Frequency and Potential Risk Factors Associated with the Development of Asymptomatic T2 Hyperintense Cervical Spine Lesions on MRI in Patients with Relapsing-Remitting Multiple Sclerosis
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Background
Multiple sclerosis (MS) is one of the most common non-traumatic neurologic disorders affecting young adults in the United States. Brain MRI is an important tool for monitoring disease activity and treatment efficacy in people with MS. Spinal cord (SC) imaging has been less consistently used for monitoring inflammatory disease activity, and the frequency of clinically silent breakthrough disease in the SC is still unknown. Given the particular vulnerability of the cervical spinal cord (c-SC) to inflammatory demyelination, it is important to evaluate the necessity of routine c-SC scanning or to ascertain appropriate strategies for its monitoring, considering the burden of each scan on a person with MS, including scanner discomfort and cost.
Objective
To determine how frequently follow-up magnetic resonance imaging (MRI) of the cervical spinal cord (c-SC) in patients with relapsing remitting multiple sclerosis (RRMS) reveals asymptomatic T2 hyperintense lesions, either in combination or in the absence of new MRI brain lesions, and to identify potential associated risk factors for developing such lesions.
Methods
Patients aged 18-65 years who were diagnosed with RRMS and were seen in longitudinal follow-up at the Johns Hopkins MS Center from January 1, 2014, to December 1, 2019, with an MRI brain and C spine performed during that period, were included. The results of up to four c-SC scans were considered during this study period. Asymptomatic new lesions were identified as new hyperintense T2 lesions, with or without enhancement, observed on MRI during routine follow-up surveillance. Univariate and multivariable-adjusted logistic regression (sex at birth, age, race, and current disease modifying therapy [DMT] category) were employed to identify factors associated with the development of an asymptomatic c-SC lesion for the first scan. Additionally, a mixed-effects logistic regression analysis was performed to assess factors associated with developing asymptomatic lesions across successive scans.
Results
A total of 869 individuals were included in the cohort, contributing a median of 3 (interquartile range: 2,4) scans per person. The proportion of incidental asymptomatic lesions identified ranged from 4.8 to 12.1% across the four scans analyzed in the study. Among those with new lesions in the c-SC, roughly half also showed concomitant new activity on brain MRI. The multivariate model was notable for Black/African Americans having higher odds of an asymptomatic new lesion (OR= 3.26, 95% CI 0.79, 5.93, p<0.0001), a result that persisted in mixed effects logistic regression models (OR = 1.73, 95% CI = 1.27, 2.35, p = 0.001). Higher-efficacy therapies were associated with higher odds of detection of a new lesion in the mixed-effects model, an association that was not present when considering just the first scan results as the outcome.
Conclusion
While the association of higher-efficacy therapy is presumed to be related to confounding by indication, Black/African American individuals with MS appear to be at higher risk of developing an asymptomatic c-SC lesion on MRI surveillance, which could suggest higher value of ordering asymptomatic screening imaging of the cord in this subpopulation. Ultimately, however, a very small percentage of the overall population of those with MS has a new cord lesion in the absence of symptoms, and half of those have a new lesion on screening brain MRI. These findings should motivate the creation and validation of predictive models to inform the utility cord imaging at a given timepoint for a given individual with MS, which could enhance healthcare quality and reduce costs.
