Nervous System & Special Senses

Seizures: first seizure workup in adults

Clinical Overview and When to Suspect First Seizure in Adults

— Abrupt onset, stereotyped motor activity (tonic-clonic, focal clonic, automatisms)

— Postictal confusion lasting minutes to hours (a key Step 3 discriminator)

— Lateral tongue bite, urinary incontinence, head version, cyanosis

— Witnessed loss of awareness with amnesia for the event

— Provoked (acute symptomatic): within 7 days of an identifiable insult — hyponatremia, hypoglycemia, alcohol/benzo withdrawal, acute stroke, head trauma, drug toxicity, eclampsia, CNS infection.

— Unprovoked: no acute precipitant; mandates evaluation for underlying epileptogenic substrate.

Board pearl: A single unprovoked seizure with a normal EEG, normal MRI, and normal neuro exam carries ~30–40% 2-year recurrence risk. Add an abnormal EEG, structural lesion, nocturnal event, or focal features and recurrence approaches 60%+ — meeting the ILAE practical epilepsy definition (one seizure + ≥60% recurrence risk = epilepsy diagnosis after a single event).

Step 3 management: Frame every first-seizure encounter around three questions — Was it really a seizure? Was it provoked? What is the recurrence risk?

Definition: A seizure is a transient occurrence of signs/symptoms due to abnormal excessive or synchronous neuronal activity in the brain. A "first seizure" workup applies to an adult presenting with an unprovoked or apparently unprovoked event without a prior diagnosis of epilepsy.

Epidemiology: Lifetime risk of at least one seizure ≈ 8–10%; lifetime risk of epilepsy ≈ 3%. Bimodal incidence — young adults (trauma, substances, idiopathic) and >60 yo (stroke, tumor, neurodegenerative disease).

When to suspect a true seizure:

Provoked vs unprovoked: Critical early branch point.

Why the distinction matters: Provoked seizures typically do not require long-term antiseizure medication (ASM) if the trigger is corrected; unprovoked seizures may warrant ASM, especially with high-recurrence features.

Presentation Patterns and Key History

— Sudden LOC, tonic stiffening 10–20 sec, then rhythmic clonic jerks 1–2 min

— Cyanosis, frothing, lateral tongue bite, incontinence

— Postictal confusion, headache, myalgias, often sleep for hours

— Focal aware (simple partial): preserved consciousness; sensory, motor, autonomic, or psychic phenomena (déjà vu, rising epigastric sensation in mesial temporal)

— Focal impaired awareness (complex partial): staring, automatisms (lip-smacking, picking), 30–120 sec, postictal confusion

— May secondarily generalize

— Timing, duration, witnessed sequence

— Triggers: sleep deprivation, alcohol, flashing lights, fever, missed meds

— Substance use — cocaine, methamphetamine, tramadol, bupropion, MDMA

— Alcohol pattern (withdrawal seizures typically 6–48 hr after cessation)

— Medication review — fluoroquinolones, beta-lactams in renal failure, theophylline, clozapine

— Prior febrile seizures, head trauma (especially with LOC), CNS infection, stroke

— Family history of epilepsy

— Sleep, mood, recent illness, pregnancy status

Key distinction: Convulsive syncope vs seizure. Syncope can produce brief myoclonic jerks (<15 sec), but lacks prolonged tonic phase, tongue bite is tip not lateral, recovery is rapid (<1 min) without true postictal confusion, and there's usually a prodrome of lightheadedness/diaphoresis. Lateral tongue laceration has ~100% specificity for GTC.

Board pearl: Postictal Todd paralysis (focal weakness lasting minutes to 48 hr) mimics stroke — but follows seizure and resolves. Don't give tPA without imaging clarifying.

Eyewitness history is the single most valuable diagnostic tool — call the witness directly if possible. Self-report alone is often unreliable due to postictal amnesia.

Generalized tonic-clonic (GTC):

Focal seizures (formerly partial):

Absence (rare new onset in adults): brief 5–10 sec lapses without postictal phase

Aura: suggests focal onset — stereotyped warning preceding event

Critical history elements:

Physical Exam Findings and Hemodynamic Assessment

— Airway: position lateral, suction; intubate if not protecting airway

— Breathing: SpO2, capnography; transient hypoxia common

— Circulation: BP, HR, rhythm strip — exclude arrhythmic syncope masquerading as seizure

— Glucose fingerstick immediately — hypoglycemia is a reversible cause and a CCS reflex order

— Vitals: fever suggests CNS infection or sepsis-provoked event; HTN urgency can provoke

— Skin: neurocutaneous stigmata — ash-leaf spots, shagreen patches (TSC), café-au-lait (NF1), port-wine (Sturge-Weber); track marks; signs of trauma

— Head: scalp lacerations, hemotympanum, Battle sign, raccoon eyes

— Oral: lateral tongue laceration (highly specific), dental trauma

— Musculoskeletal: posterior shoulder dislocation, vertebral compression fracture from GTC

— Mental status — postictal confusion expected; persistent or fluctuating obtundation raises NCSE concern

— Cranial nerves, gaze deviation (postictal away from focus)

— Motor: focal weakness suggests Todd paralysis or underlying structural lesion

— Reflexes, plantar responses

— Meningismus — Kernig, Brudzinski; do not anchor on postictal stiffness

— Funduscopy — papilledema → urgent imaging before LP

CCS pearl: First-order set for adult first seizure in the ED — fingerstick glucose, CBC, BMP, magnesium, calcium, phosphorus, LFTs, urine tox, urine pregnancy (in women of childbearing age), ECG, CT head non-contrast, prolactin only rarely useful. Advance simulation clock cautiously; reassess neuro q15–30 min until baseline.

