In patients with type 2 spinal muscular atrophy (SMA), the severity of functional impairment at baseline can assist in predicting the magnitude of changes over time, as well as the onset of scoliosis and the need for noninvasive ventilation, according to study results published in Neurology.
Previous studies have shown that patients with type 2 SMA, an autosomal recessive disorder characterized by degeneration of alpha motor neurons in the spinal cord, frequently have relatively stable disease on short-term follow-up, but progressive loss of function is expected in the long term. The goal of the study was to explore the long-term patterns of progression in patients assessed before and after age 5 using the Hammersmith Functional Motor Scale-Expanded (HFMSE) and to identify baseline variables that may affect the disease course.
The single-center retrospective study included patients with a genetically confirmed diagnosis of SMA with mutations in the SMN1 gene and a clinically confirmed diagnosis of type 2 SMA.
The cohort included 73 patients (age 2.6 to 25 years; mean age 6 years 10 months), including 28 patients who were first assessed before age 5 years with more consistent longitudinal data and a longer follow-up period.
Mean HFMSE total score of the cohort at baseline was 14.3±9.8. The results of the piecewise regression analysis showed an improvement in scores in younger children with type 2 SMA. The point of slope change was approximately 5 years, with a decrease in total scores of 1.97 units per year between age 5 and 13 years, indicating a progressive loss of function.
The researchers explained that these findings confirm that there is an overall progression and that this progression is not linear. There was an overall trend toward improvement until age 5, followed by a steep deterioration until puberty and relative stabilization thereafter.
Patients were divided into 3 subgroups using cutoff points of 10 and 22 on the HFMSE at baseline. The rate of progression, measured as annual changes, was higher in the group with the highest baseline HFMSE scores and lower in the group with low scores at baseline. Furthermore, the subgroup with the lowest HFMSE scores at baseline had the earliest progression of scoliosis and the greater need for introducing noninvasive ventilation.
The researchers acknowledged several study limitations, including a relatively short follow-up for a number of patients, a change in the method used to measure height during the course of the study, and having a sample size too small to accurately assess other important factors.
“Our results confirm that, despite the variability in changes and the possibility of improvement in the first years of life, all patients with type 2 SMA show a clear and progressive decline on the long-term follow-up, regardless of their scores at baseline,” concluded the researchers.
The researchers also note that baseline findings may “help to predict the magnitude of changes over time and, more generally, the onset of scoliosis
and need for noninvasive ventilation.”
Mercuri E, Lucibello S, Pera MC, et al. Long-term progression in type II spinal muscular atrophy: A retrospective observational study [published online August 26, 2019]. Neurology. doi:10.1212/WNL.0000000000008166