New research findings buck the conventional belief that multiple sclerosis (MS) begins in the brain’s white matter and progresses to the cortex. The collaborative study conducted by the Mayo Clinic, headquartered in Rochester, Minn, and Cleveland Clinic, Cleveland, Ohio, indicates that MS may progress from the outermost layers of the brain to its deepest parts.

Claudia F. Lucchinetti, MD, co-lead author of the study, and Mayo Clinic neurologist, reiterates the results, “Our study shows the cortex is involved early in MS and may even be the initial target of the disease,” Lucchinetti says. Lucchinetti adds that focus should be re-directed to inflammation in the cortex when investigating the causes and progression of MS.

Researchers say understanding how the cortex is involved in the disease is critical to creating new therapies for MS. The study reportedly examined brain tissues from patients in the earliest stages of MS. Timothy Coetzee, PhD, chief research officer at the National Multiple Sclerosis Society emphasizes that, “What’s unique about the study, and the reason the National MS Society funded this international team of researchers, is that it offers a rare view of MS early in the disease,” Coetzee explains.

According to researchers, they studied the Mayo resource of white-matter biopsies taken primarily from patients who were initially suspected of having a tumor but were eventually proven to have MS.  Reportedly, one-fourth of the biopsies included tiny fragments of cortex. Study results suggested that cortical demyelinating lesions of early-MS patients resembled those found at autopsy with the exception of early lesions, which were highly inflammatory. Researchers say these findings reinforced the belief that treatments targeting inflammation in the disease may ameliorate MS effects on the cortex and white matter.

Researchers also reported a high frequency of cortical demyleination lesions. Additional results indicated 20% of the white matter biopsies exhibited inflammatory demyelination contained entirely in the cortex. Inflammation, the study says, was also present in the meninges. 

Lucchinetti reports that the study’s findings along with experimental data from MS animal models reinforced researchers’ “outside-in” theory about the disease. The study’s results also indicate a need to utilize magnetic resonance imaging (MRI) to investigate further into the cortical lesions of MS, as cortical damage is reported to be an important correlate of progressive disability and cognitive dysfunction in MS.

The study was recently published in the New England Journal of Medicine.

Source: Mayo Clinic