Board pearl: Persistent confusion >30–60 min after apparent seizure → consider nonconvulsive status epilepticus — get urgent EEG.

Immediate priorities (ABC):

General exam:

Neurologic exam (the cornerstone):

Cardiac assessment: Listen for murmurs (HOCM, AS — exertional syncope mimic); palpate pulses; orthostatic vitals once stable.

Diagnostic Workup — Initial Labs, Imaging, ECG

— Fingerstick glucose, BMP (Na, glucose, BUN/Cr, Ca), Mg, phosphorus

— CBC with differential

— LFTs (baseline before ASM; hepatic encephalopathy mimic)

— Urine toxicology — cocaine, amphetamines, PCP, synthetic cannabinoids

— Urine pregnancy test in reproductive-age women (changes ASM choice and imaging)

— Serum alcohol level; consider ethylene glycol/methanol if osmolar gap

— Creatine kinase — elevated after GTC; useful retrospective marker

— Rule out long QT (torsades-related syncope), Brugada, WPW, AV block, ischemia

— Cardiogenic syncope with anoxic jerks is the most commonly missed mimic

— Ammonia if hepatic disease

— Troponin if chest pain or ECG changes

— Lactate — modest rise (3–5) typical post-GTC; very high suggests another etiology

— HIV testing if risk factors (opportunistic CNS infection)

— All adults with first seizure (per ACEP)

— Especially urgent: focal deficit, persistent altered mental status, head trauma, fever, anticoagulation, immunosuppression, HIV, malignancy, age >40, new headache

— Preferred study for all unprovoked first seizures; outpatient if ED CT normal and patient stable

— Detects mesial temporal sclerosis, cortical dysplasia, low-grade tumor, cavernoma, AVM, prior stroke missed on CT

Step 3 management: Even if ED CT is unremarkable, MRI brain is still indicated for any first unprovoked seizure — arrange before or at first outpatient neurology follow-up. Don't sign off until it's scheduled.

Board pearl: Post-ictal lactic acidosis resolves within 1–2 hours; if not, look for another cause.

Universal labs (provoked-cause screen):

ECG — mandatory:

Targeted labs by context:

Neuroimaging — CT head non-contrast in the ED for:

MRI brain with epilepsy protocol:

Lumbar puncture: if fever, meningismus, immunocompromised, persistent altered mentation, or suspicion of SAH after negative CT.

Diagnostic Workup — EEG and Advanced Studies

— Indicated in all adults with a first unprovoked seizure (AAN/AES Level B recommendation)

— Goal: identify epileptiform abnormalities that predict recurrence and classify epilepsy syndrome

— Routine 20–30 min EEG sensitivity only ~25–50% on first study

— Early EEG within 24–48 hr improves yield (captures postictal slowing and interictal discharges before they fade)

— Sleep-deprived EEG increases yield by ~20–30%

— If routine EEG is normal but suspicion remains, proceed to ambulatory 24–72 hr EEG or inpatient video-EEG

— Focal interictal epileptiform discharges (spikes, sharp waves) → focal epilepsy, higher recurrence

— Generalized spike-wave (3 Hz) → idiopathic generalized epilepsy

— Focal slowing → underlying structural lesion (correlate with MRI)

— Periodic discharges (LPDs, GPDs) → consider NCSE, anoxic injury

— Thin coronal T2/FLAIR through hippocampi, 3D volumetric T1

— Detects subtle focal cortical dysplasia, hippocampal sclerosis

— PET/SPECT — for refractory focal epilepsy, presurgical evaluation

— Autoimmune encephalitis panel (NMDA-R, LGI1, CASPR2, GAD-65) — young adults, subacute behavioral change, faciobrachial dystonic seizures, refractory presentation

— Genetic testing — early-onset, family history, syndromic features

— Cardiac event monitor — if convulsive syncope still suspected

Key distinction: A normal EEG does not exclude epilepsy (interictal discharges are intermittent). An abnormal EEG with epileptiform discharges substantially raises recurrence risk (~60% at 2 yr) and supports starting ASM after a single seizure.

Board pearl: Provocation maneuvers — sleep deprivation, hyperventilation (activates absence), photic stimulation (juvenile myoclonic epilepsy) — increase EEG yield.

