Epilepsy is the fourth most common neurologic disorder in the United States. Approximately 3.4 million people in the United States have epilepsy.1 An estimated 1 in 26 people will develop epilepsy in their lifetime, which is double the number who will develop autism spectrum disorder, multiple sclerosis, and Parkinson disease combined.1,2 Epilepsy is not a disease but a disorder with numerous etiologies. Its active sign/symptom is seizures, but seizures do not always equal epilepsy.

Was the Seizure Epileptic?

  • A frantic patient/caregiver calls your office to report a recent seizure. What do you do as a provider? Much will depend upon the patient and situation.
  • Is this a first-time event?
  • Is this a patient with a known history of seizures and, if so, was the semiology consistent with their typical seizure events?
  • What were the circumstances surrounding the event? Were any typical seizure triggers present?

Capture of a seizure event through epileptiform electrographic changes on electroencephalography (EEG) is the gold standard for diagnosis of epilepsy, but a normal EEG without event capture does not rule epilepsy out.3 Epileptic seizures and their broad differential diagnosis often can be determined clinically by an in-depth history and physical examination. The semiology, chronology, situation in which the event occurred, and/or clinical observation of the event often can be enough to allow diagnosis. Other disorders to rule out include provoked seizure, convulsive syncope, movement disorders (eg, tics), and, in some cases, nonepileptic physiologic or psychological events.

The International League Against Epilepsy (ILAE)4 defines epilepsy as:

  • At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart. Two seizures within 24 hours, regardless of cause, or presentation in status epilepticus as a first-time event does not meet the criteria for an epilepsy diagnosis.
  • One unprovoked (or reflex) seizure and a probability of further seizures over the next 10 years that is similar to the general recurrence risk after 2 unprovoked seizures (at least 60%). For instance, a single seizure accompanied by a lesion on magnetic resonance imaging (MRI) consistent with a likely seizure focus or interictal epileptiform discharges on EEG would meet the criteria for an epilepsy diagnosis.
  • Diagnosis of an epilepsy syndrome such as childhood absence epilepsy, Dravet syndrome, or Lennox-Gastaut syndrome.

There are 2 overarching seizure types: focal and generalized. Focal seizure activity originates in 1 hemisphere in the brain and may or may not spread to other parts of the cortex. Focal seizures can be further separated into focal aware (formerly called simple partial) and focal impaired awareness (formerly called complex partial) seizures.5 Generalized seizure activity originates in both hemispheres simultaneously as demonstrated on EEG.

Differentiating between focal and generalized seizures is important for determining treatment options. Although focal seizures theoretically can be treated with all available antiseizure medications (ASM), as well as neuromodulation devices and resective surgery, not all agents for generalized epilepsy are indicated for focal seizures or are as effective as those for focal seizures.

Treatment of Ongoing Seizures
Clinicians should look for triggers in patients with a history of presumed focal seizures who have ongoing typical seizures and semiology that is consistent with their historical events. Common triggers for epileptic seizures include medication nonadherence, sleep deprivation, stress, acute illness (especially urinary tract infections), catamenial pattern, overheating or heat stroke, flashing or flickering lights, and binge drinking.6-8

It is also important to be aware of psychological comorbidities because they increase susceptibility to stress as a trigger.6 Furthermore, the relationship between depression and epilepsy is bidirectional. Approximately 25% of people with epilepsy (PWE) have comorbid depression; this rate is 4 to 5 times higher than that seen in the general population.9 PWE also have higher rates of death from suicide than the general population (0.5% vs 0.01%).9 In addition, patients with a history of depression are at higher risk of developing epilepsy (4- to 7-fold increased risk).9 Approximately 70% of PWE with anxiety and depression are not treated for these comorbidities due to concerns that antidepressants may lower the seizure threshold. However, treating mood disorders in PWE actually may improve seizure control.9 Bupropion is the only antidepressant that should be avoided in PWE.10

When managing a patient with ongoing seizures, clinicians must consider if the patient’s disorder meets the criteria for drug-resistant epilepsy (DRE), also referred to as intractable or refractory epilepsy. DRE is defined as failure of adequate trials of 2 tolerated and appropriately chosen and used ASM schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom.11 Although nearly two-thirds of seizures among PWE are well controlled by the first or second ASM prescribed, regardless of the specific ASM(s) used, more than one-third of PWE are considered to have DRE.12

In a patient presenting with DRE, it is important to confirm the diagnosis, rule out potential adherence issues, and determine whether ASM dosage and duration have been optimized for the patient’s seizure type.11

