Myasthenia Gravis: History
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Subjects: Pathology | Sport Sciences
Contributor:
Bruno Corrado
,
Benedetto Giardulli
,
Massimo Costa

Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness and fatigue. The cause is a postsynaptic defect of neuromuscular transmission, which brings, in the majority of patients, to develop autoantibodies directed against the postsynaptic nicotinic acetylcholine receptor (AChR).

  • congenital myasthenic syndromes
  • muscle weakness
  • myasthenia gravis
  • neuromuscular junction
  • physical therapy modalities
  • rehabilitation
  • neurology

1. Introduction

The annual incidence of MG is 8–10 cases per 1 million persons and its prevalence is 150–250 cases per 1 million persons [1]. MG can affect people of any age, typically starting in women under 40 and men over 60. Muscle specific kinase myasthenia gravis (MuSK-MG) is a rare subgroup of MG affecting mainly women during childbearing years [2].

2. Clinical Manifestation

The clinical manifestation of MG is weakness of skeletal muscles, which increases with fatigue and during the day, often with nearly normal muscle strength in the morning. The muscular weakness can be localized or generalized, and usually is more proximal than distal [3]. Eye and oropharyngeal muscles are often affected, but the distribution of muscle weakness is highly variable [4]. Muscle weakness causes common symptoms of MG that include: fatigue, breathing difficulties, ptosis, diplopia, hypomimia, problems with chewing and swallowing, and dysarthria. Myasthenic crisis is a complication of MG characterized by worsening of muscle weakness, resulting in respiratory failure that requires intubation and mechanical ventilation. MG and thymic neoplasms are frequently associated; one half of cortical thymoma patients develop MG, while 15% of MG patients have thymomas [5][6]. MG has an extensive impact on physical, psychological, and social wellbeing of the patients, causing a reduced health related quality of life (HRQoL): the more severe muscle symptoms and disability, the lower the physical components of the outcome [7][8][9][10].

3. Diagnosis

The diagnostic approach to MG can be difficult and is focused on confirming the clinical diagnosis established by the history and typical examination findings. Point-of-care tests (the ice pack test, alone or combined with sustained upgaze, and the edrophonium test) are sensitive, but they have major limitations due to concerns about excess false-positive results [11]. The most reliable laboratory methods that aid in the confirmation are serologic tests for autoantibodies and electrophysiological studies (repetitive nerve stimulation—RNS, and single-fiber electromyography—SFEMG). MG can be classified in the following main subgroups defined on the basis of clinical, antibody, and thymic features: late onset, early onset, ocular, seronegative, thymoma, lipoprotein receptor–related protein 4 (LRP4), and MuSK [12]. According to the Osserman and Genkins classification, the clinical severity of MG is graded in five stages (I, ocular signs only; IIA, generalized mild muscle weakness; IIB, generalized moderate weakness and/or bulbar dysfunction; III, acute fulminating presentation and/or respiratory dysfunction; IV, late generalized weakness) [13].

4. Medical Treatment and Rehabilitation

Treatment of MG includes acetylcholinesterase inhibitors (e.g., pyridostigmine, edrophonium, and ephedrine), thymectomy, immunosuppressive agents (e.g., prednisone, azathioprine, rituximab, tocilizumab, and mycophenolate mofetil), and short-term immunomodulation with plasma-exchange and intravenous immunoglobulin (IVIG) [14][15][16][17][18].

Rehabilitation is defined as “a set of measures that assist individuals who experience disability to achieve and maintain optimal physical, sensory, intellectual, psychological and social functioning in interaction with their environment” (World Health Organization. World Report on Disability. Geneva, Switzerland: WHO; 2011). It is a complex process of delivering a coordinated interdisciplinary care program, comprising a series of individualized and goal-oriented therapies tailored for specific patient needs. The goal of rehabilitation is to improve functional independence and enhance participation with emphasis on patient education and self-management. In neuromuscular disorders, an effective rehabilitation program can help maximize the patient’s physical and psychosocial functions as well as maintain a patient’s quality of life [19][20][21][22]. Furthermore, an effective rehabilitation program can minimize secondary medical comorbidities, prevent or limit physical deformities, and allow the patient to integrate into society [23][24][25][26].

According to experts’ recommendations, rehabilitation is essential in the management of possible MG complications such as contractures and respiratory failure [27]. However, it is well known that typical MG weakness increases with exercise and repetitive muscle use [28]. It follows that it is not clear whether exercise is beneficial or harmful for patients with MG. Therefore, the role of exercise in the management of these patients remains controversial [29][30]. Because muscle weakness is the main problem, muscular exercise would be valuable if it helped to counteract the loss of muscle tissue and strength.

Respiratory training has proven to be a very effective approach in the management of fatigable weakness and respiratory failure, both of which strongly limit the performance of daily activities in people with MG[13][31][32][33][34][35][36][37][38]. The benefits of respiratory training included not only a measurable improvement in respiratory muscle strength, in respiratory endurance, and in physical performance [31][32][33][39][40], but also a reduction in the incidence of several MG complications, like dyspnea [41]. Furthermore, sustained hyperpnea training was considered a more appropriate approach than respiratory strength training in people with MG, because it reduced significantly diaphragm and abdominal muscles fatigue [40]. In addition, respiratory training improved MG subjective symptoms, like fatigability. The effects of respiratory training can be explained by the fact that a long-term respiratory muscle endurance training reduces the patient’s respiratory rate. As a consequence, the work of breathing decreases the breathing reserve during physical activity and improves overall physical fitness. Respiratory training could be also practiced at home under the supervision of clinicians in order to enhance the conventional pharmaceutical therapy [40].

Balance training consists of exercises that target the sensorimotor system in order to improve function and reduce the risk of falls [42]. Additionally, balance training could also increase bone density, which can be reduced due to the sedentary lifestyle caused by muscle weakness and fatigue [43]. The positive effect of balance exercises on symptoms might be explained by an increase in the number of mitochondria within muscles, by the musculoskeletal mass building, and by the impulse to lactate degradation [44]. Consequently, this would lead to more efficient neuromuscular transmission, to the increase ability of muscles to cope with fatigue, and to improved strength and endurance [45]. Moreover, the increased visual-vestibular integration would lead to a better balance, since vestibular input has been suggested to play a key role in balance control [46][47].

Eventually, psychotherapy in combination with physical training (aerobic, stretching, and breathing strategies) could improve patient’s fatigue more than physical training alone [48]. Moreover, group therapy could modify a MG patient’s lifestyle since it helps to manage anxiety, depression, and social isolation [48].

