Pediatrics (System-Integrated)

Infantile spasms (West syndrome): recognition and management

Clinical Overview and When to Suspect Infantile Spasms

— Epileptic spasms (clusters of brief axial flexor/extensor jerks)

— Hypsarrhythmia on EEG (chaotic, high-voltage, multifocal)

— Developmental regression or arrest

— Structural: hypoxic-ischemic injury, stroke, malformations of cortical development (lissencephaly, focal cortical dysplasia), tuberous sclerosis complex (TSC)

— Genetic: ARX, CDKL5, STXBP1, TSC1/2, trisomy 21

— Metabolic: pyridoxine dependency, biotinidase deficiency, PKU, mitochondrial disorders

— Infectious: congenital CMV, prior meningitis/encephalitis

— Unknown (~10–15%, formerly "cryptogenic")

— Infant with brief, symmetric, repetitive flexion ("jackknife") or extension spells, often in clusters on awakening

— Frequently misdiagnosed as colic, GERD, startle, or Moro reflex — average diagnostic delay is weeks to months, which directly worsens neurodevelopmental outcome

— Loss of acquired milestones (social smile, head control, visual tracking) or decreased visual engagement

Infantile spasms (IS) = age-specific epileptic encephalopathy, peak onset 3–12 months (90% by age 1), part of the West syndrome triad:

Incidence ~2–5 per 10,000 live births; slight male predominance

Etiology is heterogeneous — categorized as:

When to suspect on the wards or clinic:

Board pearl: Any infant with new "clusters of crunches" plus developmental plateau gets a same-day or next-day video EEG — IS is a neurologic emergency because time-to-treatment correlates with cognitive outcome.

Step 3 management: In the outpatient setting, if a parent shows you a phone video of clustered flexor spasms, do not schedule routine neurology follow-up — arrange urgent pediatric neurology referral and inpatient or rapid-access EEG within 24–48 hours. Document the video in the chart; parental cell phone video is often the diagnostic moment.

Untreated IS evolves into Lennox-Gastaut in ~20% and chronic refractory epilepsy with intellectual disability in the majority.

Presentation Patterns and Key History

— Sudden, brief (1–2 sec) symmetric contraction of neck, trunk, and extremities

— Flexor ("salaam"/jackknife): head/arms flex, knees draw up

— Extensor: head/trunk extend, arms abduct (less common alone)

— Mixed flexor-extensor is most common overall

— Clusters of 5–50+ spasms over minutes, often on awakening or before sleep

— Infant frequently cries or appears startled/scared after a cluster — a useful clue distinguishing from benign myoclonus

— Loss of social smile, decreased eye contact, no longer tracking faces

— Regression of head control, rolling, babbling

— Visual inattention ("the baby stopped looking at me") is a frequent early sign

— Prematurity, HIE, perinatal stroke, neonatal hypoglycemia, intracranial hemorrhage

— TORCH exposure, especially CMV

— Tuberous sclerosis (parental hypomelanotic macules, seizures, renal AMLs)

— Consanguinity → suspect metabolic/recessive disorders

— Prior siblings with epilepsy or developmental delay

— Ash-leaf spots noted by parents under bath light

— Café-au-lait macules

— Benign myoclonus of infancy: clusters look similar but EEG is normal and development is preserved

— Sandifer syndrome (GERD): dystonic posturing temporally linked to feeds, not clusters on waking

— Shuddering attacks: brief, no postictal change, normal development

— Moro/startle: triggered by stimulus, single event

Spasm semiology — the cardinal feature:

Developmental history — the second pillar:

Birth and perinatal history:

Family history:

Skin exam clues elicited by history:

Key distinction: Differentiate from common mimics by clustering and post-event behavior:

Board pearl: Ask parents to record video on their phone before the visit; many spasms occur at home and are missed in clinic. A 30-second cluster video is essentially diagnostic when paired with hypsarrhythmia.

Quantify: number of spasms per cluster, clusters per day, time of day, and date of first event — needed for treatment-response tracking.

Physical Exam Findings and Neurodevelopmental Assessment

— Decreased visual attention, poor social engagement, absent or asymmetric smile

— Hypotonia (axial > appendicular) is common

— May appear "settled" between clusters — exam often normal between events, which falsely reassures clinicians

— Wood's lamp to identify hypomelanotic (ash-leaf) macules → tuberous sclerosis

— Shagreen patch (lumbosacral), facial angiofibromas (typically older), forehead fibrous plaque

— Café-au-lait macules → NF1 (less commonly causes IS)

— Linear sebaceous nevus, hypopigmented whorls (incontinentia pigmenti, hypomelanosis of Ito)

— Measure and plot OFC; microcephaly suggests structural/genetic cause, macrocephaly suggests megalencephaly or hydrocephalus

— Dysmorphic features → chromosomal/syndromic

— Fontanelle, sutures

— Funduscopy for chorioretinitis (congenital CMV/toxo), retinal hamartomas (TSC), optic atrophy

— Track-and-fix to assess cortical visual impairment — common in IS

— Tone (axial vs appendicular), spontaneous movement, primitive reflexes (persistence of Moro beyond 6 months is abnormal)

