# Lecture 20: Seizures and Epilepsy ## Unit 2.5: Neuroscience --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Define seizures and epilepsy and explain the ILAE 2017 classification system for seizure types and epilepsy syndromes 2. Describe the pathophysiology of seizures including excitation-inhibition imbalance and epileptogenesis 3. Differentiate focal seizures (aware versus impaired awareness) from generalized seizures based on clinical features and EEG patterns 4. Outline the systematic approach to evaluating a patient with new-onset seizures including differential diagnosis and diagnostic workup 5. Explain the mechanisms of action and clinical applications of major antiseizure medications with attention to side effects and special populations 6. Describe the definition, causes, and stepwise management protocol for status epilepticus --- ## Lecture Outline ### I. Definitions and Classification Framework Understanding the precise definitions and classification of seizures and epilepsy is fundamental to diagnosis and management. A seizure is defined as a transient occurrence of signs and symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain. This definition emphasizes that seizures represent a symptom—an electrical event—rather than a disease in themselves. Epilepsy, in contrast, represents a disease characterized by an enduring predisposition to generate seizures. The modern definition of epilepsy requires at least two unprovoked seizures occurring more than 24 hours apart, OR one unprovoked seizure combined with a high probability of recurrence (greater than 60%), OR the diagnosis of an established epilepsy syndrome. This updated definition allows treatment after a single seizure when recurrence risk is high, acknowledging that waiting for a second seizure may not serve the patient's best interest. Provoked or acute symptomatic seizures occur in the setting of an identifiable acute cause such as metabolic derangement, intoxication, or acute brain injury. These seizures do not qualify for a diagnosis of epilepsy because they may not recur once the provoking factor resolves. The ILAE 2017 classification organizes seizures first by onset: focal seizures begin in networks limited to one hemisphere, while generalized seizures engage bilateral networks from the very beginning. Unknown onset applies when the beginning of the seizure is not witnessed. Focal seizures are further classified by awareness (aware versus impaired awareness) and by initial manifestation (motor versus non-motor). When focal seizures spread to involve both hemispheres, they are termed focal to bilateral tonic-clonic, replacing the older term "secondary generalization." Beyond seizure type, epilepsy classification proceeds through additional levels: epilepsy type (focal, generalized, combined focal and generalized, or unknown) and finally epilepsy syndrome when a constellation of features including age of onset, seizure types, EEG findings, imaging characteristics, and sometimes genetic etiology creates a recognizable pattern. Etiology is classified as genetic, structural, metabolic, immune, infectious, or unknown, and these categories are not mutually exclusive. Panel A illustrates the ILAE 2017 classification framework as a hierarchical flowchart progressing from seizure type at the base through epilepsy type to epilepsy syndrome at the top, with etiology categories alongside. Panel B compares focal versus generalized seizure onset with brain diagrams showing focal activity confined to one hemisphere versus bilateral synchronous activity from onset. Panel C displays examples of epilepsy syndromes with their characteristic age ranges and features. Panel D presents the etiological categories with representative examples in each. --- ### II. Seizure Pathophysiology Normal brain function depends on a precise balance between excitation and inhibition. Glutamate serves as the principal excitatory neurotransmitter, activating NMDA and AMPA receptors to depolarize postsynaptic neurons. GABA provides the counterbalancing inhibition through GABA-A receptors (fast inhibition via chloride channels) and GABA-B receptors (slow inhibition via potassium channels). This equilibrium allows controlled neuronal signaling while preventing runaway excitation. Seizures occur when this balance tips toward hyperexcitability. This can result from excessive excitation (increased glutamatergic activity), reduced inhibition (decreased GABAergic activity), or both. At the cellular level, ion channel dysfunction plays a critical role. Abnormal sodium channels that fail to inactivate properly can cause repetitive firing. Dysfunctional potassium channels impair repolarization. Calcium channel abnormalities alter neurotransmitter release and intrinsic excitability. Many genetic epilepsies result from mutations in ion channel genes, explaining their designation as channelopathies. The phenomenon of hypersynchronization transforms