Complex Neuropsychiatric and Laboratory-Instrumental Diagnostics in Determination of Tactics of Therapeutic Management of Patients with Spinal Muscular Atrophy: Regional Experience

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Abstract

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare hereditary disabling disease and the most common hereditary cause of infant deaths. The timely comprehensive diagnosis of SMA permits to plan therapeutic tactics and preserve the quality of patients’ life. One of the objectives of the given work is a review of the actual literature data on etiopathogenesis, clinical presentation, valid diagnosis and modern effective tactics of SMA management.

AIM: To evaluate the management tactics of patients with SMA taking into account neuropsychiatric symptoms, to analyze problems of proposal and organization of measures aimed at improvement of the quality of medical care, on the basis of the practical experience of the Samara region and with consideration of the current state of the problem.

MATERIALS AND METHODS: In the work, the data of the archive of Seredavin Samara Regional Clinical Hospital were analyzed, 132 medical histories of 77 patients were processed with discharge dates from January 2008 to February 2022 with the following diagnoses (according to the code of the International Classification of Diseases and Health Related Problem, 10th revision (ICD-10)): G12.0 (spinal muscular atrophy, type I [Werdnig–Hoffmann disease], G12.1 (other hereditary SMA), G12.8 (other SMA and related syndromes) and G12.9 (unspecified SMA). The analysis of the results of clinical, laboratory, instrumental and neuropsychiatric diagnostic methods was performed in comparison with the tactics of therapeutic management of these patients. For statistical processing of the data, methods of descriptive statistics were used.

RESULTS: Socio-demographic data. As of February 2022, 58 patients were registered (mean age 38.4 (41.3) years, of them 32 (55.2%) were individuals of female gender including 21 children (mean age 12.3 (7.4) years, 14 (24.1%) girls), with the following diagnoses according to ICD-10: G12.0 (n = 7; 12.0%; only children), G12.1 (children: n = 14; 24.1%; adults: n = 29; 50.0%), G12.8 (n = 6; 10.3%; only adults), G12.9 (n = 2; 3.4%; only adults). Clinical data. Motor disorders from a mild proximal lower paraparesis (n = 13; 22.4%) to pronounced tetraparesis (n = 7; 12.0%). The study of mental status was limited to evaluation of the state of consciousness and effectiveness of contact. Data on therapy. Until 2021, symptomatic therapy of SMA was conducted in the region, since March 2021, 8 children (13.8% of the total sample) aged 7.3 (8.8) years received nusinersen, another 8 children (13.8%) aged 9.5 (6.9) years received risdiplam; parents of 3 more children (5.2%) refused taking drugs. Of adult patients (n = 37; 63.8%; 35.3 (23.6) years) with confirmed SMA 5q (n = 10; 17.2%, 35.3 (19.0) years), 1 patient received nusinersen, the rest 9 patients (15.5%) did not receive therapy, 3 (5.2%) were achieving the right to receive drugs (at the moment of the analysis).

CONCLUSION: The data analysis revealed deficit of early SMA diagnosis (at the moment of the diagnosis, all the patients were already having pronounced symptoms), of assessment of affective and cognitive disorders, monitoring of treatment effectiveness (absence of validated scales for motor skills assessment), and also showed low availability of treatment for adult patients, which requires reorganization of care of patients with SMA in the region taking into account the revealed factors).

About the authors

Arseniy Ya. Gayduk

International Centre for Education and Research in Neuropsychiatry; Research Institute for Healthcare Organization and Medical Management of Moscow Healthcare Department

Author for correspondence.
Email: a.j.gayduk@gmail.com
ORCID iD: 0000-0002-4015-3162
SPIN-code: 6119-6992
Russian Federation, Samara; Moscow

Paul Cumming

University of Bern

Email: paul.k.cumming@gmail.com
ORCID iD: 0000-0002-0257-9621
Scopus Author ID: https://www.scopus.com/authid/detail.uri?authorId=7004304659
ResearcherId: https://www.researchgate.net/profile/Paul-Cumming-2

MD, PhD, Professor

Switzerland, Bern

Viktoriya V. Chernikova

Samara State Medical University

Email: v.v.chernikova@mail.ru
ORCID iD: 0000-0002-2147-9212

ассистент кафедры неврологии и нейрохирургии

Russian Federation, Samara

Yan V. Vlasov

Samara State Medical University

Email: sams99@inbox.ru
ORCID iD: 0000-0002-9471-9088
SPIN-code: 1494-6296

MD, Dr. Sci. (Med.), Professor

Russian Federation, Samara

Dar’ya A. Smirnova

International Centre for Education and Research in Neuropsychiatry; V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology

Email: daria.smirnova.md.phd@gmail.com
ORCID iD: 0000-0002-9591-4918
SPIN-code: 8248-0194
Scopus Author ID: https://www.scopus.com/authid/detail.uri?authorId=55086067800

MD, Cand. Sci. (Med.)

