Cognitive performance of children with spinal muscular atrophy: A systematic review

Abstract

Spinal muscular atrophy (SMA) is genetic and progressive, caused by large bi-allelic deletions in the SMN1 gene, or the association of a large deletion and a null variant. Objective: To evaluate the evidence about cognitive outcomes in spinal muscular atrophy (SMA). Methods: Searches on the PUBMED/Medline, Web of Knowledge and Scielo databases retrieved 26 studies (1989 to 2019, descriptors “spinal muscular atrophy” and “cognition”). Nine studies were selected according to the eligibility criteria: (1) cognition tested in individuals with SMA; (2) written in English or Spanish. The Risk of Bias in Non-Randomized Studies of Interventions was used to describe design, bias, participants, evaluation protocol and main findings. This study was registered on the International prospective register of systematic reviews (PROSPERO). Results: Three studies described normal cognition. In another three studies, cognitive outcomes were above average. Cognitive impairment was found in three studies. Poor cognitive performance was more frequently reported in studies that were recent, included children with SMA type I and that employed visual/auditory attention and executive function tests. Protocols and cognitive domains varied, precluding metanalysis. Conclusion: The severity of motor impairment may be related to cognitive outcomes: studies that included a higher number/percentage of children with SMA type I found cognitive impairment. The establishment of gold-standard protocols is necessary. Further studies should compare the cognitive outcomes of subjects with SMA types I to IV.

Frontotemporal Pathology in Motor Neuron Disease Phenotypes: Insights From Neuroimaging

“…This study reported a possible adaptive mechanism of an inverse correlation between executive function and physical ability, but the level of executive function did not exceed healthy controls (116). In contrast, there are indications of attention and executive function deficits in children with type I SMA (120,126).…”

“…For the most part, neuropsychological studies demonstrate preserved cognition (116)(117)(118)(119). This is with the caveat that these studies are mostly limited to children and omit the more severe clinical phenotypes (120). Some aspects of childhood development are even deemed superior compared to healthy controls (121)(122)(123)(124)(125).…”

New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges

“…Moreover, the increase in muscle strength promotes the worsening of contractures, therefore intensive stretching and the use of standing frame or knee-ankle-foot-orthoses when possible have to be envisaged. The reported cognitive involvement might be more frequent in longer-surviving SMA type I patients and this aspect has to be elucidated in long term follow-up [ 99 ].…”

Cognitive Impairment in Adult Patients with 5q-Associated Spinal Muscular Atrophy

“…Another recently published study focuses on the cognitive performance of adult SMA patients compared to patients suffering from ALS [ 32 ]. In previous studies, cognitive performance of children with SMA varies from average [ 21 , 33 ], above-average [ 18 ], and below-average [ 19 , 20 , 22 ]. In a study by Rivière et al spatial cognition was in the normal range in patients with SMA type 2 compared to healthy children [ 33 ].…”

“…Clinicians have noted their keen interest in their surroundings, their mental acuity, and their observational abilities in relation to the very pronounced physical limitations [ 17 , 18 ]. It was speculated whether the development of knowledge and cognitive skills might be a creative method of compensating for their many restrictions [ 18 , 19 ]. Based on patient’s reports with SMA type 2 and 3, it is assumed that they might focus on different physical activities during their leisure time compared to patients without physical disability [ 17 , 18 ] for example reading books or listen to music instead of sports or physical activity.…”