Eduovisual
Pediatrics (System-Integrated)
Lennox-Gastaut syndrome: recognition and management
— Multiple drug-resistant seizure types (especially tonic seizures in sleep, atypical absence, atonic/drop attacks)
— EEG with slow (<2.5 Hz) spike-and-wave in wakefulness and paroxysmal fast activity (10–20 Hz) in sleep
— Cognitive and behavioral impairment (often progressive)
— Onset typically ages 3–8 (peak 3–5)
— Accounts for ~1–4% of childhood epilepsies but a disproportionate share of refractory cases
— Slight male predominance
— Symptomatic (70–80%): prior infantile spasms/West syndrome (~20–30% evolve to LGS), tuberous sclerosis complex, hypoxic-ischemic encephalopathy, cortical malformations (lissencephaly, focal cortical dysplasia), CNS infections, trauma, genetic (CHD2, SCN2A, SCN8A, GABRB3, STXBP1, DNM1)
— Cryptogenic/unknown (20–30%): previously normal development
— Preschooler with multiple seizure types, especially drop attacks causing injury
— Plateau or regression in development
— Pharmacoresistance to ≥2 appropriately chosen ASMs
— History of West syndrome now with new seizure semiologies
— High morbidity: injury from drops, status epilepticus (especially nonconvulsive status, NCSE), cognitive decline, premature mortality (SUDEP risk)
— Lifelong care: ambulatory neurology, school accommodations, transition planning to adult care
Board pearl: A child with a history of infantile spasms who at age 4 develops tonic seizures during sleep + drop attacks + slow spike-wave on EEG is LGS until proven otherwise—do not just label it "refractory epilepsy." Early recognition changes drug choice and prognosis counseling.
— Tonic seizures (hallmark): brief axial stiffening, arms extended/flexed, often emerge from sleep; may be subtle (eye deviation, apnea). Present in >90%.
— Atonic/drop attacks: sudden loss of tone → face-plant falls, dental/facial trauma, helmet use common
— Atypical absence: gradual onset/offset staring with partial responsiveness, automatisms, eyelid flutter — distinguishes from typical absence
— Myoclonic, focal, and generalized tonic-clonic seizures may coexist
— Nonconvulsive status epilepticus (NCSE): prolonged confusion, drooling, behavioral arrest, subtle myoclonus — occurs in 50–75% at some point
— Developmental trajectory: Was there a plateau or regression? Loss of language, social engagement?
— Prior epilepsy syndromes: infantile spasms, neonatal seizures
— Perinatal history: HIE, prematurity, NICU course
— Family history: consanguinity, epilepsy, genetic syndromes
— Seizure burden: frequency, injury history, ED visits, prior ICU/status admissions
— Medication history: which ASMs tried, doses, response, adverse effects, adherence
— Triggers: sleep deprivation, illness, missed doses, photic (less common)
— Autism spectrum features, ADHD-like inattention, aggression, sleep fragmentation
— School performance, IEP status, communication level
— Caregiver burnout, financial strain (rescue meds, helmets, durable equipment), respite needs
Key distinction: Typical absence (childhood absence epilepsy) is brief (<20 s), abrupt onset/offset, 3 Hz spike-wave, normal development, responds to ethosuximide. Atypical absence in LGS is longer, gradual, slow spike-wave (<2.5 Hz), and accompanies developmental delay plus other seizure types. Missing this distinction leads to wrong drug (ethosuximide alone is insufficient) and wrong prognosis.
Step 3 management: Always document seizure diary, rescue plan, and most recent EEG/MRI date at every visit — these drive medication decisions.