individual neuronal hyperexcitability into a seizure. Normally, neurons fire asynchronously with varied timing. During a seizure, large populations of neurons begin firing together in rhythmic, synchronized bursts. This synchronous activity produces the large-amplitude EEG patterns characteristic of epileptiform discharges. Epileptogenesis describes the process by which a normal brain becomes capable of generating spontaneous seizures. Following an inciting event such as traumatic brain injury, stroke, or CNS infection, a latent period ensues during which molecular and cellular changes transform the neural network. These changes include altered ion channel expression, synaptic reorganization, neuronal death and neurogenesis, changes in glial function, and inflammatory responses. Eventually, this remodeled network begins producing spontaneous recurrent seizures—chronic epilepsy. Understanding seizures as network phenomena rather than simply cellular phenomena has important implications. Focal seizures arise from localized networks that may involve specific cortical regions, while generalized seizures engage widespread bilateral networks from onset. The spread of seizure activity follows anatomical connectivity, explaining patterns such as the Jacksonian march in motor cortex seizures. Panel A diagrams the excitation-inhibition balance showing glutamatergic synapses with NMDA/AMPA receptors opposing GABAergic synapses with GABA-A receptors. Panel B illustrates ion channel dysfunction with sodium, potassium, and calcium channels and how abnormalities contribute to hyperexcitability. Panel C depicts the epileptogenesis timeline from inciting event through latent period to chronic epilepsy with cellular changes indicated. Panel D compares normal asynchronous neuronal firing with hypersynchronized seizure activity in network diagrams. --- ### III. Focal Seizures Focal seizures originate within networks limited to one cerebral hemisphere. The clinical manifestations depend entirely on which cortical region generates the abnormal activity, making focal seizures particularly valuable for localization. Focal aware seizures (previously termed simple partial seizures) occur with preservation of consciousness and awareness throughout the episode. The patient experiences symptoms, recognizes them as abnormal, and can later describe the event. These seizures typically last seconds to less than two minutes. When a focal aware seizure represents the initial portion of a larger seizure, patients often describe it as an "aura"—a warning that a more significant event is coming. The symptoms of focal aware seizures vary by anatomical origin. Frontal lobe seizures produce motor phenomena including tonic posturing, clonic jerking, or version (forced head and eye deviation). The motor strip's somatotopic organization means seizures may march from hand to arm to face, termed a Jacksonian march. Temporal lobe seizures, arising from mesial temporal structures, characteristically produce experiential phenomena: déjà vu (inappropriate familiarity), jamais vu (inappropriate unfamiliarity), fear or anxiety, and the classic "epigastric rising sensation"—an indescribable feeling rising from the abdomen toward the throat. Parietal lobe seizures cause sensory disturbances including tingling, numbness, or distorted body perception. Occipital seizures produce visual phenomena such as flashing lights, colors, or formed visual hallucinations. Focal impaired awareness seizures (previously complex partial seizures) involve alteration of consciousness. The patient becomes unresponsive and cannot interact normally with the environment, though they may exhibit automatic behaviors called automatisms. These include oral automatisms (lip smacking, chewing, swallowing), manual automatisms (fumbling, picking movements), and gestural automatisms (patting, rubbing). Temporal lobe origin is most common, producing the classic picture of a motionless stare, oral automatisms, and postictal confusion lasting minutes to hours. Focal to bilateral tonic-clonic seizures occur when focal seizure activity spreads to involve both hemispheres. The seizure may begin with recognizable focal features—an aura, focal motor activity, or automatisms—before progressing to bilateral tonic-clonic convulsion indistinguishable from a primarily generalized tonic-clonic seizure. Witnesses may or may not observe the focal onset depending on how rapidly secondary generalization occurs. Panel A shows a brain diagram with color-coded cortical regions and their associated focal seizure symptoms (frontal-motor, temporal-experiential, parietal-sensory, occipital-visual). Panel B illustrates the clinical appearance of a focal impaired awareness seizure with automatisms including lip smacking and picking movements. Panel C demonstrates the Jacksonian march progressing across the motor homunculus. Panel D diagrams focal to bilateral tonic-clonic spread showing focal