This entry is adapted from the peer-reviewed paper 10.3390/jfmk5040071

References

  1. Aisling S Carr; Chris R. Cardwell; Peter O McCarron; John McConville; A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurology 2010, 10, 46-46, 10.1186/1471-2377-10-46.
  2. Ernestina Santos; Antonio Braga; Denis Gabriel; Sara Duarte; Ana Martins Da Silva; Ilda Matos; Marta Freijo; Joao Martins; Fernando Silveira; Goreti Nadais; et al. MuSK myasthenia gravis and pregnancy. Neuromuscular Disorders 2018, 28, 150-153, 10.1016/j.nmd.2017.11.014.
  3. Alon Abraham; Charles D. Kassardjian; Hans D. Katzberg; Vera Bril; Ari Breiner; Selective or predominant triceps muscle weakness in African–American patients with myasthenia gravis. Neuromuscular Disorders 2017, 27, 646-649, 10.1016/j.nmd.2017.04.009.
  4. Robert H.P. De Meel; Martijn R. Tannemaat; J. J. G. M. Verschuuren; Heterogeneity and shifts in distribution of muscle weakness in myasthenia gravis.. Neuromuscular Disorders 2019, 29, 664-670, 10.1016/j.nmd.2019.07.006.
  5. Ritesh Kumar; Myasthenia gravis and thymic neoplasms: A brief review. World Journal of Clinical Cases 2015, 3, 980-3, 10.12998/wjcc.v3.i12.980.
  6. Vasiliki Zouvelou, Efstratios Karavasilis, Georgios Velonakis; Benign thymic enlargement in myasthenia gravis. Neuromuscular Disorders February 26, 2018, VOLUME 28, ISSUE 5, P454-455, https://doi.org/10.1016/j.nmd.2018.02.010.
  7. L. Padua MD, PhD A. Evoli MD I. Aprile MD P. Caliandro MD P. D'Amico MD A. Rabini MD P. Tonali MD; Quality of life in patients with myasthenia gravis. Muscle & Nerve 19 February 2002, 25, 466–467, https://doi.org/10.1002/mus.10035.
  8. Paul, R.H.; Nash, J.M.; Cohen, R.A.; Gilchrist, J.M.; Goldstein, J.M.; Quality of life and well-being of patients with myasthenia gravis.. Muscle Nerve 2001, 24, 512–516, https://doi.org/10.1002/mus.1034.
  9. Ezequiel Fernandes Oliveira; Sergio Roberto Nacif; Jessica Julioti Urbano; Anderson Soares Silva; Claudia Santos Oliveira; Eduardo Araujo Perez; Melissa Nunes Polaro; Berenice Cataldo Oliveira Valerio; Roberto Stirbulov; Giuseppe Insalaco; et al. Sleep, lung function, and quality of life in patients with myasthenia gravis: A cross-sectional study. Neuromuscular Disorders 2017, 27, 120-127, 10.1016/j.nmd.2016.11.015.
  10. Tomoyuiki Kawada; Sleep evaluation in patients with myasthenia gravis. Neuromuscular Disorders 2018, 28, 376, 10.1016/j.nmd.2018.01.006.
  11. Hyun Joo Kee; Hee Kyung Yang; Jeong-Min Hwang; Kyung Seok Park; Evaluation and validation of sustained upgaze combined with the ice-pack test for ocular myasthenia gravis in Asians. Neuromuscular Disorders 2019, 29, 296-301, 10.1016/j.nmd.2018.12.011.
  12. Nils Erik Gilhus; Myasthenia Gravis. New England Journal of Medicine 2016, 375, 2570-2581, 10.1056/nejmra1602678.
  13. K E Osserman; G Genkins; Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients.. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 1971, 38, 497–537, .
  14. Evoli, A.; Myasthenia gravis: New developments in research and treatment.. Curr. Opin. Neurol. 2017, 30, 464–470, .
  15. Peragallo, J.H.; Pediatric Myasthenia Gravis. Semin. Pediatr. Neurol. 2017, 24, 116–121, .
  16. Dagur Ingi Jonsson; Ritva Pirskanen; Fredrik Piehl; Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab. Neuromuscular Disorders 2017, 27, 565-568, 10.1016/j.nmd.2017.03.007.
  17. A. F. Lipka; Charlotte Vrinten; Erik W. Van Zwet; Kirsten J.M. Schimmel; Martina C. Cornel; Marja R. Kuijpers; Yechiel A. Hekster; Stephanie S. Weinreich; J. J. G. M. Verschuuren; Ephedrine treatment for autoimmune myasthenia gravis. Neuromuscular Disorders 2017, 27, 259-265, 10.1016/j.nmd.2016.11.009.
  18. Ricardo H. Roda; Leana Doherty; Andrea M. Corse; Stopping oral steroid-sparing agents at initiation of rituximab in myasthenia gravis.. Neuromuscular Disorders 2019, 29, 554-561, 10.1016/j.nmd.2019.06.002.
  19. Bruno Corrado; Gianluca Ciardi; Facioscapulohumeral distrophy and physiotherapy: a literary review. Journal of Physical Therapy Science 2015, 27, 2381-2385, 10.1589/jpts.27.2381.
  20. Corrado, B.; Ciardi, G.; Bargigli, C.; Rehabilitation Management of the Charcot-Marie-Tooth Syndrome: A Systematic Review of the Literature. Medicine 2016, 95, e3278, .
  21. Corrado, B.; Sommella, N.; Ciardi, G.; Raiano, E.; Scala, I.; Strisciuglio, P.; Servodio Iammarrone, C.; Can early physical therapy positively affect the onset of independent walking in infants with Down syndrome? A retrospective cohort study. Minerva Pediatr. 2018, \\, \\, 10.23736/s0026-4946.18.05041-7 .
  22. Bruno Corrado; Carla Di Luise; Clemente Servodio Iammarrone; Management of Muscle Spasticity in Children with Cerebral Palsy by Means of Extracorporeal Shockwave Therapy: A Systematic Review of the Literature.. Developmental Neurorehabilitation 2019, \\, 1-7, 10.1080/17518423.2019.1683908.
  23. Marta Fonzo; Felice Sirico; Bruno Corrado; Evidence-Based Physical Therapy for Individuals with Rett Syndrome: A Systematic Review. Brain Sciences 2020, 10, 410, 10.3390/brainsci10070410.
  24. Bruno Corrado; Gianluca Ciardi; Clemente Servodio Iammarrone; Rehabilitation management of Pompe disease, from childhood trough adulthood: A systematic review of the literature.. Neurology International 2019, 11, 7983, 10.4081/ni.2019.7983.
  25. E.A. Vola; M. Albano; C. Di Luise; V. Servodidio; M. Sansone; S. Russo; B. Corrado; C. Servodio Iammarrone; M. G. Caprio; G. Vallone; et al. Use of ultrasound shear wave to measure muscle stiffness in children with cerebral palsy. Journal of Ultrasound 2018, 21, 241-247, 10.1007/s40477-018-0313-6.
  26. B. Corrado; M. Albano; M.G. Caprio; C. Di Luise; M. Sansone; V. Servodidio; S. Russo; G. Vallone; E.A. Vola; C. Servodio Iammarrone; et al. Usefulness of point shear wave elastography to assess the effects of extracorporeal shockwaves on spastic muscles in children with cerebral palsy: an uncontrolled experimental study. Muscle Ligaments and Tendons Journal 2019, 9, 124, 10.32098/mltj.01.2019.04.
  27. Lorenzo Maggi; Pia Bernasconi; Adele D’Amico; Raffaella Brugnoni; Chiara Fiorillo; Matteo Garibaldi; Guja Astrea; Claudio Bruno; Filippo Maria Santorelli; R. Liguori; et al. Italian recommendations for diagnosis and management of congenital myasthenic syndromes. Neurological Sciences 2018, 40, 457-468, 10.1007/s10072-018-3682-x.
  28. Palermi, S.; Sacco, A.M.; Belviso, I.; Romano, V.; Montesano, P.; Corrado, B.; Sirico, F.; Guidelines for Physical Activity-A Cross-Sectional Study to Assess Their Application in the General Population. Have We Achieved Our Goal?. Int. J. Environ. Res. Public Health 2020, 17, 3980, .
  29. Bruno Corrado; Gianluca Ciardi; Luciano Fortunato; Clemente Servodio Iammarrone; Burnout syndrome among Italian physiotherapists: a cross-sectional study. European Journal of Physiotherapy 2019, 21, 240-245, 10.1080/21679169.2018.1536765.
  30. Cristina Mamédio Da Costa Santos; Cibele Andrucioli De Mattos Pimenta; Moacyr Roberto Cuce Nobre; The PICO strategy for the research question construction and evidence search. Revista Latino-Americana de Enfermagem 2007, 15, 508-511, 10.1590/s0104-11692007000300023.
  31. Shi Hui Wong; J.C. Nitz; Katrina Williams; Sandra G. Brauer; Effects of balance strategy training in myasthenia gravis: A case study series. Muscle & Nerve 2013, 49, 654-660, 10.1002/mus.24054.
  32. Martin Amadeus Rahbek; Erik Elgaard Mikkelsen; Kristian Overgaard; Lotte Vinge; Henning Andersen; Ulrik Dalgas; Exercise in myasthenia gravis: A feasibility study of aerobic and resistance training. Muscle & Nerve 2017, 56, 700-709, 10.1002/mus.25552.
  33. Elisabet Westerberg; Carl Johan Molin; Ida Lindblad; Margareta Emtner; Anna Rostedt Punga; Physical exercise in myasthenia gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study. Muscle & Nerve 2017, 56, 207-214, 10.1002/mus.25493.
  34. Indraratna, P.; Matar, W.; Myasthenia Gravis. N. Engl. J. Med 2017, 376, e25, .
  35. Benatar, M.; Sanders, D.B.; Burns, T.M.; Cutter, G.R.; Guptill, J.T.; Baggi, F.; Kaminski, H.J.; Mantegazza, R.; Meriggioli, M.N.; Quan, J.; et al. Task Force on MG Study Design of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Recommendations for myasthenia gravis clinical trials.. Muscle Nerve 2012, 45, 909–917, .
  36. M Aftabuddin; S Bhandari; Outcome of Extended Thymectomy in Myasthenia Crisis Patient.. Mymensingh Medical Journal 2016, 25, 536–541, .
  37. Chaudhuri, A.; Behan, P.O.; Myasthenic crisis. QJM 2009, 102, 97–107, .
  38. Alberto Raggi; Matilde Leonardi; Carlo Antozzi; Paolo Confalonieri; Lorenzo Maggi; Ferdinando Cornelio; Renato Mantegazza; Concordance between severity of disease, disability and health-related quality of life in Myasthenia gravis. Neurological Sciences 2009, 31, 41-45, 10.1007/s10072-009-0167-y.
  39. Sophie Freitag; Stephanie Hallebach; Irene Baumann; Petra Kalischewski; Beate Rassler; Effects of long-term respiratory muscle endurance training on respiratory and functional outcomes in patients with Myasthenia gravis.. Respiratory Medicine 2018, 144, 7-15, 10.1016/j.rmed.2018.09.001.
  40. Westerberg, E.; Molin, C.J.; Spörndly Nees, S.; Widenfalk, J.; Punga, A.R; The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study. Medicine 2018, 97, e11510, .
  41. Man Mohan Mehndiratta; Sanjay Pandey; Thierry Kuntzer; Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database of Systematic Reviews 2011, \\, \\, 10.1002/14651858.cd006986.pub3.
  42. Maria Elena Farrugia; Marina Di Marco; Denyse Kersel; Caroline Carmichael; A Physical and Psychological Approach to Managing Fatigue in Myasthenia Gravis: A Pilot Study. Journal of Neuromuscular Diseases 2018, 5, 373-385, 10.3233/jnd-170299.
  43. Vianda S. Stel; Johannes H. Smit; Saskia M. F. Pluijm; P. Lips; Consequences of falling in older men and women and risk factors for health service use and functional decline. Age and Ageing 2004, 33, 58-65, 10.1093/ageing/afh028.
  44. Antoine Dany; Amandine Rapin; Christian Réveillère; Arnaud Calmus; Vincent Tiffreau; Isabella Morrone; J.L. Novella; Damien Jolly; F. Boyer; Exploring quality of life in people with slowly-progressive neuromuscular disease. Disability and Rehabilitation 2017, 39, 1262-1270, 10.1080/09638288.2016.1191552.
  45. Jefferis, B.J.; Iliffe, S.; Kendrick, D.; Kerse, N.; Trost, S.; Lennon, L.T.; Ash, S.; Sartini, C.; Morris, R.W.; Wannamethee, S.G.; et al. How are falls and fear of falling associated with objectively measured physical activity in a cohort of community-dwelling older men?. BMC Geriatr. 2014, 14, 114, .
  46. Diana R. Toledo; José A. Barela; Age-related differences in postural control: effects of the complexity of visual manipulation and sensorimotor contribution to postural performance. Experimental Brain Research 2014, 232, 493-502, 10.1007/s00221-013-3756-1.
  47. J.C. Nitz; L. Stock; A. Khan; Health-related predictors of falls and fractures in women over 40. Osteoporosis International 2012, 24, 613-621, 10.1007/s00198-012-2004-z.
  48. Goksen Kuran Aslan; Hulya Nilgun Gurses; Halim Issever; Esen Kiyan; Effects of respiratory muscle training on pulmonary functions in patients with slowly progressive neuromuscular disease: a randomized controlled trial. Clinical Rehabilitation 2014, 28, 573-581, 10.1177/0269215513512215.
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