Skip to main content
SpringerLink
Log in

Exploring variability in cognitive functioning in patients with spinal muscular atrophy: a scoping review

  • Review Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

The cognitive functioning of individuals with spinal muscular atrophy (SMA) is not well understood, prompting a call for more research to better grasp cognitive involvement in SMA. This study aims to explore recent findings regarding cognitive outcomes in SMA patients, including correlations between clinical features and cognitive abilities. The investigation seeks to identify commonly used measures for assessing cognitive function in this patient population. A scoping review following the Joanna Briggs Institute methodology examined literature until December 2023. Two databases were searched along with relevant article references using specific terms such as “spinal muscular atrophy,” “SMA,” “cognitive,” “abilities,” “functions,” “intellective,” or “intellectual.” Screening focused on titles and abstracts from English language peer-reviewed journals. After the initial research, 1452 articles were identified. Subsequent screening and selection led to the inclusion of 13 articles in the review. Among these studies, four indicated a cognitive trend within the normal range for SMA patients. In four other studies, the majority of patients fell within the normal range. However, smaller proportions were observed to be either above or below the norm compared to the controls. Three studies reported noted cognitive performance below the average, while two showed above-average scores. The scoping review suggests that most SMA patients have cognitive abilities similar to the general population, with types II and III showing even lesser impact. However, certain cognitive domains may be affected in type I patients, highlighting the need for further research to fully understand cognitive involvement in SMA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data will be available on request to the corresponding author.

References

  1. Coratti G, Ricci M, Capasso A et al (2023) Prevalence of spinal muscular atrophy in the era of disease-modifying therapies: an Italian nationwide survey. Neurology 100:522–528. https://doi.org/10.1212/WNL.0000000000201654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mercuri E, Pera MC, Scoto M et al (2020) Spinal muscular atrophy - insights and challenges in the treatment era. Nat Rev Neurol 16:706–715. https://doi.org/10.1038/s41582-020-00413-4

    Article  CAS  PubMed  Google Scholar 

  3. Burr P, Reddivari AKR (2023) Spinal muscle atrophy. In: StatPearls. StatPearls Publishing, Treasure Island (FL)

  4. Kolb SJ, Kissel JT (2011) Spinal muscular atrophy: a timely review. Arch Neurol 68:979–984. https://doi.org/10.1001/archneurol.2011.74

    Article  PubMed  Google Scholar 

  5. de-Andrés-Beltrán B, Güeita-Rodríguez J, Palacios-Ceña D, Rodríguez-Fernández ÁL (2023) Clinical and functional characteristics of a new phenotype of SMA type I among a national sample of Spanish children: a cross-sectional study. Children (Basel) 10:892. https://doi.org/10.3390/children10050892

    Article  PubMed  Google Scholar 

  6. Wang CH, Finkel RS, Bertini ES et al (2007) Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 22:1027–1049. https://doi.org/10.1177/0883073807305788

    Article  PubMed  Google Scholar 

  7. Kaufmann P, McDermott MP, Darras BT et al (2011) Observational study of spinal muscular atrophy type 2 and 3: functional outcomes over 1 year. Arch Neurol 68:779–786. https://doi.org/10.1001/archneurol.2010.373

    Article  PubMed  Google Scholar 

  8. Trabacca A, Lucarelli E, Pacifico R et al (2020) The international classification of functioning, disability and health-children and youth as a framework for the management of spinal muscular atrophy in the era of gene therapy: a proof-of-concept study. Eur J Phys Rehabil Med 56:243–251. https://doi.org/10.23736/S1973-9087.20.05968-7

    Article  PubMed  Google Scholar 

  9. S L, L B, S R, et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80. https://doi.org/10.1016/0092-8674(95)90460-3

  10. To C, Ca P (1996) The neurobiology of childhood spinal muscular atrophy. Neurobiol Dis 3. https://doi.org/10.1006/nbdi.1996.0010