— Asymmetry → focal structural lesion (stroke, cortical dysplasia)

— DTRs, clonus

— Use ASQ-3 or Bayley-style milestones; compare to prior well-child notes for regression

— Document the date of last documented normal milestone

— Cardiac rhabdomyomas (TSC) — listen for murmur

— Hepatosplenomegaly → metabolic storage disease, congenital infection

General observation:

Skin exam — mandatory and high-yield:

Head and craniofacial:

Eyes:

Neurologic exam:

Developmental screen:

Cardiac and abdominal exam:

CCS pearl: On a CCS case, after "spasms" appear in the stem, order vital signs, OFC, full skin exam with Wood's lamp, funduscopy, and developmental assessment before jumping to EEG — these physical findings frequently localize the etiology and change the workup branch (e.g., TSC findings → renal US, echo, brain MRI looking for tubers).

Board pearl: Approximately 10–25% of infantile spasms cases are due to TSC — every IS exam must include Wood's lamp.

Diagnostic Workup — Initial Studies

— Standard: video EEG including both wakefulness and sleep (spasms and hypsarrhythmia are most prominent in non-REM sleep and on awakening)

— Hypsarrhythmia: chaotic, asynchronous, very-high-voltage (>200 µV) multifocal spikes/polyspikes on disorganized background

— Modified hypsarrhythmia variants (asymmetric, with preserved rhythmicity, fragmented) are equally diagnostic

— Ictal correlate of a spasm: high-voltage generalized slow wave followed by electrodecrement ("electrodecremental response")

— Brain MRI with and without contrast is required in all cases (not CT) — identifies cortical malformations, tubers, stroke, leukodystrophy, HIE pattern

— MRI often deferred until after acute treatment initiation if it would delay therapy, but should occur during the same admission

— CBC, CMP, glucose, calcium, magnesium, phosphate, ammonia, lactate, pyruvate

— Urinalysis with urine organic acids, serum amino acids, acylcarnitine profile

— Newborn screen review — confirm completed and normal (biotinidase, PKU, etc.)

— Consider CSF: glucose (glucose transporter deficiency — paired serum), lactate, amino acids, neurotransmitters if metabolic concern

— Chromosomal microarray as first-tier

— Epilepsy gene panel or whole-exome sequencing if microarray nondiagnostic — yield ~30–40%

— TSC1/TSC2 testing if clinical features support

— CMV PCR (urine or saliva) if congenital infection suspected

— Renal ultrasound (angiomyolipomas), echocardiogram (rhabdomyomas), dilated eye exam

EEG is the diagnostic centerpiece — obtain urgently:

Neuroimaging:

Initial laboratory studies (broad but targeted):

Genetic testing:

Infectious:

If TSC suspected:

Step 3 management: Do not delay treatment awaiting MRI or genetics — start first-line therapy as soon as hypsarrhythmia and clinical spasms are confirmed. Etiologic workup proceeds in parallel.

Board pearl: A "normal" routine 20-minute EEG does not exclude IS — you need prolonged video EEG capturing sleep. If clinical suspicion is high and a short EEG is normal, repeat with sleep recording.

Diagnostic Workup — Advanced and Confirmatory Studies

— If initial EEG is borderline or atypical, 24-hour or overnight video EEG captures sleep transitions when hypsarrhythmia is most florid

— Post-treatment EEG at ~2 weeks confirms resolution of hypsarrhythmia — clinical cessation alone is insufficient

— High-resolution 3T MRI with epilepsy protocol if standard MRI is normal but cause unclear — better detects focal cortical dysplasia

— FDG-PET or ictal SPECT if surgical candidacy is being evaluated (focal hypometabolism may reveal an occult dysplasia)

— Repeat MRI at age 2 if initial study at <6 months was nondiagnostic — myelination maturation can unmask subtle dysplasias

— CSF neurotransmitters and pterins

— Pyridoxine (B6) trial: IV pyridoxine 100 mg under EEG monitoring for pyridoxine-dependent epilepsy (ALDH7A1) — can be life-saving and treatable

— Pyridoxal-5-phosphate trial if pyridoxine fails (PNPO deficiency)

— Biotinidase activity, very-long-chain fatty acids, transferrin isoforms (CDG)

— Molybdenum cofactor (uric acid low, sulfite high)

— If panel negative → trio whole-exome sequencing (proband + both parents); yield up to 40–50% in unexplained IS

— Mitochondrial DNA sequencing if lactate elevated or maternal pattern

— Formal exam to assess cortical visual impairment, optic atrophy, hamartomas — informs prognosis and rehab

— Newborn hearing rescreen; CMV-related hearing loss may evolve

Extended/repeat video EEG:

Advanced neuroimaging:

Metabolic second-tier (if first-tier negative and clinical suspicion remains):

Genetic deep dive:

Ophthalmologic evaluation:

Audiology:

Key distinction: Clinical remission ≠ EEG remission. The therapeutic goal of first-line treatment is simultaneous cessation of clinical spasms AND resolution of hypsarrhythmia on repeat EEG at ~2 weeks. Persistent hypsarrhythmia despite clinical quiescence mandates treatment escalation.

