Neurologic examination in infants with hypoxic-ischemic encephalopathy at age 9 to 14 months: Use of optimality scores and correlation with magnetic resonance imaging findings

doi:10.1067/mpd.2001.111325

The Journal of Pediatrics

Volume 138, Issue 3, March 2001, Pages 332-337

https://doi.org/10.1067/mpd.2001.111325 Get rights and content

Abstract

Objectives: To evaluate whether a structured and scorable neurologic examination (The Hammersmith Infant Neurological Examination) correlates with early magnetic resonance imaging findings in a group of infants with hypoxic-ischemic encephalopathy (HIE) and whether the scores of this assessment can predict the locomotor function in these children. Study design: A total of 53 term infants fulfilling the criteria for HIE underwent scanning within 4 weeks from delivery with a 1 Tesla HPQ magnet. The scores from the neurologic examination performed between 9 to 14 months were correlated to the neonatal magnetic resonance imaging findings and to the maximal locomotor function defined at the ages of 2 and 4 years. Results: The scores were always optimal in the infants with normal or minor neonatal magnetic resonance imaging findings. The lowest scores were associated with severe basal ganglia and white matter lesions. All the infants who had a global score between 67 and 78 at 1 year were able to walk independently at 2 years and without restrictions at 4 years. Scores between 40 and 67 were associated with restricted mobility and scores <40 with severely limited self-mobility at 2 and 4 years. Conclusions: The use of a standardized neurologic optimality scoring system gives additional prognostic information, easily available in the clinic, on the severity of the functional motor outcome in infants with HIE. (J Pediatr 2001;138:332-7)

Section snippets

Subjects and Methods

Ethical permission for this study was obtained from the Hammersmith Hospital Research Ethics Committee. The infants described in this study are part of a large prospective cohort of term infants who were born with perinatal hypoxic-ischemic brain injury and who were born at or referred to the Hammersmith Hospital, London, for MRI. The diagnosis of HIE was made in infants who showed signs of fetal distress before delivery such as abnormal cardiotocograph recordings, that is, decreased

Results

Between October 1991 and November 1997, 114 term infants fulfilling our criteria for HIE underwent scanning in our unit. Twenty-five of these infants died within the first year (15 had stage 2 HIE and 10 had stage 3). Thirty-five infants were referred from outside hospitals and either had their first scan outside the neonatal period (n = 8) or were not seen at the times designated for this study (n = 27). One infant had a postnatal infection and had new MRI findings at that time. There were no

Discussion

The results of this study showed that approximately 40% of the infants in our cohort had suboptimal scores on neurologic examination and that the magnitude of the suboptimal scores was related to the pattern of MRI lesion. The scores were always optimal in the infants with normal neonatal MRI findings or moderate white matter lesions. In contrast, very severe lesions such as severe basal ganglia and subcortical or diffuse white matter lesions were always associated with the lowest scores.

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Cited by (97)

