Spinal Cord Atrophy as a Prognostic Marker for Progressive Disease in Relapsing MS

Relapsing-remitting Multiple sclerosis diagnosis in form.
In an observational study, researchers studied the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive multiple sclerosis.

In patients with relapsing-remitting multiple sclerosis (RRMS), the presence of spinal cord atrophy is predictive of conversion to secondary progressive multiple sclerosis (SPMS), according to a study published in in the journal Annals of Neurology.

Understanding the development of silent progression and progressive MS in MS has been challenging for neurologists. In relapse-onset MS, the term “progression” has been commonly associated with SPMS—this is when inflammation-related relapses cease and neurodegenerative processes lead to continuous disability accumulation. However, a recent insidious relapse-free disability worsening, identified as silent progression, was reported early in the relapsing phase in a subset of patients, according to the researchers. This suggests widespread neurodegeneration may occur during the early stages of disease, a process that remains elusive, the researchers noted.

The objective of the current study was to explore the role played by spinal cord and brain atrophy for silent progression and conversion to SPMS, via use of a novel technique to accurately capture upper cervical cord area measurements from legacy brain magnetic resonance imaging (MRI) scans. 

A single-center observational study was conducted among patients recruited from the ongoing prospective Expression, Proteomics, Imaging, Clinical (EPIC) study at the University of California San Francisco MS Center. A total of 360 patients with RRMS and 47 with SPMS, along with 80 matched control individuals, participated in the study. Data from the entire study cohort were used, with all patients who remained in the RRMS phase stratified according to whether they remained stable or progressed silently during the 12-year observation period.

The definition of “silent progression” used in the current study was derived from the theory that clinically silent neurodegeneration (measured as central nervous system atrophy on MRI) precedes and is predictive of relapse-free worsening on the Expanded Disability Status Scale, and, in some instances, eventually an SPMS course, and that this neurodegeneration can occur both in patients with and in those without disease relapse.

During the 12-year observational period, patient subsets with RRMS who converted to SPMS or silently progressed (n=54 and n=159, respectively) were compared with clinically matched patients with RRMS who remained in the RRMS phase or were stable (n=54 and n-147, respectively). Brain MRIs were used to evaluate the utility of brain and spinal cord measures to predict silent progression and conversion from RRMS to SPMS.

Participants who developed SPMS demonstrated significantly more rapid rates of cervical cord atrophy 4 years prior to conversion compared with matched RRMS control individuals (–2.19% per year vs –0.88% per year, respectively; P <.001). Following conversion, spinal cord atrophy rates decelerated (–1.63% per year; P =.010) toward the rates reported in patients with SMPS at study entry (–1.04%). Every 1% more rapid rate of spinal cord atrophy was associated with a significantly 69% and 53% shorter time to silent progression and SPMS conversion, respectively (P <.0001 for both).

Study limitations included a confounding variability from hard-/software differences in atrophy rates due to the large longitudinal cohort.

The researchers concluded that cervical cord atrophy, which is frequently present from the earliest stages of MS, is predictive of the speed of silent progression and conversion to SPMS. “Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase,” the researchers concluded.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Bischof A, Papinutto N, Keshavan A, et al. Spinal cord atrophy predicts progressive disease in relapsing multiple sclerosis. Ann Neurol. Published online December 8, 2021. doi:10.1002/ana.26281