— Skin: hypopigmented ash-leaf macules, angiofibromas, shagreen patch (tuberous sclerosis); café-au-lait (NF1); port-wine in V1 (Sturge-Weber); hypomelanosis of Ito
— Head: microcephaly (HIE, malformations), macrocephaly (megalencephaly), dysmorphic features (genetic syndromes)
— Eyes: retinal hamartomas (TSC), chorioretinal lacunae (Aicardi), optic atrophy
— Oral/dental: trauma from drop attacks, gingival hyperplasia (phenytoin), tongue lacerations
— Mental status: alertness, language level, eye contact, joint attention
— Cranial nerves: visual fields, ocular motility
— Motor: tone (often hypotonic axially, may have spasticity), strength, asymmetry suggesting structural lesion
— Reflexes/Babinski
— Coordination/gait: ataxia from cerebellar involvement or ASM toxicity (especially phenytoin, carbamazepine)
— Movement abnormalities: stereotypies, dystonia
— Forehead/chin lacerations, dental fractures, healing abrasions, helmet-fit assessment
— C-spine concerns if recurrent falls
— Use age-appropriate tools (ASQ, Bayley, Vineland)
— Document baseline so regression can be detected
— Assess adaptive function, not just IQ — drives services
— Plot height/weight/BMI — ASMs cause weight loss (topiramate, felbamate, zonisamide, stiripentol, cannabidiol) or gain (valproate)
— Pubertal staging in adolescents (valproate → PCOS risk)
Board pearl: A child with refractory mixed seizures plus hypopigmented macules under Wood's lamp → think tuberous sclerosis–associated LGS; this opens the door to vigabatrin (especially if prior infantile spasms) and everolimus (mTOR inhibitor) as targeted therapy.
Step 3 management: Examine the helmet and the mouth — visible injury patterns reveal seizure control quality better than parental report.
— Interictal awake: slow (<2.5 Hz) generalized spike-and-wave, often with multifocal discharges, abnormal background slowing
— Sleep: generalized paroxysmal fast activity (GPFA) at 10–20 Hz, bursts lasting ~2–10 sec — strongly supports LGS and correlates with tonic seizures
— Ictal patterns: electrodecrement with tonic seizures; rhythmic slow waves with atypical absence
— Order prolonged video EEG (24-hr or longer) to capture multiple seizure types and rule out NCSE
— Repeat EEG over time — patterns evolve
— MRI brain with epilepsy protocol (thin cuts, FLAIR, DWI, contrast if indicated) is mandatory at diagnosis
— Looks for: cortical malformations (focal cortical dysplasia, polymicrogyria, lissencephaly), tubers, hippocampal sclerosis, gliosis from prior HIE, tumors
— CT only if MRI unavailable or acute trauma
— CBC, CMP (baseline for ASM monitoring — LFTs, renal, electrolytes, ammonia if valproate considered)
— Glucose, lactate, ammonia if metabolic concern
— Pregnancy test in adolescents before ASM initiation/change
— Vitamin D, calcium (chronic ASM use → osteopenia)
— Lipid panel if starting ketogenic diet
— Baseline ECG before starting sodium-channel blockers (lamotrigine, rufinamide → shortened QT with rufinamide; cardiac conduction with phenytoin)
CCS pearl: On a CCS-style case, order video EEG, MRI brain, CBC, CMP, ECG, and pregnancy test (if applicable) as the initial diagnostic bundle when LGS is suspected. Do not order routine LP unless clinical suspicion for infection/inflammation.
Key distinction: A single routine 20-minute EEG can miss LGS — it may show only nonspecific slowing. Sleep-deprived or prolonged EEG capturing N2 sleep is essential to demonstrate GPFA, the most specific finding.
— Epilepsy gene panel (next-generation sequencing) covering SCN1A, SCN2A, SCN8A, CHD2, GABRB3, STXBP1, DNM1, FOXG1, ALG13, IQSEC2
— Chromosomal microarray for copy number variants (ring chromosome 20, deletions)
— Whole-exome sequencing if panel negative and cryptogenic
— Trio testing (proband + parents) increases yield by identifying de novo variants
— Yield: 20–40% in cryptogenic LGS; results can change management (e.g., avoid sodium-channel blockers in SCN1A loss-of-function; mTOR inhibitors in TSC)
— Plasma amino acids, urine organic acids, acylcarnitines
— CSF studies: glucose (GLUT1 deficiency → ketogenic diet responsive), lactate, neurotransmitters
— Ammonia, lactate, very-long-chain fatty acids
— Consider mitochondrial workup
— 3T MRI with epilepsy protocol if 1.5T was nondiagnostic
— PET/SPECT and MEG for presurgical evaluation when a focal lesion is suspected
— fMRI/Wada for language lateralization in older children pre-surgery
— Baseline cognitive, language, adaptive, and behavioral assessment
— Repeat every 1–2 years to track encephalopathy and guide schooling
Board pearl: GLUT1 deficiency (SLC2A1) can mimic LGS phenotype and is exquisitely responsive to the ketogenic diet — check CSF/serum glucose ratio (<0.45) and gene testing in any cryptogenic case.
