Electrographic seizures in neonates correlate with poor neurodevelopmental outcome

Objective: To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and to compare the outcome of neonates with ESz with those who were at risk but did not have ESz recorded. Methods: The EEG and outcome data were reviewed from 68 infants who met at-risk criteria for neonatal seizures and underwent prolonged continuous EEG monitoring. Forty infants had ESz. The control group contained 28 infants monitored for at least 18 hours and found not to have ESz. Outcomes for both groups were evaluated using hospital and follow-up clinic records and a standardized telephone interview. Results: The etiology of ESz included asphyxia (n = 23), stroke (n = 7), and other (n = 10, intraparenchymal, subdural, and subarachnoid bleeding; meningitis; sepsis; hyponatremia; and unknown). The cumulative recorded ESz duration was 8 minutes to 30 hours. Forty-three percent of infants with ESz spent 38 minutes to 32 hours in electrographic status. Despite doses of 40 mg/kg of phenobarbital and 20 mg/kg of phenytoin, 30% of infants continued to have ESz. Ten infants with ESz and one without died from causes related to neurologic instability. The occurrence of ESz was correlated with microcephaly (p = 0.04), severe cerebral palsy (CP) (p = 0.03), and failure to thrive (p = 0.03). In the subgroup of infants with asphyxia, those with ESz were more likely to die of neurologic causes (p = 0.02) and have microcephaly (p = 0.05) or severe CP (p = 0.04). Additionally, those with the greatest number of ESz were more likely to have these severe outcomes. Conclusion: The authors’ data indicate an association between the amount of electrographic seizure activity and subsequent mortality and morbidity in at-risk infants in general and in infants with perinatal asphyxia. Only with more effective treatment of neonatal electrographic seizures can their potential contribution to poor neurodevelopmental outcome, independent of degree of insult, be ascertained.

[1]  R. Briggs,et al.  31P Nuclear Magnetic Resonance Study of the Effect of Hypoxemia on Neonatal Status Epilepticus , 1986, Pediatric Research.

[2]  G. Holmes,et al.  Age-dependent effects of glutamate toxicity in the hippocampus. , 1996, Brain research. Developmental brain research.

[3]  E. Roland,et al.  Perinatal hypoxic—Ischemic thalamic injury: Clinical features and neuroimaging , 1998, Annals of neurology.

[4]  O. Pryds,et al.  Regional cerebral blood flow during seizures in neonates. , 1998, The Journal of pediatrics.

[5]  Eli M. Mizrahi,et al.  Characterization and classification of neonatal seizures , 1987, Neurology.

[6]  G. Holmes,et al.  Recurrent seizures in immature rats: effect on auditory and visual discrimination. , 1996, Brain research. Developmental brain research.

[7]  M. Gorey,et al.  The syndrome of acute near-total intrauterine asphyxia in the term infant. , 1998, Pediatric neurology.

[8]  Myers Re,et al.  Four patterns of perinatal brain damage and their conditions of occurrence in primates. , 1975, Advances in neurology.

[9]  M J Painter,et al.  Neonatal seizures: electroclinical dissociation. , 1991, Pediatric neurology.

[10]  J Connell,et al.  Continuous EEG monitoring of neonatal seizures: diagnostic and prognostic considerations. , 1989, Archives of disease in childhood.

[11]  P. Schwartzkroin,et al.  Development of rabbit hippocampus: physiology. , 1981, Brain research.

[12]  J Connell,et al.  Clinical and EEG response to anticonvulsants in neonatal seizures. , 1989, Archives of disease in childhood.

[13]  R. Clancy,et al.  Neurologic outcome after electroencephalographically proven neonatal seizures. , 1991, Pediatrics.

[14]  Y. Ben-Ari,et al.  Consequences of neonatal seizures in the rat: Morphological and behavioral effects , 1998, Annals of neurology.

[15]  J. Coyle,et al.  Neurochemical aspects of the ontogenesis of gabanergic neurons in the rat brain , 1976, Brain Research.

[16]  Y. Ben-Ari,et al.  Giant synaptic potentials in immature rat CA3 hippocampal neurones. , 1989, The Journal of physiology.

[17]  R. Myers,et al.  Four patterns of perinatal brain damage and their conditions of occurrence in primates. , 1975, Advances in neurology.

[18]  C. Wasterlain,et al.  Posthypoxic treatment with felbamate is neuroprotective in a rat model of hypoxia‐ischemia , 1993, Neurology.

[19]  Y. Ben-Ari,et al.  GABA: an excitatory transmitter in early postnatal life , 1991, Trends in Neurosciences.

[20]  I Rosén,et al.  Silent Seizures in Sick Infants in Early Life , 1985, Acta paediatrica Scandinavica.

[21]  M J Painter,et al.  Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae. , 1993, Pediatrics.

[22]  M. Delivoria-Papadopoulos,et al.  Cerebral metabolic effects of neonatal seizures measured with in vivo 31P NMR spectroscopy , 1986, Annals of neurology.

[23]  A M Bye,et al.  Spatial and Temporal Characteristics of Neonatal Seizures , 1995, Epilepsia.

[24]  Y. Ben‐Ari,et al.  Maturation of kainic acid seizure-brain damage syndrome in the rat. II. Histopathological sequelae , 1984, Neuroscience.

[25]  P. Stanton,et al.  Resistance of the immature hippocampus to seizure-induced synaptic reorganization. , 1991, Brain research. Developmental brain research.

[26]  A. Legido,et al.  Occult Neonatal Seizures , 1988, Epilepsia.

[27]  J Burchfiel,et al.  EEG Background as Predictor of Electrographic Seizures in High‐Risk Neonates , 1998, Epilepsia.

[28]  C. Wasterlain Effects of neonatal status epilepticus on rat brain development , 1976, Neurology.

[29]  M. Johnston Selective vulnerability in the neonatal brain , 1998, Annals of neurology.

[30]  A. Cole,et al.  Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood , 1999, Neurology.

[31]  R R Clancy,et al.  The Contribution of EEG to the Understanding of Neonatal Seizures , 1996, Epilepsia.

[32]  A. Bye,et al.  Outcome of neonates with electrographically identified seizures, or at risk of seizures. , 1997, Pediatric neurology.

[33]  G. Holmes,et al.  Consequences of recurrent seizures during early brain development , 1999, Neuroscience.

[34]  A. Legido,et al.  Postnatal Epilepsy After EEG‐Confirmed Neonatal Seizures , 1991, Epilepsia.

[35]  G. Holmes,et al.  Effects of neonatal seizures on subsequent seizure-induced brain injury , 1999, Neurology.

[36]  R. Palisano,et al.  Development and reliability of a system to classify gross motor function in children with cerebral palsy , 1997, Developmental medicine and child neurology.

[37]  N Paneth,et al.  Phenobarbital compared with phenytoin for the treatment of neonatal seizures. , 1999, The New England journal of medicine.

[38]  R. Coen,et al.  Continuous monitoring of the electroencephalogram following perinatal asphyxia. , 1982, The Journal of pediatrics.

[39]  M J Painter,et al.  Ictal and Interictal Electrographic Seizure Durations in Preterm and Term Neonates , 1993, Epilepsia.

[40]  G. Holmes,et al.  Age‐Dependent Cognitive and Behavioral Deficits After Kainic Acid Seizures , 1993, Epilepsia.

[41]  A. Legido,et al.  The Exact Ictal and Interictal Duration of Electroencephalographic Neonatal Seizures , 1987, Epilepsia.

[42]  A. Bye,et al.  Electroencephalograms, clinical observations and the monitoring of neonatal seizures , 1995, Journal of paediatrics and child health.