Melanie Ehrler1, Michael von Rhein1,2, Oliver Kretschmar3, Beatrice Latal1, and Ruth O'Gorman Tuura4
1Child Development Center, University Children's Hospital, Zurich, Switzerland, 2Developmental Pediatrics, Cantonal Hospital Winterthur, Winterthur, Switzerland, 3Cardiology, University Children's Hospital, Zurich, Switzerland, 4Center for MR Research, University Children's Hospital, Zurich, Switzerland
Synopsis
Children
with congenital heart diseases (CHD) undergoing open-heart surgery are at an
increased risk of motor impairment, but little is known about the
neuroanatomical correlates of these deficits. The purpose of the present study
was to examine the link between corticospinal tract (CST) microstructure,
assessed with diffusion tensor MRI, and motor function in a cohort of
adolescents with operated CHD. Compared to age-matched controls, adolescents with
CHD showed lower CST anisotropy which correlated with worse fine motor function
and poorer movement quality. CHD may therefore lead to alterations in motor
tract development, increasing the risk of persistent motor impairments.
Introduction
Congenital
heart disease (CHD) represents the most common neonatal malformation, affecting
approximately 0.8% of live births.1 With advances in surgical and
neonatal care, survival rates have increased and adolescents and adults now
outnumber children with CHD.2 However, CHD patients are at an
increased risk of neurodevelopmental impairments affecting both the cognitive
and motor domains.3 Neuroimaging
studies have revealed a link between cognitive deficits and reduced brain
volumes4-5 or altered microstructure6 in children or
adolescents with CHD, but little is known about the neuroanatomical correlates
of persistent motor deficits in this population. The purpose of the present
study was to examine the link between corticospinal tract (CST) microstructure and
gross and fine motor function in a cohort of adolescents with CHD, in
comparison to an age-matched control group.Methods
The
participant group consisted of 47 adolescents with CHD who underwent full-flow
cardiopulmonary bypass surgery before the age of 6 years (mean age at MRI: 13.7
years), and an age matched control group of 44 healthy adolescents (mean age at
MRI: 13.9 years). Diffusion tensor imaging (DTI) data were collected
using a PGSE sequence with 21 sampling directions, using a GE 3T HD.xt MRI
scanner (GE Healthcare, Waukesha, WI, USA).
DTI images were skull-stripped and corrected for eddy current effects,
and the diffusion tensor was fitted using the tools within the FSL software
library. The fractional anisotropy (FA) maps were then normalized into MNI
space using the tbss registration tools, and the left and right CSTs from each
participant were extracted using the Johns Hopkins University Tractography
atlas. Data for the mean FA within each CST were then exported for further
statistical analysis.
Motor function was evaluated from all CHD patients and 40/44
adolescents in the control group with the Zürich Neuromotor Assessment (ZNA),
an extensive battery of motor tests including timed performance tests for gross
and fine motor function.7 Briefly, gross motor function was assessed
from dynamic and static balance, and fine motor function was assessed with a
pegboard test, including an assessment of associated movements.8 IQ
was estimated for all participants using the Wechsler Intelligence Scale for
Children, 4th edition, (WISC‐IV), and socioeconomic status was assessed using a
six point scale based on maternal education and paternal occupation.
Group differences in the CST FA between the patient and
control groups were tested with linear regression models correcting for age and
sex, and correlations between the FA values and the motor scores in the patient
group were assessed with linear regression models, including age and sex as
covariates, and Pearson’s R. All statistical analyses were performed with R version
3.5.3.Results
CHD
patients demonstrated significantly lower FA in the right CST in comparison to the control group (t(87)=2.105, p=0.04), and a trend towards lower FA in the left CST (t(87)
= 1.85, p = 0.07). IQ was within the normal range for both
groups, but was lower in the CHD group (t(84)=-2.51, p< 0.01), and a
nonsignificant difference in SES was also observed (t(76)=-1.98, p=0.052), with
the control group showing a trend towards higher SES. Both groups showed a wide
inter-subject variability in gross and fine motor skills, but CHD patients
showed significantly lower Z-scores in every domain apart from that of static
balance (table 1). FA within the left and right CST correlated inversely with the
performance time (left: R=0.24, p=0.04; right: R=0.25, p=0.04) and FA within the left CST correlated with movement
quality (i.e. associated movements, R=-0.24, p=0.03) required for performing
the pegboard test (figures 1 and 2). However, no significant interactions were
present (all p>0.23). Associations between gross motor function tests and
CST FA were nonsignificant after including age, sex and group as covariates (all
p>0.12).Discussion
Adolescents
with CHD show lower CST FA values which were significantly associated with fine
motor function and quality, but not with gross motor function. No significant
interaction was present, indicating that the relationship between CST FA and
fine motor function and quality does not differ between CHD patients and
controls.
The
relationship between CST FA and fine motor function indicates that persistent
impairments in fine motor function may arise from atypical development of the
primary motor pathway in the presence of a heart defect. The apparent lack of a
significant association between CST FA and gross motor function may be due to
increased variability, resulting in lower statistical power, or may reflect the
importance of other factors such as physical fitness on gross motor function.
Alternatively, other pathways outside the CST may also be important for the
development of gross motor skills.Conclusion
Adolescents
with congenital heart diseases (CHD) show lower corticospinal tract FA which
correlated with fine motor performance and quality. CHD may therefore lead to
alterations in motor tract development, increasing the risk of motor
impairments.Acknowledgements
Swiss Heart Foundation, Else Kröner-Fresenius FoundationReferences
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