myasthenia gravis: sleep quality, quality of life, and disease severity

MYASTHENIA GRAVIS: SLEEP QUALITY, QUALITY OF LIFE,AND DISEASE SEVERITYELENA HERNANDEZ MARTINEZ DE LAPISCINA, MD, MARIA ELENA ERRO AGUIRRE, MD, PhD,

TERESA AYUSO BLANCO, MD, PhD, and IVONNE JERICO PASCUAL, MD, PhD

Department of Neurology, Complejo Hospitalario de Navarra, Irunlarrea Street, 3, 31008 Pamplona, Spain

Accepted 24 December 2011

ABSTRACT: Introduction: There is much research on qualityof life in myasthenia gravis (MG), and its relationship to diseaseseverity is well-established. However, evidence regarding sleepdisturbance in MG is inconclusive. Methods: To evaluate sleepand quality of life among clinically stable MG patients, 54 sub-jects were investigated by means of the Pittsburgh Sleep Qual-ity Index (PSQI), Epworth Sleepiness Scale (ESS) and 15-Item-Quality-Of-Life Instrument for MG (MG-QOL15). Results: Apathological PSQI score, which was observed in 59% ofpatients, was increased in subjects with active disease com-pared with patients in clinical remission [odds ratio ¼ 4.3; confi-dence interval 95% (1.0–17.6); P ¼ 0.04]. We found arelationship between PSQI and MG-QOL15 scores in patientswith clinically active disease (r ¼ 0.62; P < 0.001). Conclu-sions: Our study highlights the high prevalence of sleep disturb-ance among MG patients. Disease severity may be consideredto be a MG-specific risk factor for patient-reported sleep dis-turbance. The MG-QOL15 and PSQI should be used to esti-mate the impact of the disease on sleep and quality of life.

Muscle Nerve 46: 174–180, 2012

Myasthenia gravis (MG) is an autoimmune disor-der of the neuromuscular junction. Acetylcholineesterase inhibitors, corticosteroids, and immuno-suppressive drugs are used to treat MG. Unfortu-nately, therapies for MG do not always produce acomplete remission of the disease, so clinical activ-ity may significantly decrease quality of life. Thereis much research on quality of life (QOL) in MGpatients,1–7 and a correlation between QOL anddisease severity has been established.1–3,6,7

However, very little is known about the relation-ship between MG, sleep-related disorders and sleepquality. An increased incidence of sleep disorders,especially sleep disordered breathing8,9 (SDB) andobstructive sleep apnea10 (OSA) has been noted inMG patients. However, other authors have notfound an excess risk of sleep disorders.11 An associ-ation between corticosteroid use and risk of sleepdisorders has been reported,10 but the influence ofdisease severity on sleep quality is not clear. Someauthors have reported an increased prevalence of

poor sleep quality in symptomatic MG patientscompared with controls,12 while others did notfind an inverse correlation between disease severityand sleep quality.10,11 Thus, data on sleep-relateddisorders and sleep quality in MG are scarce andinconclusive. The aim of this study was to evaluateself-perceived sleep quality in clinically stable MGpatients and to search for MG-specific risk factorsfor poor sleep quality.

We also explored quality of life in clinically sta-ble MG patients and assessed whether there was arelationship between disease severity, quality oflife, and subjective sleep quality.

