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Increased White Matter Aerobic Glycolysis in Multiple Sclerosis
Matthew R Brier1,2, Bradley Judge1, Chunwei Ying2
1Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Annals of Neurology
|December 23, 2024
Summary
Multiple sclerosis (MS) involves increased white matter glycolysis early in the disease, worsening with duration and disability. This metabolic shift occurs independently of inflammation in normal-appearing white matter, suggesting metabolic optimization as a therapeutic target.
Area of Science:
- Neuroscience
- Metabolic Research
- Neuroimmunology
Background:
- Multiple sclerosis (MS) treatments reduce relapses but not progressive disability.
- MS is linked to metabolic disruptions and cerebral metabolic stress, impacting tissue injury and remyelination.
- Myelin homeostasis is energy-intensive, relying heavily on glycolysis.
Purpose of the Study:
- To investigate cerebral metabolic changes in MS.
- To determine when these metabolic changes occur during the disease course.
- To assess the relationship between metabolic changes and microstructural alterations.
Main Methods:
- Combined fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) were used.
- Cerebral metabolic rate of glucose and oxygen were measured to quantify glycolysis.
- The study included 12 healthy controls, 20 treatment-naïve relapsing MS patients, and 13 non-relapsing MS patients.
Main Results:
- Newly diagnosed MS patients showed increased glucose utilization and reduced oxygen utilization in normal-appearing white matter, indicating elevated glycolysis.
- Increased glycolysis correlated with longer disease duration and higher disability.
- While hypermetabolism in lesions was linked to inflammation, this association was absent in normal-appearing white matter.
Conclusions:
- Elevated white matter glycolysis is a key feature of cerebral metabolism in MS, appearing early and increasing with disease progression.
- This metabolic change is independent of inflammation in normal-appearing white matter.
- Targeting the metabolic environment may be crucial for therapies aimed at reducing progressive disability in MS.
