Makindo Medical Notes

Infantile spasms are a neonatal/infantile epileptic emergency – not because of cardiorespiratory compromise, but because ongoing spasms and the underlying encephalopathy can devastate neurodevelopment if not treated quickly. Early recognition by parents, GPs and juniors shortens the “diagnostic delay”, which is strongly linked to cognitive outcome. Think of it as the “stroke equivalent” in infant epilepsy: diagnose fast, EEG fast, treat fast.

Definitions & the classic triad

• Infantile spasms (now often called epileptic spasms in infancy) are brief, stereotyped flexor and/or extensor movements, usually occurring in clusters.
• They typically start between 3–7 months of age (peak ~4–6 months).
• West syndrome = triad of:
  • Epileptic spasms
  • Hypsarrhythmia on EEG (chaotic, high-voltage, multifocal discharges)
  • Developmental arrest or regression

Many children with “infantile spasms” do not initially fulfil the full triad, but the label is often used interchangeably with West syndrome in clinical practice.

Typical clinical picture 🧐

• Spasm semiology
  • Sudden flexion of neck and trunk with adduction of arms (“jack-knife” or “salaam” attacks).
  • Can be pure flexor, pure extensor, or mixed; may look like a brief head-nod, startle or colic-type crunching.
  • Each spasm lasts only 1–2 seconds, but they occur in clusters of tens to hundreds, often every few seconds.
• Timing
  • Classically on waking from sleep or falling asleep.
  • Parents may describe “odd shuddering in bursts” or the baby “folding in half repeatedly”.
• Development
  • Loss of milestones or plateau: loss of social smile, reduced babbling, poorer eye contact, hypotonia or irritability.
  • Some infants already have developmental delay before the onset (symptomatic cases).

The key clinical teaching point for students: clustered stereotyped events + developmental concern in a 3–8 month old = infantile spasms until proven otherwise.

Aetiology – “symptomatic until proven otherwise” 🧬

• Structural – hypoxic–ischaemic encephalopathy, malformations of cortical development, periventricular leukomalacia, stroke, post-meningitis/encephalitis, intracranial haemorrhage.
• Genetic –
  • Tuberous sclerosis complex (TSC) (key association – look for hypomelanotic macules, cardiac rhabdomyomas).
  • Trisomy 21, CDKL5, ARX and many other epilepsy genes.
• Metabolic – pyridoxine-dependent epilepsy, mitochondrial disease, inborn errors of metabolism.
• Idiopathic/cryptogenic – normal development before onset and no identifiable cause on imaging/genetics; these have better outcomes.

Pathophysiologically, different aetiologies converge onto an abnormal cortico–subcortical network in the immature brain with disordered GABAergic and glutamatergic signalling. Hormonal therapies (ACTH/steroids) probably work by suppressing corticotropin-releasing hormone (CRH), a potent pro-convulsant in early life, while vigabatrin raises brain GABA levels by inhibiting GABA transaminase. :contentReference[oaicite:0]{index=0}

Initial assessment & red flags in clinic / ED

• History
  • Age at onset, video from parents, description of clusters, clear on/off periods.
  • Perinatal history (HIE, prematurity), family history of epilepsy or TSC.
  • Developmental trajectory – any regression.
• Examination
  • Neuro exam: tone, reflexes, visual attention, head circumference.
  • Skin: hypopigmented macules, shagreen patches, facial angiofibromas (TSC), neurocutaneous stigmata.
  • Dysmorphic features suggesting syndromic aetiology.
• Red flags – suspected infantile spasms in any child <2 years is a same-day paediatric neurology issue (NICE: urgent tertiary referral and EEG within 24 hours). :contentReference[oaicite:1]{index=1}

Key investigations 🔍

• EEG (ideally video EEG with sleep)
  • Diagnostic pattern = hypsarrhythmia: very high-amplitude, chaotic slow background with multifocal spikes.
  • Variants (“modified hypsarrhythmia”) may occur, especially in TSC or on treatment.
  • EEG may initially be non-diagnostic; repeat, especially capturing sleep, if suspicion remains high.
• MRI brain
  • High-resolution MRI to look for structural cause (cortical dysplasia, HIE changes, tubers in TSC, etc.).
• Metabolic / genetic work-up
  • Guided by history and local protocol – may include metabolic screen, chromosomal microarray, epilepsy gene panel.

