Treating Seizures after Hypoxic-Ischemic Encephalopathy—Current Controversies and Future Directions

Seizures are common in newborn infants with hypoxic-ischemic encephalopathy and are highly associated with adverse neurodevelopmental outcomes. The impact of seizure activity on the developing brain and the most effective way to manage these seizures remain surprisingly poorly understood, particular...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-07, Vol.22 (13), p.7121
Main Authors: Zhou, Kelly Q., McDouall, Alice, Drury, Paul P., Lear, Christopher A., Cho, Kenta H. T., Bennet, Laura, Gunn, Alistair J., Davidson, Joanne O.
Format: Article
Language:English
Subjects:
Adults
Anticonvulsants
antiepileptic drugs
asphyxia
Brain damage
Brain injury
Clinical trials
Convulsions & seizures
Encephalopathy
Epilepsy
Etiracetam
Hypothermia
Hypotheses
Hypoxia
hypoxic-ischemic encephalopathy
Ischemia
Neonates
Neurotoxicity
Phenobarbital
Phenytoin
Review
Seizures
therapeutic hypothermia
Traumatic brain injury
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Summary:Seizures are common in newborn infants with hypoxic-ischemic encephalopathy and are highly associated with adverse neurodevelopmental outcomes. The impact of seizure activity on the developing brain and the most effective way to manage these seizures remain surprisingly poorly understood, particularly in the era of therapeutic hypothermia. Critically, the extent to which seizures exacerbate brain injury or merely reflect the underlying evolution of injury is unclear. Current anticonvulsants, such as phenobarbital and phenytoin have poor efficacy and preclinical studies suggest that most anticonvulsants are associated with adverse effects on the developing brain. Levetiracetam seems to have less potential neurotoxic effects than other anticonvulsants but may not be more effective. Given that therapeutic hypothermia itself has significant anticonvulsant effects, randomized controlled trials of anticonvulsants combined with therapeutic hypothermia, are required to properly determine the safety and efficacy of these drugs. Small clinical studies suggest that prophylactic phenobarbital administration may improve neurodevelopmental outcomes compared to delayed administration; however, larger high-quality studies are required to confirm this. In conclusion, there is a distinct lack of high-quality evidence for whether and to what extent neonatal seizures exacerbate brain damage after hypoxia-ischemia and how best to manage them in the era of therapeutic hypothermia.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22137121