Deep grey matter injury (Weeke score >9.5) and persistent severe aEEG background suppression at 72 hours are robust early independent predictors of epilepsy by age 2 years in neonates with HIE treated with therapeutic hypothermia.
15% of neonates with moderate-to-severe HIE treated with therapeutic hypothermia developed epilepsy by 24 months of age.
Deep grey matter injury on brain MRI (Weeke score >9.5) was an independent predictor of epilepsy in multivariate analysis.
Persistent severe aEEG background suppression at 72 hours was an independent predictor of epilepsy in multivariate analysis.
All patients who developed epilepsy also had concurrent cerebral palsy with significant motor impairment.
The study used a combination of clinical staging, continuous aEEG monitoring, and brain MRI with Weeke scoring as neonatal evaluations to predict later epilepsy.
This research followed 127 babies diagnosed with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) — a condition where the brain is deprived of oxygen around the time of birth — who were treated with therapeutic hypothermia (controlled whole-body cooling, the standard treatment). The study tracked which babies went on to develop epilepsy by age 2, finding that 15% (19 babies) did. By analyzing brain MRI scans and continuous brain activity monitoring (aEEG) done during the cooling treatment, the researchers identified two early warning signs that strongly predicted later epilepsy: injury to the deep grey matter structures of the brain on MRI (using a scoring system called the Weeke score), and failure of brain electrical activity to recover by 72 hours on the aEEG monitor. These two factors remained significant even after accounting for other variables, with deep grey matter injury associated with over 100 times higher odds of developing epilepsy and persistent brain activity suppression at 72 hours associated with about 25 times higher odds. Notably, every single baby who developed epilepsy also had cerebral palsy with significant motor impairment, suggesting epilepsy in this context is part of a broader pattern of severe neurological injury rather than an isolated outcome. This research suggests that doctors caring for newborns treated with therapeutic hypothermia can use information available very early — specifically the brain MRI results and whether brain electrical activity recovers within 72 hours — to identify which babies are at highest risk for developing epilepsy. This early identification could help families and medical teams plan for intensive monitoring and multidisciplinary follow-up care for the highest-risk infants.
Calligaris S, Jozefkowicz M, Cáceres M, Erripa J, Reyes Valenzuela G, Gomez J, et al.. (2026). Early predictors for later epilepsy after therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy.. Epilepsy & behavior : E&B. https://doi.org/10.1016/j.yebeh.2026.111130