Nervous System & Special Senses

Epilepsy: outpatient antiepileptic management

Clinical Overview and When to Suspect Epilepsy

— ≥2 unprovoked seizures >24 hours apart

— 1 unprovoked seizure with ≥60% recurrence risk over 10 years (e.g., remote stroke, structural lesion on MRI, abnormal EEG with epileptiform discharges)

— Diagnosis of an epilepsy syndrome (e.g., JME, childhood absence)

— Stereotyped spells with postictal confusion lasting minutes to hours

— Tongue lateral bitemark, urinary incontinence, witnessed convulsion

— Recurrent "déjà vu," olfactory hallucinations, or rising epigastric aura (temporal lobe focal seizures)

— Morning myoclonus + sleep-deprivation triggers in a teen/young adult → JME

— Brief staring spells with blink/lip-smacking automatisms, no postictal phase → absence (kids) vs focal impaired awareness (adults)

Definition (ILAE 2014): Epilepsy is diagnosed when any one criterion is met:

Provoked vs unprovoked: Provoked (acute symptomatic) seizures from hypoglycemia, hyponatremia (<125), alcohol/benzo withdrawal, uremia, eclampsia, acute stroke, meningitis, or drugs (bupropion, tramadol, clozapine) do not establish epilepsy and generally do not require chronic antiepileptic drug (AED) therapy — treat the cause.

Epidemiology: Bimodal — peaks in early childhood and after age 60. In adults >60, cerebrovascular disease is the leading etiology (~30–40%); in young adults consider genetic generalized epilepsies, trauma, and substance use.

When to suspect in clinic:

Step 3 management: After a first unprovoked seizure in an adult, the decision to start an AED is risk-stratified, not automatic. Order MRI brain (epilepsy protocol) and EEG; if either shows an epileptogenic lesion or epileptiform discharges, recurrence risk crosses the 60% threshold and you treat as epilepsy.

Board pearl: A single seizure + normal EEG + normal MRI + no clear etiology = ~30% 2-year recurrence; shared decision-making on AED initiation, weighed against driving and occupational risk.

Presentation Patterns and Key History

— Focal aware (formerly simple partial): preserved consciousness, motor/sensory/autonomic/psychic aura

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

— Focal to bilateral tonic-clonic: focal onset that generalizes — often missed; ask about aura

— Generalized tonic-clonic: abrupt LOC, no aura, symmetric convulsion, tongue bite, postictal stupor

— Absence: 5–10 sec staring, no postictal phase, provoked by hyperventilation, 3-Hz spike-wave

— Myoclonic: brief shock-like jerks, often morning, preserved awareness

— Witness account (patient often amnestic) — get a phone video if possible

— Aura (localizes focus: olfactory = mesial temporal; visual = occipital; Jacksonian march = motor cortex)

— Duration, postictal time, Todd's paralysis (focal weakness up to 48h after focal motor seizure)

— Triggers: sleep deprivation, alcohol, photic stimulation, missed doses, fever, menstrual cycle (catamenial)

— Sleep-related (frontal lobe), morning (JME), with fever in child <6 (febrile sz, usually not epilepsy)

Classify seizure type first — this drives drug choice:

History elements to extract:

Red flags suggesting structural cause: focal onset in adult, progressive headache, new focal deficits, weight loss, HIV/immunosuppression → urgent MRI ± contrast.

Comorbid history: prior head trauma (especially LOC >30 min or skull fracture), CNS infection, stroke, perinatal hypoxia, family history of epilepsy, prior febrile seizures.

Medication and substance review: bupropion, tramadol, clozapine, theophylline, fluoroquinolones, isoniazid, lidocaine; cocaine, methamphetamine; alcohol or benzodiazepine withdrawal.

Key distinction: Syncope vs seizure — convulsive syncope may have brief myoclonic jerks (<15 sec) but lacks tongue bite (lateral), prolonged postictal confusion, or incontinence. Pallor and presyncopal prodrome favor syncope; aura and lateral tongue bite favor seizure.

Physical Exam Findings (and Interictal Assessment)

— BP and HR — orthostatics if syncope on differential

— Fever → consider CNS infection, especially in immunocompromised

— Cardiac auscultation — murmurs/arrhythmia point to cardiogenic syncope mimicking seizure

— Ash-leaf spots, shagreen patch, facial angiofibromas → tuberous sclerosis

— Café-au-lait macules, axillary freckling, Lisch nodules → NF1

— Port-wine stain in V1 distribution → Sturge-Weber (leptomeningeal angioma, focal seizures)

— Focal deficits suggest structural lesion (tumor, AVM, prior stroke) → MRI mandatory

— Todd's paralysis: transient focal weakness post-seizure, resolves <48h; does NOT equal stroke but must be distinguished from one

— Visual field cut → occipital or temporal lesion

— Cognitive impairment may reflect underlying neurodegenerative process or AED burden

— Always check 12-lead ECG on first presentation — exclude long QT, Brugada, AV block masquerading as seizure

— Carotid bruits in elderly with new focal seizures (post-stroke epilepsy)

Interictal exam is usually normal — abnormal findings raise suspicion for a structural or systemic cause.

General/vital signs:

Skin findings (neurocutaneous syndromes):

Neurologic exam:

Oral exam: lateral tongue laceration is highly specific for generalized tonic-clonic seizure (tip-of-tongue bite favors syncope/psychogenic).