  11. Mendonça RH, Rocha AJ, Lozano-Arango A et al (2019) Severe brain involvement in 5q spinal muscular atrophy type 0. Ann Neurol 86:458–462. https://doi.org/10.1002/ana.25549

    Article  CAS  PubMed  Google Scholar 

  12. Reilly A, Chehade L, Kothary R (2023) Curing SMA: are we there yet? Gene Ther 30:8–17. https://doi.org/10.1038/s41434-022-00349-y

    Article  CAS  PubMed  Google Scholar 

  13. Trabacca A (2020) Neuromuscular diseases rehabilitation in the era of gene therapy. Neurol Sci 41:1971–1972. https://doi.org/10.1007/s10072-020-04280-1

    Article  PubMed  Google Scholar 

  14. Duong T, Staunton H, Braid J et al (2021) A patient-centered evaluation of meaningful change on the 32-item motor function measure in spinal muscular atrophy using qualitative and quantitative data. Front Neurol 12:770423. https://doi.org/10.3389/fneur.2021.770423

    Article  PubMed  Google Scholar 

  15. Antonaci L, Pera MC, Mercuri E (2023) New therapies for spinal muscular atrophy: where we stand and what is next. Eur J Pediatr 182:2935–2942. https://doi.org/10.1007/s00431-023-04883-8

    Article  PubMed  PubMed Central  Google Scholar 

  16. Finkel RS, Mercuri E, Meyer OH et al (2018) Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord 28:197–207. https://doi.org/10.1016/j.nmd.2017.11.004

    Article  PubMed  Google Scholar 

  17. Lipnick SL, Agniel DM, Aggarwal R et al (2019) Systemic nature of spinal muscular atrophy revealed by studying insurance claims. PLoS One 14:e0213680. https://doi.org/10.1371/journal.pone.0213680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ramos DM, d’Ydewalle C, Gabbeta V et al (2019) Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment. J Clin Invest 129:4817–4831. https://doi.org/10.1172/JCI124120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dangouloff T, Servais L (2019) Clinical evidence supporting early treatment of patients with spinal muscular atrophy: current perspectives. Ther Clin Risk Manag 15:1153–1161. https://doi.org/10.2147/TCRM.S172291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Masson R, Brusa C, Scoto M, Baranello G (2021) Brain, cognition, and language development in spinal muscular atrophy type 1: a scoping review. Dev Med Child Neurol 63:527–536. https://doi.org/10.1111/dmcn.14798

    Article  PubMed  Google Scholar 

  21. Polido GJ, de Miranda MMV, Carvas N et al (2019) Cognitive performance of children with spinal muscular atrophy: a systematic review. Dement Neuropsychol 13:436–443. https://doi.org/10.1590/1980-57642018dn13-040011

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kizina K, Akkaya Y, Jokisch D et al (2021) Cognitive impairment in adult patients with 5q-associated spinal muscular atrophy. Brain Sci 11:1184. https://doi.org/10.3390/brainsci11091184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. von Gontard A, Zerres K, Backes M et al (2002) Intelligence and cognitive function in children and adolescents with spinal muscular atrophy. Neuromuscul Disord 12:130–136. https://doi.org/10.1016/S0960-8966(01)00274-7

    Article  Google Scholar 

  24. Osmanovic A, Wieselmann G, Mix L et al (2020) Cognitive performance of patients with adult 5q-spinal muscular atrophy and with amyotrophic lateral sclerosis. Brain Sci 11:8. https://doi.org/10.3390/brainsci11010008

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mix L, Schreiber-Katz O, Wurster CD et al (2021) Executive function is inversely correlated with physical function: the cognitive profile of adult spinal muscular atrophy (SMA). Orphanet J Rare Dis 16:10. https://doi.org/10.1186/s13023-020-01661-9

