Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis
JAMA Neurol. 2022. doi:10.1001/jamaneurol.2022.1025
Question Is disability progression independent of relapse activity (PIRA) in relapsing multiple sclerosis associated with increased rates and specific patterns of brain atrophy?
Findings In this cohort study that included 516 patients with relapsing multiple sclerosis and 1904 brain magnetic resonance imaging scans, PIRA was associated with significantly increased brain volume loss. With respect to clinically stable patients, patients with PIRA presented an accelerated total brain atrophy, which was particularly evident in the cerebral cortex.
Meaning The association between PIRA and brain atrophy points at the need to identify insidious disease progression in patients with relapsing multiple sclerosis and to further investigate therapeutic approaches to prevent irreversible brain tissue loss in these patients.
Importance The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood.
Objective To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss.
Design, Setting, and Participants In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021.
Exposures According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability.
Main Outcomes and Measures Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models.
Results Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, −0.36; 95% CI, −0.60 to −0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, −0.18; 95% CI, −0.34 to −0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity.
Conclusions and Relevance Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.
So the way I read this is that people who are worsening clinically have more evidence of brain shrinkage but this appartently is not associated with relapse. I guess one could say that’s interesting but one could also say ” So what”. We have been told that you may have ten lesional events for every clinical attack. So things are going on that are not clinical attacks. I can accept this but one could also say “it’s behind you” because one could say the deterioration will develop over time and the damage may have happened before you look and we have also made the point that damage in the spinal cord may play out with damage in the cortical grey matter in the brain. If you only look in the brain you are unlikey to find the cause.
They say “These results point to the need to promptly identify patients with PIRA in clinical practice, because they may benefit from optimized therapeutic regimens. In this context, clinical trials to assess the potential benefit of treatment escalation/induction in patients with RMS and PIRA are warranted.
So what treatment are on offer.
Disclaimer: These are the views of the author