Cognitive outcome and its neural correlates after cardiorespiratory arrest in childhood

Abstract

Hypoxia-ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia-ischaemia in adults, but it is relatively rare in infants and children. While the effects of adult CA on brain and cognition have been widely studied, to date, there are no studies examining the neurodevelopmental outcome of children who suffered CA early in life. Here, we studied the long-term outcome of 28 children who suffered early CA (i.e., before age 16). They were compared to a group of control participants (n = 28) matched for age, sex and socio-economic status. The patient group had impairments in the domains of memory, language and academic attainment (measured using standardised tests). Individual scores within the impaired range were most commonly found within the memory domain (79%), followed by academic attainment (50%), and language (36%). The patient group also had reduced whole brain grey matter volume, and reduced volume and fractional anisotropy of the white matter. In addition, lower performance on memory tests was correlated with bilaterally reduced volume of the hippocampi, thalami, and striatum, while lower attainment scores were correlated with bilateral reduction of fractional anisotropy in the superior cerebellar peduncle, the main output tract of the cerebellum. We conclude that patients who suffered early CA are at risk of developing specific cognitive deficits associated with structural brain abnormalities. RESEARCH HIGHLIGHTS: Our data shed light on the long-term outcome and associated neural mechanisms after paediatric hypoxia-ischaemia as a result of cardiorespiratory arrest. Patients had impaired scores on memory, language and academic attainment. Memory impairments were associated with smaller hippocampi, thalami, and striatum. Lower academic attainment correlated with reduced fractional anisotropy of the superior cerebellar peduncle.

Keywords: hippocampus; language; memory; striatum; thalamus.

FIGURE 1

White matter tracts and grey matter structures of interest. Top panel: white matter tracts of interest (JHU Atlas; Ling and Rumpel, 2006): Yellow: superior cerebellar peduncle, Red: ILF/IFOF, Green: AF/SLF, Blue: Fornix. Bottom panel: grey matter regions of interest: Blue: hippocampus, Orange: putamen, Red: thalamus, Green: caudate nucleus. Structures are displayed on axial slices in MNI space.

FIGURE 2

Group differences in cognitive outcome. Y axis represents the factor scores. The box represents the interquartile range (IQR), and the hinges represent the minimum and maximum values (excluding outliers). Small full circles represent values which are > 1.5 times the IQR, below Q1 or above Q3.

FIGURE 3

Group differences in whole brain measurements. Top: Grey matter, white matter and cerebrospinal fluid volumes (litre); Bottom panel: mean fractional anisotropy (FA), medial diffusivity (MD) and radial diffusivity (RD); in the control group (blue) and the patient group (green). Stars represent outliers, defined as values which are > 3 times the IQR either above Q3 or below Q1. Full circles represent values which are > 1.5 times the IQR. Black asterisk indicates significant group difference.

FIGURE 4

Group differences in structures of interest. Top: Volumes of the hippocampus (hippo), caudate nucleus (caudate), putamen and thalamus. Bottom: Mean FA of the AF/SLF, ILF/IFOF, SCP and fornix. Stars represent outliers, defined as values which are > 3 times the IQR either above Q3 or below Q1. Full circles represent values which are > 1.5 times the IQR. Black asterisk indicates significant group difference.

FIGURE 5

Examples of grey matter structures of interest in patient and control participants. T1‐weighted scans of a patient (P) and a control participant (C) matched for age and sex (in brackets). x, y, z coordinates are indicated above the images in MNI space. Brain structures are manually delineated or highlighted, for presentation purposes only.

FIGURE 6

Correlations between memory scores and volumes of subcortical structures in the patient group. Y axis represents memory scores derived from the PCA; x axis represents volumes of right hemispheric (red) and left hemispheric (blue) subcortical structures (mm³); straight lines represent linear correlations; curved lines represent 95% confidence interval of the mean.