Safety markers for isotonic exercises without weights in hereditary myopathies

Authors:

Suslov Vasily Mikhailovich — PhD in Medical Sciences (Cand. Med. Sci.), Associate Professor of the Department of Rehabilitation, Federal State Budgetary Educational Institution of Higher Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of the Russian Federation, 2 Litovskaya Street, 194100 St. Petersburg, Russian Federation; e-mail: vms.92@mail.ru; https://orcid.org/0000-0002-5903-8789.

Liberman Larisa Nikolaevna — assistant at the Department of Rehabilitation, Federal State Budgetary Educational Institution of Higher Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of the Russian Federation, 2 Litovskaya Street, 194100 St. Petersburg, Russian Federation; e-mail: lalieber74@gmail.com; https://orcid.org/0009-0002-5791-6872.

Ponomarenko Gennadiy Nikolaevich — ^responding Member of the Russian Academy of Sciences, Honored Scientist of the Russian Federation, Grand PhD in Medical sciences (Dr. Med. Sci), Professor, Director General of the Albrecht Federal Scientific and Educational Centre of Medical and Socia Expertise and Rehabilitation, 50 Bestuzhevskaya Street, 195067 St. Petersburg, Russian Federation; Head of the Department of Physical and Rehabilitation Medicine of the North-Western State Medical University named after I.I. Mechnikov, 47 Piskarevskiy Ave., 195067 St. Petersburg, Russian Federation; e-mail: ponomarenko_g@mail.ru; https://orcid.org/0000-0001-7853-4473.

Rudenko Dmitry Igorevich — Grand PhD in Medical Sciences (Dr. Med. Sci.), assistant of the Department of Rehabilitation, Federal State Budgetary Educational Institution of Higher Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of the Russian Federation, 2 Litovskaya Street, 194100 St. Petersburg, Russian Federation; e-mail: dmrud_h2@mail.ru; https://orcid.org/0009-0008-2770-6755.

Suslova Galina Anatolyevna — Grand PhD in Medical Sciences (Dr. Med. Sci.), professor, Head of the Department of Rehabilitation, Federal State Budgetary Educational Institution of Higher Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of the Russian Federation, 2 Litovskaya Street, 194100 St. Petersburg, Russian Federation; e-mail: docgas@mail.ru; https://orcid.org/0000-0002-7448-762X.

Rostacheva Elena Aleksandrovna — assistant at the Department of Rehabilitation, Federal State Budgetary Educational Institution of Higher Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of the Russian Federation, 2 Litovskaya Street, 194100 St. Petersburg, Russian Federation; e-mail: ele-ova@yandex.ru; https://orcid.org/0009-0007-6909-1923.

Annotation:

Introduction. Hereditary myopathies are a large heterogeneous group of neuromuscular diseases characterized by disturbances in the metabolism and structure of muscle fibers. Currently, there are limited data and isolated studies on the effectiveness and safety of various training programs for this group of diseases. Incorrectly dosed physical activity can lead to damage to skeletal muscles and progression of the disease.

Aim. To evaluate the information content of instrumental and biochemical markers of the safety of a complex of isotonic exercises performed without weights using biochemical and clinical markers of skeletal muscle damage.

Materials and methods. A total of 31 patients with hereditary myopathies were examined, including Duchenne and Becker muscular dystrophy and congenital nemaline myopathy. All patients performed a set of developed exercises 3 times a week for 4 months. An examination was done to assess safety criteria.

Results. According to the results obtained, in all control groups an increase in the activity of creatine kinase and lactate dehydrogenase were detected after training (p<0.05). But according to muscle MRI, no statistically significant changes before and after training in the MR signal were detected in all the studied muscles of the pelvic girdle and thighs in all patient groups. During the rehabilitation course, no clinically significant adverse events were recorded in the group of patients with Duchenne muscular dystrophy; all identified events correspond to the natural course of the disease.

Discussion. Despite the detected increase in enzyme activity in the venous blood after the training, MRI data of skeletal muscles did not demonstrate statistically significant changes, which indicates the absence of an active inflammatory process and negative dynamics at the time of the study, which indicates good tolerability of the physical exercises performed.

Summary. Thus, we can conclude that it is impossible to use creatine kinase and lactate dehydrogenase as isolated markers of negative dynamics when assessing the effect of physical activity on patients with hereditary myopathies. The developed complex of physical exercises performed on patients does not lead to clinically significant negative dynamics and is safe based on data from clinical, laboratory and instrumental markers.

List of cited literature:

1. Cardamone M, Darras BT, Ryan MM. Inherited myopathies and muscular dystrophies. SeminNeurol. 2008;2:250-9. DOI: 10.1055/s-2008-1062269.

2. Emery AE. The muscular dystrophies. Lancet. 2002; 359(9307):687-95. DOI: 10.1016/S0140-6736(02)07815-7.

3. Bimkrant DJ, Bushby K, Bann CM, Apkon Sd et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018; 17(3):251-67. DOI: 10.1016/S1474-4422(18)30024-3.

4. Sussman M. Duchenne muscular dystrophy. The Journal of the American Academy of Orthopaedic Surgeons 2002; 10: 138-51.

5. Flanigan KM. Duchenne and Becker muscular dystrophies. Neurol Clin. 2014;32(3):671-88. DOI: 10.1016/j.ncl.2014.05.002.