Board pearl: Always trial pyridoxine in unexplained IS — missing pyridoxine-dependent epilepsy is a classic exam pitfall and the disorder is fully treatable with lifelong B6.

Risk Stratification and First-Line Management Logic

— Treatment lag >3–4 weeks from spasm onset is associated with worse developmental outcomes independent of etiology

— This is why IS is treated as a pediatric neurologic emergency

— High-dose ACTH (adrenocorticotropic hormone, IM)

— High-dose oral prednisolone (equally effective in most studies, lower cost, oral route)

— Vigabatrin — drug of choice if TSC is the etiology; also used as first-line in non-TSC cases in some protocols or when steroids contraindicated

— TSC confirmed or strongly suspected → vigabatrin first (response rates >90% in TSC)

— Non-TSC etiology → hormonal therapy (ACTH or prednisolone) preferred; combination hormonal + vigabatrin is superior to hormonal alone in some trials (UKISS) for non-TSC

— Contraindications to steroids (active infection, severe immunocompromise) → vigabatrin

— Unknown etiology with prompt treatment: best prognosis, ~50% normal development

— TSC: variable; early vigabatrin improves outcomes

— Structural (HIE, malformation): guarded

— Genetic (CDKL5, ARX): typically poor regardless of seizure control

— Weight, BP, glucose, electrolytes, CBC, CXR, PPD/IGRA (for steroids), ophthalmologic baseline (for vigabatrin retinal toxicity), developmental assessment

Treatment goal: rapid, complete cessation of spasms AND hypsarrhythmia, ideally within 2 weeks of initiating therapy — early response correlates with better cognitive outcomes

Time-to-treatment matters:

First-line options (United States standard):

Choosing among first-line:

Etiology-based stratification of prognosis:

Pre-treatment baseline:

Step 3 management: Initiate first-line therapy as an inpatient in most US centers — allows BP/glucose monitoring on steroids, parental injection teaching for ACTH, and rapid EEG response assessment. Discharge with a clear written taper, home BP/glucose log, and scheduled repeat EEG at ~2 weeks.

Board pearl: The single most important predictor of good developmental outcome (modifiable) is short lead-time to effective treatment — every day matters.

Pharmacotherapy — First-Line Regimens in Detail

— Dose: typical US regimen 150 U/m²/day IM divided BID for 2 weeks, then taper over 2 weeks

— Mechanism: presumed direct CNS effect on CRH receptors, plus glucocorticoid effect

— Adverse effects: hypertension, hyperglycemia, immunosuppression, irritability, Cushingoid features, GI bleeding, hypokalemia, cardiomyopathy

— Monitoring: BP at home daily, weekly weight, glucose checks, electrolytes, watch for infection

— Prophylaxis: PPI, sometimes PCP prophylaxis at higher doses

— Cost: historically extremely expensive in US (often >$100K/course) — prior authorization required

— Dose: 40–60 mg/day divided, increased to 60 mg if no response by day 7; 2-week course then taper

— Equally efficacious to ACTH in head-to-head data

— Same adverse effect profile as ACTH (HTN, hyperglycemia, infection risk, irritability)

— Oral, lower cost, no injections — often preferred by families

— Dose: start 50 mg/kg/day, titrate to 100–150 mg/kg/day divided BID

— Mechanism: irreversible GABA transaminase inhibitor → increases CNS GABA

— First-line in TSC

— Major toxicity: permanent peripheral visual field constriction (concentric VF loss) — REMS program in US; baseline and serial visual assessments (ERG in infants)

— Also: MRI white matter changes (usually reversible), sedation, hypotonia

— UKISS-2 trial: combination superior to hormonal alone in non-TSC IS for spasm cessation at day 14 and 18 months

— Used increasingly in US centers for non-TSC IS

— Clinical: daily spasm diary; goal complete cessation by day 14

— EEG: repeat at ~2 weeks post-initiation to confirm hypsarrhythmia resolution

— Switch to the alternate first-line agent (e.g., steroids → vigabatrin, or vice versa)

— Then consider ketogenic diet, topiramate, zonisamide, valproate, pyridoxine, or epilepsy surgery evaluation

ACTH (corticotropin):

High-dose oral prednisolone:

Vigabatrin:

Combination therapy (hormonal + vigabatrin):

Response assessment:

If first-line fails (no response or relapse):

Board pearl: Vigabatrin's irreversible retinal toxicity is dose- and duration-dependent — limit exposure to the shortest effective course (typically 6 months if effective, longer in TSC), and document informed consent in the chart.

