A team of investigators at Cleveland Clinic discover a novel subtype of multiple sclerosis which features neuronal loss but no demyelination of the brain’s white matter.
A new subtype of multiple sclerosis has been discovered by investigators from the Cleveland Clinic, a discovery that provides insight into the individualized nature of the rare disease.
Demyelination of cerebral white matter has long been considered to be the driver of neuronal degeneration and permanent neurological disability in those with multiple sclerosis (MS). However, now, for the first time, investigators found that the new subtype—referred to as myelocortical MS (MCMS)—features neuronal loss but no demyelination of the brain’s white matter.
For their research, the team of investigators, led by Bruce Trapp, PhD, set to find pathological evidence of cortical neuronal loss independent of cerebral white-matter demyelination by looking at post-mortem brains that belonged to patients with multiple sclerosis.
To do this, Dr. Trapp and his team removed the brain and spinal cords from 100 patients who had died with multiple sclerosis between May 1998 and November 2012. The team conducted their retrospective analysis of the autopsies between September 2011 and February 2018.
For the study, published in the journal Lancet Neurology, they examined centimeter-thick slices of cerebral hemispheres and identified 12 individuals with MCMS, as indicated by demyelinated lesions in the spinal cord and cerebral cortex, but none in the cerebral white matter.
The team matched the individuals with MCMS by age, sex, MRI protocol, MS disease subtype, disease duration, and Expanded Disability Status Scale, with individuals who had traditional MS. Using myelin protein immunocytochemistry, the investigators compared the demyelinated lesion area in tissue sections of cerebral white matter, spinal cord, and cerebral cortex of individuals with MCMS with those collected from individuals with traditional MS. The investigators also compared neuronal densities in cortical layers III, V, and VI from 5 cortical regions that are not directly connected to the spinal cord in both groups.
The investigators found that demyelinated lesions were detected in the spinal cord and cerebral cortex, but not in cerebral white matter of those with MCMS. Cortical demyelinated lesion area was found to be similar across both groups of individuals; however, spinal cord demyelinated area was found to be significantly greater in those with traditional MS compared to those with MCMS.
“Despite the lack of cerebral white-matter demyelination in MCMS, mean cortical neuronal densities were significantly decreased compared with control brains in layer III, V, and VI. In contrast, mean cortical neuronal densities were decreased in traditional MS brains compared with those from the controls in layer V, but not in layers III and VI,” the authors write. Knowing that there was less inflammation present in the brains of patients with MCMS suggests that these patients might respond better to anti-inflammatory therapies indicated for MS.
"The importance of this research is two-fold. The identification of this new MS subtype highlights the need to develop more sensitive strategies for properly diagnosing and understanding the pathology of MCMS," Daniel Ontaneda, MD, clinical director of the brain donation program at Cleveland Clinic's Mellen Center for Treatment and Research in MS, stressed in a recent statement. "We are hopeful these findings will lead to new tailored treatment strategies for patients living with different forms of MS."