensive epilepsy center. The evaluation may require further testing (video-EEG monitoring, interictal EEG, and brain imaging) to exclude seizure mimics, confirm the diagnosis of epilepsy, and better define the epilepsy syndrome and underlying classification, which are all important for directing treatment (algorithm 3). (See "Evaluation and management of drug-resistant epilepsy", section on 'Evaluation'.)

In well-selected patients with DRE (eg, those with focal epilepsy), epilepsy surgery is superior to medical therapy. Epilepsy surgery is particularly appropriate for patients with DRE when seizures are disabling or reduce the quality of life due to impairment of consciousness, injury, high seizure frequency, or increased risk of mortality. For patients in whom epilepsy surgery is not an option or whose seizures persist after surgery, treatment options include further empiric trials with other ASMs appropriate for their epilepsy syndrome, neurostimulation (eg, vagus nerve stimulation, responsive cortical stimulation, deep brain stimulation), or ketogenic dietary therapy.

The treatment of DRE is reviewed in greater detail separately:

●(See "Epilepsy surgery: Presurgical evaluation".)

●(See "Resective and ablative surgical treatment of epilepsy in adults".)

●(See "Evaluation and management of drug-resistant epilepsy", section on 'Neurostimulation'.)

●(See "Vagus nerve stimulation therapy for the treatment of epilepsy".)

●(See "Ketogenic dietary therapies for the treatment of epilepsy".)

SPECIFIC POPULATIONS AND ETIOLOGIES

Females of childbearing age — A number of issues are important in females of childbearing potential, especially if they are considering becoming or are already pregnant. Clinicians should regularly review these issues with their female patients with epilepsy. Pregnancies should be planned, and females with epilepsy require close follow-up in pregnancy. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period".)

Effect of antiseizure medications on the fetus — There is an increased risk of both major and minor malformations in fetuses exposed to antiseizure medication (ASM), particularly valproate. In addition, there is accumulating evidence from observational studies that ASM therapy during pregnancy may have deleterious effects on cognitive and developmental outcomes of exposed children later in life. (See "Risks associated with epilepsy during pregnancy and the postpartum period", section on 'Effects of ASMs on the fetus and child'.)

There are strong data regarding increased risk of malformations and adverse developmental outcomes with valproate. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Choice of antiseizure medication'.)

Folic acid supplementation — Folate should be routinely prescribed to all females of childbearing age taking ASMs. Patients taking valproate or carbamazepine should receive daily folic acid supplementation (up to 4 mg/day) for one to three months prior to conception. Females who are taking other ASMs should take the more standard lower dose of folic acid (0.4 to 0.8 mg/day). (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Folic acid supplementation'.)

Contraception — Enzyme-inducing ASMs lower the efficacy of hormonal contraceptives (eg, oral contraceptive pills, vaginal ring, etonogestrel implant). This issue is discussed in greater detail separately. (See "Management of epilepsy during preconception, pregnancy, and the postpartum period", section on 'Contraception'.)

Fertility — While a number of studies have suggested that females with epilepsy have increased rates of infertility, with an estimated risk that ranges from approximately 9 to 38 percent in different reports [16-18], other studies have not confirmed this finding [19,20]. It is also uncertain whether this association is linked to epilepsy itself or to ASM treatment.

Potential confounding factors in assessing a possible association of epilepsy with infertility include lower marriage rates and a lower rate of planned pregnancies. The latter may result because of concerns about teratogenicity, ability to care for a child, and an increased risk of epilepsy in a child [21].

There is evidence that suggests that ASM use may affect fertility. In a prospective cohort study of 375 females with epilepsy, infertility was linked to polytherapy, as well as to older age and lower education [16]. Valproate, in particular, has been linked to an increased risk of polycystic ovary disease, a leading cause of infertility in females [22]. (See "Epidemiology, phenotype, and genetics of the polycystic ovary syndrome in adults", section on 'High-risk groups'.)

Catamenial epilepsy — Approximately 40 percent of females with epilepsy report an association between the occurrence of their seizures and certain phases of their menstrual cycle [23]. Catamenial seizure clustering can occur in females with any seizure type and epilepsy syndrome but may be more common among females with focal compared with generalized epilepsy [24-28] and among those with left-sided temporal epilepsy compared with right-sided, multifocal, or extratemporal epilepsy [29,30].

