No clinically-significant changes in cognitive function were observed in adult patients with spinal muscular atrophy (SMA) with type 2 or 3 disease after 14 months of treatment with nusinersen, according to a study published in BMC Neurology.

While statistically-significant improvements were observed in components of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS), the differences were not above the thresholds of clinical significance described in a previous study.

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Since no cognitive assessment tools have been validated specifically for patients with SMA yet, the authors used the ECAS since it is able to take into account both cognitive and motor disabilities, even though it was designed for ALS. 

In the ALS-specific portions of the ECAS, a 4-point improvement, from 78 to 82 points, was observed between baseline and 14 months of nusinersen treatment. A 2-point improvement was observed in the nonALS-specific portion of the test while an increase of 7 points was observed for the ECAS total score. 

Studies of the ECAS in healthy controls found improvements in the ECAS which were interpreted as being due to casual practice. A previous study suggested that to reach clinical significance, improvements had to be greater than or equal to 8, 4, and 9 points in the ALS-specific, nonALS-specific, and ECAS total scores, respectively. 

“Based on these recommendations, no clinically significant changes after 14 months of nusinersen treatment were found in our SMA cohort and observed improvements could rather be explained by a practice effect. Based on our findings we may additionally conclude that nusinersen initiation treatment does not have a negative impact on cognition either,” the authors wrote.

Previous studies have suggested that SMA is a multi-systemic disease and could affect cognitive abilities in adult patients. One study found that cognitive abilities were within normal ranges for adult patients with SMA but that executive function was inversely correlated with motor function. In contrast, another study found that patients with SMA type 2 had lower IQ index scores in working memory and perceptual reasoning compared to the general population.

No significant correlations were found between changes in the ECAS score and changes in motor outcome scores including the Hammersmith Functional Motor Scale Expanded, Revised Upper Limb Module, and the ALS Functional Rating Scale Revised.

A total of 23 adult patients with SMA (9 with SMA type 2 and 14 with SMA type 3) were included in the study at a single site in Dresden, Germany. The mean baseline age of the patients was 38.1 years, but patients with SMA type 2 were significantly younger than those with SMA type 3 (mean 31.9 years vs 42.1 years).


Vidovic M, Freigang M, Aust E, et al. Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen. BMC Neurol. Published online June 6, 2023. doi:10.1186/s12883-023-03261-z