Musculoskeletal: posterior shoulder dislocation (classic for tonic-clonic), compression fractures of vertebrae, rhabdomyolysis tenderness.

Hemodynamic and cardiac assessment:

Board pearl: Any adult with new-onset focal seizure needs MRI brain with epilepsy protocol (thin coronal cuts through hippocampus, FLAIR) — not just a CT. CT misses mesial temporal sclerosis, low-grade tumors, and cortical dysplasia.

Step 3 management: Document a baseline neuro exam at every visit — emerging focal findings on a stable AED regimen mandate repeat imaging to exclude tumor or vascular lesion.

Diagnostic Workup — Initial Labs, Imaging, ECG

— CBC, BMP (glucose, Na⁺, Ca²⁺, Mg²⁺), LFTs, prolactin only rarely useful (rises 10–20 min post-GTC but poor sensitivity — not routine)

— Toxicology screen if any suspicion of substance use

— Pregnancy test in any woman of childbearing potential — drives AED choice

— HIV, RPR if risk factors and unexplained CNS pathology

— 12-lead ECG — exclude long QT, Brugada, heart block (syncope mimics)

— MRI brain with epilepsy protocol is the standard — thin coronal T2/FLAIR through hippocampi, T1 volumetric, contrast if tumor/infection/MS suspected

— Non-contrast head CT acceptable in ED for acute trauma, hemorrhage, or when MRI unavailable, but always follow with MRI outpatient

— Findings: mesial temporal sclerosis (hippocampal atrophy + ↑FLAIR), focal cortical dysplasia, cavernoma, low-grade glioma, prior stroke, AVM

— Routine 20–30 min EEG within 24–48 hours of seizure increases yield (sleep-deprived EEG raises sensitivity further)

— Single normal EEG does NOT exclude epilepsy (sensitivity ~25–50% per study; up to 80–90% with repeat/sleep-deprived/ambulatory)

— Findings: focal epileptiform discharges, 3-Hz generalized spike-wave (absence), 4–6 Hz polyspike-wave (JME), photoparoxysmal response

First-seizure workup (outpatient, adult):

Imaging:

EEG:

AED levels (only if patient already on therapy): check at trough, particularly for phenytoin (correct for albumin), valproate, carbamazepine, phenobarbital. Newer agents (levetiracetam, lamotrigine) — levels less commonly used clinically.

CCS pearl: On first-seizure CCS case, advance the clock with MRI brain + EEG + BMP + ECG + pregnancy test ordered same visit; do not start AED before classification unless seizure recurs or risk is clearly high.

Board pearl: Lumbar puncture only if fever, immunocompromise, persistent altered mental status, or suspected SAH after negative CT.

Diagnostic Workup — Advanced or Confirmatory Studies

— Sleep-deprived EEG — second-line if routine EEG normal; sensitivity ~80%

— Ambulatory 24–72 hour EEG — captures interictal discharges over time

— Video-EEG monitoring (vEEG) in epilepsy monitoring unit (EMU) — gold standard for:

· Differentiating epileptic from psychogenic nonepileptic spells (PNES)

· Pre-surgical localization in drug-resistant epilepsy

· Characterizing seizure semiology

— 3T MRI epilepsy protocol — first re-look

— PET (FDG) — interictal hypometabolism in seizure focus

— Ictal SPECT — hyperperfusion at onset

— MEG, fMRI — language/motor mapping pre-resection

— Consider in early-onset, developmental delay, family history, or syndromic features (Dravet → SCN1A; GLUT1 deficiency; familial mesial temporal)

— Affects drug choice — e.g., avoid sodium channel blockers in Dravet/SCN1A

Repeat/extended EEG:

Advanced imaging in drug-resistant cases:

Drug-resistant epilepsy definition (ILAE): failure of 2 appropriately chosen, tolerated AEDs (mono- or combo) to achieve sustained seizure freedom → refer to epilepsy center for surgical evaluation. ~30% of epilepsy patients become drug-resistant.

Genetic testing:

Neuropsychological testing: baseline cognitive assessment before epilepsy surgery; also helpful when AED-related cognitive complaints arise.

Wada test or fMRI: language and memory lateralization before temporal lobectomy.

Key distinction: PNES vs epileptic seizures — PNES features include eyes closed during event (forced closure), side-to-side head movement, pelvic thrusting, prolonged duration (>2 min), waxing/waning intensity, lack of postictal confusion, normal lactate, and normal ictal EEG on vEEG. Many patients have both conditions (~10–20%).

Step 3 management: Failure of two appropriate AEDs = refer to comprehensive epilepsy center. Do not keep cycling through monotherapies indefinitely — delayed referral worsens surgical outcomes and quality of life.