●Mechanisms – In general, research suggests that catamenial seizure patterns result from cyclic changes in hormone levels during the menstrual cycle; changes in ASM levels due to endogenous metabolic effects may also contribute. Estrogen levels peak mid-cycle and then, in females who do not conceive, fall through the onset of menses. It is during the late part of the menstrual cycle (just before the onset of menses), during a relative drop in estrogen levels, that seizures most often cluster [24,31]. Periovulatory (mid-cycle) seizure clustering can also occur.

●Treatment – The mainstay of treatment of catamenial seizures is an ASM that is most effective for the patient's epilepsy syndrome.

When catamenial seizures are not controlled with ASMs, clinicians may consider use of adjunctive continuous estrogen-progestin contraceptive on the theoretical basis that suppressing estrogen fluctuations will lead to better seizure control. However, data are limited, and several small placebo-controlled randomized clinical trials have failed to demonstrate benefit of hormonal therapy for reducing seizure frequency with catamenial epilepsy [32]. The largest of these trials included 294 females with poorly controlled seizures and found no difference for progesterone compared with placebo [33]. The rationale and use of hormonal prophylaxis for catamenial epilepsy is similar to that in estrogen-associated migraine, which is reviewed separately. (See "Estrogen-associated migraine headache, including menstrual migraine".)

Intermittent benzodiazepine treatment timed according to the vulnerable phase of the menstrual cycle is another possible treatment strategy. Clobazam is the only benzodiazepine studied systematically for this purpose. In a double-blind cross-over study, clobazam (20 to 30 mg/day) was administered for 10 days in the high-risk phase of the menstrual cycle in 18 females with catamenial epilepsy [34]. Fourteen patients reported better seizure control with clobazam than placebo. Long-term follow-up of patients who continued to use this treatment strategy revealed seizure remission and/or significant reduction of seizures in five of nine patients [35]. These limited data support a fairly common practice of treating catamenial seizure exacerbations with intermittent benzodiazepines with a long-acting agent such as lorazepam. A reasonable dose of lorazepam in this setting is 0.5 to 1 mg two to three times daily.

Very limited data suggest that appropriately timed acetazolamide may have some benefit in catamenial epilepsy [36-38]. Other investigational strategies include gonadotropin analogs and neurosteroids such as ganaxolone [39-41].

Older patients — ASM use in older adult patients is complicated by several factors, including age-related alterations in protein binding, reduced hepatic metabolism, and diminished renal clearance of medications. In addition, medical comorbidities and polypharmacy are more often a concern in older adults. The selection of ASM treatment in older adults is discussed separately. (See "Initial treatment of epilepsy in adults", section on 'Older adults'.)

Poststroke seizures — Stroke is the most common cause of seizures and epilepsy in population studies of adults over the age of 35 [42]. Most seizures following stroke are focal at onset, but secondary generalization is common, particularly in patients with late-onset seizures. Early poststroke seizures are defined as acute symptomatic seizures if they occur within seven days of acute stroke onset [43]. Late poststroke seizures are defined as seizures that occur beyond seven days after acute stroke onset. A retrospective report found that poststroke seizures were associated with an increased risk for developing dementia [44].

●Pathogenesis – The pathogenesis of early-onset poststroke seizures may be related to local ion shifts, release of high levels of excitotoxic neurotransmitters in the area of ischemic injury, blood-brain barrier disruption, cellular hypoxia, electrolyte imbalance, and hemorrhagic transformation [45,46].

By contrast, late-onset poststroke seizures are likely caused by gliotic scarring, selective neuronal loss, and disruption of neuronal networks from an underlying permanent lesion, leading to persistent changes in neuronal excitability [46]. This probably accounts for the fact that the risk of chronic epilepsy is higher in patients with late rather than early occurrence of seizures. In one study, for example, 118 patients who had a thrombotic stroke had a bimodal distribution of seizures either within two weeks or from 6 to 12 months after the stroke [47]. Epilepsy developed in more patients with late than those with early seizures (90 and 35 percent, respectively).