Non-Pharmacologic and Surgical Management

— High-fat, low-carbohydrate, adequate-protein diet inducing ketosis

— Effective second/third-line option; spasm cessation in ~30–50% of refractory cases

— Requires inpatient initiation in most centers, dietician support, carnitine and micronutrient supplementation

— Adverse effects: acidosis, hypoglycemia, kidney stones, growth restriction, hyperlipidemia, constipation

— Contraindications: fatty acid oxidation defects, pyruvate carboxylase deficiency, primary carnitine deficiency, porphyria

— Indicated for focal structural lesions identified on MRI/PET (cortical dysplasia, tuber, stroke, tumor) producing refractory spasms

— Hemispherectomy for diffuse unilateral pathology (Sturge-Weber, hemimegalencephaly, large MCA infarct)

— Lesionectomy or tuberectomy for discrete lesions

— Earlier surgery → better developmental outcome when refractory; do not delay surgical referral hoping for medication response if MRI shows a resectable lesion

— Topiramate, zonisamide, valproate, levetiracetam, benzodiazepines (nitrazepam, clobazam)

— Used as add-ons or when first-line fails/is contraindicated

Ketogenic diet:

Epilepsy surgery:

Other antiseizure medications (less effective for IS specifically):

Vagal nerve stimulation, responsive neurostimulation: limited evidence in infants; later option in chronic refractory epilepsy that evolves

Cannabidiol (Epidiolex): FDA-approved for Lennox-Gastaut, Dravet, TSC-associated seizures ≥1 year — role in pure IS still emerging

Step 3 management: A child with refractory IS and an MRI lesion (focal cortical dysplasia, large tuber, infarct) should be referred to a Level 4 epilepsy surgery center promptly, not cycled indefinitely through more medications — surgical cure is possible and developmental window is narrow.

Board pearl: Refractory IS + unilateral MRI lesion + persistent hypsarrhythmia → think surgical workup with PET/SPECT, not another ASM.

Special Populations — Comorbidities and Organ Dysfunction

— Steroids and ACTH cause profound immunosuppression — screen for active TB (PPT/IGRA), varicella exposure, and ensure live vaccines deferred

— Avoid live vaccines (MMR, varicella, rotavirus, live influenza) during and for ~3 months after hormonal therapy

— Inactivated vaccines may be given but immune response is blunted

— ACTH/prednisolone can cause significant hypertension; home BP monitoring is standard

— Rare but reported: hypertrophic cardiomyopathy with ACTH — baseline echo not routine but obtain if murmur, poor feeding, or prolonged course

— Treat HTN with amlodipine or other infant-appropriate agent if persistent

— Hyperglycemia during steroid course — periodic glucose checks; rare to require insulin

— Vigabatrin is renally excreted — reduce dose in renal impairment (uncommon in infants but consider in chronic kidney disease)

— Valproate hepatotoxic and contraindicated <2 years with suspected metabolic disease (POLG mutation risk)

— Topiramate: monitor for metabolic acidosis, oligohidrosis

— Both ACTH and prednisolone suppress the HPA axis — stress-dose steroids required for surgery or serious illness for up to 6 months post-taper

— Provide families with a wallet card and discharge instructions

— Screen for renal angiomyolipomas (US), cardiac rhabdomyomas (echo), retinal hamartomas

— mTOR inhibitors (everolimus) may have role in refractory TSC-associated epilepsy

Concurrent infection or immunocompromise:

Hypertension and cardiomyopathy:

Glycemic effects:

Renal/hepatic considerations:

Adrenal axis:

Patients with TSC:

CCS pearl: Before discharging an infant after hormonal therapy, order home BP cuff, glucose meter, PPI, written sick-day stress-dose plan, and 2-week neurology follow-up with repeat EEG — missing any one of these is a common CCS deduction.

Board pearl: A child on/recently off ACTH or prednisolone presenting with shock or severe illness needs empiric hydrocortisone stress dose — adrenal suppression persists for months.

Special Populations — Genetic Syndromes and Etiologic Subgroups

— Up to 25% of IS cases; vigabatrin first-line (response >90%)

— Some centers initiate vigabatrin preemptively in infants with TSC at first sign of EEG abnormality before clinical spasms (EPISTOP trial) — improves outcomes

— Multidisciplinary surveillance: renal US, echo, eye exam, skin, dental, neuropsych

— Increased IS incidence; excellent response to ACTH or vigabatrin with often favorable cognitive prognosis relative to baseline trisomy 21 expectations

— Screen for cardiac defects before steroid therapy (volume/pressure considerations)

— CDKL5 — predominantly girls, early-onset refractory epilepsy, severe developmental impairment

— ARX — boys, often with genital anomalies and lissencephaly

— Generally poor response to standard first-line

— Neonatal or early infantile refractory seizures including spasms

— Lifelong pyridoxine supplementation; add folinic acid; lysine-restricted diet may help

— CSF/serum glucose ratio <0.5; ketogenic diet is treatment of choice

— Periventricular calcifications, polymicrogyria, hearing loss

— Consider ganciclovir/valganciclovir if identified in neonatal period for hearing preservation

— Higher IS risk; standard treatment still applies but prognosis driven by underlying injury

— Resume routine inactivated vaccines on schedule; defer live vaccines per timing above

— Pertussis-containing vaccines are not contraindicated in IS — old myth

Tuberous sclerosis complex (TSC):

Down syndrome (trisomy 21):

X-linked disorders (ARX, CDKL5):

Pyridoxine-dependent epilepsy (ALDH7A1):

Glucose transporter 1 (GLUT1) deficiency:

Congenital CMV:

Premature infants with HIE/PVL:

Vaccination considerations:

Key distinction: Vigabatrin is preferred first-line in TSC; hormonal therapy (ACTH or oral prednisolone) is preferred first-line in non-TSC IS. This single-fact distinction appears repeatedly on boards.

