Abstract
Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia represent the three autoantibody-mediated disorders at the neuromuscular junction. They give muscle weakness and fatigability as their dominating symptoms. The weakness has usually a preferred localization to some but not all muscles. MG subgroups reflect pathogenesis and direct therapy. Patients should always be classified according to type of antibody, thymus pathology, age at symptom onset and generalized versus pure ocular symptoms. LEMS and neuromyotonia are subgrouped according to paraneoplasia or not. All conditions have well-defined autoantibodies that bind in vivo and directly induce the muscle weakness. Therapy includes symptomatic drugs influencing the acetylcholine receptor activity in the postsynaptic membrane and immunosuppressive treatment influencing the pathogenic autoantibodies. This immunoactive treatment is not yet specific for the disease-inducing antigen-antibody interaction. Treatment is usually effective, and most patients obtain mild symptoms only or a full clinical remission. Comorbidities need to be treated, especially a thymoma in paraneoplastic MG or neuromyotonia and a lung cancer in paraneoplastic LEMS. Supportive therapy is important, and a well-adapted daily training program is recommended. Severe exacerbations (myasthenic crisis) with the need for respiratory support are rare, occur mainly together with infections, and need immediate intensive care.
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References
Beeson D. Congenital myasthenic syndromes: recent advances. Curr Opin Neurol. 2016;29:565–71.
Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016;375:2570–81.
Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis – autoantibody characteristics and their implications for therapy. Nat Rev Neurol. 2016;12:259–U291.
Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14:1023–36.
Titulaer MJ, Lang B, Verschuuren J. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10:1098–107.
Lang B, Makuch M, Moloney T, et al. Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies. J Neurol Neurosurg Psychiatry. 2017;88:353–61.
Hong Y, Zisimopoulou P, Trakas N, et al. Multiple antibody detection in ’seronegative’ myasthenia gravis patients. Eur J Neurol. 2017;24:844–50.
Kerty E, Elsais A, Argov Z, Evoli A, Gilhus NE. EFNS/ENS Guidelines for the treatment of ocular myasthenia. Eur J Neurol. 2014;21:687–93.
Heldal AT, Owe JF, Gilhus NE, Romi F. SEROPOSITIVE MYASTHENIA GRAVIS: A NATIONWIDE EPIDEMIOLOGIC STUDY. Neurology. 2009;73:150–1.
Carr AS, Cardwell CR, McCarron PO, McConville J. A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurol. 2010;10:46.
Hong Y, Skeie GO, Zisimopoulou P, et al. Juvenile-onset myasthenia gravis: autoantibody status, clinical characteristics and genetic polymorphisms. J Neurol. 2017;264:955–62.
Pedersen EG, Hallas J, Hansen K, Jensen PEH, Gaist D. Late-onset myasthenia not on the increase: a nationwide register study in Denmark, 1996-2009. Eur J Neurol. 2013;20:309–14.
Guptill JT, Sanders DB, Evoli A. ANTI-MuSK Antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve. 2011;44:36–40.
Hong Y, Li HF, Skeie GO, et al. Autoantibody profile and clinical characteristics in a cohort of Chinese adult myasthenia gravis patients. J Neuroimmunol. 2016;298:51–7.
Boldingh MI, Maniaol A, Brunborg C, et al. Prevalence and clinical aspects of immigrants with myasthenia gravis in northern europe. Muscle Nerve. 2017;55:819–27.
Romi F, Hong Y, Gilhus NE. Pathophysiology and immunological profile of myasthenia gravis and its subgroups. Curr Opin Immunol. 2017;49:9–13.
Wirtz PW, Nijnuis MG, Sotodeh M, et al. The epidemiology of myasthenia gravis, Lambert-Eaton myasthenic syndrome and their associated tumours in the northern part of the province of South Holland. J Neurol. 2003;250:698–701.
Titulaer MJ, Wirtz PW, Kuks JBM, et al. The Lambert-Eaton myasthenic syndrome 1988-2008: A clinical picture in 97 patients. J Neuroimmunol. 2008;201:153–8.
Titulaer MJ, Maddison P, Sont JK, et al. Clinical Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumor Association Prediction Score Accurately Predicts Small-Cell Lung Cancer in the LEMS. J Clin Oncol. 2011;29:902–8.
Vinge L, Andersen H. Muscle strength and fatigue in newly diagnosed patients with myasthenia gravis. Muscle Nerve. 2016;54:709–14.
Andersen JB, Gilhus NE, Sanders DB. Factors affecting outcome in myasthenia gravis. Muscle Nerve. 2016;54:1041–9.
Popperud TH, Boldingh MI, Rasmussen M, Kerty E. Juvenile myasthenia gravis in Norway: Clinical characteristics, treatment, and long-term outcome in a nationwide population-based cohort. Eur J Paediatr Neurol. 2017;21:707–14.