●Epidemiology – A 2020 systematic review and meta-analysis of seizures occurring after acute ischemic stroke reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy) included 25 studies with 13,573 patients [48]. The pooled incidence of poststroke seizures was 5.9 percent. Among studies reporting the time of seizure onset, the incidence of early poststroke seizures (occurring within seven days) was 3.2 percent, while the incidence of late poststroke seizures (occurring after seven days) was 6.7 percent. Similarly, a 2023 systematic review and meta-analysis of observational studies found that the pooled incidence of early and late poststroke seizures in adults was 5 and 7 percent, respectively [49].

The risk of late poststroke seizures may increase over time. In a population-based study of over 3000 patients presenting with first stroke, poststroke epilepsy (defined as ≥2 unprovoked seizures occurring after the acute phase of stroke) developed in 213 patients (6.4 percent) after a mean follow-up of four years [50]. The estimated cumulative incidence of epilepsy rose from 3.5 percent at one year, which is similar to estimates from prior studies with shorter-term follow-up, to over 12 percent at 10 years.

●Risk factors – The most consistently identified risk factors for acute and late poststroke seizures are worse stroke severity, cortical location, and hemorrhagic lesions [46,49-54]. For primary intracerebral hemorrhage, subcortical hematoma location may actually pose higher risk for late seizures than cortical location [55]. Younger age has been reported as a risk factor for late seizures in at least one large study [50]. One prospective study found that preexisting dementia was a risk factor for late seizures (odds ratio [OR] 4.66, CI 1.34-16.21) but not for early seizures [56]. Dementia is a risk factor for epilepsy in patients without stroke as well. (See "Seizures and epilepsy in older adults: Etiology, clinical presentation, and diagnosis".)

●When to start treatment – Early poststroke seizures (within seven days of stroke onset) are considered acute symptomatic (provoked) seizures with a low risk of recurrence; short-term ASM treatment is often used for one to four weeks following an early poststroke seizure, but long-term ASM treatment is not indicated if early seizures resolve [57]. Guidelines from the American Heart Association/American Stroke Association state that recurrent seizures after acute ischemic stroke should be treated like recurrent seizures that occur with other acute neurologic conditions [58].

By contrast, late poststroke seizures are considered to have an increased risk of recurrence similar to unprovoked seizures due to a focal brain lesion [57,59], and long-term ASM therapy is required in most cases.

However, given the relatively low frequency of recurrent seizures after stroke, the absence of absolute predictors of poststroke epilepsy, and limited evidence base [59], the decision of when to treat patients for a poststroke seizure is difficult.

Additional aspects of poststroke seizure management following intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage are reviewed elsewhere:

•(See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Seizure management'.)

•(See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Seizure prophylaxis'.)

•(See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Seizures'.)

●Status epilepticus – Status epilepticus is relatively uncommon after stroke. In a report of 180 patients with poststroke seizures who were followed for an average of 3.7 years, status epilepticus developed in 17 patients (9 percent); early onset of status epilepticus (within the first seven days after stroke) was reported in seven patients [60].

Efficacy of antiseizure medications in poststroke epilepsy – The efficacy of specific ASMs for poststroke seizures has not been rigorously assessed in controlled trials, although most seizures can be controlled with a single agent [61]. The evidence does not clearly support one specific ASM over another [62]. A 2025 systematic review and network meta-analysis identified 15 eligible studies, including three randomized controlled trials and two prospective and 19 retrospective nonrandomized cohorts [63]. Among 13 ASMs studied, levetiracetam and lamotrigine had the most favorable profiles with respect to lower seizure recurrence, adverse events, drug discontinuation, and mortality. However, the included studies had a moderate (n = 3) or high (n = 12) risk of bias. Additional limitations included marked variation in design, follow-up duration, and sample size of the included studies, as well as lack of data for seizure type, stroke subtype, and ASM doses.

Studies suggest that newer ASMs have similar efficacy but a more favorable adverse event profile in older patients (see "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects" and "Seizures and epilepsy in older adults: Treatment and prognosis"). In one prospective randomized trial, the lamotrigine treatment arm had fewer dropouts due to adverse events than did the carbamazepine arm; lamotrigine appeared to be more efficacious, although this did not reach statistical significance [64]. Gabapentin has been associated with 80 percent seizure remission in one uncontrolled study of poststroke epilepsy [65].

