Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial

Abstract

BACKGROUND: The impact of treating electrographic seizures in hypoxic ischemic encephalopathy (HIE) is unknown. METHODS:Neonates $36 weeks with moderate or severe HIE were randomly assigned to either treatment of electrographic seizures alone (ESG) or treatment of clinical seizures (CSG). Conventional EEG video was monitored in both groups for up to 96 hours. Cumulative electrographic seizure burden (SB) was calculated in seconds and converted to log units for analysis. MRI scans were scored for severity of brain injury. Infants underwent neurodevelopmental evaluation at 18 to 24 months. Statistical analyses were performed by using SAS 9.3 version (SAS Institute, Inc, Cary, NC).RESULTS: Thirty-five of 69 neonates (51%) who were randomly assigned and included in the study developed seizures (15 in ESG and 20 in CSG). Excluding infants with status epilepticus, median SB (interquartile range) in seconds in ESG (n = 10) was lower than in CSG (n = 16) (449 [113-2070] vs 2226 [760-7654]; P = .02). ESG had fewer seizures with shorter time to treatment (P = .04). Twenty-four of 30 (80%) surviving infants with seizures underwent neurodevelopmental evaluation at 18 to 24 months. Increasing SB in the combined cohort was significantly associated with higher brain injury scores (P , .03) and lower performance scores across all 3 domains on BSID III (P = .03). CONCLUSIONS:In neonates with HIE, EEG monitoring and treatment of electrographic seizures results in significant reduction in SB. SB is associated with more severe brain injury and significantly lower performance scores across all domains on BSID III. WHAT'S KNOWN ON THIS SUBJECT:Continuous conventional EEG video is currently gold standard for identifying neonatal seizures and a substantial proportion of neonatal seizures are electrographic. Currently there is no direct evidence that EEG monitoring, seizure identification, or treatment impacts long-term outcomes. WHAT THIS STUDY ADDS:In neonates with hypoxic ischemic encephalopathy, EEG monitoring and treatment of electrographic seizures results in significant reduction in seizure burden. Increasing seizure burden is associated with more severe brain injury and significantly lower performance scores on Bayley Scales of Infant Development III.

Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy

“…The importance of neonatal seizure burden for outcome has been highlighted by many researchers,2, 7, 9, 22 but in HIE it has not been fully quantified for long‐term outcome 7, 12, 14. In critically ill children with diseases of mixed aetiologies, including neonates with HIE, MSB of more than 12 minutes per hour was found to be associated with an increase in short‐term neurological decline, independent of the diagnosis or severity of illness 22.…”

“…However, current protocols for therapeutic hypothermia are more effective in moderate than severe encephalopathy,1 and the TSB is significantly reduced in neonates undergoing therapeutic hypothermia with clinically moderate but not severe HIE 10. In HIE cohorts with hypothermia, seizures on cEEG were associated with more severe structural brain damage, although 40% of neonates with seizures may have a normal MRI 13, 14…”

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening

“…The constants relate to the pre-selection of 80% power and a level of significance of 0.05 (two-sided test). An equal number of patients in each group (N/2) was also assumed as per current practice in studies on treatments for neonatal seizures [4,5,13,15,16]. showing the variability of seizures in neonates (the black line in A and B refers to the same neonate) [7,10].…”

“…It is generally accepted that the accumulated duration of seizures, or seizure burden, as measured by multi-channel EEG, should be the quantitative measure of choice when assessing anti-epileptic drug (AED) efficacy [4,5,[11][12][13]. This is based on the assumption that a high seizure burden causes further damage to the already compromised neonatal brain [14][15][16]. An evidence based AED trial should, therefore, be powered so that it takes into account the natural time course of neonatal seizures.…”

Preventing deaths from complications of labour and delivery

“…Continuous EEG studies show that an electrographic seizure burden often remains after anticonvulsant treatment [59,60]. Whether treating all electrographic seizures is necessary is unclear, as both the seizure burden and the use of anticonvulsant drugs adversely influence neurodevelopmental outcome [61,62]. Anticonvulsants can usually be stopped before discharge especially regarding concern on effects of anticonvulsants on the immature brain [63].…”