Literature Review

Progressive disability in MS explained?


From Neurology

Complete resolution

Results showed that 72% of patients with MOGAD experienced complete resolution of the brain index lesion, compared with 17% of patients with MS and 14% of patients with NMOSD (P < .001).

Similarly, 79% of the MOGAD group experienced complete resolution of the myelitis index lesion, compared with no members of the MS or NMOSD groups (P < .001 for both comparisons).

Complete resolution of all T2-abnormalities at MRI follow-up was more common in the MOGAD group than in the other two groups.

For brain attacks, complete resolution occurred in 39% of patients with MOGAD, 10% of patients with NMOSD, and 5% of patients with MS. For spinal cord attacks, complete resolution occurred in 79% of patients with MOGAD, versus none of the patients with NMOSD or MS.

Median reduction in T2 lesion area on follow-up axial brain MRI was larger in patients with MOGAD (213 mm2) than in those with NMOSD (104 mm2; P = .02) or MS (36 mm2; P < .001).

Reductions in lesion size on sagittal spine MRI follow-up were similar between the MOGAD (262 mm2) and NMOSD (309 mm2) groups; both experienced greater reductions than the MS group (23 mm2; P < .001).

Lesion prevention

Dr. Flanagan noted that the diagnosis of MOGAD is based on a test for MOG antibody, but sometimes false positive results occur. “A single follow-up MRI can be useful, showing that if all the lesions went away, you would be more confident that it would be MOGAD,” he said.

Study participants with MS experienced less lesion healing than the patients with MOGAD or NMOSD.

“We now have very effective medications in MS to prevent new lesions from occurring,” Dr. Flanagan said. The study highlights the importance of lesion prevention, “because when you do get a lesion, it does tend to stay and not recover completely,” he added.

He noted that the resolution of lesions in the study population may reflect remyelination. Future research examining whether remyelination is more efficient in MOGAD than in the other disorders could possibly lead to new approaches for MS treatment, said Dr. Flanagan.

“Maybe some of the MOGAD lesions are from edema. When we use steroids, that tends to resolve and not leave a scar. So, that’s another possibility. We’d like to better understand that,” he said.

Differences in pathology

Commenting on the findings, Bruce Cree, MD, PhD, professor of neurology, Weill Institute for Neurosciences, University of California, San Francisco, noted that the study is one of the first to systematically examine and compare MRI lesion evolution across three disease states.

“What they put their finger on are differences in the fundamental pathology of these three different diseases,” said Dr. Cree, who was not involved with the research.

The study’s cross-sectional comparison was its main strength, he noted.

“The main weakness, from my point of view, is that in these three disorders, optic nerve involvement is very common,” Dr. Cree said. “In this paper, no analysis of optic nerve lesions by MRI was performed.”

The researchers acknowledge this limitation and explain that they did not have consistent, dedicated orbital imaging for such an analysis.

Dr. Cree noted that the findings also provide a reminder that the pathogenesis of MOGAD is not yet clear.

“We know that these anti-MOG antibodies are associated with this demyelinating disorder, but whether these antibodies have a pathogenic role has yet to be clearly demonstrated,” said Dr. Cree. “What is actually going on within these lesions [is also] not fully understood.”

The finding that MOGAD lesions can resolve completely suggests that repair mechanisms are at work within the brain and spinal cord, he noted.

Being able to understand and comprehend what those mechanisms at work are and why they occur in MOGAD but not in NMOSD or MS “would be of enormous clinical advantage,” he said.

The current study also highlights the importance of incorporating imaging into clinical trials that study these rare disorders, especially serial imaging for MOGAD, Dr. Cree added.

This imaging is vital not only for developing new treatments but also for understanding the clinical impact of a given medication. “We really need rigorous imaging to be applied to these rare disorders, just as was done with MS,” Dr. Cree concluded.

The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Flanagan has received research support from MedImmune/Viela Bio. Dr. Cree is working with two of the researchers on the steering committee for the N-MOmentum trial of inebilizumab in patients with NMOSD. He has reported no relevant financial relationships.

A version of this article first appeared on


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