Russian Federation, Samara; Saint-Petersburg

References

  1. Zabnenkova VV, Dadali EL, Polyakov AV. Proximal spinal muscular atrophy types I–IV: Specific features of molecular genetic diagnosis. Neuromuscular Diseases. 2013;(3):27–31. (In Russ).
  2. De Queiroz Campos Araujo Ap, Araujo M, Swoboda KJ. Vascular perfusion abnormalities in infants with spinal muscular atrophy // The Journal of Pediatrics. 2009;155(2):292–4. doi: 10.1016/j.jpeds.2009.01.071
  3. Kimizu T, Ida S, Okamoto K, et al. Spinal Muscular Atrophy: Diagnosis, Incidence, and Newborn Screening in Japan. International Journal of Neonatal Screening. 2021;7(3):45. doi: 10.3390/ijns7030045
  4. Sugarman EA, Nagan N, Zhu H, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. European Journal of Human Genetics. 2012;20(1):27–32. doi: 10.1038/ejhg.2011.134
  5. Singh NN, Shishimorova M, Cao LC, et al. A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy. RNA Biology. 2009;6(3):341–50. doi: 10.4161/rna.6.3.8723
  6. Brzustowicz LM, Lehner T, Castilla LH, et al. Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3. Nature. 1990;344(6266):540–1. doi: 10.1038/344540a0
  7. Oskoui M, Darras BT, DeVivo DC. Chapter 1. In: Sumner CJ, Paushkin S, Ko CP, editors. Spinal Muscular Atrophy: Disease Mechanisms. 1st ed. Academic Press; 2016.
  8. Dadali EL, Nikitin SS, Konovalov FA, et al. Spinal muscular atrophy with lower limbs phenotype: clinical and genetic description of novel mutation in the DYNC1H1 gene. Neuromuscular Diseases. 2018;8(2):59–67. (In Russ). doi: 10.17650/2222-8721-2018-8-2-59-67
  9. Mix L, Schreiber-Katz O, Wurster CD, et al. Executive function is inversely correlated with physical function: the cognitive profile of adult Spinal Muscular Atrophy (SMA). Orphanet Journal of Rare Diseases. 2021;16(1):10. doi: 10.1186/s13023-020-01661-9
  10. Zappa G, LoMauro A., Baranello G, et al. Intellectual abilities, language comprehension, speech, and motor function in children with spinal muscular atrophy type 1. Journal of Neurodevelopmental Disorders. 2021;13(1):9. doi: 10.1186/s11689-021-09355-4
  11. Rivière J. Locomotion autonome et cognition spatiale: le paradoxe de l'amyotrophie spinale infantile [Self-produced locomotion and spatial cognition: a new light from spinal muscular atrophy]. Archives de Pediatrie. 2007;14(3):279–84. (In Fr.). doi: 10.1016/j.arcped.2006.10.011
  12. Polido GJ, de Miranda MMV, Carvas N, et al. Cognitive performance of children with spinal muscular atrophy: A systematic review. Dementia & Neuropsychologia. 2019;13(4):436–43. doi: 10.1590/1980-57642018dn13-040011
  13. Masson R, Brusa C, Scoto M, et al. Brain, cognition, and language development in spinal muscular atrophy type 1: a scoping review. Developmental Medicine & Child Neurology. 2021;63(5):527–36. doi: 10.1111/dmcn.14798
  14. Young SD, Montes J, Kramer SS, et al. Perceived Fatigue in Spinal Muscular Atrophy: A Pilot Study. Journal of Neuromuscular Diseases. 2019;6(1):109–17. doi: 10.3233/JND-180342
  15. Kizina K, Akkaya Y, Jokisch D, et al. Cognitive Impairment in Adult Patients with 5q-Associated Spinal Muscular Atrophy. Brain Sciences. 2021;11(9):1184. doi: 10.3390/brainsci11091184
  16. Schmidt H, Felisatti A, von Aster M, et al. Neuromuscular Diseases Affect Number Representation and Processing: An Exploratory Study. Frontiers in Psychology. 2021;12:697881. doi: 10.3389/fpsyg.2021.697881
  17. Klinicheskiye rekomendatsii MZ RF. Proksimal’naya spinal’naya myshechnaya atrofiya 5q. 2021. Available at: https://f-sma.ru/wp-content/uploads/2020/08/klinrecsma2021.pdf. Accessed: 2022 February 14. (In Russ).
  18. Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders. 2018;28(2):103–15. doi: 10.1016/j.nmd.2017.11.005
