Pediatrics (System-Integrated)

Pediatric epilepsy syndromes: overview

Clinical Overview and When to Suspect Pediatric Epilepsy Syndromes

— Stereotyped events at a characteristic age (neonate, infant, toddler, school-age, adolescent)

— Developmental regression or plateau with seizures

— Multiple seizure types in the same child

— Family history of epilepsy or febrile seizures

— Specific triggers: sleep, awakening, photic stimulation, fever, hyperventilation

— Neonatal: benign familial neonatal epilepsy, early infantile epileptic encephalopathy (Ohtahara)

— Infancy: infantile epileptic spasms syndrome (West), Dravet

— Childhood: Lennox-Gastaut, childhood absence epilepsy (CAE), self-limited epilepsy with centrotemporal spikes (SeLECTS, formerly BECTS/Rolandic), Landau-Kleffner

— Adolescence: juvenile myoclonic epilepsy (JME), juvenile absence epilepsy

Definition: Epilepsy = ≥2 unprovoked seizures >24h apart, OR 1 unprovoked seizure with ≥60% recurrence risk (e.g., abnormal EEG, remote symptomatic lesion), OR diagnosis of a defined epilepsy syndrome.

Pediatric epilepsy syndromes are age-dependent constellations of seizure type(s), EEG pattern, exam findings, etiology, and prognosis. Recognition drives drug choice and prognostic counseling — far more than seizure semiology alone.

When to suspect a syndrome (not just "a seizure"):

Core syndromes the Step 3 examinee must recognize cold:

Epidemiology: ~1% of children have epilepsy; 60–70% become seizure-free on monotherapy; many self-limited syndromes remit with puberty.

Step 3 management: When a child presents with a "first seizure," your workflow is: (1) confirm it was a seizure (vs syncope, breath-holding, parasomnia, tics), (2) identify provoking factors (fever, trauma, hyponatremia, hypoglycemia), (3) classify seizure type, (4) then ask: does this fit a syndrome? Syndrome classification changes AED selection (e.g., avoid sodium channel blockers in Dravet) and the decision to treat at all (SeLECTS often warrants observation).

Board pearl: A single unprovoked seizure with a normal EEG and normal MRI in a developmentally normal child = observation, no AED.

Presentation Patterns and Key History

— Time of day (awakening → JME; sleep → SeLECTS, LGS tonic)

— Triggers (fever → Dravet; hyperventilation → CAE; photic/sleep loss → JME)

— Developmental trajectory (regression → West, Dravet, LGS, LKS)

— Family history of similar events

Infantile epileptic spasms syndrome (West): 3–12 months. Clusters of brief flexor/extensor spasms ("jackknife"/"Salaam") on awakening; parents often think colic or startle. Triad: spasms + hypsarrhythmia on EEG + developmental regression.

Dravet syndrome: Onset 6 months. Prolonged febrile hemiclonic seizures in a previously normal infant, often triggered by hot baths, fever, vaccination. Multiple seizure types emerge by age 2 with developmental slowing.

Lennox-Gastaut syndrome (LGS): 3–8 years. Multiple seizure types — tonic (especially nocturnal), atonic ("drop attacks"), atypical absence — plus cognitive impairment. Often evolves from West syndrome.

Childhood absence epilepsy (CAE): 4–10 years. Daily, brief (5–15 sec) staring spells with behavioral arrest, no postictal phase, provoked by hyperventilation. Teacher complaints of "daydreaming." Normal development.

SeLECTS (Rolandic): 3–13 years. Nocturnal focal seizures with unilateral facial twitching, drooling, dysarthria, hemibody tonic-clonic activity; child often awake and aware of mouth involvement but unable to speak. Remits by puberty.

Juvenile myoclonic epilepsy (JME): 12–18 years. Early-morning myoclonic jerks (drops cereal spoon, "clumsy mornings"), generalized tonic-clonic seizures on awakening, and absences. Triggers: sleep deprivation, alcohol, photic stimulation.

Landau-Kleffner: 3–7 years. Acquired auditory verbal agnosia (loss of receptive language) with subclinical or overt seizures; EEG worse in slow-wave sleep.

Key history questions:

Key distinction: Daydreaming (can be interrupted by touch, no EEG change) vs CAE (cannot be interrupted, 3-Hz generalized spike-and-wave on EEG with hyperventilation). Always provoke with 3 minutes of hyperventilation in clinic when suspecting absence.

Physical Exam Findings and Neurodevelopmental Assessment

— Ash-leaf macules, shagreen patch, facial angiofibromas → tuberous sclerosis (major cause of infantile spasms)

— Café-au-lait macules ≥6, axillary freckling → NF1

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

— Hypomelanotic whorls along Blaschko lines → hypomelanosis of Ito

— Hypotonia + delayed milestones → encephalopathy (West, Dravet, LGS)

— Focal deficits, asymmetric reflexes, hemiparesis → structural lesion, cortical dysplasia, prior stroke

— Ataxia, tremor → Dravet (later course), Angelman, mitochondrial disease

— Visual fixation/tracking deficits → cortical visual impairment from encephalopathy

— Hyperventilation 3 min → induces absence in CAE (high yield)

— Photic stimulation during EEG → JME, photosensitive epilepsies

General principles: Between seizures, most children with self-limited syndromes (CAE, SeLECTS, JME) have a completely normal neurologic exam. Abnormal exam findings push you toward symptomatic/encephalopathic syndromes (West, LGS, Dravet) or a structural etiology.

Skin exam — neurocutaneous clues:

Head circumference: Microcephaly suggests congenital infection, malformation, or genetic encephalopathy; macrocephaly suggests megalencephaly, leukodystrophy, or glutaric aciduria.

Dysmorphology: Subtle features may indicate Angelman (happy demeanor, ataxia, seizures), Rett (hand-wringing, regression in girls), or chromosomal microdeletion.

Neurologic exam:

Developmental assessment: Document language, motor, social milestones at every visit. Regression is a red flag demanding urgent workup (MRI, metabolic, genetic).

