Metabolic dysfunction in multiple sclerosis: Elevated lactate and impaired post-exercise creatine response in the...

Area of Science:

• Neuroscience
• Metabolic research
• Clinical neurology

Background:

• Multiple Sclerosis (MS) is associated with altered brain metabolism and chronic fatigue.
• The precise relationship between brain metabolites, fatigue, and physical exertion in MS is not fully understood.
• The anterior cingulate cortex (ACC), crucial for interoception and fatigue perception, is a key region of interest.

Purpose of the Study:

• To investigate differences in brain metabolite concentrations (lactate, glutamate+glutamine (Glx), total creatine (tCr)) in the ACC of people with MS (pwMS) compared to controls.
• To examine how these metabolites change before and after a fatiguing physical task.
• To explore the correlation between metabolite levels, fatigue perception, and perceived effort.

Main Methods:

• Magnetic Resonance Spectroscopy (MRS) was used to measure ACC metabolite concentrations in 22 pwMS and 22 matched controls.
• Participants underwent MRS before and after performing fatiguing isometric wrist extension tasks.
• Perceptual measures of state fatigue and effort were collected, and linear mixed models were employed for analysis.

Main Results:

• PwMS demonstrated higher ACC lactate concentrations than controls, both at rest and post-exercise.
• Total creatine (tCr) showed a significant group-by-exercise interaction, decreasing in controls but remaining stable in pwMS post-exercise.
• No significant differences in Glx were found, and metabolite levels did not correlate with baseline fatigue; however, lactate changes correlated with perceived effort in pwMS.

Conclusions:

• This study reveals distinct metabolic profiles in pwMS, including elevated lactate and stable post-exercise tCr, suggesting impaired energy metabolism potentially linked to mitochondrial dysfunction.
• These observed metabolic alterations, while not directly correlating with perceived fatigue, may play a role in the pathophysiology of MS-related fatigue.
• The findings highlight the utility of MRS in characterizing metabolic changes in MS and their potential contribution to symptoms.