Myasthenia gravis: do not forget the patient perspective

•Myasthenia gravis patients have a significant disease burden in addition to muscle weakness.•Fatigue is prominent subgroup of with myasthenia gravis.•Patient-reported data illustrate limitations daily activities and quality life gravis.•Comorbidities treatment side-effects should be evaluated all gravis.•Optimal specialized care for local, national global perspective. Patients chronic often worries about the future experience impairment functions life. Symptoms such as fatigue, pain, insomnia, depression are common, secondary primary manifestation. Doctors tend focus on specific disease-related symptoms signs, ongoing activity improvement or deterioration relevant biomarkers. Myasthenia (MG) weakness some but not skeletal muscles single symptom [[1]Gilhus N.E. Verschuuren J.J. gravis: classification therapeutic strategies.Lancet Neurol. 2015; 14: 1023-1036Abstract Full Text PDF PubMed Scopus (441) Google Scholar]. Antibodies acetylcholine receptors (AChR), muscle-specific kinase (MuSK), lipoprotein-related peptide (LRP4) postsynaptic membrane MG induce [[2]Gilhus Tzartos S. Evoli A. Palaces J. Burns T.M. gravis.Nature Rev Dis Primers. 2019; 5: 30Crossref (76) In 10-20% patients, no serum antibodies detected by standard assays. AChR, MuSK LRP4 bind selectively sole action impairing neuromuscular transmission, thus reducing function. However, describe fatigue more important than aims at restoring function transmission [[3]Gilhus junction.Curr Opin 2012; 25: 523-529Crossref (49) This can done symptomatically increasing availability through inhibition esterase, suppression immune response against membrane. Supportive additional therapies aiming total patient incapacities neglected. Most do well. long-term study, 75% had remission only mild symptoms, 3% lasting severe [[4]Andersen J.B. Gilhus Sanders D.B. Factors affecting outcome gravis.Muscle Nerve. 2016; 54: 1041-1049Crossref (29) There hardly any increased mortality due [5Owe J.F. Daltveit A.K. Causes death among Norway between 1951 2001.J Neurol Neurosurg Psychiat. 2006; 77: 203-207Crossref (41) Scholar, 6Hansen J.S. Danielsen D.H. Somnier F.E. Frøslev T. Jakobsen Johnsen S.P. et al.Mortality nationwide population-based follow-up study Denmark.Muscle 53: 73-77Crossref (18) 7Westerberg E. Punga A.R. Mortality rates causes Swedish patients.Neuromusc Dis. 2020; 30: 815-824Abstract (2) around 20 % obtain complete stable [[8]Mantegazza R. Antozzi C. When deemed refractory: clinical signposts strategies.Ther Adv 2018; 11: 1-11Crossref (55) Scholar], 15-25% respond satisfactorily first second-line treatments retrospective, Chinese 2154 9% least one crisis use respiratory support [[9]Huang X. Liu W.B. Men L.N. Feng H.Y. Li Y. Luo C.M. al.Clinical features southern China: retrospective review 2,154 cases over 22 years.Neurol Sci. 2013; 34: 911-917Crossref (40) implies considerable costs individual well society [[10]Landfeldt Pogoryelova O. Sejersen Zethraeus N. Breiner Lochmuller H. Economic systematic review.Pharmacoeconom. 38: 715-728Crossref (3) Patient reports, either score formal measures complaints during ordinary consultations, how other aspects actual strength their self-evaluation current health status. Fatigue does necessarily correlate [[11]Ruiter A.M. Tannemaat M.R. gravis. A literature.Neuromusc 631-639Abstract (7) peripheral (due microdamage activity) central (with brain component) Daily functions, working capacity determined arm ptosis alone. Patient-reported tools include MG-ADL, Impairment Index MG-QOL15 Scholar,[12]Barnett Herbelin L. Dimachkie M.M. Barohn R.J. Measuring gravis.Neurol Clin. 36: 339-353Abstract (21) Scholar,[13]Burns Sadjadi Utsugisawa K. Gwathmey K.G. Joshi Jones al.International clinimetric evaluation MG-QoL15, resulting slight revision subesequent MG-QoL15R.Muscle 1015-1022Crossref (37) Scholar The scores reflect satisfaction, adaptability status, severity [[14]Menon D. Barnett Bril V. Comparison simple question acceptable state gravis.Eur J 27: 2286-2291Crossref aim this that our very patient, less so treating neurologists. authors opinion paper, consisting expert neurologists suggested representatives organizations from three European countries, consensus process selected aspects. Consensus was reached several digital meetings where high priority were accepted, without further process. author searched Web Science key words each aspect combined, most papers. co-authors supplemented patient's perspective combines