Spinal Cord Atrophy Greater in Secondary Progressive MS

Nancy A. Melville

March 01, 2019

DALLAS — Atrophy in the spinal cord, imaged on brain MRI, shows a significantly faster acceleration in multiple sclerosis (MS) patients who advance to secondary progressive disease compared with those who remain in relapsing-remitting MS (RRMS), with differences between the two emerging as far as 4 years prior to disease progression, new research shows.

"We show for the first time that spinal cord atrophy rates are faster in relapsing-remitting MS patients who later converted to secondary progressive disease compared to a matched group of patients who remained relapsing-remitting MS over 2 decades," coauthor Antje Bischof, MD, from Basel University Hospital, in Basel, Switzerland, told Medscape Medical News.

"Our results suggest cervical cord atrophy rate at C1 level as a prognostic biomarker for the conversion to secondary progressive MS and could be useful for treatment decisions early in the disease course, and for the study of genetic, epidemiologic and immune variables in MS," she said.

The research was presented here at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019.

With MRI revealing an ever-expanding array of invaluable insights into how MS manifests itself, the strongest correlations with disability have been observed in the spinal cord, Bischof noted.

To more closely investigate the role of spinal cord atrophy in impending conversion from RRMS to more advanced stages of MS, Bischof and her colleagues enrolled 54 subjects who had converted to secondary progressive MS and compared them with 54 age-matched, sex-matched, and disease duration-matched RRMS patients who did not progress over the study's 12-year observation period.

An additional 54 age-matched and sex-matched healthy controls were also evaluated with MRI in the study. Overall, participants had a mean age of about 47.

The analysis of brain volumetrics and spinal cord area C1 showed that in those who advanced to secondary progressive MS there was a significantly higher rate of spinal cord atrophy prior to their conversion (-2.15 % per year; standard error (SE), 0.19) compared with the matched RRMS patients who did not convert to secondary progressive MS over the same period (-0.74% per year; SE, 0.19; P < .0001).

Furthermore, the differences between the groups were seen beginning as far as 4 years prior to conversion to secondary progressive MS, with little overlap between the two groups.

Baseline brain volumes, while lower in MS patients compared with healthy controls, were not significantly different between those with RRMS and those who progressed to secondary disease.

Interestingly, the study showed no other significant differences between those who did and did not convert from RRMS to secondary progressive MS in terms of T1 and T2 lesion volumes or regional and global brain volumes at baseline and over the 12 years of the study.

The observation of the differences up to 4 years prior to conversion was particularly notable, Bischof said.

"It was indeed surprising to see the rapid cord atrophy rates up to 4 years before the conversion to secondary progressive disease," she said.

"[This] indicates that those patients who later converted likely have a more severe spinal cord volume loss already early in the disease course when compared to those relapsing patients who remain relapsing for more than two decades since disease onset."

In addition to helping in the assessment of the long-term impact of treatment in clinical trials as well as legacy datasets, the findings could have important clinical implications in terms of allowing for an early stratification of patients at risk for severe disability, providing guidance of individualized treatment decisions, Bischof said.

Moving ahead, key questions that remain to be answered are the exact mechanisms that lead to the spinal cord atrophy, she noted.

"Currently there is a lack of understanding of the factors that drive the neurodegenerative processes including the destruction of axons and neuronal loss in the spinal cord," she said.

"It remains unclear whether neurodegeneration occurs as an independent primary process or rather secondary to autoimmune-mediated inflammatory processes."

The study offers insights that could be valuable on a variety of levels, said Benjamin Segal, MD, director of the University of Michigan's Multiple Sclerosis Center and the Holtom-Garrett Program in Neuroimmunology, Ann Arbor, in commenting on the research.

"One of the most interesting findings was the spinal cord diameter is actually smaller in patients who are going to transition to progressive MS before the clinical transition takes place, so this could be a prognostic marker of patients who are going to accumulate disability in the future," he told Medscape Medical News.

“That could be very valuable in terms of clinical trial design, as well as how you personalize clinical trials and ultimately treatments if you can enrich your studies with a subset of patients who have remitting/relapsing MS but are likely to enter the progressive phase."

Segal, who was not associated with the current study, added that the findings are notable for being novel.

"There is a lot of literature showing a correlation between spinal cord atrophy and disability, but the finding that the spinal cord diameter can be a predictor of transition to a progressive phase is novel, and I think important."

The authors have disclosed no relevant financial relationships. Segal recently had an investigator-initiated grant sponsored by Genentech.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. Abstract #P157. Presented February 28, 2019.

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