Provocative maneuvers in clinic:

Board pearl: A toddler with infantile spasms — always examine the skin under a Wood's lamp for ash-leaf macules; tuberous sclerosis is found in 10–25% of West syndrome and changes both treatment (vigabatrin first-line in TSC) and family counseling (autosomal dominant, screen parents).

Step 3 management: Document a Vineland or ASQ-3 baseline at diagnosis — needed for school IEP/504 planning and to track treatment response.

Diagnostic Workup — Initial Labs, Imaging, and EEG

— Glucose, sodium, calcium, magnesium in every child; add ammonia, lactate, urine ketones in infants or with regression

— Toxicology screen in adolescents (cocaine, amphetamines, bupropion, TCAs)

— LP only if meningitis suspected or infant <6 months with fever and seizure

— CT head emergently only if focal deficit, prolonged postictal state, trauma, or VP shunt — otherwise defer to outpatient MRI

— Obtain in all children with unprovoked seizure or suspected epilepsy syndrome

— Standard 20–30 min awake + drowsy + sleep EEG with hyperventilation and photic stimulation

— If initial EEG normal but clinical suspicion high → sleep-deprived EEG or 24-hr ambulatory/video EEG

— Syndrome-defining EEG patterns:

– Hypsarrhythmia (chaotic high-voltage, multifocal spikes) → West

– 3-Hz generalized spike-and-wave → CAE

– 4–6 Hz polyspike-and-wave → JME

– Slow spike-and-wave <2.5 Hz + paroxysmal fast activity in sleep → LGS

– Centrotemporal spikes activated by drowsiness/sleep → SeLECTS

– Electrical status epilepticus in sleep (ESES/CSWS) → Landau-Kleffner

— Indicated for all focal-onset epilepsies, abnormal exam, developmental regression, or AED-refractory seizures

— Not required for clearly defined idiopathic generalized syndromes (CAE, JME) with normal exam

— Looks for: mesial temporal sclerosis, focal cortical dysplasia, tubers, polymicrogyria, prior infarct, tumor

First unprovoked seizure — initial workup priorities:

EEG — the central test:

MRI brain (epilepsy protocol with thin coronal cuts):

CCS pearl: When ordering EEG, specify "with hyperventilation, photic stimulation, awake and sleep" — a routine EEG without provocation can miss CAE and JME and yields a falsely reassuring read.

Board pearl: Never delay treatment of suspected infantile spasms waiting for MRI — initiate ACTH/vigabatrin once hypsarrhythmia is confirmed; every week of untreated spasms worsens developmental outcome.

Diagnostic Workup — Advanced and Confirmatory Studies

— Epilepsy gene panel (next-gen sequencing, 100–500 genes) first-line for infantile-onset seizures, drug-resistant epilepsy, developmental and epileptic encephalopathies

— Chromosomal microarray if dysmorphic features, intellectual disability, or autism overlap

— Whole-exome sequencing if panel negative and clinical suspicion remains

— Specific high-yield genes:

– SCN1A → Dravet syndrome (sodium channel blockers worsen seizures — avoid carbamazepine, phenytoin, lamotrigine)

– CDKL5, ARX, STXBP1 → early infantile encephalopathies

– KCNQ2/3 → benign familial neonatal seizures

– GLUT1 (SLC2A1) → glucose transporter deficiency; ketogenic diet is treatment

– PCDH19 → cluster seizures in girls

— Serum amino acids, urine organic acids, acylcarnitine profile, ammonia, lactate

— CSF glucose:serum ratio (low in GLUT1 deficiency, <0.4)

— CSF neurotransmitters, pyridoxine trial (pyridoxine-dependent epilepsy)

— Indications: distinguish epileptic from non-epileptic events, characterize seizure semiology, presurgical localization, classify drug-resistant epilepsy

— Captures psychogenic non-epileptic seizures — common in adolescents, often with comorbid trauma/anxiety

— 3T MRI epilepsy protocol, FDG-PET (interictal hypometabolism in epileptogenic zone), ictal SPECT, MEG, functional MRI for language/motor mapping, Wada test in older children

Genetic testing — now standard of care for early-onset and refractory epilepsies:

Metabolic workup (if regression, hypoglycemia, lactic acidosis, infant onset, refractory):

Video-EEG monitoring (inpatient epilepsy monitoring unit):

Advanced presurgical imaging (for drug-resistant focal epilepsy):

Key distinction: Drug-resistant epilepsy = failure of 2 appropriately chosen, adequately dosed AEDs (ILAE definition). At that point, refer to a comprehensive epilepsy center — do not cycle through endless drugs. Surgical candidacy and dietary therapy must be considered.

Step 3 management: For any child <2 years with unexplained epilepsy, send SCN1A and a broad gene panel — diagnosis of Dravet within the first year prevents harmful sodium-channel-blocker exposure and qualifies the child for fenfluramine, stiripentol, and cannabidiol.

Risk Stratification and First-Line Management Logic

— Treat if: abnormal EEG with epileptiform discharges, abnormal MRI (structural lesion), abnormal neurologic exam, nocturnal seizure, or syndrome diagnosed

— Observe if: single unprovoked seizure, normal EEG, normal MRI, normal exam, no family history — recurrence risk ~30–40%, and early AED does not change long-term prognosis

— Always treat: infantile spasms, Dravet, LGS, status epilepticus presentation

— Focal epilepsies (SeLECTS, structural focal): oxcarbazepine, levetiracetam, lamotrigine

— Generalized epilepsies (CAE, JME, JAE): ethosuximide (absence only), valproate, lamotrigine, levetiracetam

— Infantile spasms: ACTH or oral high-dose prednisolone; vigabatrin first-line if TSC

— Dravet: valproate + clobazam first-line; add stiripentol, fenfluramine, or cannabidiol; AVOID sodium channel blockers

— LGS: valproate first; add lamotrigine, rufinamide, clobazam, cannabidiol, or felbamate

— Absence/JME: carbamazepine, oxcarbazepine, phenytoin, gabapentin, tiagabine — worsen generalized seizures

— Dravet: lamotrigine, carbamazepine, phenytoin

— Avoid valproate in girls of childbearing potential when alternatives exist (teratogenicity, polycystic ovaries)

— Monotherapy, lowest effective dose, no breakthrough seizures, minimal side effects

— ~50% seizure-free on first drug; ~13% on second; only ~4% on third → refer to epilepsy center after 2 failures

Decision 1 — Do we treat after a first seizure?