Electroencephalography (EEG) — cornerstone of unprovoked first-seizure evaluation:

Timing matters:

EEG findings of interest:

MRI epilepsy protocol (preferred over standard MRI):

Other advanced testing (selected cases):

Risk Stratification and Decision to Treat After a First Seizure

— Prior brain insult — stroke, trauma, CNS infection, tumor

— Epileptiform abnormalities on EEG

— Significant abnormality on brain imaging (structural lesion)

— Nocturnal seizure

— No high-risk features: ~30–40% recurrence at 2 yr → ASM optional

— One+ feature: 50–70% recurrence → strongly consider ASM

— Two+ unprovoked seizures >24 hr apart → epilepsy diagnosis, treat

— Patient occupation (driver, pilot, machinery operator, healthcare worker)

— Childcare responsibilities, social risk of recurrence

— Pregnancy plans

— Comorbidities and polypharmacy

— Patient preference re: medication adverse effects vs recurrence risk

— Treat the underlying cause — correct sodium, glucose, magnesium; manage withdrawal with benzodiazepines; treat infection; discontinue offending drugs

— Generally no chronic ASM if isolated provoked event with reversible trigger

— Exception: acute symptomatic seizures from severe structural injury (large hemorrhagic stroke, severe TBI) may warrant short-course prophylaxis (e.g., 7 days levetiracetam post-TBI)

Step 3 management: "Treat the patient, not the EEG alone." If MRI shows a lesion (e.g., cavernoma) and EEG is epileptiform — start ASM after a single event and refer to neurology.

Board pearl: Early ASM treatment reduces 2-year recurrence by ~35% but does not alter long-term remission rates — counsel accordingly.

Core decision: Start an antiseizure medication after one unprovoked seizure, or wait? Driven by 2-year recurrence risk.

AAN/AES 2015 guideline framework — high-recurrence features (any one increases risk):

Risk tiers:

Shared decision-making elements (Step 3 emphasizes):

What about provoked seizures?

Status epilepticus on presentation: Different pathway — IV lorazepam first-line, fosphenytoin/levetiracetam/valproate second-line, then anesthesia for refractory.

Pharmacotherapy — First-Line ASM Selection

— Levetiracetam — broad spectrum, no hepatic metabolism, minimal interactions, IV/PO, rapid titration. Adverse: irritability, depression, suicidality screening required.

— Lamotrigine — excellent tolerability, mood-stabilizing; slow titration (8 weeks) to avoid SJS/TEN; preferred in pregnancy

— Lacosamide — well-tolerated; check PR interval (sodium channel modulator)

— Older: carbamazepine, oxcarbazepine — HLA-B*1502 screen in Asian ancestry (SJS risk); hyponatremia with oxcarbazepine

— Valproate — most effective but teratogenic (neural tube defects, ~10% major malformation, lower IQ) — avoid in women of childbearing potential

— Levetiracetam — broad spectrum, preferred in pregnancy

— Lamotrigine — good for GTC, may worsen myoclonus

— Absence-specific: ethosuximide (children); valproate

— Take consistently; missed doses are the leading cause of "breakthrough"

— No abrupt discontinuation

— Driving restrictions (state-specific, typically 3–12 months seizure-free)

— Suicidality monitoring — FDA class warning for all ASMs

— Rash → stop immediately, especially lamotrigine

— Pregnancy planning before conception

— Baseline and periodic CBC, LFTs for enzyme-inducing or hepatotoxic ASMs

— Sodium for oxcarbazepine/carbamazepine

— Levels not routinely needed for levetiracetam/lamotrigine; useful for phenytoin (free level if hypoalbuminemia), valproate, carbamazepine

Board pearl: Levetiracetam is the most common Step 3 "first ASM" answer — broad spectrum, no titration needed, IV available, minimal interactions, safe in renal dose-adjustment, pregnancy category acceptable.

Step 3 management: In a woman of reproductive age, default to levetiracetam or lamotrigine; document folic acid 0.4–4 mg daily and contraception counseling.

Choice driven by seizure type, comorbidities, sex, age, pregnancy potential, drug interactions.

Focal-onset seizures (first-line):

Generalized-onset (tonic-clonic, myoclonic, absence):

Counseling at initiation:

Monitoring:

Acute Management and Status Epilepticus

— Position lateral, suction, O2 via NRB, two large-bore IVs

— Fingerstick glucose; thiamine 100 mg IV before dextrose in alcohol use

— Continuous cardiac/SpO2 monitoring

— Labs: BMP, Mg, Ca, CBC, LFTs, ammonia, tox, ASM levels, lactate, ABG

— Lorazepam 0.1 mg/kg IV (typically 4 mg, repeat once in 5 min) — first line

— Midazolam 10 mg IM if no IV access — equivalent efficacy (RAMPART trial)

— Diazepam 0.15 mg/kg IV alternative; PR if no IV

— Levetiracetam 60 mg/kg (max 4.5 g) — preferred; no BP/cardiac concerns

— Fosphenytoin 20 mg PE/kg — monitor BP, telemetry, infusion site (purple glove with phenytoin)

— Valproate 40 mg/kg — avoid in hepatic disease, pregnancy

— ESETT trial: all three roughly equivalent — levetiracetam often preferred for safety

— Intubate; continuous IV anesthetic — midazolam, propofol, or pentobarbital infusion

— Continuous EEG monitoring — target burst-suppression

— ICU admission mandatory

CCS pearl: Order set sequence on the clock — "lorazepam 4 mg IV now → if seizing at 5 min, repeat lorazepam 4 mg → at 10 min, levetiracetam 60 mg/kg IV load → call neurology, consult anesthesia for intubation if persists, transfer to ICU, order continuous EEG."