Step 3 management: Send genetic + metabolic testing before committing to lifelong polytherapy; a precise diagnosis may unlock targeted therapy (vigabatrin for TSC, everolimus, fenfluramine in select channelopathies) and end the diagnostic odyssey for families.
— Complete seizure freedom is rare (<10%)
— Realistic targets: reduce drop attacks (highest morbidity), prevent NCSE, minimize ASM toxicity, preserve cognition and quality of life
— Counsel families upfront that LGS is a chronic encephalopathy requiring lifelong management
— Dominant seizure type (drops vs. tonic vs. atypical absence vs. NCSE) — drives drug selection
— Etiology (structural focal lesion → consider surgery; genetic → precision therapy; cryptogenic → broad-spectrum ASMs)
— Comorbidity burden: behavior, sleep, GI, orthopedic
— Caregiver capacity and adherence
— Step 1: Optimize one broad-spectrum ASM (valproate first-line in most)
— Step 2: Add second agent targeting dominant seizure type (lamotrigine for drops, rufinamide for tonic/atonic, clobazam for mixed, topiramate for generalized)
— Step 3: Consider third-line/adjunctive (cannabidiol, fenfluramine, felbamate)
— Step 4: Non-pharmacologic: ketogenic diet, VNS, corpus callosotomy, resective surgery if focal lesion
— Avoid polypharmacy creep — each added drug raises toxicity, drug-drug interactions, and cognitive burden
— Carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, tiagabine, vigabatrin (outside TSC) can worsen atypical absence, myoclonic, or tonic seizures
Step 3 management: When asked the "next best step" in a child with refractory mixed seizures and slow spike-wave, the answer is rarely "add a fourth drug" — it is refer to a comprehensive epilepsy center for surgical/dietary/device evaluation once 2 appropriate ASMs have failed (definition of drug-resistant epilepsy per ILAE).
— Valproate (VPA): broadest spectrum; effective against tonic, atonic, atypical absence, myoclonic, GTC
— Dose: 15–60 mg/kg/day divided
— Monitor: LFTs, ammonia, CBC, weight, menstrual history; avoid <2 yr on polytherapy (hepatotoxicity risk), avoid in suspected mitochondrial disease (POLG mutation → fatal hepatotoxicity)
— Lamotrigine: add-on for drop attacks; titrate slowly (especially with VPA) to avoid Stevens-Johnson syndrome — VPA doubles lamotrigine levels, so start at half-dose and titrate over 8+ weeks
— Topiramate: effective for tonic, atonic, GTC; AEs: weight loss, cognitive slowing, nephrolithiasis, oligohidrosis, metabolic acidosis, narrow-angle glaucoma
— Rufinamide: reduces tonic-atonic seizures; AEs: shortened QT (baseline ECG), somnolence; contraindicated in familial short QT syndrome
— Clobazam: benzodiazepine adjunct, effective across seizure types; AEs: sedation, tolerance, behavioral disinhibition; CYP2C19 poor metabolizers accumulate active metabolite
— Cannabidiol (Epidiolex): FDA-approved for LGS ≥1 yr; reduces drop seizures ~40%; AEs: somnolence, elevated transaminases (especially with VPA — check LFTs at baseline, 1, 3, 6 months), diarrhea, decreased appetite
— Felbamate: effective but reserved due to aplastic anemia (1:5,000) and hepatic failure — requires written informed consent and biweekly CBC/LFTs
— Intranasal/buccal midazolam, rectal diazepam, intranasal diazepam — every family needs a written seizure action plan
Board pearl: Lamotrigine + valproate is a high-yield interaction: VPA inhibits glucuronidation → ↑ lamotrigine levels → ↑ SJS/TEN risk. Halve the lamotrigine starting dose and titrate over ≥8 weeks. This is a frequent Step 3 question.
Step 3 management: Document baseline labs and a written rescue plan before discharge from every encounter where ASMs are changed.