onset expanding to involve both hemispheres. --- ### IV. Generalized Seizures Generalized seizures engage bilateral cortical networks from the very onset—there is no preceding focal activity. The classification distinguishes motor from non-motor generalized seizures. Absence seizures represent the paradigmatic generalized non-motor seizure. They typically occur in children aged 4-12 years and manifest as brief episodes of behavioral arrest lasting 5-10 seconds. The child suddenly stops activity, stares blankly with possible subtle eyelid fluttering, then immediately resumes normal activity as if nothing happened. There is no postictal confusion. The onset and offset are characteristically abrupt—the seizure switches on and off like a light switch. Hyperventilation reliably triggers absence seizures during EEG, and the recording shows pathognomonic 3 Hz generalized spike-and-wave discharges. Absence seizures may occur dozens to hundreds of times daily, often mistaken for daydreaming or inattention until properly diagnosed. Generalized tonic-clonic seizures (GTC, formerly grand mal) are the most dramatic seizure type. They begin with the tonic phase: sudden bilateral muscle stiffening causing the patient to fall, often with forced expiration producing an "epileptic cry." This phase lasts 10-20 seconds. The clonic phase follows, consisting of bilateral rhythmic jerking movements that gradually slow and then stop, typically lasting 30-90 seconds total. During the seizure, patients may bite the lateral tongue (a highly specific finding), become cyanotic from respiratory impairment, and lose bladder or bowel control. The postictal phase features deep unresponsiveness, then confusion, fatigue, headache, and muscle soreness lasting minutes to hours. Myoclonic seizures consist of brief, shock-like jerks lasting milliseconds. Consciousness is typically preserved because the discharge is too brief to impair awareness. The jerks are bilateral and often affect the arms more than legs, sometimes causing patients to throw objects they are holding. Myoclonic seizures are particularly associated with juvenile myoclonic epilepsy (JME) and often cluster in the morning shortly after awakening. Other generalized motor seizures include tonic seizures (pure stiffening without clonic phase), clonic seizures (rhythmic jerking without tonic phase), and atonic seizures. Atonic seizures, also called drop attacks, cause sudden loss of postural tone resulting in falls. These are especially dangerous because the patient has no warning and cannot protect themselves, leading to facial injuries. Atonic seizures are characteristic of severe epilepsy syndromes like Lennox-Gastaut. Panel A displays an EEG tracing of typical absence epilepsy showing the characteristic 3 Hz generalized spike-and-wave pattern with clinical correlate of behavioral arrest. Panel B illustrates the phases of a generalized tonic-clonic seizure: tonic stiffening, clonic jerking, and postictal recovery. Panel C demonstrates myoclonic jerks with their characteristic bilateral arm involvement and shock-like quality. Panel D shows atonic seizure mechanism with sudden loss of postural tone causing a fall. --- ### V. Epilepsy Syndromes An epilepsy syndrome is a complex of features including seizure types, age of onset, EEG findings, imaging patterns, and sometimes genetic etiology that together form a recognizable clinical entity. Syndrome diagnosis carries important implications for treatment choice, prognosis, and counseling. Childhood absence epilepsy (CAE) affects children aged 4-10 years, with typical absence seizures occurring multiple times daily. EEG shows the characteristic 3 Hz generalized spike-and-wave discharges. First-line treatments are ethosuximide (effective only for absence) or valproate (broader spectrum). The prognosis is generally favorable—most children outgrow CAE by adolescence, though some develop GTC seizures or progress to juvenile absence epilepsy. Juvenile myoclonic epilepsy (JME) is the most common generalized epilepsy syndrome, typically presenting between ages 12-18. The seizure repertoire includes myoclonic seizures (often occurring shortly after awakening), generalized tonic-clonic seizures, and sometimes absence seizures. Sleep deprivation and alcohol are prominent triggers. EEG shows 4-6 Hz generalized polyspike-and-wave discharges. Valproate is highly effective but should be avoided in women of childbearing potential due to teratogenicity; lamotrigine and levetiracetam are alternatives. JME is a lifelong condition—seizures are usually well-controlled but return if medication is stopped. Temporal lobe epilepsy (TLE) is the most common focal epilepsy syndrome in adults. The most frequent underlying pathology is hippocampal sclerosis—atrophy and gliosis of mesial temporal structures, often following prolonged febrile seizures in childhood or other early insults. The typical seizure begins with an aura (déjà