More Microscopic Brain Damage Seen in SPMS Than in RRMS

People with secondary progressive multiple sclerosis (SPMS) have more microscopic damage in normal-appearing brain tissue than do patients with relapsing-remitting multiple sclerosis (RRMS), according to a new imaging study.

These patients also have a greater number of chronic active lesions than those with RRMS.

“Using advanced diffusion MRI and image texture analysis methods, we found significant differences between RRMS and SPMS subjects across a wide range of measures of brain microstructure,” the researchers wrote.

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The study, “Advanced diffusion MRI and image texture analysis detect widespread brain structural differences between relapsing-remitting and secondary progressive multiple sclerosis,” was published in Frontiers in Human Neuroscience.

Most people with multiple sclerosis are initially diagnosed with RRMS, which is characterized by periods of sudden attacks of worsening symptoms (relapses) interspersed with periods where symptoms ease or disappear (remissions). SPMS is a stage of disease that can develop after RRMS and is characterized by the gradual worsening of symptoms over time, regardless of relapse activity.

Neurological symptoms in RRMS are thought to be driven more by active inflammation, whereas SPMS progression is driven more by the gradual dysfunction and death of neurons. However, the biological mechanisms underlying the transition from RRMS to SPMS, and the consequent differences in patterns of brain damage, remain poorly understood.

A team of researchers at the University of Calgary conducted an analysis of advanced MRI data to learn more. Using two previously acquired datasets, the scientists assessed brain imaging data from 20 people with RRMS and nine with SPMS.

The average age was 40.7 years for RRMS patients and 58.2 years for those with SPMS. As expected, because SPMS is a more advanced disease stage, these patients generally had a longer disease duration and more substantial disability.

All of the patients had lesions in white matter (the part of brain tissue that contains nerve fibers connecting different brain regions), with one to 111 individual lesions identified in each patient’s brain. The average number of lesions was significantly lower in patients with RRMS than in those with SPMS (29.5 vs. 48.6 lesions).

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SPMS patients found to have more ‘smoldering’ lesions

Results showed that SPMS patients also had significantly more “smoldering” lesions showing signs of chronic inflammation, which were determined using a novel approach.

In addition to comparing lesions — which represent substantial, clearly visible damage to the white matter — the researchers also conducted “texture” analyses. Simplistically, these are mathematical assessments that looked at differences among individual points (voxels) in the image of the brain acquired by MRI.

The general goal of texture analysis is to identify microscopic damage to nerve fibers that is not substantial enough to be visible as a lesion, but may still interfere with normal neuronal signaling.

Across nearly all of the mathematical measures assessed as part of the texture analysis, the SPMS patients showed more signs of microscopic damage in normal-appearing white matter (NAWM) than those with RRMS. This microscopic damage was observed in the whole brain as well as in specific nerve fiber tracts known to affect patient function.

“The SPMS individuals show greater NAWM damage across nearly all diffusion and phase congruency-based texture measures of the whole brain,” the researchers wrote.

“Our findings indicate that there is increased tissue damage in the NAWM of SPMS at both micro- and macroscopic levels,” they concluded.

The team noted that this analysis was limited by the small number of patients. Still, the researchers said the results “may provide a useful foundation for future studies of disease progression in MS, as represented by joint analysis of different scales of tissue pathology.”