— High-fat, low-carbohydrate, adequate-protein diet inducing ketosis
— ~50% of LGS patients achieve ≥50% seizure reduction
— Variants: classic 4:1 KD, modified Atkins, low-glycemic-index treatment, MCT diet — choose based on age, feeding route, family capacity
— Contraindications: fatty acid oxidation disorders, pyruvate carboxylase deficiency, porphyria, primary carnitine deficiency — screen with acylcarnitines and organic acids first
— Monitor: growth, lipids, urine ketones, kidney stones, bone density, carnitine
— First-line in GLUT1 deficiency and pyruvate dehydrogenase deficiency
— Implanted device delivering intermittent left vagal stimulation
— ~50% achieve ≥50% reduction; benefit may grow over 1–2 years
— AEs: hoarseness, cough, dyspnea during stimulation; MRI compatibility requires specific protocols
— Magnet for on-demand stimulation during aura
— Palliative disconnection of corpus callosum (anterior 2/3 or complete)
— Best for disabling drop attacks — reduces atonic/tonic falls in ~70–80%
— Does not cure; may unmask focal seizures
— Risk: disconnection syndrome (usually transient in children)
— Reserved for cases with a clear focal structural lesion concordant with EEG
— Can be curative if focal cortical dysplasia or tuber is identified as seizure-onset zone
— Emerging options; centrolateral/centromedian thalamic DBS shows promise in generalized epilepsies
CCS pearl: For a child with disabling drop attacks refractory to ≥2 ASMs, the highest-yield next step is referral to a comprehensive epilepsy center for KD trial, VNS, or corpus callosotomy — not endless ASM substitutions.
— Valproate: contraindicated in significant hepatic dysfunction; black-box hepatotoxicity, especially in children <2 yr on polytherapy or with mitochondrial disease (POLG variants) — screen POLG before VPA if cryptogenic regressive epilepsy
— Felbamate: acute hepatic failure risk — avoid in hepatic disease
— Cannabidiol: dose-dependent transaminitis, particularly with concomitant VPA — reduce dose or hold if ALT >3× ULN
— Lamotrigine, clobazam: reduce dose in moderate-severe hepatic impairment
— Topiramate, zonisamide: ↑ risk of nephrolithiasis (carbonic anhydrase inhibition) — encourage hydration, avoid combining with KD if possible
— Levetiracetam, gabapentin, pregabalin: renally cleared — dose-adjust by CrCl
— Rufinamide: modest renal adjustment
— Start transition planning at age 12–14; transfer to adult epileptologist typically by 18–21
— Address sexual health, contraception, driving laws (vary by state — most require 3–12 months seizure-free)
— Bone health: chronic enzyme-inducing ASMs and VPA → osteopenia; check 25-OH vitamin D, supplement, consider DEXA
— Mental health screening: depression and suicidality are increased; screen at each visit (PHQ-9 in capable patients)
— Seizure semiology evolves — tonic seizures persist, atypical absence may decrease, focal seizures may emerge
— EEG may lose classic slow spike-wave pattern, complicating diagnosis if no prior records
— Polypharmacy review essential — many adults on 4–5 ASMs from childhood
Board pearl: Before initiating valproate in any child with developmental regression of unclear etiology, test for POLG mutations — VPA can precipitate fatal Alpers-Huttenlocher hepatocerebral degeneration.
Step 3 management: Build a written transition packet (diagnosis, EEG/MRI summary, medication trial history, surgical history, rescue plan, advance care preferences) and hand it to the family before age 18.