Antoine JC, Camdessanche JP. Paraneoplastic neuropathies. Curr Opin Neurol. 2017;30:513–20.
Zisimopoulou P, Evangelakou P, Tzartos J, et al. A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun. 2014;52:139–45.
Tsonis AI, Zisimopoulou P, Lazaridis K, et al. MuSK autoantibodies in myasthenia gravis detected by cell based assay - A multinational study. J Neuroimmunol. 2015;284:10–7.
Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database of Syst Rev. 2011.
Kucukali CI, Kurtuncu M, Akcay HI, Tuzun E, Oge AE. Peripheral nerve hyperexcitability syndromes. Rev Neurosci. 2015;26:239–51.
Maddison P. Neuromyotonia. Clin Neurophysiol. 2006;117:2118–27.
Binks S, Vincent A, Palace J. Myasthenia gravis: a clinical-immunological update. J Neurol. 2016;263:826–34.
Koneczny I, Stevens JAA, De Rosa A, et al. IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients. J Autoimmun. 2017;77:104–15.
Zhang B, Tzartos JS, Belimezi M, et al. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol. 2012;69:445–51.
Romi F, Skeie GO, Gilhus NE, Aarli JA. Striational antibodies in myasthenia gravis - Reactivity and possible clinical significance. Arch Neurol. 2005;62:442–6.
Skeie GO, Mygland A, Treves S, Gilhus NE, Aarli JA, Zorzato F. Ryanodine receptor antibodies in myasthenia gravis: Epitope mapping and effect on calcium release in vitro. Muscle Nerve. 2003;27:81–9.
Gasperi C, Melms A, Schoser B, et al. Anti-agrin autoantibodies in myasthenia gravis. Neurology. 2014;82:1976–83.
Suzuki S, Baba A, Kaida K, et al. Cardiac involvements in myasthenia gravis associated with anti-Kv1.4 antibodies. Eur J Neurol. 2014;21:223–30.
Romi F, Suzuki S, Suzuki N, Petzold A, Plant GT, Gilhus NE. Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis. J Neurol. 2012;259:1312–6.
Gilhus NE, Willcox N, Harcourt G, et al. Antigen presentation by thymoma epithelial-cells from myasthenia-gravis patients to potentially pathogenic t-cells. J Neuroimmunol. 1995;56:65–76.
Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Strobel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12:875–84.
Myking AO, Skeie GO, Varhaug JE, Andersen KS, Gilhus NE, Aarli JA. The histomorphology of the thymus in late onset, non-thymoma myasthenia gravis. Eur J Neurol. 1998;5:401–5.
Cavalcante P, Serafini B, Rosicarelli B, et al. Epstein-Barr Virus persistence and reactivation in myasthenia gravis thymus. Ann Neurol. 2010;67:726–38.
Gilhus NE. Myasthenia and the neuromuscular junction. Curr Opin Neurol. 2012;25:523–9.
Avidan N, Le Panse R, Berrih-Aknin S, Miller A. Genetic basis of myasthenia gravis - A comprehensive review. J Autoimmun. 2014;52:146–53.
Pirskanen R. Genetic aspects in myasthenia-gravis - family study of 264 finnish patients. Acta Neurol Scand. 1977;56:365–88.
Salvado M, Canela M, Maria J, et al. Study of the prevalence of familial autoimmune myasthenia gravis in a Spanish cohort. J Neurol Sci. 2016;360:110–4.
Lisak RP, Barcellos L. New Insights Into the Genetics of Autoimmune Myasthenia Gravis An Evolving Story. JAMA Neurol. 2015;72:386–7.
Renton AE, Pliner HA, Provenzano C, et al. A Genome-Wide Association Study of Myasthenia Gravis. JAMA Neurol. 2015;72:396–404.
Bach JF. The etiology of autoimmune diseases: the case of myasthenia gravis. In: Wolfe GI, Meriggioli MN, Ciafaloni E, Ruff RL, editors. Myasthenia Gravis and Related Disorders I. Boston: Wiley Periodicals; 2012. p. 33–9.
Verschuuren J, Strijbos E, Vincent A. Neuromuscular junction disorders. Handbook of clinical neurology. Amsterdam: Elsevier; 2016;133:447–466..
Takamori M. Lambert-Eaton myasthenic syndrome: Search for alternative autoimmune targets and possible compensatory mechanisms based on presynaptic calcium homeostasis. J Neuroimmunol. 2008;201:145–52.
Titulaer MJ, Verschuuren J. Lambert-Eaton myasthenic syndrome - Tumor versus nontumor forms. In: Kaminski HJ, Barohn RJ, editors. Myasthenia gravis and related disorders: 11th international conference; 2008. p. 129–34.