Board pearl: All infants with new IS need chromosomal microarray + epilepsy gene panel as part of workup — yield is high enough to change counseling, recurrence risk, and sometimes treatment.

Complications and Adverse Outcomes

— Intellectual disability in 70–90% even with treatment; severity depends heavily on etiology and treatment delay

— Autism spectrum disorder in 30–35%

— Cerebral palsy, especially in structural etiologies

— Cortical visual impairment

— Lennox-Gastaut syndrome in ~20% — multiple seizure types (tonic, atypical absence, atonic), slow spike-and-wave on EEG, often refractory

— Focal epilepsy or other generalized epilepsies

— Persistent refractory epilepsy in ~50–60%

— Overall ~5–10%, mostly driven by underlying disorder, not seizures themselves

— SUDEP risk elevated in refractory epilepsy

— ACTH/prednisolone: hypertension, hyperglycemia, infection (sepsis, opportunistic), GI bleed, irritability, cushingoid appearance, transient cardiomyopathy, adrenal suppression

— Vigabatrin: permanent visual field constriction (~30% with prolonged use), reversible MRI signal changes in basal ganglia/thalamus

— Ketogenic diet: acidosis, kidney stones, dyslipidemia, growth restriction

— High caregiver burden, depression, financial strain

— Sibling impact; need for early intervention enrollment, IEP/IFSP planning

— Disrupted sleep architecture, feeding difficulties, GERD, aspiration risk

— Many children require G-tube placement

Neurodevelopmental complications (the dominant long-term morbidity):

Evolution to other epilepsy syndromes:

Mortality:

Treatment-related complications:

Family/psychosocial impact:

Sleep and feeding:

Board pearl: When counseling families, frame the two parallel problems: (1) controlling seizures and (2) supporting development — successful seizure control does not guarantee normal development, particularly in structural/genetic etiologies.

Step 3 management: Refer every IS patient to early intervention (Part C services, age <3) at diagnosis, not after treatment fails — federal entitlement, free to families, and earlier enrollment improves outcomes. Document referral in discharge plan.

When to Escalate Care — Inpatient Triage and Consults

— Any infant with suspected IS should be admitted or seen same-day at a pediatric neurology center for video EEG and treatment initiation

— Do not manage IS as an outpatient first encounter at a general pediatrician's office

— Pediatric neurology / epileptology — primary

— Genetics — for etiologic workup, recurrence counseling

— Ophthalmology — baseline and vigabatrin monitoring

— Developmental pediatrics / early intervention

— Nutrition / dietician — for ketogenic diet candidates

— Cardiology — if structural disease (TSC), or pre-steroid baseline if indicated

— Status epilepticus (not classic for IS but possible)

— Respiratory compromise during cluster

— Severe steroid complications (sepsis, GI hemorrhage, hypertensive emergency)

— No response to first-line at 2 weeks (persistent spasms or hypsarrhythmia) → switch to alternate first-line

— Relapse after initial response (~30%) → repeat course or switch agents

— Refractory after both hormonal and vigabatrin → ketogenic diet, surgical evaluation

— Refractory spasms despite two first-line agents

— Focal lesion on MRI potentially amenable to surgery

— Diagnostic uncertainty (atypical EEG, mixed semiology)

— Need for advanced imaging (PET/SPECT), invasive monitoring, or hemispherectomy

— Recurrence of spasms (parents instructed to record video and call immediately)

— New focal seizures, loss of previously regained milestones

— Steroid-related: BP >95th percentile, fever, vomiting/melena, lethargy

Initial diagnosis is itself an escalation event:

Mandatory consultations:

ICU criteria:

Indications for treatment escalation:

When to refer to a Level 4 epilepsy center:

Outpatient red flags requiring urgent re-evaluation post-discharge:

CCS pearl: When the simulated case shows a parent reporting "the jerks started coming back," the correct next move is same-day video EEG and pediatric neurology contact, then likely reinitiation or switch of therapy — not "follow up in clinic in 2 weeks."

Board pearl: "Treatment lag of >3 weeks" is a recurring board-quality distractor — always pick the option that escalates fastest.

Key Differentials — Other Pediatric Epilepsy and Movement Disorders

— Clusters of myoclonic jerks resembling spasms, but EEG is completely normal and development is normal

— Resolves spontaneously by age 2; reassurance only

— True epilepsy with brief myoclonic seizures; EEG shows generalized spike-wave but no hypsarrhythmia

— Responds to valproate; better prognosis

— Neonatal onset (vs IS at 3–12 months)

— EEG shows burst-suppression (vs hypsarrhythmia)

— Often evolve into IS at ~3–6 months

— Etiology heavily genetic/metabolic; prognosis poor

— Fever-triggered prolonged seizures starting <1 year, then multiple seizure types

— Different EEG pattern, no hypsarrhythmia

— Onset typically 1–8 years (older than IS)

— Multiple seizure types, slow spike-and-wave (1.5–2.5 Hz)

— Frequent evolution from prior IS

— Differentiated by focal EEG findings and asymmetric semiology

— Longer duration (seconds–minutes) than spasms (1–2 sec); different EEG pattern; common in LGS

Benign (non-epileptic) myoclonus of infancy:

Benign myoclonic epilepsy of infancy:

Early myoclonic encephalopathy (EME) and Ohtahara syndrome (early infantile epileptic encephalopathy):

Dravet syndrome (SCN1A):

Lennox-Gastaut syndrome:

Focal/partial seizures with subtle motor manifestations:

Tonic seizures:

Key distinction: Spasm = brief (~1–2 sec) axial contraction in clusters; tonic seizure = sustained contraction (>5 sec); myoclonus = very brief, often single jerk. Duration and clustering are the discriminating features by history.

