New Multiple Sclerosis Subtype Uncovered in Brain Analyses

Bruce Trapp, PhD

A new, novel multiple sclerosis (MS) subtype has been identified by investigators at the Cleveland Clinic.

In a new study released Tuesday evening, investigators, led by Bruce Trapp, PhD, have identified MS subtype myelocortical MS (MCMS)—a form of the neurological disease that differs in its effect on patients’ brains.

Whereas traditional MS is characterized by its neurodegeneration and demyelination of the brain’s white matter, the investigators observed that in post-mortem tissue analysis, patients with MCMS only suffered from the former, not the latter.

In an interview with MD Magazine®'s sister publication Neurology Live, Trapp shared that the discovery initially came during an autopsy he conducted on the donated brain of a patient with MS. Trapp was shocked to see no distinctive lesions on the brain—an indicator of white matter demyelination.

“We went back and continued to look, and we found out that these patients without cerebral white matter demyelination represented 12% of our autopsy program, so it’s a significant cohort,” Trapp said.

The MS subtype identification as ‘myelocortical’ came from patients exhibiting spinal cord demyelination and cortical lesions, Trapp explained. The particularities of the subtype will give investigators a new platform to observe how white matter demyelination and neuron viability overlap in patients with MS.

Trapp and his team collected the brains and spinal cords of 100 deceased patients between May 1998 and November 2012, while conducting a retrospective analysis of the autopsies between September 2011 and February 2018. The patients were previously diagnosed with traditional MS.

A total of 12 patients were identified as having MCMS, indicated by demyelinated lesions in the spinal cord and cerebral cortex, but none in the cerebral white matter.

According to their analysis, the cortical demyelinated lesion area was similar between patients with the new subtype and typical MS (median 4.45%; [interquartile range (IQR) 2.54-10.81] in MCMS vs 9.74% [IQR 1.35-19.50] in typical MS; P = .5512); however, the area of spinal cord demyelination was significantly greater in patients with MCMS (median 3.81% [IQR 1.72-7.42] in MCMS vs 13.81% [IQR 6.51-29.01] in typical MS; P = .0083).

Mean cortical neuronal densities were also significantly decreased compared to control brains (349.8 neurons per mm² [SD 51.9] in MCMS vs 419.0 [43.6] in controls in layer III [P = .0104]; 355.6 [SD 43.6] vs 454.2 [SD 48.3] in later V [P = .0006] and 336.6 [SD 50.9] vs 458.3 [SD 48.4] in layer VI [P = .0049]). In brains of patients with typical MS, mean cortical neuronal densities were reportedly decreased versus control in layer V, but not layers III and VI.

Investigators also found less inflammation in the brains of patients with MCMS, meaning these patients could possibly respond better to anti-inflammatory therapies indicated for MS. At the same time, such undiagnosed patients may be detrimental to clinical trials observing the effects of remyelination in patients with traditional MS.

It is this detriment that makes the prospect of potential in vivo MCMS diagnosis much more coveted by clinicians. It is not currently an option, Trapp said, but the data and samples collected by the Cleveland Clinic could lead to a platform by which they develop biomarkers that differentiate the 2 forms of MS.

“For general neurologists, knowing that this subtype of MS exists is important,” Trapp explained. “Now, will that make them change treatment direction in a given patient? At this point, probably not. What we need to do is to be able to identify these patients while they’re still alive.”

The study, "Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study," was published in Lancet Neurology.