An analysis published in the European Journal of Neurology investigated 4-year outcomes in patients with spinal muscular atrophy (SMA) type 2 and type 3, focusing on changes in the Hammersmith Functional Motor Scale Expanded (HFMSE) relative to functional status, age, and number of spinal motor neuron 2 (SMN2) copies. The study highlights the variability in disease progression among individuals with SMA, suggesting that average changes across different SMA cohorts may not serve as reliable benchmarks.
The HFMSE, designed in 2003, evaluates motor abilities and disease progression in children with SMA2 and SMA3. It is a composite score accounting for 20 physical activities, providing a personal history of patients’ physical abilities. Changes in a patient's ability to perform activities such as standing, crawling, rolling, and sitting allow clinicians to reliably interpret improvements and decline in motor functioning.
Study Design and Patient Population
The study utilized a combination of retrospective analysis and prospective data collection from international datasets, including the Pediatric Neuromuscular Clinical Research Network for SMA in the US, Italy, and UK-SMA REACH, as well as networks in Spain and Belgium. Data spanned from 2003 to 2022. The HFMSE evaluated 33 items with scores ranging from 0-2, where 0 indicates inability to perform a physical activity, 1 indicates achievement with modifications, and 2 indicates performance without modification.
The final dataset included 388 patients with SMA (226 with SMA2 and 162 with SMA3). Approximately 60% of individuals with SMA3 experienced clinical onset before the age of 3 (SMA3a), and just under 25% experienced clinical onset after 3 years of age (SMA3b).
Key Findings
After four years, patients with SMA2 exhibited an average HFMSE change of -2.2, with approximately a -0.58 change occurring each year. A sensitivity analysis for the SMA2 cohort revealed a 4-year change of -3.94 (95% CI, -4.29 to -2.39), estimating a -0.69 change annually (95% CI, -0.87 to -0.50). The largest average change for sitters was observed between the ages of 5 and 14 years, while the most minimal change occurred in individuals who lost the ability to sit without support.
The SMA3 cohort experienced a 4-year change of -2.75, or -2.82 (95% CI, -4.29 to -1.34) after the sensitivity analysis. Annual changes were approximately -0.82, or -0.81 (95% CI, -1.11 to -0.52) after the sensitivity analysis. In this group, the biggest mean motor changes occurred for individuals aged 7 to 15 years and in those over 15 years in the SMA3a subgroup.
Predictors of Change and Clinical Implications
Notably, baseline scores and patient age were the most predictive of change over the 4-year period. According to the authors, the variability observed reinforces the idea that mean changes across different SMA cohorts are not reliable benchmarks, as they encompass a wide spectrum of individual variations in disease progression and treatment response.
