Dataset Information

Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia?

ABSTRACT:

Background and purpose

To determine the apparent diffusion coefficient (ADC) in specific infratentorial brain structures during the first week of life and its relation with neuromotor outcome for Hypoxic-ischemic encephalopathy (HIE) in term neonates with and without whole-body hypothermia (TH).

Materials and methods

We retrospectively evaluated 45 MRI studies performed in the first week of life of term neonates born between 2010 and 2013 at Boston Children's Hospital. Selected cases were classified into three groups: 1) HIE neonates who underwent TH, 2) HIE normothermics (TN), and 3) controls. The neuromotor outcome was categorized as normal, abnormal and death. The ADCmean was calculated for six infratentorial brain regions.

Results

A total of 45 infants were included: 28 HIE TH treated, 8 HIE TN, and 9 controls. The mean gestational age was 39 weeks; 57.8% were male; 11.1% were non-survivors. The median age at MRI was 3 days (interquartile range, 1-4 days). A statistically significant relationship was shown between motor outcome or death and the ADCmean in the vermis (P = 0.002), cerebellar left hemisphere (P = 0.002), midbrain (P = 0.009), pons (P = 0.014) and medulla (P = 0.005). In patients treated with TH, the ADC mean remained significantly lower than that in the controls only in the hemispheres (P = 0.01). In comparison with abnormal motor outcome, ADCmean was lowest in the left hemisphere (P = 0.003), vermis (P = 0.003), pons (P = 0.0036) and medulla (P = 0.008) in case of death.

Conclusion

ADCmean values during the first week of life in the left hemisphere, vermis, pons and medulla are related to motor outcome or death in infants with HIE either with or without hypothermic therapy. Therefore, this objective tool can be assessed prospectively to determine if it can be used to establish prognosis in the first week of life, particularly in severe cases of HIE.

SUBMITTER: Arca-Diaz G

PROVIDER: S-EPMC5501430 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia?

Arca-Díaz Gemma G Re Thomas J TJ Drottar Marie M Fortuno Carmen Rosa CR De Macedo-Rodrigues Katyucia K Im Kiho K Figueras-Aloy Josep J Grant Patricia Ellen PE

PloS one 20170707 7

<h4>Background and purpose</h4>To determine the apparent diffusion coefficient (ADC) in specific infratentorial brain structures during the first week of life and its relation with neuromotor outcome for Hypoxic-ischemic encephalopathy (HIE) in term neonates with and without whole-body hypothermia (TH).<h4>Materials and methods</h4>We retrospectively evaluated 45 MRI studies performed in the first week of life of term neonates born between 2010 and 2013 at Boston Children's Hospital. Selected ca ...[more]

PMID: 28686592

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Project description:Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2-3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment.Term newborns (gestational age ? 36 weeks and birth weight ? 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests.This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns.

Project description:BackgroundTheophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies.MethodsA population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5 mg/kg intravenous (i.v.) load then 1.8 mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10 mg/L) associated with clinical response was examined.ResultsBirth weight was a significant predictor of theophylline clearance and volume of distribution (p < 0.05). The median half-life was 39.5 h (range 27.2-50.4). An aminophylline loading dose of 7 mg/kg followed by 1.6 mg/kg q12h was predicted to achieve target concentrations in 84% of simulated neonates.ConclusionsIn neonates with HIE undergoing hypothermia, theophylline clearance was low with a 50% longer half-life compared to full-term normothermic neonates without HIE. Dosing strategies need to consider the unique pharmacokinetic needs of this population.ImpactTheophylline is a potential renal-protective therapy in neonates with HIE undergoing therapeutic hypothermia; however, the pharmacokinetics and dose needs in this population are not known. Theophylline clearance was low in neonates with HIE undergoing therapeutic hypothermia with a 50% longer half-life compared to full-term normothermic neonates without HIE. As theophylline is advanced in clinical development, dosing strategies will need to consider the unique pharmacokinetic needs of neonates with HIE undergoing therapeutic hypothermia.

Dataset Information

Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia?

Background and purpose

Materials and methods

Results

Conclusion

Publications

Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia?

Similar Datasets

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