Board pearl: Always check glucose and give thiamine before D50 in any seizing patient — missing Wernicke prophylaxis is a tested error.

Status epilepticus (SE): Continuous seizure ≥5 min, or ≥2 seizures without return to baseline. Time-critical — neuronal injury accelerates after 30 min.

Step 0 — supportive (first 5 min):

Stage 1 — Initial therapy (5–20 min): Benzodiazepines

Stage 2 — Urgent control (20–40 min): Choose one IV ASM

Stage 3 — Refractory SE (>40 min):

Super-refractory SE (>24 hr despite anesthesia): ketamine, immunotherapy (if autoimmune), ketogenic diet, surgery selectively.

Special Populations — Elderly and Renal/Hepatic Impairment

— Most common etiology: cerebrovascular disease (~30–50%) — both acute stroke and remote infarct

— Other: neurodegenerative (Alzheimer, vascular dementia), tumor (primary or metastatic), subdural hematoma (especially with anticoagulation, falls), metabolic

— Presentations often atypical — confusion episodes, "spells," focal twitching, nonconvulsive status epilepticus masquerading as delirium → low threshold for EEG in unexplained altered mentation

— Levetiracetam and lamotrigine preferred — fewer interactions, better cognitive profile

— Avoid phenytoin (cognitive effects, osteoporosis, interactions), benzodiazepines chronically (falls), valproate (tremor, thrombocytopenia)

— Start low, go slow — half typical doses

— Reconcile polypharmacy: enzyme-inducing ASMs affect warfarin, DOACs, statins

— Levetiracetam — renally cleared; CrCl 30–50: 250–750 mg BID; CrCl <30: reduce further; supplemental dose after HD

— Gabapentin/pregabalin — renally cleared, accumulate

— Topiramate — partial renal clearance, dose reduce

— Lamotrigine, valproate, carbamazepine, phenytoin — primarily hepatic, generally safe in renal disease

— Avoid or dose-reduce valproate (hepatotoxicity), carbamazepine, phenytoin

— Levetiracetam, gabapentin, lacosamide safer hepatic options

— Check albumin — phenytoin is highly protein-bound; measure free phenytoin in hypoalbuminemia or uremia (total level misleadingly low)

Step 3 management: Elderly patient with new "confusional spells" + normal CT + waxing/waning sensorium → order continuous EEG to rule out NCSE before labeling delirium.

Board pearl: Bone health — long-term enzyme-inducing ASMs (phenytoin, carbamazepine, phenobarbital, primidone) cause vitamin D deficiency and osteoporosis. Check 25-OH vitamin D, supplement calcium/D, consider DEXA in chronic users.

Elderly (>60 yo) — fastest-growing first-seizure demographic:

Drug choice in elderly:

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy and Women of Reproductive Age

— Folic acid 0.4–4 mg daily — neural tube defect prevention; higher dose (4 mg) if on valproate/carbamazepine or prior NTD pregnancy

— Optimize to monotherapy at lowest effective dose before conception

— Avoid valproate (major malformation rate ~10%, IQ reduction ~9 points) and topiramate (cleft lip/palate, low birth weight) when possible

— Preferred: lamotrigine, levetiracetam — lowest teratogenicity (~2–3%, similar to baseline)

— Do not stop ASMs abruptly — convulsive seizures harm fetus and mother more than ASMs in most cases

— Lamotrigine and levetiracetam levels decline in pregnancy (increased clearance, estrogen induction of glucuronidation) — monitor levels monthly, increase dose to maintain prepregnancy concentration

— Anatomy ultrasound at 18–20 weeks; consider fetal echo if on valproate/carbamazepine

— Vitamin K 10 mg PO daily in last month if on enzyme-inducing ASM (phenytoin, carbamazepine, phenobarbital) — prevents neonatal hemorrhagic disease

— Vaginal delivery preferred; seizures during labor → benzodiazepine

— Seizure in pregnancy >20 wk with preeclampsia features → magnesium sulfate 4–6 g IV load, then 1–2 g/hr, deliver the fetus

— Mg is not a standard ASM but is first-line for eclampsia

— Enzyme-inducing ASMs reduce OCP efficacy → use IUD or DMPA

— OCPs reduce lamotrigine levels → dose adjustment

Key distinction: New-onset seizure in pregnancy >20 wk = eclampsia until proven otherwise — give Mg, lower BP, deliver. Do not anchor on "epilepsy."

Board pearl: Pregnancy registries (NAEP) show valproate is the worst, lamotrigine and levetiracetam are the best for fetal outcomes.

Preconception counseling (every visit, every reproductive-age woman with epilepsy):

During pregnancy:

Eclampsia is a special category:

Postpartum: Taper ASM dose back to pre-pregnancy over weeks (avoid toxicity). Breastfeeding generally safe — levetiracetam, lamotrigine well-tolerated.