Board pearl: The triad (spasms + hypsarrhythmia + developmental regression) at age 3–12 months is specific for West syndrome / IS. Change any element materially (different age, different EEG, single events) and the diagnosis shifts.

Key Differentials — Non-Epileptic Mimics

— Dystonic posturing, head tilt, opisthotonos temporally linked to feeds

— Normal EEG, normal development, often with feeding difficulties or failure to thrive

— Treat the reflux → resolves

— Brief tremor-like episodes, normal awareness, no postictal change, normal EEG and development

— Often familial (essential tremor link)

— Exaggerated startle to stimuli, stiffness, normal EEG

— Treat with clonazepam

— Provoked by upset/pain; cyanotic or pallid; brief LOC; resolves with age

— Repetitive movements that can be interrupted, normal EEG, no impaired awareness

— Triad of head nodding, head tilt, nystagmus in infants 6–12 months; rule out optic pathway glioma with MRI

— Moro persisting beyond 6 months — abnormal but distinct from spasms

— Metabolic seizures with discrete electrolyte cause; EEG normal once corrected

— Dyskinesias of glutaric aciduria, GLUT1, etc.

— Rare in infants; consider in older toddlers

Sandifer syndrome (GERD):

Shuddering attacks:

Hyperekplexia (startle disease, GLRA1 mutation):

Breath-holding spells:

Self-stimulation / gratification behaviors:

Spasmus nutans:

Tonic neonatal reflexes persisting abnormally:

Hypocalcemic or hypoglycemic seizures:

Inborn errors of metabolism with non-epileptic movement disorders:

Functional/non-epileptic spells:

Key distinction: The single most important step when something looks like spasms but isn't sure is video EEG capturing the event. Home video plus EEG resolves nearly every diagnostic ambiguity.

Step 3 management: If a Step 3 vignette gives you a 9-month-old with "spells that look like reflux" but mentions loss of social smile or developmental regression, the answer is not "increase the omeprazole" — it is video EEG to rule out infantile spasms. The developmental component is the discriminating clue.

Board pearl: Developmental regression flips any "benign" movement disorder differential toward IS.

Secondary Prevention, Discharge Medications, and Long-Term Plan

— First-line agent with explicit dosing and taper schedule in writing (ACTH IM with syringes, prednisolone with oral syringe, or vigabatrin BID dosing)

— PPI (omeprazole/lansoprazole) during steroids for GI protection

— Potassium supplementation if hypokalemia on steroids

— Stress-dose hydrocortisone instructions and wallet card for 6 months post-taper

— Antihypertensive (amlodipine) if BP elevated

— Other ASMs only if added as adjunct

— Home BP cuff (infant-appropriate) with logbook

— Glucose meter with target ranges

— Spasm diary — count clusters and spasms per day

— Cell phone video for any new event

— Defer live vaccines until ~3 months after steroid taper completion

— Continue inactivated vaccines on schedule (DTaP, Hib, pneumococcal, hepatitis B, IPV, inactivated influenza)

— Document a revised immunization schedule in the chart

— Vigabatrin typically continued 6 months if effective and non-TSC; longer in TSC

— Hormonal therapy is a finite course (4–6 weeks total including taper), not maintenance

— If new seizure types emerge → add agent appropriate to type

— ~30% relapse after initial response — families educated to record video and call urgently

— Repeat course of first-line vs switch agent

— Early intervention referral (Part C, <3 years) at discharge — PT, OT, speech, developmental therapy

— Schedule transition to IEP at age 3 via local school district

— Discuss recurrence risk based on identified or suspected etiology; offer sibling testing where relevant

Discharge medication checklist after initial admission:

Home monitoring tools to provide:

Vaccination plan:

Long-term antiseizure medication strategy:

Relapse plan:

Developmental and rehab services:

Genetic counseling:

Step 3 management: A written, individualized care plan at discharge (medications, monitoring, red flags, vaccination, EI referral, follow-up dates) is the Step 3-correct deliverable — generic instructions are a deduction.

Board pearl: Stress-dose steroid teaching is the most commonly missed discharge item.

