Neonatal seizures

What is the differential diagnosis in a term infant with seizures?

There are a wide range of problems resulting in seizures in the neonatal period. The most common cause of seizures is following a hypoxic-ischaemic insult. There may be a history of fetal distress and the infant is usually depressed at birth.

CNS infection must be excluded: the commonest organisms are group B streptococcus and E. Coli. Herpes simplex encephalitis can also present with seizures. The history may indicate risk factors for sepsis (prolonged rupture of membrane, maternal pyrexia) and the baby is usually quite unwell with meningitis or encephalitis.

Birth trauma can result in subarachnoid or subdural haemorrhages. Although more common with instrumental deliveries, it is usually seen following ventouse extraction.

A number of inborn errors of metabolism present with seizures, including non-ketotic hyperglycinaemia, maple syrup urine disease, urea cycle defects and pyridoxine deficiency. Features to look for are a positive family history, persistent acidosis and unusual odours. The seizures are usually unresponsive to conventional treatment.

Hypoglycaemia can cause seizures. Severe hypoglycaemia is more common in infants of diabetic mothers and other causes of hyperinsulinism, as well as inborn errors of metabolism.

Maternal opiate abuse can result in severe withdrawal including seizures. Associated features of drug withdrawal should be looked for as well as positive urine toxicology.

Other causes of seizures include CNS malformation, benign familial neonatal convulsions and cerebral artery infarction.

Investigating neonatal seizures:

Because a wide range of conditions may present with seizures a broad range of investigations should be carried out in order not to miss rare but potentially treatable conditions.

  • Baseline investigations should include blood glucose, urea and electrolytes, blood gas analysis and blood and CSF culture.
  • Blood should also be taken for ammonia, plasma amino acids, congenital infection screen and lactate. Urine should be sent for toxicology and organic acids.
  • A cranial ultrasound scan should be performed and if available, cerebral function monitoring (CFM) commenced. An EEG should be requested and if possible further neuroimaging with CT or MRI performed.

Management of neonatal seizures:

Although the aim should be to identify and if possible treat the underlying cause, it is important to control the seizures themselves if they are prolonged or frequent. Repeated seizures decrease energy reserves and release excitatory amino acids which are damaging and cause kindling of further seizures. Levene suggests treating if more than 3 seizures per hour or there is a single prolonged seizure lasting more than 3 minutes. Both seizures and anticonvulsants can cause respiratory depression and so there should be a low threshold to mechanically ventilate the infant.

The following regimen is suggested:

  • Phenobarbitone 20 mg/kg IV as a loading dose slowly over 20 minutes. Repeat a second loading dose of 10-20 mg/kg IV if baby continues to have seizures (max total dose 40mg/kg).
  • If this does not work, consider Levetiracetam (Keppra) 20mg/kg IV loading dose followed by a repeat loading dose and then maintenance dose of 10mg/kg bd or Phenytoin 20mg/kg IV over 30 minutes (Phenytoin should not be given any faster than 1mg/minute). Do not give Phenytoin if there are signs of cardiovascular compromise. Severe bradycardia or ventricular tachycardia may occur after Phenytoin administration. Treatment of this is to discontinue the drug and initiate resuscitation measures.
  • If seizures are ongoing, consider Midazolam 150-200micrograms/kg loading dose given by slow IV injection over 5 minutes followed by continuous infusion of 60micrograms/kg/hr, increasing as required.

Seizures as a result of hypoxic-ischaemic encephalopathy, inborn errors of metabolism and structural brain malformations can be difficult to treat. A trial of pyridoxine should be given if the seizures do not respond to conventional therapy and the diagnosis is unclear.

For more information please read the latest EoE guidelines on the management on neonatal seizures in term infants: EoE GUIDELINES_ Seizures_v1.3_140318