MATERIALS AND METHODS

Subjects. This retrospective, noncontrolled, cross-sectional study was conducted between 1 January2010 and 31 May 2010. Patients were recruitedfrom the outpatient neurology clinic of our hospi-tal. Our inclusion and exclusion criteria have beenpreviously used by other authors.6 Inclusion crite-ria were: (1) age greater than 18 years; (2) adiagnosis of ocular or generalized MG based onclinical examination and supported by positiveacetylcholine receptors (AchRs) antibodies and/orneurophysiologic evidence of a neuromuscularjunction disorder (abnormal repetitive nerve stim-ulation or abnormal single-fiber electromyographystudies); and (3) stable clinical condition (lack ofworsening of baseline signs and symptoms requir-ing modification of treatment) and unchangedtherapy during the 6 months preceding the study.Exclusion criteria were: (1) psychiatric diseases ormedical conditions which might affect cardiac orrespiratory function and predispose to sleep disor-ders (heart disease, chronic obstructive pulmonarydisease, asthma) and (2) previously diagnosedsleep disorder. We recruited 59 MG patients. Fourpatients were not clinically stable, and 1 patienthad a laryngeal neoplasm and depression whichmay have impacted sleep quality and QOL. fifty-four patients were finally included in our study.

Demographic, anthropometric and clinical datawere collected. Clinical data included time fromonset, AchR positivity, presence of thymoma, MGseverity and distribution at time of study, andchronic therapy for MG during the 6 months pre-ceding this study. According to MG severity anddistribution at the time of study, patients were

Abbreviations: AchRs, nicotinergic acetylcholine receptors; ANOVA,analysis of variance; BMI, body mass index; ESS, Epworth SleepinessScale; HRQOL, health related quality of life; MG, myasthenia gravis;MGFA, Myasthenia Gravis Foundation of America; MG-QOL15, 15-item-quality-of-life instrument for MG; OSA, obstructive sleep apnea; PSQI,Pittsburgh Sleep Quality Index; QOL, quality of life; SD, simple standarddeviation; SDB, sleep disordered breathing; X, mean values

Correspondence to: E. Hern�andez Martınez De Lapiscina; e-mail:[email protected]

VC 2012 Wiley Periodicals, Inc.Published online 6 January 2012 in Wiley Online Library(wileyonlinelibrary.com). DOI 10.1002/mus.23296

Key words: Epworth Sleepiness Scale, Health-related quality of lifeMyasthenia gravis, sleep disorders, Pittsburgh Sleep Quality Index

174 MG, Sleep Quality, and QOL MUSCLE & NERVE August 2012

categorized into three different categories: (remis-sion, ocular, and generalized). ‘‘Remission’’ wasdefined as having no symptoms and no signs onneurological evaluation. We were aware that ourdefinition of ‘‘remission’’ differed from the oneprovided by the Task Force of the Medical Scien-tific Advisory Board of the Myasthenia Gravis Foun-dation of America (MGFA),13 as we categorizedasymptomatic patients who were taking acetylcho-linesterase inhibitors into the ‘‘remission’’ category.The reason was that our aim was to assess the rela-tionship between disease severity and sleep qualityirrespective of acetylcholinesterase inhibitor andimmunosuppressive therapy status. ‘‘Ocular’’ wasdefined as having only ocular symptoms or signssuch as diplopia, ophthalmoplegia, or/and ptosis.‘‘Generalized’’ was defined as having symptoms orsigns in other distributions. Patients belonging tothe generalized category were subclassified accord-ing to the MGFA classification criteria.13 Therapyincluded pyridostigmine, prednisone, and immu-nosuppressive agents such as azathioprine, cyclo-sporine, mycophenolate mofetil, and tacrolimus.

All subjects gave informed consent to partici-pate, and the study was approved by the Local Eth-ical Committee.

Questionnaires. Three outcome variables weremeasured: subjective sleepiness (Epworth Sleepi-ness Scale, ESS), sleep quality (Pittsburgh SleepQuality Index, PSQI), and general quality of life(15-Item Quality-Of-Life Instrument for MyastheniaGravis, MG-QOL15).

The presence of daytime somnolence wasassessed using ESS.14 This questionnaire measuresthe probability of falling asleep for 8 different situa-tions in daily life. Scores higher than 10 are consid-ered to reflect abnormal daytime somnolence.

PSQI15 was used to evaluate sleep quality dur-ing the previous month. The global score rangesfrom 0 to 21. The cutoff is 5 points, thus a PSQIscore greater than 5 suggests poor sleep quality.