Fleisher J, Richie M, Price R, Scherer S, Dalmau J, Lancaster E. Acquired neuromyotonia heralding recurrent thymoma in myasthenia gravis. JAMA Neurol. 2013;70:1311–4.
Song J, Jing SS, Quan C, et al. Isaacs syndrome with CASPR2 antibody: A series of three cases. J Clin Neurosci. 2017;41:63–6.
Irani SR, Pettingill P, Kleopa KA, et al. Morvan syndrome: clinical and serological observations in 29 cases. Ann Neurol. 2012;72:241–55.
Heldal AT, Eide GE, Romi F, Owe JF, Gilhus NE. Repeated acetylcholine receptor antibody-concentrations and association to clinical myasthenia gravis development. PLoS One. 2014;9:e114060.
Stergiou C, Lazaridis K, Zouvelou V, et al. Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen. J Neuroimmunol. 2016;292:108–15.
Priola AM, Priola SM, Giraudo MT, et al. Chemical-shift and diffusion-weighted magnetic resonance imaging of thymus in myasthenia gravis usefulness of quantitative assessment. Investig Radiol. 2015;50:228–38.
Priola AM, Priola SM, Gned D, Giraudo MT, Fornari A, Veltri A. Comparison of CT and chemical-shift MRI for differentiating thymoma from non-thymomatous conditions in myasthenia gravis: value of qualitative and quantitative assessment. Clin Radiol. 2016;71:E157–69.
Gilhus NE, Nacu A, Andersen JB, Owe JF. Myasthenia gravis and risks for comorbidity. Eur J Neurol. 2015;22:17–23.
Nacu A, Andersen JB, Lisnic V, Owe JF, Gilhus NE. Complicating autoimmune diseases in myasthenia gravis: a review. Autoimmunity. 2015;48:362–8.
Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology. 2016;87:419–25.
Skeie GO, Apostolski S, Evoli A, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2010;17:893–902.
Iorio R, Damato V, Alboini PE, Evoli A. Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol. 2015;262:1115–9.
Randall KL. Rituximab in autoimmune diseases. Aust Prescr. 2016;39:131–4.
Sanders DB, McDermott M, Thornton C, et al. A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis. Neurology. 2008;71:394–9.
Sanders DB, Hart IK, Mantegazza R, et al. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology. 2008;71:400–6.
Evoli A, Alboini PE, Damato V, et al. Myasthenia gravis with antibodies to MuSK: an update. Ann N Y Acad Sci. 2018;1412:82–9.
Wolfe GIKH, Aban IB, Minisman G, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375:511–22.
Howard JF, Barohn RJ, Cutter GR, et al. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve. 2013;48:76–84.
Gilhus NE. Eculizumab: a treatment option for mysthenia gravis? Lancet Neurol. 2017;16:947–8.
Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database of Systematic Reviews. 2012.
Beecher G, Anderson D, Siddiqi ZA. Subcutaneous immunoglobulin in myasthenia gravis exacerbation A prospective, open-label trial. Neurology. 2017;89:1135–41.
Kiessling P, Lledo-Garcia R, Watanabe S, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9:eaan1208.
Rahbek MA, Mikkelsen EE, Overgaard K, Vinge L, Andersen H, Dalgas U. Exercise in myasthenia gravis: a feasibility study of aerobic and resistance training. Muscle Nerve. 2017;56:700–9.
Andersen JB, Owe JF, Engeland A, Gilhus NE. Total drug treatment and comorbidity in myasthenia gravis: a population-based cohort study. Eur J Neurol. 2014;21:948–55.
Hoff JM, Daltveit AK, Gilhus NE. Myasthenia gravis in pregnancy and birth: identifying risk factors, optimising care. Eur J Neurol. 2007;14:38–43.
Norwood F, Dhanjal M, Hill M, et al. Myasthenia in pregnancy: best practice guidelines from a UK multispecialty working group. J Neurol Neurosurg Psychiatry. 2014;85:538–43.
Hoff JM, Daltveit AK, Gilhus NE. Myasthenia gravis - Consequences for pregnancy, delivery, and the newborn. Neurology. 2003;61:1362–6.
Hacohen Y, Jacobson LW, Byrne S, et al. Fetal acetylcholine receptor inactivation syndrome A myopathy due to maternal antibodies. Neurol Neuroimmunol Neuroinflammation. 2015;2:e57.
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Gilhus, N.E. (2019). Myasthenia Gravis and Other Immune-Mediated Disorders of the Neuromuscular Junction. In: Mitoma, H., Manto, M. (eds) Neuroimmune Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-19515-1_26
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