Infantile Spasms (West Syndrome)
Summary
Infantile Spasms (IS), also known as West Syndrome, is a severe epileptic encephalopathy occurring in infancy, typically between 3-12 months of age. It is characterised by a classic triad: Infantile Spasms (brief, sudden symmetric flexion or extension movements – "Salaam attacks"), Developmental Regression or Arrest, and Hypsarrhythmia (chaotic, high-amplitude EEG pattern). The prognosis is often poor, with high rates of subsequent intellectual disability, autism, and evolution to other epilepsy syndromes (e.g., Lennox-Gastaut Syndrome). Underlying aetiologies are diverse (Structural, Genetic, Metabolic, Unknown). Treatment is urgent – first-line options are Vigabatrin (especially for Tuberous Sclerosis Complex) or High-Dose Steroids (ACTH or Prednisolone). Early diagnosis and treatment improve outcomes. [1,2]
Clinical Pearls
"Salaam Attack": The classic flexor spasm – sudden flexion of neck, trunk, and arms, like a "salaam" greeting or "jackknife" motion. Often occurs in clusters.
Hypsarrhythmia is KEY: A chaotic, disorganised, very high-amplitude EEG pattern with multifocal spikes. Pathognomonic of West Syndrome.
Urgent Treatment Needed: Delay in treatment worsens neurodevelopmental outcome. Treat within 2-4 weeks of diagnosis.
Tuberous Sclerosis = Vigabatrin: Vigabatrin is particularly effective for IS associated with Tuberous Sclerosis Complex (TSC).
Demographics
- Age of Onset: 3-12 months. Peak 4-6 months.
- Incidence: 2-5 per 10,000 live births.
- Sex: Male > Female (Slightly).
Aetiology
| Category | Examples | Proportion |
|---|---|---|
| Structural | Tuberous Sclerosis Complex (TSC – Major cause), HIE, Cortical Malformations, Stroke, Trauma. | ~40-50% |
| Genetic | Gene mutations (e.g., ARX, CDKL5, STXBP1), Chromosomal (e.g., Down Syndrome). | ~10-20% |
| Metabolic | PKU, Biotinidase Deficiency, Pyridoxine Dependency. | ~5% |
| Unknown (Cryptogenic/Idiopathic) | No cause identified. | ~30% (Better prognosis). |
Mechanism (Poorly Understood)
- Underlying Brain Abnormality: Structural lesion, Genetic mutation, Metabolic dysfunction affects developing brain.
- Cortical-Subcortical Network Dysfunction: Abnormal interactions between cortex, thalamus, and brainstem.
- Immature Brain Vulnerability: Specific susceptibility of infant brain (3-12 months) to this seizure type.
- Hypsarrhythmia: Reflects profound disorganisation of cortical electrical activity.
- Encephalopathy: Ongoing seizure activity and/or underlying pathology causes developmental regression/arrest.
| Condition | Key Features |
|---|---|
| Infantile Spasms (West Syndrome) | 3-12 months. Spasms in clusters. Developmental regression. Hypsarrhythmia on EEG. |
| Benign Myoclonus of Infancy | Normal development. Normal EEG. Self-limiting. |
| Startle Disease (Hyperekplexia) | Exaggerated startle. Stiffness as neonate. GLRA1 mutation. |
| Gastro-Oesophageal Reflux / Sandifer Syndrome | Posturing episodes. Related to feeds. No EEG abnormality. |
| Shuddering Attacks | Shivering episodes. Normal development. Normal EEG. Benign. |
| Dravet Syndrome | Fever-triggered seizures. SCN1A mutation. Later onset of myoclonic/atonic seizures. Different EEG. |
The Classic Triad (West Syndrome)
| Feature | Description |
|---|---|
| 1. Infantile Spasms | Brief (1-2 seconds), sudden, symmetric movements. Usually in Clusters (5-100+ spasms separated by seconds to minutes). Often on waking. |
| 2. Developmental Regression / Arrest | Loss of previously acquired milestones (e.g., Stops smiling, Loses eye contact, Reduced social interaction). May also be developmental arrest. |