— Pregnancies are often unplanned given cognitive impairment — proactive contraception counseling is essential
— Valproate: highest teratogenicity of all ASMs — neural tube defects (1–2%), cardiac/facial/limb anomalies, and reduced IQ (~9 points) and ↑ autism risk in exposed offspring. Avoid in pregnancy when possible; if essential, use lowest effective dose, divided dosing, and folate 4–5 mg/day preconception
— Topiramate: cleft lip/palate risk; also reduces oral contraceptive efficacy at doses >200 mg/day
— Lamotrigine, levetiracetam: preferred in pregnancy when feasible; levels drop in pregnancy (↑ glucuronidation) — monitor levels and increase dose; reduce postpartum
— Phenytoin, carbamazepine, phenobarbital: enzyme inducers — reduce hormonal contraceptive efficacy; use copper or 52-mg levonorgestrel IUD or depot medroxyprogesterone
— Long-acting reversible contraception (LARC) preferred — IUD or implant unaffected (mostly) by enzyme induction
— Document capacity and shared decision-making with guardian when appropriate
— Weight-based, divided dosing; infants/toddlers have higher clearance — may need higher mg/kg
— Avoid abrupt withdrawal of any ASM — risk of status epilepticus
— Liquid formulations and crushable tablets for G-tube–fed children
— Standard schedule; inactivated influenza annually; counsel that vaccines do not cause epilepsy but fevers may trigger seizures — treat fever promptly
— Continue ASMs through morning of surgery with sip of water; resume promptly post-op; have IV equivalents (levetiracetam, valproate, lacosamide) ready
— Avoid pro-convulsant agents (meperidine, tramadol, bupropion)
Key distinction: Among ASMs used in LGS, valproate has the worst pregnancy profile but the best efficacy — a classic Step 3 risk-benefit dilemma in a peripubertal female. The board-favored move: switch to lamotrigine or levetiracetam preconception with overlapping titration.
— Injury from drop attacks: facial/dental trauma, fractures, traumatic brain injury — helmets, environmental safety
— Status epilepticus (both convulsive and nonconvulsive): 50–75% lifetime risk; NCSE often missed, presents as confusion or behavioral change
— SUDEP (sudden unexpected death in epilepsy): ~1–9 per 1000 patient-years in refractory epilepsy; risk factors include GTCs, nocturnal seizures, polypharmacy, poor adherence; counsel families and discuss nocturnal supervision/seizure-detection devices
— Progressive intellectual disability in most (IQ <50 in ~85% after 5 years)
— Autism spectrum features, ADHD, aggression, self-injury
— Behavioral regression with clobazam (disinhibition) or levetiracetam (irritability — treat with pyridoxine 50–100 mg/day as adjunct)
— VPA: hepatotoxicity, pancreatitis, hyperammonemia, thrombocytopenia, weight gain, PCOS, tremor
— Topiramate: cognitive slowing, kidney stones, metabolic acidosis, oligohidrosis (heat stroke risk in summer)
— Lamotrigine: SJS/TEN, DRESS, HLH
— Felbamate: aplastic anemia, hepatic failure
— Phenytoin: gingival hyperplasia, hirsutism, cerebellar atrophy
— Vigabatrin: irreversible peripheral visual field constriction
— Osteopenia, vitamin D deficiency
— Dental caries (medications, poor oral hygiene)
— Constipation, GERD, aspiration pneumonia (dysphagia)
— Sleep disorders — OSA worsens seizure control
— Failure to thrive vs. obesity depending on ASM profile
— Caregiver depression, financial strain, sibling impact, loss of employment
— Marital stress — screen and refer
Board pearl: A child on lamotrigine for 2 weeks who develops fever, rash, lymphadenopathy, and transaminitis has DRESS — stop drug immediately, supportive care, consider systemic steroids; do not rechallenge.
— Convulsive status epilepticus (seizure >5 min or recurrent without recovery): IV lorazepam 0.1 mg/kg (or IM midazolam if no IV) → IV fosphenytoin/levetiracetam/valproate → continuous infusion (midazolam, propofol, pentobarbital) for refractory SE; intubate as needed
— Nonconvulsive status: suspect when prolonged altered mental status — obtain emergent EEG; treat similarly but more graded benzodiazepine approach
— Cluster seizures unresponsive to home rescue (>3 seizures in 24 hr, or 2 within 1 hr)
— New focal neurologic deficit, suspected head injury, prolonged postictal state >30 min
— Suspected serious ASM reaction: SJS/TEN, DRESS, hepatic failure, pancreatitis, aplastic anemia
— Failure of 2 appropriately chosen ASMs → comprehensive epilepsy center for surgical/dietary/device evaluation (definition of drug-resistant epilepsy)
— Regression in development, change in seizure semiology, or new EEG findings
— Suspected genetic/metabolic etiology
— Pediatric epileptologist (q3–6 months)
— Developmental pediatrics, neuropsychology, PT/OT/speech, dietitian if KD
— Social work and care coordination
— Status epilepticus, ASM toxicity, KD initiation (often inpatient 3–5 days for monitoring), VNS implantation recovery, surgical evaluation with prolonged video EEG
CCS pearl: A patient with LGS arriving altered with subtle facial twitching — order stat EEG and finger-stick glucose, give IV lorazepam empirically, and admit for continuous EEG. Do not wait for "improvement"; NCSE in LGS is common and underdiagnosed.
