Quantitative MR spectroscopic imaging in metachromatic leukodystrophy: value for prognosis and treatment

Rappard, Diane F. van; Klauser, Antoine; Steenweg, Marjan E.; Boelens, Jaap Jan; Bugiani, Marianna; Knaap, Marjo S. van der; Wolf, Nicole I.; Pouwels, Petra J. W.

doi:10.1136/jnnp-2017-316364

Cited by 27 publications

(34 citation statements)

References 25 publications

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“…The treatment effect of HCT most likely influenced the longitudinal differences between treated eligible patients (approaching control values in NAWM and pyramidal tracts), and untreated non-eligible patients (increasingly abnormal values). This is in line with our observation that metabolite concentrations observed with magnetic resonance spectroscopy partially normalized in successfully transplanted patients, whilst concentrations for non-treated patients further deteriorated [ 30 ].…”

Section: Discussionsupporting

confidence: 90%

“…These changes most likely reflect a multitude of pathological processes such as accumulation of metachromatic material, followed by myelin and axonal loss. The differences between untreated and treated patients indicate that diffusion measures are positively affected by HCT, further emphasizing the beneficial effects of this intervention on WM and supporting the findings of other quantitative MR measures as proton MR spectroscopy [ 30 ]. Altogether, quantitative MR measures provide more insight into time-dependent disease mechanisms and might in the future aid in determining the right window for intervention.…”

Section: Discussionmentioning

confidence: 52%

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Diffusion tensor imaging in metachromatic leukodystrophy

et al. 2018

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ObjectiveWe aimed to gain more insight into the pathomechanisms of metachromatic leukodystrophy (MLD), by comparing magnitude and direction of diffusion between patients and controls at diagnosis and during follow-up.MethodsFour late-infantile, 16 juvenile and 8 adult onset MLD patients [of which 13 considered eligible for hematopoietic cell transplantation (HCT)] and 47 controls were examined using diffusion tensor imaging. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were quantified and compared between groups using tract-based spatial statistics (TBSS). Diffusion measures were determined for normal-appearing white matter (NAWM), corpus callosum, thalamus (all based on subject-wise segmentation), and pyramidal tracts, determined with probabilistic tractography. Measures were compared between HCT-eligible patients, non-eligible patients and controls using general linear model and nonparametric permutation analyses (randomise) for TBSS data, considering family-wise error corrected p < 0.05 significant.ResultsThroughout white matter (WM), FA was decreased and MD and RD increased in both patient groups compared to controls, while AD was decreased in NAWM and corpus callosum. In the thalamus, no differences in FA were observed, but all diffusivities were increased in both patient groups. Differences were most pronounced between controls and patients non-eligible for HCT. Longitudinally (median follow-up 3.9 years), diffusion measures remained relatively stable for HCT-treated patients, but were progressively abnormal for non-eligible patients.InterpretationThe observed diffusion measures confirm that brain microstructure is changed in MLD, reflecting different pathological processes including loss of myelin and sulfatide accumulation. The observation of both increased and decreased AD probably reflects a balance between myelin and axonal loss vs. intracellular sulfatide storage in macrophages, depending on region and disease stage.Electronic supplementary materialThe online version of this article (10.1007/s00415-018-8765-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 52%

Diffusion tensor imaging in metachromatic leukodystrophy

et al. 2018

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“…To date, MLD is diagnosed by clinical manifestations, using genetic analysis for mutations in the ARSA and PSAP genes (68), magnetic resonance imaging (MRI) of the brain (69-71) and biochemical tests of the ARSA enzymatic activity in skin fibroblasts, leukocytes and urine of patients (31,72). Moreover, approaches such as determining the level of sulfatides in plasma and urine by mass spectrometry (73), quantitative determination of metabolites in tissues by magnetic resonance spectroscopy (MRS) (74) and the evaluation of the peripheral nerve size using ultrasound (75) can provide additional information, both for the diagnosis and the evaluation of MLD treatment effectiveness.…”

Section: Mld Diagnosismentioning

confidence: 99%

“…In contrast, it is believed that Ins can have a positive effect on the functioning of the nervous system, however this remains to be investigated. Thus, the method allows determining abnormal concentrations of chemical compounds in a white matter, which can be used to diagnose and predict the clinical course of MLD (74). Although this method is not commonly accepted for the MLD diagnosis, it can be useful to investigate pathological changes for research purposes.…”

Section: Mld Diagnosismentioning

confidence: 99%

Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

et al. 2020

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“…An MRI scoring system also exists for staging MLD patients [112]. Proton magnetic resonance spectroscopy can also be used in staging, because characteristic metabolic changes occur as disease progresses [113]. Elevated cerebrospinal fluid protein and cytokines have been described in MLD [114,115].…”

Section: Recommendationsmentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation to Treat Leukodystrophies: Clinical Practice Guidelines from the Hunter's Hope Leukodystrophy Care Network

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et al. 2019

Biology of Blood and Marrow Transplantation

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The leukodystrophies are a heterogeneous group of inherited diseases characterized by progressive demyelination of the central nervous system leading to devastating neurologic symptoms and premature death. Hematopoietic stem cell transplantation (HSCT) has been successfully used to treat certain leukodystrophies, including adrenoleukodystrophy, globoid leukodystrophy (Krabbe disease), and metachromatic leukodystrophy, over the past 30 years. To date, these complex patients have primarily been transplanted at a limited number of pediatric centers. As the number of cases identified through pregnancy and newborn screening is increasing, additional centers will be required to treat these children. Hunter's Hope created the Leukodystrophy Care Network in part to create and standardize high-quality clinical practice guidelines to guide the care of affected patients. In this report the clinical guidelines for the care of pediatric patients with leukodystrophies undergoing treatment with HSCT are presented. The initial transplant evaluation, determination of patient eligibility, donor selection, conditioning, supportive care, and post-transplant follow-up are discussed. Throughout these guidelines the need for early detection and treatment and the role of the partnership between families and multidisciplinary providers are emphasized.

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Quantitative MR spectroscopic imaging in metachromatic leukodystrophy: value for prognosis and treatment

Abstract: In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.

Cited by 27 publications

References 25 publications

Diffusion tensor imaging in metachromatic leukodystrophy

Diffusion tensor imaging in metachromatic leukodystrophy

Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

Hematopoietic Stem Cell Transplantation to Treat Leukodystrophies: Clinical Practice Guidelines from the Hunter's Hope Leukodystrophy Care Network

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