Iowa Neonatology Handbook: Neurology

Neonatal Seizures

1. Background
   
   It is important to recognize the presence of seizures in the neonatal period since they are often related to a significant underlying illness. In addition, seizures may be sustained for considerable periods of time, interfering with essential supportive care. There are 4 major types of seizures in neonates:
   
   1. Subtle seizures are relatively common in the neonatal period and are more often encountered in the preterm than full term infant. Such seizures include oral-buccal-lingual movements, certain ocular phenomena, peculiar limb movements, autonomic alterations and apnea.
      
   2. Clonic seizures include focal and multifocal varieties which may migrate to another part of the body in a non-ordered fashion.
      
   3. Tonic seizures include focal episodes (less common) and generalized episodes (more common). Generalized tonic seizures may mimic decerebrate and decorticate posturing.
      
   4. Myclonic seizures may be focal, multifocal or generalized and are the least common of the four varieties during the neonatal period.
      
   Seizure-like phenomena may not be accompanied by seizure activity on EEG and possibly represent movements or posturing generated by diencephalon-brainstem activity when released from the inhibitory effects of the cerebral cortex. Careful clinical assessment is often necessary to distinguish seizure from nonseizure activity. Non-seizure activity is usually provoked by sensory stimulation, suppressed by passive restraint, associated with normal eye movements, and not accompanied by autonomic phenomena.
   
2. Pathophysiology
   
   A number of etiologies should be considered for neonatal seizure. These include:
   
   1. Asphyxia/hypoxia-ischemia: There is usually an interval of time between the event and the onset of seizures, but this interval is quite variable (1-36 hr).
      
   2. Intracranial hemorrhage: Seizures may be a manifestation of any form of intracranial hemorrhage including subarachnoid, intraventricular or intraparenchymal hemorrhage.
      
   3. Metabolic disturbances: Seizures may accompany alterations of glucose, calcium or sodium homeostasis, as well as inborn errors of metabolism, e.g., hyperammonenia.
      
   4. Intracranial infection: Meningitis, encephalitis.
      
   5. Drug withdrawal: Heroin, methadone.
      
   6. Structural defects of the central nervous system.
      
3. Diagnosis
   
   A detailed history of prenatal and postnatal events is paramount in diagnosing neonatal seizures. At the time of the seizure, attention should be directed to identifying treatable causes, as outlined in the previous section. A short term screening EEG may be helpful in establishing diagnosis and prognosis. Other studies, including head ultrasound, CT or MRI and skull X-rays, should be considered depending upon the history obtained.
   
4. Treatment
   
   Once a seizure has been diagnosed, treatment directed at the underlying disease needs to be initiated. Anticonvulsant therapy includes the following:
   
   1. Phenobarbital is the drug of first choice to treat neonatal seizures. It is relatively effective, the side effects are well appreciated, and the pharmacokinetics are reasonably well understood for term and preterm infants. A loading dose of phenobarbital (20 mg/kg) will achieve a therapeutic level of approximately 20 µg/ml, which is not affected by birth weight or gestational age. The intravenous route is preferred because of the more rapid onset of action and more reproducible effects on blood levels. The maintenance dose of phenobarbital is lower in the first week of life (3.5 mg/kg/day) and increases to 5 mg/kg/day with increasing postnatal age.
      
   2. Dilantin is often the second drug of choice to be added when seizures are not controlled by phenobarbital alone. A loading dose of 20 mg/kg intravenously will achieve therapeutic blood levels (approximately 15 µg/ml) and a maintenance dose is 5 mg/kg/day.
      
   3. Lorazepam is useful for infants with "uncontrolled" seizures in spite of therapy with phenobarbital and dilantin. The usual dose is 0.05 - 0.1 mg/kg per dose. Due to the possibility of respiratory depression (especially with phenobarbital on board), the safest use of these drugs is when ventilatory support has been initiated.

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