6. Domingos J, Sarkozy A, Scoto M, Muntoni F. Dystrophinopathies and Limb-Girdle Muscular Dystrophies. Neuropediatrics. 2017;48(4):262-72. DOI: 10.1055/s-0037-1601860.

7. Tawil R. Facioscapulohumeral muscular dystrophy. Handb Clin Neurol. 2018;148:541-8. DOI: 10.1016/B978-0-444-64076-5.00035-1.

8. Romero NB, Clarke NF. Congenital myopathies. Handb Clin Neurol. 2013;113:1321-36. DOI: 10.1016/B978-0-444-59565-2.00004-6.

9. Kazakov VM, Rudenko DI, Stuchevskaya TR, Kolinin VO. Vrozhdennye miopatii. Obzor kliniko-geneticheskih i morfologicheskih osobennostej otdelnyh form [Congenital myopathies. Review of clinical, genetic and morphological features of individual forms]. Nevrologicheskij zhurnal [Neurological Journal]. 2018;23(1):9-15. DOI: 10.18821/1560-9545-2018-23-1-9-15. (In Russian).

10. Shieh PB. Muscular dystrophies and other genetic myopathies. Neurol Clin. 2013;31(4):1009-29. DOI: 10.1016/j.ncl.2013.04.004.

11. Narasimhaiah D, Uppin MS, Ranganath P. Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update. Indian J PatholMicrobiol. 2022;65:259-70. DOI: 10.4103/ijpm.ijpm_1074_21.

12. Voet NB, van der Kooi EL, Riphagen II, Lindeman E et al. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2013;(7):CD003907. DOI: 10.1002/14651858.CD003907.pub4.

13. Cruz-Guzman OR. Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status. Biomed. Res. Int. 2015: 891-972.

14. Deconinck, N. Pathophysiology of Duchenne muscular dystrophy: current hypotheses. Pediatr. Neurol. 2007;36(1):1-7.

15. McMillan HJ, Gregas M, Darras BT, Kang PB. Serum transaminase levels in boys with Duchenne and Becker muscular dystrophy. Pediatrics. 2011;127(1):132-6. DOI: 10.1542/peds.2010-0929.

16. Rodriguez-Cruz M, Almeida-Becerril T, Atilano-Miguel S, Cardenas-Conejo A et al. Natural History of Serum Enzyme Levels in Duchenne Muscular Dystrophy and Implications for Clinical Practice. Am J PhysMedRehabil. 2020;99(12):1121-8. DOI: 10.1097/PHM.0000000000001500.

17. Malm C, Sjodin TL, Sjoberg B et al. Leukocytes, cytokines, growth factors and hormones in human skeletal muscle and blood after uphill or downhill running. J Physiol, 2004;556:983-1000.

18. Brancaccio P, Maffulli N, Limongelli FM. Creatine kinase monitoring in sport medicine. BrMed Bull. 2007;209:81-2. DOI: 10.1093/bmb/ldm014.

19. Andersen SP, Sveen ML, Hansen RS, Madsen KL et al. Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy. MuscleNerve. 2013;48(6):897-901. DOI: 10.1002/mus.23846.

20. Totsuka M, Nakaji S, Suzuki K, Sugawara K et al. Break point of serum creatine kinase release after endurance exercise. J ApplPhysiol. 2002;93(4): 1280-6. DOI: 10.1152/japplphysiol.01270.2001.

21. Hathout Y, Seol H, Han MH, Zhang A et al. Clinical utility of serum biomarkers in Duchenne muscular dystrophy. ClinProteomics. 2016;13:9. DOI: 10.1186/s12014-016-9109-x.

22. Kim EY, Lee JW, Suh MR, Choi WA et al. Correlation of Serum Creatine Kinase Level With Pulmonary Function in Duchenne Muscular Dystrophy. Ann Rehabil Med. 2017;41(2):306-12. DOI: 10.5535/arm.2017.41.2.306.

23. Zygmunt AM, Wong BL, Horn PS, Lambert J et al. A longitudinal study of creatine kinase and creatinine levels in Duchenne muscular dystrophy. MuscleNerve. 2023;67(2):138-45. DOI: 10.1002/mus.27760.

24. Mankodi A, Azzabou N, Bulea T, Reyngoudt H et al. Skeletal muscle water T2 as a biomarker of disease status and exercise effects in patients with Duchenne muscular dystrophy. NeuromusculDisord. 2017;27(8):705-14. DOI: 10.1016/j.nmd.2017.04.008.

25. Suslov VM, Suslova GA, Lytaev SA. Clinical and MRI markers of muscles damage in ambulant and non-ambulant DMD patients. Archives of Physical Medicine and Rehabilitation. 2022;103(3):18. DOI: 10.1016/j.apmr.2022.01.049.

26. Suslov VM, Suslova GA, Lytaev SA. MRI assessment of motor capabilities in patient with Duchenne muscular dystrophy according to the Motor Function Measure scale. Tomography. 2022;8(2):948-60. DOI: 10.3390/tomography8020076.