Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

Cavalleri, Francesca; Lugli, Licia; Pugliese, Marisa; D’Amico, Roberto; Todeschini, Alice; Casa, Elisa Della; Gallo, Claudio; Frassoldati, Rossella; Ferrari, Fabrizio

doi:10.1007/s00247-014-2945-9

Cited by 32 publications

(14 citation statements)

References 20 publications

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“…Only a few published studies have addressed the predictive value of ADC measurements in neonates with HIE, and most of these were performed in normothermia-treated infants [16,17]. In a meta-analysis [3], ADC was reported to have a sensitivity of 66% (95% CI: 52-79) and a specificity of 64% (95% CI: 35-87).…”

Section: Discussionmentioning

confidence: 99%

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

Heursen

Ojeda

Fernández³

et al. 2017

Neonatology

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Background: Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. Objectives: To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). Methods: This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). Results: The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). Conclusions: Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome.

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Section: Discussionmentioning

confidence: 99%

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

Heursen

Ojeda

Fernández³

et al. 2017

Neonatology

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“…Diffusion-weighted imaging (DWI) is a sensitive imaging modality to detect ischemic changes, in earliest phase; depending on early restricted diffusion within ischemic brain tissue 25 . In addition, it provides quantitative apparent diffusion coefficient (ADC) values within brain tissue 26 .…”

Section: Discussionmentioning

confidence: 99%

Diffusion-Weighted MRI and Urinary Activin-A are Correlated with the Degree of Hypoxic Ischemic Encephalopathy in Neonates

Maher¹,

Abdelazim²,

Eissawy³

et al. 2017

Preprint

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Background: Early identification and prevention of hypoxic ischemic encephalopathy (HIE) may reduce neonatal mortality and morbidity. Objective: We aimed to correlate between urinary Activin-A and MRI (conventional and Diffusion-weighted) and the severity of HIE in fullterm neonates. Methods: Forty-five full-term neonates with HIE admitted to NICU and 15 normal neonates were enrolled into the study. The concentration of urinary Activin-A was determined using enzyme immunoassay kits and MRI were done. Correlations between urinary Activin-A and MRI with the degree of HIE were done. Results: Urinary Activin-A levels were significantly higher in neonates with HIE than controls (P<0.001). It was positively correlated with the clinical grading of HIE and a cutoff value of 0.08µg/l on day-1 after birth had a sensitivity of 98.6% and specificity of 97.1% for prediction of HIE. DW-MRI detected HIE with a high sensitivity (85%) compared to the low sensitivity of conventional MRI (35%). An ADC value of ≤ 0.8 was the best sensitivity-specificity cutoff point for detecting severe ischemic injury. DW-MRI imaging was positively correlated with Urinary Activin-A and both of them were positively correlated with the clinical grades of HIE (P < 0.001). Conclusions: DW-MRI imaging is correlated well with urinary Activin-A in full-term neonates with HIE and both of them are correlated with the degree of HIE. Early determination of urinary Activin-A combined with DW-MRI imaging can early detect HIE and its severity in fullterm neonates with HIE.

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“…White matter injury remains a prominent component of neurologic injury in HIE despite the use of therapeutic hypothermia, [46, 47] and white matter injuries predict neurodevelopmental outcomes in survivors of HIE. [7] The difference in cell-specific UPR activation may be due to high protein synthesis in myelinating glia [55] that could impart vulnerability to temperature-related ER stress. The UPR is associated with apoptosis in myelinating glia in multiple sclerosis and Charcot-Marie-Tooth.…”

Section: Discussionmentioning

confidence: 99%

“…[5] Cortical and white matter injuries on MRI predict neurodevelopmental and motor impairments in survivors of HIE. [6, 7] Thus, there is need to define the mechanisms through which apoptotic cascades are activated after HI, hypothermia, and rewarming; to clarify targets for adjuvant therapies; and to minimize off-target effects from hypothermia and rewarming.…”

Section: Introductionmentioning

confidence: 99%

Hypothermia and Rewarming Activate a Macroglial Unfolded Protein Response Independent of Hypoxic-Ischemic Brain Injury in Neonatal Piglets

Lee¹,

Wang²,

Reyes³

et al. 2016

Dev Neurosci

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Therapeutic hypothermia provides incomplete neuroprotection after hypoxia-ischemia (HI)-induced brain injury in neonates. We previously showed that cortical neuron and white matter apoptosis are promoted by hypothermia and early rewarming in a piglet model of HI. The unfolded protein response (UPR) may be one of the potential mediators of this cell death. Here, neonatal piglets underwent HI or sham surgery followed by 29 h of normothermia, 2 h of normothermia + 27 h of hypothermia or 18 h of hypothermia + rewarming. Piglets recovered for 29 h. Immunohistochemistry for endoplasmic reticulum to nucleus signaling-1 protein (ERN1), a marker of UPR activation, was used to determine the ratios of ERN1+ macroglia and neurons in the motor subcortical white matter and cerebral cortex. The ERN1+ macroglia were immunophenotyped as oligodendrocytes and astrocytes by immunofluorescent colabeling. Temperature (p = 0.046) and HI (p < 0.001) independently affected the ratio of ERN1+ macroglia. In sham piglets, sustained hypothermia (p = 0.011) and rewarming (p = 0.004) increased the ERN1+ macroglia ratio above that in normothermia. HI prior to hypothermia diminished the UPR. Ratios of ERN1+ macroglia correlated with white matter apoptotic profile counts in shams (r = 0.472; p = 0.026), thereby associating UPR activation with white matter apoptosis during hypothermia and rewarming. Accordingly, macroglial cell counts decreased in shams that received sustained hypothermia (p = 0.009) or rewarming (p = 0.007) compared to those in normothermic shams. HI prior to hypothermia neutralized the macroglial cell loss. Neither HI nor temperature affected ERN1+ neuron ratios. In summary, delayed hypothermia and rewarming activate the macroglial UPR, which is associated with white matter apoptosis. HI may decrease the macroglial endoplasmic reticulum stress response after hypothermia and rewarming.

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Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

Abstract: DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes.

Cited by 32 publications

References 20 publications

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

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

Diffusion-Weighted MRI and Urinary Activin-A are Correlated with the Degree of Hypoxic Ischemic Encephalopathy in Neonates

Hypothermia and Rewarming Activate a Macroglial Unfolded Protein Response Independent of Hypoxic-Ischemic Brain Injury in Neonatal Piglets

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