Seizures and Epilepsy for the Primary Care Provider

Educational Objectives

The goal of this program is to improve management of seizures. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate among various diagnoses which may present with seizures.
2. Apply the most recent guidelines when diagnosing seizures and epilepsy.
3. Maximize treatment of epilepsy while minimizing adverse effects associated with use of antiseizure medication.

Summary

Seizures vs other spells: in the emergency department, clinicians encounter seizures, as well as all other types of spells; seizures can be acutely symptomatic or unprovoked; a thorough history of the spell is more important than diagnostic testing and physical examination (both of which are often negative); no blood testing exists for diagnosing seizures

History: detailed history about the initial spell is helpful, as patients may con fuse subsequent experiences with the interpretations of doctors or observers; obtain details about timing, duration, subsequent confusion, and loss of consciousness (LOC); clarify what the patient means by “blackout”; obtain information from reliable witnesses or cell phone videos; determine whether motor vehicle accidents involved only one car

Differential diagnosis: 95% of syncope episodes involve brief LOC (though may be prolonged with cardiac arrhythmia or outflow obstruction); a few muscle jerks are possible with syncope; LOC is apparent with ≈50% of psychogenic seizures, and 40% to 60% of admitted patients exhibit nonepileptic spells; migraine rarely causes LOC but typically presents with other symptoms (headache is usually present); microsleeps can mimic seizures or other spells; vestibular disorders may cause dizziness without LOC; transient ischemic attacks do not induce LOC; grand mal seizures typically last 1 to 2 min and are often followed by postictal amnesia; unlike seizures, patients who experience syncope quickly recover and can recall event details; psychogenic nonepileptic spells are often associated with a history of abuse (particularly in women); seizures are characterized by evolving, generalized tonic-clonic movements, whereas nonepileptic spells are associated with inconsistent, monorhythmic (nonevolving) movements; psychogenic disorders can manifest with hyperventilation, panic, or dissociative fugue; isolated hallucinations (common with, eg, schizophrenia, Lewy Body dementia) are uncommon with epilepsy

Terminology: seizure — characterized by abnormal and excessive excitation of neurons; ≈10% of the population experiences a seizure (including febrile convulsions) in their lifetime; acute symptomatic seizures are often provoked by medical illness; epilepsy — ≥2 unprovoked seizures, or one seizure with an enduring predisposition to generate additional seizures, as indicated by electroencephalography (EEG); ictal — during a seizure; interictal — between seizures; postictal — after a seizure; aura — an experience or feeling that occurs before the focal seizure; prodromes — behaviors or events that occur hours to days before any type of seizure, often manifesting as irritability; semiology — clinical characteristics of a seizure

Diagnosis: acute symptomatic seizures can be caused by high-dose tramadol or ciprofloxacin; single seizure is diagnosed following an unprovoked seizure in a patient <60 yr of age with normal EEG; new-onset epilepsy is diagnosed with ≥1 seizure, EEG suggesting high risk for recurrence, or a patient ≥60 yr of age; with a single seizure, recurrence risk is 30% to 40% and treatment is not advised; however, patients diagnosed with new-onset epilepsy must take long-term antiepileptic medication or stop driving for 6 mo; EEG interpretation — can be challenging because of artifact; EEGs are often overread and require training to accurately interpret; 2% to 6% of individuals display epileptiform activity on EEG; an interictal EEG may be normal in a person with epilepsy; seizures — categorized as generalized or focal; complex focal seizures (the most common type in adults) typically last a few minutes, while absence seizures last only 10 to 20 sec; primary generalized epilepsy (includes, eg, absence seizures, atonic epilepsy, juvenile myoclonic epilepsy) is rare in patients >30 yr of age

Management: spells have many triggers, including medications and recreational drugs; manage underlying medical conditions; while medication is not necessary for young individuals following a single seizure, driving needs to be restricted; if treatment is indicated, choose a single medication at the lowest therapeutic dose, and reconsider diagnosis with no response; brain magnetic resonance imaging is recommended for all patients with focal seizures

Antiseizure medication (ASM)

First-generation ASMs: less frequently prescribed because of their sedative effects (especially in combination), large number of specific adverse effects, complex pharmacokinetics, drug-drug interactions, nonlinear dose response, and narrow-spectrum activity; phenytoin — difficult to titrate and causes gingival issues; phenobarbital — remains in use (albeit spare) for certain pediatric cases; valproic acid — has broad-spectrum efficacy; contraindicated in women of childbearing age; valproic acid induces sedation and parkinsonian tremor in elderly individuals

