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Not all abnormal movements (particularly in premature babies) are seizures and clinical
differentiation of seizure from non-seizure activity may be very difficult.
Electroencephalography (EEG) (particularly prolonged with simultaneous video-recording
of the clinical episodes and abnormal movements), may resolve some of this difficulty.
However, there is frequently an element of ‘electroclinical dissociation’ whereby
electroencephalographic ‘seizures’ (i.e. epileptiform activity) have an uncertain and
inconstant relationship with clinical seizures and this phenomenon is more likely the younger
the infant.

The aetiologies of neonatal seizures are multiple. In most cases the underlying aetiology can
be determined from preceding events, the clinical course (including the pregnancy), family
history and physical examination. If there is no definite history of perinatal asphyxia, an
initial ‘screen’ should be undertaken:

 Blood glucose, calcium, magnesium, urea, electrolytes and acid-base status
 Full blood count and film examination
 CSF analysis (glucose [with a simultaneous fasting blood glucose], protein, cell count)
 Cultures of blood, CSF, urine and faeces
 Cranial ultrasonography (only of use when looking for evidence of haemorrhage or a

major cerebral malformation).

Further investigations should be performed depending upon the clinical situation and results
of the initial evaluations:

 Blood ammonia, lactate, uric acid and liver enzymes; biotinidase level; if the blood
creatinine level is consistently low, further more detailed biochemical and genetic
analyses should be undertaken looking for evidence of abnormalities of creatinine
synthesis (e.g. GAMT deficiency)

 Blood and urine amino acids, urinary organic acids
 Urine-reducing substances; urine sulphite levels
 ‘TORCH’ antibody studies (for congenital infections)
 MRI head (for cerebral malformations/dysgenesis)
 Diagnostic use of pyridoxine (vitamin B6) and/or pyridoxal-5-phosphate
 CSF analysis (glucose, lactate, amino acids)
 Chromosome and DNA analysis. There are an increasing number of gene abnormalities

associated with infantile epilepsies  discuss with genetics team.

The condition of pyridoxine-dependent seizures is a rare autosomal recessive disorder that
presents characteristically within the first week of life with intractable seizures and a
markedly abnormal (almost hypsarrhythmic-like, often with a burst-suppression pattern)
EEG4. However, it may also ‘present’ before birth with intrauterine seizures, or late, even up
to 12 or l8 months of age. Clinical response to intravenous pyridoxine (vitamin B6) is often
immediate as is normalisation of the EEG, although the latter may be delayed for days or
weeks. Therefore a trial of oral pyridoxine (2030 mg/kg/day) should be given for at least
three weeks. Some infants have an abnormality further down the metabolic pathway and
require treatment with pyridoxal-5-phosphate as pyridoxine will not be effective in these
infants. Some clinicians now would recommend using pyridoxal-5-phosphate instead of
pyridoxine to ensure that all infants who have a defect in this metabolic pathway will be
treated in an appropriate manner6. Also, it is recommended that any infant under the age of
l8 months with intractable seizures of unknown cause should receive a similar trial of
pyridoxine. A biochemical marker (elevated levels of pipecolic acid in plasma, urine and/or
CSF) and genetic abnormalities have recently been identified in a number of infants with