Childhood Cerebral X-Linked Adrenoleukodystrophy: Diffusion Tensor Imaging Measurements for Prediction of Clinical Outcome after Hematopoietic Stem Cell Transplantation

McKinney, Alexander M.; Nascene, David; Miller, Weston P.; Eisengart, Julie B.; Loes, D. J.; Benson, Mark D.; Tolar, Jakub; Orchard, Paul J.; Ziegler, Richard; Zhang, Lei; Provenzale, James M.

doi:10.3174/ajnr.a3232

Cited by 24 publications

(25 citation statements)

References 25 publications

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“…As would be expected based on prior literature, the pre-HSCT Loes score strongly correlated with the 1 year clinical NFS score ( r= 0.813, p<0.0001 ). 9–10,19 Regarding the neurocognitive measures, moderate correlations existed between the baseline Loes score and the 1 year neurocognitive FSIQ, PIQ, and VIQ scores, but these did not reach clinical significance ( r= ⁻0.596 –⁻0.646, p=0.068–0.090 ) after correction for multiple comparisons (Table 2). …”

Section: Resultsmentioning

confidence: 99%

“…In this regard, the expense of travel, care, and MRI for multiple trips is a known factor contributing to this limitation. 19 Similarly, it is difficult to obtain a large number of age-matched controls for MRP, as most pediatric indications for MRI do not necessitate contrast. A third potential limitation was the use of “relative”, rather than absolute, perfusion measurements; however, relative measurements of CBV or CBF are typically more reproducible than absolute ones.…”

Section: Discussionmentioning

confidence: 99%

“…This was performed in the method of prior studies. 8,19 Both neuroradiologists were blinded to the clinical data.…”

Section: Methodsmentioning

confidence: 99%

“…9–10 For the cALD cohort, the NFS was retrospectively constructed from detailed clinical assessments in the medical record by a pediatric HSCT specialist ( WM ). 9–10,19 Neurocognitive scores from the Wechsler Intelligence Scale Series, including FSIQ, PIQ, and VIQ were prospectively obtained by dedicated examination from one of several neuropsychologists both pre-HSCT and at 1 year, as described previously. 19–21 Both the pediatric transplantation specialist and the neuropsychologists were blinded to the MRI data.…”

Section: Methodsmentioning

confidence: 99%

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Childhood Cerebral Adrenoleukodystrophy: MR Perfusion Measurements and Their Use in Predicting Clinical Outcome after Hematopoietic Stem Cell Transplantation

McKinney¹,

Benson²,

Nascene³

et al. 2016

AJNR Am J Neuroradiol

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Background and Purpose To prospectively measure MR perfusion (MRP) parameters in patients with cerebral adrenoleukodystrophy (cALD) pre- and post-hematopoietic stem cell transplantation (HSCT), and to correlate those measurements with the clinical outcome. Materials and Methods Ten cALD patients prospectively underwent DSC-MRP at <45 days pre-(baseline), 30–60 days post-, and 1 year post-HSCT. MRP measurements in the 10 patients and 8 controls were obtained from the parietooccipital WM (POWM), callosal splenium (SCC), leading enhancing edge (LEE), and normal-appearing frontal white matter (NAFWM). MR severity (Loes) scores and clinical neurologic function (NFS) and neurocognitive scores were also obtained. MRP values were analyzed in the cALD patients at each time point, and compared to controls. Correlations were calculated between the pre-HSCT MRP values and 1-year clinical scores, with p-value adjustment for multiple comparisons. Results At baseline in cALD patients, both rCBV and rCBF within the SCC and POWM significantly differed from controls (p=0.005–0.031), and remained so 1 year post-HSCT (p=0.003–0.005). Meanwhile, no MRP parameter within the LEE differed significantly from controls at baseline or at 1 year (p=0.074–0.999), nor significantly changed by 1 year post-HSCT (p=0.142–0.887). Baseline Loes scores correlated with 1 year NFS (r=0.813, p<0.0001), while SCC rCBV also significantly correlated with 1 year NFS, as well as the neurocognitive FSIQ and PIQ scores (r=−0.730–0.815, p=0.007–0.038). Conclusion LEE measurements likely remain normal post-HSCT in cALD, suggesting local disease stabilization. Meanwhile, POWM and SCC rCBV and rCBF values worsen, signifying irreversible injury. Baseline SCC rCBV may predict clinical outcomes following HSCT.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…This was performed in the method of prior studies. 8,19 Both neuroradiologists were blinded to the clinical data.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Childhood Cerebral Adrenoleukodystrophy: MR Perfusion Measurements and Their Use in Predicting Clinical Outcome after Hematopoietic Stem Cell Transplantation