Contraception interactions:

Complications and Adverse Outcomes

— Tongue/oral laceration, dental fractures

— Posterior shoulder dislocation, humeral fracture

— Vertebral compression fractures (thoracic) from severe GTC

— Head trauma from fall — subdural hematoma especially in elderly/anticoagulated

— Burns, drowning (bathtubs especially), MVA

— Todd paralysis — focal weakness up to 48 hr

— Postictal psychosis — confused, agitated state, usually after cluster; lucid interval then psychiatric symptoms

— Postictal headache, myalgia

— Neuronal injury, especially hippocampal (mesial temporal sclerosis can develop)

— Hyperthermia, lactic acidosis, hyperkalemia, AKI, cardiac arrhythmia

— Mortality 10–20% for convulsive SE; higher in elderly, anoxic etiology

— Incidence ~1 per 1,000 patient-years; higher with frequent GTCs, nocturnal seizures, poor adherence

— Counsel patients — adherence and seizure freedom are the strongest protective factors

— Depression and anxiety prevalence ~30–50%

— Suicide risk elevated — class warning on all ASMs

— Screen PHQ-9 at follow-up

— SJS/TEN — lamotrigine, carbamazepine, phenytoin

— DRESS — aromatic ASMs; fever, rash, eosinophilia, hepatitis

— Aplastic anemia, agranulocytosis — felbamate, carbamazepine

— Hepatic failure — valproate (especially under 2 yo or POLG mutations)

Board pearl: SUDEP counseling is now standard of care and a frequent ethics-flavored test item. Frequent GTCs are the dominant modifiable risk factor.

Step 3 management: After any GTC, check CK and basic metabolic panel; aggressive hydration if CK >5,000 to prevent pigment nephropathy.

Seizure-related injury:

Aspiration pneumonia — postictal obtundation; check CXR if hypoxic or fevered next day

Rhabdomyolysis — elevated CK after prolonged GTC; hydrate, monitor renal function and potassium

Postictal complications:

Status epilepticus complications:

SUDEP (Sudden Unexpected Death in Epilepsy):

Psychiatric comorbidity:

Cognitive effects: topiramate ("dopamax"), phenobarbital, high-dose valproate

Idiosyncratic drug reactions:

When to Escalate Care — Admission and Consults

— Single, brief, self-terminating seizure

— Returned fully to neurologic baseline

— Normal labs and CT

— Identified, correctable provocateur (e.g., missed dose, mild hyponatremia treated)

— Reliable follow-up arranged with neurology within 1–2 weeks

— Safe disposition (sober, accompanied, transportation arranged — no driving)

— Status epilepticus (admit to ICU)

— Persistent altered mental status or focal deficit

— Multiple seizures in 24 hr

— Abnormal neuroimaging requiring further evaluation (tumor, hemorrhage, abscess)

— CNS infection suspected

— Eclampsia

— Severe metabolic derangement requiring correction

— Significant injury (fracture, aspiration, head trauma with abnormal CT)

— Suspected nonconvulsive status — for continuous EEG

— Unreliable outpatient follow-up or psychosocial risk

— Convulsive or nonconvulsive status epilepticus

— Need for continuous EEG with anesthetic infusion

— Airway compromise, post-intubation

— Hemodynamic instability

— Neurology — all first unprovoked seizures, within 2 weeks outpatient minimum; same-day if abnormal imaging, status, or diagnostic uncertainty

— Neurosurgery — structural lesion (tumor, hemorrhage, abscess)

— Psychiatry — suspected PNES (psychogenic nonepileptic spells), suicidality

— Cardiology — if convulsive syncope on differential, abnormal ECG, structural heart disease

— Obstetrics — pregnant patients, especially >20 weeks

CCS pearl: On the simulated case, schedule the outpatient neurology appointment and the MRI before ending the case — examiners look for transition-of-care completeness, not just acute stabilization.

Board pearl: Threshold for continuous EEG is low — any unexplained altered mental status persisting >30–60 min post-event, comatose ICU patient with risk factors, or patient on anesthetic for SE.

Discharge from ED is reasonable when:

Admit for inpatient observation/workup when:

ICU admission triggers:

Consults:

Key Differentials — Other Causes of Seizure

— Stroke (acute or remote) — most common in elderly; cortical infarcts especially epileptogenic

— Tumor — glioma, meningioma, metastasis; consider with focal features and progressive symptoms

— Traumatic brain injury — remote TBI can cause epilepsy years later

— Vascular malformations — AVM, cavernoma

— Cortical dysplasia, mesial temporal sclerosis (suspect with prolonged febrile seizures in childhood)

— Subdural/epidural hematoma

— Hippocampal sclerosis — classic temporal lobe epilepsy

— Bacterial meningitis, viral encephalitis (HSV — temporal predilection)

— Brain abscess

— Neurocysticercosis — leading cause worldwide; calcified cysts on CT in immigrants from endemic regions

— Tuberculoma

— HIV-related: PML, toxoplasmosis, primary CNS lymphoma

— Autoimmune encephalitis — NMDA-R (young women, ovarian teratoma, psychiatric prodrome), LGI1 (faciobrachial dystonic seizures, hyponatremia)

— Juvenile myoclonic epilepsy — morning myoclonus, GTCs, photosensitivity, onset teens

— Idiopathic generalized epilepsy — generalized spike-wave on EEG

— Genetic focal epilepsies (autosomal dominant nocturnal frontal lobe epilepsy, etc.)