Decision 2 — Match the drug to the syndrome (NOT just the seizure type):

Decision 3 — Drugs to AVOID by syndrome:

Treatment goals:

Board pearl: CAE first-line is ethosuximide (superior efficacy + best cognitive profile vs valproate/lamotrigine per landmark CAE trial). Only use valproate if generalized tonic-clonic seizures coexist.

Step 3 management: Counsel families at diagnosis on seizure first aid (side position, time the seizure, nothing in mouth, call 911 if >5 min), driving rules for teens, swimming with a buddy, and avoiding sleep deprivation/alcohol.

Pharmacotherapy — First-Line Drug Regimens

— Dose: 10–15 mg/kg/day → titrate to 20–40 mg/kg/day divided BID

— Side effects: GI upset (take with food), hiccups, drowsiness, rare aplastic anemia/SJS

— Monitor: CBC at baseline and periodically; does not cover generalized tonic-clonic seizures

— Dose: 10–15 mg/kg/day → 20–60 mg/kg/day divided BID-TID

— Side effects: hepatotoxicity (boxed warning, esp. <2 yo and POLG mutations), pancreatitis, hyperammonemia, thrombocytopenia, weight gain, hair loss, tremor, PCOS, teratogen (neural tube defects, decreased IQ)

— Monitor: LFTs, CBC, ammonia, level (50–100 mcg/mL)

— Avoid in girls of reproductive age and infants with suspected mitochondrial disease

— Dose: 10 mg/kg/day → 20–60 mg/kg/day divided BID

— Side effects: behavioral irritability, aggression, depression (especially in children with baseline behavioral concerns); pyridoxine 50–100 mg/day may mitigate

— No drug interactions, no level monitoring needed → favored in polypharmacy

— Slow titration mandatory (5 weeks) to reduce SJS/TEN risk; risk higher with concurrent valproate (inhibits glucuronidation — halve lamotrigine dose)

— Side effects: rash, insomnia, headache

— Dose: 8–10 mg/kg/day → 30–45 mg/kg/day

— Side effects: hyponatremia (SIADH), rash, diplopia; HLA-B*1502 screening in Asian ancestry

— ACTH 150 U/m²/day IM × 2 weeks then taper; or prednisolone 40–60 mg/day × 2 weeks

— Monitor: BP, glucose, electrolytes, infection, weight gain, irritability

— Irreversible peripheral visual field constriction in 30–50% — baseline and serial ophthalmology/visual field testing required (REMS program)

Ethosuximide (CAE first-line)

Valproate (broad-spectrum: JME, LGS, mixed)

Levetiracetam (broad-spectrum, easy to use)

Lamotrigine (broad-spectrum; JME maintenance, LGS, focal)

Oxcarbazepine (focal; SeLECTS if treating)

ACTH or high-dose prednisolone (infantile spasms)

Vigabatrin (infantile spasms, especially TSC)

Board pearl: Any new rash on lamotrigine, oxcarbazepine, carbamazepine, phenytoin, or phenobarbital → stop immediately and evaluate for SJS/TEN/DRESS.

Non-Pharmacologic and Advanced Therapies

— First-line treatment for GLUT1 deficiency and pyruvate dehydrogenase deficiency — bypasses defective glucose metabolism

— Strong evidence in LGS, Dravet, infantile spasms refractory to ACTH/vigabatrin, Doose syndrome

— Variants: classic 4:1 ratio, modified Atkins (easier for adolescents), low-glycemic-index treatment

— Monitor: growth, lipids, urine ketones, renal stones (citrate prophylaxis), carnitine, vitamin D, selenium

— Contraindicated in fatty acid oxidation defects, pyruvate carboxylase deficiency, porphyria

— Implantable device; adjunct for drug-resistant focal or generalized epilepsy when surgery not feasible

— ~50% achieve ≥50% seizure reduction; benefit grows over 1–2 years

— Side effects: hoarseness, cough, dyspnea with stimulation

— MRI compatible only with specific protocols

— Curative intent when an epileptogenic focus is identified and resectable without unacceptable deficit

— Best outcomes: mesial temporal lobectomy for hippocampal sclerosis (60–80% seizure-free), lesionectomy for focal cortical dysplasia, tumor, cavernoma

— Hemispherectomy for catastrophic unilateral epilepsies (Rasmussen encephalitis, Sturge-Weber, large dysplasia, perinatal infarct)

— Corpus callosotomy: palliative for drop attacks in LGS

Ketogenic diet (high-fat, low-carb, adequate-protein):

Vagus nerve stimulation (VNS):

Responsive neurostimulation (RNS) and deep brain stimulation (DBS): Emerging for adolescents/adults with focal seizures from eloquent cortex or bilateral foci.

Resective epilepsy surgery:

Cannabidiol (Epidiolex): FDA-approved for Dravet, LGS, and TSC-associated seizures ≥1 year old. Monitor LFTs; interacts with clobazam (raises N-desmethylclobazam → sedation).

Fenfluramine: FDA-approved for Dravet and LGS; requires baseline and serial echocardiograms (valvulopathy/pulmonary HTN risk per REMS).

Step 3 management: Refer to a Level 4 epilepsy center after 2 failed appropriately chosen AEDs — early surgical evaluation in lesional epilepsy preserves development and cognition. Do not let a child accumulate 5–10 years of refractory seizures before referral.

Board pearl: Mesial temporal sclerosis on MRI + concordant ictal EEG = surgical home run; medical therapy alone is inferior.

