Neuroimaging markers of safety of physical therapy exercises in children with muscular dystrophies

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: Muscular dystrophies are a broad and heterogeneous group of hereditary neuromuscular disorders, most commonly manifesting with primary symmetric involvement of proximal skeletal muscles in the upper and lower limbs. Patients with these disorders are at increased risk of muscle fiber damage if exercises and their intensity are inappropriately selected during physical therapy. At present, no neuroimaging markers are available to assess the safety of physical exercise in patients with inherited myopathies. Quantitative MRI criteria for detecting clinically significant changes in skeletal muscles have also not been developed.

AIM: This study aimed to evaluate the safety of physical therapy exercises in pediatric patients with muscular dystrophies using neuroimaging, clinical, and laboratory methods.

METHODS: The study included 86 patients with genetically confirmed Duchenne muscular dystrophy (mean age 7.5 ± 2.4 years) and 42 patients with limb-girdle muscular dystrophies (mean age 11.8 ± 3.3 years). All patients underwent a 4-month rehabilitation program consisting of aerobic physical therapy exercises, stretching, and cycle ergometer training. Safety was assessed using clinical, laboratory, and neuroimaging measures.

RESULTS: According to MRI findings, no statistically significant increase in T2 water signal intensity was observed after aerobic exercises without load in the major muscle groups of the pelvic and shoulder girdles, thighs, and calves in either group, indicating no progression of nonspecific inflammation or edema. All reported adverse events were mild and short-term, did not affect the rehabilitation, or require additional pharmacological or non-pharmacological treatment. Eight cases of skeletal muscle injury were observed, attributable to concentric or eccentric exercises. In the Duchenne muscular dystrophy group, the mean skeletal muscle signal intensity before exercise was 34.9 ± 1.0 ms and increased to 44.1 ± 3.7 ms during follow-up (p <0.01). In the limb-girdle muscular dystrophies group, signal intensity was 33.6 ± 2.3 ms and 44.3 ± 4.1 ms, respectively (p <0.01).

CONCLUSION: Thus, the developed rehabilitation program, which includes aerobic exercises without load, does not result in skeletal muscle damage in patients with various forms of muscular dystrophy, as confirmed by neuroimaging, clinical, and laboratory assessments. In patients with Duchenne muscular dystrophy, skeletal muscle MR signal intensity from water increased on average by 20.4 ± 5.8%, whereas in patients with limb-girdle muscular dystrophies it increased by 23.8 ± 6.3%. This increase is clinically significant and indicates skeletal muscle injury accompanied by corresponding symptoms.

Full Text

Restricted Access

About the authors

Vasily M. Suslov

St. Petersburg State Pediatric Medical University

Author for correspondence.
Email: vms.92@mail.ru
ORCID iD: 0000-0002-5903-8789
SPIN-code: 4482-9918

Suslov, MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, Saint Petersburg

Dmitry I. Rudenko

St. Petersburg State Pediatric Medical University

Email: dmrud_h2@mail.ru
ORCID iD: 0009-0008-2770-6755
SPIN-code: 8002-0690

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Gennady N. Ponomarenko

Federal Scientific and Aducational Centre of Medical and Social Expertis and Rehabilitation n. a. G.A. Albrecht

Email: ponomarenko_g@mail.ru
ORCID iD: 0000-0001-7853-4473
SPIN-code: 8234-7005

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Galina A. Suslova

St. Petersburg State Pediatric Medical University

Email: docgas@mail.ru
ORCID iD: 0000-0002-7448-762X
SPIN-code: 8110-0058

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Damir A. Malekov

St. Petersburg State Pediatric Medical University

Email: d.a.malekov@gmail.com
ORCID iD: 0000-0002-1358-4725
SPIN-code: 8804-4630
Russian Federation, Saint Petersburg

Aleksandra D. Suslova

Children's City Polyclinic No. 29, Saint Petersburg

Email: fifa379@mail.ru
ORCID iD: 0009-0009-4979-1951
Russian Federation, Saint Petersburg