Second-generation ASMs: less sedating; exhibit linear pharmacokinetics; levetiracetam — may cause irritability (20-30%) or somnolence but is generally well tolerated and typically considered the treatment of choice; adjust dose for patients with renal failure; lamotrigine — well-tolerated and exhibits broad-spectrum efficacy, but requires gradual dose escalation because of the risk for severe skin rashes (possibly fatal), especially during the summer months; estrogen can affect drug efficacy, necessitating higher doses during pregnancy

Third-generation ASMs: gabapentin — more useful for pain management than epilepsy; topiramate — beneficial for treatment of epilepsy; tiagabine — caused as many seizures as it cured and is thus no longer used; oxcarbazepine — better tolerated than carbamazepine; zonisamide — beneficial for treatment of epilepsy; ezogabine — became unpopular because of a side effect of blue skin discoloration; clobazam — particularly effective for severe epilepsy; cenobamate — Chung et al (2020) demonstrated a seizure-free rate of ≈30% for cenobamate, even in patients in whom other epilepsy drugs were unsuccessful; lacosamide — effective; slow titration is needed in the outpatient setting to avoid dizziness; cannabis (marijuana) — while not highly effective for epilepsy, its relaxing effects can be helpful; discontinuation of heavy cannabis use for 3 days can induce a seizure in patients with epilepsy; pharmaceutical-grade cannabidiol is sometimes used for severe epilepsy

Treatment tips for primary care providers: carbamazepine and oxcarbazepine — unlike carbamazepine (requires 2-4 wk to metabolize), oxcarbazepine does not cause dizziness; however, both medications can cause hyponatremia, especially in older adults; add-on medications — lamotrigine or oxcarbazepine can be added to levetiracetam; zonisamide also induces weight loss and does not induce the adverse cognitive effects seen with topiramate; lacosamide is another option for add-on treatment; valproic acid, although effective, is discouraged in women of childbearing age and may cause tremor; topiramate is a broad-spectrum drug suitable for migraines and induction of weight loss, but may lead to adverse cognitive effects at high doses; ≈67% of patients with epilepsy generally achieve seizure control with ASMs; management — order medication blood levels, even for the newer agents; adherence is essential; pill organizers can help ensure consistency in medication use; certain ASMs (eg, levetiracetam) can be doubled after a missed dose without increased adverse effects, while others (eg, lamotrigine, carbamazepine) cannot; avoid seizure-triggering medications (eg, bupropion, quinolone, tramadol); low-carbohydrate diets may also help reduce seizure frequency; surgical options (eg, lesionectomy, temporal lobectomy) are highly effective for specific cases; device-based interventions, including vagus nerve and responsive nerve stimulation, have shown success in managing refractory epilepsy

Readings

Andrade C. Epilepsy, antiepileptic drugs, and adverse pregnancy outcomes, 2: major congenital malformations with antiepileptic drug monotherapy. J Clin Psychiatry. 2024;85(3):24f15432. doi:10.4088/JCP.24f15432; Chung SS, French JA, Kowalski J, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020;94(22):e2311-e2322. doi:10.1212/WNL.0000000000009530; Elmer S, Reddy DS. Therapeutic basis of generic substitution of antiseizure medications. J Pharmacol Exp Ther. 2022;381(2):188-196. doi:10.1124/jpet.121.000994; Gavvala JR, Schuele SU. New-onset seizure in adults and adolescents: a review. JAMA. 2016;316(24):2657-2668. doi:10.1001/jama.2016.18625; Larkin TM, Cohen-Oram AN, Catalano G, et al. Overdose with levetiracetam: a case report and review of the literature. J Clin Pharm Ther. 2013;38(1):68-70. doi:10.1111/j.1365-2710.2012.01361.x; Löscher W, Klein P. The pharmacology and clinical efficacy of antiseizure medications: from bromide salts to cenobamate and beyond. CNS Drugs. 2021;35(9):935-963. doi:10.1007/s40263-021-00827-8. Erratum in: CNS Drugs. 2021;35(9):1033-1034. doi:10.1007/s40263-021-00853-6; Myers L, Trobliger R, Bortnik K, et al. Are there gender differences in those diagnosed with psychogenic nonepileptic seizures? Epilepsy Behav. 2018;78:161-165. doi:10.1016/j.yebeh.2017.10.019.

Disclosures

For this program, members of the faculty and the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Bell was recorded at Neuroscience Conference 2024: Neurology for the Primary Care Provider, held July 14, 2024, in Greenville, NC, and presented by East Carolina Brody School of Medicine. For information about upcoming CME activities from this presenter, please visit https://www.easternahec.net. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

IM720201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.