Step 3 management: Every clinic note for an LGS patient should answer three questions: (1) seizure frequency since last visit, (2) any injuries or ED visits, (3) is rescue medication current and accessible at home AND school?
— Onset 2–5 yr, previously normal development
— Myoclonic-atonic drop attacks, GTCs, atypical absence
— EEG: 2–5 Hz generalized spike-wave, no GPFA, often normal background
— Better prognosis — ~⅔ achieve remission; KD highly effective
— Key distinction: Doose patients are developmentally normal at onset and lack tonic seizures; LGS patients have tonic seizures, GPFA in sleep, and encephalopathy
— Onset in infancy with prolonged febrile seizures
— Multiple seizure types emerge by age 2; developmental slowing
— Avoid sodium-channel blockers (carbamazepine, oxcarbazepine, lamotrigine, phenytoin) — worsen seizures
— Treatments: valproate, clobazam, stiripentol, fenfluramine, cannabidiol
— Genetic testing distinguishes from LGS
— Marked sleep-activated epileptiform activity (>85% spike-wave index)
— Cognitive/language regression
— Treated with high-dose benzodiazepines, steroids/ACTH, IVIG
— Key distinction: CSWS dominates sleep EEG without GPFA bursts; language regression more prominent
— Onset 3–12 months: clusters of spasms, hypsarrhythmia on EEG, developmental arrest
— ~20–30% evolve into LGS — same patient, different phase
— Treat with ACTH, oral prednisolone, or vigabatrin (especially TSC)
— Brief typical absences, 3 Hz generalized spike-wave, normal development, ethosuximide-responsive — clearly distinct
Board pearl: A 4-year-old with new drop attacks and normal development with 3 Hz spike-wave is Doose, not LGS — KD is dramatically effective, and prognosis is good. Don't lump all drop-attack epilepsies as LGS.
— Vasovagal, cardiac (long QT, CPVT, HCM) — can produce brief tonic posturing and myoclonus
— Clue: pallor, postural trigger, brief duration, rapid recovery
— Obtain ECG; consider tilt-table
— Long QT syndrome — especially LQT2/3 with auditory triggers or sleep events
— Always ECG with QTc in any child with apparent generalized seizures and family history of sudden death
— Can coexist with true epilepsy in 10–30% of refractory cases
— Clues: side-to-side head shaking, asynchronous limb movements, eyes forcibly closed, pelvic thrusting, prolonged duration without postictal phase, normal ictal EEG
— Video EEG is diagnostic gold standard — capture event with no electrographic correlate
— Tics, stereotypies (especially in autism), paroxysmal kinesigenic dyskinesia, hyperekplexia (exaggerated startle, GLRA1 mutations — treated with clonazepam)
— Sandifer syndrome (GERD with dystonic posturing) in young children
— Parasomnias (night terrors, confusional arousals), REM behavior disorder, periodic limb movements — can mimic nocturnal tonic seizures
— Polysomnography with EEG montage if uncertain
— Hypoglycemia, hyponatremia, hypocalcemia — always check glucose and electrolytes in altered/seizing child
— Inborn errors: urea cycle defects, organic acidemias — recurrent encephalopathy with vomiting and elevated ammonia
— TCAs, bupropion, isoniazid (pyridoxine-responsive), sympathomimetics, anticholinergics — check vitals, pupils, urine drug screen
Key distinction: A "refractory LGS" patient who suddenly worsens with high-frequency dramatic events that are discordant from prior semiology should prompt evaluation for superimposed PNES — video EEG confirms and avoids unnecessary ASM escalation.