Sleep-related epilepsy — Several epilepsy syndromes manifest with seizures that occur exclusively or predominantly during sleep. Most are focal epilepsy syndromes with genetic or structural etiologies. The most common of these is nocturnal frontal lobe epilepsy (NFLE), also referred to as "sleep-related hypermotor epilepsy." Nocturnal temporal, parietal, and occipital lobe epilepsies also occur but are less common and have overlapping clinical features with NFLE. Most have an onset in adolescence or early adulthood. The clinical features, diagnosis, differential diagnosis, and management of sleep-related epilepsy are discussed separately. (See "Sleep-related epilepsy syndromes", section on 'Sleep-related focal epilepsies'.)

Brain tumors and head trauma — The treatment of epilepsy in the setting of brain tumors and head trauma is discussed separately. (See "Seizures in patients with primary and metastatic brain tumors" and "Posttraumatic seizures and epilepsy".)

COMORBIDITIES AND COMPLICATIONS — 

Epilepsy is a chronic disease associated with an increased risk of a variety of psychiatric and medical comorbidities that can adversely impact quality of life as well as life expectancy. Comorbidities can arise due to common underlying predispositions, direct effects of seizures, underlying epilepsy etiologies, and adverse effects of antiseizure medications (ASMs) and other therapies.

Common comorbidities and complications of epilepsy include the following:

●Psychosocial issues – People with epilepsy suffer from loss of independence, underemployment, poorer social status, decreased leisure time, decreased physical activity, and increased substance use compared with unaffected adults.

●Depression and anxiety – These are particularly common in adults with epilepsy; screening for them should be a routine part of long-term follow-up.

●Psychotic disorders – In addition to comorbid primary psychiatric disorders such as schizophrenia, psychotic disorders may be related to epilepsy itself (ie, interictal psychosis, postictal psychosis) or secondary to ASMs.

●Cognitive impairment – This is often present at the time of diagnosis and may worsen over time. Contributing factors include underlying epilepsy etiology, adverse effects of medications and other epilepsy therapies, frequent or prolonged seizures, and comorbid depression and anxiety.

●Sleep disorders – Obstructive sleep apnea (OSA) and insomnia are common in people with epilepsy and may contribute to worsened seizure control and quality of life.

●Medical comorbidities – Adults with epilepsy have increased rates of medical comorbidities including heart disease, hypertension, stroke, obesity, and metabolic bone disease.

●Accidents and injuries – People with epilepsy are at risk for seizure-related personal injury, such as falls, bone fractures, drowning, and other accidents.

●Premature mortality – People with epilepsy are at substantially increased risk for premature mortality compared with the general population. Important causes of death directly attributable to epilepsy include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide.

These and other comorbidities and complications of epilepsy in adults are discussed separately. (See "Comorbidities and complications of epilepsy in adults".)

DRIVING AND OTHER ACTIVITIES

Driving restrictions — States vary widely in driver licensing requirements for patients with epilepsy. The most common requirements are that patients be free of seizures for a specified period of time and that they submit a clinician's evaluation of their ability to drive safely.

Clinicians should also consider the potential neurotoxic adverse effects of antiseizure medications (ASMs), such as sedation and double vision (table 6), when counseling patients about driving.

A listing of individual state driving requirements can be found on the Epilepsy Foundation website at https://www.epilepsy.com/driving-laws. Additional details about driving restrictions in patients with epilepsy are discussed separately. (See "Driving restrictions for people with seizures and epilepsy".)

Sports and exercise — Questions may arise about participation in sports and other activities, and clinicians may be asked to provide medical clearance before a patient can participate. These decisions should be individualized, weighing not only the potential risks of participation but also the benefits of physical exercise and social engagement [66,67].

Factors to consider include the type of sport or activity, the probability of a seizure occurring during the activity and related implications, the amount of supervision available during the activity, the patient's seizure type and severity, the consistency of any prodromal symptoms, relevant seizure precipitants, a history of seizure-related accidents or injuries, recent seizure control, degree of adherence to therapy, and the willingness of the patient and parents to take on risk. The International League Against Epilepsy has published a consensus-based guideline on sports participation in patients with epilepsy, which divides sports into three risk categories and proposes a decision-making framework for each risk category [66].

Other precautions — Patients with epilepsy should be aware of common seizure triggers or precipitating factors, including sleep deprivation, alcohol, certain medications (table 8), and infection or systemic illness.

