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non-ketotic hyperglycinaemia, pyridoxine/pyridoxal-5-phosphate disorders, carnitine
palmitoyl transferase deficiency, and biotinidase deficiency).

In terms of treatment AEDs are often not effective. Sodium valproate, phenobarbitone,
vigabatrin, benzodiazepines and zonisamide have all demonstrated some limited
effectiveness, as has the ketogenic diet. Treatable metabolic disorders should be identified
early as appropriate treatments are of clinical benefit. Children with focal structural brain
malformations should be referred to an epilepsy surgery programme as epilepsy surgery may
be effective in terms of both seizure control and neurodevelopmental outcome.

Prognosis is poor in this condition with 25% of children dying in infancy. Many infants with
Ohtahara syndrome will evolve into West Syndrome during infancy.

West syndrome18,19

This syndrome is one of the most severe that occurs in the first year of life with typical age
of onset between 3 and 10 months (peak 6–8 months). The full syndrome comprises an
electroclinical triad, although only the first two features are required to diagnose the
syndrome:

 Epileptic spasms (flexor and extensor seizures occurring typically in clusters, with
between five and 50 per cluster usually on or soon after waking).

 Hypsarrhythmia on the EEG (though this is not present in all infants with West syndrome
at presentation and may be demonstrated only in sleep).

 Developmental delay (not invariable at the onset of the spasms and therefore not essential
for the diagnosis of the syndrome).

Approximately 80% are ‘symptomatic’ and are due to an identified aetiology. Common
causes include:

 Structural brain disorders
- Malformations of cortical development (e.g. lissencephaly, cortical dysplasia)
- Neurocutaneous syndromes (tuberous sclerosis, incontinentia pigmenti,
neurofibromatosis)
- Acquired brain injury (e.g. a sequel to hypoxic-ischaemic (perinatal asphyxia)
encephalopathy, post- meningoencephalitis)

 Metabolic disorders (e.g. biotinidase deficiency, Menke’s disease, phenylketonuria,
non-ketotic hyperglycinaemia, mitochondrial cytopathy)

 Chromosomal disorders (Down syndrome, Miller-Dieker syndrome)
 Genetic causes (ARX, CDKL5, SPTAN1, STXBP1).

There are however many other causes.

The remaining 20% is ‘cryptogenic’ with no obvious cause. Almost certainly this number
will fall over the forthcoming years with further advances in functional neuroimaging (MRI,
tractography and magnetoelectroencephalography [MEG]), molecular genetics and
biochemistry.

The investigation of infantile spasms depends largely on the individual child and its previous
medical (particularly perinatal) history. All infants require imaging with MRI. A negative
(normal) CT should never be regarded as excluding a structural lesion.