Risk Stratification and First-Line Management Logic

— Start AED if any of:

· Abnormal MRI showing epileptogenic lesion

· Epileptiform discharges on EEG

· Nocturnal seizure

· Focal neurologic exam

· Status epilepticus as first presentation

· Patient preference based on occupational/driving needs

— Defer AED if: isolated seizure, normal MRI, normal EEG, identifiable transient trigger removed (sleep deprivation, alcohol binge) — recurrence ~30% over 2 years

— Focal epilepsy: levetiracetam, lamotrigine, carbamazepine, oxcarbazepine, lacosamide

— Generalized epilepsy (GTC, absence, myoclonic): valproate (highest efficacy but teratogenic), lamotrigine, levetiracetam, topiramate

— Absence specifically: ethosuximide first-line in children with absence only; valproate if also GTC

— JME: valproate (males), levetiracetam or lamotrigine (women of childbearing potential); avoid carbamazepine, phenytoin, oxcarbazepine — can worsen myoclonus/absence

— Childbearing potential → avoid valproate, topiramate, phenobarbital, phenytoin

— Obesity → avoid valproate, gabapentin (weight gain); consider topiramate, zonisamide (weight loss)

— Renal disease → avoid levetiracetam without dose adjustment

— Hepatic disease → avoid valproate

— Mood disorder → lamotrigine (mood-stabilizing), avoid levetiracetam (irritability/depression)

Decision to start an AED after first unprovoked seizure:

MESS trial takeaway: Immediate AED reduces 2-year recurrence (~30% → 20%) but does NOT improve long-term seizure-free outcomes at 5 years — informs shared decision-making.

Choose AED based on seizure type and patient factors:

Patient-specific modifiers:

Board pearl: Lamotrigine and levetiracetam are the most commonly chosen first-line broad-spectrum AEDs in adults due to favorable efficacy/tolerability and pregnancy data.

Step 3 management: Aim for monotherapy at the lowest effective dose; titrate slowly to balance efficacy and side effects.

Pharmacotherapy — First-Line Drug Regimens

— Broad spectrum (focal + generalized), renally cleared, minimal interactions

— Start 500 mg BID, titrate to 1000–1500 mg BID

— AE: irritability, depression, aggression ("Keppra rage") — counsel patients/family; pyridoxine 50–100 mg/day may mitigate

— No level monitoring needed clinically

— Broad spectrum, mood-stabilizing, best pregnancy safety profile

— Slow titration over 6–8 weeks to avoid Stevens-Johnson syndrome (start 25 mg/day)

— Valproate doubles lamotrigine levels (inhibits glucuronidation) → halve dose; OCPs and pregnancy lower levels

— AE: rash (≤10%, SJS/TEN <1%), insomnia, dizziness

— Most effective for generalized epilepsies, especially JME

— AE: weight gain, tremor, alopecia, hepatotoxicity, pancreatitis, thrombocytopenia, hyperammonemia, PCOS

— Teratogenic — neural tube defects, ~10% major malformations, lowest IQ in offspring → contraindicated in pregnancy/childbearing women unless no alternative

— Focal epilepsy; avoid in generalized epilepsy — worsens absence/myoclonic

— HLA-B*1502 testing in Asian patients before initiation (SJS risk)

— AE: hyponatremia (SIADH, more with oxcarbazepine), agranulocytosis, aplastic anemia, autoinduction, multiple CYP3A4 interactions

Levetiracetam (Keppra):

Lamotrigine:

Valproate:

Carbamazepine/oxcarbazepine:

Lacosamide: sodium channel modulator; clean side effect profile; check PR interval (can prolong)

Topiramate: weight loss, paresthesias, kidney stones, metabolic acidosis, cognitive slowing ("dopamax"), narrow-angle glaucoma; teratogenic (cleft palate, low birth weight)

Ethosuximide: absence only; AE — GI upset, hiccups, SLE-like reaction

Step 3 management: Titrate one drug to maximum tolerated dose before switching; if first AED fails, cross-titrate to a second monotherapy rather than immediately combining. Combine only after 2 failed monotherapies.

Board pearl: Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital, primidone, topiramate >200 mg) reduce efficacy of OCPs, warfarin, DOACs, statins, and many oncologic drugs — review every visit.

Refractory Epilepsy: Combination Therapy, Surgery, and Devices

— Combine drugs with different mechanisms (e.g., levetiracetam + lamotrigine)

— Avoid stacking sodium channel blockers (additive dizziness, diplopia)

— Watch for pharmacokinetic interactions (valproate ↑ lamotrigine)

— Anterior temporal lobectomy for mesial temporal sclerosis is the most successful resective surgery — 60–80% seizure-free at 1 year vs ~5% with continued medical therapy (Wiebe trial)

— Lesionectomy for cavernoma, focal cortical dysplasia, low-grade tumor

— Hemispherectomy for hemispheric syndromes (Rasmussen, Sturge-Weber)

— Corpus callosotomy palliative for drop attacks

— Vagus nerve stimulator (VNS): adjunctive, ~50% reduction in 50% of patients; AE — hoarseness, cough

— Responsive neurostimulation (RNS): intracranial closed-loop device

— Deep brain stimulation (DBS) of anterior thalamus — FDA approved for refractory focal epilepsy

— Ketogenic diet — highly effective in pediatric refractory epilepsy (Dravet, Lennox-Gastaut, GLUT1 deficiency); modified Atkins used in adults

When two appropriate monotherapies have failed → drug-resistant epilepsy — refer to comprehensive epilepsy center.