Health-related quality of life (HRQOL) wasmeasured using the MG-QOL15.6 This question-naire is a validated tool for assessing HRQOL inMG patients in the clinical practice setting.

Procedure and Statistical Analysis. After a briefdescription of demographic and clinical data ofpatients included in our study, we explored subjec-tive sleep quality.

First, we described PSQI and ESS scores consid-ered as both continuous and categorical variables(thresholds described above) according to previ-ously mentioned disease severity categories.

To evaluate MG-specific risk factors for patient-reported sleep disorders, we dichotomized thePSQI variable into 2 categories according to the

PSQI cutoff point (PSQI score �4: normal vs.PSQI score >5: pathological). We categorized MGpatients according to this new variable, and we per-formed univariate analyses to compare demo-graphic and clinical data between these 2 catego-ries, considering patients with a normal PSQIscore as a reference category. Then, we selectedsignificant variables in these univariate analysesand data from previous studies10,11 to constructthe multiple regression model. We fitted a logisticregression adjusted for age, gender, body massindex (BMI), disease severity, mean dose of pyri-dostigmine, need for prednisone and use of immu-nosuppressive drugs. Because there were only 6patients in the ocular category, we merged thegeneral and ocular categories to develop a newdichotomized variable to summarize disease sever-ity (remission vs. clinical disease activity). This newvariable was the one included in the multivariatemodel to measured disease severity.

We evaluated quality of life using the MG-QOL15 scale, and we explored results in the 3 pre-viously established categories.

Finally, we assessed the correlation between theMG-QOL15 total score and PSQI global score.

We used proportions to describe qualitativeresults. Quantitative data were presented by provid-ing the mean values (X) with simple standard devi-ation (SD). Univariate analyses were made with achi-squared test or a Fisher test for categorical vari-ables and a t-test for independent groups for con-tinuous variables. A one-way analysis of variance(ANOVA) was used to compare PSQI global scoresand PSQI component subscores according to thedifferent categories of disease severity. We fittedpost hoc analysis with the Bonferroni test if theANOVA P-value reached statistical significance.Correlations were calculated with the Pearson Cor-relation Coefficient. A P-value below 0.05 was con-sidered to be statistically significant.

Statistical analyses were carried out in SPSS17.0 (SPSS Inc., Chicago, IL, USA).

RESULTS

Demographic and Clinical Data. A total of 54 clini-cally stable MG patients (28 female mean age 66.16 16.9) were included. Twenty five patients wereclassified as remission, 6 as ocular and 23 as gener-alized MG. Most subjects received pyridostigmine.A total of 55.6% of patients received prednisone,and 32% of patients required immunosuppressiveagents. Further details about baseline characteris-tics can be found in Table 1.

Patient-Reported Sleep Disturbances. We found amean ESS score of 6.02 (SD ¼ 3.75). 14.8% ofpatients had a pathological ESS score (ESS > 10).The prevalence of a pathological ESS score was

MG, Sleep Quality, and QOL MUSCLE & NERVE August 2012 175

higher among patients with generalized MG thanit was in patients in clinical remission (30.4% vs.4% P ¼ 0.02). However, we did not find significantdifferences in the quantitative ESS scores betweenthe generalized, ocular, and remission categories(see Table 2).

The mean PSQI score was 7.31 (SD ¼ 4.47) inour patients. We identified patient-reported sleepdisturbances in nearly 60% of patients (PSQI > 5).A pathological PSQI score was found in 82.6% ofpatients in the generalized category, 50% in theocular category and 40% in the remission category.A statistically significant difference was only foundbetween the generalized group and the remissioncategory (82.6% vs. 40%; P < 0.003). PSQI globalscores and PSQI component subscores accordingto different categories of disease severity can befound in Table 2. Patients included in the general-ized category had the worst results in the PSQI

global score and in the scores of almost all PSQIcomponents. The 3 categories did not differ onthe PSQI component score related to sleepduration, sleep disturbance and use of sleep medi-cations. The need to wake up in the middle of thenight or early morning and trouble breathing com-fortably were the most commonly reported causesfor sleep disturbances among patients belongingto the 3 categories. Subjective sleep quality, sleeplatency, sleep efficiency, and daytime dysfunctionPSQI component scores were significantly higherin patients in the generalized category comparedwith the remission category.