Volumetric changes in brain MRI of infants with hypoxic-ischemic encephalopathy and abnormal neurodevelopment who underwent therapeutic hypothermia
2024, Brain Research
Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication that can result in 40–60 % of long-term morbidity. Magnetic Resonance Imaging (MRI) is a noninvasive method which is usually performed before discharge to visually assess acquired cerebral lesions associated with HIE and severity of lesions possibly providing a guide for detecting adverse outcomes. This study aims to evaluate the impact of HIE on brain volume changes observed in MRI scans performed at a mean 10 days of life, which can serve as a prognostic indicator for abnormal neurodevelopmental (ND) outcomes at 18–24 months among HIE infants.
We retrospectively identified a cohort of HIE patients between June 2013 and March 2017. The inclusion criteria for therapeutic hypothermia (TH) were a gestational age ≥35 weeks, a birth weight ≥1800 g, and the presence of ≥ moderate HIE. Brain MRI was performed at a mean 10 days of life and brain volumes (total brain volume, cerebral volume, cerebellar volume, brain stem volume, and ventricle volume) were measured for quantitative assessment. At 18–24 months, the infants returned for follow-up evaluations, during which their cognitive, language, and motor skills were assessed using the Bayley Scales of Infant and Toddler Development III.
The study recruited a total of 240 infants between 2013 and 2017 for volumetric brain MRI evaluation. Among these, 83 were normal control infants, 107 were TH-treated HIE infants and 37 were HIE infants who did not receive TH due to contraindications. Clinical evaluation was further proceeded. We compared the brain volumes between the normal control infants (n = 83) with normal ND but TH-treated HIE infants (n = 76), abnormal ND TH-treated HIE infants (n = 31), and the severe HIE MRI group with no TH (n = 37). The abnormal ND TH-treated HIE infants demonstrated a significant decrease in brainstem volume and an increase in ventricle size (p < 0.001) (Table 4). Lastly, the severe brain MRI group who did not receive TH showed significantly smaller brain stem (p = 0.006), cerebellar (p = 0.006) and cerebrum volumes (p = 0.027), accompanied by larger ventricular size (p = 0.013) compared to the normal control group (Table 5).
In addition to assessing the location of brain injuries in MRI scans, the reduction in brain stem volume coupled with an increase in ventricular volume in HIE infants may serve as a biomarker indicating severe HIE and adverse long-term ND outcomes among HIE infants who either received therapeutic hypothermia (TH) treatment or not.
Predictive value of the test of infant motor performance and the Hammersmith infant neurological examination for cerebral palsy in infants
2022, Early Human Development
Current recommendations for early detection tools for cerebral palsy (CP) include assessments that vary in feasibility and resource requirements. The predictive value of less resource-intensive tools has not been fully explored.
To determine the predictive value of the Test of Infant Motor Performance (TIMP) at 3–4 months corrected age (CA) for CP, and whether administration of both the TIMP and the Hammersmith Infant Neurological Exam (HINE) improves early CP detection.
Five-year retrospective observational study of infants who received the TIMP and the HINE at 3–4 months CA in a high-risk follow-up clinic. TIMP and HINE cut-off scores (alone and in combination) were compared for CP discriminatory ability.
Of patients with HINE scores (n = 1389; 676 [48.7 %] female; median gestational age at birth 31 weeks [interquartile range 29–34 weeks]), 1343 had concurrent TIMP scores available.
Clinical diagnosis of CP.
HINE total score <57 had optimal CP predictive value (AUC = 0.815; 77 % sensitivity; 91 % specificity) compared to optimal TIMP cut-off (1 SD below the mean, AUC = 0.71; 52 % sensitivity; 94 % specificity) and all tested TIMP and HINE combinations (all p < 0.001).
HINE total score <57 at 3–4 months CA had the best CP predictive value, confirming its value absent first-line detection tools. Concurrent administration of TIMP did not improve predictive value.
Neurological and developmental outcomes following neonatal encephalopathy treated with therapeutic hypothermia
2021, Seminars in Fetal and Neonatal Medicine
In randomized trials, therapeutic hypothermia (TH) is associated with reduced prevalence of the composite outcome mortality or neurodevelopmental morbidity in infants with neonatal encephalopathy (NE). Following systematic review, the reduction in prevalence of both mortality and infant neuromorbidity is clear. Among three trials reporting school age outcomes, the effects of NE and TH suggest that such benefit persists into middle childhood, but none of the major trials were powered to detect differences in these outcomes. Cognitive, educational and behavioural outcomes are all adversely affected by NE in children without moderate or severe neuromorbidity. High-quality longitudinal studies of neurocognitive and educational outcomes following NE in the era of TH, including studies incorporating multimodal neuroimaging assessments, are required to characterise deficits more precisely so that robust interventional targets may be developed, and resource planning can occur. Understanding the impact of NE on families and important educational, social, and behavioural outcomes in childhood is critical to attempts to optimise outcomes through interventions.
Wavelet-based neurovascular coupling can predict brain abnormalities in neonatal encephalopathy
2021, NeuroImage: Clinical
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates, but quantitative methods to predict outcomes early in their course of illness remain elusive. Real-time physiologic biomarkers of neurologic injury are needed in order to predict which neonates will benefit from therapies. Neurovascular coupling (NVC) describes the correlation of neural activity with cerebral blood flow, and the degree of impairment could predict those at risk for poor outcomes.
To determine if neurovascular coupling (NVC) calculated in the first 24-hours of life based on wavelet transform coherence analysis (WTC) of near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) can predict abnormal brain MRI in neonatal HIE.