    Article  PubMed  PubMed Central  Google Scholar 

  26. Vidovic M, Freigang M, Aust E et al (2023) Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen. BMC Neurol 23:216. https://doi.org/10.1186/s12883-023-03261-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Buchignani B, Cicala G, Moriconi F et al (2023) Profile of cognitive abilities in spinal muscular atrophy type II and III: what is the role of motor impairment? Neuromuscul Disord 33:711–717. https://doi.org/10.1016/j.nmd.2023.08.005

    Article  PubMed  Google Scholar 

  28. Ngawa M, Dal Farra F, Marinescu A-D, Servais L (2023) Longitudinal developmental profile of newborns and toddlers treated for spinal muscular atrophy. Ther Adv Neurol Disord 16:17562864231154336. https://doi.org/10.1177/17562864231154335

    Article  Google Scholar 

  29. Zappa G, LoMauro A, Baranello G et al (2021) Intellectual abilities, language comprehension, speech, and motor function in children with spinal muscular atrophy type 1. J Neurodev Disord 13:9. https://doi.org/10.1186/s11689-021-09355-4

    Article  PubMed  PubMed Central  Google Scholar 

  30. Polido GJ, Barbosa AF, Morimoto CH et al (2017) Matching pairs difficulty in children with spinal muscular atrophy type I. Neuromuscul Disord 27:419–427. https://doi.org/10.1016/j.nmd.2017.01.017

    Article  PubMed  Google Scholar 

  31. Tosi M, Cumbo F, Catteruccia M et al (2023) Neurocognitive profile of a cohort of SMA type 1 pediatric patients and emotional aspects, resilience and coping strategies of their caregivers. Eur J Paediatr Neurol 43:36–43. https://doi.org/10.1016/j.ejpn.2023.02.004

    Article  CAS  PubMed  Google Scholar 

  32. Lenzoni S, Semenza C, Calligaro D et al (2022) Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study. Neuromuscul Disord 32:672–677. https://doi.org/10.1016/j.nmd.2022.05.005

    Article  PubMed  Google Scholar 

  33. Hu Y, Wei L, Li A et al (2023) Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment. Front Neurol 14:1226043. https://doi.org/10.3389/fneur.2023.1226043

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kölbel H, Kopka M, Modler L et al (2024) Impaired neurodevelopment in children with 5q-SMA - 2 years after newborn screening. J Neuromuscul Dis 11:143–151. https://doi.org/10.3233/JND-230136

    Article  PubMed  PubMed Central  Google Scholar 

  35. D’Angelo MG, Bresolin N (2006) Cognitive impairment in neuromuscular disorders. Muscle Nerve 34:16–33. https://doi.org/10.1002/mus.20535

    Article  CAS  PubMed  Google Scholar 

  36. Billard C, Gillet P, Barthez M-A et al (1998) Reading ability and processing in Duchenne muscular dystrophy and spinal muscular atrophy. Dev Med Child Neurol 40:12–20. https://doi.org/10.1111/j.1469-8749.1998.tb15351.x

    Article  CAS  PubMed  Google Scholar 

  37. Rivière J, Lécuyer R (2002) Spatial cognition in young children with spinal muscular atrophy. Dev Neuropsychol 21:273–283. https://doi.org/10.1207/S15326942DN2103_4

    Article  PubMed  Google Scholar 

  38. Rivière J, Lécuyer R (2003) The C-not-B error: a comparative study. Cogn Dev 18:285–297. https://doi.org/10.1016/S0885-2014(03)00003-0

    Article  Google Scholar 

  39. Rivière J, Lécuyer R, Hickmann M (2009) Early locomotion and the development of spatial language: evidence from young children with motor impairments. Euro J Dev Psychol 6:548–566. https://doi.org/10.1080/17405620701345712

    Article  Google Scholar 

  40. Chung BHY, Wong VCN, Ip P (2004) Spinal muscular atrophy: survival pattern and functional status. Pediatrics 114:e548–e553. https://doi.org/10.1542/peds.2004-0668

