Children with SMA should be monitored for cognitive function

Study: Intellectual development should be important outcome in patients

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Children with spinal muscular atrophy (SMA) type 1 who start treatment with approved therapies after their symptoms emerge may be more likely to show below average cognitive, communication, and motor skills than those who start treatment before their symptoms, a study found.

Cognitive function appeared to be most impaired in these children after about a year, but steadily improved over time.

“Intellectual development follow-up should be included in standard of care, and guidance should be provided to parents for optimal intellectual stimulation of very weak infants,” the study’s researchers wrote in the study, “Longitudinal developmental profile of newborns and toddlers treated for spinal muscular atrophy,” which was published in Therapeutic Advances in Neurological Disorders.

Left untreated, SMA is marked by progressive muscle weakness and wasting. But SMA-specific treatments have “dramatically disrupted the natural course of the disease,” according to researchers.

Three treatments have been approved in the U.S. and Europe: Evrysdi (risdiplam), Spinraza (nusinersen), and Zolgensma (onasemnogene abeparvovec).

This means a significantly longer life expectancy for patients with early-onset and severe forms, such as SMA type 1, which involves symptoms that emerge at birth or within the first months of life. Without treatment, patients usually die by age 2.

As these patients begin to live longer, it remains to be seen whether they have normal cognitive and intellectual development into childhood, leading researchers in Belgium to evaluate the long-term intellectual development of 18 children younger than 3 with an SMA diagnosis who were seen and treated at their clinic over three years — from September 2018 to January 2022.

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Assessing pre- and post-symptomatic cognitive development

Eleven children had been diagnosed with SMA type 1 after they started exhibiting symptoms (post-symptomatic group). The remaining 7 were diagnosed before symptoms (pre-symptomatic group), due to newborn screening or because they had an affected sibling.

Spinraza was the most common initial treatment (11 children), followed by Zolgensma (four), and Evrysdi (three). Eight children originally given Spinraza were switched to Evrysdi during the study.

Intellectual capacity was assessed by a neuropsychologist and physical therapist using the Bayley Scales of Infant and Toddler Development third edition (BSID-III), which assesses motor, communicative, and cognitive function. In the presymptomatic group, all but one child scored in the average range on the motor section of the BSID-III at their last assessment. The remaining child was considered low average. In contrast, 10 of the 11 post-symptomatic children had abnormal motor function. Regarding communication abilities, four of seven presymptomatic children were in the average range, one was low average, one was abnormal, and another wasn’t tested. In the post-symptomatic group, five of the 11 children were average, another five were in the abnormal range, and one scored in the low average range.

While six of seven pre-symptomatic children were in the normal/average range for cognitive function, more post-symptomatic patients scored below average. Among those 11 children, seven scored in the average range, three were low average, and one was abnormal — this child was having seizures and severe cognitive impairment.

Regarding changes in cognition over time, it appeared cognition was generally at its lowest from 6-12 months of age, but tended to improve over time.

Overall, “presymptomatic patients had better motor outcomes than postsymptomatic patients,” the researchers wrote, noting this is in line with real world experience suggesting earlier treatment leads to better motor outcomes.

Communicative and cognitive abilities in young children with SMA warrants further investigation, they said.

While adults with SMA typically don’t have cognitive dysfunction, its possible that more severe forms of the disease could affect brain function in ways that treatments don’t completely correct. Still, the findings require additional follow-up with a larger group of patients.

“More data are thus needed, not only from clinical trials, but also from the real-world experience, ” the researchers wrote, noting the results suggest nevertheless that “intellectual development should be considered as an important outcome in treated SMA1 patients,” and could be an “important factor in treatment choice.”