Special Populations — Hepatic, Renal, and Comorbid Disease

— Avoid valproate — risk of fulminant hepatic failure, especially in children <2 years and those with POLG mutations (Alpers syndrome). Always send POLG before starting valproate in unexplained infantile epileptic encephalopathy.

— Avoid felbamate (aplastic anemia, hepatotoxicity)

— Preferred: levetiracetam, gabapentin (renally cleared, hepatic-safe)

— Lamotrigine, carbamazepine: reduce dose and monitor LFTs

— Levetiracetam, gabapentin, pregabalin, topiramate, vigabatrin are renally cleared — reduce dose by CrCl

— Preferred in CKD: lamotrigine, valproate, carbamazepine (hepatic clearance)

— Hemodialysis removes levetiracetam, gabapentin, topiramate — give post-dialysis supplement

— Avoid drugs prolonging QT in combination; rufinamide shortens QT (contraindicated in familial short QT syndrome)

— ADHD coexists in ~30% of children with epilepsy — stimulants are safe in well-controlled epilepsy and do not lower seizure threshold meaningfully

— Depression/anxiety screening at every visit; SSRIs preferred (sertraline, escitalopram) — avoid bupropion (lowers threshold)

— Levetiracetam-induced irritability — switch to brivaracetam or another agent; trial pyridoxine 50–100 mg/day

— Higher epilepsy prevalence; lower threshold for EEG when regression

— Avoid drugs worsening behavior (levetiracetam, perampanel, phenobarbital, topiramate cognitive effects)

— Enzyme inducers (carbamazepine, phenytoin, phenobarbital, primidone): reduce OCP efficacy, warfarin, chemotherapy, antiretrovirals

— Valproate inhibits glucuronidation → doubles lamotrigine level (halve dose, slower titration)

— Topiramate, zonisamide: carbonic anhydrase inhibitors → metabolic acidosis, kidney stones, oligohidrosis/heat intolerance

Hepatic impairment / mitochondrial disease:

Renal impairment:

Cardiac comorbidity / long QT:

Behavioral/psychiatric comorbidity:

Autism / intellectual disability:

Drug interactions to memorize:

Step 3 management: Before starting an enzyme-inducing AED in an adolescent female, counsel on OCP failure and recommend a non-hormonal or higher-estrogen method, or switch to a non-inducing AED (levetiracetam, lamotrigine).

Board pearl: Vitamin D deficiency is common on chronic enzyme-inducing AEDs — supplement and check 25-OH vitamin D annually.

Special Populations — Pregnancy, Adolescents, and Transition of Care

— Valproate is teratogenic — neural tube defects (1–2%), cardiac defects, hypospadias, autism, mean IQ reduction ~9 points in exposed children. Avoid unless no alternative.

— Topiramate: cleft lip/palate risk

— Phenobarbital, phenytoin, carbamazepine: moderate teratogenic risk

— Preferred in pregnancy: lamotrigine and levetiracetam — lowest major malformation rates (~2–3%)

— All women of reproductive age on AEDs: folic acid 4 mg/day preconception (vs 0.4–0.8 mg in general population)

— Do not stop AEDs — uncontrolled seizures harm fetus more than most modern AEDs

— Lamotrigine and levetiracetam levels fall ~50% by third trimester due to increased glucuronidation/clearance — check levels monthly, increase dose, then taper post-partum to avoid toxicity

— Vitamin K 10 mg/day orally in last month for enzyme-inducer users (reduces neonatal hemorrhagic disease)

— Breastfeeding compatible with most AEDs; monitor infant for sedation with phenobarbital, benzodiazepines

— Enzyme-inducing AEDs reduce hormonal contraceptive efficacy → use copper IUD, levonorgestrel IUD, or depot medroxyprogesterone; or pair with barrier

— Lamotrigine: estrogen-containing OCPs reduce lamotrigine levels by 50% — increase dose during active pills, reduce during placebo week

— Driving: state-specific seizure-free intervals (typically 6–12 months); document counseling

— Alcohol, sleep deprivation, recreational drugs (esp. stimulants, cocaine) — all lower threshold, especially in JME

— Mental health: 2–3× rate of depression/suicidality; screen with PHQ-9 at every visit

— SUDEP risk discussion (see chunk 11)

Adolescent girls and women of childbearing potential:

Pregnancy management:

Contraception:

Adolescent issues:

Transition to adult neurology: Start at age 14–16; structured transition clinic ideal. Many self-limited syndromes (CAE, SeLECTS) remit and the patient can be safely weaned; JME usually requires lifelong therapy despite remission appearance.

Step 3 management: A 16-year-old girl with newly diagnosed JME — start levetiracetam or lamotrigine, not valproate; document teratogenicity counseling; prescribe folic acid 4 mg/day; provide reproductive planning resources.

Board pearl: Lamotrigine + estrogen-containing OCP = falling lamotrigine levels = breakthrough seizures. Always reconcile contraception when adjusting lamotrigine.

Complications and Adverse Outcomes

— Incidence: ~1 per 4,500 children/year; ~1 per 1,000 adults/year with epilepsy; higher in drug-resistant generalized tonic-clonic seizures

— Risk factors: uncontrolled GTCs, nocturnal seizures, sleeping prone, polytherapy, missed doses, alcohol

— Risk reduction: seizure control (most important), nocturnal supervision/monitors, avoid sleep deprivation, adherence

— Counsel every family about SUDEP at diagnosis (ethical/medicolegal standard of care)

— Defined as ≥5 min continuous seizure or ≥2 seizures without recovery

— 10–25% mortality; cognitive sequelae in survivors

— Treatment ladder: benzodiazepine (IM midazolam 0.2 mg/kg, IV lorazepam 0.1 mg/kg, rectal diazepam 0.5 mg/kg) → IV fosphenytoin 20 PE/kg OR levetiracetam 60 mg/kg OR valproate 40 mg/kg → intubate and continuous infusion (midazolam, pentobarbital)

— Epileptic encephalopathies (West, LGS, Dravet, Landau-Kleffner, ESES) — seizures themselves and interictal discharges impair development

— Phenobarbital and topiramate cause measurable cognitive slowing

— Untreated absences impair school performance via thousands of micro-lapses

— Valproate → PCOS, weight gain, hyperinsulinemia

— Topiramate, zonisamide → weight loss, kidney stones, acidosis

— Carbamazepine, oxcarbazepine → hyponatremia (SIADH)

SUDEP (Sudden Unexpected Death in Epilepsy):

Status epilepticus:

Injuries: Tongue laceration, posterior shoulder dislocation, vertebral compression fractures, drowning (50× general population risk in epilepsy — shower instead of bath, swim with buddy), burns, MVCs.

