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Seizures - management in the neonate

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The incidence of neonatal seizures in term infants is 0.7-2.8 per 1000 live births and is higher in the preterm population1-4. 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.

See Seizure Record Chart

Types of seizures

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

Type Physical features EEG
Subtle Eye signs - eyelid fluttering, eye deviation, fixed open stare, blinking
Apnoea
Cycling, boxing, stepping, swimming movement of limbs
Mouthing, chewing, lip-smacking, smiling
Often no EEG changes.
EEG changes most likely to occur with ocular manifestations
Tonic Stiffening
Decerebrate posturing
EEG variable
Clonic Repetitive jerking, distinct from jittering
Can be unifocal or multifocal
Usually changes identified
Myoclonic Rare
Sleep myoclonus is benign
EEG often normal
Background EEG can be abnormal

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

  1. Phenobarbitone 20 mg/kg loading dose (slow IV infusion over 30 mins)
    If the initial 20 mg/kg dose is ineffective, additional doses of 5-10 mg/Kg can be administered until either seizures have ceased or a total dose of 40 mg/Kg has been given.5
  2. Phenytoin 20 mg/kg (slow IV infusion over 30 mins, i.e < 1 mg/kg/min)
    Cardiac rate and rhythm should be monitored during the infusion.
  3. Paraldehyde 200-400 mg/kg IV
    Infuse over 2 hours in a 5% solution made up in 5% glucose6.
    OR
    Clonazepam 100-200 micrograms/kg (intravenously over 30 seconds)
    and if control not achieved then Clonazepam intravenous infusion 10-30 micrograms/kg/hour.
    OR
    Midazolam 0.05 to 0.15mg/kg as a slow push over 5 minutes
    can be repeated 2-4 hourly as required or given as a continuous infusion (10-60micrograms/kg/hour)

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 period8. 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

  1. Curtis PD, Matthews TG, Clarke TA, et al. Neonatal seizures: the Dublin Collaborative study. Arch Dis Child 1988;63:1065-8.
  2. Lanska MJ, Lanska RJ, Baumann, RJ, Kryscio RJ. A population based study of neonatal seizures in Fayette County, Kentucky. Neurology 1995;45:724-32.
  3. Lien JM, Towers CV, Quilligan EJ et al. Term early-onset neonatal seizures: obstetric characteristics, etiologic classifications, and perinatal care. Obstet Gynecol 1995;85:163-9.
  4. Scher MS, Aso K, Beggarly ME, et al. Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae. Pediatr 1993;91:128-34.
  5. Gilman JT, Gal P, Duchowny MS, Weaver RL, Ransom JL. Rapid sequential phenobarbital treatment of neonatal seizures. Pediatr 1989;83:674-8.
  6. Koren G, Butt W; Rajchgot P, et al. Intravenous paraldehyde for seizure control in newborn infants. Neurology 1986;36:108-11
  7. Evans D, Levene M. Neonatal Seizures. Arch Dis Child. 1998;78:F70-75
  8. Hellstrom Westas L, Blennow G, Lindroth M, Rosen I, Svenningsen NW. Low risk of seizure recurrence after early withdrawal of antiepileptic treatment in the neonatal period. Arch Dis Child 1995;72: F97-101

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Document Control

  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse