Skip to main content

Advertisement

SpringerLink
Log in

Strictly monitored exercise programs reduce motor deterioration in ALS: preliminary results of a randomized controlled trial

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The objective of our study was to perform a randomized controlled trial (RCT) aimed to evaluate the effects of three strictly monitored exercise programs (SMEP) compared to “usual care” (UCP) in a cohort of ALS patients. We included patients with definite and probable ALS and disease duration ≤24 months. Patients were randomized to receive a SMEPs or a UCP. SMEPs included three subgroups of treatment: active exercises associated with cycloergometer activity (1A), only active (1B) and passive (1C) exercises, respectively. Moreover, SMEP patients and their caregivers were trained to a daily home-based passive exercise program. The UCP group was treated with passive and stretching exercises twice weekly. The treatment period for both groups was 6 months (T180), and patients were assessed by revised ALS Functional Rating Scale (ALSFRS-R),  % Forced Vital Capacity (FVC %), and McGill Quality of Life (MGQoL) questionnaire. ALSFRS-R score was also evaluated at 6 months after the treatment period (T360). Sixty ALS patients were randomly assigned to one of two arms: SMEP Group included 30 patients, ten subjects for each subgroup (1A, 1B, and 1C); 30 patients were included in the UCP Group. At T180 and T360, SMEPs group had significantly higher ALSFRS-R score compared to the UCP group (32.8 ± 6.5 vs 28.7 ± 7.5, p = 0.0298; 27.5 ± 7.6 vs 23.3 ± 7.6, p = 0.0338, respectively). No effects of SMEPs on survival, respiratory decline and MGQol were found. In conclusion, although no effect on survival was demonstrated, our data suggest that a strictly monitored exercise program may significantly reduce motor deterioration in ALS patients.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brooks BR, Sanjak M, Belden D, Juhasz-Poscine K, Waclawik A (2000) Natural history of amyotrophic lateral sclerosis. In: Brown RHJ, Meininger V, Swash M (eds) Amyotrophic lateral sclerosis. Dunitz, London, pp 31–58

    Google Scholar 

  2. Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7:710–723

    Article  CAS  PubMed  Google Scholar 

  3. Logroscino G, Traynor BJ, Hardiman O, Chio’ A, Couratier P, Mitchell JD, Swingler RJ, Beghi E (2008) Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry 79:6–11

    Article  CAS  PubMed  Google Scholar 

  4. Wijesekera LC, Leigh PN (2009) Amyotrophic lateral sclerosis. Orphanet J Rare Dis 4:3

    Article  PubMed Central  PubMed  Google Scholar 

  5. Swash M, Desai J (2000) Motor neuron disease: classification and nomenclature. Amyotroph Lateral Scler Other Motor Neuron Disord 1:105–112

    Article  CAS  PubMed  Google Scholar 

  6. Cleveland DW, Rothstein JD (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2:806–819

    Article  CAS  PubMed  Google Scholar 

  7. Sreedharan J, Brown RH Jr (2013) Amyotrophic lateral sclerosis: problems and prospects. Ann Neurol 74:309–316. doi:10.1002/ana.24012.Review

    Article  CAS  PubMed  Google Scholar 

  8. Carter GT, Joyce NC, Abresch AL, Smith AE, VandeKeift GK (2012) Using palliative care in progressive neuromuscular disease to maximize quality of life. Phys Med Rehabil Clin N Am 23:903–909. doi:10.1016/j.pmr.2012.08.002 (epub 2012 Oct 17 review)

    Article  PubMed  Google Scholar 

  9. Prell T, Grosskreutz J (2013) The involvement of the cerebellum in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 14:507–515. doi:10.3109/21678421.2013.812661

    Article  CAS  PubMed  Google Scholar 

  10. Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, Nieman DC, Swain DP, American College of Sports Medicine (2011) American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 43:1334–1359

    Article  PubMed  Google Scholar 

  11. Serfass RC, Gerberich SG (1984) Exercise for optimal health: strategies and motivational considerations. Prev Med 13:79–99

    Article  CAS  PubMed  Google Scholar 

  12. American College of Sports Medicine, Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg CR, Salem GJ, Skinner JS (2009) American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc 41:1510–1530

    Article  Google Scholar 

  13. Seron P, Lanas F, Pardo Hernandez H, Bonfill Cosp X (2014) Exercise for people with high cardiovascular risk. Cochrane Database Syst Rev 13(8):CD009387

    Google Scholar 

  14. Svensson M, Lexell J, Deierborg T (2014) Effects of physical exercise on neuroinflammation, neuroplasticity, neurodegeneration, and behavior: what we can learn from animal models in clinical settings. Neurorehabil Neural Repair 29:577–589. doi:10.1177/1545968314562108 epub 2014 Dec 19

    Article  PubMed  Google Scholar 

  15. Van Praag H, Fleshner M, Schwartz MW, Mattson MP (2014) Exercise, energy intake, glucose homeostasis, and the brain. J Neurosci 12(34):15139–15149

