Epilepsy in Adults

Background

• Epilepsy is a disease of the brain defined by any 1 of the following:
  • 2 or more unprovoked or reflex seizures occurring > 24 hours apart
  • single unprovoked (or reflex) seizure and high risk of recurrence over the next 10 years (similar high risk [≥ 60%] that occurs after 2 unprovoked seizures)
  • diagnosis of an epilepsy syndrome
• Lifetime prevalence of any seizure is about 10%, but most of these do not progress to epilepsy. Types of seizure not considered to be epilepsy include provoked seizure (resulting from toxins, medications, drugs of abuse, or metabolic factors) and single unprovoked seizure without an increased risk of recurrent seizures.
• The lifetime prevalence of epilepsy is about 2%-3%.
• Seizure types and epilepsy syndromes can be characterized and classified by clinical presentation and/or by electroencephalogram (EEG) characteristics.
  • Generalized seizures can be classified as tonic-clonic, absence, myoclonic, clonic, tonic, or atonic. They usually present with impaired consciousness but can present with at least partial awareness such as with absence seizures with eyelid myoclonias or myoclonic seizures.
  • Focal seizures (formerly known as partial seizures) originate within networks limited to 1 hemisphere of the brain with localized symptoms, but can rapidly evolve into bilateral convulsive seizures with similar appearance as generalized onset tonic-clonic seizures. Awareness may or may not be impaired.
  • Status epilepticus (SE) is defined as 5 minutes or more of a continuous seizure, or 2 or more discrete seizures without complete recovery of consciousness between seizures and may occur with any of the above seizure types (see Status Epilepticus in Adults for details).

Evaluation

• Historical elements suggestive of seizure include an initial aura; loss of responsiveness with blank stare; automatisms, such as lip smacking and chewing; staring; and a period of postictal confusion.
• Most seizures may last for several minutes; seizures lasting ≥ 5 minutes raise suspicion of SE (see Status Epilepticus in Adults for details).
• A diagnosis of epilepsy is based on fulfilling any 1 of following clinical criteria:
  • 2 or more unprovoked or reflex seizures occurring > 24 hours apart
  • single unprovoked (or reflex) seizure and high risk of recurrence over the next 10 years (similar high risk [≥ 60%] that occurs after 2 unprovoked seizures
  • diagnosis of an epilepsy syndrome.
• Consider an EEG for supporting a diagnosis of epilepsy, for classifying seizure type and epilepsy syndrome, for helping to assess recurrence risk, and for differentiating an epileptic seizure from nonepileptic events, such as, syncope, migraine, and nonphysiologic events.
• Long-term video EEG monitoring may provide a definitive diagnosis when there are diagnostic difficulties after clinical assessment and standard and/or ambulatory EEG.
• All adults with new-onset epilepsy should have neuroimaging using magnetic resonance imaging (MRI) with specialized epilepsy protocol as the preferred study, with computed tomography (CT) as an initial alternative in the emergency room setting.
• A separate electrocardiogram (ECG) is recommended in adults with suspected epilepsy based on the potential for the misdiagnosis of seizure-like attacks with a cardiovascular cause.
• Routine blood studies are not usually helpful in previously healthy patients but liver function tests, complete blood count, electrolytes, glucose, calcium, and serum albumin can be useful prior to starting antiseizure medications (ASMs), and may identify metabolic derangements in ill patients presenting with seizure.
• Do not routinely measure serum prolactin for the diagnosis of epilepsy.
• Consider evaluation for autoimmune encephalitis in patients with new-onset frequent seizures or SE when a cause is not apparent on an initial evaluation, particularly when seizures are accompanied by a cognitive or personality change, autonomic seizures, dystonia, or mesial temporal lesions on an MRI.

Management

• Avoid precipitating factors of seizures, such as, sleep deprivation, fever, and alcohol.
• Antiseizure medications are the main treatment and are usually initiated after the second epileptic seizure or first epileptic seizure if there is evidence of a neurologic deficit, epileptiform abnormality on EEG, a remote structural abnormality on neuroimaging, or if the risk of further seizures is unacceptable.
  • ASM drug selection is based on the type of epilepsy (focal or generalized), adverse effect profile, patient preference, and other patient-specific factors. Some generalized seizures preferentially respond to particular medications.
    