  19. Hong J–M, Zhao M, He J, et al. Genetic screening method for analyzing survival motor neuron copy number in spinal muscular atrophy by multiplex ligation-dependent probe amplification and droplet digital polymerase chain reaction. Chinese Medical Journal. 2020;133(20):2510–1. doi: 10.1097/CM9.0000000000001102
  20. Feng Y, Ge X, Meng L, et al. The next generation of population-based spinal muscular atrophy carrier screening: comprehensive pan-ethnic SMN1 copy-number and sequence variant analysis by massively parallel sequencing. Genetics in Medicine. 2017;19(8):936–44. doi: 10.1038/gim.2016.215
  21. Lopez–Lopez D, Loucera C, Carmona R, et al. SMN1 copy-number and sequence variant analysis from next-generation sequencing data. Human Mutation. 2020;41(12):2073–7. doi: 10.1002/humu.24120
  22. Alves CCR, Zhang R, Johnstone AJ, et al. Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy. Neurology. 2020;94(9):e921–31. doi: 10.1212/WNL.0000000000008762
  23. Freigang M, Wurster CD, Hagenacker T, et al. Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment. Annals of Clinical and Translational Neurology. 2021;8(5):1049–63. doi: 10.1002/acn3.51340
  24. Yuan A, Rao MV, Veeranna, et al. Neurofilaments and Neurofilament Proteins in Health and Disease. Cold Spring Harbor Perspectives in Biology. 2017;9(4):a018309. doi: 10.1101/cshperspect.a018309
  25. Kobayashi DT, Shi J, Stephen L, et al. SMA-MAP: a plasma protein panel for spinal muscular atrophy. PLoS One. 2013;8(4):e60113. doi: 10.1371/journal.pone.0060113
  26. Kolb SJ, Coffey CS, Yankey JW, et al. Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. Annals of Clinical and Translational Neurology. 2016;3(2):132–45. doi: 10.1002/acn3.283
  27. Weng W–C, Hsu Y–K, Chang F–M, et al. CMAP changes upon symptom onset and during treatment in spinal muscular atrophy patients: lessons learned from newborn screening. Genetics in Medicine. 2021;23(2):415–20. doi: 10.1038/s41436-020-00987-w
  28. Kariyawasam D, D'Silva A, Howells J, et al. Motor unit changes in children with symptomatic spinal muscular atrophy treated with nusinersen. Journal of Neurology, Neurosurgery, and Psychiatry. 2020;92(1):78–85. doi: 10.1136/jnnp-2020-324254
  29. Durmus H, Yilmaz R, Gulsen–Parman Y, et al. Muscle magnetic resonance imaging in spinal muscular atrophy type 3: Selective and progressive involvement. Muscle & Nerve. 2017;55(5):651–6. doi: 10.1002/mus.25385
  30. Regensburger AP, Wagner AL, Hanslik G, et al. Ultra-high-frequency ultrasound in patients with spinal muscular atrophy: A retrospective feasibility study. Muscle & Nerve. 2020;61(3):E18–E21. doi: 10.1002/mus.26796
  31. Pino MG, Rich KA, Kolb SJ. Update on Biomarkers in Spinal Muscular Atrophy. Biomarker Insights. 2021;16:11772719211035643. doi: 10.1177/11772719211035643
  32. Gosudarstvennyy reyestr lekarstvennykh sredstv, 2022. Available at: https://grls.rosminzdrav.ru/Default.aspx. Accessed: 2022 February 14. (In Russ).
  33. Materialy Kruglogo stola (2021). Formirovaniye gosudarstvennykh garantiy lekarstvennogo obespecheniya patsiyentov so spinal’noy myshechnoy atrofiyey (SMA) starshe 18 let. Rossiyskaya Gazeta. 08/12/2021. Available at: https://rg.ru/2021/12/08/v-mediacentre-rg-obsudili-problemy-s-lekarstvennym-obespecheniem-pacientov-so-sma-starshe-18-let.html. Accessed: 2022 February 14. (In Russ).
  34. Waldrop MA, Karingada C, Storey MA, et al. Gene Therapy for Spinal Muscular Atrophy: Safety and Early Outcomes. Pediatrics. 2021;146(3):e20200729. doi: 10.1542/peds.2020-0729
  35. Keinath MC, Prior DE, Prior TW. Spinal Muscular Atrophy: Mutations, Testing, and Clinical Relevance. The Application of Clinical Genetics. 2021;14:11–25. doi: 10.2147/TACG.S239603

Copyright (c) 2022 Gayduk A.Y., Cumming P., Chernikova V.V., Vlasov Y.V., Smirnova D.A.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


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