    Article  Google Scholar 

  16. Mahoney DJ, Rodriguez C, Devries M, Yasuda N, Tarnopolsky MA (2004) Effects of high-intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis. Muscle Nerve 29:656–662

    Article  PubMed  Google Scholar 

  17. Scarmeas N, Shih T, Stern Y, Ottman R, Rowland LP (2002) Premorbid weight, body mass, and varsity athletics in ALS. Neurology 59:773–775

    Article  CAS  PubMed  Google Scholar 

  18. Chio A, Benzi G, Dossena M, Mutani R, Mora G (2005) Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 128:472–476

    Article  PubMed  Google Scholar 

  19. Drory VE, Goltsman E, Reznik JG, Mosek A, Korczyn AD (2001) The value of muscle exercise in patients with amyotrophic lateral sclerosis. J Neurol Sci 191:133–137

    Article  CAS  PubMed  Google Scholar 

  20. Dal Bello-Haas VD, Florence JM, Kloos AD, Scheirbecker J, Lopate G, Hayes SM, Pioro EP, Mitsumoto H (2007) A randomized controlled trial of resistance exercise in individuals with ALS. Neurology 68:2003–2007

    Article  PubMed  Google Scholar 

  21. Dal Bello-Haas V, Florence JM (2013) Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Rev 5:CD005229

    PubMed  Google Scholar 

  22. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21

    Article  CAS  PubMed  Google Scholar 

  23. Cohen SR, Mount BM, Strobel MG, Bui F (1995) The McGill Quality of Life Questionnaire: a measure of quality of life appropriate for people with advanced disease. A preliminary study of validity and acceptability. Palliat Med 9:207–219

    Article  CAS  PubMed  Google Scholar 

  24. Franchignoni F, Mora G, Giordano A, Volanti P, Chiò A (2013) Evidence of multidimensionality in the ALSFRS-R Scale: a critical appraisal on its measurement properties using Rasch analysis. J Neurol Neurosurg Psychiatry 84:1340–1345

    Article  PubMed  Google Scholar 

  25. Munsat TL (1980) Commentary. In: Mulder DW (ed) The diagnosis and treatment of amyotrophic lateral sclerosis. Houghton Mifflin, Boston, pp 214–215

    Google Scholar 

  26. Bennett RL, Knowlton GC (1958) Overwork weakness in partially denervated skeletal muscle. Clin Orthop 12:711–715

    Google Scholar 

  27. Johnson EW, Braddom R (1971) Overwork weakness in facioscapulohumeral muscular dystrophy. Arch Phys Med Rehabil 52:333–336

    CAS  PubMed  Google Scholar 

  28. Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700

    Article  CAS  PubMed  Google Scholar 

  29. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Speizer FE, Willett WC (1994) A prospective study of family history and the risk of colorectal cancer. N Engl J Med 331:1669–1674

    Article  CAS  PubMed  Google Scholar 

  30. Boillee S, Van de Velde C, Cleveland DW (2006) ALS: a disease of motor neurons and their non neuronal neighbors. Neuron 52:39–59

    Article  CAS  PubMed  Google Scholar 

  31. Ilieva H, Polymenidou M, Cleveland DW (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 187:761–772

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156:65–72

    Article  CAS  PubMed  Google Scholar 

  33. Krasnianski A, Deschauer M, Neudecker S, Gellerich FN, Müller T, Schoser BG, Krasnianski M, Zierz S (2005) Mitochondrial changes in skeletal muscle in amyotrophic lateral sclerosis and other neurogenic atrophies. Brain 128:1870–1876

    Article  PubMed  Google Scholar 

  34. Dupuis L, Gonzalez de Aguilar JL, Echaniz-Laguna A, Loeffler JP (2006) Mitochondrial dysfunction in amyotrophic lateral sclerosis also affects skeletal muscle. Muscle Nerve 34:253–254

    Article  PubMed  Google Scholar 

  35. Aguirre T, Van Den Bosch L, Goetschalckx K, Tilkin P, Mathijs G, Cassiman JJ, Robberecht W (1998) Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress. Ann Neurol 43:452–457

    Article  CAS  PubMed  Google Scholar 

  36. McEachern G, Kassovska-Bratinova S, Raha S, Tarnopolsky MA, Turnbull J, Bourgeois J, Robinson B (2000) Manganese superoxide dismutase levels are elevated in a proportion of amyotrophic lateral sclerosis patient cell lines. Biochem Biophys Res Commun 273:359–363

    Article  CAS  PubMed  Google Scholar 

  37. Cova E, Cereda C, Galli A, Curti D, Finotti C, Di Poto C, Corato M, Mazzini G, Ceroni M (2006) Modified expression of Bcl-2 and SOD1 proteins in lymphocytes from sporadic ALS patients. Neurosci Lett 399:186–190

