Researchers have identified a correlation between higher levels of glutamate, which occurs naturally in the brain as a byproduct of metabolism, and greater disease burden in multiple sclerosis patients. The study is the first to measure glutamate toxicity in the brain over time and suggests an improved method for tracking multiple sclerosis and predicting its course.

The research team employed a novel technique to measure glutamate levels in clinical trial multiple sclerosis patients. The technique was based on a sophisticated form of imaging known as proton MR spectroscopy, which uses simple radio-frequency pulses targeting specific brain chemicals.

Glutamate, a neurotransmitter, in normal levels performs fundamental processes like memory and sensory perception. In excess, it triggers a cascade of negative reactions in the brain leading to many of the complications associated with neurologic diseases such as multiple sclerosis, Parkinson's disease, stroke, ALS (amyotrophic lateral sclerosis or Lou Gehrig's disease) and Alzheimer's by destroying nerve cells and causing seizures, injury after stroke, and the perception of pain, among other problems.

"This is the first time that we have had the ability to measure glutamate toxicity in the brain in real time, which gives us a marker for monitoring disease progression as well as our treatment of the disease," said Daniel Pelletier, study author.

Elevated levels of glutamate in the brain are understood clinically as a cause of cell injury and death. Injury to neuro-axons, which are the long fibers that extend from the cell body of a neuron cell toward other nerve cells, is partly responsible for disability progression in multiple sclerosis. In a previous study using proton MR spectroscopic imaging, the research team reported that multiple sclerosis brains have significant elevation of glutamate concentrations. For this study, researchers looked for levels of glutamate and levels of NAA (n-acteylaspartate), a marker of axonal integrity in mature brains, to see if a relationship existed.

The team scanned 265 multiple sclerosis patients annually and followed them for an average of 1.8 years. Accounting for disease duration and age of onset, researchers found that significant annual loss of NAA, which is a measure of neurodegeneration, was associated with concentration of glutamate. This finding indicated that the higher the level of glutamate, the greater the expected neuro-axonal loss over time.

According to the authors, the study is the largest clinical analysis to date of metabolism byproducts in the brain, and the results strongly support the link between the excess of glutamate and decline of neuro-axonal integrity in multiple sclerosis.

The finding, Pelletier says, goes beyond multiple sclerosis. "Now that we have those markers, we can quantify levels of glutamate for other neurologic diseases, which could be another way to track disease progression and therapeutic intervention."
References:
1. Daniel Pelletier, et al. University of California - San Francisco.

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