Page 58 - ILAE_Lectures_2015

• Glucose transporter 1 deficiency
• Biotinidase deficiency
• Creatine deficiency (GAMT)
• Untreated phenylketonuria

Neonates with persistent seizures or suggestive EEG background abnormalities should all
undergo a therapeutic trial with pyridoxine, pyridoxal-5-phosphate, and folinic acid58.
Unexplained and persistent hypoglycaemia should be thoroughly investigated (lactate,
ammonia, amino acids, urine organic acids, urine ketones, insulin, cortisol, free fatty acids, and
B-hydroxybutyrate).

Glycine encephalopathy (neonatal non-ketotic hyperglycinaemia)
This inborn error of metabolism usually presents as an early myoclonic encephalopathy (see
above) with seizures (myoclonus elicited by tactile and painful stimuli) on the second or third
day of life. Associated respiratory distress syndrome, with periodic respiration, and coma are
found. The EEG shows unusual periodic discharges on a near silent background28.

Glucose transporter type 1 syndrome
Glucose transporter deficiency is a cause of seizures starting in the first three months of life,
with mixed seizures types, postnatal microcephaly and encephalopathy later in the first year of
life29.

Pyridoxine dependency
Pyridoxine dependent seizures are a rare but treatable subgroup of neonatal seizures, which
can begin in intrauterine life30. Seizures of multiple types usually begin shortly after birth and
are resistant to conventional antiepileptic drugs (AEDs). There may be encephalopathy and/or
structural brain abnormalities. The EEG shows burst-suppression pattern, which may be
interrupted by focal seizures or other generalised epileptiform activity. Pyridoxine/pyridoxine-
5-phosphate is required for the synthesis of several neurotransmitters, including gamma amino
butyric acid (GABA), monoamines and others. Mutations in the ALDH7A1 gene, which
encodes antiquitin, were recently described in some children with pyridoxine-dependent
seizures and linkage to 5q31 in some affected families. Pipecolic acid in plasma and
cerebrospinal fluid is considered a possible metabolic marker for this disorder30. When
pyridoxine dependency is suspected, 100–200 mg of pyridoxine should be given intravenously
under EEG control. The seizures will abruptly stop (within minutes) and the EEG will
normalise during the next few hours. Acute suppression of EEG activity occurs occasionally
and may be associated with acute cardiovascular collapse. A subgroup of affected babies
responds only to very high doses given for two weeks. A closely related disorder with a similar
clinical picture has now been identified as pyridoxal-5-phosphate dependent seizure.

Folinic acid responsive seizures are a rare cause of neonatal seizures with clinically similar
features to pyridoxine dependent seizures30.

Seizures in hypoxic-ischaemic encephalopathy
Hypoxic ischaemic encephalopathy (HIE) is a common and important cause of seizure in
neonates born at term. The characteristic time of onset of seizures in HIE is 836 hours after
birth. Seizures occurring before that are usually ‘clinical only’ and are due to an abnormal
increase in tone. This appears to be similar to animal studies in which the EEG activity in lambs
with an intrapartum insult is at first depressed, and then evolves to show seizure activity about
eight hours after birth31. An EEG obtained shortly after birth in which electrographic seizure
activity was already manifest, would strongly suggest an insult over eight hours before
delivery. Early background EEG activity is a relatively reliable prognostic indicator for
outcome32,33.