Cognitive and developmental impact:

Bone health: Long-term enzyme-inducing AEDs and valproate → low bone mineral density, fractures. Vitamin D, calcium, DEXA in long-term users.

Endocrine/metabolic:

Hematologic/dermatologic: SJS/TEN/DRESS (lamotrigine, carbamazepine, phenytoin, phenobarbital — HLA-B*1502 in Asian ancestry mandates pre-screening for carbamazepine).

Psychiatric: Depression, anxiety, psychosis (especially with levetiracetam, perampanel, vigabatrin, topiramate). Suicidality boxed warning on all AEDs.

Board pearl: Drowning risk is dramatically elevated — counsel shower, not bath, and never swim alone, even when seizures are well-controlled.

Step 3 management: Every clinic visit: ask about adherence, missed doses, mood, sleep, breakthrough seizures, driving, and aura/seizure diary review.

When to Escalate Care — ED, ICU, and Specialty Consultation

— Seizure lasting >5 minutes (status epilepticus)

— Two or more seizures without return to baseline between them

— First seizure with focal deficit, fever, headache, head trauma, immunocompromise, or VP shunt

— Suspected infantile spasms (urgent admission for EEG and treatment initiation)

— Suspected meningitis/encephalitis with seizure

— Suspected non-accidental trauma in infant with seizure

— Refractory status epilepticus requiring continuous infusion (midazolam, pentobarbital, ketamine) and continuous EEG monitoring

— Airway compromise, respiratory depression from benzodiazepines

— New encephalopathy with seizures (autoimmune encephalitis, FIRES)

— Severe metabolic derangement (DKA, hyponatremia, hypocalcemia) triggering seizures

— First unprovoked seizure in any child

— Suspected epilepsy syndrome

— Developmental regression with seizures

— Breakthrough seizures on therapy

— Pregnancy planning while on AEDs

— Drug-resistant epilepsy (failed 2 appropriately chosen AEDs at adequate dose)

— Suspected surgical candidacy (lesional epilepsy, mesial temporal sclerosis)

— Diagnostic uncertainty (epileptic vs psychogenic vs movement disorder)

— Catastrophic infantile epilepsies (West, Dravet, LGS) — multidisciplinary team

— Genetics — early-onset, refractory, dysmorphic, family history, regression

— Neuropsychology — baseline before surgery, school IEP planning, monitoring AED cognitive effects

— Ophthalmology — baseline and serial for vigabatrin (REMS)

— Cardiology — baseline echo before fenfluramine

— Developmental pediatrics / early intervention — under age 3 with delays

— Social work / Child Life — adherence, school advocacy, financial assistance

Send to ED immediately:

PICU admission criteria:

Urgent neurology referral (within days–weeks):

Comprehensive epilepsy center referral (Level 4):

Other consults:

CCS pearl: In a CCS case of pediatric status epilepticus: (1) ABC + IV access + glucose check immediately, (2) lorazepam 0.1 mg/kg IV, (3) repeat at 5 min if seizing, (4) load fosphenytoin or levetiracetam, (5) labs (CBC, BMP, Ca, Mg, AED levels, tox screen), (6) head CT if focal/trauma, (7) admit to PICU with continuous EEG if not stopped. Advance the clock in small increments.

Board pearl: Any child with new-onset refractory status epilepticus (NORSE) or FIRES → admit, send autoimmune encephalitis panel (NMDA-R, LGI1, GABA-B, MOG), start empiric high-dose steroids/IVIG.

Key Differentials — Other Paroxysmal Neurologic Events

— Prodrome (lightheaded, nausea, tunnel vision, pallor) → brief LOC with limp posture and 5–15 sec of myoclonic jerks ("convulsive syncope") → rapid recovery, no postictal confusion

— Triggers: standing, blood draw, hot environment

— Always ECG to exclude long QT, HCM, WPW in any child with exertional or sudden syncope; family history of sudden death is a red flag

— 6 months–4 years; cyanotic type (after crying, brief LOC, sometimes jerks) or pallid type (after minor injury, vagally mediated)

— Normal EEG; iron deficiency association — check ferritin and supplement; resolves by age 4–5

— Sleep terrors (ages 4–8, first third of night, screaming, inconsolable, no memory) — distinguishable from nocturnal frontal lobe seizures by lack of stereotypy and rare frequency

— Confusional arousals, sleepwalking, REM behavior disorder

— Suppressible, urge before tic, no LOC, normal EEG

— Sandifer syndrome — dystonic posturing with GERD in infants; resolves with reflux treatment

— Shuddering attacks, jitteriness in neonates — normal startle, suppressible

— Paroxysmal kinesigenic dyskinesia in older children

— Adolescents, often female, comorbid trauma/anxiety; eyes closed (epileptic seizures usually eyes open), pelvic thrusting, side-to-side head movement, prolonged duration, no postictal confusion, normal lactate, no tongue laceration

— Diagnosis by video-EEG capture; treatment is psychotherapy, not AED escalation

Within "seizure-like" episodes — the mimics that fool everyone:

Syncope (vasovagal, cardiogenic):

Breath-holding spells:

Parasomnias:

Tics and stereotypies:

Benign paroxysmal vertigo of childhood and benign paroxysmal torticollis — migraine variants in infants/toddlers

Migraine with aura: Visual scintillations, gradual march, headache follows

Movement disorders:

Psychogenic non-epileptic seizures (PNES):

Key distinction: Convulsive syncope (5–15 sec of jerks after limp LOC) vs generalized tonic-clonic seizure (sustained 1–2 min tonic-clonic with postictal confusion, tongue bite, incontinence). ECG and tilt history make the call.

