Epilepsi

01Pathophysiology

Epilepsy results from an imbalance between excitatory and inhibitory neurotransmission in the cerebral cortex. At its core, the disease reflects excessive neuronal synchronization and hyperexcitability. Under normal conditions, GABAergic inhibitory interneurons provide a counterbalance to glutamatergic excitatory signaling. In epilepsy, this balance tips in favor of excitation through a variety of mechanisms: gain-of-function mutations in sodium or calcium channels (prolonging depolarization), loss-of-function mutations in potassium or GABA receptor channels (reducing repolarization and inhibition), or structural disruptions to cortical circuitry (such as cortical dysplasia or hippocampal sclerosis) that create abnormal excitatory loops.

Focal seizures originate from a discrete cortical focus. The clinical manifestation depends entirely on the location of this focus. A seizure arising from the motor cortex produces contralateral rhythmic jerking. A seizure in the temporal lobe produces an aura (often described as a rising epigastric sensation, deja vu, or fear), followed by behavioral arrest and oral automatisms. This is the direct link between anatomy and symptoms that test writers exploit: the clinical description tells you where the seizure starts.

Generalized seizures involve bilateral cortical networks from onset. Absence seizures result from abnormal oscillatory activity in thalamocortical circuits, producing the characteristic 3 Hz spike-and-wave discharges on EEG and the abrupt onset/offset staring spells without post-ictal confusion. Generalized tonic-clonic seizures involve widespread cortical activation, first producing tonic stiffening (sustained depolarization) followed by clonic jerking (rhythmic cycles of depolarization and repolarization), then a prolonged post-ictal phase reflecting neuronal exhaustion and transient cortical suppression.

Epileptogenesis refers to the process by which a normal brain becomes prone to seizures after an initial insult. After a traumatic brain injury or stroke, for example, the surrounding brain tissue undergoes gliosis, loss of inhibitory interneurons, and sprouting of aberrant excitatory connections. This creates a hyperexcitable network that can generate spontaneous seizures weeks to years later. This explains why there is often a latent period between a brain insult and the first seizure, and why a new-onset seizure in an older adult should prompt urgent evaluation for a structural lesion such as a tumor or stroke.

02Classification and Clinical Manifestation

The International League Against Epilepsy (ILAE) classification is the framework used on exams. The first determination is seizure onset type, which drives all downstream decisions.

Seizure Classification by Onset

Selected Epilepsy Syndromes

03Diagnostic Workup

The first step after a witnessed seizure is to determine whether the seizure was provoked or unprovoked. This distinction is foundational. A provoked seizure (due to hypoglycemia, hyponatremia, alcohol withdrawal, or acute drug intoxication) does not warrant a diagnosis of epilepsy and does not require long-term antiseizure medication. Basic laboratory studies including glucose, a comprehensive metabolic panel, and a toxicology screen should be obtained in every patient presenting with a first seizure.

EEG is the best initial test for evaluating the type and etiology of seizures. A routine 20- to 40-minute EEG captures interictal epileptiform discharges in approximately 50% of patients with epilepsy on the first study. If the initial EEG is normal, sleep-deprived EEG increases the diagnostic yield. The EEG pattern often determines the diagnosis: 3 Hz generalized spike-and-wave points to childhood absence epilepsy, while focal temporal sharp waves suggest temporal lobe epilepsy. Be aware that a normal EEG does not rule out epilepsy; it only means that no epileptiform activity was captured during the recording window.

MRI of the brain is indicated in virtually all patients with new-onset seizures, except in children with a classic presentation of childhood absence epilepsy or benign rolandic epilepsy. MRI is superior to CT in detecting cortical dysplasia, hippocampal sclerosis, low-grade tumors, and cavernous malformations. In the acute setting (emergency department), a non-contrast CT may be obtained first to rapidly rule out hemorrhage or a large mass, but MRI is always the preferred imaging modality when epilepsy is suspected.

Prolonged video-EEG monitoring is reserved for patients in whom the diagnosis is uncertain (to differentiate epileptic seizures from psychogenic nonepileptic events) or for pre-surgical evaluation in drug-resistant epilepsy. This is the gold standard for correlating clinical behavior with electrographic activity.

