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A new subtype of multiple sclerosis (MS) has been proposed that supports the concept that neurodegeneration and demyelination can occur independently in the disease.

Known as myelocortical multiple sclerosis, the subtype is characterized by demyelination only in the spinal cord and cerebral cortex but not in cerebral white matter, said Bruce Trapp, PhD, of the Cleveland Clinic, and colleagues.

In a postmortem study of 100 MS patients, 12 individuals had MS lesions in the spinal cord and cerebral cortex but not in brain white matter, the researchers reported in . While the cortical demyelinated lesion area was similar between these myelocortical MS patients and traditional MS patients, the spinal cord demyelinated area was greater in typical MS patients. Despite having no cerebral white matter demyelination, myelocortical MS brains had reduced neuronal density and cortical thickness.

"This study opens up a new arena in MS research," Trapp said in a statement. "It is the first to provide pathological evidence that neuronal degeneration can occur without white matter myelin loss in the brains of patients with the disease."

In this study, the researchers studied brains and spinal cords from 100 patients who had died with MS between May 1998 and November 2012, examining centimeter-thick slices of cerebral hemispheres. The team compared 12 patients with myelocortical MS with 12 patients with typical MS, matched for age, sex, MRI protocol, MS disease subtype, disease duration, and Expanded Disability Status Scale, plus healthy controls.

Myelocortical MS patients did not have demyelinated lesions in cerebral white matter, but did have similar areas of demyelinated lesions in the cerebral cortex as typical MS patients (median myelocortical MS 4.45% versus typical MS 9.74%, P=0.5512). Myelocortical MS patients had a significantly smaller area of spinal cord demyelination (median myelocortical MS 3.81% versus typical MS 13.81%, P=0.0083), however.

Compared with healthy controls, myelocortical MS patients had significantly lower mean cortical neuronal densities in layer III, layer V, and layer VI. By contrast, typical MS patients had lower cortical neuronal densities only in layer V compared with controls.

On MRI, the researchers saw abnormalities in the cerebral white matter of myelocortical MS patients in T2-weighted, T1-weighted, and magnetization transfer ratios (MTR) images. But myelocortical MS appeared indistinguishable from traditional MS, which may be because part of the neurons become swollen in myelocortical MS and look like lesions that indicate white matter myelin loss, the investigators noted.

"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 cause and pathogenesis of abnormal T2-T1-MTR regions in these patients are unknown, but cortical neuronal degeneration and swollen myelinated axons might be attractive targets for neuroprotective therapies, the researchers observed. They added that identifying living people with myelocortical MS will require sensitive brain imaging that can reliably delineate myelinated and demyelinated cerebral white matter.

The study has several limitations, including selection bias, Trapp and co-authors noted. Because patients in the study died from complications related to advanced MS, the prevalence of myelocortical MS may not be the same in other populations, and the findings might not apply to earlier stages of the disease.