present situation prognosis, effects side-effects, benefits versus risks procedures treatments, pharmacological drugs, comorbidity, best expertise. Controlled studies sparse, exact knowledge limited, authors’ personal has been included. Discussing make it easier adapt living MG. especially newly diagnosed who usually lot questions concerns. evidence-based information available, presented patients. registry both impaired even when moderate. limitations, diplopia driving. More explained numerous demanding tasks modern people work leisure time. An factor may lead consequences functions. competitive labour market, expectations family life, comorbidity. North American 1140 large proportion measured [[15]Cutter G. Xin H.C. Aban I. Allman P.H. Farzaneh-Far al.Cross-sectional analysis registry: Disability treatment.Muscle 60: 707-715Crossref (15) clearly related treatment. Younger women reported poorer disease-specific active immunosuppressive drug might improved cohort. population two countries (Norway Netherlands) health-related reduced generalized whereas those ocular scored similar healthy controls [[16]Boldingh M.I. Dekker Maniaol A.H. Brunborg Lipka A.F. Niks E.H. al.An up-date -results based cohorts.Health Qual Life Outcomes. 13: 115Crossref Female gender, age, determinant lower Physical activity, job, socio-economic factors, psychological well-being , comorbidity determinants Quality compared previous decades despite effective cross-sectional 1815 found distinct reduction [[17]Dong Chong M.K.C. Wu Y.S. Kaminski Cutter Xu al.Gender differences China.Health 18: 296Crossref correlated strength. Main factors associated comorbidities, female sex, unemployment. lifestyle counteracted social did influence results. Side-effects an impact [[18]Bacci E.D. Coyne K.S. Poon J.L. Harris Boscoe A.N. Understanding side therapy life.BMC 19: 335Crossref (8) need ration activities. means they unable combine full-time jobs perform home. Frost al almost six times higher odds market participation sick leave general Danish [[19]Frost Svendsen M.L. Rahbek Stapelfeldt Nielsen C.V. Lund Labour Denmark 1997-2011: cohort study.BMC 16: 224Crossref Females affected. Immunosuppressive treatment, proxy severity, negatively labour-market participation. refractory worked fewer hours well-controlled [[20]Harris I.B. Employment Gravis Foundation America Registry analysis.Muscle 700-706Crossref short-term absence study. Among 165 Australian 40% stopped MG, 20% changed occupation [[21]Blum Lee Gillis McEniery D.F. Reddel McCombe P. Clinical patients.J Clin Neurosci. 22: 1164-1169Abstract (25) therefore income, pensions, challenges regarding various types insurance. network. Muscle cause them abstain gatherings. Some feel inadequate responsibilities, break-ups divorces because disease. Many loss longer being able live used to. Social Scholar,[17]Dong Scholar. variability day represent challenge seen doctor employer, appear symptom-free, obvious functional extra support. Later could change considerably. assess effect treatments. important. Even moderate minimal weak tired. Nearly third consecutive responded “no” asked whether satisfied overall status dissatisfied worse score, likely unemployed [[22]Mendoza M. Tran Katzberg H.D. Patient-acceptable states gravis.Neurology. 95: E1617-E1618Crossref greater [[23]Barnett Kapral Kulkarni Davis conceptual framework evaluating Impairments gravis.Plos One. 2014; 9: e98089Crossref (17) includes lack energy, tiredness, exhaustion, 40-80% much figure Scholar,24Tran 58: 197-203Crossref 25Hoffmann Ramm Grittner U. Kohler Siedler Meisel risk life.Brain Behavior. 6: e00538Crossref (31) 26Elsais Wyller V.B. Loge J.H. Kerty muscular weakness?.BMC 132Crossref (32) frequent correlates activities, [[25]Hoffmann Presence strongly using scale eight patient-reported items 257 Canadian centre, correlation after immunomodulatory [[24]Tran Seemingly conflicting results probably covers range meanings pathogenesis different methods. Chronic complicate interfere parameters trials perhaps explain negative Personalities differ controls, frequency psychiatric disturbances corresponds [[27]Doering Henze Schussler Coping implications psychotherapy.Arch 1993; 50: 617-620Crossref (22) although affective comorbidities [[28]Law Flaherty Bandyopadhyay gravis.Cureus. 12: e9184PubMed Depression occurs 10-30% [29Gavrilov Y.V. Alekseeva Kreis O.A. Valko P.O. Weber K.P. heterogeneous intriguing entity.J 267: 1802-1811Crossref 30Suzuki Suzuki Nagane Masuda Kabasawa al.Factors depressive multicentre study.BMJ Open. 2011; 1e000313Crossref 31Aysal F. Karamustafalioglu Ozcelik B. Yilmaz Yumrukcal al.The relationship anxiety modality study.Noropsik Ars-Arch Neuropsych. 