Important disability contributors missed
The odds ratio of 3-month confirmed worsening on the T25FW at 96 weeks was 2.25 for patients with more than 10 cumulative new or newly enlarging T2 lesions (P = .03). The OR of 3-month confirmed worsening on the NHPT at 96 weeks was 3.04 for patients with more than 10 such lesions (P = .03).
Greater normalized brain volume loss at 48 weeks was associated with a greater risk for worsening disability on the NHPT at 48 and 96 weeks. For patients with a volume loss greater than 1.5%, the OR of worsening NHPT at 96 weeks was 4.69 (P = .05).
Although previous cross-sectional studies have shown correlations between brain volume and cognitive dysfunction, the current investigators found no association between change in SDMT performance and MRI measures.
From the ASCEND dataset, they found that performance on the SDMT unexpectedly improved with time, perhaps because of a practice effect.
“The SDMT may therefore not adequately reflect the steady cognitive decline that people with SPMS experience,” the investigators wrote.
The lack of association between MRI measures and clinical outcomes may indicate that traditional MRI does not measure important contributors to disability, they noted.
“Although the investigated volume measures in this study are currently the most commonly used in clinical trials, newer MRI metrics such as thalamic or corpus callosum atrophy may have a closer relation to clinical outcome,” they added.
‘Interesting and provocative’
Commenting on the findings, E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children, Toronto, called the study “interesting and provocative.”
“Other studies previously have shown associations between disability and progression, but many have been cross-sectional,” said Dr. Yeh, who was not involved with the research.
The current study is longitudinal and analyzes carefully documented follow-up data from a clinical trial, she noted. However, the 2-year follow-up period was short, considering the pace at which whole brain volume change occurs, Dr. Yeh said.
Some patients with MS have greater brain volume loss than others. Because of this variability, researchers often examine a population’s average brain volume loss. “When you look at averages, it makes it more difficult to understand if the larger brain volume losses are actually associated with change,” said Dr. Yeh.
She noted that because the study population had high EDSS scores at baseline, it is not surprising that the NHPT and the T25FW were more strongly associated with change in brain volume than the EDSS was. Large changes in EDSS score probably did not occur during follow-up, she added.
“We’ll continue to use the EDSS, because it’s what we have,” said Dr. Yeh. However, newer measures, such as the NHPT and the T25FW, may provide better information, she said. Similarly, composite measures of cognition, such as the Brief International Cognitive Assessment for MS, may be superior to the SDMT but take longer to administer.
“We need to look more deeply at which MRI measures are the best for predicting outcome and that correlate well in a short period of time,” said Dr. Yeh.
These measures could include specific regional brain volumes “and more advanced measures that look at axonal injury or axonal loss.” Studies with longer follow-up are also necessary, she concluded.
The investigators and Dr. Yeh have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.