MS patients’ symptom severity linked to gray matter myelin loss

The amount of myelin lost in the gray matter of multiple sclerosis (MS) patients’ brains may indicate a more debilitating form of the disease, according to a new study.

MS has long been considered an inflammatory disease of the brain’s white matter, where myelin — the fatty, protective sheath that surrounds nerve fibers — is most abundant. But the magnetic resonance imaging (MRI) study showed smaller amounts of myelin can also be found in gray matter, which is made up of mostly nerve cells and serves as the brain’s information processing center.

MS breaks down the myelin sheath in the brain and spinal cord in a process called demyelination, which can cause scarring and lesions and variety of debilitating neurological symptoms. While the amount of myelin in gray matter is small, it is very important to proper function because it protects the nerve fibers that connect different parts of the brain.

"The fact that MS patients lose myelin not only in white but also in gray matter has been proven by earlier post-mortem pathological studies," Vasily L. Yarnykh, study author and associate professor in the department of radiology at University of Washington, said in a press release. "However, the clinical significance of the myelin loss, or demyelination, in gray matter has not been established because of the absence of appropriate imaging methods."

For the study, Yarnykh and colleagues at the University of Washington in Seattle looked at 30 MS patients, including 18 with the most common form of the disease — relapsing-remitting MS (RRMS) — and 12 with a more advanced form of the disease called secondary progressive MS (SPMS). They also included 14 healthy control participants without MS.

Using a special MRI technique that provides information on the content of biological macromolecules — molecules present in tissues composed of a large number of atoms, such as proteins, lipids and carbohydrates — called macromolecular proton fraction (MPF) mapping, researchers constructed 3D images to get a closer look at healthy white matter, gray matter and lesions associated with the disease. They then compared their observations with clinical tests that indicated neurological dysfunction in MS patients.

Study authors found that MPF in both white and gray matter was significantly lower in patients with RRMS, compared with the healthy control group. SPMS patients had an even larger reduction in MPF in both normal-looking tissue and lesions when compared to RRMS patients with the greatest loss of gray-matter myelin. The results indicated that MS patients with the most debilitating symptoms were those who lost the most myelin from the gray matter of their brains.

"The major finding of the study is that the loss of myelin in gray matter caused by MS in its relative amount is comparable to or even larger than that in white matter," Yarnykh said. "Furthermore, gray matter demyelination is much more advanced in patients with secondary-progressive MS, and it is very strongly related to patients' disability. As such, we believe that information about gray matter myelin damage in MS is of primary clinical relevance."

The researchers said their improved MRI technique could help provide better treatments aimed at protecting and restoring myelin in MS patients.

The study is published online in the journal Radiology.