A 2015 clinical trial found that treatment for severe and moderate neonatal seizures can reduce the impact of cumulative electrographic seizure burden in infants born with hypoxic ischemic encephalopathy (HIE). This American Academy of Pediatrics trial used EEG video (video to monitor brain activity) and standard medication for neonatal seizures to reduce the impact. The trial concluded that this data in combination with other studies can ultimately prove that this method can reduce the severity of brain injury. Preethi Srinivasakumar, MD, John Zempel, MD, PhD, Shamik Trivedi, MD, Michael Wallendorf, PhD, Rakesh Rao, MD, Barbara Smith, R.EEG, T, Terrie Inder, MD, and Amit M. Mathur, MD all contributed to the clinical trial from 2007 to 2011.
HIE Causes Neonatal Seizures
Neonatal seizures are the most common neurological disease in infants. Hypoxic ischemic encephalopathy (HIE) (lack of oxygen and blood flow to the brain, causing brain dysfunction) is the most common cause of neonatal seizures. A seizure is an abnormal electrical discharge in the brain that causes neurological damage. A seizure can present physical signs (such as convulsions, sensory disturbances, or loss of consciousness), which result from abnormal electrical discharges in the brain. However, some infants with seizure activity on medical testing (known as EEG), have no physical signs of seizure. By understanding, diagnosing and treating seizures, even when signs are not apparent, further injury to the brain can be reduced.
Understanding Cumulative Electrographic Seizure Burden (SB)
In this trial, 50 infants with moderate to severe HIE were randomly assigned to two groups: electrographic and clinical. The electrographic group received EEG monitoring for their seizures. The clinical group was monitored for physician signs of seizure. In evaluating the infants, whether electrographically or clinically, doctors monitored the duration of seizures over a defined period of time, which is defined by seizure burden. For this controlled trial, SB was defined by two points.
1) How long a seizure would last – The doctors measured the seizures in seconds. Seizures that last for five minutes or longer are called status epilepticus. The longer a seizure lasts, the more severe it is.
2) If a seizure had apparent signs – Electrographic seizures are uncontrollable electrical impulses in the brain that can sometimes only be seen through EEG monitoring. Clinical seizures are more apparent, and may demonstrate body limpness, loss of consciousness, long stares and pedaling motions of the legs.
Severity of Seizures Linked to Severity of Injury
There was a direct relationship between the severity of seizures and the severity of brain injury (which was shown by MRIs). All babies who had status epilepticus also had a severe brain injury. If the injury was severe, the seizures were longer and more frequent.
The doctors specifically chose neonates who were less than 36 weeks gestation at birth and over 24 hours of age. This allowed the doctors to exclude the neonates whose seizures were not related to HIE. They also excluded infants who had electrographic status epilepticus at the beginning of the trial.
Both groups were monitored with conventional EEG video for 96 hours and received targeted treatments for their seizures. According to the trial, continuous EEG video is standard for identifying neonatal seizures. While the electrographic seizure group received the fullest extent of video monitoring, the clinical group did not. No EEG seizure detection data was visibly available for the clinical seizure group. Both groups were given phenobarbital and fosphenytoin for neonatal seizures. Seizures of any kind must be treated immediately to avoid further brain injury.
Testing for Severity of Injury
Infants were given MRIs (brain scans) to test for severity of injury. Each MRI was taken between seven and 10 days of the newborn’s life. The doctors used standardized methods and conventional imaging and sequences to score the participants.
The trial showed that a combination of EEG video monitoring and standard medication for seizures can reduce seizure burden for infants who suffer from electrographic seizures. There was a significant reduction in the total cumulative electrographic seizure burden when compared to treatment for clinical seizures. The doctors concluded that this may suggest that targeted treatment for electrographic seizures in infants with HIE can reduce brain injury.
The trial was performed in the Departments of Pediatrics, neurology, and Biostatistics, Washington University in St Louis, St Louis Missouri; Clinical Neurophysiology Laboratory, St Louis Children’s Hospital, St Louis, Missouri; and Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.
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