The incidence of neonatal seizures in term infants is 0.7-2.8 per 1000 live births and is higher in the preterm population ^1-4. In term infants hypoxic-ischemic encephalopathy is the most common cause, but other causes include intracranial haemorrhage, infection, metabolic abnormalities, CNS malformations and drug withdrawal.

Link to Seizure Record Chart

Types of Seizures

The clinical manifestations of neonatal seizures differ from those in older children. Five major varieties are described:

• subtle
• generalised tonic
• multifocal clonic
• focal clonic, and
• myoclonic.

Jitteriness is not a seizure but is frequently confused with one and may be a sign of cerebral irritation.

History, Examination, and Investigation

• It is important to obtain a careful perinatal history and perform a physical examination.
• Hypoglycaemia or meningitis should be recognised and treated promptly.
• Investigation should include:
  • blood glucose
  • FBC and PCV
  • Blood gas
  • sodium, potassium, magnesium, calcium and phosphate.
  • Further investigation including lumbar puncture, cerebral ultrasound, metabolic screen and CT or MRI will depend on the individual case.

Indication for Treatment

• Untreated seizures may continue for extended periods of time, interfere with ventilation or precipitate cardiovascular collapse.
• Cardio-respiratory compromise may impair cerebral vascular autoregulation and predispose to secondary brain injury.

In general if seizure duration >3 min or frequency or >3 per hour treatment is required.

• Ensure that ventilation and perfusion are adequate and any hypoglycaemia is corrected.
• Drugs should be given intravenously to achieve a rapid onset of action and predictable blood levels.

Usual Sequence of Therapy

• Convert to maintenance therapy when seizures controlled (usually not >48hrs infusion)  ⁷.

• N.B. If there are recurrent seizures with no obvious cause consider pyridoxine dependency.
  • A therapeutic trial of pyridoxine IV 50 -100 mg may be helpful (this may be considered during EEG).

EEG

• It is not necessary to defer therapy until an EEG can be obtained. However, EEG may assist in confirming that subtle phenomena are seizures or to determine if a paralysed infant is having seizures.
• The interictal EEG may be useful in estimating prognosis particularly in HIE.

Maintenance Therapy

• Phenobarbitone 3-6 mg/kg/day. IV, IM, or oral.
• Phenytoin 3-8 mg/kg/day IV only (oral absorption is erratic)

• Maintenance therapy should begin 12 hrs after the loading dose and is given divided q 12 hrs.

• Drug levels are important when these drugs are used for maintenance.
• Slow elimination rates in asphyxiated infants, secondary to hepatic and/or renal involvement, may lead to drug accumulation.
• Also maintenance administration of phenytoin is difficult because of its nonlinear kinetics and rapid decrease in elimination rates in the first weeks of life.

Duration of Therapy

• Optimal duration of therapy depends principally on the likelihood of recurrence of seizures.
• Following HIE there is a low risk of seizure recurrence after early withdrawal of anticonvulsant in the neonatal period ⁸.
  • Hence, it is usual to discontinue the anticonvulsant prior to discharge.
• However, infants with prolonged or difficult seizures and those who continue to show abnormality on EEG may benefit from continuing treatment (usually monotherapy with phenobarbitone).

• The neurodevelopmental outcome depends on the cause of seizures. Major cerebral malformations have a poor prognosis whilst the outcome from HIE, infection, and metabolic abnormalities will be variable. It is important that all infants with neonatal seizures receive adequate follow up.

References