Finally, patients were categorized according toPSQI score (PSQI � 5 vs. PSQI > 5), and we fittedunivariate analyses to compare demographic andclinical data. Absence of remission (68.8% vs.31.8%; P ¼ 0.007) and need for immunosuppressiveagents (43.8% vs. 18.2%; P ¼ 0.050) were increased

Table 1. Baseline data according to categories of MG disease severity.

Variables (N¼54) Global sample N¼54 Remission N¼25 (46.3) Ocular N¼6 (11.1) Generalized N¼23 (42.6)

Age (years) 66.1616.9 68.6618.2 68.5614.7 62.7615.9Gender female [n (%)] 28 (51.9) 11 (44.0) 4 (66.7) 13 (56.5)BMI* (kg/m2) 26.366.5 27.067.00 21.1610.6 27.064.0Duration MG (years) 9.369.1 8.267.4 9.666.6 10.3611.2AchR† antibody positive (mM) n[%]) 48 (88.9) 21 (84.0) 5 (83.3) 22 (95.7)Thymoma [n (%)] 8 (14.8) 3 (12.0) 0 (0) 5 (21.7)Treatment#

Pyridostigmine [n (%)] 52 (96.2) 23 (92.0) 6 (100) 23 (100)Pyridostigmine mean dose (mg/24h) 196.1676.4 163.2676.5 175.0661.2 237.4660.1Prednisone [n (%)] 30 (55.6) 11 (44.0) 0 (0) 19 (82.6)Prednisone mean dose (mg/48 h) 12.6620.5 6.9612.7 ---- 22.2625.6Immunosuppressive agents‡ [n (%)] 18 (32) 5 (20.0) 1 (16.7) 12 (52.2)

Mean 6 standard deviation (SD) unless otherwise stated.*Body mass index.†Nicotinergic acetylcholine receptors.#Treatment during 6 months preceding the study.‡Azathioprine, cyclosporine, mycophenolate mofetil, and tacrolimus.

Table 2. ESS and PSQI scores according to categories of MG disease severity.

Generalized Ocular Remission ANOVA (G-O) (G-R) (O-R)

ESS>10 (n [%]) 7 (30.4) 0 (0) 1 (4.0) ---- 0.289 0.02 1.000ESS Score 7.264.2 5.763.6 5.063.1 0.139

Generalized Ocular Remission ANOVA (G-O) (G-R) (O-R)

PSQI>5 [n (%)] 19 (82.6) 3 (50.0) 10 (40) ---- 0.131 0.003 0.676PSQI Global 9.364.5 7.064.9 5.663.7 0.012 0.706 0.010 1.000PSQI ComponentSubjective sleep quality 1.660.9 1.361.2 0.860.9 0.020 1.000 0.016 0.804Sleep latency 2.061.1 1.561.4 1.161.2 0.042 1.000 0.037 1.000Sleep duration 1.161.0 1.561.4 0.861.0 0.280Sleep efficiency 1.961.1 0.861.2 161.2 0.024 0.175 0.038 1.000Sleep disturbances 1.160.5 0.860.4 1.060.3 0.279Use of sleep medications 0.561.0 0.260.4 0.260.8 0.572Daytime dysfunction 1.160.7 0.860.4 0.560.6 0.020 1.000 0.017 0.823

Mean 6 standard deviation (SD) unless otherwise stated. One-way analysis of variance (ANOVA) and Bonferroni test for multiple comparisons were usedfor quantitative data. Chi-squared test or Fisher tests were used for qualitative data.


in patients with a pathological PSQI global scorecompared with reference category (see Table 3). Alogistic regression analysis (see Table 4) revealedthat patients with a pathological PSQI global scorewere more likely to not be in clinical remission[odds ratio (OR) ¼ 4.28; confidence interval (CI)95% (1.04–17.6); P ¼ 0.044]. There were no statis-tically significant differences in other variables.