WTC analysis was performed between dynamic oscillations of simultaneously recorded aEEG and cerebral tissue oxygen saturation (SctO2) signals for the first 24 h after birth. The squared cross-wavelet coherence, R², of the time–frequency domain described by the WTC, is a localized correlation coefficient (ranging between 0 and 1) between these two signals in the time–frequency domain. Statistical analysis was based on Monte Carlo simulation with a 95% confidence interval to identify the time–frequency areas from the WTC scalograms. Brain MRI was performed on all neonates and classified as normal or abnormal based on an accepted classification system for HIE. Wavelet metrics of % significant SctO2-aEEG coherence was compared between the normal and abnormal MRI groups.
This prospective study recruited a total of 36 neonates with HIE. A total of 10 had an abnormal brain MRI while 26 had normal MRI. The analysis showed that the SctO2-aEEG coherence between the group with normal and abnormal MRI were significantly different (p = 0.0007) in a very low-frequency (VLF) range of 0.06–0.2 mHz. Using receiver operating characteristic (ROC) curves, the use of WTC-analysis of NVC had an area under the curve (AUC) of 0.808, and with a cutoff of 10% NVC. Sensitivity was 69%, specificity was 90%, positive predictive value (PPV) was 94%, and negative predictive value (NPV) was 52% for predicting brain injury on MRI. This was superior to the clinical Total Sarnat score (TSS) where AUC was 0.442 with sensitivity 61.5%, specificity 30%, PPV 75%, and NPV 31%.
NVC is a promising neurophysiological biomarker in neonates with HIE, and in our prospective cohort was superior to the clinical Total Sarnat score for prediction of abnormal brain MRI.
Prospective qualification of early cerebral biomarkers in a randomised trial of treatment with xenon combined with moderate hypothermia after birth asphyxia
2019, EBioMedicine
The TOBY-Xe proof of concept randomised trial found no effect of xenon combined with hypothermia after birth asphyxia on the lactate to N-acetyl aspartate ratio (Lac/NAA) in the thalamus and fractional anisotropy (FA) in white matter tracts measured within 15 days of birth. To confirm that these biomarkers are qualified to predict long-term outcome after neural rescue therapy we assessed surviving participants at 2–3 years of age.
Of the 92 infants in TOBY-Xe, one was omitted from the study, 69 survived and we assessed 62 participants, 32 in the hypothermia and xenon and 30 in the hypothermia only groups. We examined the relation between Lac/NAA and FA and the scores of the Bayley Scales of Infant and Toddler Development III and calculated their predictive accuracy for moderate or severe disability or death.
Fifteen of 62 participants (24%) developed moderate/severe disability, and 22/92 (24%) died.
The Lac/NAA ratio (difference in medians 0.628, 95% CI -0.392 to 4.684) and FA (difference in means −0.055, 95% CI -0.033 to −0.077) differed significantly between participants with or without moderate or severe disability or death and were significantly related with development scores in both groups. Adverse outcomes were correctly identified in 95.65% of cases by Lac/NAA and 78.79% by FA, with adequate mean calibration of the model.
The results confirm the qualification of the cerebral magnetic resonance biomarkers employed in the TOBY-Xe study as predictors of outcome after neuroprotective therapy.
The Centre for the Developing Brain, King's College London, UK.
Update on the current management of newborns with neonatal encephalopathy
2019, Current Problems in Pediatric and Adolescent Health Care
Hypoxic-ischemic encephalopathy is a subtype of neonatal encephalopathy and a major contributor to global neonatal morbidity and mortality. Despite advances in obstetric and neonatal care there are still challenges in accurate determination of etiology of neonatal encephalopathy. Thus, identification of intrapartum risk factors and comprehensive evaluation of the neonate is important to determine the etiology and severity of neonatal encephalopathy. In developed countries, therapeutic hypothermia as a standard of care therapy for neonates with hypoxic-ischemic encephalopathy has proven to decrease incidence of death and neurodevelopmental disabilities, including cerebral palsy in surviving children. Advances in neuroimaging, brain monitoring modalities, and biomarkers of brain injury have improved the ability to diagnose, monitor, and treat newborns with encephalopathy. However, challenges remain in early identification of neonates at risk for hypoxic-ischemic brain injury, and determination of the timing and extent of brain injury. Using imaging studies such as Neonatal MRI and MR spectroscopy have proven to be most useful in predicting outcomes in infants with encephalopathy within the first week of life, although comprehensive neurodevelopmental assessments still remains the gold standard for determining long term outcomes. Future studies are needed to identify other newborns with encephalopathy that might benefit from therapeutic hypothermia and to determine the efficacy of other adjunctive neuroprotective strategies. This review focuses on newer evidence and advances in diagnoses and management of infants with neonatal encephalopathy, including novel therapies, as well as prognostication of outcomes to childhood.

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^*: Reprint requests: Eugenio Mercuri, MD, Department of Paediatrics, Hammersmith Hospital, Du Cane Rd, London W12 OHS, UK.

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Original ArticlesNeurologic examination in infants with hypoxic-ischemic encephalopathy at age 9 to 14 months: Use of optimality scores and correlation with magnetic resonance imaging findings*

Abstract

Section snippets

Subjects and Methods

Results

Discussion

J Pediatr

Brain Dev

Pediatr Neurol

The asphyxiated newborn infant

Hypoxic-ischaemic encephalopathy

Prognostic value of early MR imaging in term infants with severe perinatal asphyxia

Neuropaediatrics

Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome

Arch Dis Child

Neonatal encephalopathy following fetal distress: a clinical and electrophysical study

Arch Neurol

Original Articles
Neurologic examination in infants with hypoxic-ischemic encephalopathy at age 9 to 14 months: Use of optimality scores and correlation with magnetic resonance imaging findings*