White matter injury after neonatal encephalopathy is associated with thalamic metabolite perturbations

Abstract

Background: Although thalamic magnetic resonance (MR) spectroscopy (MRS) accurately predicts adverse outcomes after neonatal encephalopathy, its utility in infants without MR visible deep brain nuclei injury is not known. We examined thalamic MRS metabolite perturbations in encephalopathic infants with white matter (WM) injury with or without cortical injury and its associations with adverse outcomes. Methods: We performed a subgroup analysis of all infants recruited to the MARBLE study with isolated WM or mixed WM/cortical injury, but no visible injury to the basal ganglia/thalamus (BGT) or posterior limb of the internal capsule (PLIC). We used binary logistic regression to examine the association of MRS biomarkers with three outcomes (i) WM injury score (1 vs. 2/3); (ii) cortical injury scores (0/1 vs. 2/3); and (iii) adverse outcomes (defined as death, moderate/severe disability) at two years (yes/no). We also assessed the accuracy of MRS for predicting adverse outcome. Findings: Of the 107 infants included in the analysis, five had adverse outcome. Reduced thalamic N-acetylaspartate concentration [NAA] (odds ratio 0.4 (95% CI 0.18À0.93)) and elevated thalamic Lactate/NAA peak area ratio (odds ratio 3.37 (95% CI 1.45À7.82)) were significantly associated with higher WM injury scores, but not with cortical injury. Thalamic [NAA] (5.6 mmol/kg/wet weight) had the best accuracy for predicting adverse outcomes (sensitivity 1.00 (95% CI 0.16À1.00); specificity 0.95 (95% CI 0.84À0.99)). Interpretation: Thalamic NAA is reduced in encephalopathic infants without MR visible deep brain nuclei injury and may be a useful predictor of adverse outcomes.

Predictive Models of Neurodevelopmental Outcomes After Neonatal Hypoxic-Ischemic Encephalopathy

“…White matter injury was also evaluated for the cumulative model but did not reach significance, which is in line with a recent study revealing that white matter injury had the lowest specificity of the MRI biomarkers evaluated, with only 7% of the infants with white matter injury developing NDI at 2 years. 20 Previous studies have revealed that deep gray matter injury, such as bilateral basal ganglia changes, has an 84% sensitivity but a 42% specificity for death or central motor deficit at 1 year, 21 although diffusion imaging of the basal ganglia and thalamus has revealed much higher specificities for death or NDI of 95% and 98%, respectively. 22 Additionally, MRS has been evaluated as a prognostic biomarker, and deep gray matter lactate to N-acetyl aspartate ratio is one of the most accurate quantitative magnetic resonance biomarkers in the neonatal period for predicting NDI.…”

GluN2B-containing NMDA receptor attenuated neuronal apoptosis in the mouse model of HIBD through inhibiting endoplasmic reticulum stress-activated PERK/eIF2α signaling pathway

“…This might provide new insights for treating HIBD. Currently, hypothermia therapy is the only approved treatment method, but its high cost and uncertain prognostic effects remain a concern (Ranjan and Gulati, 2023;Thayyil et al, 2023). Treatment starting within 6 h shows neuroprotective effects, posing a huge challenge for early diagnosis of HIBD.…”

Perinatal Brain Injury and Inflammation: Lessons from Experimental Murine Models

“…During development, grey and white matter injuries have been associated with sub-acute and chronic hypoxia-ischemia. Importantly, white matter injury is common in pre-term babies; however, results are contrasting in term babies, in whom white matter injury has been linked with chronic hypoxia, but not in areas of high metabolic activity like the thalamus [ 118 ]. These differences in white matter injury in pre-term and term babies may be a reflection on the maturation of oligodendrocytes in pre-term and full-term babies [ 69 ].…”