Brain structure and neurocognitive development in sickle cell disease; a longitudinal cohort study (BRICK study)

Sickle cell disease (SCD) is a hereditary red blood cell blood disorder with a
prevalence of approximately 2,000 patients in the Netherlands. It is
characterized by chronic hemolytic anemia, recurrent painful vaso-occlusive
ischemic events, a higher risk of overwhelming bacterial infections due to
functional asplenia, and progressive multi-organ damage leading to a lower life
expectancy. A severe complication of SCD, which greatly affects health-related
quality of life, is cognitive decline. Although this may be accompanied by
neurological sequelae identifiable on brain imaging techniques, this may also
occur without imaging abnormalities. Particularly, patients with severe SCD
(HbSS or HbSβº genotype) are at an increased risk for cerebral infarcts, both
of arterial and venous origin, as well as silent infarctions. Advanced
techniques in Magnetic Resonance Imaging (MRI) have recently revealed even
more prevalent volumetric and microstructural white matter abnormalities. In
comparison to non-SCD children, it has been demonstrated that white and grey
matter volume expand significantly slower in SCD. Advanced neuroradiology in
SCD has only been performed in research settings and clinical implications of
these structural brain changes and the association between different
radiographic findings and their chronological sequence in appearance, are yet
to be determined.

The primary objective is to evaluate longitudinal developmental changes in
brain structure in patients aged 6-18 years with SCD. The secondary objective
is to analyze the longitudinal relations between biomarkers, demographic
characteristics, brain structure, neurocognitive functioning, behavioral
functioning and developmental changes in brain structure.

Longitudinal cohort study (BRICK) with a duration of 4 years.

By creating an advanced model for structural neurological, neurocognitive
functioning in SCD, we will gain more insight into the pathophysiological
origins and risk factors for SCD-related brain abnormalities. This will support
development of preventive and supportive strategies as well as the initiation
and evaluation of therapeutic interventions. Previous experience with the
performance of brain MRI scans combined with recent research, indicates that
the emotional burden placed on young children when undergoing a brain MR scan,
are proportionate to the emotional burden placed on adults when they undergo a
brain MR-scan. Furthermore, children will be offered the opportunity to become
acquainted with the research procedure by witnessing an MRI scan session prior
before participation.