August 28, 2018
"This study opens up a new arena in MS research. 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," lead investigator Bruce Trapp, PhD, chair of the Cleveland Clinic's Lerner Research Institute Department of Neurosciences and the study's lead author, said in a press release.
The study was published online August 21 in Lancet Neurology.
Trapp and his team studied the brains and spinal cords of 100 deceased patients who were previously diagnosed with typical MS that included cerebral white matter lesions. Twelve of these individuals (12%) had demyelinated lesions in the spinal cord and cerebral cortex, but not in cerebral white matter.
"Cerebral white matter demyelination is sort of the pathological and MRI imaging hallmark of MS. So to find 12% of patients in our study without this is a significant observation," Trapp told Medscape Medical News.
The researchers compared the brains and spinal cords of the 12 patients with myelocortical MS with those of 12 patients with typical MS. Although both patients with myelocortical MS and those with typical MS had typical MS lesions in the spinal cord and cerebral cortex, only the typical MS patients had lesions in the cerebral white matter.
Despite having no typical MS lesions in cerebral white matter, patients with myelocortical MS had reduced neuronal density and cortical thickness — hallmarks of neurodegeneration also observed in typical MS. "This supports the concept that neurodegeneration can be independent of demyelination in these myelocortical patients," Trapp said.
He said it's also noteworthy that myelocortical MS was indistinguishable from typical MS on MRI.
"The cerebral white matter had abnormalities in myelocortical patients despite the fact that they weren't demyelinated. We think these abnormal signals are coming from swollen white matter, or swollen myelinated axons," Trapp said.
"Unfortunately, at present, we cannot identify the myelocortical MS patients while they are alive. One future direction is improving our MRI modalities to be more sensitive to myelin," he added.
Douglas S. Landsman, PhD, associate vice president for biomedical research at the National Multiple Sclerosis Society, said this research is important for two reasons.
"In addition to reporting on a neurodegenerative process in MS that is independent of typical white matter demyelination, the new observations highlight the need for improved imaging techniques that can help investigators and clinicians better understand lesions visualized on MRI," Landsman told Medscape Medical News.
"If these findings are confirmed, the pathological differences detected in these studies may provide new insights for designing clinical trials and treating patients with MS," said Landsman.
Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, noted that new and improved advanced MRI metrics that can adequately detect subpial lesions and differentiate between myelinated and demyelinated white matter would aid in longitudinal evaluation of different pathophysiological subtypes and confirmation of the study results.
These findings, he added, "provides us with further evidence that cortical neuronal loss can be independent from white matter demyelination, potentially suggesting a different pathophysiology."
Currently, he said, MS is classified according to clinical differences, and the ability to classify based on neuropathological data is attractive.
"It would be of interest to determine whether patients with 'myelocortical MS' respond to anti-inflammatory medications in a different manner than do patients with 'typical MS.'"
The study was supported by the National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society. Trapp has disclosed various relationships with Sanofi Genzyme, Genentech, Novartis, Biogen, Disarm Therapeutics, Renovo Neural, and Lunbeck Foundation. Landsman and Harel have disclosed no relevant financial relationships.