vu, fear, epigastric rising), progresses to impaired awareness with automatisms, and may secondarily generalize. MRI shows hippocampal atrophy and T2/FLAIR hyperintensity. Many patients with TLE become drug-resistant, but surgical resection (anterior temporal lobectomy) produces seizure freedom in 60-70% of carefully selected patients. Lennox-Gastaut syndrome represents a severe epileptic encephalopathy of childhood. Onset occurs between ages 1-7 years, often preceded by infantile spasms (West syndrome). Multiple seizure types occur, including tonic seizures (especially during sleep), atonic seizures, and atypical absence. EEG shows characteristic slow spike-and-wave discharges below 2.5 Hz. Cognitive impairment is progressive and often severe. Treatment is difficult, typically requiring multiple medications, and the prognosis is poor with lifelong disability. Panel A compares EEG findings in CAE (3 Hz spike-wave) versus JME (4-6 Hz polyspike-wave). Panel B shows MRI findings in temporal lobe epilepsy with hippocampal atrophy and T2 signal abnormality compared to normal. Panel C presents the age distribution of major epilepsy syndromes from infancy through adulthood. Panel D illustrates the slow spike-wave pattern of Lennox-Gastaut syndrome with corresponding clinical features. --- ### VI. Evaluation of New-Onset Seizures The evaluation of a patient presenting with a first seizure requires systematic history, examination, and testing to establish the diagnosis, exclude dangerous etiologies, and assess recurrence risk. History is paramount. Since patients often cannot recall their seizures, witness accounts are invaluable. Key questions address prior similar events (often revealing previously unrecognized seizures), potential provoking factors (sleep deprivation, alcohol use or withdrawal, drug use, concurrent illness), any warning symptoms or aura, the event itself (initial manifestations, progression, duration), and the postictal state (confusion duration, focal weakness, headache). Specific findings strongly suggest seizure: lateral tongue biting (highly specific for GTC), prolonged postictal confusion, and witnessed rhythmic clonic activity. Differential diagnosis is critical because many conditions mimic seizures. Syncope is the most common mimic—the convulsive movements seen in some syncopal episodes (convulsive syncope) can resemble seizures. Features favoring syncope include postural triggers, prodromal lightheadedness or tunnel vision, pallor, rapid recovery, and absence of postictal confusion. Psychogenic nonepileptic seizures (PNES) are episodes resembling seizures but without abnormal electrical activity; features suggesting PNES include variable and prolonged episodes, eyes held closed, asynchronous limb movements, and lack of postictal confusion. Other mimics include migraine with aura (gradual onset, followed by headache), transient ischemic attack (negative symptoms, brief), parasomnias, and movement disorders. The diagnostic workup begins with basic laboratory studies to identify provoking factors: glucose, sodium, calcium, magnesium, and toxicology screen. Electroencephalography (EEG) assesses for epileptiform activity, though a single routine EEG has only about 50% sensitivity for epilepsy. Brain MRI with epilepsy protocol (thin cuts through temporal lobes, specific sequences) identifies structural causes including hippocampal sclerosis, tumors, vascular malformations, and cortical malformations. Lumbar puncture is indicated when CNS infection is suspected. Recurrence risk assessment guides treatment decisions. Factors increasing recurrence risk include abnormal EEG with epileptiform discharges, structural brain lesion, nocturnal seizure, prior neurological insult, and status epilepticus as presentation. When two or more risk factors are present, recurrence risk exceeds 60%, meeting the definition of epilepsy and justifying treatment after a single seizure. Panel A presents a flowchart for systematic history-taking in new-onset seizures covering prodrome, event, and postictal phases. Panel B creates a comparison table differentiating seizure from its common mimics (syncope, PNES, migraine). Panel C outlines the diagnostic workup algorithm including labs, EEG, and MRI indications. Panel D displays a risk stratification tool showing factors that increase recurrence risk with management recommendations. --- ### VII. Electroencephalography in Epilepsy The electroencephalogram (EEG) remains essential in epilepsy diagnosis and classification. Understanding normal EEG patterns and epileptiform abnormalities enables interpretation of this critical test. Normal EEG background rhythms vary with the patient's state. Alpha rhythm (8-13 Hz) predominates over the posterior regions when the patient is awake with eyes closed and attenuates with eye opening (alpha blocking). Beta activity (>13 Hz) appears predominantly over frontal regions and may be enhanced by sedative medications. Theta