Board pearl: Eyes forced shut during the event = highly suggestive of PNES; eyes open and deviated = epileptic.

Key Differentials — Provoked Seizures and Systemic Causes

— Hypoglycemia — neonates of diabetic mothers, congenital hyperinsulinism, fatty acid oxidation defects, sepsis

— Hyponatremia — water intoxication (dilute formula, swimming pool ingestion), SIADH, oxcarbazepine

— Hypocalcemia — DiGeorge in neonates, vitamin D deficiency, hypoparathyroidism

— Hypomagnesemia — rare, suspect with hypocalcemia

— Pyridoxine-dependent epilepsy — neonatal refractory seizures responsive to IV pyridoxine 100 mg trial

— Hyperammonemia — urea cycle defects in neonates with vomiting, lethargy, seizures

— Meningitis/encephalitis — fever + altered mental status + seizure → LP after head CT if focal

— Herpes encephalitis — temporal lobe seizures, mesial temporal MRI changes, empiric acyclovir

— Neurocysticercosis — endemic regions; new-onset focal seizures in school-age child with ring-enhancing lesion

— Cerebral malaria in returning travelers

— Simple: generalized, <15 min, once in 24h, age 6 months–5 years, fever ≥38°C — no workup beyond fever source

— Complex: focal, >15 min, recurrent in 24h — consider EEG, MRI, possibly LP

— Recurrence risk ~30%; future epilepsy risk only modestly increased (~2–5%, higher with complex features)

— Do NOT give chronic AEDs for febrile seizures

— Bupropion, TCAs, cocaine, amphetamines, isoniazid (pyridoxine reverses), lithium, organophosphates, lead encephalopathy

A provoked (acute symptomatic) seizure is NOT epilepsy — by definition, it occurs within 7 days of an acute insult. Distinguishing is critical because treatment is the underlying cause, not chronic AEDs.

Metabolic provocations:

Infectious:

Febrile seizures (the most common "seizure" in pediatrics — not epilepsy):

Toxic:

Traumatic: Concussive convulsion (within seconds of impact, benign); post-traumatic seizures in first week (acute symptomatic) vs late post-traumatic epilepsy (>1 week — chronic)

Stroke/vascular: Arterial ischemic stroke, sinus venous thrombosis (especially with dehydration, sickle cell), AVM hemorrhage, moyamoya

Tumor: New focal seizure + persistent headache + papilledema → urgent MRI

Step 3 management: A 9-month-old with simple febrile seizure, fully recovered, focus identified (otitis media) — discharge home with antipyretic counseling, no EEG, no MRI, no AED. Reassure: febrile seizures are common (2–5%) and benign.

Board pearl: Any neonatal seizure refractory to standard AEDs → IV pyridoxine 100 mg trial under EEG — pyridoxine-dependent epilepsy is treatable and missed without trial.

Long-Term Management, Discharge Plans, and AED Withdrawal

— Use 90-day refills, automatic pharmacy reminders, pill organizers, smartphone alarms

— Adolescents: address autonomy by transferring responsibility gradually

— Confirm formulary coverage at each visit — switching between generic manufacturers can cause breakthrough seizures (especially narrow-therapeutic-index drugs like lamotrigine, phenytoin)

— Date, time, duration, semiology, triggers, missed doses

— Mobile apps (e.g., Seizure Tracker) — share with neurology

— Sleep hygiene (8+ hours, regular schedule) — critical in JME

— Avoid alcohol, recreational drugs, dehydration

— Photic precautions in photosensitive epilepsy (limit screen time, polarized glasses, cover one eye if exposed to strobes)

— Routine vaccines are SAFE — including in Dravet, despite historical concern (fever may trigger seizure but vaccines do not cause Dravet — SCN1A is the cause)

— Influenza vaccine annually; pneumococcal per schedule

— Pre-treat with acetaminophen if fever-triggered seizures

— Individualized Healthcare Plan (IHP) and IEP/504 plan in place

— Rescue medication (rectal diazepam, intranasal midazolam, buccal midazolam) at school with trained staff

— Activity allowances: most sports OK with helmet/supervision; avoid scuba diving, solo swimming, rock climbing, hang gliding

— 2 years seizure-free AND normal EEG AND normal exam AND non-progressive syndrome

— Wean over 3–6 months

— Recurrence risk ~25–30% overall; higher with abnormal EEG, focal/symptomatic epilepsy, JME (rarely withdrawn — high relapse)

— Self-limited syndromes (CAE, SeLECTS): good candidates for withdrawal after puberty

— JME: lifelong therapy in most patients despite years of control

— Vitamin D annually on enzyme inducers

— Lipids and weight on valproate

— Mood screen each visit

Adherence and refill strategy:

Seizure diary:

Trigger avoidance:

Vaccinations:

School plan:

AED withdrawal — when to consider:

Bone, mood, metabolic surveillance:

Step 3 management: For a 12-year-old with CAE seizure-free for 2 years on ethosuximide with normal EEG — discuss gradual withdrawal over 3–6 months with explicit driving and supervision precautions during taper.

Board pearl: Never withdraw JME therapy — relapse rate exceeds 80% even after years of seizure freedom.

Follow-Up, Monitoring, and Counseling Cadence

— After diagnosis: 2–4 weeks (titration check), then every 3 months × 1 year, then every 6 months when stable

— Breakthrough seizure: within 1–2 weeks

— Drug-resistant: every 1–3 months with epilepsy center

— Seizure frequency, semiology, triggers (review diary)

— Adherence (ask non-judgmentally: "How many doses do you miss in a typical week?")

