Neonatal seizures rarely result in an epilepsy diagnosis by 2 years of age, but seizures that persist into early childhood are associated with a high risk of neurodevelopmental problems, according to a multicenter study presented at AES2020, the virtual meeting of the American Epilepsy Society.
In this multicenter study of infants who survived acute symptomatic neonatal seizures, 13 percent had post-neonatal epilepsy by age 24 months. Although half were seizure-free for at least six months at last follow-up, 80 percent had clearly abnormal development, said the lead study author Renée Shellhaas, MD, clinical professor of pediatrics at the University of Michigan in Ann Arbor and director of research in the division of pediatric neurology at Michigan Medicine.
The researchers assessed 282 infants who were born between July 2015 and March 2018 at nine neonatal seizure registry sites. All infants had acute symptomatic neonatal seizures.
Infants with neonatal onset epilepsy syndromes were excluded.
The investigators evaluated post-neonatal functional development and epilepsy at ages 12, 18, and 24 months using the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) scale. By 24 months, 37 of the 282 children who had experienced neonatal seizures were diagnosed with epilepsy.
Dr. Shellhaas said that 80 percent of the children who developed epilepsy had WIDEA-FS scores worse than two standard deviations below the normal population mean.
“Additionally, up to a third of infants who developed epilepsy had treatment-resistant, frequent daily seizures. This shows a broad range of epilepsy outcomes—from no epilepsy in the majority to treatment-resistant epilepsy in a high-risk few," she told Neurology Today At the Meetings.
Risk factors for post-neonatal epilepsy included EEG-confirmed seizures on multiple days and an abnormal neurological examination upon discharge from a neonatal seizure admission, Dr. Shellhaas noted. “Families whose children have these risk factors should be specifically counseled about infantile seizure semiologies—focal seizures and infantile spasms, in particular."
“Nine of the 37 infants who developed epilepsy in our cohort already had epilepsy by the time they reached the age of 3 months," she said. “In addition, most of the infants who had an abnormal EEG at 3 months did not go on to develop epilepsy. Therefore, we found that a routine EEG at age 3 months does not seem to be clinically helpful for screening for post-neonatal epilepsy risk."
Notably, five infants already had hypsarrhythmia on their three-month EEGs, which indicates a very high risk for infantile spasms, Dr. Shellhaas said. “We suggest that infants with risk factors—especially neonatal seizures on three or more days, and/or severely abnormal EEG backgrounds, and abnormal neurological examinations, as well as those with brainstem or basal ganglia injury—should be followed especially closely by their pediatrician and child neurologist. Waiting until 3 months of age to follow-up with a child neurologist is too long for many of these high-risk infants."
“One of the strengths of this study is that all of the seizures were confirmed to be seizures," commented Dennis Dlugos, MD, professor of neurology and pediatrics at the University of Pennsylvania Medical School, who was not involved with the study. “No previous prospective studies have confirmed that a sick newborn is having EEG-confirmed seizures. In older literature, it has sometimes been difficult to determine what was a clinical neonatal seizure, but we know that clinical identification of neonatal seizures is difficult, and without EEG confirmation it is hard to know who is having a seizure or not."
“The good news is that just one in 7.5 of these children with neonatal seizures will go on to have epilepsy," he said. “The bad news is that one in 7.5 of these children will go on to have epilepsy, so whether that 13 percent rate is considered high or low depends upon your perspective."
“The children in this study had what we call provoked seizures, that is, they were provoked by an underlying cause such as hypoxic ischemic encephalopathy, head trauma, bleeding, infection, or metabolic abnormalities. Epilepsy is defined as unprovoked seizures," noted Dr. Dlugos.
“Here, the acute or unprovoked symptomatic seizures were studied to see how many of them went on to develop epilepsy," he said. “The seizures being studied in this presentation are symptoms of an underlying condition. In these children, we try to minimize the injury, but reversing the injury is a lofty goal. In neonatal care, we are trying to reverse or minimize the injury."
Dr. Dlugos said that the bottom line for parents is that the child “in most cases will not go on to have epilepsy. The 87 percent figure is good, we would like it to be better, but that is encouraging news. The other encouraging news is that if the kids do develop epilepsy most respond to treatment."
Drs. Shellhaas and Dlugos had no relevant disclosures.
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AES Abstract 99: Shellhaas R, Wusthoff C, Numis A, et al. Early-life epilepsy after acute symptomatic neonatal seizures—A prospective multicenter study.