04Management and Treatment

First-Line Antiseizure Medications

Status Epilepticus Management

After a first unprovoked seizure, the decision to start an antiseizure medication is nuanced. A single unprovoked seizure carries a recurrence risk of approximately 40% to 50% over 2 years. Treatment is recommended when the recurrence risk is high: abnormal EEG with epileptiform discharges, structural lesion on MRI, nocturnal seizure, or a prior brain insult (remote symptomatic etiology). After two or more unprovoked seizures separated by more than 24 hours, the diagnosis of epilepsy is established and treatment is indicated, as the recurrence risk exceeds 60%.

Drug selection depends on seizure type, patient age, sex, and comorbidities. For focal epilepsy, levetiracetam and lamotrigine are the most commonly used first-line agents due to their favorable side-effect profiles and lack of significant drug interactions. Carbamazepine remains effective but carries a risk of hyponatremia and Stevens-Johnson syndrome (especially in patients with HLA-B*1502, common in Southeast Asian populations). For generalized epilepsy, valproate is highly effective across seizure types (tonic-clonic, absence, myoclonic) but is contraindicated in pregnancy due to neural tube defects and neurodevelopmental harm. In women of childbearing age, levetiracetam or lamotrigine is preferred.

A critical exam concept: certain ASMs can worsen certain seizure types. Carbamazepine, oxcarbazepine, phenytoin, and gabapentin can exacerbate absence and myoclonic seizures. This is a frequently tested trap. If a patient with JME (myoclonic jerks + generalized tonic-clonic seizures) is started on carbamazepine and the myoclonus worsens, the next best step is to switch to valproate or levetiracetam.

Status epilepticus is defined as continuous seizure activity lasting 5 minutes or longer, or two or more seizures without return to baseline. The immediate first step is always IV benzodiazepine (lorazepam is preferred intravenously). This is one of the most tested management sequences in medical licensing exams. If benzodiazepines fail, the second-line agent is an IV loading dose of fosphenytoin, levetiracetam, or valproate. Refractory status epilepticus (failure of first- and second-line agents) requires ICU admission and continuous infusion of an anesthetic agent with continuous EEG monitoring.

Medication withdrawal may be considered after 2 or more seizure-free years, but this decision requires careful risk stratification. The risk of recurrence after withdrawal is higher in patients with an abnormal EEG, structural brain lesion, or juvenile myoclonic epilepsy (which typically requires lifelong treatment).

Surgical evaluation is indicated for drug-resistant epilepsy, defined as failure of two appropriately chosen and adequately dosed ASMs. The most common and most successful epilepsy surgery is anterior temporal lobectomy for mesial temporal lobe epilepsy with hippocampal sclerosis. Pre-surgical evaluation includes prolonged video-EEG, high-resolution MRI, neuropsychological testing, and sometimes PET, SPECT, or intracranial EEG.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common way students lose points on epilepsy questions is by failing to classify the seizure type before selecting a drug. The vignette will describe a clinical event, and the correct answer depends entirely on whether the seizure is focal or generalized. If you pick carbamazepine for a patient who actually has juvenile myoclonic epilepsy (a generalized syndrome), you will make the patient worse, and that is exactly the wrong answer the test writer designed. Always classify first, then treat.

A second frequent trap involves the first seizure scenario. Many students reflexively choose to start an antiseizure medication after a single unprovoked seizure, but the correct answer depends on risk stratification. If the EEG is normal, MRI is normal, and the neurological exam is normal, observation without medication is a valid and often tested correct answer.

The status epilepticus sequence is tested repeatedly. The first step is always a benzodiazepine. Students who jump to phenytoin or levetiracetam as the initial therapy will get it wrong. The question will sometimes frame the scenario such that the patient has been seizing for "over 5 minutes" or "arrives to the emergency department with ongoing seizure activity." This is your cue: give the benzodiazepine first.

Watch for the psychogenic nonepileptic event disguised as refractory seizures. A vignette describing a patient who has "seizures" unresponsive to multiple medications, with closed eyes during the event, and a normal EEG, is pointing you toward PNEE, not drug-resistant epilepsy. The next best step is video-EEG monitoring, not adding another medication.

Finally, be alert to the teratogenicity question. A young woman with epilepsy who is planning pregnancy or discovers she is pregnant will appear in a vignette. Valproate must be avoided (neural tube defects, cognitive impairment in offspring). The correct answer is to switch to lamotrigine or levetiracetam and ensure adequate folic acid supplementation. Never abruptly discontinue an ASM in a pregnant patient, as uncontrolled seizures pose their own risks to the fetus.

The core competency tested across epilepsy questions is your ability to classify the seizure, match it to the correct drug, recognize status epilepticus, and identify when the presentation is not epilepsy at all.