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

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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: To determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT).

METHODS: 21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.

RESULTS: In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.

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

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
Publication statusPublished - 1 Jan 2018

Cite this

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title = "Quantitative MR spectroscopic imaging in metachromatic leukodystrophy: value for prognosis and treatment",
abstract = "OBJECTIVE: To determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT).METHODS: 21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.RESULTS: In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.CONCLUSION: In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.",
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year = "2018",
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Quantitative MR spectroscopic imaging in metachromatic leukodystrophy : value for prognosis and treatment. / van Rappard, Diane F; Klauser, Antoine; Steenweg, Marjan E; Boelens, Jaap Jan; Bugiani, Marianna; van der Knaap, Marjo S; Wolf, Nicole I; Pouwels, Petra J W.

In: Journal of Neurology, Neurosurgery and Psychiatry, 01.01.2018, p. 105-111.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Quantitative MR spectroscopic imaging in metachromatic leukodystrophy

T2 - value for prognosis and treatment

AU - van Rappard, Diane F

AU - Klauser, Antoine

AU - Steenweg, Marjan E

AU - Boelens, Jaap Jan

AU - Bugiani, Marianna

AU - van der Knaap, Marjo S

AU - Wolf, Nicole I

AU - Pouwels, Petra J W

N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - OBJECTIVE: To determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT).METHODS: 21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.RESULTS: In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.CONCLUSION: In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.

AB - OBJECTIVE: To determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT).METHODS: 21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations.RESULTS: In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate.CONCLUSION: In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.

KW - Journal Article

U2 - 10.1136/jnnp-2017-316364

DO - 10.1136/jnnp-2017-316364

M3 - Article

SP - 105

EP - 111

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

ER -