Abstracts

Rationale: Therapeutic hypothermia (TH) is becoming standard of care for newborns with hypoxic-ischemic encephalopathy (HIE). While neonatal seizure is considered an important risk factor for brain injury in this population, recent studies suggest that the outcome after seizures is not uniformly poor. We describe the association between isolated or recurrent seizures and status epilepticus (SE) and outcome using brain MRI as an early outcome measure. Methods: Consecutive newborns who underwent whole body cooling at Bambino Gesú Children's Hospital, Rome and University Hospital of Modena, Italy between March 2009 and June 2012 were studied with continuous V-EEG monitoring during TH and rewarming. Criteria for TH were based on those used in randomized controlled trial. SE was defined as continuous seizure activity for at least 30 minutes or recurrent seizures for over 50% of 1-3 hours recording time. Seizures were treated with antiepileptic drugs including midazolam, phenobarbital, phenytoin and levetiracetam according to institutional guidelines. MRI was performed shortly after rewarming and injury was scored as "none-mild" or "moderate-severe" using a system strongly predictive of neurodevelopmental outcome following neonatal HIE (Barkovich et al. AJNR, 1998). Results: 44 patients (22 males) who completed 72 hours TH with continuous video-EEG monitoring were included in this study. Video-EEG was initiated at mean of 6.8 hours (range 2-18) and it had a mean duration of 75 hours (range 13-138). Seizures were identified in 22/44 (50%) patients. Seizures onset varied from 2 to 78 hours of life (mean: 23.8 hours of life). While most newborns with seizures (20/22, 91%) had seizure onset during TH, 1 (4.5%) presented with seizures during rewarming and 1 (4.5%) shortly after rewarming. Among the 22 newborns with seizures, 14 (63%) presented with isolated or recurrent seizures and 8 (37%) had SE. 12 patients (55%) never showed a clinical correlate during seizures, including 4 with subclinical SE. 1 patient with SE died shortly after TH was completed and could not be studied with MRI. 28 infants (65%) had none-mild MRI injury while moderate-severe MRI injury was observed in 15 children (35%). Among those neonates with isolated-recurrent seizures, 8 (57%) had none-mild brain injury and 6 (43%) had moderate-severe injury. All neonates who had SE had moderate-severe brain MRI injury. 22 neonates never had seizures. Among those, 20 (91%) had a normal MRI and 2 had moderate-severe MRI injury. Conclusions: While isolated or recurrent seizures were recorded in 43% of infants with moderate to severe brain injury, not all were associated with moderate to severe damage, as 57% of neonates with seizures were spared from brain injury. In contrast, SE was diagnosed only in newborns with unfavorable outcomes such as death or severely abnormal MRI. Finally, the high rate of subclinical seizures strongly suggests that continuous EEG monitoring is required for seizure detection and treatment in this population.