Brain Structure and Neurocognitive Development in Sickle Cell Disease; a Longitudinal Cohort Study (BRICK Study)

Summary

Sickle cell disease (SCD) is an autosomal recessive red blood cell blood disorder. One especially vital organ affected in SCD is the brain. Individuals with SCD have an increased risk of both overt cerebral infarctions and silent infarctions. The latter are brain lesions without apparent neurological sequelae. Since cortical neurons in the brain lack the ability to regenerate, tissue damage accumulates throughout the already shortened lifespan of individuals with SCD, resulting in far-reaching consequences such as significant cognitive impairment. Currently, only hematological stem cell transplantation can halt the multiorgan tissue damage. However, the criteria to determine the timing of curative therapy do not center the brain, despite that subtle anomalies of this critical organ can have long-lasting consequences. Since it is not yet known whether brain tissue damage precedes, parallels, or lags behind non-brain tissue damage, it is critical to map these effects in youth with SCD. While importantly comparing images with a healthy reference population. Understanding how the brain is affected is critical for clinical decision making, such as timing of potentially curative interventions but also, to prevent long term irreversible brain damage in youth with SCD. In this study, a cohort of 84 SCD patients between the ages of 6 and 18 at baseline, will undergo MR imaging, neurological examination, neuropsychological assessment and blood sampling three times in total, with intervals of two years; results will be innovatively compared with children included in the Generation R population study (±8000 MRIs children and (young)adults) 6-20 years of age). Our hypothesis, based on the inability of the brain to generate new cortical neurons following cell death, is that brain function is impaired earlier than other organ systems and that there is an age-dependent limit in the brain's ability to remodel itself based on neuroplasticity.

Conditions

• Brain Development Abnormality
• Sickle Cell Disease

Interventions

DIAGNOSTIC_TEST

MR scan of the brain

Subjects will undergo MRI of the head, blood sampling and neurological examination on the same day or spread over 2 days. On a separate day from blood sampling and undergoing an MRI scan, the neuropsychological assessment will take place. The interval between the MRI scan and the neuropsychological assessment will be a maximum of 2 months. These measurements will be performed a total of 3 times with an interval of 2 years.

DIAGNOSTIC_TEST

Blood work

Lab work for current lab values and biobanking

DIAGNOSTIC_TEST

Neurological examination

Classical neurological examination

DIAGNOSTIC_TEST

Neuropsychological assessment

Overview of standard neurocognitive assessment tools in BRICK study Children and adolescents (Young) Adults * Wechsler Intelligence Test for Children- Fifth edition (WISC-V) (6-16 YOA) Wechsler Adult Intelligence Scale- Fourth edition WAIS-IV (16-24 YOA) * A Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II) * Narrative memory * Word fluency * Route finding NEPSY-II * World Fluency * Additional Questionnaires (6-18 years): * Child Behavior Checklist (CBCL) * Teacher Report Form (TRF) * Youth Self Report (YSR) * Behavior Rating Inventory of Executive Function (BRIEF), parent- and teacher-report) * Conners-3® • Additional Questionnaires (18+ years): * Adult Self-Report (ASR) / Adult Behavior Checklist (ABCL) (in case of IQ\<70) * Behavior Rating Inventory of Executive Function Adult version (BRIEF-A), self-report / informant-report (in case of IQ\<70) * Conners' Adult ADHD Rating Scales (CAARS) Emma toolbox

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  collaborator OTHER

• Dr. Marjon H. Cnossen MD PhD

  lead OTHER

Eligibility

Min Age

6 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-20

Primary Completion

2025-07-01

Completion

2025-07-01

Countries

• Netherlands

Study Locations