Rational polytherapy principles:

Adjunctive options: perampanel, brivaracetam, cenobamate, clobazam, zonisamide, vigabatrin (visual field defect — reserved for infantile spasms/refractory)

Epilepsy surgery:

Neuromodulation devices:

Dietary therapy:

Cannabidiol (Epidiolex): FDA-approved for Dravet, Lennox-Gastaut, tuberous sclerosis; monitor LFTs; interacts with clobazam (↑ N-desmethyl metabolite)

CCS pearl: On a refractory epilepsy CCS, the high-yield order is "Refer to comprehensive epilepsy center for surgical evaluation" — this is often the right answer over adding a 3rd AED.

Board pearl: Surgical candidacy is highest when MRI lesion + concordant EEG + concordant semiology + no eloquent cortex involvement. Delay to surgery averages 17–20 years — Step 3 expects you to refer early.

Special Populations — Elderly and Renal/Hepatic Impairment

— Stroke is the leading cause of new-onset epilepsy >60

— Other causes: neurodegenerative disease (Alzheimer, dementia with Lewy bodies), tumors, subdural hematoma

— Lower seizure threshold; lower AED doses often effective

— Preferred AEDs: lamotrigine and levetiracetam — efficacy comparable to carbamazepine but fewer side effects and interactions (VA Cooperative trial)

— Avoid: phenytoin (cognitive AEs, osteoporosis, gait/falls), phenobarbital (sedation), carbamazepine (hyponatremia, interactions), valproate (tremor, parkinsonism, thrombocytopenia)

— Sedating AEDs ↑ fall and fracture risk; check baseline DEXA and supplement vitamin D

— Review for QT-prolonging combinations

— Dose-reduce renally cleared AEDs: levetiracetam, gabapentin, pregabalin, topiramate, lacosamide, vigabatrin

— Levetiracetam: CrCl 50–80 → 500–1000 mg BID; <30 → 250–500 mg BID; HD → supplemental dose post-dialysis

— Lamotrigine, valproate, carbamazepine — minimal renal adjustment

— Avoid valproate (hepatotoxicity, hyperammonemia)

— Carbamazepine, phenytoin, phenobarbital — caution, hepatically metabolized

— Preferred: levetiracetam, gabapentin, pregabalin (renally cleared)

— Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital, primidone) and valproate ↑ osteoporosis risk via vitamin D metabolism

— Check 25-OH vitamin D yearly, DEXA in long-term users >5 years or postmenopausal women

— Supplement vitamin D 1000–2000 IU/day and calcium 1200 mg/day

Elderly considerations:

Polypharmacy and falls:

Renal impairment:

Hepatic impairment:

Bone health:

Step 3 management: A 75-year-old with new focal seizure post-stroke → start levetiracetam (renally adjusted) or lamotrigine — these are board-correct over phenytoin or carbamazepine.

Board pearl: Elderly patients with epilepsy have higher mortality than younger; aggressive seizure control + fall prevention + bone health are core outpatient management.

Special Populations — Pregnancy and Women of Childbearing Potential

— Goal: lowest effective dose of safest AED in monotherapy before conception

— Folic acid 0.4–4 mg/day (higher dose 4 mg if on valproate or carbamazepine, or prior NTD)

— Discuss contraception — enzyme-inducing AEDs reduce efficacy of estrogen-containing OCPs and progestin-only pills; recommend copper or levonorgestrel IUD, or depot if OCP needed

— Lamotrigine paradoxically decreases efficacy of OCPs and OCPs decrease lamotrigine levels — anticipate dose changes

— Valproate ~10% (neural tube defects, cardiac, facial, low IQ) — contraindicated unless absolutely no alternative

— Topiramate ~4% (cleft palate, low birth weight)

— Phenobarbital ~6%, phenytoin ~6%, carbamazepine ~5%

— Lamotrigine ~2%, levetiracetam ~2% — safest, preferred

— Continue AED — uncontrolled GTC seizures cause maternal trauma, fetal hypoxia, miscarriage

— Lamotrigine levels fall ~50% in pregnancy due to ↑ glucuronidation — monitor levels monthly and uptitrate; levetiracetam clearance also rises

— Vitamin K 10 mg/day in the last month if on enzyme-inducing AEDs (prevents neonatal hemorrhage)

— Enroll in North American AED Pregnancy Registry

— Taper AED back to pre-pregnancy dose over 2–3 weeks to avoid toxicity

— Breastfeeding is encouraged on most AEDs — lamotrigine, levetiracetam, carbamazepine compatible; phenobarbital and primidone may sedate infant

— Absence: ethosuximide

— JME: valproate (males), lamotrigine/levetiracetam (females)

— Lennox-Gastaut: valproate, lamotrigine, rufinamide, cannabidiol

— Infantile spasms (West): ACTH, vigabatrin (especially tuberous sclerosis)

Preconception counseling is mandatory for every female of childbearing potential with epilepsy:

AED teratogenic risk (major malformation rates):

During pregnancy:

Postpartum:

Pediatric epilepsy syndromes (brief):

Board pearl: A 28-year-old woman with JME planning pregnancy on valproate → switch to lamotrigine or levetiracetam preconception and add folate.

