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Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis
Antoine M Klauser1, Oliver T Wiebenga2, Anand Jc Eijlers3
1Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands/Department of Radiology and Medical Informatics, University of Geneva, Switzerland.
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.
Insights
Increased glutamate levels predict new multiple sclerosis lesions. Mild lesions show rising creatine and choline during formation, offering insights into white matter disease progression.
Area of Science:
- Neuroimaging
- Metabolomics
- Multiple Sclerosis Pathophysiology
Background:
- Multiple sclerosis (MS) is defined by white matter lesions visible via T2-weighted MRI.
- Early metabolic changes preceding lesion development in MS remain largely uncharacterized.
Purpose of the Study:
- To detect metabolite alterations that precede white matter lesion formation in MS.
- To correlate metabolic changes with the pathological severity of lesions over time.
Main Methods:
- Longitudinal study of 59 relapsing-remitting MS patients with four MRI scans (6-month intervals).
- Utilized short-echo time magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI).
Main Results:
- Glutamate levels increased 6-12 months before new T2-visible lesions appeared (p=0.039).
- Increases in creatine and choline correlated with diffusion changes (radial and axial diffusivity) preceding lesion onset.
- Mild lesions showed elevated creatine and choline during formation, unlike severe lesions.
Conclusions:
- Elevated glutamate serves as an early indicator for new white matter lesions in MS.
- Metabolic shifts involving creatine and choline are associated with the development of mild MS lesions.