— Hyponatremia (<125), hypoglycemia, hypocalcemia, hypomagnesemia, hyperglycemic hyperosmolar (paradoxically, nonketotic hyperglycemia provokes focal seizures)

— Uremia, hepatic encephalopathy

— Alcohol/benzo withdrawal (6–48 hr)

— Drugs: cocaine, methamphetamine, tramadol, bupropion, isoniazid (give pyridoxine), theophylline, beta-lactams in renal failure, fluoroquinolones, clozapine

Key distinction: Nonketotic hyperglycemia causes focal motor seizures without ketosis — correct glucose, seizures resolve; ASMs less effective until glucose normalized.

Board pearl: Isoniazid toxicity → seizures refractory to benzodiazepines → give pyridoxine (B6) 1 g per gram of INH ingested.

Even within "seizure" the etiology shapes management. After confirming a true seizure, classify the cause:

Structural (focal substrate):

Infectious/inflammatory:

Idiopathic/genetic epilepsy syndromes:

Metabolic/toxic provoked:

Key Differentials — Seizure Mimics (Non-Epileptic)

— Vasovagal — prodrome (warmth, nausea, lightheadedness), pallor, rapid recovery

— Cardiogenic — exertional, no prodrome; check ECG (long QT, Brugada, HOCM, AS, AV block)

— Orthostatic — postural change; check orthostatics

— Convulsive syncope — brief myoclonic jerks during anoxic phase, no postictal confusion, <15 sec — most frequently misdiagnosed as seizure

— Long duration (>2 min), forced eye closure, pelvic thrusting, side-to-side head shaking, asynchronous limb movements, fluctuating course, recall of event, lack of postictal confusion

— Often history of trauma, abuse, psychiatric comorbidity

— Normal prolactin, normal lactate post-event (vs elevated post true GTC)

— Video-EEG is diagnostic gold standard

— Management: psychiatric referral, not ASMs; avoid iatrogenic harm

— Negative symptoms (loss of function) vs seizure positive symptoms (clonic activity, paresthesias spreading)

— No postictal confusion; deficits resolve fully <24 hr

— Gradual march of visual scintillations over 20–30 min, followed by headache

— Compare seizure aura which is brief, stereotyped, and followed by ictal event

— Hemifacial spasm, dystonia, paroxysmal kinesigenic dyskinesia

— Preserved consciousness, no postictal phase

— Parasomnias (REM behavior disorder, sleepwalking), narcolepsy with cataplexy, hypnic jerks

Key distinction: Postictal prolactin elevation (2–3x baseline, drawn 10–20 min after) supports true GTC vs PNES — but normal prolactin doesn't exclude seizure. Useful only in specific timing window.

Board pearl: Lateral tongue laceration, postictal confusion >5 min, and CK elevation all strongly favor true seizure over syncope or PNES.

Syncope (most common mimic):

Psychogenic nonepileptic spells (PNES) — formerly "pseudoseizures":

TIA:

Migraine with aura:

Movement disorders:

Sleep disorders:

Transient global amnesia: sudden anterograde amnesia, preserved consciousness, age >50, resolves within 24 hr

Metabolic encephalopathies: asterixis, multifocal myoclonus, but no focal-onset stereotyped event

Secondary Prevention and Long-Term Plan

— Adherence counseling — pill organizers, smartphone reminders, refill synchronization

— Monotherapy at lowest effective dose; titrate to seizure freedom or maximum tolerated

— Add second agent only if monotherapy fails at therapeutic dose

— ~50–70% achieve seizure freedom on first or second monotherapy

— Drug-resistant epilepsy = failure of 2 appropriate ASMs → refer to epilepsy center for presurgical evaluation, neurostimulation (VNS, RNS, DBS), or ketogenic diet

— Sleep hygiene — sleep deprivation is a potent trigger

— Alcohol moderation/avoidance

— Stress management

— Avoid recreational drugs

— Photosensitivity precautions if photosensitive epilepsy (sunglasses, screen breaks)

— Bathing — showers preferred over baths; avoid solo swimming, climbing, scuba

— Discuss after 2 years seizure-free with normal EEG and no high-risk features

— Slow taper over months; 30–40% recurrence after withdrawal

— Lifelong therapy often warranted for JME, structural lesions, refractory courses

— Bone health — vitamin D, calcium, DEXA if chronic enzyme-inducing ASM

— Mental health — depression and anxiety screening at every visit

— Reproductive planning — recurring counseling

— Cardiovascular risk if epilepsy from stroke — secondary prevention (statin, antiplatelet, BP control)

Step 3 management: A patient seizure-free for 2 years on monotherapy with normal EEG and no MRI lesion is a reasonable candidate to discuss ASM withdrawal — but decision belongs in neurology clinic, not ED disposition.

Board pearl: The single most important predictor of remission is seizure freedom on monotherapy within the first year — drives prognosis discussion.

