Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia

Heursen, Eva-Marie; Ojeda, Amaya Zuazo; Fernández, Isabel Benavente; Gomez, Gema Jimenez; Fernández-Colima, Rosalía Campuzano; Paz-Expósito, José; López, Simón Pedro Lubián

doi:10.1159/000456707

Cited by 15 publications

(14 citation statements)

References 23 publications

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“…Importantly, chronic myelin disruption and associated axonopathy are apparent contributors to poor neurodevelopment after HIE, as shown by consistent correlation between microstructural lesions in the PLIC and frontal and parietal white matter, and mental, language and locomotor impairments. 7 , 26 , 29 Consistent with these reports, this study indicated modest reduction in MBP area fraction and structural tract integrity in parasagittal white matter at 7 days post-insult. Exploratory post-hoc tests suggested improvement to sham-ischaemic levels ( P = 0.06) in the first, but not second, parasagittal gyrus of rEpo-treated foetuses.…”

Section: Discussionsupporting

confidence: 87%

Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep

Wassink

Davidson

Crisostomo

et al. 2021

Brain Communications

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Therapeutic hypothermia for hypoxic-ischaemic encephalopathy provides partial white matter protection. Recombinant erythropoietin reduces demyelination after hypoxia-ischaemia, but it is unclear whether adjunct erythropoietin treatment can further improve outcomes after therapeutic hypothermia. Term-equivalent fetal sheep received sham-ischaemia (n = 9) or cerebral ischaemia for 30 min (ischaemia-vehicle, n = 8), followed by intravenous infusion of recombinant erythropoietin (ischaemia-Epo, n = 8; 5000 IU/kg bolus dose, then 833.3 IU/kg/h), cerebral hypothermia (ischaemia-hypothermia, n = 8), or recombinant erythropoietin plus hypothermia (ischaemia-Epo-hypothermia, n = 8), from 3 to 72 h post-ischaemia. Fetal brains were harvested at 7 days after cerebral ischaemia. Ischaemia was associated with marked loss of total Olig2-positive oligodendrocytes with reduced density of myelin and linearity of the white matter tracts (P < 0.01), and microglial induction and increased caspase-3-positive apoptosis. Cerebral hypothermia improved the total number of oligodendrocytes and restored myelin basic protein (P < 0.01), whereas recombinant erythropoietin partially improved myelin basic protein density and tract linearity. Both interventions suppressed microgliosis and caspase-3 (P < 0.05). Co-treatment improved 2',3'-cyclic-nucleotide 3'-phosphodiesterase-myelin density compared to hypothermia, but had no other additive effect. These findings suggest that although hypothermia and recombinant erythropoietin independently protect white matter after severe hypoxia-ischaemia, they have partially overlapping anti-inflammatory and anti-apoptotic effects, with little additive benefit of combination therapy.

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Section: Discussionsupporting

confidence: 87%

Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep

Wassink

Davidson

Crisostomo

et al. 2021

Brain Communications

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“…Multiple studies reported that lower apparent diffusion coefficient (ADC) values during the first 7–10 days were associated with adverse outcomes. This included lower ADC values in the basal ganglia [69, 72], the centrum semiovale [56, 70], the caudate nucleus [53], the PLIC [53, 56, 70, 71], the frontal or parietal WM [53, 70], and the posterior WM [56]. DWI of the thalami could be included in the meta-analyses.…”

Section: Resultsmentioning

confidence: 99%

“…Injury to the (posterior part of the) corpus callosum was related to adverse outcomes in 3 studies [53, 58, 68]. ADC values in the cerebellum and brainstem [70], as well as cortical ADC values [71], were not related to outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…Eleven studies performed quantitative analyses on diffusion imaging data, i.e., 5 using DWI within the first week of life [56,58,[68][69][70] and 6 using DTI [20,53,57,62,71,72]. Multiple studies reported that lower apparent diffusion coefficient (ADC) values during the first 7-10 days were associated with adverse outcomes.…”