References

  1. Angelini C. LGMD. Identification, description and classification. Acta Myol. 2020;39(4):207–217. doi: 10.36185/2532-1900-024
  2. Bouchard C, Tremblay JP. Limb-Girdle Muscular Dystrophies Classification and Therapies. J Clin Med. 2023;12(14):4769. doi: 10.3390/jcm12144769
  3. Romitti PA, Zhu Y, Puzhankara S, et al Prevalence of Duchenne and Becker muscular dystrophies in the United States. Pediatrics. 2015;135(3):513–521. doi: 10.1542/peds.2014-2044
  4. Salari N, Fatahi B, Valipour E, et al. Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis. J Orthop Surg Res. 2022;17(1):96. doi: 10.1186/s13018-022-02996-8
  5. Liu W, Pajusalu S, Lake NJ, et al. Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases. Genet Med. 2019;21(11):2512–2520. doi: 10.1038/s41436-019-0544-8
  6. Shnayder NA, Nikolayeva TYa, Boroeva EN, et al. Autosomal dominant limb-girdle muscular dystrophy: Leyden–Möbius pelvifemoral form. Neuromuscular diseases. 2013;(1):46–62. EDN: PXJIDL
  7. Johnson NE, Statland JM. The Limb-Girdle Muscular Dystrophies. Continuum (Minneap Minn). 2022;28(6):1698–1714. doi: 10.1212/CON.0000000000001178
  8. Sidorova OP, Kotov AS, Bunak MS, Filyushkin YuN. New classification of limb-girdle muscular dystrophy. Neuromuscular diseases. 2022;12(3):10–16. doi: 10.17650/2222-8721-2022-12-3-10-16 EDN: LSCMFN
  9. Suslov VM, Ivanov DO, Rudenko DI, Liberman LN, Suslova GA. Clinical case, disease course dynamics in a patient with Emery–Dreifuss muscular dystrophy caused by a mutation in the SYNE2 gene. Pediatr. 2024;15(6):83–91. (In Russ.) doi: 10.17816/PED15583-91
  10. Narasimhaiah D, Uppin MS, Ranganath P. Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update. Indian J PatholMicrobiol. 2022;65(Suppl):S259–S270. doi: 10.4103/ijpm.ijpm_1074_21
  11. Tawil R. Facioscapulohumeral muscular dystrophy. Handb Clin Neurol. 2018;148:541–548. doi: 10.1016/B978-0-444-64076-5.00035-1
  12. Younger DS. Childhood muscular dystrophies. Handb Clin Neurol. 2023;195:461–496. doi: 10.1016/B978-0-323-98818-6.00024-8
  13. Kitaeva VE, Kotov AS, Bunak MS. Progressive Muscle Dystrophies. Russian Neurological Journal. 2021;26(2):43–57.
  14. Suslov VM, Lieberman LN, Ponomarenko GN, et al. Safety markers for isotonic exercises without weights in hereditary myopathies. Fizicheskaya i reabilitacionnaya medicina. 2023;5(4):18–27. doi: 10.26211/2658-4522-2023-5-4-18-27 EDN: EFIAZH
  15. Birnkrant DJ, Bushby K, Bann CM, et al.; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251–267. doi: 10.1016/S1474-4422(18)30024-3
  16. Jackson MJ, Round JM, Newham DJ, Edwards RH. An examination of some factors influencing creatine kinase in the blood of patients with muscular dystrophy. Muscle Nerve. 1987;10(1):15–21. doi: 10.1002/mus.880100105
  17. Mao B, Xiong H, Jiao H, et al. Value of muscle enzyme analysis in differential diagnosis of childhood myopathic hyper-creatine kinase-emia. Beijing Da Xue Xue Bao Yi Xue Ban. 2014;46(1):130–7. (In Chinese).
  18. Zhu Y, Zhang H, Sun Y, et al. Serum Enzyme Profiles Differentiate Five Types of Muscular Dystrophy. Dis Markers. 2015;2015:543282. doi: 10.1155/2015/543282
  19. Bekkelund SI. Leisure physical exercise and creatine kinase activity. The Tromsø study. Scand J Med Sci Sports. 2020;30(12):2437–2444. doi: 10.1111/sms.13809
  20. Koch AJ, Pereira R, Machado M. The creatine kinase response to resistance exercise. J Musculoskelet Neuronal Interact. 2014;14(1):68–77.
  21. Azzabou N, Loureiro de Sousa P, Caldas E, Carlier PG. Validation of a generic approach to muscle water T2 determination at 3T in fat-infiltrated skeletal muscle. J Magn Reson Imaging. 2015;41(3): 645–53. doi: 10.1002/jmri.24613
  22. Marty B, Baudin PY, Reyngoudt H, et al. Simultaneous muscle water T2 and fat fraction mapping using transverse relaxometry with stimulated echo compensation. NMR Biomed. 2016;29(4):431–43. doi: 10.1002/nbm.3459
  23. Moore U, Caldas de Almeida Araújo E, Reyngoudt H, et al. Water T2 could predict functional decline in patients with dysferlinopathy. J Cachexia Sarcopenia Muscle. 2022;13(6):2888–2897. doi: 10.1002/jcsm.13063
  24. Lott DJ, Taivassalo T, Senesac CR, et al. Walking activity in a large cohort of boys with Duchenne muscular dystrophy. Muscle Nerve. 2021;63(2):192–198. doi: 10.1002/mus.27119
  25. McMillan HJ, Gregas M, Darras BT, Kang PB. Serum transaminase levels in boys with Duchenne and Becker muscular dystrophy. Pediatrics. 2011;127(1):e132–6. doi: 10.1542/peds.2010-0929
  26. Rodríguez-Cruz M, Almeida-Becerril T, Atilano-Miguel S, et al. Natural History of Serum Enzyme Levels in Duchenne Muscular Dystrophy and Implications for Clinical Practice. Am J Phys Med Rehabil. 2020;99(12):1121–1128. doi: 10.1097/PHM.0000000000001500
  27. 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(Pt 3):983–1000. doi: 10.1113/jphysiol.2003.056598
  28. Dombernowsky NW, Ölmestig JNE, Witting N, Kruuse C. Role of neuronal nitric oxide synthase (nNOS) in Duchenne and Becker muscular dystrophies — Still a possible treatment modality? Neuromuscul Disord. 2018;28(11):914–926. doi: 10.1016/j.nmd.2018.09.001
  29. Brancaccio P, Maffulli N, Limongelli FM. Creatine kinase monitoring in sport medicine. Br Med Bull. 2007;81–82:209–30. doi: 10.1093/bmb/ldm014
  30. Bellinger AM, Reiken S, Carlson C, et al. Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med. 2009;15(3):325–30. doi: 10.1038/nm.1916
  31. Flanigan KM. Duchenne and Becker muscular dystrophies. Neurol Clin. 2014;32(3):671–88, viii. doi: 10.1016/j.ncl.2014.05.002
  32. Andersen SP, Sveen ML, Hansen RS, et al. Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy. Muscle Nerve. 2013;48(6):897–901. doi: 10.1002/mus.23846
  33. Totsuka M, Nakaji S, Suzuki K, Sugawara K, Sato K. Break point of serum creatine kinase release after endurance exercise. J Appl Physiol (1985). 2002;93(4):1280–6. doi: 10.1152/japplphysiol.01270.2001
  34. Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021;7(1):13. doi: 10.1038/s41572-021-00248-3