rhythm (4-7 Hz) appears during drowsiness and light sleep. Delta activity (<4 Hz) predominates during deep sleep. The presence of normal organized background rhythms reflects cortical function and helps assess encephalopathy. Epileptiform discharges are patterns suggesting a tendency toward seizures. Spikes are sharply contoured transients lasting less than 70 milliseconds. Sharp waves have similar morphology but longer duration (70-200 milliseconds). Both stand out from the background, have a characteristic morphology with a fast rise and slower fall, and are followed by a slow-wave component. Spike-and-wave complexes consist of a spike immediately followed by a high-amplitude slow wave. Polyspike-and-wave complexes feature multiple spikes before the slow wave. Specific EEG patterns characterize particular syndromes. The 3 Hz spike-and-wave pattern is pathognomonic for childhood absence epilepsy, activated by hyperventilation. Juvenile myoclonic epilepsy shows faster 4-6 Hz generalized polyspike-and-wave discharges. Temporal lobe epilepsy shows spikes or sharp waves over the temporal regions, often with phase reversal indicating the maximum at temporal electrodes. Hypsarrhythmia—a chaotic pattern of high-amplitude slow waves and multifocal spikes—characterizes infantile spasms. The slow spike-and-wave pattern below 2.5 Hz defines Lennox-Gastaut syndrome. EEG limitations must be acknowledged. A single routine 20-30 minute EEG has only approximately 50% sensitivity for detecting epileptiform abnormalities in patients with epilepsy. Yield improves with sleep deprivation before recording, prolonged monitoring, and repeat studies. Conversely, some epileptiform patterns occur in people who never have seizures. A normal EEG does not exclude epilepsy—clinical diagnosis takes precedence when history is compelling. Panel A displays examples of normal EEG rhythms (alpha, beta, theta, delta) with their frequencies, locations, and associated states. Panel B illustrates epileptiform discharges including spikes, sharp waves, and spike-wave complexes with their defining characteristics. Panel C compares EEG patterns across syndromes: 3 Hz spike-wave (absence), temporal spikes (TLE), polyspike-wave (JME), and slow spike-wave (LGS). Panel D demonstrates how EEG localization works using phase reversal to identify the maximum of a temporal spike. --- ### VIII. Antiseizure Medications Antiseizure medications (ASMs, also called antiepileptic drugs or AEDs) represent the mainstay of epilepsy treatment. Understanding their mechanisms and appropriate selection is fundamental to management. The major mechanisms of action target ion channels or neurotransmitter systems. Sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin, lamotrigine, lacosamide) prolong the inactivated state of voltage-gated sodium channels, preventing the repetitive firing underlying seizures. They are particularly effective for focal seizures. Calcium channel blockers target different channel subtypes: ethosuximide blocks T-type calcium channels in thalamic neurons, making it specifically effective for absence seizures. GABAergic drugs enhance inhibition: phenobarbital and benzodiazepines allosterically potentiate GABA-A receptors, while vigabatrin irreversibly inhibits GABA transaminase. Glutamate antagonists reduce excitation: perampanel blocks AMPA receptors, while topiramate has multiple mechanisms including glutamate reduction. SV2A modulators (levetiracetam, brivaracetam) bind synaptic vesicle protein 2A, modulating neurotransmitter release through incompletely understood mechanisms. Valproate has multiple mechanisms including sodium channel blockade, T-type calcium channel effects, and GABA enhancement. Drug selection depends on seizure type and epilepsy syndrome. For focal seizures, first-line options include lamotrigine, levetiracetam, and carbamazepine or oxcarbazepine. For generalized tonic-clonic seizures, valproate, lamotrigine, and levetiracetam are appropriate. For absence seizures specifically, ethosuximide is highly effective but only for absence; valproate treats absence plus other seizure types. For myoclonic seizures, valproate and levetiracetam are effective; some drugs (carbamazepine, phenytoin) may worsen myoclonic and absence seizures and should be avoided in generalized epilepsies. Important adverse effects guide prescribing. Phenytoin causes gingival hyperplasia, hirsutism, coarsening of facial features, and cerebellar atrophy with chronic use; Stevens-Johnson syndrome is rare but serious. Carbamazepine causes hyponatremia and carries risk of aplastic anemia and Stevens-Johnson syndrome, particularly in patients of Asian ancestry with HLA-B*1502 allele who should be screened. Valproate causes weight gain, tremor, hair loss, and hepatotoxicity; most importantly, it is highly teratogenic causing neural tube defects and should be avoided in women of childbearing potential. Lamotrigine requires slow