Complications and Adverse Outcomes

— Continuous seizure >5 min or ≥2 seizures without recovery

— Mortality 10–20%; aggressive management mandatory (see chunk 12)

— Incidence ~1/1000 patient-years in general epilepsy; ~1/150 in refractory

— Risk factors: uncontrolled GTC seizures (especially nocturnal), male sex, young adult, AED non-adherence, polytherapy

— Risk reduction: seizure freedom, supervised sleep, nocturnal monitoring, seizure-alert devices — counsel every patient on SUDEP, this is now standard of care

— Fractures (compression vertebral, posterior shoulder dislocation), burns, drowning (bathtub > pool), motor vehicle crashes, tongue laceration

— Aspiration pneumonia post-ictal

— Stevens-Johnson/TEN: lamotrigine, carbamazepine, phenytoin (HLA-B1502 in Asians, HLA-A3101 broadly)

— DRESS syndrome: carbamazepine, phenytoin, phenobarbital, lamotrigine — 2–8 weeks after start, fever, rash, eosinophilia, hepatitis

— Hepatotoxicity: valproate (especially <2 yo or POLG mutation), felbamate

— Aplastic anemia/agranulocytosis: carbamazepine, felbamate

— Hyponatremia: carbamazepine, oxcarbazepine — check Na⁺ if confusion or worsening seizures

— Suicidality: FDA black box on all AEDs — screen with PHQ-9 at every visit

— Cognitive AEs: topiramate, phenobarbital, zonisamide

— Visual field defects: vigabatrin (permanent — Amsler grid/perimetry q6mo)

Status epilepticus:

SUDEP (Sudden Unexpected Death in Epilepsy):

Injury from seizures:

AED-specific adverse effects:

Psychiatric comorbidity: 30–50% of epilepsy patients have depression or anxiety — undertreated, contributes to disability and SUDEP.

Bone disease: osteoporosis with chronic enzyme-inducing AEDs or valproate.

PCOS: valproate ↑ risk of menstrual irregularity, hyperandrogenism, weight gain.

Step 3 management: Counsel every epilepsy patient about SUDEP, driving restrictions, water safety, and AED adherence at the diagnostic visit — document the discussion.

Board pearl: New rash within 8 weeks of starting lamotrigine, carbamazepine, or phenytoin → stop the drug immediately, evaluate for SJS/DRESS.

When to Escalate Care — ICU, Consult, Inpatient Triage

— 0–5 min: ABCs, IV access ×2, fingerstick glucose, labs (BMP, Mg, Ca, CBC, LFTs, AED levels, tox screen, ABG), continuous ECG/EEG, supplemental O₂

— 5–20 min (first-line): IV lorazepam 0.1 mg/kg (max 4 mg) ×1–2 doses, or IM midazolam 10 mg if no IV, or rectal/buccal diazepam

— 20–40 min (second-line): IV levetiracetam 60 mg/kg (max 4500 mg) OR fosphenytoin 20 mg PE/kg OR valproate 40 mg/kg — ESETT trial showed equivalence

— >40 min (refractory SE): intubate, ICU, midazolam, propofol, or pentobarbital infusion; continuous EEG

— >24 h on infusion = super-refractory SE — ketamine, immunotherapy if autoimmune suspected

— Status epilepticus or cluster of seizures

— New focal neurologic deficit

— Suspected acute structural cause (stroke, hemorrhage, tumor, meningitis)

— First seizure in immunocompromised patient

— Hyponatremia <125, hypoglycemia, eclampsia

— Possible PNES requiring vEEG diagnosis (elective EMU)

— Failure of 1–2 AEDs → neurology/epilepsy referral

— Pregnancy or pregnancy planning

— Suspected drug-resistant epilepsy → comprehensive epilepsy center

— Status epilepticus → ICU + neurology

Status epilepticus pathway (CCS-ready):

Indications for hospital admission from clinic/ED:

Specialist consultation triggers:

CCS pearl: In a status epilepticus CCS case, the 5-minute order is lorazepam IV + fingerstick glucose + thiamine + IV access + airway assessment, followed immediately by a loading dose AED without waiting for the benzo to "work." Time is brain.

Step 3 management: Patients with breakthrough seizure on a previously stable regimen → check adherence first (most common cause), then AED level, then look for triggers (sleep, alcohol, infection, new drug interaction, electrolyte derangement) before escalating dose.

Key Differentials — Same-Category (Paroxysmal Neurologic) Causes

— ~20–30% of patients referred to EMU; often coexist with epilepsy

— Features: longer duration, asymmetric/asynchronous movements, eyes closed forcibly, pelvic thrusting, side-to-side head movement, preserved consciousness during convulsion, no postictal confusion, normal ictal EEG, normal lactate

— Associated with psychiatric trauma, abuse history

— Treatment: CBT, not AEDs; communicate diagnosis carefully without dismissing

— Brief tonic posturing or myoclonic jerks (<15 sec) during cerebral hypoperfusion

— Prodrome of lightheadedness, pallor, sweating; rapid recovery without postictal phase

— Tilt-table test, Holter, ECG to identify cardiac cause

— Basilar migraine, hemiplegic migraine — auras can mimic focal seizures; headache prominent

— Migralepsy — migraine-triggered seizure

— Sudden anterograde amnesia lasting hours, intact personal identity, no other neuro deficits; not a seizure

— Negative phenomena (weakness, numbness, aphasia); seizures cause positive phenomena (jerking, tingling)

— TIA lacks postictal confusion; sudden onset, vascular distribution

— REM sleep behavior disorder, parasomnias (sleepwalking, night terrors), narcolepsy with cataplexy — differentiate via polysomnography

— Paroxysmal kinesigenic dyskinesia, tics, myoclonus from metabolic causes

— Autonomic surge, derealization, fear; can mimic temporal lobe aura but no LOC or amnesia

Psychogenic nonepileptic seizures (PNES):

Syncope (convulsive):

Migraine variants:

Transient global amnesia (TGA):

Transient ischemic attack:

Sleep disorders:

Movement disorders:

Panic attacks:

Key distinction: Positive phenomena (jerking, tingling, visual scintillations) favor seizure/migraine; negative phenomena (weakness, numbness, vision loss) favor TIA/stroke.

