Dr Antje BischofAntje Bischof, MD
Study findings presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum have shown that accelerated cord atrophy precedes a patient’s conversion from relapsing-remitting multiple sclerosis (MS) to secondary progressive disease.

The results were suggestive that cervical cord atrophy at the C1 level could have potential application in a number of areas, including the long-term measurement of treatment effect in clinical trials, and for the early stratification of patients at risk for severe disability in order to better guide individualized treatment decisions.

“Cervical cord atrophy, as obtained from routine brain [magnetic resonance imaging], is a strong indicator of impending conversion to secondary progressive MS,” said Antje Bischof, MD, from the Weill Institute for Neurosciences at the University of California San Francisco, in a presentation at the Forum in Dallas, Texas.

“This data indicates that already during the relapsing phase the patients have a lot of loss of cervical cord that might relate to their clinical disability that we see later on,” Bischof added. “This may be just one of the processes that are now becoming evident to us.”

At the start of her presentation, Bischof noted that the understanding of progressive disease is one of the major challenges in treating MS. This lack of understanding about disease progression and disability, however, could be alleviated to some extent with the use of  MRI measures. To this point, she said, the spinal cord area has shown a strong link to MS disability and can help discriminate progressive and relapsing-remitting disease subtypes.

The study explored 54 patients with relapsing-remitting MS and matched them with 54 patients who converted to secondary progressive disease, as well as 54 healthy controls. The main outcomes from baseline were brain lesion load, as measured by T1 and T2 lesion volume; global brain volumes, including whole brain, white matter, grey matter, and cortical grey matter; regional brain volumes in the thalamus, putamen, and caudate; and spinal cord area at the C1 level.

“These data are based on a modest sample size due to the low number of patients converting from relapsing-remitting MS to secondary progressive MS during the 12-year observation period,” Bischof explained. “Confirmation with independent datasets is in progress to reproduce the results.”

After 12 years, the annualized cord atrophy rates discriminated between the matched groups pre-conversion, which was shown to be measurable up to 4 years prior to conversion to secondary disease.  Those who remained with relapsing-remitting disease showed a -0.74% rate per year compared to the rate of -2.15% per year for those who converted (P <.001). There was no effect shown by relapse rate, disease duration, new or enlarging lesions, disease-modifying treatments, or slowly enlarging lesions.

“We tried to do a very comprehensive review of all metrics that are currently available because many studies only look at 1 specific parameter, and then we don’t know if there are correlations with other metrics,” Bischof said. “We looked at brain volumes at baseline, over time, and in conversion, and we didn’t find any significant differences between these 2 groups, for all these metrics.”

This lack of significant differences was true for cortical grey matter volume, total grey matter volume, lateral ventricular volume, whole brain volume, and white matter volume. Additionally, there were no differences shown between T1 or T2 lesions at baseline or over time.

“Not only could this have an impact in future trials, but also looking back at all of the legacy datasets that we have already, worldwide,” Bischof said. “These have been well curated, and we can measure the effects. We can also use this to study the role that genetic, epidemiologic, and immune variables have on MS.”
REFERENCE
1. Bischof A. Accelerated cord atrophy precedes conversion to secondary progressive disease in multiple sclerosis. Presented at: ACTRIMS Forum; February 28 to March 2, 2019; Dallas, TX.