    Article  PubMed  Google Scholar 

  41. Barja S, Muñoz C, Cancino N et al (2013) Audiovisual stimulation in children with severely limited motor function: does it improve their quality of life? Rev Neurol 57:103–111

    PubMed  Google Scholar 

  42. Dubowitz V (1967) Infantile muscular atrophy–a broad spectrum. Clin Proc Child Hosp Dist Columbia 23:223–239

    CAS  PubMed  Google Scholar 

  43. Valkenborghs SR, Noetel M, Hillman CH et al (2019) The impact of physical activity on brain structure and function in youth: a systematic review. Pediatrics 144:e20184032. https://doi.org/10.1542/peds.2018-4032

    Article  PubMed  Google Scholar 

  44. Günther R, Wurster CD, Cordts I et al (2019) Patient-reported prevalence of non-motor symptoms is low in adult patients suffering from 5q spinal muscular atrophy. Front Neurol 10:1098. https://doi.org/10.3389/fneur.2019.01098

  45. WAIS-IV - Wechsler Adult Intelligence Scale – Fourth Edition | Testzentrale. https://www.testzentrale.de/shop/wechsler-adult-intelligence-scale-fourth-edition.html. Accessed 2 Feb 2024

  46. Piovesana AM, Harrison JL, Ducat JJ (2019) The development of a motor-free short-form of the Wechsler Intelligence Scale for Children-Fifth Edition. Assessment 26:1564–1572. https://doi.org/10.1177/1073191117748741

    Article  PubMed  Google Scholar 

  47. Raven J (2000) The raven’s progressive matrices: change and stability over culture and time. Cogn Psychol 41:1–48. https://doi.org/10.1006/cogp.1999.0735

    Article  CAS  PubMed  Google Scholar 

  48. Raven JC, Raven J, Schmidtke A, Court JH (1980) Raven-Matrizen-test: coloured progressive matrices - CPM : Manual, 2, verb edn. Beltz, Weinheim

    Google Scholar 

  49. Abrahams S, Newton J, Niven E et al (2014) Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener 15:9–14. https://doi.org/10.3109/21678421.2013.805784

    Article  PubMed  Google Scholar 

  50. Lulé D, Burkhardt C, Abdulla S et al (2015) The edinburgh cognitive and behavioural amyotrophic lateral sclerosis screen: a cross-sectional comparison of established screening tools in a German-Swiss population. Amyotroph Lateral Scler Frontotemporal Degener 16:16–23. https://doi.org/10.3109/21678421.2014.959451

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by funds from PNRR-MR1-2022–12376937 (to GG, MR, and AT).

Author information

Author notes

  1. Gabriele Giannotta and Marta Ruggiero contributed equally to this study.

Authors and Affiliations

  1. Unit for Severe Disabilities in Developmental Age and Young Adults (Developmental Neurology and Neurorehabilitation), Associazione “La Nostra Famiglia” – IRCCS “E. Medea”, Scientific Hospital for Neurorehabilitation, Brindisi, Italy

    Gabriele Giannotta, Marta Ruggiero & Marta De Rinaldis

  2. Scientific Institute IRCCS “E. Medea”, Scientific Direction, Via Don L. Monza 20, 23842, Bosisio Parini (LC), Italy

    Antonio Trabacca

Authors
  1. Gabriele Giannotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Ruggiero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marta De Rinaldis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Trabacca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Trabacca.

Ethics declarations

Ethics approval

Not applicable since no participants were recruited during the execution of this study.

Human and animal rights

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Consent for publication

This manuscript has been approved for publication by all authors.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giannotta, G., Ruggiero, M., De Rinaldis, M. et al. Exploring variability in cognitive functioning in patients with spinal muscular atrophy: a scoping review. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07503-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10072-024-07503-x

Keywords

Search

Navigation