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Mean T2 water signal intensity values in the pelvic and shoulder girdle, thigh, and calf muscles of patients with Duchenne muscular dystrophy before and after physical therapy exercise. On the x-axis: “1”, values before training, “2”, values after training.

Download (89KB)
Indexing metadata
3. Fig. 2. Mean T2 water signal intensity values in the pelvic and shoulder girdle, thigh, and calf muscles of patients with limb-girdle muscular dystrophy before and after physical therapy exercise. On the x-axis: “1”, values before training, “2”, values after training.

Download (98KB)
Indexing metadata
4. Fig. 3. T2 water signal intensity changes in patients with Duchenne muscular dystrophy.

Download (36KB)
Indexing metadata
5. Fig. 4. T2 water signal intensity changes in patients with limb-girdle muscular dystrophies.

Download (36KB)
Indexing metadata
6. Fig. 5. MRI images of the right thigh muscles of a 9-year-7-month-old patient with Duchenne muscular dystrophy before exercise (images 1) and during follow-up after concentric exercises (images 2): A, MSME images (TE = 80 ms) with selective extraction of T2 water signal (wT2); B, STIR images (TE = 60 ms).

Download (101KB)
Indexing metadata
7. Fig. 6. MRI images of the right shoulder muscles of a 17-year-old patient with limb-girdle muscular dystrophy type 2A before exercise (images 1) and during follow-up (images 2): A, MSME images (TE = 80 ms) with selective extraction of T2 water signal (wT2); B, STIR images (TE = 60 ms).

Download (118KB)
Indexing metadata

Copyright (c) 2025 Eco-Vector

License URL: https://eco-vector.com/for_authors.php#07
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 86508 от 11.12.2023. 
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ЭЛ № ФС 77 - 80650 от 15.03.2021 г.