The death of nerve cells (depicted here) causes disability in MS.
Multiple sclerosis (MS) is very unpredictable; its symptoms can vary from relatively mild to disabling.
It might also cause a major disruption between the brain and the body. Currently, there is no cure for MS.
The researchers who made the new discovery, from the Cleveland Clinic in Ohio, believe that their findings increase scientific understanding of how the underlying mechanisms of MS differ from case to case.
The team has named the new subtype myelocortical MS (MCMS). They write in the journal Lancet Neurology that MCMS is characterized by the death of the brain's nerve cells, but without any damage to the protective coating of the neurons, which is a traditional hallmark of MS.
Typically in MS, immune cells destroy this fatty protective substance known as myelin in a process known as demyelination. Previously, scientists had assumed that demyelination is what ultimately leads to the death of neurons in MS.
It is the death of neurons that causes irreversible disability in people with MS, so understanding why neurons die is key to identifying new treatment targets for the disease.
Subtype identified by analyzing 100 brains
The signs of MCMS in brain tissue, however, are indistinguishable from those of traditional cases of MS when viewed using MRI.
It was only by examining postmortem tissue from people with MS that the researchers were able to identify the new subtype; they found that some lesions thought to be indicative of myelin loss on MRI were, instead, signs of neuronal swelling.
In the new study, the researchers examined postmortem brain tissue from 100 people with MS who had donated their brains to scientific research. The researchers determined from this analysis that 12 of the brains had not experienced demyelination.
The team then performed a microscopic comparison of these 12 brains with 12 brains exhibiting traditional MS signs of demyelination, as well as brains from people who had no neurological disease.
The brains classified as having MCMS and those that exhibited signs of demyelination both showed lesions considered typical of MS in the spinal cord and the cerebral cortex. Both groups of brains had a lower density of neurons compared with the brains of healthy people.
However, only the brains considered by the researchers to have traditional MS had lesions in the white matter of the brain, which comprises myelin.
More 'sensitive strategies' needed
The authors concluded that degeneration of the brain's neurons and demyelination are functions of MS that can occur separately, and that new imaging techniques are needed to accurately diagnose these distinct subtypes in living patients.
Daniel Ontaneda, clinical director of the brain donation program at Cleveland Clinic's Mellen Center for Treatment and Research in MS, explains.
"The importance of this research is twofold," he says. "The identification of this new MS subtype highlights the need to develop more sensitive strategies for properly diagnosing and understanding the pathology of MCMS."
"We are hopeful these findings will lead to new tailored treatment strategies for patients living with different forms of MS."
"This study opens up a new arena in MS research," adds team leader Bruce Trapp, who holds the Morris R. and Ruth V. Graham Endowed Chair in Biomedical Research.
"It is the first to provide pathological evidence," he adds, "that neuronal degeneration can occur without white matter myelin loss in the brains of patients with the disease. This information highlights the need for combination therapies to stop disability progression in MS."