Myasthenia gravis resident survival guide
| 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
- Thymus abnormalities:[1][2][3][4][5]
- Genetic:[6][7][8][9][10][11]
- Environment:[12][13][14][15][16][17]
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
- Consider thymectomy in nonthymomatous, generalized MG patients with AChR-Ab, aged 18–50 years, especially if the patients is with AChR-Ab+ and fails to respon to immunosupressive trial.[19]
- Use small doses of corticosteroids as the initial immunosupressive agent in ocular MG.[20]
- Use rituximab early in patients with MuSK-Ab+ MG who have an unsatisfactory response to initial immunotherapy.[21]
- Use methotrexate as a steroid-sparing agent in patients with generalized MG who have not tolerated or responded to steroid-sparing agents.[22]
- Considere eculizumab in the treatment of severe, refractory, AChR-Ab+ generalized MG.[23]
- Use early aggressive treatment with high-dose steroids in combination with plasma exchange or IVIg in patients who develop overt MG while on immune checkpoint inhibitors.[24]
Don'ts
- Do not use or use with caution the following drugs in myasthenia gravis: aminoglycosides, beta blockers, botulin toxin, chloroquine, hydroxychloroquine, corticosteroids, penicillamine, fluoroquinolones, procainamides, macrolides, quinine, and statins.[24]
References
- ↑ Drachman DB (June 1994). "Myasthenia gravis". N. Engl. J. Med. 330 (25): 1797–810. doi:10.1056/NEJM199406233302507. PMID 8190158.
- ↑ Vincent A (October 2002). "Unravelling the pathogenesis of myasthenia gravis". Nat. Rev. Immunol. 2 (10): 797–804. doi:10.1038/nri916. PMID 12360217.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Wittbrodt ET (February 1997). "Drugs and myasthenia gravis. An update". Arch. Intern. Med. 157 (4): 399–408. PMID 9046891.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 24.0 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.