    Article  CAS  PubMed  Google Scholar 

  38. Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S, Belia S, Wannenes F, Nicoletti C, Del Prete Z et al (2008) Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab 8:425–436

    Article  CAS  PubMed  Google Scholar 

  39. Wong M, Martin LJ (2010) Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice. Hum Mol Genet 19:2284–2302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Dupuis L, Gonzalez de Aguilar JL, Echaniz-Laguna A, Eschbach J, Rene F, Oudart H, Halter B, Huze C, Schaeffer L, Bouillaud F et al (2009) Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons. PLoS One 4:e5390

    Article  PubMed Central  PubMed  Google Scholar 

  41. Zhou J, Yi J, Fu R, Liu E, Siddique T, Ríos E, Deng HX (2010) Hyperactive intracellular calcium signaling associated with localized mitochondrial defects in skeletal muscle of an animal model of amyotrophic lateral sclerosis. J Biol Chem 285:705–712

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Léger B, Vergani L, Sorarù G, Hespel P, Derave W, Gobelet C, D’Ascenzio C, Angelini C, Russell AP (2006) Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1. FASEB J 20:583–585

    PubMed  Google Scholar 

  43. Lunetta C, Serafini M, Prelle A, Magni P, Dozio E, Ruscica M, Sassone J, Colciago C, Moggio M, Corbo M, Silani V (2012) Impaired expression of insulin-like growth factor-1 system in skeletal muscle of amyotrophic lateral sclerosis patients. Muscle Nerve 45:200–208

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Chen GQ, Mou CY, Yang YQ, Wang S, Zhao ZW (2011) Exercise training has beneficial anti-atrophy effects by inhibiting oxidative stress-induced MuRF1 up regulation in rats with diabetes. Life Sci 89:44–49

    Article  CAS  PubMed  Google Scholar 

  45. Carilho R, de Carvalho M, Swash M, Pinto S, Pinto A, Costa J (2014) Vascular endothelial growth factor and amyotrophic lateral sclerosis: the interplay with exercise and noninvasive ventilation. Muscle Nerve 49:545–550

    Article  PubMed  Google Scholar 

  46. Pupillo E, Messina P, Giussani G et al (2014) Physical activity and amyotrophic lateral sclerosis: a European population-based case-control study. Ann Neurol. 75:708–716

    Article  PubMed  Google Scholar 

  47. Veldink JH, Bar PR, Joosten EAJ, Otten M, Wokke JH, van den Berg LH (2003) Sexual differences in onset of disease and response to exercise in a transgenic model of ALS. Neuromusc Disord 13:737–743

    Article  CAS  PubMed  Google Scholar 

  48. Liebetanz D, Hagemann K, von Lewinski F, Kahler E, Paulus W (2004) Extensive exercise is not harmful in amyotrophic lateral sclerosis. Eur J Neurosci 20:3115–3120

    Article  PubMed  Google Scholar 

  49. Veldink JH, Kalmijn S, Groeneveld GJ, Titulaer MJ, Wokke JH, van den Berg LH (2005) Physical activity and the association with sporadic ALS. Neurology 64:241–245

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank our patients and their caregivers for the support to our study. We are grateful to Zevi’s family for having supported the study.

Author information

Author notes

    Authors and Affiliations

    1. NEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Niguarda Ca‘ Granda Hospital, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy

      Christian Lunetta, Andrea Lizio, Valeria A. Sansone, Eleonora Maestri, Massimo Bettinelli, Valentina Gatti & Mario Giovanni Melazzini

    2. Neurorehabilitation Unit, University of Milan, Milan, Italy

      Valeria A. Sansone

    3. Department of Neurorehabilitation Sciences, Italian Auxologico Institute IRCCS, Milan, Italy

      Nadia Maria Cellotto

    4. Department of Neurology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

      Giovanni Meola

    5. Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy

      Massimo Corbo

    Authors
    1. Christian Lunetta
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Andrea Lizio
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Valeria A. Sansone
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Nadia Maria Cellotto
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Eleonora Maestri
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Massimo Bettinelli
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Valentina Gatti
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Mario Giovanni Melazzini
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Giovanni Meola
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Massimo Corbo
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Christian Lunetta.

    Ethics declarations

    Conflicts of interest

    The authors report no conflicts of interest relevant to the manuscript. The authors alone are responsible for the content and writing of the paper.

    Ethical standard

    The study procedures were approved by our Institutional Review Board according to ethical principles and guidelines for the protection of human subjects for research.

    Additional information

    C. Lunetta and A. Lizio contributed equally to the manuscript.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Lunetta, C., Lizio, A., Sansone, V.A. et al. Strictly monitored exercise programs reduce motor deterioration in ALS: preliminary results of a randomized controlled trial. J Neurol 263, 52–60 (2016). https://doi.org/10.1007/s00415-015-7924-z

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00415-015-7924-z

    Keywords

    Search

    Navigation