— Side effects (mood, sleep, cognition, GI, rash, hair, weight, menstrual)

— School performance, social functioning

— Driving status (for teens)

— Mood/suicidality screen (PHQ-9 in adolescents)

— Reproductive planning in adolescent females

— Valproate: baseline LFTs, CBC, ammonia; repeat at 1, 3, 6 months and annually; level if breakthrough seizures

— Carbamazepine, oxcarbazepine: CBC, sodium, LFTs at baseline and periodically

— Phenytoin: levels (free phenytoin if hypoalbuminemia), gum hygiene

— Topiramate, zonisamide: bicarbonate (acidosis), urinalysis (stones)

— Lamotrigine, levetiracetam: generally no routine labs

— Vigabatrin: ophthalmology every 3 months

— Vitamin D and bone health: annually on chronic enzyme inducers

— Repeat at 6–12 months in self-limited syndromes to track resolution

— Before AED withdrawal (must be normal)

— Any change in seizure semiology or frequency

— Baseline at diagnosis if syndrome at risk for cognitive impact

— Before and after epilepsy surgery

— Annually in school-age children with active seizures

— Epilepsy Foundation, syndrome-specific patient organizations (Dravet Syndrome Foundation, LGS Foundation, TS Alliance)

— Camp programs for affected children

— Genetic counseling for recurrence risk

— Medical alert bracelet

— Early intervention (<3 years) for any developmental delay

— Speech therapy in Landau-Kleffner, LGS, Dravet

— OT/PT for motor delays; behavioral therapy for autism/ADHD comorbidity

Visit schedule (typical):

At each visit — structured review:

Laboratory monitoring:

EEG follow-up:

Neuropsychological testing:

Family counseling and resources:

Rehabilitation/therapies:

Board pearl: Lamotrigine rash within first 8 weeks of titration → stop and assess — even mild rash can progress to SJS/TEN if continued.

Step 3 management: Schedule annual influenza vaccine, dental cleaning (especially on phenytoin), DEXA every 2–3 years on long-term enzyme inducers, and reproductive counseling check-ins for adolescent females.

Ethical, Legal, and Patient Safety Considerations

— Vary by state; most require 6–12 months seizure-free before licensing

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

— Document the conversation about driving restrictions at every visit; medicolegal liability if undocumented and the patient causes an MVC

— Epilepsy qualifies for 504 plan accommodations (rescue meds, rest area, missed-work makeup)

— IEP if cognitive/learning impact

— Schools may not exclude children with epilepsy from activities without medical justification

— For adolescents 12–17: include them in decision-making (assent); parents provide consent

— Discuss teratogenicity with adolescent females before starting any AED — even if not currently sexually active (autonomy and future planning)

— SUDEP disclosure is now considered standard of care — document the conversation

— Variants of uncertain significance, incidental findings, implications for siblings/parents

— Pre-test counseling on insurance discrimination (GINA protects health insurance but NOT life/disability/long-term care insurance)

— Suspected non-accidental trauma presenting as seizure in infant → CPS report

— Pediatric drowning event → CPS evaluation for supervision adequacy

— Pediatric-to-adult neurology transition — high risk of medication errors, lost follow-up, breakthrough seizures

— Structured transition plan starting age 14–16; transition summary document; warm handoff

— Adolescents leaving home for college: ensure local neurologist, pharmacy refill plan, rescue medication accessible, roommate aware of seizure first aid

— Adolescent disclosing alcohol/drug use that triggers seizures — confidential within reason, but driving safety may require breaking confidentiality if imminent harm

— Suicidality on AEDs requires direct intervention and family disclosure

— Newer AEDs and cannabidiol are expensive; prior authorization advocacy is part of the job

— Ketogenic diet requires specialized dietitian — may not be available in all settings; consider telehealth referral to comprehensive center

Driving laws:

School and ADA:

Informed consent and shared decision-making:

Genetic testing ethics:

Mandatory reporting:

Transition of care risks (Step 3 staple):

Confidentiality vs safety:

Equity and access:

Step 3 management: A 16-year-old with JME on valproate, seizure-free, planning college 4 hours away — before transition: switch to lamotrigine or levetiracetam (teratogen avoidance), establish college-area neurologist, provide written seizure action plan to roommate/RA, confirm pharmacy access, document driving rules.

Board pearl: Document, document, document — driving counseling, SUDEP discussion, teratogenicity counseling, transition planning. The undocumented conversation legally did not happen.

High-Yield Associations and Rapid-Fire Clinical Facts

Hypsarrhythmia + flexor spasms + regression = West syndrome → ACTH or prednisolone; vigabatrin first if TSC

Triad of LGS: multiple seizure types (tonic, atonic, atypical absence) + slow spike-wave <2.5 Hz + cognitive impairment

CAE first-line drug = ethosuximide (CAE trial: best efficacy + best attention profile vs valproate/lamotrigine)

JME triad: myoclonic jerks on awakening + GTC on awakening + absences; lifelong treatment, avoid sodium channel blockers

SeLECTS (Rolandic): nocturnal facial twitching, hypersalivation; often no treatment needed — remits by puberty

Dravet: SCN1A mutation; prolonged febrile hemiclonic seizures <1 year; AVOID sodium channel blockers (lamotrigine, carbamazepine, phenytoin)

GLUT1 deficiency: low CSF glucose, seizures + movement disorder + microcephaly → ketogenic diet is treatment

Pyridoxine-dependent epilepsy: neonatal refractory seizures → IV pyridoxine trial under EEG

Landau-Kleffner: acquired aphasia + ESES on sleep EEG → steroids, IVIG, sometimes multiple subpial transections

Tuberous sclerosis features: ash-leaf macules, facial angiofibromas, shagreen patch, cardiac rhabdomyomas, renal angiomyolipomas, cortical tubers → vigabatrin first-line for spasms; everolimus for refractory seizures

Sturge-Weber: port-wine stain V1, leptomeningeal angioma, focal seizures, hemiparesis → consider hemispherectomy

Mesial temporal sclerosis = best surgical outcome (60–80% seizure-free post-resection)