| 3. Hypsarrhythmia (EEG) | Chaotic, high-amplitude, slow waves with multifocal independent spikes. May be modified or asymmetric. |
Types of Spasms
| Type | Description | Association |
|---|---|---|
| Flexor Spasms | Head/Trunk flexion, Arms flexed/adducted. "Salaam" or "Jackknife". | Most common. |
| Extensor Spasms | Head/Trunk extension, Arms extended/abducted. | Less common. |
| Mixed | Combination of flexion and extension. | Common. |
| Subtle/Asymmetric | Eye deviation, Head nod only. May be unilateral. | May be missed. |
Timing
Associated Features
EEG (Essential)
| Finding | Notes |
|---|---|
| Hypsarrhythmia | High-amplitude (>200 μV), Chaotic, Slow waves with Multifocal independent spikes. No normal background rhythm. |
| Ictal EEG (During Spasm) | Decrement (Sudden flattening/reduction of amplitude) or high-amplitude slow wave. |
| Modified Hypsarrhythmia | Asymmetric, Focal elements, or less chaotic. Still consistent with IS. |
| Timing | May require prolonged video-EEG / Sleep EEG to capture. Hypsarrhythmia often most prominent in sleep. |
Investigations for Underlying Aetiology
| Investigation | Rationale |
|---|---|
| MRI Brain | Essential. Look for structural abnormalities (Cortical malformations, TSC lesions, HIE changes). |
| Genetic Testing | Chromosomal Microarray. Epilepsy Gene Panel. Consider Whole Exome Sequencing. |
| Metabolic Screen | Lactate, Ammonia, Amino Acids, Organic Acids, Pyridoxine dependency trial, Biotinidase. |
| Ophthalmology (Fundoscopy) | TSC (Retinal hamartomas). Metabolic conditions. |
| Dermatology Examination | TSC (Ash-leaf spots – UV light – Hyperpigmented patches). |
| Echocardiogram | TSC (Cardiac rhabdomyomas). |
| Renal USS | TSC (Angiomyolipomas). |
Tuberous Sclerosis Complex (TSC) Workup
- High suspicion if: Multiple cortical tubers on MRI, Cardiac rhabdomyomas, Ash-leaf macules.
- Genetic Testing: TSC1/TSC2 genes.
Management Algorithm
SUSPECTED INFANTILE SPASMS
(Spasms in Clusters + Developmental Regression)
↓
URGENT EEG (Video-EEG if possible)
- CONFIRM HYPSARRHYTHMIA / ICTAL PATTERN
↓
MRI BRAIN (Essential for Aetiology)
+ METABOLIC / GENETIC SCREEN
+ TSC EVALUATION (Skin, Eyes, Heart, Kidneys)
↓
TREATMENT (URGENT – WITHIN 2-4 WEEKS)
┌─────────────────────────────────────────────────────────────┐
│ FIRST-LINE OPTIONS: │
│ │
│ 1. VIGABATRIN │
│ - First-line if TUBEROUS SCLEROSIS (TSC) is cause. │
│ - Start 50mg/kg/day, increase to 100-150mg/kg/day. │
│ - Effective for TSC-related IS (80-90% response). │
│ - Risk: IRREVERSIBLE VISUAL FIELD DEFECT (Retinal │
│ toxicity) – Regular ophthalmology monitoring. │
│ │
│ 2. HIGH-DOSE STEROIDS │
│ - ACTH (Tetracosactide depot): 0.5-1mg IM/IV on │
│ alternate days for 2-6 weeks, then taper. │
│ (Most evidence for efficacy). │
│ - OR High-Dose Prednisolone: 4mg/kg/day for 2-4 weeks, │
│ then taper. │
│ - Side Effects: Hypertension, Infection risk, Irritability,│
│ Cushing's, Electrolyte disturbance. │
│ - Preferred if NON-TSC aetiology. │
└─────────────────────────────────────────────────────────────┘
↓
ASSESS RESPONSE (2-4 WEEKS)
- Clinical: Cessation of spasms.
- EEG: Resolution of Hypsarrhythmia.
┌────────────────┴────────────────┐
RESPONSE NO RESPONSE
(Spasms stop, EEG improves) (Spasms persist)
↓ ↓
CONTINUE / WEAN SECOND-LINE / ALTERNATIVE
TREATMENT - Switch ACTH ↔ Vigabatrin
+ LONG-TERM AEDs - Combination Therapy
(Often needed) - Other AEDs: Topiramate, Nitrazepam
- Ketogenic Diet
- Epilepsy Surgery (If Focal Lesion)
↓
LONG-TERM FOLLOW-UP
- Developmental Monitoring (High risk of ID, Autism).