If ASM started (epilepsy diagnosed or high-risk single seizure):

Lifestyle modifications:

ASM withdrawal consideration:

Comorbidity management:

Vaccines: annual influenza; standard adult schedule

Follow-Up, Monitoring, and Counseling

— Outpatient neurology within 1–2 weeks of first seizure

— MRI brain (epilepsy protocol) before or at this visit if not done

— Outpatient EEG (routine or sleep-deprived) if not obtained in ED

— Repeat clinic visit at 4–6 weeks to assess ASM tolerance and adherence

— Then every 3 months while titrating; every 6–12 months once stable

— Seizure diary — date, time, duration, trigger, postictal duration, witness account

— Adverse effect review — sedation, mood, rash, weight, tremor, GI

— Labs as drug-specific (BMP for oxcarbazepine, CBC/LFTs for valproate/carbamazepine, vitamin D for chronic enzyme inducers)

— ASM level only if non-adherence, breakthrough, toxicity, or pregnancy

— State-specific laws — seizure-free intervals typically 3–12 months

— Some states mandate physician reporting (CA, NJ, OR, PA, DE, NV)

— Document discussion explicitly in chart at every visit

— Patient assumes responsibility for compliance in non-reporting states

— Commercial drivers (CDL), pilots, machinery operators — usually disqualified during active epilepsy

— Workplace accommodations through HR/occupational health

— Showers > baths; no solo swimming

— Ground-floor cooking when possible, induction stove preferable

— Helmet for cycling/skating; avoid heights, ladders, scaffolding

— Sleep in supine or lateral position; consider seizure detection devices for nocturnal seizures

— Recognize prodrome/aura; abort with seizure plan

— Family/caregiver training on first aid — protect from injury, lateral position, do not put anything in mouth, time the seizure, call 911 if >5 min or repeated

— Rescue medication — nasal midazolam or rectal diazepam for seizure clusters at home

— MedicAlert bracelet

Board pearl: Always document driving counseling — it's the single most litigated and tested transition-of-care element in epilepsy.

Follow-up cadence:

Monitoring parameters:

Driving:

Occupational counseling:

Safety counseling:

Patient education:

Ethical, Legal, and Patient Safety Considerations

— Six US states mandate physician reporting of seizure disorders to DMV; most others delegate to the patient

— Even in non-reporting states, document that you counseled the patient not to drive and the seizure-free interval required

— A common Step 3 scenario: patient asks you not to tell the DMV; refuses to stop driving despite recent seizure → in mandatory-reporting states, physician duty supersedes confidentiality; in non-mandatory states, persuade and document, consider notifying if imminent harm (varies by state)

— Postictal patients lack capacity — defer non-emergent decisions until baseline restored

— Consent for AEDs should address teratogenicity in reproductive-age women — document discussion of valproate risks before prescribing

— FDA class warning on all ASMs (~2x baseline risk) — screen at every visit

— Do not withhold needed therapy, but document risk discussion

— Epilepsy diagnosis can affect employability — patients control disclosure to employer unless safety-sensitive occupation (CDL, pilot, surgeon — these may have mandatory disclosure)

— ADA protections apply

— Suspected child abuse, elder abuse, intimate partner violence if discovered during workup of "spells"

— Some states: gunshot/stab wounds, certain communicable diseases

— Ensure outpatient follow-up scheduled with neurology

— Medication reconciliation at discharge

— Communicate driving restriction in writing — to patient and PCP

— Provide seizure action plan and rescue med if appropriate

— Verify patient has affordable access to ASM (generic levetiracetam, lamotrigine cheap; newer agents may need prior auth)

Step 3 management: Patient refuses to stop driving after a first seizure in a non-reporting state — escalate counseling, involve family, document extensively, and in cases of clear imminent harm to public, consider breach of confidentiality permissible (state-specific). When in doubt, consult risk management.

Board pearl: "Document the driving conversation" is the single most tested patient-safety item in adult epilepsy care.

Driving and physician reporting:

Informed consent and capacity:

Suicidality:

Confidentiality and employment:

Mandatory reporting:

Transitions of care (Step 3 favorite):

Research/genetic ethics: Genetic testing for epilepsy syndromes may have implications for family members — pretest counseling required.

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: "Morning jerks dropping the toothbrush in a teenager" → JME → start levetiracetam (or valproate if male); avoid carbamazepine (worsens myoclonus).

Lateral tongue laceration → true GTC seizure (specific)

Postictal Todd paralysis → focal seizure with structural substrate; resolves <48 hr

Postictal confusion >30 min → consider NCSE, get EEG

3 Hz spike-and-wave → absence epilepsy

Polyspike-wave on EEG + morning myoclonus → juvenile myoclonic epilepsy; lifelong valproate or levetiracetam

Hippocampal atrophy/sclerosis on MRI → mesial temporal lobe epilepsy; often surgically curable

Calcified cystic lesions on CT in immigrant → neurocysticercosis (albendazole + steroids + ASM)

Temporal lobe FLAIR hyperintensity, fever, AMS → HSV encephalitis (acyclovir empirically)

Young woman + psychiatric prodrome + orofacial dyskinesia + seizures → anti-NMDA-R encephalitis; check ovarian teratoma

Faciobrachial dystonic seizures + hyponatremia in older adult → anti-LGI1 encephalitis

Seizure in first 24 hr after ischemic stroke → acute symptomatic; not necessarily chronic ASM

Seizure 1 week after large cortical stroke → epileptogenic, often chronic ASM

New seizure + headache + immunosuppressed (HIV, transplant) → toxoplasmosis, lymphoma, PML — MRI with contrast

