SMA may affect some cognitive abilities in type 2 and 3 children

Lower test scores for working memory, processing speed seen in study

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by Andrea Lobo |

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Here, a child is shown trying to form and express a thought.

Intellectual disability is not common among children with type 2 and 3 spinal muscular atrophy (SMA), but some aspects of cognitive function might be impaired in these children, according to a recent study.

In particular, performance in specific tasks involving working memory — easily accessible information retained for a short time in the brain — correlated with motor function scores, while processing speed — how fast the brain receives and responds to information — was more affected in SMA type 3 than SMA type 2 patients.

“One possible explanation is that the [cognitive] performances could have been affected by motor impairment,” the researchers wrote, adding that further studies are needed to better understand the mechanisms of brain involvement in SMA.

The study, “Profile of cognitive abilities in spinal muscular atrophy type II and III: what is the role of motor impairment?,” was published in the journal Neuromuscular Disorders.

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Concerns being raised that SMA may be associated with problems in cognition

SMA is a genetic condition characterized by progressive muscle weakness and atrophy. Mutations in the SMN1 gene that lead to insufficient survival motor neuron (SMN) protein levels cause the disease.

It is usually classified into five disease types according to a person’s age at symptom onset and the motor skills achieved. In SMA type 2, children develop symptoms between 6 and 18 months of age and, if untreated, never achieve the ability to stand or walk independently.

In SMA type 3, symptoms usually appear after age 18 months, when children generally have started walking, or in adolescence.

Recently, concern is being expressed regarding brain development and cognitive impairment in children with SMA, with some studies suggesting possible brain involvement. One issue is whether the disease might directly affect the brain, or if such involvement is secondary to motor disability.

“So far the number of studies systematically evaluating cognitive function in type [2] and [3] is very scanty, with only a few studies exploring possible association between the levels of motor difficulties with specific difficulties in cognitive function,” the researchers, all in Italy, wrote.

These scientists analyzed the cognitive profile of 57 children, 38 with SMA type 2 and 19 with SMA type 3, at three centers in their country. Their mean age was 9.15 years, and 29 were girls (51%).

At the time of their evaluation, 38 patients (67%) were able to sit independently and 18 (31%) were able to walk independently. One child was not able to maintain a sitting position without assistance. All were receiving special educational care for motor disabilities, and not for cognitive disabilities.

Children tested for overall intellectual abilities, and in specific areas

Most were being treated with disease-modifying therapies (95%), with 94% receiving Spinraza (nusinersen) and 6% Evrysdi (risdiplam). Treatment start ranged from six months to 13 years.

Patients’ global intelligence was assessed using Wechsler scales appropriate to their age: WPPSI-III for children between 2 years and 6 years old, and WISC-IV for children 6 to 16 years old.

These scales provide a Full-Scale Intelligent Quotient (FSIQ) representing overall intellectual ability, and index scores measuring different domains, such as verbal and nonverbal intelligence, working memory — easily accessible information held temporarily in the brain — and processing speed, or how fast the brain receives, understands, and responds to information.

Across the entire group, 72% of the children had normal FSIQ, 14% had borderline intellectual abilities, and 11% had above normal FSIQ. Two children (3%) had mild intellectual disability.

Among the 11 children evaluated using the WPPSI-III scale, 82% had normal FSIQ, one had borderline intellectual functioning, and one had mild intellectual disability (9% each). Their mean index scores were all in the normal range, with relatively low scores in performance, and high scores in verbal index.

Of the 46 children assessed with the WISC-IV scale, 70% had normal FSIQ, 15% had borderline intellectual functioning, 13% had above normal FSIQ, and one (2%) had mild intellectual disability. An analysis showed the mean scores all to be in the normal range, with relatively low scores in working memory and processing speed, and high scores in verbal comprehension.

In this patient group, those between ages 6 and 17, there were no significant differences concerning SMA type, gender, or functional status, except for working memory, which was significantly better in children with SMA type 2.

“It is of interest that their scores had an inverse correlation with the overall severity of the SMA phenotypes,” the researchers wrote. “Our findings … are in agreement and expand recent findings, showing that in SMA adults executive function, which includes working memory abilities, is inversely correlated with motor impairment.”

But “the interpretation of the mechanism underlying these findings is still controversial,” they added.

Cognitive issues not common in types 2 and 3, but some abilities may be affected

Moreover, the FSIQ scores in these patients did not associate with the motor function scores, assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module for spinal muscular atrophy (RULM).

However, processing speed significantly correlated with functional motor scores, indicating that a better motor function is related to a higher processing speed.

Motor abilities also positively correlated with some specific measures of intellectual ability, particularly those related to processing speed and perceptual reasoning indexes. Perceptual reasoning is the ability to take in visual information and interpret it to solve problems.

“In conclusion, our results suggest that intellectual disability is not frequent in type [2] and [3] SMA,” the researchers wrote. However, some specific cognitive functions may be, at least partly, affected by SMA motor impairment.

“Further studies, using comprehensive cognitive tests that do not require active movements … may help to obtain a more appropriate profile of cognitive abilities,” the researchers added.