title: Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.
abstract: Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York. Electronic address: nsg11@columbia.edu.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Green
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Monica
authors.initials: M
authors.lastname: Bhatia
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York.
authors.forename: Erica Y
authors.initials: EY
authors.lastname: Griffith
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Mahvish
authors.initials: M
authors.lastname: Qureshi
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Courtney
authors.initials: C
authors.lastname: Briamonte
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Mirko
authors.initials: M
authors.lastname: Savone
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sands
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Department of Radiology, Columbia University Medical Center, New York, New York.
authors.forename: Angela
authors.initials: A
authors.lastname: Lignelli
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000000981:diagnostic imaging / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008833:Microcirculation; D012189:Retrospective Studies; D055815:Young Adult
keywords: Hematopoietic cell transplantation; Magnetic resonance imaging brain; Quality of life; Sickle cell disease; White matter hyperintensity