Cerebral Perfusion Imaging in Children with Sickle Cell Disease

Sickle cell disease is the most common cause of brain infarcts in children. The
incidence of sickle cell disease in Europe is increasing; it is the most common
hereditary disease in Great-Britain.
Sickle cell disease is en hereditary haemoglobinopathy that causes hemolysis
and vaso-occlusion. Vaso-occlsuion leads to irreversible damage in multiple
organs e.g. heart, lungs and brain. The cumulative incidence of symptomatic
brain infarcts at the age of 9 is 10%. At the age of 18, a silent infarct can
be seen on MRI in 35% of children.
It is possible to prevent overt brain infarcts (brain infarcts that cause
neurological symptoms) by administration of blood transfusions. Blood
transfusion schemes have multiple side effects, like accumulation of iron or
allo-immunisation. Therefore, patients who are at a high risk of overt cerebral
infarcts are screened by means of trans-cranial ultrasonography.
However, most patients suffer from silent infarcts, with neuropsychological
disfunctioning and impairment of cognitive development. Early recognition of
patients at high risk of silent infarction is of great importance in adequate
prevention or treatment.
A previous study by this group (Stroke 2009) indicated that children with
sickle cell disease have asymmetries in cerebral perfusion that cannot be
observed in healthy age-matched controls. This could represent an early stage
of pathology in which intervention might prevent further neurologic damage.
The purpose of this study is to evaluate if perfusion asymmetries are indeed
related to silent infarction and to identify patients at high risk of silent
infarction by using advanced perfusion imaging techniques.

To sess the relationship between cerebral perfusion and clinical findings
(neurological and neuropsychological) in patients with sickle cell disease.
To compare iamging fincdings in children with and without sickle cell disease.

Prospective cohort study

Group relatedness
This researchquestion is group related. The required knowledge can not be
obtained by scanning adult patients.
the pathologic process that causes cerebral damage starts at an early age. The
research question thus requires inclusion of subjects in whom this process did
not yet cause irreversible damage.
In order to be able to prevent children from silent infarction, early
identification of patients who are at risk, is of great importance. Because of
the group-relatedness of the research question, an age matched healthy control
group is also needed.

Risks are negligible
In the ccmo memorandum of December 2002 "Niet-therapeutisch onderzoek bij
wilsonbekwamen: 'nee-tenzij'" a negligible risk is interpreted as a risk that
is similar to the risks of everyday life. It is usual for children with sickle
cell disease to undergo blood sampling, ultrasonography or MR imaging of the
brain. The risks associated with participation in this study are thus
comparable to risks of everyday lif in children with sickle cell disease.

Minimal burden
In the ccmo memorandum "Toetsingkader niet-therapeutisch MRI-onderzoek bij
minderjarigen of wilsonbekwame proefpersonen" it is stated that MR imaging in
children aged eight years and older is acceptable, provided that:
- extensive information is provided to parents and children
- pedagogical support is given
- there is a possibility to practice
- participation is stopped in case of resistance
- research is combined with required diagnostic tests in case of patients

This study will be carried out according to these guidelines. Moreover, the
code of behaviour in case of resistance "Verzet in het kader van medisch
wetenschappelijk onderzoek (NVK)" will be followed. This means that
participation will be stopped in case of resistance. Parents, doctors and
researchers will take care that the child is not feeling uncomfortable or
showing any form of resistance.
(Protocol, appendix page 18).