Myasthenia gravis resident survival guide

Jump to navigation Jump to search
Myasthenia gravis Resident Survival Guide Microchapters
Overview
Causes
Diagnosis
Treatment
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: , Moises Romo, M.D., Fahimeh Shojaei, M.D.

Synonyms and Keywords: Myasthenia gravis management, Myasthenia gravis workup, Myasthenia gravis approach, approach to Myasthenia gravis, Myasthenia gravis treatment

Overview

Myasthenia gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. The diagnosis is maily clinical, although ordering acetylcholine autoantibodies may sometimes be necessary. Physical examination of patients with myasthenia gravis is usually remarkable for: downward lip corners and depress face, asymmetrical ptosis, incomplete eye closure, Cogan's lid twitch, peek sign, weakness of oropharyngeal muscles, respiratory muscle weakness, dropped head syndrome, and proximal muscle weakness. Thoracic immaging may reveal a mediastinal mass (thymoma). Edrophonium test is used in patients with obvious ptosis or ophthalmoparesis. Myasthenia is treated medically with cholinesterase inhibitors or immunosuppressants and in selected cases with thymectomy.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

  • Myasthenia gravis is not a life-threatening condition that may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Diagnosis

Shown below is an algorithm summarizing the diagnosis of Generalized weakness according to the American Academy of Neurology guidelines:

 
 
 
Generalized weakness symptoms
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
True motor weakness?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Evaluate for causes of fatigue or muscle pain
 
Fluctuating
 
 
 
 
 
Constant
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myasthenia Gravis
Lambert-Eaton syndrome
Periodic paralysis
Metabolic myopathy
 
Acquiered
 
 
 
 
 
Life-long/chronic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Polymyositis
Dermatomyositis
•Inclusion body myopathy
Amyotrophic lateral sclerosis
Multifocal motor neuropathy
 
Non-progessive
 
 
 
 
 
 
 
Progressive
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Congenital myopathy
Congenital dystrophy
 
Ocular
•Kearns-sayre syndrome
•Oculopharyngeal dystrophy
Ocular dystrophy
 
Facial
•Fascioscapulohumeral dystrophy
Myotonic dystrophy
 
Upper extremities
•Emery-Dreiffus dystrophy
•Hereditary distal myopathy
 
Lower extremities
Duchenne's muscular dystrophy
Becker's muscular dystrophy
Sarcoglycanopathies
Spinal muscular atrophy
•Limb girdle dystrophy


Treatment

Shown below is an algorithm summarizing the treatment of myasthenia gravis according the the European Academy of Neurology guidelines:[18]

 
 
 
 
 
 
 
 
 
 
Myasthenia gravis
 
 
 
 
 
 
 
 
Considere early thymectomy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ocular; mild symptoms
 
 
 
 
Moderate to severe symptoms
 
 
Impedeing myasthenic crisis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Start AChEI
 
 
 
Monitor FVC and clinically
 
Start AChEI (most patients will requiere steroids early)
 
 
Monitor close in HDU/ITU
Plasma exchange (5 cycles
IVIg 0.4g/kg/d x 5 days)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No improvement
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Start steroids
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Target dose ocular- 0.5mg/kg/day
Target dose generalized- 1mg/kg/day
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Target dose achieved or in remission at a small dose for 2-3 months
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reduce prednisolone gradually<be> Taper by 10mg/month until on 30 mg OD; then by 5mg/month until on 15 mg OD; then by 1-2mg/month to the smallest possible dose
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unable to reduce prednisolone or frequent relapses
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Start steroids-sparing drugs: azathioprine (check TPMT), mycophenolate or methotrexate
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unable to tolerate
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider cyclosporin, tacrolimus, cyclophosphamide or rituximab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treat as refractory myasthenia gravis if no improvement or undesirable side effects despite adequate dose and duration of 2 steroid-sparing agents
 