Health-Related Quality of Life. The mean MG-QOL15 global score was 10.9 (SD ¼ 10.9). MG-OOL15 global score and each item’s responseoptions among patients belonging to the three previ-ously mentioned categories are described in Table 5.

The remission and the ocular categories selectednormal (‘‘not at all’’) scores for almost all of thetest items except for ‘‘trouble using my eyes,’’ whichwas commonly selected by patients in the ocular cat-egory. The most severe response options (‘‘quitea bit’’ and ‘‘very much’’) were most frequentlyselected by patients in the generalized category.

Finally, we found a statistically significant corre-lation between MG-QOL15 and PQSI question-naires (r ¼ þ0.621; P < 0.001). When performed

separate analyses for patients in clinical remissionand for patients with active disease, we onlyobserved a significant correlation in the lattergroup (see Table 6). We did not find a correlationbetween MG-QOL15 and ESS questionnaires (r ¼þ0.256; P ¼ 0.062).

DISCUSSION

Nearly 15% of our patients had a pathological ESSscore. A pathological PSQI score was found in 59%of patients. Prevalence of a pathological PSQIscore was higher in subjects with clinical disease ac-tivity compared with those who were in clinicalremission. Lack of clinical remission was related toa higher MG-QOL15 score. We found a relation-ship between PSQI and MG-QOL15 in patientswith clinical disease activity.

Previous studies have reported a higher preva-lence of daytime sleepiness measured by ESSamong MG patients. Quera-Salva et al. found that 4of 12 (33%) subjects reported daytime sleepiness.9

Nicolle et al. found a pathological ESS score in25% (21/84) of their patients.10 Prudlo et al. foundthat 31.5% (6/19) of their patients complained of

Table 3. Comparison of baseline characteristics according to PSQI category.

Variables PSQI � 4 PSQI > 5 P Value

No. (n) 22 32Age (years) 63.8619.1 67.6615.3 0.428Gender Female [n (%)] 11 (50) 17 (53.1) 0.821BMI* (kg/m2) 25.767.0 26.866.3 0.574Duration MG (years) 8.066.2 10.1610.6 0.412Positive AchR† antibody (mM) [n(%)] 20 (90.9) 28 (87.5) 0.695Thymoma [n (%)] 2 (9.1) 6 (18.8) 0.326MG Severity at time of studyPresence of ocular or generalized disease [n (%)] 7 (31.8) 22 (68.8) 0.007

Treatment during 6 months preceding the studyPyridostigmine mean dose (mg/24 h) 175.9 680.9 210.0671.1 0.108Prednisone [n (%)] 9 (40.9) 21 (65.6) 0.073Prednisone mean dose (mg/48h) 8.7613.5 15.3624.0 0.251Immunosuppressive agents‡ [n (%)] 4 (18.2) 14 (43.8) 0.050

Mean 6 Standard Deviation (SD) unless otherwise stated.*Body Mass Index; †nicotinergic acetylcholine receptors; ‡Azathioprine, cyclosporine, mycophenolate mofetil, and tacrolimus.

Table 4. Odds ratios and 95% confidence intervals of contributing factors for a pathological PSQI score in MG patients.

