Whole-body MRI can track subtle muscle changes in SMA, study finds
Quantitative scans can detect muscle loss better than clinical tests
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- Whole-body quantitative MRI, or qMRI, was shown to detect subtle muscle loss in adults with SMA, even with treatment, in a new study.
- The researchers found that qMRI is more sensitive than clinical tests for tracking SMA disease progression.
- In adults with SMA, the most pronounced changes in muscle over time were seen the lower legs.
Whole-body quantitative MRI, or qMRI, can track long-term subtle muscle changes throughout the body among adults with spinal muscular atrophy (SMA), despite treatment and clinical stability, a new study reported.
In fact, qMRI was seen to work better than clinical testing over time in detecting muscle measures of disease severity in adults with SMA, according to the researchers.
In this study, scientists in Germany used the whole-body MRI scans to assess the effects of the approved SMA therapy Spinraza (nusinersen) across more than a dozen muscles in the body.
“The results suggest that qMRI may be a sensitive and objective biomarker for detecting subtle disease progression in adult SMA, potentially surpassing clinical measures,” the researchers wrote.
The study, “Quantitative Whole-Body Muscle MRI in Adults With Spinal Muscular Atrophy – A Sensitive Tool for Long-Time Evaluation of Disease Progression,” was published in the European Journal of Neurology.
In SMA, the progressive loss of specialized nerve cells in the spinal cord and brain — together known as the central nervous system — leads to muscle weakness and atrophy, or wasting. While the chronic neuromuscular disease mainly affects body movement, it can also cause problems with speech, swallowing, and breathing.
As muscles weaken, their fibers break down and are eventually replaced by fat cells, leading to worsening SMA symptoms. However, this is a slow process that’s hard to detect with the naked eye or even in physical strength tests.
qMRI can measure the exact percentage of muscle replace by fat
qMRI is a noninvasive imaging technique that can measure the fat fraction in muscles — that is, the exact percentage of a muscle replaced by fat. When applied to the thigh muscles of young adults with SMA in one study, qMRI showed muscle decline despite stable strength and motor function over one year.
Now, to further explore its potential as a sensitive biomarker for progression and treatment response in SMA, the research team investigated long-term disease progression in adults receiving Spinraza. The team, led by scientists at University Medicine Halle, used whole-body qMRI to assess 20 muscles.
Clinical data was collected from two women and seven men with SMA, ages 31-66, who underwent whole-body muscle qMRI before and after starting Spinraza. Among them, one had SMA type 2, six had type 3, and two had type 4.
From qMRI data, the muscular fat fraction (mFF) was calculated for each muscle and for muscle groups. Disease severity was assessed using measures of overall motor function (HFMS-EXP) and arm and hand function (RULM). The six-minute walk test (6MWT) was used to evaluate endurance and mobility, while muscle damage was assessed by blood marker (CK).
When the researchers examined pretreatment data, most patients showed moderate clinical impairment. Those who had lived with SMA symptoms longer had higher mFF values and worse clinical scores. Yet, the mFF was not associated with age at disease onset or age at MRI, the team noted.
Across all muscles, higher mFF values were significantly associated with worse results on the HFMS-EXP, 6MWT, and RULM assessments, as well as lower CK levels. Similar patterns were observed for mFF in the upper- and lower-leg muscle groups.
Among individual muscles, high mFF in the thigh muscles, particularly the hamstrings, and in the lower leg muscles correlated with worse HFMS-EXP and 6MWT scores. Correlations were also observed between lower RULM scores and higher mFF in the arm, shoulder, and trunk muscles.
Clinical measures showed no consistent changes in disease severity
Over a median follow-up of 4.5 years, mFF averaged across all analyzed muscles increased significantly, with an average absolute increase of 2.18% and an average annual increase of 0.47%.
The most pronounced changes occurred in the lower leg muscles (absolute increase: 4.05%; annual increase: 0.94%), whereas changes in the thigh muscles were more moderate (absolute increase: 1.81%; annual increase: 0.4%).
These results highlight the limited sensitivity of conventional clinical scores for detecting subtle longitudinal changes at the individual level. … [Whole-body quantitative] MRI parameters may represent a more sensitive complementary tool for longitudinal monitoring.
In contrast to the qMRI findings, no consistent changes were observed in the annual change rates of any of the clinical measures of disease severity. Also, no relevant correlations were identified between annual changes in mFF and changes in any of these clinical outcomes, the researchers noted.
“This aligns with the slower disease progression typically observed in adult-onset cases” of SMA, the researchers wrote.
Overall, according to the team, “these results highlight the limited sensitivity of conventional clinical scores for detecting subtle longitudinal changes at the individual level.” The researchers suggested that “qMRI parameters may represent a more sensitive complementary tool for longitudinal monitoring.”
Among the study’s limitations, the researchers noted the small number of patients evaluated. As such, the team stressed that “further studies involving larger cohorts are needed to confirm these results and ensure their generalizability” among people with SMA.
