The independent effect of clinical neonatal seizures and their treatment on longterm neurodevelopmental outcome in 77 term newborns at risk for hypoxic-ischemic encephalopathy (HIE) was determined in a study at University of California San Francisco. Clinical seizures were recorded and graded prospectively assigning points (0-10) for frequency, status, medications, and EEG abnormal background and epileptiform discharges. Eleven children (14.3%) had severe neonatal seizures (composite seizure score >4), 14 (18.2%) had mild/moderate seizures (score 1 to 3), and 52 (67.5%) had no seizures (seizure score 0). Of the 25 infants with seizures, EEG was abnormal in 14 (56%). The severity of HIE measured by MRI was most highly associated with cognitive outcome, measured by WPPSI-R and neuromotor score, at age 4 years. The pattern of the HIE correlated with severity of seizures (P<0.0001); basal nuclei predominant patern was associated with severe seizures, and the watershed pattern with mild/moderate seizures. Children with severe seizures had a lower FSIQ than those with mild/moderate seizures (P<0.0001). 
COMMENT. The authors conclude that clinical neonatal seizures with birth asphyxia are associated with worse neurodevelopmental outcome, independent of the severity of hypoxic-ischemic brain injury. The effect of the seizures themselves could not be differentiated from the cognitive effects of treatment with phenobarbital and phenytoin, however. Also, almost half of patients with clinical seizures had a normal EEG. Seizure severity was graded by frequency, medication use, and EEG, but not by seizure pattern. According to Volpe JJ (In Gluck L. Editor. Intrauterine Asphyxia and the Developing Fetal Brain. Chicago. Year Book Med Pub, 1977) , virtually all infants with HIE related seizures have “subtle” seizures. Subtle seizures are manifested by 1) tonic horizontal deviation or jerking of eyes; 2) eye-lid blinking or fluttering; 3) sucking, smacking of lips; 4) ‘swimming” or “rowing” movements of limbs; and/or 5) apneic spells. Infants also exhibit multifocal clonic seizures or decerebrate/decorticate tonic seizures in addition to subtle seizures, but not generalized tonic-clonic seizures, the type expected to result in brain injury.
Subtle seizures described as “breast-stroke swimming movements” were previously reported in studies of seizure patterns in newborn animals . Transient opisthotonus, tremors, and clonic movements were also characteristic of newborn seizure patterns, but in rats aged 1 to 15 days subjected to graded electroshock, a generalized tonic clonic seizure could not be elicited. Failure to induce convulsions in the newborn rat was associated with a low level of carbonic anhydrase in the brain. The maximal seizure pattern was correlated with increasing age and the higher maturational levels of carbonic anhydrase in the brain of older animals. Observation of the newborn seizure pattern in addition to seizure frequency and EEG discharges might permit closer correlation with severity of HIE and outcome. If neonatal seizures do contribute to HIE brain injury, inhibition of the development of brain carbonic anhydrase would be expected to lessen the severity of neonatal seizures and result in improved neurodevelopmental outcome. Detailed EEG monitoring is essential for confirmation of diagnosis of neonatal seizures, especially subtle seizures.