title: Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A Biomarker for Inflammation and Predictor of Outcome following Transplantation in Higher Risk Patients.
abstract: OBJECTIVE
  Outcomes following hematopoietic stem cell transplantation for higher risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MR imaging gadolinium intensity scoring system improves prediction of neurologic outcome.
  
  
  METHODS
  We developed a 4-point scale of gadolinium intensity relative to the choroid plexus: 0 = no enhancement; 1 = hypointense; 2 = isointense; 3 = hyperintense. The interobserver concordance of the scale was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with CSF chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplantation. For 25 evaluable higher risk patients (Loes ≥10), the gadolinium intensity score was compared with longer term posttransplantation clinical change.
  
  
  RESULTS
  The gadolinium intensity scoring system showed good interobserver reproducibility (κ = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant CSF chitotriosidase activity in nanograms/milliliter/hour: 0: 2717, n = 5; 1: 3218, n = 13; 2: 6497, n = 23; and 3: 12,030, n = 23 (P < .01). For 25 evaluable higher risk patients, more intense pretransplantation brain MR imaging gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplantation: 0/1: adrenoleukodystrophy neurologic function scale score difference = 4.3, n = 7; 2/3: adrenoleukodystrophy neurologic function scale score difference = 10.4, n = 18 (P = .05).
  
  
  CONCLUSIONS
  Gadolinium enhancement intensity on brain MR imaging can be scored simply and reproducibly for cerebral adrenoleukodystrophy. The enhancement score significantly correlates with chitotriosidase. In boys with higher risk cerebral disease (Loes ≥10), the enhancement score itself predicts neurologic outcome following treatment. Such data may help guide treatment decisions for clinicians and families.
authors.affiliation: From the Division of Pediatric Blood and Marrow Transplant (W.P.M., T.C.L., P.J.O.), Department of Pediatrics mill4991@umn.edu.
authors.forename: W P
authors.identifier: http://orcid.org/0000-0003-3168-3337
authors.initials: WP
authors.lastname: Miller
authors.affiliation: Division of Hematology and Oncology (L.F.M.), Department of Pediatrics, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: L F
authors.identifier: http://orcid.org/0000-0002-2623-461X
authors.initials: LF
authors.lastname: Mantovani
authors.affiliation: University of Minnesota Medical School (J.M.), Minneapolis, Minnesota.
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-8457-5925
authors.initials: J
authors.lastname: Muzic
authors.affiliation: Departments of Diagnostic Radiology (J.B.R., R.S.G., D.R.N.).
authors.forename: J B
authors.identifier: http://orcid.org/0000-0002-1958-2448
authors.initials: JB
authors.lastname: Rykken
authors.affiliation: Departments of Diagnostic Radiology (J.B.R., R.S.G., D.R.N.).
authors.forename: R S
authors.identifier: http://orcid.org/0000-0003-2976-1519
authors.initials: RS
authors.lastname: Gawande
authors.affiliation: From the Division of Pediatric Blood and Marrow Transplant (W.P.M., T.C.L., P.J.O.), Department of Pediatrics.
authors.forename: T C
authors.identifier: http://orcid.org/0000-0001-9174-8919
authors.initials: TC
authors.lastname: Lund
authors.affiliation: Biostatistics Core (R.M.S.), Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: R M
authors.identifier: http://orcid.org/0000-0003-2398-5466
authors.initials: RM
authors.lastname: Shanley
authors.affiliation: Neurology (G.V.R.), University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: G V
authors.identifier: http://orcid.org/0000-0002-7528-1906
authors.initials: GV
authors.lastname: Raymond
authors.affiliation: From the Division of Pediatric Blood and Marrow Transplant (W.P.M., T.C.L., P.J.O.), Department of Pediatrics.
authors.forename: P J
authors.identifier: http://orcid.org/0000-0001-9426-1292
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Departments of Diagnostic Radiology (J.B.R., R.S.G., D.R.N.).
authors.forename: D R
authors.identifier: http://orcid.org/0000-0002-2468-7359
authors.initials: DR
authors.lastname: Nascene
mesh_terms: D000326:Adrenoleukodystrophy / Q000473:pathology* / Q000628:therapy*; D001921:Brain / Q000503:physiopathology; D002648:Child; D003287:Contrast Media; D005682:Gadolinium; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015203:Reproducibility of Results; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D005682:Gadolinium