A new therapeutic paradigm has heightened the need for meaningful measures of assessing patients.
As new treatments have become available for people with 5q spinal muscular atrophy (SMA), a new report is highlighting the limitations of the measures used to assess motor function in this rare patient group.
The authors wrote that although gene-based therapies like nusinersen (Spinraza), onasemnogene abeparvovec (Zolgensma), and risdiplam (Evrysdi) have led to improvements for people with SMA, they have also heightened the need for meaningful ways to assess patient progress.
In the new study, published in European Journal of Neurology, they evaluated the existing scales, identifying 2 main categories: motor function scales and bedside functional scales.
“On the one hand, motor function scales assess the ability of a patient to perform certain tasks in the clinic, which are used as proxies of day-to-day patients’ functionality,” they wrote.
Commonly used motor function scales include the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module, they noted. The drawbacks of such assessments, however, are that they require trained staff to administer, were initially developed for pediatric patients, and have not been formally validated in adults.
Bedside functional scales include the Egen classification 2 (EK2) scale, the revised version of Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the SMA Functional Rating Scale. These use patient signs and symptoms to assess function. Bedside scales are faster, the authors said, but as with motor-function tests, they have not been thoroughly evaluated in adults.
To assess the validity of these scales, as well as their sensitivity to change (responsiveness), the investigators recruited 79 people with SMA and followed them for an average of 16 months. Patients were evaluated every 6 to 12 months with a variety of motor or functional scales administered by neurologists or physical therapists.
The results showed significant agreement between scales.
“All motor function and bedside functional scales showed either strong or very strong correlation with each other,” the authors said.
The EK2 and the ALSFRS-R and the HFMSE and ALSFRS-R had the greatest correlations, they said. All of the scales were able to distinguish between functional subgroups (walkers, sitters, and nonsitters), but the authors said there was “considerable overlap” between scales.
“ALSFRS-R showed a strong discriminating ability between walkers, sitters, and nonsitters, and HFMSE between walkers and sitters,” the investigators said.
Yet, the scales had overall low responsiveness.
“In walkers, no measure appeared to adequately capture worsening during follow up, while ALSFRS-R was the most responsive measure in sitters and forced vital capacity in nonsitters,” they wrote. “In treated patients, the responsiveness was overall low, too, with some exceptions.”
ALSFRS-R and HFMSE had moderate responsiveness in walkers, and EK2 was moderately responsive in sitters and nonsitters.
The authors said there were strengths and limitations to their study. It was a relatively large cohort of adults aged 15 and older, although they said there was variance in baseline characteristics and in the intervals between visits. Larger, longer studies would help validate their results, they said.
In their conclusion, the authors said the study helped clarify that the current methods of assessing people with SMA have both benefits and drawbacks.
“Overall, bedside functional scales showed some advantages over motor scales, although all showed limited responsiveness,” they wrote. “Therefore, new outcome measures are warranted in adult SMA patients.”
Vázquez-Costa JF, Povedano M, Nascimiento-Osorio AE, et al. Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy. Eur J Neurol. Published online September 1, 2022. doi:10.1111/ene.15542