— Updated seizure action plan (written, including rescue medication name/dose/route, when to call 911)
— Verified rescue medication at home AND school (intranasal midazolam preferred — easy administration)
— Reconciled ASM list with doses, schedule, and last therapeutic levels
— Follow-up appointment scheduled before discharge (epileptology within 4–6 weeks)
— Helmet for drop attacks if not already in place
— Safety counseling: supervised bathing (shower seat, never tub immersion alone), no swimming alone, avoid heights, water temperature limits, bed rails or floor mattress to prevent fall-from-bed injuries
— Driving: counsel adolescents per state law (most US states require 3–12 months seizure-free)
— SUDEP risk discussion: documented annually; consider nocturnal supervision, seizure-detection devices (Empatica, SAMi)
— Vitamin D 1000–2000 IU/day, adequate calcium; check 25-OH D annually; DEXA in adolescents on long-term enzyme-inducing ASMs
— Cleanings every 6 months; gingival hyperplasia surveillance on phenytoin
— Annual influenza, COVID-19 boosters per CDC; pneumococcal if indicated; treat fevers promptly to reduce seizure triggers
— Treat OSA, constipation, GERD, dysphagia aggressively — each can worsen seizure control
— Mental health screening (depression, anxiety) at every visit in cognitively capable patients and caregivers
— IEP/504 plan, seizure action plan filed with school nurse, classroom aide if needed
— Connect family to Lennox-Gastaut Foundation, Epilepsy Foundation for peer support and respite
Step 3 management: Document SUDEP counseling annually — this is a quality measure and a frequent malpractice gap.
— Epileptology visit every 3–6 months when stable; more frequent during titration or after status
— Primary care every 6–12 months for growth, immunizations, mental health, comorbidity screening
— Valproate: LFTs, CBC, ammonia at baseline, 1, 3, 6 months, then every 6–12 months; level if breakthrough seizures or toxicity
— Lamotrigine: levels in pregnancy or breakthrough seizures; no routine labs needed otherwise
— Cannabidiol: LFTs at baseline, 1, 3, 6 months, then periodically; more often if on VPA
— Felbamate: CBC and LFTs every 2 weeks initially, then monthly
— Topiramate: serum bicarbonate annually; renal stones screening
— Rufinamide: ECG annually
— Fenfluramine: echocardiogram baseline, every 6 months while on therapy, and 3–6 months after discontinuation (REMS requirement)
— Vigabatrin: visual field testing every 3 months
— Repeat prolonged EEG annually or with significant semiology change or suspected NCSE
— MRI repeat if new focal features or before surgical evaluation
— Seizure first aid for family and school
— SUDEP, water safety, driving, bathing precautions
— Pregnancy planning in adolescents
— Medication adherence — missed doses are the #1 cause of breakthrough seizures
— Genetic counseling if heritable etiology identified
— Advance care planning in severe phenotypes
— Ongoing PT/OT/speech, behavioral therapy, applied behavior analysis if autism features
— Adaptive equipment, AAC devices for nonverbal patients
Board pearl: Fenfluramine is highly effective in LGS but requires REMS echocardiogram monitoring because of historical valvulopathy/pulmonary HTN risk from anorectic use — a common Step 3 detail.
Step 3 management: At every visit, ask: "When did you last refill rescue medication, and does it have at least 6 months until expiration?"
— Most LGS patients have intellectual disability — obtain consent from legal guardian/parent; involve adolescent assent when possible
— At age 18, formal guardianship or supported decision-making arrangements should be established before major decisions; document capacity assessment
— High-risk therapies (felbamate, surgery, KD initiation) require especially explicit risk-benefit documentation including aplastic anemia, hepatic failure, surgical morbidity
— Suspected child abuse/neglect: report to CPS if injury pattern is inconsistent with seizure history (e.g., posterior rib fractures, bruising in non-ambulatory child, burns in stocking distribution)
— Conversely, frequent ED visits for seizure injuries are NOT abuse — document carefully to protect families from inappropriate reports
— Driving: in some states (e.g., California, Pennsylvania), physicians are mandated to report a patient with uncontrolled seizures to DMV; know your state law
— Pediatric → adult neurology transition is a leading cause of medication errors and seizure escalation; use written transition packets and warm handoffs
— Hospital discharge: medication reconciliation including rescue meds and KD ratios; confirm pharmacy can fill specialty drugs (CBD, fenfluramine require REMS-registered pharmacies)
— Many LGS regimens involve off-label combinations; document rationale
— Prior authorization advocacy: physicians often must write letters of medical necessity for CBD, fenfluramine, KD formula coverage
— In severe phenotypes with frequent status, recurrent aspiration, and progressive decline, palliative care consultation is appropriate — not incompatible with active treatment
— Discuss DNR/DNI, MOLST/POLST forms, hospice eligibility when appropriate
— Many families seek clinical trials; ensure consent reflects realistic expectations and includes assent
Board pearl: A 14-year-old with LGS sustains a femur fracture from a drop attack and child protective services contacts you. The correct action is to document the seizure history, EEG findings, and injury mechanism thoroughly and communicate directly with the CPS worker — not to defensively refuse cooperation. Most reports resolve with clinical clarification.