Variables B E.T. Wald gl Sig. Exp (B)

CIs 95% for EXP (B)

Inferior Superior

Age .025 .021 1.514 1 .219 1.026 .985 1.068Gender .080 .653 .015 1 .902 1.084 .301 3.898BMI* .018 .050 .137 1 .712 1.019 .924 1.123Presence of ocular or generalized activity 1.455 .722 4.061 1 .044 4.283 1.041 17.624Pyridostigmine (mean dose) .001 .005 .057 1 .811 1.001 .992 1.010Prednisone treatment .444 .748 .352 1 .553 1.559 .360 6.752Immunosuppressive agents† .799 .768 1.083 1 .298 2.223 .494 10.015

*Body mass index; †Azathioprine, cyclosporine, mycophenolate mofetil, and tacrolimus.


mild or moderate somnolence (ESS � 8).11 Ourfindings were not directly comparable to those stud-ies, because our patients were less severely affected.While only 43% of our patients complained of gen-eralized muscle weakness, generalized disease wasfound in 100%, 85%, and 70% of patients in theseries of Quera-Salva et al.,9 Nicolle et al.,10 andPrudlo et al.,11 respectively. Considering onlypatients with generalized disease, we found a similarprevalence (30%) of daytime sleepiness. Therefore,our data indicate that there is excessive daytimesleepiness in well-controlled MG patients.

A significant sleep disturbance was found in59% of patients. Similar to previously publishedstudies,12 subjective sleep quality, sleep durationand sleep efficiency were reduced, while sleeplatency was increased in clinically stable MG

patients. By contrast, only 20.8% of the Spanishgeneral population report a significant sleep dis-turbance (at least one insomnia symptom at least 3nights per week) in a recent cross-sectional studyperformed in a sample of 4065 individuals.16

We found an inverse association between dis-ease severity and prevalence of patient-reportedsleep disturbance. A cross-sectional case-controlstudy found that MG patients had more pathologi-cal PSQI scores than did healthy controls.12 Otherauthors suggested that disease severity did not cor-relate with sleep disorders.10,11 However, our find-ings were not directly comparable to those studiesby the fact that the severity of MG was measureddifferently. The study of Prudlo et al.11 includedonly symptomatic MG patients, and Nicolle et al.10

analyzed the influence of disease severity while cat-egorizing the sample into 2 categories using theMGFA classification (MGFA<III vs. MGFA�III).We studied disease severity in terms of remissionor not remission. We suggest that the lack ofremission should be considered as an independentMG-specific risk factor for sleep disturbance.

Some authors have found that patients withOSA were more likely to be on corticosteroid ther-apy during the year preceding the study10 (29% inOSA negative vs. 50% in OSA positive). We didnot find an association between sleep quality and

Table 5. MG-QOL15 according to MG disease severity categories.

Categories of MG’s severity

Remission Ocular Generalized

MG-QOL15 Global Score 3.665.2 8.867.4 19.3610.5

Percentage of responses per test item according to MG severity

Remission Ocular Generalized

0 1 2 3 4 0 1 2 3 4 0 1 2 3 4

1. I am frustrated by my MG 64 20 16 0 0 67 7 0 17 0 13 1 21 31 42. I have trouble using my eyes 92 0 4 4 0 17 1 66 0 0 39 7 26 9 93. I have trouble eating because of MG 96 0 4 0 0 100 0 0 0 0 52 9 30 9 04. I have limited my social activity because of MG 72 16 12 0 0 50 0 50 0 0 17 30 18 18 175. My MG limits my ability to enjoy hobbies

and fun activities72 16 8 4 0 50 33 17 0 0 17 13 39 22 9

6. I have trouble meeting the needs ofmy family because of my MG

100 0 0 0 0 100 0 0 0 0 83 4 9 4 0

7. I have to make plans around my MG 72 16 8 4 0 50 16 16 0 21 6 21 17 138. My occupational skills and job status have

been negatively affected by MG84 4 12 0 0 50 0 33 0 16 39 13 9 9 30

9. I have difficulty speaking due to MG 96 0 4 0 0 100 0 0 0 0 74 3 4 9 010. I have trouble driving due to MG 100 0 0 0 0 84 0 16 0 0 74 4 9 9 411. I am depressed about my MG 88 8 0 4 0 83 7 0 0 0 31 2 26 17 412. I have trouble walking due to MG 88 4 4 0 4 83 0 17 0 0 30 2 35 4 913. I have trouble getting around public