Section: Quantitative Analysis Of Diffusion Imagingmentioning

confidence: 99%

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Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis

et al. 2020

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Introduction: Prediction of neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy remains an important challenge. Various studies have shown that the predictive ability of different modalities changed after the introduction of therapeutic hypothermia. This paper reviews the diagnostic test accuracy of the different modalities that are being used to predict neurodevelopmental outcomes following therapeutic hypothermia. Methods: A systematic literature search was performed using Embase and PubMed. Two reviewers independently included eligible studies and extracted data. The quality of the studies was assessed using the Quality in Prognosis Studies Tool. Meta-analyses were performed where possible. Results: Forty-seven articles and 3 conference abstracts were included, reporting on 3,072infants of whom 39% died or had an adverse neurodevelopmental outcome. A meta-analysis could be performed using 37 articles on (amplitude-integrated) electroencephalography (EEG), conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopy (1H-MRS). Amplitude-integrated EEG (aEEG) at 24 and 72 h showed similar high diagnostic OR, while aEEG at 6 h and EEG performed less, both due to a low specificity. For MRI, most studies reported scoring systems in which early (<8 days) MRI performed better than late (≥8 days) MRI. Injury to the posterior limb of the internal capsule on MRI or to the thalami on DWI were strong individual predictors, as was an increased lactate/N-acetylaspartate peak on 1H-MRS. Conclusions: In the era of therapeutic hypothermia, the different modalities remain good predictors of neurodevelopmental outcome. However, timing should be taken into account. aEEG may initially be false positive and gets more reliable after 24 h. In contrast, MRI should be used during the first week, as its predictive value decreases afterwards.

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“…Arterial spin labeling (ASL) has been validated as an effective noncontrast method for demonstrating perfusion deficits by demonstrating global hypoperfusion in BD with diffusely impaired cerebral blood flow on visual and quantitative analysis [ 16 , 17 ]. Diffusion weighted imaging (DWI) shows promise, and apparent diffusion coefficient (ADC) values obtained at high gradient strengths (b750–2000) have been shown to be helpful prognostic indicators in patients with HIE, with decreased ADC values predicting poorer outcomes [ 18 – 20 ]. Still, current use of high b-value DWI does not quantify perfusion and cannot be used to discriminate between the cellular injury of HIE and hypoperfusion related to BD.…”

Section: Introductionmentioning

confidence: 99%

Low b-value diffusion weighted imaging is promising in the diagnosis of brain death and hypoxic-ischemic injury secondary to cardiopulmonary arrest

et al. 2018

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BackgroundCardiorespiratory arrest can result in a spectrum of hypoxic ischemic brain injury leading to global hypoperfusion and brain death (BD). Because up to 40% of patients with BD are viable organ donors, avoiding delayed diagnosis of this condition is critical. High b-value diffusion weighted imaging (DWI) measures primarily molecular self-diffusion; however, low b-values are sensitive to perfusion. We investigated the feasibility of low b-value DWI in discriminating the global hypoperfusion of BD and hypoxic ischemic encephalopathy (HIE).MethodsWe retrospectively reviewed cardiorespiratory arrest subjects with a diagnosis of HIE or BD. Inclusion criteria included brain DWI acquired at both low (50 s/mm2) and high (1000–2000 s/mm2) b-values. Automated segmentation was used to determine mean b50 apparent diffusion coefficient (ADC) values in gray and white matter regions. Normal subjects with DWI at both values were used as age- and sex-matched controls.ResultsWe evaluated 64 patients (45 with cardiorespiratory arrest and 19 normal). Cardiorespiratory arrest patients with BD had markedly lower mean b50 ADC in gray matter regions compared with HIE (0.70 ± 0.18 vs. 1.95 ± 0.25 × 10−3 mm2/s, p < 0.001) and normal subjects (vs. 1.79 ± 0.12 × 10−3 mm2/s, p < 0.001). HIE had higher mean b50 ADC compared with normal (1.95 ± 0.25 vs. 1.79 ± 0.12 × 10−3 mm2/s, p = 0.016). There was wide separation of gray matter ADC values in BD subjects compared with age matched normal and HIE subjects. White matter values were also markedly decreased in the BD population, although they were less predictive than gray matter.ConclusionLow b-value DWI is promising for the discrimination of HIE with maintained perfusion and brain death in cardiorespiratory arrest.

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Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia

Cited by 15 publications

References 23 publications

Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep

Recombinant erythropoietin does not augment hypothermic white matter protection after global cerebral ischaemia in near-term fetal sheep

Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis

Low b-value diffusion weighted imaging is promising in the diagnosis of brain death and hypoxic-ischemic injury secondary to cardiopulmonary arrest

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