Study points to MRI marker tied to RRMS-to-SPMS conversion
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The upper cervical spinal cord, visible on routine brain MRI scans, may help researchers assess MS progression risk. (Photo by iStock)
Changes in the upper part of the spinal cord may help identify people with relapsing-remitting multiple sclerosis (RRMS) who are at higher risk of converting to the secondary progressive form of the disease (SPMS), a study reports.
People with RRMS who later developed SPMS tended to have a lower upper cervical cord area (UCCA), a measure of spinal cord size in the neck, suggesting more spinal cord shrinkage or atrophy. In a smaller subgroup with repeat MRI data, they also showed a faster decline in UCCA over time than people who did not convert to SPMS.
This portion of the spinal cord, which is located in the neck, is typically captured by routine brain MRI scans. “In the context of limited established biomarkers for SPMS conversion and given the feasibility of extracting UCCA from routine brain MRI, our study highlights the practicality of this measure as a candidate biomarker,” researchers wrote.
The study, “Upper Cervical Cord Area as a Biomarker of Conversion to Secondary Progressive Multiple Sclerosis,” was published in Annals of Clinical and Translational Neurology.
Multiple sclerosis (MS) is a neurological condition characterized by damage to the brain and spinal cord. In relapsing types of MS, periods of worsening symptoms alternate with periods of relative stability. By contrast, people with progressive MS typically experience a steadier decline without clear relapses.
The vast majority of people are initially diagnosed with RRMS, but these patients can eventually progress to SPMS. However, due to a lack of reliable biomarkers, it can be difficult to determine precisely when this transition occurs or who may be at greater risk of converting to SPMS.
Research has suggested that spinal cord atrophy, or shrinkage, may be an early biomarker of progressive disease. For this reason, a team led by researchers in Lebanon set out to determine whether the upper spinal cord area was associated with later SPMS conversion in people with RRMS.
UCCA measures the size of the spinal cord at the first three vertebrae below the brain — C1, C2, and C3. Unlike other parts of the spinal cord, this area reliably appears on routine brain MRI scans, which means researchers and clinicians can calculate UCCA without any extra imaging.
The team examined medical records for 32 people with RRMS and available brain MRI scans who later developed SPMS. For comparison, they also included 65 people with RRMS who did not convert to SPMS during follow-up. They matched the groups to have similar ages and disease durations at their first visit.
Results showed that lower UCCA at the C2 and C3 vertebrae was associated with higher odds of conversion to SPMS. The researchers built a model to compare UCCA among converters and non-converters with similar demographics. After these adjustments, a 1 sq mm smaller UCCA at C2 or C3 corresponded to 9% higher odds of converting to SPMS.
However, these associations were no longer significant after adjusting for disability levels.
A subset of participants — 16 who converted to SPMS and 34 who did not — had available data from multiple MRI scans. The team assessed changes in UCCA between the first and last scans, taken a mean of about 3.4 years apart.
People who converted to SPMS had a significantly higher annual decline in UCCA, indicating faster spinal cord shrinkage, than those who did not convert. Among converters, UCCA declined by an average of about 5% to 6% per year across the three spinal cord levels measured.
“These findings align with previous studies that reported that accelerated cervical cord atrophy is associated with, and may precede, clinical conversion to SPMS,” the researchers wrote.
The association between annual UCCA decline and SPMS conversion remained significant after adjusting for disability levels, suggesting that the rate of upper spinal cord atrophy may provide information not captured by clinical assessments alone.
The study had several limitations, including its single-center retrospective design and the relatively short follow-up period. “Therefore, our findings provide support for UCCA loss as a marker of near-term SPMS conversion but cannot provide evidence for long-term prediction,” the team wrote.
Future studies should include healthy controls to help establish normal UCCA ranges and clinically meaningful thresholds for assessing progression risk, they noted.
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