- Epilepsy Follow-Up (Risk of evolution to Lennox-Gastaut).
- Ophthalmology (If Vigabatrin used).
- Manage Underlying Condition (e.g., TSC – mTOR inhibitors).
First-Line Treatments
| Agent | Dose | Indication | Notes |
|---|---|---|---|
| Vigabatrin | 100-150 mg/kg/day (divided BD) | First-line for TSC-related IS | Highly effective for TSC. Risk of irreversible visual field defect (50% at high doses). Requires ophthalmology monitoring. |
| ACTH (Tetracosactide) | 0.5-1 mg IM on alternate days | First-line for Non-TSC IS | Most evidence for efficacy. Significant side effects. |
| High-Dose Prednisolone | 4 mg/kg/day (max 60mg) | Alternative to ACTH | Easier to administer (oral). Possibly slightly less effective than ACTH. |
Second-Line Options
- Switch between ACTH and Vigabatrin (if one fails).
- Combine ACTH + Vigabatrin.
- Topiramate, Nitrazepam, Valproate.
- Ketogenic Diet.
- Epilepsy Surgery: For focal structural lesions (e.g., Focal Cortical Dysplasia, TSC tuber) – Can be very effective.
Prognosis (Often Poor)
| Outcome | Notes |
|---|---|
| Intellectual Disability | 70-90% have some degree. Severity depends on aetiology and treatment response. |
| Autism Spectrum Disorder | ~30-50%. |
| Ongoing Epilepsy | ~50-70% develop other seizure types. 20-50% evolve to Lennox-Gastaut Syndrome. |
| Normal Development | 10-20% (More likely if Cryptogenic/Idiopathic and early treatment response). |
Factors for Better Prognosis
- Cryptogenic/Unknown aetiology.
- Rapid response to treatment.
- Early treatment initiation.
- No prior developmental delay.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Treatment of Infantile Spasms | BPNA (UK) | ACTH or Vigabatrin first-line. Vigabatrin preferred for TSC. |
| ILAE Guidance | ILAE | Similar. Emphasise early treatment. |
Landmark Trials
- UKISS Trial (2004): Hormonal treatment (ACTH/Prednisolone) more effective than Vigabatrin for cessation of spasms in non-TSC IS.
What are Infantile Spasms?
Infantile Spasms are a type of seizure that happens in babies, usually between 3 and 12 months old. The baby has sudden, brief jerking movements – often bending forward as if doing a "sit-up" – that happen in clusters, especially when waking up.
Why is this serious?
Infantile Spasms are a sign that the brain is not working properly at a critical time for development. Without treatment, babies often stop learning new skills or lose skills they already had. There is a risk of long-term learning difficulties.
What causes it?
There are many possible causes, including problems with brain development, genetic conditions, or metabolic problems. One important cause is Tuberous Sclerosis (a genetic condition causing growths in the brain and other organs). Sometimes no cause is found.
How is it treated?
We use strong medications to stop the spasms as quickly as possible. The main treatments are:
- Steroids (injections or high-dose tablets).
- Vigabatrin (especially if Tuberous Sclerosis is the cause). Early treatment gives the best chance of protecting your baby's development.
Primary Sources
- Lux AL, et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months. Lancet Neurol. 2005;4(11):712-7. PMID: 16239178.
- Hancock EC, et al. Treatment of infantile spasms. Cochrane Database Syst Rev. 2013;(6):CD001770. PMID: 23740541.
Common Exam Questions
- Classic Triad (West Syndrome): "What are the three features of West Syndrome?"
- Answer: Infantile Spasms (Salaam attacks), Developmental Regression, Hypsarrhythmia on EEG.
- EEG Finding: "What is the characteristic EEG pattern?"
- Answer: Hypsarrhythmia – Chaotic, high-amplitude, slow waves with multifocal independent spikes.
- Treatment for TSC-Related IS: "First-line treatment for Infantile Spasms caused by Tuberous Sclerosis?"
- Answer: Vigabatrin.
- Long-Term Risk: "What epilepsy syndrome may Infantile Spasms evolve into?"
- Answer: Lennox-Gastaut Syndrome.
Viva Points
- Vigabatrin Visual Toxicity: Explain the risk of irreversible visual field defect and need for monitoring.
- Urgency of Treatment: Emphasise that early treatment (within 2-4 weeks) improves outcomes.
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