Infantile Spasms

Infantile spasms are epileptic spasms occurring in clusters in infants, usually with hypsarrhythmia on EEG and developmental arrest or regression (West syndrome). They are a neurological emergency because delayed treatment worsens developmental outcome.

The incidence is about 0.25 to 0.4 in every 1,000 live births. Onset is between 3 and 12 months, with a peak at 4 to 7 months.

Causes. Structural (hypoxic ischaemic injury, malformations of cortical development, tumours, stroke), genetic (tuberous sclerosis in about 10 to 15%, CDKL5, STXBP1, ARX, trisomy 21), metabolic and infectious causes; about one third are unknown.

Prognosis. Developmental delay or intellectual disability is common, and later epilepsy occurs in over half. Outcome depends on the cause and on the lead time to treatment.

Pathophysiology.

Disorganised cortical and subcortical networks, with excess corticotropin releasing hormone and abnormal thalamic and brainstem connectivity, produce spasms and chaotic EEG activity.

Age dependent brain development predisposes to this pattern.

• Brief (1 to 2 seconds) flexor, extensor or mixed spasms of the head, trunk and limbs, in clusters of 5 to 50, often on waking or after feeding.
• Developmental arrest, loss of eye contact and social smile, or regression.
• Associated features of the cause: skin patches (tuberous sclerosis), microcephaly or asymmetry.
• Parents may report startles, colic or reflux.

Red flags.

• Clusters of spasms in any infant, especially with regression.
• Asymmetric spasms or focal signs.
• Spasms with skin features of tuberous sclerosis.

• Video EEG, including sleep, within days: hypsarrhythmia (chaotic high voltage background with multifocal spikes) or modified patterns; record clusters.
• MRI brain with epilepsy specific sequences, ideally with myelination sequences.
• Genetic testing (microarray, gene panel or exome) and metabolic screening when the cause is not clear.
• Skin and eye examination, echocardiography and renal ultrasound if tuberous sclerosis is suspected.

Differential diagnosis. Benign myoclonus of infancy, infantile colic, gastro oesophageal reflux, Moro reflexes, tonic seizures, other seizure types and non-epileptic events.

• Start treatment within days of diagnosis; this is an emergency, and the aim is cessation of spasms and normalisation of the EEG.
• Prednisolone 10 mg orally four times daily (40 mg daily) for 14 days, increased to 20 mg three times daily (60 mg daily) after 7 days if spasms continue, followed by a taper over 2 weeks. Maximum 60 mg daily. Monitor blood pressure, glucose, electrolytes, weight, infection and behaviour; give gastroprotection. Avoid live vaccines during treatment; no renal adjustment; use caution in infection and hypertension.
• Adrenocorticotropic hormone (repository corticotropin) 150 units/m2 daily intramuscularly in 2 divided doses for 2 weeks, then a taper over about 2 weeks. Maximum 150 units/m2 daily in the first phase. Monitor blood pressure, glucose, electrolytes, infection and cardiac function; avoid in heart failure, uncontrolled infection, hypertension and live vaccines; local availability and cost vary.
• Vigabatrin is first line in tuberous sclerosis and is a second line option otherwise: 50 mg/kg orally daily in 2 divided doses, increased over 3 to 4 days to 100 mg/kg daily. Maximum 150 mg/kg daily. Monitor response at 2 weeks, MRI signal change, sedation and vision; stop if there is no response after 2 to 4 weeks, and limit use to about 6 months if effective. Reduce dose when creatinine clearance is under 60 mL/min; irreversible visual field loss is the main risk, so use the lowest effective dose and shortest course.
• Combination steroid plus vigabatrin may give faster response in some infants through specialist care.
• Non-responders: ketogenic diet, other antiseizure drugs, and early surgery for a focal lesion.
• Lifelong care for developmental, behavioural and epilepsy outcomes.

Monitoring. Clinical response at 2 weeks, then EEG at 2 to 4 weeks and 3 months; development review at 6 months and yearly.

Referral and escalation. Immediate paediatric neurology contact for any suspected infantile spasms; epilepsy surgery assessment for focal lesions.

Special groups. Tuberous sclerosis: vigabatrin first line and early screening for cardiac, renal and eye disease.