Researchers found that comparing the levels of two molecules in the brain detected with a form of MRI scanning was able to reliably predict MS progression in two independent groups of people with MS. With further study, this may be a useful tool for tracking the benefits of potential treatments in clinical trials aimed at protecting the nervous system from damage. Sara Llufriu, MD, PhD (Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain) and Daniel Pelletier, MD (Yale University) and colleagues from the University of California-San Francisco report on the study in JAMA Neurology (2014;71(7):840-847). Dr. Pelletier was supported during this study by a Harry Weaver Neuroscience Fellowship from the National MS Society.
Background: MS involves immune-system attacks on the brain and spinal cord, damaging nerve fiber-insulating myelin and nerve fibers themselves. There is currently no way to predict whether a person’s MS will progress over time, and also no good way of detecting MS progression without waiting potentially years for clinical signs of disability to appear. Finding ways to reliably predict progression would better inform treatment decisions early on in the disease course, and also provide important tools for shortening the time it takes to determine whether investigational treatments in clinical trials are slowing or stopping progression.
Magnetic resonance imaging (MRI) can pinpoint MS immune activity in the brain, but they aren’t specific enough at helping doctors to track the damage that occurs as MS progresses or to help predict who will experience long-term disability. Research on other methods of detecting signs of progression, such as brain atrophy (shrinkage), is ongoing to improve the ability to detect and predict MS progression in non-invasive ways.
A method called magnetic resonance spectroscopy uses magnetic resonance technology to analyze the chemical components of the brain, and creates a graphic display showing the amount of specific molecules detected. One molecule of interest is NAA (N-acetyl-aspartate), which is found largely in nerve fibers (axons). Lower than usual levels of NAA are thought to reflect axonal damage in the brain. Another is myo-inositol (mI), a molecule derived from astrocytes, star-shaped brain cells known for supporting the brain’s structure which are also responsible for scarring in MS brain lesions. This team tested the idea that creating a ratio of the levels of these two molecules – reflecting both nervous system damage and increases in astrocytes – would correlate with MS progression.
The Study: The team first completed a preliminary study of 59 people with MS and 43 controls without MS, and then replicated the study in another set of 220 people with MS. They obtained NAA, mI and myelin water fraction data. Participants were evaluated using clinical measures of disease progression and imaging assessments of brain volume changes annually for four years.
In both the preliminary and replication studies, the ratio of mI to NAA was predictive of disease progression – both in terms of clinical examinations and in terms of imaging measures of brain volume loss. This suggests that the damage and astrocyte activity compared with this ratio is relevant to factors that underlie disease progression. Although the differences in levels of the molecules was deemed too variable between patients to make this a useful tool to predict any individual’s future disease course, with further study, this ratio may be a useful tool for tracking the benefits of potential treatments in clinical trials aimed at protecting the nervous system from damage.
Conclusion: “Altogether, this study constitutes an impressive piece of research…,” commented MS imaging expert David H. Miller, MD (University College London Institute of Neurology, London) in an accompanying editorial. “The study findings are of special significance in the ongoing search for robust predictors of long-term MS progression.”
Read about the efforts of the National MS Society to find solutions for people with progressive MS.