Neonatal seizures: little difference between EEG and clinical treatment

Mortality, disability similar results

In neonates admitted to neonatal intensive care units (NICU), treatment of purely electrographic seizures in addition to those that were clinically evident made little difference in terms of death or severe disability at 2 years, according to a randomized trial.

Chances of the main outcome at the age of 2 years: death; a development score including motor, language and cognitive functions; or the presence of cerebral palsy, blindness or deafness – were not significantly different in the electrographic / clinical treatment group compared to the clinical treatment alone group.

The result occurred in 44% versus 31%, respectively (OR 1.83, 95% CI 0.96 to 3.49, P= 0.14), reported Rod Hunt, PhD, of Monash University in Australia, and the co-authors of JAMA network open.

“In this randomized controlled trial, there was little evidence of a difference in mortality or morbidity at 2 years between an electrographic seizure group and a clinical seizure group, however, our study was low powered,” the researchers wrote. .

“There was little evidence of a difference in side outcomes, including the time taken to suck food, seizure burden or brain injury score,” they added.

The researchers studied NICU patients with at least 35 weeks gestation admitted with encephalopathy and less than 48 hours old. “Recruitment began in March 2012 and ended prematurely in 212 newborns in January 2016 due to slow trials and loss of balance at some sites with the publication of Srinivasakumar in October 2015, suggesting that treatment of all electrographic seizures was beneficial, “Hunt and colleagues noted.

Inclusion criteria were neonatal encephalopathy (including coma, stupor or depressed mental state), hypoxic-ischemic lesions (HES) or suspected neonatal seizures, regardless of the cause. All participants underwent electroencephalographic (EEG) monitoring.

The researchers evaluated 86 newborns in the electrographic / clinical seizure group (in which both electrographic and clinically evident seizures were treated, with the EEG screen visible) and 86 in the clinical seizures group (in which only the clinically evident seizures were treated). clinically obvious were processed and the EEG screen was covered). A brain injury score was determined by MRI.

The primary outcome measure was determined at age 2 as death; severe disability defined as scores in any domain of development more than 2 standard deviations below the Australian mean assessed with the Bayley Scales for the Development of Newborns and Infants, 3rd Edition (BSID -III>); or cerebral palsy, blindness or deafness.

The mean gestational age was 39.2 weeks and 58% were male. Moderate to severe EHI was observed in 72% of cases. The other causes of seizures were arterial ischemic stroke (10%), extraaxial hemorrhage (8%), sino-venous thrombosis (2%), genetic epilepsies (2%) and hypoglycemia (1 %).

Electrographic seizures were observed in 84% of the whole. For the electrographic / clinical and clinical groups, anticonvulsant drugs were used in 86% and 69%, respectively.

A total of 9% of newborns in the EEG / clinical seizures group and 4% in the clinical seizure group died before the 2-year assessment (OR 2.66, 95% CI 0.81-8.78 ). Postnatal epilepsy developed in 6% of the EEG / clinical versus 4% in the clinical group, with no significant difference between the groups.

Cognitive scores on the BSID-III were worse in the electrographic / clinical group compared to the clinical only group, with a significant difference in point scores (mean difference -6.5 points in favor of the clinical group (95% CI -1.2 to -11.8, P= 0.01).

“Contrary to our hypothesis, we report an association of improved cognitive outcome at 2 years in the clinical seizure group,” wrote Hunt and colleagues. “Most neonatal seizures are subclinical, that is, EEG epileptogenic discharges occur without any time-related motor or autonomic clinical symptoms, and, moreover, the diagnosis of clinical seizures in neonates is very unreliable, “wrote Martin Offringa, MD, PhD, and Brian Kalish, MD, both of the University of Toronto in Canada, in an accompanying editorial.

“As a result, neuromonitoring with amplitude integrated EEG (aEEG) or continuous EEG (cEEG) has become the standard of care among tertiary NICUs,” continued Offringa and Kalish. “Yet, while EEG monitoring in the NICU enables precisely guided diagnostic and therapeutic approaches, an unresolved question in neonatology and neonatal neurology is whether treatment of subclinical electrographic seizures is beneficial.”

“This is the largest study to date comparing two current clinical approaches to the management of neonatal seizures in the NICU,” the editorialists noted. “The inclusion of early stage patients with a range of seizure etiologies is very pragmatic and reflects clinical practice, in which the precise cause of seizures is often unknown at the time of initiation of treatment. ”

Given the uncertainties about treatments, including the effectiveness of phenobarbital (often considered a first-line treatment for neonatal seizures), “it is imperative that we rationalize the dose and duration of anticonvulsant administration during periods reviews of neurodevelopment, and that our management decisions be based on good – studies that show that drug interventions do more good than harm, ”they added.

Seizures in newborns are associated with an increased risk of death and neurodevelopmental disorders and are often treated aggressively. The causes differ for term infants (EHI, stroke, malformations, metabolic changes) compared to premature infants (intraventricular hemorrhage and infections), and their clinical manifestations differ considerably from later semiology. Uncertainty remains as to the best treatments and the trade-offs between the adverse effects of seizures compared to their treatment.

Limitations of the trial include that recruitment was stopped early and the study did not have sufficient power. In addition, the study used a compressed 1 or 2 channel EEG (aEEG) representation different from the full channel cEEG, which limits the generalization of parameters using the more resource intensive cEEG monitoring.

1. A randomized trial found that treating purely electrographic seizures in addition to those clinically evident in newborns made little difference in terms of death or severe disability at 2 years.

2. Chances of the main outcome at the age of 2 years: death; a development score including motor, language and cognitive functions; or the presence of cerebral palsy, blindness or deafness – were not significantly different in the electrographic / clinical treatment group compared to the clinical treatment alone group.

Paul Smyth, MD, Contributing Writer, BreakingMED ™

This study was funded by the Australian National Board of Health and Medical Research.

Hunt had no disclosure.

Offringa and Kalish have had no disclosure.

Cat ID: 34

Subject ID: 82,34,730,34,138,192,925