A new subtype of multiple sclerosis (MS) called myelocortical MS is characterized by demyelination only in the spinal cord and cerebral cortex and not in the cerebral white matter, according to a study published online ahead of print August 21 in the Lancet Neurology. The findings are based on an examination of the brains and spinal cords of 100 patients who died of MS.
Bruce D. Trapp, PhD, the Morris R. and Ruth V. Graham Endowed Chair in Biomedical Research at 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 MS, characterized by the absence of areas of cerebral white-matter discoloration indicative of demyelinated lesions.
The authors then compared these individuals with 12 individuals with typical MS matched by age, sex, MRI protocol, MS disease subtype, disease duration, and Expanded Disability Status Scale.
They found that while individuals with myelocortical MS did not have demyelinated lesions in the cerebral white matter, they had areas of demyelinated lesions in the cerebral cortex similar to individuals with typical MS (median 4.45% vs. 9.74% respectively, P = .5512). However, the individuals with myelocortical MS had a significantly smaller area of spinal cord demyelination (median 3.81% vs. 13.81%, P = .0083).
Individuals with myelocortical MS 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 MS only had a lower cortical neuronal density in layer V when compared with controls.
Dr. Trapp and colleagues also saw that in typical MS, neuronal density decreased as the area of brain white-matter demyelination increased. However, this negative linear correlation was not seen in myelocortical MS.
On MRI, researchers were still able to see abnormalities in the cerebral white matter in individuals with myelocortical MS, 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 MS and with typical MS, although individuals with typical MS had significantly greater MTR lesion volumes.
“We propose that myelocortical MS is characterized by spinal cord demyelination, subpial cortical demyelination, and an absence of cerebral white-matter demyelination,” Dr. Trapp and colleagues 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 MS.”
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 MS. They suggested that it was therefore not appropriate to conclude that the prevalence of myelocortical MS seen in their sample would be similar across the MS population, nor were the findings likely to apply to people with earlier stage disease.
The study was funded by the U.S. National Institutes of Health and National Multiple Sclerosis Society. One author was an employee of Renovo Neural, and three authors were employees of Biogen. One author declared a pending patent related to automated lesion segmentation from MRI images, and four authors declared funding, fees, and non-financial support from pharmaceutical companies.
Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurol. 2018 Aug 21 [Epub ahead of print].