Rate of Brain Atrophy May Predict Risk for Clinical Disease Progression in MS

In patients with multiple sclerosis (MS), clinical progression of disease is associated with lower baseline brain volume, along with a higher rate of concurrent whole brain tissue atrophy, according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, held in San Diego, California, from February 23 to 25.

MS prognostication is a challenge among clinicians who attempt to make personalized treatment choices at a patient’s bedside. To help with decision-making, quantitative volumetric magnetic resonance imaging (MRI) has become readily available. According to previous observations, the best predictor of MS disability progression is a pathological cutoff of -0.4% for a change in longitudinal brain volume.

Researchers conducted a retrospective, longitudinal study at a single tertiary care center. They sought to establish MRI volumetric biomarkers linked to concurrent disability progression in individuals with MS. The following inclusion criteria were applicable:

• Age >18 years
• Fulfilling 2017 McDonald criteria for MS or clinically isolated syndrome (CIS)
• Completing an Expanded Disability Status Scale (EDSS) evaluation on 2 or more separate clinical visits
• Having undergone ≥2 brain MRI scans with use of the same hardware/software protocol, which were separated by a minimum of 18 months

Disability progression was defined as worsening EDSS by 0.5 if baseline score was ≥4.5 and worsening EDSS of 1 if baseline score was <4.5.

The researchers used FSL-SIENA/X to determine white matter and gray matter volumes, normalized whole brain volume, and change in brain volume. Data analysis was conducted with the use of univariable and multivariable regression, as well as adaptive spline models, with disability progression as the dependent variable in

STATA v17.0. Covariates used in the model were as follows:

• Annualized brain atrophy rate
• Change in disease-modifying therapy (DMT)
• Age at onset of MS
• Duration of DMT

A total of 212 participants with confirmed MS were included in the study. The mean patient age was 52 years. Overall, 23.6% of the participants were men; 78.77% of the patients had relapsing MS; and 18.39% had progressive MS. The median follow-up time in the study was 5.75 years.

The researchers found that 23.11% (49 of 212) of the participants demonstrated disability progression over the observation period. Adjustments for baseline brain volume, EDSS, and duration of observation were accomplished with multivariate logistic regression models.

Annualized percent of brain volume change (odds ratio [OR], 0.42; 95% CI, 0.19-0.93; P =.033) and baseline brain volume (OR, 0.9; 95% CI, 0.90-0.99; P =.024) both were significantly associated with disability progression. With spline modeling, –0.53% was identified as the earliest cutoff for annualized brain volume loss that was associated with disability progression. Baseline deep gray areas significantly associated with disability progression included the caudate (P =.004), the hippocampus (P =.016), and the thalamus (P =.022).

The researchers concluded, “Brain MRI characteristics such as brain volume atrophy are useful potential biomarkers to risk stratify patients [with MS] at risk of ongoing clinical deterioration.”