Long-term neurodevelopmental outcome after perinatal arterial ischemic stroke

Perinatal arterial ischemic stroke (PAIS) is a type of perinatal brain injury
that occurs in ~1:5000 live births, and leads to major developmental
disabilities including cerebral palsy, cognitive impairment, epilepsy, language
disorders, and behavioral problems. To study the effect of PAIS in specific
brain regions on developmental outcome, long-term follow-up data is needed.
Therefore, our research group has set up the Neonatal Stroke Registry Utrecht
(NSRU), where clinical characteristics, neuro-imaging data, and
neurodevelopmental outcomes gathered during routine clinical follow-up are
stored. However, clinical follow-up is usually performed until around five
years of age, and studies that report neurodevelopmental outcomes in children
with PAIS past early school age are scarce. Evidence from the preterm infant
population suggests that children with neonatal brain injury might grow into
their deficit, and that neurodevelopmental impairments only become apparent at
a later age. Some studies suggest a similar finding for perinatal stroke,
although evidence is limited. Therefore, this study aims to study the effect of
PAIS on motor, cognitive, behavioral, executive, and language functioning in
children at 8-14 years of age, and to assess how brain development and
connectivity after PAIS, evaluated by MRI, relates to neurodevelopmental
outcome.

The main goal of this study is to determine motor, cognitive, behavioral,
executive, and language functioning of children with PAIS at school age.
Furthermore, we will analyze the effect of PAIS on brain growth, development,
and connectivity using advanced MRI. This will allow us to study long-term
brain development in relation with school age-outcomes following PAIS, and to
investigate whether the rate of neurodevelopmental impairment changes
longitudinally.

In this observational, cross-sectional study, children will be invited for one
testing day in the Wilhelmina Children*s Hospital (WKZ). Children will be
subjected to advanced MRI scanning (including DTI and resting-state fMRI), an
motor assessment by the physical therapist, and extensive neuropsychological
testing using standardized developmental skill tests, such as the WISC (IQ),
but also additional language, behavioral, and executive functioning
assessments. Questionnaires on daily functioning, behavior, language,
well-being and quality of life will be administered to parents, teachers, and
children during, and/or after the testing day. With the data acquired during
this study in combination with the data from the NSRU, we are able to generate
an unique dataset with multiple MRI scans and neurodevelopmental outcome
measures performed longitudinally.

Assessment of the motor and neurocognitive development will be non-invasive,
and is routinely performed during clinical follow-up. Most children enjoy these
assessments, since they are designed in a playful manner. To prevent the
children from fatigue due to testing, multiple breaks will be scheduled. The
children will undergo an MRI of the brain, which takes approximately 45
minutes. Sedative medication will not be used, nor will intravenous contrast.
MRI in children is shown to be save and minimal invasive as it is not based on
X-rays. Risks associated with participation are limited, if not negligible, as
MRI has been performed for clinical purposes in almost all follow-up centres
for many years. Therefore, considerable collective expertise has been gained in
MRI techniques and associated practical issues in teenaged children (METC
01/229). It might however be frightening for children as the MRI tunnel is
quite small and makes a lot of noise. We will prepare the children with an MRI
video and explanation. Nevertheless, if there is too much anxiety or
restlessness during scanning, the scan protocol can be shortened or stopped at
any moment.