A new subtype of multiple sclerosis called myelocortical multiple sclerosis is characterized by demyelination only in the spinal cord and cerebral cortex and not in the cerebral white matter.
Copyright (2018), with permission from Elsevier
MRI in myelocortical multiple sclerosis (left) and typical multiple sclerosis. Reprinted from The Lancet Neurology.
A paper published online Aug. 21 in Lancet Neurology presents the results of a study of the brains and spinal cords of 100 patients who died of multiple sclerosis.
Bruce D. Trapp, PhD, of the Lerner Research Institute at the Cleveland Clinic in Ohio, and his coauthors wrote that while the demyelination of cerebral white matter is a pathologic hallmark of multiple sclerosis, previous research has found only around half of cerebral T2-weighted hyperintense white matter lesions are demyelinated, and these lesions account for less than a third of variance in the rate of brain atrophy.
“In the absence of specific MRI metrics for demyelination, the relationship between cerebral white-matter demyelination and neurodegeneration remains speculative,” they wrote.
In this study, researchers scanned the brains with MRI before autopsy, then took centimeter-thick hemispheric slices to study the white-matter lesions. They identified 12 individuals as having what they describe as ‘myelocortical multiple sclerosis,’ characterized by the absence of areas of cerebral white-matter discoloration indicative of demyelinated lesions.
The authors then compared these individuals to 12 individuals with typical multiple sclerosis matched by age, sex, MRI protocol, multiple sclerosis disease subtype, disease duration, and Expanded Disability Status Scale.
They found that while individuals with myelocortical multiple sclerosis did not have demyelinated lesions in the cerebral white matter, they had similar areas of demyelinated lesions in the cerebral cortex to individuals with typical multiple sclerosis (median 4.45% vs. 9.74% respectively, P = .5512).
However, the individuals with myelocortical multiple sclerosis had a significantly smaller area of spinal cord demyelination (median 3.81% vs. 13.81%, P = .0083).
Individuals with myelocortical multiple sclerosis also had significantly lower mean cortical neuronal densities, compared with healthy control brains in layer III, layer V, and layer VI. But individuals with typical multiple sclerosis only had a lower cortical neuronal density in layer V when compared with controls.
Researchers also saw that in typical multiple sclerosis, neuronal density decreased as the area of brain white-matter demyelination increased. However, this negative linear correlation was not seen in myelocortical multiple sclerosis.
On MRI, researchers were still able to see abnormalities in the cerebral white matter in individuals with myelocortical multiple sclerosis, in T2-weighted, T1-weighted and magnetization transfer ratios (MTR) images.
They also found similar total T2-weighted and T1-weighted lesion volumes in individuals with myelocortical and with typical multiple sclerosis, although individuals with typical multiple sclerosis had significantly greater MTR lesion volumes.
“We propose that myelocortical multiple sclerosis is characterized by spinal cord demyelination, subpial cortical demyelination, and an absence of cerebral white-matter demyelination,” the authors wrote. “Our findings indicate that abnormal cerebral white-matter T2-T1-MTR regions of interest are not always demyelinated, and this pathological evidence suggests that cerebral white-matter demyelination and cortical neuronal degeneration can be independent events in myelocortical multiple sclerosis.”
The authors noted that their study may have been affected by selection bias, as all the patients in the study had died from complications of advanced multiple sclerosis. They suggested that it was therefore not appropriate to conclude that the prevalence of myelocortical multiple sclerosis seen in their sample would be similar across the multiple sclerosis population, nor were the findings likely to apply to people with earlier stage disease.