  • When initiating ASMs, monotherapy is generally preferred.
    • If the first ASM fails to control seizures, add a different ASM and then slowly taper the first ASM.
    • If ≥ 2 monotherapy regimens fail to control seizure, consider combination ASM therapy.
  • First-line drugs by epilepsy type include but are not limited to:
    • For focal-onset seizures (with or without alterations of consciousness) including focal seizures that rapidly evolve into bilateral tonic-clonic seizure - monotherapy with carbamazepine, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, valproate derivatives (except in female persons of childbearing potential), or zonisamide.
    • For generalized-onset seizures (or if generalized-onset seizure cannot be ruled out) - monotherapy with lamotrigine, levetiracetam, topiramate, valproate derivatives (except in female persons of childbearing potential), or zonisamide.
    • Do not consider valproate derivatives in women and girls of childbearing potential due to teratogenic effects, unless alternate treatments are not suitable and the patient has been fully informed about the harms.
  • Consider benzodiazepines such as lorazepam, diazepam (can be given as a rectal gel), and midazolam (has a buccal mucosa formulation) for prolonged (SE) or as rescue for repeated seizures (see Status Epilepticus in Adults for details).
• Consider adjunct ASMs for treatment-resistant epilepsy:
  • For focal onset seizures - adjunct brivaracetam, clobazam, or pregabalin; other ASMs can also be considered, but, due to their adverse effect profiles, felbamate, perampanel, phenobarbital, phenytoin, and vigabatrin are generally less commonly used.
  • For generalized onset seizures - adjunct valproate derivative (unless contraindicated), lamotrigine, levetiracetam, and others.
• Consider drug interactions related to ASMs:
  • Certain ASMs may decrease the effectiveness of hormonal contraception, may increase the risk of fetal malformations, and/or increase the risk of poor neurodevelopmental outcomes and care must be taken in selection of an ASM regimen in women of child-bearing age.
  • Use caution in geriatric patients due to the risk of falls, psychomotor impairment, and metabolic derangements caused by many ASMs.
• Monitoring of laboratory work:
  • In patients on enzyme-inducing drugs (such as carbamazepine, oxcarbazepine, phenytoin, topiramate, or barbiturates) a complete blood count, electrolytes, liver function studies, and bone metabolism studies (such as vitamin D, calcium, and alkaline phosphatase) can be monitored every 2-5 years.
  • Routine drug levels and monitoring is not recommended and should only be performed if clinically indicated.
• Referral to epilepsy center or epilepsy specialist is recommended if seizures persist after > 1 year of treatment. Earlier referral can be considered, such as if structural lesion on brain magnetic resonance imaging, a specific epilepsy syndrome on electroencephalogram, diagnostic uncertainty, unacceptable adverse effects, psychological comorbidity, and for women of childbearing age.
• Surgical resection or laser ablation may reduce seizures in well-selected patients with focal epilepsy, such as with unilateral temporal mesial sclerosis, low-grade glial tumors, and cavernous hemangiomas.
• Other treatments:
  • A ketogenic diet is a high fat, low carbohydrate, adequate protein diet which is associated with seizure reduction in adults with generalized and partial epilepsy refractory to treatment. Low glycemic index and modified Atkins diets have also found beneficial in adults with epilepsy.
  • Consider vagal nerve stimulators and invasive brain stimulators as adjunctive therapy in adults with seizures (focal or generalized) refractory to antiseizure medications but who are not suitable for resective surgery.
• ASM discontinuation can be considered in patients with normal EEG and MRI who have been seizure-free for > 2 years, with slowly tapering of medications one at a time over several months under the direction of a neurologist.
• Advise patients with a first seizure to not drive until medically cleared and to report the seizure to a motor vehicle or driving license agency. Note that in the United States, laws vary from state to state with regard to seizure diagnosis restrictions on driving and mandatory physician reporting of patients with seizures.
• Inform adults with epilepsy about risks of and precautions against sudden unexpected death in epilepsy (SUDEP).