Board pearl: Eyes closed during a convulsion = PNES until proven otherwise; eyes open = epileptic seizure (>95% specificity).

Key Differentials — Other-Category (Systemic) Causes

— Hypoglycemia — fingerstick at every seizure presentation

— Hyponatremia <125 mEq/L — correct slowly (≤8 mEq/24h to avoid osmotic demyelination)

— Hypocalcemia, hypomagnesemia

— Uremia — uremic encephalopathy and dialysis disequilibrium

— Hepatic encephalopathy

— Hyperammonemia (valproate-induced or from urea cycle defect)

— Bupropion (dose-dependent), tramadol, clozapine, theophylline, isoniazid (give pyridoxine), fluoroquinolones, beta-lactams in renal failure (cefepime neurotoxicity), lidocaine, meperidine (normeperidine), MDMA, cocaine, methamphetamine

— Alcohol withdrawal — peak 12–48 h; treat with benzodiazepines, NOT chronic AED

— Benzodiazepine withdrawal

— Barbiturate withdrawal

— Meningitis, encephalitis (HSV → temporal lobe seizures), neurocysticercosis (most common cause worldwide), brain abscess, HIV CNS opportunistic infection (toxoplasmosis, PML, CMV)

— Anti-NMDA receptor encephalitis (young women, ovarian teratoma, psychiatric prodrome, seizures, dyskinesias)

— LGI1, CASPR2 — limbic encephalitis, faciobrachial dystonic seizures

— Treat with IVIG/steroids/PLEX, rituximab; remove underlying tumor

Metabolic/toxic provoked seizures (do NOT treat as epilepsy):

Drug-induced seizures (provoked, treat the cause):

Withdrawal seizures:

Infectious:

Autoimmune encephalitis:

Structural: stroke, intracerebral hemorrhage, subdural hematoma, tumor (glioma, meningioma, metastasis), AVM, cavernoma, mesial temporal sclerosis

Eclampsia: seizure in pregnant patient >20 weeks → IV magnesium sulfate, delivery, BP control; NOT a chronic epilepsy

Step 3 management: A first-time seizure with serum Na⁺ 118 → correct sodium; do not start an AED. A seizure in a chronic alcoholic 24 h after last drink → benzodiazepines and supportive care; do not start an AED.

Board pearl: Autoimmune encephalitis is increasingly tested — young patient with new seizures + psychiatric symptoms + memory deficits → check anti-NMDA antibodies in serum and CSF, pelvic US for teratoma.

Secondary Prevention / Discharge Plan / Long-Term Management

— Non-adherence is the #1 cause of breakthrough seizures — pill organizers, phone reminders, once-daily dosing when possible

— Avoid abrupt discontinuation — taper over weeks-months under supervision

— Sleep hygiene — sleep deprivation triggers seizures across all syndromes, especially JME

— Alcohol moderation; avoid binge drinking

— Identify and avoid medication interactions (review at every visit)

— Manage fever in pediatric patients with febrile seizures

— Photosensitivity (5%): avoid strobe lights, screen flicker

— Driving: state-specific seizure-free intervals (typically 3–6 months in most US states); mandatory reporting in CA, DE, NV, NJ, OR, PA — know your state

— Bathing: showers preferred over baths; never swim alone

— Avoid heights, heavy machinery, contact sports during uncontrolled phase

— Pregnancy planning (chunk 10)

— Identification bracelet

— Screen for depression and anxiety annually (PHQ-9, GAD-7); treat with SSRI (sertraline preferred — low seizure risk; avoid bupropion)

— Cardiovascular risk modification (stroke prevention) in elderly

— Bone health: vitamin D, calcium, DEXA

— 2 years seizure-free → consider taper if normal EEG, normal MRI, single seizure type, monotherapy at low dose, patient preference

— Recurrence risk after withdrawal ~30–50%; counsel accordingly

— Do NOT withdraw JME — lifelong AED typically required

AED adherence is the single most important predictor of seizure control:

Trigger avoidance:

Lifestyle counseling:

Comorbidity management:

AED withdrawal consideration:

Vaccinations: annual influenza; pneumococcal per ACIP if other risk factors.

Step 3 management: At every clinic visit, document: seizure diary count, adherence, side effects, mood screen, drug interactions, driving status, contraception plan, SUDEP counseling refresh.

Board pearl: After 2 years seizure-free with a clean workup, shared decision-making AED taper is reasonable for many syndromes — but never JME, never severe symptomatic epilepsies.