Do's

Don'ts

References

  1. Drachman DB (June 1994). "Myasthenia gravis". N. Engl. J. Med. 330 (25): 1797–810. doi:10.1056/NEJM199406233302507. PMID 8190158.
  2. Vincent A (October 2002). "Unravelling the pathogenesis of myasthenia gravis". Nat. Rev. Immunol. 2 (10): 797–804. doi:10.1038/nri916. PMID 12360217.
  3. Willcox N, Leite MI, Kadota Y, Jones M, Meager A, Subrahmanyam P, Dasgupta B, Morgan BP, Vincent A (2008). "Autoimmunizing mechanisms in thymoma and thymus". Ann. N. Y. Acad. Sci. 1132: 163–73. doi:10.1196/annals.1405.021. PMID 18567866.
  4. Leite MI, Jones M, Ströbel P, Marx A, Gold R, Niks E, Verschuuren JJ, Berrih-Aknin S, Scaravilli F, Canelhas A, Morgan BP, Vincent A, Willcox N (September 2007). "Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status". Am. J. Pathol. 171 (3): 893–905. doi:10.2353/ajpath.2007.070240. PMC 1959483. PMID 17675582.
  5. Hohlfeld R, Wekerle H (September 2008). "Reflections on the "intrathymic pathogenesis" of myasthenia gravis". J. Neuroimmunol. 201-202: 21–7. doi:10.1016/j.jneuroim.2008.05.020. PMID 18644632.
  6. Feltkamp TE, van den Berg-Loonen PM, Nijenhuis LE, Engelfriet CP, van Rossum AL, van Loghem JJ, Oosterhuis HJ (January 1974). "Myasthenia gravis, autoantibodies, and HL-A antigens". Br Med J. 1 (5899): 131–3. PMC 1633001. PMID 4544224.
  7. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T (April 2004). "A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes". Nat. Genet. 36 (4): 337–8. doi:10.1038/ng1323. PMID 15004560.
  8. Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner VE, Gonzalez-Munoz A, Clark J, Veijola R, Cubbon R, Chen SL, Rosa R, Cumiskey AM, Serreze DV, Gregory S, Rogers J, Lyons PA, Healy B, Smink LJ, Todd JA, Peterson LB, Wicker LS, Santamaria P (March 2007). "Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity". Nat. Genet. 39 (3): 329–37. doi:10.1038/ng1958. PMC 2886969. PMID 17277778.
  9. Raknes G, Skeie GO, Gilhus NE, Aadland S, Vedeler C (January 1998). "FcgammaRIIA and FcgammaRIIIB polymorphisms in myasthenia gravis". J. Neuroimmunol. 81 (1–2): 173–6. PMID 9521619.
  10. van der Pol WL, Jansen MD, Kuks JB, de Baets M, Leppers-van de Straat FG, Wokke JH, van de Winkel JG, van den Berg LH (November 2003). "Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients". J. Neuroimmunol. 144 (1–2): 143–7. PMID 14597109.
  11. Kristiansen OP, Larsen ZM, Pociot F (February 2000). "CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity?". Genes Immun. 1 (3): 170–84. doi:10.1038/sj.gene.6363655. PMID 11196709.
  12. Scoppetta C, Onorati P, Eusebi F, Fini M, Evoli A, Vincent A (March 2003). "Autoimmune myasthenia gravis after cardiac surgery". J. Neurol. Neurosurg. Psychiatry. 74 (3): 392–3. PMC 1738331. PMID 12588942.
  13. Resatoglu AG, Tok M, Yemisci M, Yener N, Yener A (February 2006). "Autoimmune myasthenia gravis after coronary artery bypass surgery". Ann. Thorac. Surg. 81 (2): 725–6. doi:10.1016/j.athoracsur.2004.10.027. PMID 16427886.
  14. Wittbrodt ET (February 1997). "Drugs and myasthenia gravis. An update". Arch. Intern. Med. 157 (4): 399–408. PMID 9046891.
  15. Fujimaki K, Takasaki H, Koharazawa H, Takabayashi M, Yamaji S, Baba Y, Kanamori H, Ishigatsubo Y (July 2005). "Idiopathic thrombocytopenic purpura and myasthenia gravis after fludarabine treatment for chronic lymphocytic leukemia". Leuk. Lymphoma. 46 (7): 1101–2. doi:10.1080/10428190500063054. PMID 16019566.