titration due to rash risk including Stevens-Johnson syndrome; interaction with valproate increases this risk. Levetiracetam commonly causes behavioral changes and irritability. Topiramate impairs cognition ("dopamax"), causes weight loss, and increases risk of kidney stones. Special populations require modified approaches. In pregnancy, lamotrigine and levetiracetam are preferred; valproate should be avoided. Elderly patients need lower doses due to altered pharmacokinetics and increased sensitivity. Drug interactions are important: enzyme-inducing ASMs (phenytoin, carbamazepine, phenobarbital) reduce efficacy of oral contraceptives and many other medications. Panel A diagrams the mechanisms of antiseizure medications at the neuronal level, showing where sodium channel blockers, calcium channel blockers, GABA enhancers, and glutamate antagonists act. Panel B presents a flowchart for drug selection based on seizure type and syndrome. Panel C tabulates major adverse effects of common antiseizure medications with visual icons for key toxicities. Panel D addresses special populations including pregnancy, with teratogenicity rankings and preferred agents. --- ### IX. Status Epilepticus Status epilepticus (SE) is a neurological emergency defined as a seizure lasting long enough or recurring frequently enough that recovery between attacks does not occur. The operational definition for convulsive SE is seizure activity lasting more than 5 minutes—the point at which spontaneous termination becomes unlikely and treatment should begin. Classification distinguishes several forms. Convulsive SE involves obvious motor manifestations (tonic-clonic activity) and represents the most dangerous form due to systemic complications. Non-convulsive SE features continuous or recurrent seizure activity without prominent motor features; patients appear confused or obtunded, and diagnosis requires EEG. Refractory SE persists despite adequate treatment with first-line (benzodiazepine) and second-line agents. Super-refractory SE continues for 24 hours or more despite anesthetic treatment. Causes of SE include medication non-compliance or subtherapeutic drug levels (the most common cause in patients with known epilepsy), acute precipitants (CNS infection, stroke, traumatic brain injury, metabolic derangements, drug toxicity), and de novo presentations without prior epilepsy history. In adults without known epilepsy, SE often indicates serious underlying pathology requiring urgent investigation. Treatment follows a time-based protocol. Initial stabilization (0-5 minutes) includes airway management, vital signs, intravenous access, and bedside glucose; thiamine should be given before glucose if alcohol abuse is suspected. First-line treatment (5-20 minutes) is a benzodiazepine: lorazepam 4 mg IV (may repeat once), midazolam 10 mg IM if no IV access, or diazepam 10 mg IV. Second-line treatment (20-40 minutes) employs IV fosphenytoin (20 mg PE/kg), levetiracetam (60 mg/kg up to 4500 mg), or valproate (40 mg/kg). If seizures persist beyond 40 minutes despite two adequate treatments, third-line options include phenobarbital or proceeding to anesthetic agents. Refractory SE beyond 60 minutes requires continuous IV anesthesia (propofol, midazolam infusion, or pentobarbital) with continuous EEG monitoring, typically in an ICU setting. Complications of prolonged SE are serious. Excitotoxicity causes neuronal injury independent of systemic factors. Respiratory compromise leads to hypoxia and aspiration. Muscle breakdown produces rhabdomyolysis with myoglobinuria and renal injury. Hyperthermia results from sustained muscle activity. Cardiovascular complications include arrhythmias from autonomic instability and hypotension from medications. Mortality is approximately 20% overall and higher in refractory cases. Panel A presents the status epilepticus treatment algorithm as a time-based flowchart with medication doses at each stage. Panel B shows benzodiazepine dosing options with routes of administration (IV lorazepam, IM midazolam, PR diazepam). Panel C illustrates EEG monitoring in status epilepticus showing ictal patterns and burst suppression during anesthetic treatment. Panel D diagrams the complications of prolonged status epilepticus affecting brain, heart, lungs, kidneys, and muscles. --- ### X. Special Considerations in Epilepsy Several important topics require attention beyond routine seizure management. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in patients with epilepsy, with or without evidence of a seizure and excluding documented status epilepticus. Risk factors include poorly controlled generalized tonic-clonic seizures, nocturnal seizures, young age of epilepsy onset, long epilepsy duration, and medication non-adherence. The mechanism likely involves post-ictal cardiorespiratory dysfunction—seizures can cause cardiac arrhythmias and central apnea. Prevention focuses on optimizing seizure control; nocturnal monitoring devices may provide early warning. Driving regulations vary by jurisdiction but universally require a seizure-free interval before driving. In most US states, this period ranges from 3-12 months. Physicians should know their state's requirements and counsel patients accordingly. Reporting requirements also vary—some states mandate physician reporting while others rely on patient self-reporting. Epilepsy surgery offers the possibility of seizure freedom for selected patients with drug-resistant focal epilepsy. Drug resistance is defined as failure of two appropriately chosen and used antiseizure medications. Pre-surgical evaluation includes video-EEG monitoring to capture seizures and localize onset, high-resolution MRI to identify structural lesions, PET scanning showing interictal hypometabolism, neuropsychological testing, and sometimes invasive monitoring with intracranial electrodes. Surgical options include resection of the seizure focus (such as anterior temporal lobectomy for temporal lobe epilepsy, with 60-70% seizure freedom), laser ablation for deep lesions, and neuromodulation (responsive neurostimulation, vagus nerve stimulation) when resection is not possible. Women with epilepsy face unique challenges. Enzyme-inducing ASMs (phenytoin, carbamazepine, phenobarbital) reduce oral contraceptive efficacy, requiring alternative contraception or higher hormone doses. Pregnancy requires careful planning: folic acid supplementation should begin before conception, and teratogenic medications (especially valproate) should be avoided or replaced if possible. Lamotrigine and levetiracetam have the best safety data in pregnancy. During pregnancy, ASM levels may fall (especially lamotrigine) requiring dose adjustment. Most women with epilepsy have healthy pregnancies, and breastfeeding is generally safe with most ASMs. Catamenial epilepsy—seizures clustering around menstruation—may respond to perimenstrual clobazam or hormonal manipulation. Panel A illustrates SUDEP risk factors and proposed mechanisms including post-ictal cardiorespiratory suppression. Panel B shows the pre-surgical evaluation pathway including video-EEG, MRI, PET, and invasive monitoring leading to surgical options. Panel C addresses women and epilepsy with a flowchart for contraception and pregnancy planning. Panel D presents driving considerations with a map showing state variation in seizure-free requirements. --- ## Summary - Seizures are transient events from abnormal neuronal activity; epilepsy requires recurrence or high recurrence risk and is classified by seizure type, epilepsy type, and syndrome - Pathophysiology involves excitation-inhibition imbalance with hypersynchronized firing; epileptogenesis transforms normal brain to epileptic through molecular and network changes - Focal seizures localize by symptoms (frontal-motor, temporal-experiential, parietal-sensory, occipital-visual); impaired awareness indicates temporal lobe; may secondarily generalize - Generalized seizures are bilateral from onset: absence (3 Hz spike-wave, childhood), GTC (tonic then clonic phases), myoclonic (brief jerks, JME) - Key syndromes: CAE (absence, remits), JME (myoclonic + GTC, lifelong), temporal lobe epilepsy (often drug-resistant, surgery effective), Lennox-Gastaut (severe, poor prognosis) - First seizure evaluation: history (witness accounts), differentiate from syncope/PNES, EEG, MRI; assess recurrence risk for treatment decision - ASM selection by seizure type: focal (lamotrigine, levetiracetam, carbamazepine), GTC (valproate, lamotrigine), absence (ethosuximide), myoclonic (valproate, levetiracetam) - Status epilepticus (>5 min): benzodiazepine first-line, then fosphenytoin/levetiracetam/valproate; refractory requires anesthesia and ICU --- ## Key Terms | Term | Definition | |------|------------| | Seizure | Transient occurrence of signs/symptoms due to abnormal excessive synchronous neuronal activity | | Epilepsy | Disease defined by recurrent unprovoked seizures or high recurrence risk after single seizure | | Focal seizure | Seizure originating in networks limited to one hemisphere, aware or impaired awareness | | Generalized seizure | Seizure engaging bilateral networks from onset; includes absence, tonic-clonic, myoclonic | | Absence seizure | Brief generalized seizure with staring and 3 Hz spike-wave on EEG, typically in childhood | | Epileptogenesis | Process by which normal brain develops tendency to generate spontaneous seizures | | Status epilepticus | Seizure lasting >5 minutes or recurrent seizures without recovery between | | Epileptiform discharge | EEG pattern (spikes, sharp waves, spike-wave) indicating seizure tendency | | SUDEP | Sudden unexpected death in epilepsy, likely from post-ictal cardiorespiratory failure | | Drug-resistant epilepsy | Failure of adequate trials of two appropriately chosen antiseizure medications | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*