Follow-Up, Monitoring Parameters, and Counseling

— After AED initiation: 2–4 weeks for tolerability check

— Stable on AED: every 3–6 months initially, then every 6–12 months once seizure-free

— Seizure diary or app at every visit — drives titration and surgical referral decisions

— Valproate: CBC, LFTs, ammonia at baseline, 1 month, then every 6–12 months

— Carbamazepine: CBC, Na⁺, LFTs at baseline, 1 month, then every 6–12 months

— Phenytoin: trough levels, albumin (correct level), LFTs

— Lamotrigine, levetiracetam: routine labs not required; levels only if breakthrough seizure or pregnancy

— Topiramate: bicarbonate (metabolic acidosis), watch for kidney stones

— Vigabatrin: visual field testing every 3 months (permanent visual field constriction)

— 25-OH vitamin D yearly on enzyme-inducing AEDs or valproate

— DEXA every 2–5 years in long-term users, postmenopausal women, elderly

— Document seizure-free interval at each visit

— Provide written documentation for DMV when requested

— Coordinate with occupational health for safety-sensitive jobs

— Seizure first aid (turn on side, time the seizure, do NOT put anything in mouth, call 911 if >5 min or repeated)

— Medication adherence and what to do if a dose is missed

— SUDEP awareness and supervised sleep when possible

— Pregnancy planning and contraception

— Water safety, fall precautions

— Vocational rehab for refractory epilepsy

— Epilepsy Foundation resources, support groups

— School accommodations (504 plan) for pediatric patients

Follow-up cadence:

Laboratory monitoring:

Bone health monitoring:

Mood screening: PHQ-9 and GAD-7 annually; immediate evaluation if suicidality endorsed (AED black box).

Driving and occupational counseling:

Patient education topics (revisit at least annually):

Rehabilitation and support:

Step 3 management: Breakthrough seizure on a stable regimen → check adherence + AED level + recent infections/medications + sleep/alcohol/stress before increasing dose.

Board pearl: Patients on lamotrigine in pregnancy need monthly level monitoring with dose uptitration to maintain seizure control; reduce postpartum to avoid toxicity.

Ethical, Legal, and Patient Safety Considerations

— Every US state restricts driving after a seizure; seizure-free interval typically 3–6 months (3 in some states, 12 in others)

— Mandatory physician reporting in California, Delaware, Nevada, New Jersey, Oregon, Pennsylvania — know if your state requires it

— In other states, the patient is obligated to self-report; document your counseling clearly in the chart

— Failure to counsel = potential liability if patient causes harm while driving

— AED initiation requires informed consent on teratogenicity (especially valproate in women of childbearing potential — valproate REMS-like risk discussion mandatory)

— Document discussion of SJS/DRESS risk for high-risk drugs

— Discuss SUDEP at diagnosis — concealment is no longer acceptable; AAN/AES guidelines support transparent counseling

— Postictal patients lack capacity for major decisions; defer non-urgent consents until cleared

— Patients with frequent seizures may need surrogate decision-maker for high-stakes decisions

— Balance maternal seizure control against teratogenicity; never abruptly stop an AED in pregnancy due to fear of teratogenicity — uncontrolled seizures are more dangerous

— Discuss reproductive choices preconception, not after pregnancy confirmed

— Hospital discharge after first seizure or status: ensure outpatient neurology follow-up within 2 weeks, AED prescription filled before discharge, driving counseling documented, medication reconciliation, return precautions

— Pediatric-to-adult transition: structured handoff at age 18–21 for syndromes like JME, absence; gaps in care drive non-adherence and breakthrough seizures

— AED formulary substitutions: generic-to-generic or brand-to-generic switches can cause breakthrough seizures (especially narrow-therapeutic-index drugs phenytoin, carbamazepine); request "dispense as written" when stable

— Suspected child abuse if seizures from inflicted head trauma

— Workplace injury reporting per OSHA

Driving laws:

Informed consent:

Capacity and autonomy:

Pregnancy ethics:

Transitions of care (Step 3 high-yield):

Mandatory reporting:

Step 3 management: On every epilepsy discharge, the safe-handoff bundle is AED Rx + neurology follow-up appointment + driving restriction documented + SUDEP counseling + emergency action plan.

Board pearl: The most commonly tested epilepsy ethics scenario is the patient who insists on driving despite recent seizures — counsel, document, and follow state law.

High-Yield Associations and Rapid-Fire Clinical Facts

— Carbamazepine SJS — HLA-B*1502 (Han Chinese, Thai, Filipino)

— Allopurinol SJS — HLA-B*5801

— Abacavir hypersensitivity — HLA-B*5701

— Vigabatrin → permanent visual field defect

— Ethosuximide → SLE-like syndrome, hiccups

— Topiramate → angle-closure glaucoma, kidney stones, oligohidrosis

— Felbamate → aplastic anemia, hepatic failure (restricted use)

— Phenytoin → gingival hyperplasia, hirsutism, cerebellar ataxia, megaloblastic anemia (folate), purple glove syndrome

— Phenytoin: zero-order kinetics above therapeutic range → small dose change → large level change

— Valproate inhibits lamotrigine glucuronidation → halve dose

— Carbamazepine autoinduces its own metabolism over 2–4 weeks

Juvenile myoclonic epilepsy (JME): teen onset, morning myoclonus, GTC, sleep deprivation/alcohol triggers, 4–6 Hz polyspike-wave on EEG, lifelong treatment, valproate most effective (lamotrigine/levetiracetam in women)

Mesial temporal sclerosis: history of febrile seizures, déjà vu/olfactory aura, focal impaired awareness seizures, hippocampal atrophy on MRI, best surgical outcomes