NICE emphasises rapid EEG and MRI via a tertiary paediatric neurology service, with weekly review during acute treatment and repeat sleep EEG at ~2 weeks to document electroclinical remission. :contentReference[oaicite:2]{index=2}

Management – UK / NICE approach 💊

Principle: start treatment as soon as diagnosis is confirmed – preferably the same day. Treatment success is defined as cessation of spasms and resolution of hypsarrhythmia on EEG.

First-line treatment (NICE NG217)

• Infantile spasms NOT due to TSC:
  • Offer combination therapy with high-dose oral prednisolone + vigabatrin, unless the child is at high risk of steroid side-effects. :contentReference[oaicite:3]{index=3}
• High risk of steroid toxicity (e.g. significant cardiac disease, severe infection):
  • Consider vigabatrin monotherapy as first-line. :contentReference[oaicite:4]{index=4}
• Infantile spasms due to TSC:
  • Offer vigabatrin alone as first-line; if ineffective after ~1 week, add high-dose prednisolone. :contentReference[oaicite:5]{index=5}

Practical regimens (local guideline dependent)

• Prednisolone: many UK networks use ~10 mg QDS for 2 weeks, escalating to 20 mg TDS if spasms persist, then wean over several weeks as per protocol. :contentReference[oaicite:6]{index=6}
• Vigabatrin: started at about 50 mg/kg/day and increased over a few days up to 100–150(–200) mg/kg/day in 2 divided doses, titrated to response and tolerability. :contentReference[oaicite:7]{index=7}

For students: know the drug choice and intent, not the exact dosing – in practice you always follow the local guideline and BNFc.

Monitoring & safety

• On steroids:
  • Monitor blood pressure, weight and urinary/blood glucose at least weekly.
  • Screen for varicella exposure; provide steroid card and sick-day rules.
  • Warn about infection risk and GI upset; consider PPI and infection prophylaxis per local protocol. :contentReference[oaicite:8]{index=8}
• On vigabatrin:
  • Warn about potential peripheral visual field constriction with longer-term use.
  • Can cause drowsiness, movement disorders and characteristic but usually reversible MRI changes. :contentReference[oaicite:9]{index=9}
• Follow-up:
  • Weekly reviews during acute treatment; repeat sleep EEG at ~2 weeks to confirm electroclinical remission.

Second-line options

If first-line therapy fails, NICE recommends discussion with a tertiary paediatric epilepsy specialist. Options include ketogenic diet, levetiracetam, nitrazepam, sodium valproate or topiramate as monotherapy or add-ons, usually within a specialist service. :contentReference[oaicite:10]{index=10}

Prognosis & outcomes 📈

• Prognosis depends heavily on the underlying cause and time to seizure control.
• Idiopathic/cryptogenic cases with rapid treatment have the best cognitive outcomes; many still develop other epilepsy types later (e.g. Lennox–Gastaut), but some achieve seizure freedom.
• Symptomatic cases (HIE, TSC, structural malformations) often have ongoing epilepsy and significant intellectual disability despite good spasm control.
• Parents should be counselled that treatment aims to stop spasms quickly and maximise developmental potential, but does not “guarantee normality”.

Differential diagnosis – things that confuse everyone

• Benign myoclonus of infancy – brief clusters of myoclonus but normal development and EEG; often only in wakefulness.
• Benign neonatal sleep myoclonus – myoclonic jerks only during sleep; EEG normal, stops on waking.
• Startle reflex / Moro – triggered by sudden stimuli, not stereotyped clusters on waking.
• Reflux / colic – crying, back-arching, not the stereotyped, rapid clustering seen in spasms.
• Shuddering attacks, jitteriness – often longer shivers without clear clusters and with normal awareness.

The presence of developmental regression plus abnormal interictal EEG is what really separates infantile spasms from benign mimics.

Key exam and viva points 🎓

• Age: 3–7 months; think of West syndrome when you see “6-month old with clusters of flexor spasms”.
• Triad: spasms + hypsarrhythmia + regression.
• EEG: hypsarrhythmia – “chaotic, high-amplitude interictal pattern”.
• First-line treatment (UK/NICE):
  • Non-TSC: high-dose oral prednisolone + vigabatrin combination.
  • TSC or high steroid risk: vigabatrin monotherapy first-line. :contentReference[oaicite:11]{index=11}
• Why urgent? – because prolonged, uncontrolled spasms and epileptic encephalopathy worsen long-term neurodevelopmental outcome.