Valproate — boxed warnings: hepatotoxicity (<2 yo, POLG), pancreatitis, teratogenicity

Lamotrigine + valproate = halve lamotrigine dose (glucuronidation inhibition, SJS risk)

HLA-B*1502 screening in Asian ancestry before carbamazepine (SJS/TEN risk)

Vigabatrin = peripheral visual field constriction (REMS)

Fenfluramine = valvulopathy/PAH (echo REMS)

Topiramate/zonisamide = kidney stones, metabolic acidosis, oligohidrosis

Folic acid 4 mg/day for any reproductive-age female on AED

Drug-resistant epilepsy = failure of 2 appropriately chosen AEDs → refer to Level 4 center

AED withdrawal = after 2 years seizure-free with normal EEG (except JME — usually lifelong)

SUDEP = uncontrolled GTC + nocturnal + prone position; counsel every family

Drowning risk: shower not bath, never swim alone

Board pearl: When in doubt about which AED to pick — levetiracetam is broad-spectrum, no labs needed, no interactions, safe in pregnancy — the modern Step 3 "default" answer for new-onset focal or generalized epilepsy in adolescents.

Board Question Stem Patterns

Stem 1: "A 6-year-old has multiple episodes daily of staring with eye-blinking, lasting 10 seconds, with no postictal confusion. Hyperventilation in clinic reproduces the event. EEG: 3-Hz generalized spike-and-wave." → CAE; start ethosuximide.

Stem 2: "A 16-year-old drops her cereal spoon every morning for 2 months. Recently had a generalized tonic-clonic seizure after staying up all night studying. EEG: 4–6 Hz polyspike-and-wave." → JME; start levetiracetam or lamotrigine (avoid valproate in females); lifelong therapy; sleep hygiene counseling.

Stem 3: "A 7-month-old has clusters of brief flexor spasms on awakening. Development has plateaued. Skin exam reveals three ash-leaf macules." → West syndrome with tuberous sclerosis; vigabatrin first-line.

Stem 4: "An 18-month-old with previously normal development has prolonged febrile hemiclonic seizures triggered by hot baths and vaccinations." → Dravet syndrome; send SCN1A; start valproate + clobazam; AVOID lamotrigine/carbamazepine.

Stem 5: "A 9-year-old has nocturnal seizures with right facial twitching, drooling, and inability to speak. Awake EEG normal; sleep EEG shows centrotemporal spikes." → SeLECTS; observation or oxcarbazepine if frequent/severe; reassurance — remits by puberty.

Stem 6: "A 5-year-old with prior West syndrome now has daily tonic seizures at night, drop attacks, and cognitive delay. EEG: slow spike-and-wave 1.5–2 Hz." → LGS; valproate first; consider rufinamide, cannabidiol, ketogenic diet.

Stem 7: "A 5-year-old previously verbal now has receptive language loss. EEG during sleep: continuous spike-wave activity." → Landau-Kleffner; corticosteroids or IVIG.

Stem 8: "A 3-month-old has refractory seizures unresponsive to phenobarbital and levetiracetam. Next step?" → IV pyridoxine 100 mg under EEG; consider folinic acid; metabolic and genetic workup.

Stem 9: "A 14-year-old with epilepsy on valproate now has irregular menses, weight gain, and acne." → Valproate-induced PCOS; switch to lamotrigine or levetiracetam.

Stem 10: "An 18-month-old has a 3-minute generalized tonic-clonic seizure during 39.5°C fever from otitis media. Fully recovered. Exam normal." → Simple febrile seizure; reassure, treat fever source; no EEG, no MRI, no AED.

Stem 11: "A 4-year-old with refractory epilepsy. MRI normal. CSF glucose 35, serum glucose 95 (ratio 0.37)." → GLUT1 deficiency; ketogenic diet.

Stem 12 (CCS): Status epilepticus in a 6-year-old → IV access, glucose, lorazepam, repeat at 5 min, fosphenytoin/levetiracetam, PICU + continuous EEG if not stopping.

Board pearl: When a stem mentions "previously normal development" + onset age + specific trigger + specific EEG, the answer is almost always the syndrome diagnosis, not the seizure type — and treatment hinges on the syndrome.

One-Line Recap

Pediatric epilepsy is diagnosed by identifying age-specific syndromes — defined by seizure type, EEG pattern, etiology, and developmental trajectory — because the syndrome (not the seizure) dictates the right drug, the prognosis, and whether to treat at all.

Syndrome-first thinking: Match age + semiology + EEG to a named syndrome before choosing an AED — Dravet, JME, CAE, LGS, West, SeLECTS, and Landau-Kleffner each have specific first-line and contraindicated drugs.

First-line drug by syndrome (memorize cold): CAE → ethosuximide; JME → levetiracetam or lamotrigine (avoid valproate in females); West → ACTH/prednisolone (vigabatrin in TSC); Dravet → valproate + clobazam (avoid sodium channel blockers); LGS → valproate plus add-on; SeLECTS → often observation; GLUT1 deficiency → ketogenic diet; pyridoxine-dependent → IV pyridoxine trial.

Step 3 management priorities: Counsel every family on SUDEP, drowning risk, driving rules, and seizure first aid; folic acid 4 mg/day for reproductive-age females; refer to a Level 4 epilepsy center after 2 failed appropriately chosen AEDs; consider AED withdrawal after 2 years seizure-free with normal EEG (except JME — usually lifelong); structured pediatric-to-adult transition starting age 14–16 to prevent lost follow-up and breakthrough seizures.

Red-flag escalations: Suspected infantile spasms (urgent admission), status epilepticus (PICU + continuous EEG if refractory), developmental regression with seizures (epileptic encephalopathy workup including genetic panel, MRI, metabolic studies), and lesional drug-resistant epilepsy (surgical evaluation before years of refractory seizures damage cognition).

Board pearl: The fastest way to answer a pediatric epilepsy stem on Step 3 is to first ask, "What syndrome is this?" — then drug choice, counseling, and prognosis all fall out of the syndrome label.