Neonatal encephalopathy: MRS predicts long-term brain damage

  • Lancet Neurol

  • curated by Susan London
  • Clinical Essentials
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  • Brain injury on thalamic proton magnetic resonance spectroscopy (MRS) obtained after hypothermia for neonatal encephalopathy is highly accurate in predicting neurodevelopment 2 years later.

Why this matters

  • Reliable predictors would aid early determination of neuroprotective interventions’ efficacy.

Key results

  • At median age of 23 months, 16% had adverse neurodevelopmental outcome.
  • MRS thalamic N-acetylaspartate concentration (NAA) alone had excellent predictive accuracy:
    • Area under the curve (AUC): 0.99;
    • Sensitivity: 100%;
    • Specificity: 97%.
  • For conventional assessments, AUCs:
    • Neurologic exam at 6 hours, discharge: 0.72, 0.60;
    • Abnormal amplitude integrated EEG at 6 hours: 0.73.
  • For conventional MRI measures, AUCs:
    • Cortical injury: 0.67;
    • Basal ganglia or thalamic injury: 0.81;
    • Abnormal signal in posterior limb of internal capsule: 0.82.
  • For diffusion MRI, fractional anisotropy of posterior limb of internal capsule AUC: 0.90.

Expert comment

  • In a Comment, Dr. Alistair J. Gunn and Dr. Malcolm Battin write, “… this demonstration of the extremely high prognostic accuracy for MR spectroscopic measurements of NAA concentration will enable much faster incremental studies of neonatal encephalopathy because it offers robust measurement of outcome within weeks. Moreover, the reference data from the MARBLE study will be made available, allowing MR sequences, and thus individual patient scans, to be done more rapidly within large pragmatic studies.”

Study design

  • US, UK prospective cohort study: 223 term/near-term neonates receiving therapeutic hypothermia for neonatal encephalopathy (MARBLE study).
  • MRI, thalamic proton MRS performed 4-14 days after birth.
  • Main outcome: adverse neurodevelopmental outcome (death or moderate or severe disability) at 18-24 months.
  • Funding: National Institute for Health Research UK.


  • Thalamic NAA assessed in subset.
  • Exclusion of many patients before diffusion-weighted MRI analysis.
  • Interpretation of surrogate biomarkers.