Board pearl: "Tonic seizures in sleep + drops + slow spike-wave + GPFA" is the four-line LGS quartet — recognize it on any test stem.
Step 3 management: When in doubt on a CCS LGS case, default to: prolonged video EEG, MRI brain, optimize valproate, refer to comprehensive epilepsy center, counsel on SUDEP and rescue plan.
"A 5-year-old boy with history of infantile spasms now has multiple daily falls causing facial injuries and brief stiffening episodes during sleep. Development is delayed. EEG shows slow (1.5 Hz) generalized spike-and-wave."
— Diagnosis: LGS. Next step: prolonged video EEG ± MRI, start valproate.
"A child with LGS on valproate has drop attacks. Lamotrigine is added at standard pediatric dose and titrated weekly. Two weeks later he develops fever, rash, and facial swelling."
— Answer: SJS/DRESS from too-rapid lamotrigine titration with VPA; lesson: halve LTG starting dose, titrate ≥8 weeks.
"Carbamazepine is started for a child with LGS — seizures worsen."
— Answer: Sodium-channel blockers can exacerbate atypical absence/myoclonic/atonic seizures in LGS. Switch to broad-spectrum ASM.
"Child with LGS has failed valproate, lamotrigine, and topiramate. Most disabling feature is drop attacks."
— Answer: Refer to comprehensive epilepsy center for corpus callosotomy evaluation; consider KD or VNS.
"Adolescent with LGS becomes confused, drooling, with subtle eye flutter lasting 6 hours."
— Answer: NCSE. Stat EEG and treat with benzodiazepine.
"17-year-old with LGS on valproate wants to start a family in 2 years."
— Answer: Switch preconception to lamotrigine or levetiracetam; high-dose folate; LARC until ready.
"Child with hypopigmented macules and refractory LGS phenotype."
— Answer: Tuberous sclerosis — consider everolimus (mTOR inhibitor) and vigabatrin in addition to broad-spectrum ASMs.
"Fenfluramine started for LGS — what additional monitoring?"
— Answer: Baseline and every-6-month echocardiogram for valvulopathy/pulmonary hypertension.
"Child with cryptogenic epilepsy and developmental regression started on valproate develops acute liver failure."
— Answer: Test for POLG mutation (Alpers); avoid VPA in suspected mitochondrial disease.
Board pearl: Step 3 LGS stems reward recognition of the syndrome itself plus the specific monitoring trap of whichever drug is featured — memorize the monitoring bundle for each adjunct.
Lennox-Gastaut syndrome is a childhood-onset epileptic encephalopathy defined by multiple drug-resistant seizure types (especially tonic seizures in sleep and drop attacks), slow (<2.5 Hz) spike-wave with sleep-activated paroxysmal fast activity on EEG, and cognitive impairment — managed by valproate first-line plus syndrome-specific adjuncts (lamotrigine, rufinamide, clobazam, cannabidiol, fenfluramine, topiramate, or felbamate), early referral to a comprehensive epilepsy center for ketogenic diet, VNS, or corpus callosotomy when ≥2 ASMs fail, and lifelong attention to injury prevention, SUDEP counseling, and transition of care.
Rapid-fire recap bullets:
Board pearl: If a Step 3 stem includes "tonic seizures during sleep, drop attacks, and slow spike-and-wave EEG in a developmentally delayed child" — answer Lennox-Gastaut, start valproate, and refer to comprehensive epilepsy center if ≥2 ASMs have already failed.