Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis

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Abstract

BACKGROUND: Multiple sclerosis is characterized by white matter lesions, which are visualized with conventional T2-weighted magnetic resonance imaging (MRI). Little is known about local metabolic processes preceding the appearance and during the pathological development of new lesions.

OBJECTIVE: To identify metabolite changes preceding white matter (WM) lesions and pathological severity of lesions over time.

METHODS: A total of 59 relapsing-remitting multiple sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI).

RESULTS: A total of 16 new lesions appeared within the MRSI slab in 12 patients. Glutamate increased (+1.0 mM (+19%), p = 0.039) 12 and 6 months before new lesions appeared. In these areas, the increase in creatine and choline 6 months before until lesion appearance was negatively correlated with radial diffusivity (ρ = -0.73, p = 0.002 and ρ = -0.72, p = 0.002). Increase in creatine also correlated with the increase of axial diffusivity in the same period (ρ = -0.53, p = 0.034). When splitting the lesions into "mild" and "severe" based on radial diffusivity, only mild lesions showed an increase in creatine and choline during lesion formation ( p = 0.039 and p = 0.008, respectively).

CONCLUSION: Increased glutamate heralded the appearance of new T2-visible WM lesions. In pathologically "mild" lesions, an increase in creatine and choline was found during lesion formation.

Original languageEnglish
Pages (from-to)1352458517702534
JournalMultiple Sclerosis
DOIs
Publication statusPublished - Apr 2018

Cite this

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title = "Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis",
abstract = "BACKGROUND: Multiple sclerosis is characterized by white matter lesions, which are visualized with conventional T2-weighted magnetic resonance imaging (MRI). Little is known about local metabolic processes preceding the appearance and during the pathological development of new lesions.OBJECTIVE: To identify metabolite changes preceding white matter (WM) lesions and pathological severity of lesions over time.METHODS: A total of 59 relapsing-remitting multiple sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI).RESULTS: A total of 16 new lesions appeared within the MRSI slab in 12 patients. Glutamate increased (+1.0 mM (+19{\%}), p = 0.039) 12 and 6 months before new lesions appeared. In these areas, the increase in creatine and choline 6 months before until lesion appearance was negatively correlated with radial diffusivity (ρ = -0.73, p = 0.002 and ρ = -0.72, p = 0.002). Increase in creatine also correlated with the increase of axial diffusivity in the same period (ρ = -0.53, p = 0.034). When splitting the lesions into {"}mild{"} and {"}severe{"} based on radial diffusivity, only mild lesions showed an increase in creatine and choline during lesion formation ( p = 0.039 and p = 0.008, respectively).CONCLUSION: Increased glutamate heralded the appearance of new T2-visible WM lesions. In pathologically {"}mild{"} lesions, an increase in creatine and choline was found during lesion formation.",
keywords = "Journal Article",
author = "Klauser, {Antoine M} and Wiebenga, {Oliver T} and Eijlers, {Anand Jc} and Schoonheim, {Menno M} and Uitdehaag, {Bernard Mj} and Frederik Barkhof and Pouwels, {Petra Jw} and Geurts, {Jeroen Jg}",
year = "2018",
month = "4",
doi = "10.1177/1352458517702534",
language = "English",
pages = "1352458517702534",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",

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T1 - Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis

AU - Klauser, Antoine M

AU - Wiebenga, Oliver T

AU - Eijlers, Anand Jc

AU - Schoonheim, Menno M

AU - Uitdehaag, Bernard Mj

AU - Barkhof, Frederik

AU - Pouwels, Petra Jw

AU - Geurts, Jeroen Jg

PY - 2018/4

Y1 - 2018/4

N2 - BACKGROUND: Multiple sclerosis is characterized by white matter lesions, which are visualized with conventional T2-weighted magnetic resonance imaging (MRI). Little is known about local metabolic processes preceding the appearance and during the pathological development of new lesions.OBJECTIVE: To identify metabolite changes preceding white matter (WM) lesions and pathological severity of lesions over time.METHODS: A total of 59 relapsing-remitting multiple sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI).RESULTS: A total of 16 new lesions appeared within the MRSI slab in 12 patients. Glutamate increased (+1.0 mM (+19%), p = 0.039) 12 and 6 months before new lesions appeared. In these areas, the increase in creatine and choline 6 months before until lesion appearance was negatively correlated with radial diffusivity (ρ = -0.73, p = 0.002 and ρ = -0.72, p = 0.002). Increase in creatine also correlated with the increase of axial diffusivity in the same period (ρ = -0.53, p = 0.034). When splitting the lesions into "mild" and "severe" based on radial diffusivity, only mild lesions showed an increase in creatine and choline during lesion formation ( p = 0.039 and p = 0.008, respectively).CONCLUSION: Increased glutamate heralded the appearance of new T2-visible WM lesions. In pathologically "mild" lesions, an increase in creatine and choline was found during lesion formation.

AB - BACKGROUND: Multiple sclerosis is characterized by white matter lesions, which are visualized with conventional T2-weighted magnetic resonance imaging (MRI). Little is known about local metabolic processes preceding the appearance and during the pathological development of new lesions.OBJECTIVE: To identify metabolite changes preceding white matter (WM) lesions and pathological severity of lesions over time.METHODS: A total of 59 relapsing-remitting multiple sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI).RESULTS: A total of 16 new lesions appeared within the MRSI slab in 12 patients. Glutamate increased (+1.0 mM (+19%), p = 0.039) 12 and 6 months before new lesions appeared. In these areas, the increase in creatine and choline 6 months before until lesion appearance was negatively correlated with radial diffusivity (ρ = -0.73, p = 0.002 and ρ = -0.72, p = 0.002). Increase in creatine also correlated with the increase of axial diffusivity in the same period (ρ = -0.53, p = 0.034). When splitting the lesions into "mild" and "severe" based on radial diffusivity, only mild lesions showed an increase in creatine and choline during lesion formation ( p = 0.039 and p = 0.008, respectively).CONCLUSION: Increased glutamate heralded the appearance of new T2-visible WM lesions. In pathologically "mild" lesions, an increase in creatine and choline was found during lesion formation.

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JO - Multiple Sclerosis

JF - Multiple Sclerosis

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