Follow-Up, Monitoring Parameters, and Counseling

— Day 7 phone or clinic check: spasm count, BP, glucose, side effects, weight

— ~Day 14 in-person + repeat video EEG: confirm clinical and EEG resolution; if not resolved, escalate

— Day 28 (end of taper): clinical exam, adrenal axis discussion, vaccination plan

— Monthly for 3 months, then every 3 months in year 1

— Baseline ophthalmology (ERG/VEP in infants since perimetry impossible)

— Repeat every 3 months while on therapy

— Discontinue if visual changes detected or after 6 months if non-TSC and response sustained

— Daily home BP, weekly weight, periodic glucose, stool for blood if symptoms

— Watch for infection — low threshold for evaluation

— Bayley Scales or equivalent at 6, 12, 24 months post-treatment

— Vision and hearing assessments

— ASD screening (M-CHAT-R/F) at 18 and 24 months

— At 2 weeks post-initiation

— At end of taper / before stopping vigabatrin

— If clinical concern for relapse or new seizure type

— Realistic prognosis based on etiology — avoid both false reassurance and undue pessimism

— Importance of medication adherence and avoiding abrupt discontinuation

— Recognition of relapse and emergency contact pathway

— Sibling testing if genetic etiology identified

— Connection to family advocacy groups (e.g., Infantile Spasms Action Network, TS Alliance)

— IFSP transition to IEP at age 3

— Discuss daycare safety, seizure action plan

Follow-up cadence after first-line initiation:

Routine monitoring on vigabatrin:

Routine monitoring on steroids/ACTH:

Developmental surveillance:

EEG monitoring:

Counseling topics for parents:

School and community planning:

Step 3 management: When the Step 3 stem says "infant is now 3 months post-treatment, no spasms, has not had EEG since discharge" — the correct next step is repeat EEG to confirm sustained remission, not "continue current management."

CCS pearl: Order developmental assessment and ophthalmology at every follow-up — both are commonly forgotten and both are scored.

Ethical, Legal, and Patient Safety Considerations

— Vigabatrin REMS in the US — prescriber and pharmacy registration mandatory; document discussion of irreversible visual field loss in the chart with parental signature

— Steroid/ACTH consent: discuss hypertension, hyperglycemia, infection risk, mood/behavior changes, cardiomyopathy, adrenal suppression, and the time-limited window for benefit

— Off-label combinations and ketogenic diet also warrant explicit consent

— Repetitive flexor spasms can be mistaken for non-accidental trauma (shaken baby) or vice versa — both must be entertained in unclear cases

— Conversely, unexplained intracranial findings on MRI in an infant with "spasms" warrant evaluation for abuse if history doesn't fit

— Document all clinical reasoning carefully

— High risk during transitions: ED → ward → outpatient

— Medication reconciliation for stress-dose steroids, taper schedule, and vigabatrin REMS handoff is a documented patient-safety vulnerability

— Provide a written discharge summary directly to the primary pediatrician within 48 hours; do not rely on the family to convey complex regimens

— Treatment lag is the most preventable harm in IS — institutions should have a rapid-access spasm pathway with same-day or next-day EEG

— Failure to recognize spasms misdiagnosed as colic/GERD is a recurring malpractice theme

— Families may incorrectly attribute IS to recent vaccination (especially pertussis) — IS onset overlaps with the 2–4 month vaccine window

— No causal link; counsel clearly, document, and continue inactivated immunizations on schedule

— ACTH cost (>$100K/course historically) and vigabatrin REMS create access disparities — oral prednisolone is equally effective and far cheaper, an important equity-aware choice for value-based care

— Discuss implications of genetic testing for the child and siblings, including insurance protections (GINA) and limitations (life/disability insurance not covered)

Informed consent for high-risk therapies:

Mandatory reporting and child protection:

Transition-of-care safety:

Diagnostic delay as a safety event:

Vaccine hesitancy and misinformation:

Equity and access:

Genetic information privacy:

Step 3 management: The board-correct discharge always includes a direct PCP handoff with written med list, taper, red flags, EI referral, and EEG follow-up date — gaps here are scored against you.

Board pearl: Document the vigabatrin retinal toxicity discussion explicitly — it is the most commonly cited consent failure in IS care.

High-Yield Associations and Rapid-Fire Clinical Facts

West syndrome triad: spasms + hypsarrhythmia + developmental regression/arrest

Peak age: 3–12 months (90% by age 1)

Hypsarrhythmia: chaotic, high-voltage (>200 µV), multifocal spikes on disorganized background; most evident in non-REM sleep

Ictal EEG of a spasm: high-voltage slow wave + electrodecrement

TSC is the single most common identifiable cause (~10–25%) → vigabatrin first-line

Non-TSC first-line in US: ACTH or high-dose oral prednisolone

Vigabatrin toxicity: irreversible peripheral visual field constriction; mechanism = irreversible GABA transaminase inhibition

ACTH/prednisolone toxicities: HTN, hyperglycemia, immunosuppression, irritability, cardiomyopathy, adrenal suppression

Pyridoxine-dependent epilepsy (ALDH7A1): always trial B6 in unexplained refractory infantile epilepsy

GLUT1 deficiency: low CSF/serum glucose ratio → ketogenic diet

Evolution to Lennox-Gastaut: ~20%

Long-term intellectual disability: 70–90%

Autism spectrum: ~30%

Treatment goal: cessation of spasms AND hypsarrhythmia by ~2 weeks

Mimics: Sandifer (GERD), benign myoclonus of infancy, shuddering attacks, hyperekplexia, gratification behavior

Live vaccines: defer 3 months after steroid taper; inactivated continue on schedule

Stress-dose steroids: required for ~6 months post hormonal therapy

Skin clue: Wood's lamp for ash-leaf spots → TSC

First-tier genetics: chromosomal microarray; then epilepsy panel or WES

TSC preemptive vigabatrin at EEG abnormality before clinical spasms (EPISTOP): improves outcomes

UKISS-2: combination hormonal + vigabatrin > hormonal alone in non-TSC

Pertussis vaccine does NOT cause IS — debunked association; do not withhold

EI referral (Part C, <3 years): federal entitlement, free, must be in discharge plan

Board pearl: If a board stem mentions a young infant with clustered "jackknife" episodes on awakening + losing milestones + ash-leaf macules, the diagnosis is IS due to TSC and the answer is vigabatrin — not ACTH, not prednisolone.