Lennox-Gastaut syndrome: multiple seizure types, slow spike-wave <2.5 Hz, cognitive impairment, refractory — valproate, lamotrigine, rufinamide, cannabidiol

West syndrome (infantile spasms): age 4–8 months, hypsarrhythmia, developmental regression — ACTH or vigabatrin (vigabatrin first-line if tuberous sclerosis)

Dravet syndrome: SCN1A mutation, fever-triggered prolonged seizures in infancy — avoid sodium channel blockers (carbamazepine, phenytoin worsen); use valproate, clobazam, stiripentol, cannabidiol, fenfluramine

Rolandic epilepsy (BECTS): age 6–10, nocturnal facial twitching with drooling, centrotemporal spikes, remits by adolescence, often no treatment needed

Drug ↔ HLA:

AED zebras:

Pharmacokinetic gotchas:

Board pearl: "Morning jerks + GTC after sleep deprivation in a teen" = JME — instant recognition is worth a guaranteed Step 3 point.

Board Question Stem Patterns

Stem 1 — First-seizure adult: "32 yo with witnessed GTC, normal exam, normal labs, normal MRI, normal EEG. Best next step?" → Shared decision-making, no AED required, counsel on driving (~30% recurrence)

Stem 2 — JME: "17 yo with morning jerks, recent GTC after staying up all night. EEG 4–6 Hz polyspike-wave." → Valproate (male) or levetiracetam/lamotrigine (female of childbearing potential); avoid carbamazepine

Stem 3 — Absence: "8 yo with frequent staring spells, 3-Hz spike-wave on EEG, hyperventilation provokes." → Ethosuximide

Stem 4 — Pregnant epileptic: "26 yo on valproate, plans pregnancy." → Switch to lamotrigine or levetiracetam preconception, add high-dose folate

Stem 5 — Elderly post-stroke: "75 yo, focal seizure 4 months after MCA stroke." → Levetiracetam (renally dosed) or lamotrigine; avoid phenytoin

Stem 6 — Provoked seizure: "55 yo alcoholic, GTC 24 h after last drink, Na⁺ 138, glucose normal." → Benzodiazepines, supportive care; no chronic AED

Stem 7 — Status epilepticus: "Seizure >10 min in ED." → IV lorazepam, then IV levetiracetam/fosphenytoin/valproate; intubate if refractory

Stem 8 — Lamotrigine rash: "5 weeks after starting lamotrigine, diffuse rash with mucosal involvement, fever." → Stop lamotrigine immediately, evaluate for SJS, supportive care

Stem 9 — Refractory epilepsy: "Failed levetiracetam and lamotrigine at adequate doses." → Refer to comprehensive epilepsy center for surgical evaluation

Stem 10 — Carbamazepine + Asian patient: "Han Chinese patient starting carbamazepine." → Check HLA-B*1502 first

Stem 11 — PNES: "Eyes closed during convulsion, side-to-side head movement, normal ictal EEG." → Refer to therapy/CBT, do not add AED

Stem 12 — Hyponatremia on AED: "Confused on oxcarbazepine, Na⁺ 122." → Switch AED, fluid restriction

Stem 13 — OCP failure on AED: "Pregnancy on OCPs while taking carbamazepine." → Enzyme induction reduces OCP efficacy — switch to copper or LNG IUD

Step 3 management: Pattern-match stem → recognize syndrome → select AED that is both mechanistically appropriate and patient-safe (pregnancy, age, renal, hepatic). The right answer is rarely the "newest" drug — it's the board-correct drug.

Board pearl: When in doubt on Step 3 epilepsy questions, levetiracetam is rarely wrong as a first-line broad-spectrum choice.

One-Line Recap

Outpatient epilepsy management is the longitudinal pairing of a correctly classified seizure type with the safest effective antiepileptic drug at the lowest effective dose, plus relentless attention to adherence, triggers, pregnancy planning, driving safety, SUDEP counseling, and timely referral when two appropriate monotherapies fail.

Diagnose then classify: Epilepsy = ≥2 unprovoked seizures, OR 1 seizure with high recurrence risk (lesion on MRI or epileptiform EEG); always exclude provoked causes (hypoglycemia, hyponatremia, withdrawal, drugs, eclampsia) before committing to lifelong AED therapy.

Drug choice is driven by seizure type + patient: Focal → levetiracetam, lamotrigine, lacosamide, carbamazepine; Generalized → valproate (avoid in pregnancy), lamotrigine, levetiracetam; Absence → ethosuximide; never use sodium channel blockers in generalized epilepsy or Dravet.

Counsel every visit: adherence, driving (3–6 mo seizure-free per state), contraception/pregnancy planning, SUDEP awareness, sleep, alcohol, water safety, mood (suicidality black box), bone health, drug interactions (enzyme inducers).

Escalate appropriately: failure of 2 appropriate AEDs = drug-resistant epilepsy → refer to comprehensive epilepsy center for surgical evaluation; status epilepticus = IV benzo + IV second-line AED (levetiracetam/fosphenytoin/valproate) + ICU if refractory.

Board pearl: The single highest-yield reflex in Step 3 epilepsy questions is to match the syndrome to the drug, scrub for pregnancy risk, and refuse to escalate before checking adherence and triggers — this answers more stems than any other pattern.