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Etiologies of Neonatal Seizures

Underlying Defect

Points to Remember

Hypoxic–ischemic encephalopathy

  • Leading cause of neonatal seizures in full-term infants.
  • This diagnosis should never be one of exclusion.
  • Data supporting this diagnosis (history of prolonged labor, perinatal depression, prolonged resuscitation) should be obtained and documented.

Focal ischemia/infarction

  • Second most common cause of neonatal seizures in full-term infants.
  • Most common presentation is right-sided clonic seizures due to infarction in the left middle cerebral artery territory.
  • Cerebral vein thromboses can lead to venous infarcts.

Intracranial hemorrhage

  • In term infants, subarachnoid hemorrhage is more associated with subsequent seizure than subdural hemorrhage.
  • Infratentorial subdural hemorrhages require urgent evaluation due to risk of brainstem compression.
  • In preterm infants, intraventricular hemorrhage is the most common type of ICH (see below).

Infections of the CNS

  • Can occur in utero (CMV, toxoplasmosis) or perinatally (herpes simplex, bacterial meningitis with GBS or Escherichia coli being most common).
  • Prognosis can be very grim.

Metabolic derangement

  • Transient causes (hypoglycemia, hypocalcemia, hyponatremia); see Chapter 34 for further information.
  • Inborn errors of metabolism (pyridoxine dependency, nonketotic hyperglycinemia, urea cycle defects, glutaric aciduria (type II), maple syrup urine disease, organic acidurias, cofactor deficiencies, mitochondrial defects , Zellweger Syndrome).

Structural defects

  • Defects of neuronal migration (heterotopias).
  • Defects of neuronal organization (polymicrogyria).
  • Cerebral malformation (holoprosencephaly).
  • Usually will display associated dysmorphic features on physical examination.

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Day of Life

Possible Causes


Hypoxic ischemic encephalopathy



Maternal drug use



All of the above

Inborn errors of metabolism

Drug withdrawal

CNS malformation



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Seizure Type

Clinical Manifestation


Oral–buccal–lingual or ocular movements

Autonomic dysfunction (Δ in HR, BP, Spo2)

Stereotypical stepping/swimming


Rhythmic, slow jerking

Facial, extremity, or axial involvement

Focal or generalized


Sustained limb posturing

Asymmetric position of trunk/neck

Focal or generalized


Rapid isolated jerks

Limb/trunk involvement

Generalized, multifocal, or focal

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Seizure Mimic

Clinical Manifestation


Spontaneous or provoked by stimulus

Flexion/extension are equivalent

Diminished by repositioning

Abolished with containment

Benign neonatal sleep myoclonus

Bilateral or unilateral

Synchronous or asynchronous

Occurs during sleep

Not due to a stimulus

Stimulus-evoked myoclonus

Focal or generalized

Severe CNS dysfunction

EEG may show cortical spike-wave discharge

Hyperekplexia (stiff-man syndrome)

Generalized stiffness

Autosomal dominant and recessive forms

Excessive startle responses to unexpected stimuli

Excessive stiffness following startle response

Benzodiazepines reduce symptoms




  • Support respiratory and cardiovascular function (may require endotracheal intubation and mechanical ventilation).
  • Place on continuous cardiorespiratory monitoring.
  • Correct any known causes of seizures (see above).
  • If seizures continue after correction of transient metabolic derangements, load with phenobarbital (20 mg/kg IV); can be followed by repeat doses of 5–10 mg/kg IV to a total dose of 40 mg/kg IV, if needed.
  • If seizures continue, load ...

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