Hypothermia reduces seizure burden and improves neurological outcome in severe hypoxic–ischemic encephalopathy: an observational study

Guidotti, Isotta; Lugli, Licia; Guerra, Maria P.; Ori, Luca; Gallo, Claudio; Cavalleri, Francesca; Ranzi, Andrea; Frassoldati, Rossella; Berardi, Alberto; Ferrari, Fabrizio

doi:10.1111/dmcn.13195

Cited by 30 publications

(30 citation statements)

References 21 publications

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“…Seizure onset after 24 h of EEG monitoring is reported in the literature. 5,6,8,17,23,24 Information on EEG background in those cases are scarce, although most reported neonates had severe encephalopathy. Some studies have included in the definition of excessively discontinuous pattern also more severe patterns such as burst-suppression and longer interburst interval.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of early EEG for seizures in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Predictive value of early EEG for seizures in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia

et al. 2018

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“…; Guidotti et al . ). However, the protective strategies and treatment for HIBI are currently unsatisfactory, and there is an urgent need to uncover the brain injury mechanism that is involved in HIBI in neonates in order to find new therapeutic approaches for improving the function of cognitivation and memory.…”

mentioning

confidence: 97%

“…It can occur during intrauterine fetal hypoxia and birth asphyxia, or surgical operations, such as congenital cardiac surgery (Lin et al, 2014). Recent studies have shown that hypothermia is an available approved therapy for neonatal ischemic encephalopathy (Elbahtiti et al 2016;Guidotti et al 2016). However, the protective strategies and treatment for HIBI are currently unsatisfactory, and there is an urgent need to uncover the brain injury mechanism that is involved in HIBI in neonates in order to find new therapeutic approaches for improving the function of cognitivation and memory.…”

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confidence: 99%

Autophagy activation involved in hypoxic‐ischemic brain injury induces cognitive and memory impairment in neonatal rats

Tian

et al. 2016

Journal of Neurochemistry

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Hypoxic-ischemic brain injury (HIBI) in neonates can lead to lifelong cognitive and memory impairment, but protective strategies are lacking at present. It has been demonstrated that autophagy plays a critical role in HIBI, while the function of autophagy in cognitive and memory impairment induced by HIBI in neonates has not been tested. In this study, we tested the impact of autophagy on the impairment of cognitive function and memory in HIBI neonatal rats by using a Morris water maze and investigated its possible mechanisms, which were established as HIBI model by ligating the left common carotid artery in neonatal rats, followed by 2-h hypoxia. The expression of microtubule-associated protein 1 light chain 3 (LC3)-II increased in HI group 24 h after HI in neonatal rats, while Sequestosome 1 (P62/SQSTM1), phosphorylated cAMP-response element-binding protein (p-CREB) decreased (compared with the sham group, p < 0.05), which were shown in the same left hippocampus CA3 region by immunofluorescence analysis. Brain injury of neonatal rats was aggravated significantly at 7 day after HI, coinciding with the results of Morris water maze. An autophagy inhibitor, 3-methyladenine (3-MA) pretreatment significantly attenuated the increase of LC3II and the loss of P62/SQSTM1 and p-CREB, ameliorated neuronal death, and improved the results of Morris water maze. Our results demonstrate that HIBI in neonatal rats induced excessive autophagy flux, which aggravated brain injury and induced cognitive and memory impairment during adolescence. Inhibition of autophagy reversed the results partly and improved the function of spatial learning and memory by attenuating the reduction of p-CREB. The use of autophagy modulators in the immature brain would create new opportunities for protective strategies clinically in the future.

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“…[6][7][8] For infants with HIE, the neonatal diagnosis most associated with seizures, 9 therapeutic hypothermia has emerged as a treatment to reduce seizure burden. 2,[10][11][12] Few published reports have evaluated national anticonvulsant medication prescription trends among NICU infants. 5,8 There is even less examination of anticonvulsant prescription patterns for hypothermia-treated infants with HIE.…”

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confidence: 99%

Neonatal Antiepileptic Medication Treatment Patterns: A Decade of Change

Abdi

Sánchez

et al. 2019

Am J Perinatol

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Objective This article aims to describe the frequency and characteristics of anticonvulsant medication treatments initiated in the neonatal period. Study Design We analyzed a cohort of neonates with a seizure diagnosis who were discharged from institutions in the Pediatric Health Information System between 2007 and 2016. Adjusted risk ratios and 95% confidence intervals for characteristics associated with neonatal (≤ 28 days postnatal) anticonvulsant initiation were calculated via modified Poisson regression. Results A total of 6,245 infants from 47 institutions were included. There was a decrease in both phenobarbital initiation within the neonatal period (96.9 to 91.3%, p = 0.015) and continuation at discharge (90.6 to 68.6%, p <0.001). Levetiracetam (7.9 to 39.6%, p < 0.001) initiation within the neonatal period and continuation at discharge (9.4 to 49.8%, p < 0.001) increased. Neonates born at ≥ 37 weeks' gestation and those diagnosed with intraventricular hemorrhage, ischemic/thrombotic stroke, other hemorrhagic stroke, and hypoxic ischemic encephalopathy (HIE) had a higher probability of anticonvulsant administration. The most prevalent diagnosis was HIE (n = 2,223, 44.4%). Conclusion Phenobarbital remains the most widely used neonatal seizure treatment. Levetiracetam is increasingly used as a second line therapy. Increasing levetiracetam use indicates a need for additional study to determine its effectiveness in reducing seizure burden and improving long-term outcomes.

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Hypothermia reduces seizure burden and improves neurological outcome in severe hypoxic–ischemic encephalopathy: an observational study

Abstract: Hypothermia has an antiepileptic effect in both moderate and severe neonatal HIE. The lower seizure burden in cooled newborn infants with severe HIE is more commonly associated with normal outcome at 24 months.

Cited by 30 publications

References 21 publications

Predictive value of early EEG for seizures in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia

Predictive value of early EEG for seizures in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia

Autophagy activation involved in hypoxic‐ischemic brain injury induces cognitive and memory impairment in neonatal rats

Neonatal Antiepileptic Medication Treatment Patterns: A Decade of Change

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