Patients should be advised to avoid unsupervised activities that might pose danger with sudden loss of consciousness, including bathing, swimming alone, working at heights, and operating heavy machinery. Patients also should be advised to take showers instead of baths, since bathing is associated with a risk of seizure-induced drowning.

Individuals with epilepsy are at increased risk for personal injury, accidental death, and drowning as well as psychiatric comorbidity, suicidal deaths, and sudden unexpected death in epilepsy (SUDEP). (See "Comorbidities and complications of epilepsy in adults".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in adults".)

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)" and "Patient education: Epilepsy in adults (The Basics)" and "Patient education: Epilepsy and pregnancy (The Basics)")

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

SUMMARY AND RECOMMENDATIONS

●Goals – The management of patients with epilepsy is focused on three main goals: controlling seizures, avoiding treatment adverse effects, and maintaining or restoring quality of life. (See 'Introduction and approach to treatment' above.)

●Need for antiseizure medication – Immediate antiseizure medication (ASM) therapy is usually not necessary in individuals after a single provoked seizure (algorithm 1) and is typically reserved for individuals who are at high risk of recurrent seizures or those who have had two or more unprovoked seizures (algorithm 2). (See "Initial treatment of epilepsy in adults", section on 'When to start antiseizure medication therapy'.)

Selection of an ASM is individualized based upon the seizure type; potential adverse effects; interactions with other medications; comorbid medical conditions; age and sex, including childbearing plans; lifestyle and patient preferences; and cost. (See "Initial treatment of epilepsy in adults", section on 'Selection of an antiseizure medication'.)

●Adverse events of ASMs – Common (table 6) and rare but serious (table 7) adverse events of ASMs can lead to treatment failure. Mood problems, anxiety, and depression are more prevalent in persons with epilepsy than in the general population. In addition, ASM treatment has been associated with suicidality. Patients treated with ASMs should be monitored for changes in mood and suicidality. (See 'Adverse effects of therapy' above.)

●Measures to improve outcome – Regular outpatient office visits that include patient education, review of adverse medication effects, seizure calendar, and drug monitoring are suggested to improve compliance and the likelihood of a successful outcome. (See 'Maximizing the likelihood of a successful outcome' above and "Antiseizure medication maintenance therapy and drug monitoring".)

●Initial treatment failure – For patients with breakthrough seizures or failure of initial ASM monotherapy that is adequately dosed and tolerated, adding a second ASM (combination therapy) is appropriate if the first ASM is well tolerated and improves but does not abolish seizures. ASM substitution is appropriate if the first ASM is poorly tolerated or fails to improve seizure control. (See 'Failure of initial therapy' above and "Antiseizure medication maintenance therapy and drug monitoring", section on 'Breakthrough seizures'.)

●Drug-resistant epilepsy – Drug-resistant epilepsy (DRE) may be defined as failure of adequate trials of two tolerated and appropriately chosen and administered ASMs (whether as monotherapy or in combination) to achieve sustained seizure freedom. The approach to the evaluation and treatment of DRE is summarized in the algorithm (algorithm 3) and reviewed in detail separately. (See "Evaluation and management of drug-resistant epilepsy".)

●Antiseizure medication discontinuation – Stopping ASMs can be considered in patients who have been seizure-free for more than two years. Such decisions are individualized based on an evaluation of the individual's risk of seizure recurrence, adverse effects of ASM treatment, and the medical and psychosocial consequences of a recurrent seizure. (See "Approach to the discontinuation of antiseizure medications".)

●Females and antiseizure medications – Females of childbearing potential should be counseled regarding possible teratogenic effects of ASMs and should take supplemental folate to limit the risk. Enzyme-inducing ASMs can limit the effectiveness of oral contraception; alternative forms of birth control should be considered in females taking these ASMs. (See 'Females of childbearing age' above.)

●Comorbidities and complications – Patients with epilepsy have a higher-than-expected risk of mortality (including sudden death), injury, and motor vehicle accidents. Seizure frequency is a major risk factor for these complications. It is reasonable to counsel patients regarding these risks when discussing compliance issues or aggressive treatment for DRE. (See "Comorbidities and complications of epilepsy in adults".)

●Driving restrictions – Individuals who have had a recent epileptic seizure may be restricted from driving. Patients who are experiencing substantial neurotoxic adverse effects from ASMs should also be counseled about their appropriateness for driving until such adverse effects abate. (See 'Driving and other activities' above.)