McKinney¹,

Benson²,

Nascene³

et al. 2016

AJNR Am J Neuroradiol

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“…It is of particular interest when selecting patients for bone marrow transplantation, it being a good predictor of outcome at 1 year after transplantation. To complement the classical MRI, specialized techniques such as proton MR spectroscopy imaging, magnetization transfer contrast or diffusion tensor MRI have been developed and have considerably improved the accuracy of analyses [388][389][390][391][392][393][394][395]. To complement the classical MRI, specialized techniques such as proton MR spectroscopy imaging, magnetization transfer contrast or diffusion tensor MRI have been developed and have considerably improved the accuracy of analyses [388][389][390][391][392][393][394][395].…”

Section: Neuroimagingmentioning

confidence: 99%

X-linked Adrenoleukodystrophy

Trompier¹,

Savary²

2013

Colloquium Series on the Genetic Basis of Human Disease

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Neurocognitive Trajectory of Boys Who Received a Hematopoietic Stem Cell Transplant at an Early Stage of Childhood Cerebral Adrenoleukodystrophy

et al. 2017

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IMPORTANCE Untreated childhood cerebral adrenoleukodystrophy (cALD) is a fatal disease associated with progressive cerebral demyelination and rapid, devastating neurologic decline. The standard of care to enhance long-term survival and stabilize cerebral disease is a hematopoietic stem cell transplant (HSCT). Neurologic outcomes are better when HSCT occurs at an earlier stage of cALD, yet there is limited understanding of the neurocognitive trajectory of patients who undergo HSCT.OBJECTIVES To characterize neurocognitive outcomes of boys with cALD and early-stage cerebral disease who were treated with an allogeneic HSCT and to identify disease-and treatment-related factors associated with long-term functioning. DESIGN, SETTING, AND PARTICIPANTS Baseline and follow-up neurocognitive test performance was analyzed for all boys with cALD who received an HSCT at the University of Minnesota between January 1, 1991, and October 20, 2014, and who had a pretransplant magnetic resonance imaging (MRI) severity score of less than 10 (scale range, 0-34; higher scores indicate greater severity). (verbal comprehension, perceptual [visual] reasoning, working memory, and processing speed) were the primary outcome measures. Secondary analysis at the most recent evaluation also included measures of sustained attention, verbal memory, visual-motor integration, and fine motor function. MAIN OUTCOMES AND MEASURES Longitudinal neurocognitive test performance in 4 domains RESULTSAmong the 62 boys in this study (mean [SD] age at transplant, 8.37 [2.80] years; range, 4-16 years), there was a significant association of pretransplant MRI severity and baseline verbal comprehension (r = -0.340; P = .008), perceptual reasoning (r = -0.419; P = .001), and processing speed (r = -0.285; P = .03) scores. Higher pretransplant MRI severity scores were also associated with a steeper decline in neurocognitive functioning during the 5-year follow-up period. Twenty-two of 33 patients (67%) with available long-term follow-up neurocognitive testing had severe impairment in at least 1 neurocognitive domain at the most recent evaluation.CONCLUSIONS AND RELEVANCE Boys with cALD who have greater than minimal cerebral disease detected on MRI scans at the time of an HSCT are at risk for severe, persistent neurocognitive deficits. These findings motivate further exploration of methods of detecting cerebral disease prior to development of lesions observable on MRI scans, an endeavor that may be facilitated by newborn screening for adrenoleukodystrophy. These findings may serve a benchmark role in evaluating the efficacy of novel interventions for cALD. 38. Miller WP, Mantovani LF, Muzic J, et al. Intensity of MRI gadolinium enhancement in cerebral adrenoleukodystrophy: a biomarker for inflammation and predictor of outcome following transplantation in higher risk patients. AJNR Am J Neuroradiol. 2016;37(2):367-372. 39. Orchard PJ, Lund T, Miller W, et al. Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy. J Neuroinflammation. 2011; 8:144. 40. Rocken...

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Childhood Cerebral X-Linked Adrenoleukodystrophy: Diffusion Tensor Imaging Measurements for Prediction of Clinical Outcome after Hematopoietic Stem Cell Transplantation

Cited by 24 publications

References 25 publications

Childhood Cerebral Adrenoleukodystrophy: MR Perfusion Measurements and Their Use in Predicting Clinical Outcome after Hematopoietic Stem Cell Transplantation

Childhood Cerebral Adrenoleukodystrophy: MR Perfusion Measurements and Their Use in Predicting Clinical Outcome after Hematopoietic Stem Cell Transplantation

X-linked Adrenoleukodystrophy

Neurocognitive Trajectory of Boys Who Received a Hematopoietic Stem Cell Transplant at an Early Stage of Childhood Cerebral Adrenoleukodystrophy

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