Pregnancy + seizure + HTN + proteinuria → eclampsia → magnesium, deliver

Alcoholic 12–48 hr after last drink → withdrawal seizure; benzodiazepines, thiamine

Isoniazid overdose seizure → pyridoxine

Bupropion or tramadol overdose → lower seizure threshold

Cefepime in renal failure → nonconvulsive status; check level, dose-adjust

HLA-B*1502 in Asian ancestry → screen before carbamazepine (SJS)

Valproate teratogenicity → 10% major malformation, IQ reduction

Lamotrigine + valproate → valproate doubles lamotrigine levels (titrate slower, lower dose); rash risk higher

Phenytoin + albumin → measure free phenytoin in hypoalbuminemia

SUDEP → frequent GTCs, nocturnal seizures, nonadherence — emphasize control

Board Question Stem Patterns

Board pearl: When a stem gives you a normal exam and stable patient after a first seizure, the high-yield distractor is "start phenytoin now" — the correct answer is usually arrange MRI and EEG, then decide.

Pattern 1 — First unprovoked seizure, normal workup: Adult with witnessed GTC, normal exam, normal CT, normal labs. Answer: Outpatient neurology referral with MRI brain and EEG; defer ASM pending those results unless high-risk features.

Pattern 2 — High-recurrence features: First seizure + MRI lesion + epileptiform EEG. Answer: Start ASM (levetiracetam typical).

Pattern 3 — Status epilepticus: Seizing >5 min in ED. Answer: IV lorazepam → repeat → fosphenytoin/levetiracetam/valproate load → intubate and infuse midazolam/propofol if refractory.

Pattern 4 — Eclampsia: Pregnant >20 wk with HTN, proteinuria, seizes. Answer: Magnesium sulfate, BP control, deliver.

Pattern 5 — Convulsive syncope mimic: Brief LOC with few jerks after blood draw, rapid recovery. Answer: Reassurance, orthostatic counseling — not ASM, not EEG.

Pattern 6 — PNES: Long-duration "seizure," forced eye closure, side-to-side head, normal EEG, history of trauma. Answer: Video-EEG to confirm; psychiatric referral, taper unnecessary ASMs.

Pattern 7 — Alcohol withdrawal seizure: 24–48 hr after last drink, GTC. Answer: Benzodiazepines (CIWA), thiamine, magnesium; no chronic ASM.

Pattern 8 — Elderly with "spells" and confusion: Persistent altered mentation, no overt seizures. Answer: Continuous EEG to evaluate for NCSE.

Pattern 9 — Young woman starting ASM: Answer: Folic acid, contraception counseling, avoid valproate; prefer levetiracetam or lamotrigine.

Pattern 10 — Driving question: First seizure, patient asks when can drive. Answer: State-specific; counsel against driving, document; report if mandatory state.

Pattern 11 — Drug-induced seizure: Bupropion overdose, INH toxicity, cefepime in renal failure. Answer: Treat the trigger (pyridoxine for INH); benzodiazepine acutely; ASM not usually chronic.

Pattern 12 — Anti-NMDA-R encephalitis: Young woman, psych symptoms, dyskinesias, seizures. Answer: CSF antibodies, pelvic imaging for teratoma, IVIG/steroids/rituximab.

Pattern 13 — Post-stroke seizure: Acute (<7 d) vs late (>7 d); late warrants chronic ASM.

One-Line Recap

Rapid recap bullets:

Board pearl: The most testable transition-of-care steps after ED discharge for a first seizure are (1) scheduling outpatient MRI and EEG, (2) explicit driving counseling with documentation, and (3) neurology follow-up within two weeks — miss any one and you miss the question.

The Step 3 essence: A first seizure in an adult is a clinical event demanding three structured questions — Was it truly a seizure? Was it provoked? What is the recurrence risk? — answered through eyewitness history, metabolic and toxicologic screening, ECG, neuroimaging (CT in ED, MRI outpatient), and EEG, with antiseizure medication reserved for high-risk single events or recurrent unprovoked seizures.

Workup: Glucose, BMP, Mg, Ca, LFTs, tox, ECG, CT in ED → MRI epilepsy protocol and EEG within 1–2 weeks → neurology referral universally

Treat the cause first: Correct sodium, magnesium, glucose; treat withdrawal with benzodiazepines + thiamine; stop offending drugs; deliver in eclampsia; antibiotics for CNS infection — provoked seizures rarely need chronic ASM

Start ASM after a single seizure when: EEG epileptiform, MRI lesion, prior brain insult, or nocturnal event — ≥60% recurrence justifies treatment per ILAE practical epilepsy definition

First-line ASM: Levetiracetam for most adults; lamotrigine in pregnancy and mood comorbidity; avoid valproate in women of childbearing potential; pyridoxine for INH-induced seizures

Status epilepticus: Lorazepam → levetiracetam/fosphenytoin/valproate → intubate + midazolam/propofol; continuous EEG and ICU

Counsel always: No driving (state-specific intervals, document), sleep hygiene, alcohol avoidance, adherence, SUDEP, contraception/folate in reproductive-age women, suicidality screen

Mimics to exclude: Convulsive syncope, PNES, TIA, migraine aura, parasomnia — eyewitness, ECG, video-EEG sort these out