For example, psychogenic nonepileptic seizures/spells (PNES) are misdiagnosed as DRE in 5% to 20% of patients referred to tertiary epilepsy centers.13 PNES are refractory to treatment with ASMs and often are more disabling than epileptic seizures, which usually can be controlled with medication.13 According to Krumholz et al, patients with PNES have more frequent, severe, and disabling seizures and a poorer quality of life than PWE.13

Further complicating the diagnosis, approximately 10% to 40% of patients with epileptic seizures also have PNES.13 Referral to an epilepsy center can facilitate differentiation of epilepsy from PNES and coordination of care for both disorders, including cognitive behavioral therapy for PNES. The outcome of people with PNES vary. PNES responds better when appropriate treatment is initiated early, but even then approximately 33% of patients completely stop having seizures or related problems and 50% have poor functional outcomes.13

In patients with confirmed drug-resistant focal seizures, surgical resection of the epileptic focus may be effective. However, epilepsy surgery is underused, with less than 1% of appropriate candidates being referred to surgery each year and an average 20-year delay between diagnosis and referral to a tertiary epilepsy center for surgical evaluation.14 This delay is linked to worsened surgical outcomes, even if a surgical focus can be located and deemed safe to resect. Although the likelihood of freedom from seizures after surgery is best in patients with a shorter duration of epilepsy, even patients with a long-standing history of epilepsy can benefit from surgery.15,16 Tertiary centers also can offer neuromodulation devices, dietary therapies, and multidisciplinary care for patients with both refractory focal and generalized seizure types.14

Counseling Patients With Ongoing Seizures
Shared decision-making is important when determining treatment options for PWE. First, there are no guidelines to determine which ASM may be best for a particular patient other than whether it is a broad-spectrum agent (safe for use in both generalized and focal epilepsy) or is indicated for focal seizures only. Second, provider and patient priorities may not match. If not investigated and considered, this mismatch can damage the provider-patient/caregiver relationship and result in suboptimal seizure control and patient self-management. Although providers often prioritize freedom from seizure as the primary goal of management, patients/caregivers may rate quality-of-life factors (eg, adverse drug events) more highly than freedom from seizure. Patients and providers even may define seizure control differently.17

Patient counseling should include discussion of the risks of ongoing seizures, including the risk for death from seizure-related injuries or sudden unexplained death in epilepsy (SUDEP). The risk for sudden death in PWE is 20- to 24-fold greater than that in the general population; the estimated incidence of SUDEP in adults with epilepsy is 1 in 1000 person-years.18 The incidence of SUDEP increases to 1 in 150 person-years in patients with uncontrolled seizures.19 The pathophysiology of SUDEP is not well understood and only a few risk factors are modifiable. Current prevention strategies are limited to controlling seizures, especially generalized tonic-clonic seizures, and improving medication adherence. Polypharmacy is another modifiable risk factor; patients should use the smallest number of ASMs to control seizures.19

States have varied laws governing revocation and reinstatement of driving privileges and requirements for provider reporting related to PWE. Clinicians should be aware of applicable laws and be prepared to counsel patients about them. One-third to one-half of PWE deny that they have ever been counseled about driving laws, and less than 1 in 10 report that have been counseled about driving restrictions in the emergency department.10 It is of upmost importance to discuss this issue with patients and document the discussion in the medical record.

There are several other patient education points to address. Physical activity, which can increase seizure control by improving sleep and mood, should be encouraged, with risks and appropriate safety measures considered. Employment concerns, such as the dangers of working at heights or with heavy machinery, and accommodations should be discussed and documented.

Women’s health issues, including ASM teratogenicity and drug interactions with oral contraceptives, risks to mother and fetus of seizures during pregnancy, and safety issues related to infant care, should be part of routine counseling.18 Be prepared to direct patients/caregivers to reputable national and local patient advocacy organizations for resources and support.

Management of epilepsy is complex, particularly in patients who do not respond to initial treatment. Confirming an accurate diagnosis and optimizing treatment selection, dosages, and duration of use are essential to care. If a patient with presumed or known focal epilepsy continues to have typical seizures and has reached DRE criteria, do not wait! Refer the patient to a tertiary epilepsy center to confirm the diagnosis and determine whether management has been optimized. Even if a patient does not qualify for surgery, interdisciplinary teams at these centers can improve treatment and coordinate care for many psychosocial issues affecting PWE.

Kelly Renee Conner, PhD, PA-C, received her doctorate in neuroscience from Wake Forest University School of Medicine in 2009 before completing her training as a physician assistant in 2016. That year, she joined the Wake Forest Baptist Health adult epilepsy team, where she provides inpatient care in the epilepsy monitoring unit as well as ambulatory clinical care. She also is vice-chair of the American Epilepsy Society’s Advanced Practice Provider Committee.


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