# Clinical and Neuroimaging Phenotypes of Neurodevelopmental Disorders inPediatric Sickle Cell Disease

> **NIH NIH K23** · HUGO W. MOSER RES INST KENNEDY KRIEGER · 2020 · $155,628

## Abstract

Sickle cell disease (SCD) is an inherited blood disorder with several neurological and developmental
complications. While there has been progress in terms of screening and treatment of neurological
complications, particularly in terms of overt ischemic stroke and silent cerebral infarct, children with SCD still
have worsening cognition over time in the absence of obvious brain injury. Children with SCD and attention
deficit hyperactivity disorder (ADHD) and no prior history of stroke or silent cerebral infarct, defined as
cryptogenic ADHD, represent an understudied yet important subset of this vulnerable population. We
hypothesize that cryptogenic ADHD is associated with white matter injury and plasma biomarkers associated
with brain injury. We will explore this hypothesis through the following Specific Aims.
Aim 1: Identify clinical risk factors of cryptogenic ADHD in SCD.
Through a retrospective chart review of patients from pediatric SCD neurodevelopmental and hematology
clinics, we will compare the clinical characteristics of children with SCD and cryptogenic ADHD to children with
SCD and no prior history of stroke, silent cerebral infarct, or ADHD and other neurodevelopmental disorders.
Aim 2: Establish associations between cryptogenic ADHD and white matter brain injury.
We will recruit 20 children 8 to 12 years of age with SCD and cryptogenic ADHD and 20 children with SCD
without a prior history of stroke, silent cerebral infarct, or ADHD and other neurodevelopmental disorders to
participate in a case control study. Subjects will undergo neurodevelopmental and neuropsychological
evaluations, neuroimaging protocols including DTI, arterial spin labeling, oxygen extraction fraction, and
volumetric imaging, and blood sample draw.
Aim 3: Establish associations between cryptogenic ADHD and plasma biomarkers.
Using the blood samples from the group of research subjects in Aim 2, we will measure the levels of various
neuronal and glial protein markers to identify potential plasma biomarker proteins of neurological injury. We
will compare the protein levels to DTI findings as well as neuropsychological measures.
 The proposed work will define a clinical and neuroimaging phenotype of children with SCD and cryptogenic
ADHD, establishing this population as part of the spectrum of brain injury seen in pediatric SCD. The Principal
Investigator will require additional training in the hematological management of SCD and neuroimaging
acquisition and analysis techniques to complete the proposed projects. Future research will involve use of DTI
as a measure of disease severity, predict cognitive outcomes, and monitor response to treatment in clinical
trials research and longitudinal assessment of the research group established in Aim 2 to establish their risk of
future neurological complications.

## Key facts

- **NIH application ID:** 9987698
- **Project number:** 5K23HL133455-04
- **Recipient organization:** HUGO W. MOSER RES INST KENNEDY KRIEGER
- **Principal Investigator:** EBONI I LANCE
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,628
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987698

## Citation

> US National Institutes of Health, RePORTER application 9987698, Clinical and Neuroimaging Phenotypes of Neurodevelopmental Disorders inPediatric Sickle Cell Disease (5K23HL133455-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9987698. Licensed CC0.

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