  16. Ronzière T, Auzou P, Ozsancak C, Magnier P, Sénant J, Hannequin D (2000). "[Myasthenic syndrome induced by lithium]". Presse Med (in French). 29 (19): 1043–4. PMID 10874911.
  17. Iwase T, Iwase C (March 2006). "Systemic effect of local and small-dose botulinum toxin injection to unmask subclinical myasthenia gravis". Graefes Arch. Clin. Exp. Ophthalmol. 244 (3): 415–6. doi:10.1007/s00417-005-0130-4. PMID 16175373.
  18. Jacob, Saiju (2018). "Myasthenia Gravis – A Review of Current Therapeutic Options". European Neurological Review. 13 (2): 86. doi:10.17925/ENR.2018.13.2.86. ISSN 1758-3837.
  19. Wolfe, Gil I.; Kaminski, Henry J.; Aban, Inmaculada B.; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J. Gabriel; Heckmann, Jeannine M.; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O.; Beydoun, Said R.; Chalk, Colin H.; Barboi, Alexandru C.; Amato, Anthony A.; Shaibani, Aziz I.; Katirji, Bashar; Lecky, Bryan R.F.; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T.; Rivner, Michael H.; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M.; Jackson, Carlayne E.; Garcia Ramos, Guillermo S.; Verschuuren, Jan J.G.M.; Massey, Janice M.; Kissel, John T.; Werneck, Lineu C.; Benatar, Michael; Barohn, Richard J.; Tandan, Rup; Mozaffar, Tahseen; Conwit, Robin; Odenkirchen, Joanne; Sonett, Joshua R.; Jaretzki, Alfred; Newsom-Davis, John; Cutter, Gary R. (2016). "Randomized Trial of Thymectomy in Myasthenia Gravis". New England Journal of Medicine. 375 (6): 511–522. doi:10.1056/NEJMoa1602489. ISSN 0028-4793.
  20. Europa, Tarin A.; Nel, Melissa; Heckmann, Jeannine M. (2018). "Myasthenic ophthalmoparesis: Time To resolution after initiating immune therapies". Muscle & Nerve. 58 (4): 542–549. doi:10.1002/mus.26172. ISSN 0148-639X.
  21. Beecher, Grayson; Anderson, Dustin; Siddiqi, Zaeem A. (2018). "Rituximab in refractory myasthenia gravis: Extended prospective study results". Muscle & Nerve. 58 (3): 452–455. doi:10.1002/mus.26156. ISSN 0148-639X.
  22. Pasnoor, Mamatha; He, Jianghua; Herbelin, Laura; Burns, Ted M.; Nations, Sharon; Bril, Vera; Wang, Annabel K.; Elsheikh, Bakri H.; Kissel, John T.; Saperstein, David; Shaibani, J. Aziz; Jackson, Carlayne; Swenson, Andrea; Howard, James F.; Goyal, Namita; David, William; Wicklund, Matthew; Pulley, Michael; Becker, Mara; Mozaffar, Tahseen; Benatar, Michael; Pazcuzzi, Robert; Simpson, Ericka; Rosenfeld, Jeffrey; Dimachkie, Mazen M.; Statland, Jeffrey M.; Barohn, Richard J. (2016). "A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis". Neurology. 87 (1): 57–64. doi:10.1212/WNL.0000000000002795. ISSN 0028-3878.
  23. Howard, James F.; Barohn, Richard J.; Cutter, Gary R.; Freimer, Miriam; Juel, Vern C.; Mozaffar, Tahseen; Mellion, Michelle L.; Benatar, Michael G.; Farrugia, Maria Elena; Wang, Jing Jing; Malhotra, Suneil S.; Kissel, John T. (2013). "A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis". Muscle & Nerve. 48 (1): 76–84. doi:10.1002/mus.23839. ISSN 0148-639X.
  24. 24.0 24.1 Narayanaswami, Pushpa; Sanders, Donald B.; Wolfe, Gil; Benatar, Michael; Cea, Gabriel; Evoli, Amelia; Gilhus, Nils Erik; Illa, Isabel; Kuntz, Nancy L.; Massey, Janice; Melms, Arthur; Murai, Hiroyuki; Nicolle, Michael; Palace, Jacqueline; Richman, David; Verschuuren, Jan (2021). "International Consensus Guidance for Management of Myasthenia Gravis". Neurology. 96 (3): 114–122. doi:10.1212/WNL.0000000000011124. ISSN 0028-3878.