295-300Crossref (12) represents double matched non-MG [[32]Chu H.T. Tseng C.C. Liang C.S. Yeh T.C. Hu L.Y. Yang A.C. al.Risk disorders following study.Front Psychiatry. 10: 481Crossref corticosteroid frequently treated drugs [[33]Andersen Owe Engeland Total study.Eur 21: 948-955Crossref (23) Scholar].Depression physical disabilities disease.Table 1Key points assessment evaluation, compliance effects.•Daily worst capture variability•Precipitating worsening (infection, long days, menstruation), better managed•Non-myasthenic comorbidity•Mood anxiety•Family planning written advise pregnancy puberty•Function educational establishment adaptations t reduce fatigue; rest times, shorter mid-weekday off, home.•Job entitled financial help support•Social limitations•Exercise fitness•Smoking•Weight management diet•Burden network (family, partner, children) Open table new tab Pain regarded few small studies, body pain [[34]Padua Aprile Caliandro D'Amico Rabini al.Quality 2002; 466-467Crossref Scholar,[35]Tong Delfiner Herskovitz Pain, Headache, non-motor gravis.Curr Headache Rep. 39Crossref (4) disorders. Tension-type headache [[36]Nishimoto al.Headache (MG).Neurology. 2009; 72: A178Google side-effect [[35]Tong Opiates unwanted also relaxation. Hearing Antibody-induced subacute hearing thymoma [[37]Evoli Minicuci G.M. Vitaliani Battaglia Della Marca Lauriola al.Paraneoplastic diseases thymoma.J 2007; 254: 756-762Crossref (73) Scholar,[38]Ralli Altissimi Di Stadio Mazzei Turchetta Cianfrone Relationship contemporary review.J Internat Med Res. 2017; 45: 1459-1465Crossref (13) It AChR decrease hair cells cochlea leading [[38]Ralli Scholar,[39]Hamed S.A. Elattar Hamed E.A. Irreversible cochlear damage - otoacoustic emission analysis.Acta Scand. 113: 46-54Crossref Potential experienced concerned [[40]Hehir M.K. Ciafaloni physician opinions immunosuppressant reduction.Muscle 61: 767-772Crossref (1) Those corticosteroids worried. Weight gain, mood change, gastric reflux, skin changes, fluid retention osteoporosis induced At same time, fear relapse dose Optimal inhibitors pyridostigmine balance autonomic nervous system, diarrhea, cramps, salivation, cramps flushing. encouraged, find lowest possible clinically relevant, avoid overtreatment effects. critical medications important, prescriptions potentially worsen [[41]Machado-Alba J.E. Calvo-Torres L.F. Gaviria-Mendoza Mejia-Velez C.A. Prescription profile 56: 1041-1046Crossref (6) Key listed Table 1. immunological reaction junction thymus cognitive IgG cross blood-brain barrier, [[42]Whiting P.J. Cooper Lindstrom J.M. sera nicotinic human brain.J Neuroimmunol. 1987; 205-213Abstract though truly non-brain disorder, sometimes report memory, lapses concentration difficulties. Four separate altogether 184 [43Marra Marsili Quaranta Determinants elderly patients.Muscle 40: 952-959Crossref (9) 44Sitek E.J. Bilinska Wieczorek Nyka W.M. Neuropsychological 9-14Crossref (24) 45Feldmann Kiefer Wiegard Evers Weglage Intelligence, attention, memory gravis.Nervenarzt. 2005; 76: 960-966Crossref (5) 46Paul R.H. Cohen R.A. Gilchrist Ratings subjective mental relate performance gravis.J 243-246Abstract (33) They evidence neuropsychological verbal learning, memory. completing tests, controls. Impaired tests interpreted weakness. meta-analysis 300 tested 179 concluded performed domains [[47]Mao Z.F. Yin Lu Z.Q. X.Q. Association function: meta-analysis.Ann Indian Acad 131-137Crossref (10) ability Such reports imply true dysfunction Preliminary experimental indicate cerebral involvement [[48]Sabres Cognitive mice passively antibody seropositive 399: 15-21Abstract Scholar].MG brain, acknowledged tasks. Consequences young examined 801 German [[49]Ohlraun Hoffmann Klehmet al.Impact planning: How decide why?.Muscle 52: 371-379Crossref (11) 307 already completed before onset, half abstained intended having children time 73% agreed statement neurologist low level intensive abstaining giving birth. common concern medication unborn child. explains infrequent [[50]Hoff pregnancy, delivery, newborn.Neurology. 2003; 1362-1366Crossref (105) fact commonly pyridostigmine, prednisolone azathioprine safe developing child [[51]Norwood Dhanjal Hill James Jungbluth Kyle al.Myasthenia pregnancy: practice guidelines UK multispecialty group.J 85: 538-543Crossref (84) Scholar,[52]