December 3, 2003
Neuronal cell death in multiple sclerosis (MS) occurs prior to the hallmark brain atrophy, according to findings presented here at the 89th annual meeting of the Radiological Society of North America.
"We've known about tissue atrophy for more than 100 years, but this study shows that brain cell loss precedes brain volume loss," said Oded Gonen, PhD, at a press briefing. "Magnetic resonance (MR) spectroscopy allows us a noninvasive way to monitor disease progression." Dr. Gonen is a professor of radiology at New York University School of Medicine.
Neuronal cell death may be an important marker to measure the progression of MS, and this eventually may be a therapeutic target. "First you lose the neurons, and then the axons atrophy," Dr. Gonen told Medscape. "We don't have a treatment that interrupts this process, but physicians can use these images to encourage their patients to take medications that prevent attacks."
The marker for neuronal cell death is the amino acid derivative N-acetylaspartate (NAA). Because this protein is present almost exclusively in neuronal cells, Dr. Gonen and colleagues theorized that quantifying the level of NAA by proton MR spectroscopy would give an indication of whether the patient was experiencing a loss of these cells. Therefore, they sought to quantify the relationship among NAA levels, brain volume, and disease duration to better understand the early developments in MS.
The investigators recruited 42 MS patients, 30 men and 12 women, who had relatively recently developed MS. The patients were an average of 38 years old, had had MS for a median of 5.6 years, and had a median Expanded Disability Status Scale (EDSS) score of 2.5.
The patients' cross-sectional global macroscopic and microscopic deficits were evaluated by assessing relative atrophy from MRI and by quantifying whole brain NAA with MR spectroscopy. Because the brain's NAA level was divided by the brain volume, which they obtained from MRI segmentation, the investigators used the whole-brain NAA concentrations for cross-sectional comparisons.
Both brain volume and whole-brain NAA declined significantly with disease duration, the investigators found. Brain volume declined at a rate of 0.5% per year compared with a whole-brain NAA loss of 1.8% per year (P = .033 and .005, respectively). However, neither figure correlated with the other nor with the individual patients' EDSS score, the investigators reported.
Dr. Gonen pointed out that the rate of NAA loss was more than three times that of brain volume loss. This disparity shows that NAA loss in MS precedes brain volume loss, rather than following it, he said. Because the NAA level is an earlier, more sensitive, and more specific measurement of ongoing disease activity, it may be a more useful target for both monitoring early disease and for drug discovery, he said.
The development of MR technology that has more powerful magnets is one of the developments that has made NAA measurement possible, according to A. Greg Sorenson, MD. Dr. Sorenson, who was not involved in the study, is a staff radiologist at Massachusetts General Hospital and an associate professor of radiology at Harvard Medical School in Boston.
"We have improved our sensitivity to the point that we can document neuronal deficits as a marker of disease progression in MS," Dr. Sorenson told Medscape. "That is an important half of the MS story. The fact that we can look at the neurons shows how MR spectroscopy may eventually be able to reduce MS morbidity by better understanding the disease process. This study shows how MRI will be valuable in the care of patients with MS."
RSNA 89th Scientific Assembly and Annual Meeting: Abstract K13-969. Presented Dec. 3, 2003.
Reviewed by Gary D. Vogin, MD
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