Key distinction: Hypsarrhythmia (IS) vs burst-suppression (Ohtahara/EME) vs slow spike-wave (LGS) — three age-keyed encephalopathy patterns.

Board Question Stem Patterns

— 7-month-old with "colic" or "reflux," parents describe brief flexor episodes in clusters on awakening, has stopped smiling socially

— Best next step: video EEG (not reassurance, not PPI escalation)

— Infant with new spasms and hypomelanotic macules under Wood's lamp

— Diagnosis: TSC-associated IS; answer: vigabatrin

— Same stem without TSC features: answer is ACTH or oral prednisolone

— Infant on therapy for IS develops peripheral visual field constriction on follow-up

— Drug: vigabatrin

— Infant on therapy develops hypertension and hyperglycemia: drug is ACTH or prednisolone

— Description of "chaotic, high-amplitude, multifocal spikes on disorganized background" in a 6-month-old

— Pattern: hypsarrhythmia; diagnosis: infantile spasms

— 14 days into prednisolone, persistent spasms and hypsarrhythmia

— Next step: switch to vigabatrin (or add vigabatrin) — not "increase prednisolone indefinitely"

— Infant with brief jerks in clusters but normal EEG and normal development

— Diagnosis: benign myoclonus of infancy; management: reassurance

— Neonate/infant with refractory seizures unresponsive to standard ASMs

— Next step: IV pyridoxine trial under EEG

— Refractory IS, MRI shows unilateral cortical dysplasia

— Next step: refer to Level 4 epilepsy surgery center, not another ASM

— Parent refuses vaccines after child diagnosed with IS, citing "vaccine caused this"

— Best response: counsel that no causal link; continue inactivated vaccines on schedule; defer live vaccines while on/recently off steroids

— Infant completing prednisolone taper, due for routine 6-month MMR

— Action: defer live vaccine until ~3 months after taper; provide stress-dose hydrocortisone instructions

Pattern 1 — Classic missed diagnosis:

Pattern 2 — Choose first-line by etiology:

Pattern 3 — Adverse effect recognition:

Pattern 4 — EEG interpretation:

Pattern 5 — Treatment failure / next step:

Pattern 6 — Mimic discrimination:

Pattern 7 — Metabolic salvage:

Pattern 8 — Surgical candidacy:

Pattern 9 — Vaccine question:

Pattern 10 — Discharge planning:

Board pearl: When the stem includes any combination of clusters + age 3–12 months + developmental concern, the answer almost always involves urgent EEG and a first-line agent chosen by TSC status.

One-Line Recap

High-yield recap bullets:

Infantile spasms is a pediatric neurologic emergency — recognize clustered flexor/extensor spasms with developmental regression in infants 3–12 months, confirm with video EEG showing hypsarrhythmia, treat immediately with vigabatrin (if tuberous sclerosis) or hormonal therapy with ACTH/high-dose prednisolone (non-TSC), and aim for complete clinical and EEG remission within two weeks to preserve neurodevelopmental outcome.

Triad: epileptic spasms + hypsarrhythmia (chaotic, >200 µV, multifocal) + developmental regression — peak age 3–12 months

First-line by etiology: TSC → vigabatrin; non-TSC → ACTH or high-dose oral prednisolone (equally effective); consider combination in non-TSC per UKISS-2

Workup: urgent video EEG with sleep, brain MRI, Wood's lamp skin exam, chromosomal microarray + epilepsy gene panel, metabolic screen, pyridoxine trial if refractory/unexplained

Response goal: cessation of clinical spasms AND hypsarrhythmia confirmed on repeat EEG at 2 weeks — not clinical alone

Key toxicities: vigabatrin → irreversible peripheral visual field loss (REMS, baseline + q3-month ophthalmology); steroids/ACTH → HTN, hyperglycemia, immunosuppression, adrenal suppression for ~6 months (stress-dose plan)

Refractory disease: switch to alternate first-line, then ketogenic diet, then surgical referral if focal MRI lesion — do not endlessly cycle medications

Long-term: ID in 70–90%, ASD ~30%, evolution to Lennox-Gastaut in ~20%; early intervention (Part C) referral at diagnosis is mandatory

Discharge essentials: written taper, home BP/glucose monitoring, PPI, stress-dose steroid card, deferred live vaccines, scheduled 2-week EEG, EI referral, PCP handoff

Board pearl: Time-to-treatment is the most important modifiable predictor of cognitive outcome — every day of delay matters, so treat hypsarrhythmia + spasms the day you see them.