Deborah Brauser

March 10, 2017

ORLANDO — Spinal cord gray matter (SCGM) atrophy can be detected at early stages of multiple sclerosis (MS), even when there's an absence of white matter atrophy, new research suggests.

The observational cohort study included 64 patients who had their first MS symptoms just 1 year prior. It showed that both those with progressive MS and those with relapsing MS (RMS) had significant reductions in cervical SCGM compared with their healthy peers.

Although both MS groups also had reductions in thoracic SCGM areas, it was only significant for those with the progressive form of the disease.

White matter was also significantly reduced in cervical cord areas for the progressive MS group only. Neither MS group saw significant white matter reductions in thoracic areas.

Lead author Regina Schlaeger, MD, from the University Hospital Basel, Switzerland, presented the results during a "Cutting Edge Development in MS Research" session here at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017.

The gray matter findings "were pretty surprising, especially that we found subtle and selective reductions already in relapsing patients," Dr Schlaeger told Medscape Medical News.

"Although this could be a predictor for MS, we don't know that yet," she added. "Still, I think it's a very promising biomarker."

Early Disease Course

Dr Schlaeger noted that although SCGM atrophy has been shown recently in long-standing MS, the investigators wanted to assess how early in the MS disease course it could be detected, and what spinal cord levels are affected.

They enrolled 64 patients with MS (69% women; mean age, 36.9 years) and 53 healthy volunteers (72% women; mean age, 37.4 years). All underwent axial 2D-phase sensitive inversion recovery MRI.

These images "were acquired at the intervertebral disc levels C2/C3 [cervical] and T9/T10 [thoracic]," report the researchers.

The patients with MS had an Expanded Disability Status Scale score of 2.0 at baseline and a disease duration of 1.2 years. Half had no history of spinal cord relapses.

In addition, 56.3% had RMS and 12.5% had progressive MS, with 31.3% having clinically isolated syndrome.

The full group of patients with MS had significantly smaller gray matter areas than the healthy volunteers (C2/C3, P = .005; T9/T10, P = .04), but there were no differences in white matter or total cord areas.

In addition, compared with the healthy group, cervical SCGM areas were significantly reduced in both the PMS and RMS groups.

There were also significant reductions for the progressive patients in the cervical total cord and white matter areas and in the thoracic SCGM and total cord areas.

Table. Outcome Comparisons Between MS Subgroups and Healthy Volunteers

Outcome PMS P Value RMS P Value
Cervical spinal cord areas:        
 Gray matter (%) −14 .0007 −3 .04
 Total cord (%) −10 < .0001 +2 NS*
 White matter (%) −9 .005 +3 NS
Thoracic cord areas:        
 Gray matter (%) −16 .02 −3 NS
 Total cord (%) −9 .04 +1 NS
 White matter (%) −6 NS +2 NS

*NS = not significant.

There were no significant differences between patients who did or did not have spinal cord T2 lesions, but the subgroup of patients with MS without spinal cord relapses had significant reductions in cervical (−5%; P = .01) and thoracic (−9%; P = .003) cord gray matter areas compared with the healthy volunteers group.

"This could be indicative that this is a process independent of inflammatory activities," said Dr Schlaeger.

Also in this subgroup, "a multivariable model based on cervical SCGM area as the predictor variable with age and sex as covariates explained 48% of [Expanded Disability Status Scale] variance," note the investigators. In other words, cervical gray matter area "was inversely associated with disability."

"To sum up: spinal cord gray matter atrophy can be detected in vivo already at the earliest stage of MS, affecting both the cervical and lower thoracic cord," Dr Schlaeger said.

She added that longitudinal studies are now needed to assess the rate of atrophy over time, as well as whether this biomarker really can predict disability progression.

Cutting-Edge Techniques

"These are cutting-edge, exploratory techniques that hopefully will inform us about tools that may become biological measures that will lead to better understanding of MS," session cochair Andrew D. Goodman, MD, director of the MS Center at the University of Rochester Medical Center, New York, told Medscape Medical News.

This type of data may eventually help explain "how therapies may be working or not working, and this may potentially become a diagnostic biomarker for clinical trials," said Dr Goodman, who was also cochair of the ACTRIMS 2017 program.

"As we move into the era where we're going to be doing protection and repair of the nervous system, we'll be looking for sensitive biomarkers to guide us."

He added that conventional imaging of the spinal cord is always tricky. "So certainly any new technique that could improve on that will be very welcome," said Dr Goodman. "I have no idea whether this will be such a technique, but it's possible."

The study was funded by grants from the National MS Society, the Conrad H. Hilton Foundation, the Department of Defense, the National Defense Science and Engineering Fellowship, and the Nancy Davis Foundation. Dr Schlaeger has received grants from the Swiss MS Society and the Gottfriend and Julia Bangerter Rhyner Foundation.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017: Abstracts CE1.3, LB199. Presented February 24, 2017.

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