places because of my MG88 4 8 0 0 50 33 17 0 0 30 22 22 17 9

14. I feel overwhelmed by my MG 80 4 12 4 0 66 7 0 17 0 40 2 22 13 415. I have trouble performing my personal

grooming needs96 0 4 0 0 67 17 16 0 0 61 13 22 0 4

Table 6. Pearson correlation between MG-QOL15 and PQSIscales.

Correlation Coefficient P value

Total study group þ0.621 0.001*No remission category† þ0.620 0.001*Remission category þ0.355 0.082

*A value of P < 0.01 (bilateral) was considered statistically significant.†No remission category formed by the sum of generalized and oculargroups.


corticosteroid use. However, those authors alsofound a positive relationship between BMI andsleep disorders. Because they did not perform amultivariate analysis, an independent effect of cor-ticosteroid use could not be addressed. As theauthors acknowledged, the association with cortico-steroid use could be considered to be an indirecteffect of corticosteroid-induced weight gain.

We found that patients with a PSQI > 5 weremore likely to be on immunosuppressive therapyduring the 6 months preceding this study. However,this association did not reach statistical significancein the multivariate analysis. This is consistent withpreviously published results.11 The influence of ace-tylcholinesterase inhibitors was not confirmed inaccordance with the findings of others.12,17

According to the MGFA task force recommen-dation to use HRQOL measuments,13 we used theMG-QOL15 to evaluate perception and toleranceof MG-related dysfunction. Our results showed areduction in physical, mental, and social aspects ofHRQOL for patients with clinically stable MG.Scores for each response option for each item ofthe MG-QOL15 (except for ‘‘meet the needs of thefamily’’) are similar to those reported previously,6

so it enables us to consider that our cohort is rep-resentative of other cohorts. Consistent with previ-ous works,1–3,6,7 the HRQOL decreased as diseaseseverity increased, so that patients with generalizedmuscle involvement showed the highest level ofdisability. Our results suggest that social limitations(hobbies, employment) were more importantdeterminants of the decrease in HRQOL thanphysical limitations (trouble talking, driving).

We found a statistically significant correlationbetween the MG-QOL15 and PQSI scores. Whenwe performed subgroup (remission vs. active dis-ease) analysis, a significant correlation was onlyfound in patients without clinical remission.According to other authors’ findings,12 we con-cluded that a relationship between QOL and sleepquality could be established. The correlation ofthe MG-QOL15 and PQSI remained statistically sig-nificant only in symptomatic patients. It suggestsstronger associations between MGQOL-15 and MGseverity and of PQSI and MG severity, than ofPQSI and MGQOL-15. This might lead us to con-clude that disease severity explains the decrease inboth QOL and sleep quality.

There are some important limitations of thisstudy. One limitation is the cross-sectional designwhich prevented us from establishing a causativerelationship, because we cannot ensure an appro-priate temporal sequence. Another limitation isthe small sample size. Additionally, our recruit-ment through the outpatient Neurology clinic ofour hospital resulted in a sample of primarily older

male patients. The proportion of late-onset(72.2%) and male (48.1%) patients was not con-sistent with classical epidemiological findings18;however, an unexpected incidence of MG hasbeen described in the elderly population inSpain19 and Denmark.20 These two demographicissues may explain the high proportion of patientswith sleep complaints found in our study. Despitethis, multivariate analysis enables us to considerdisease severity as a risk factor for sleep disturb-ance regardless age and gender distribution. Fur-thermore, our sample was not well distributed interms of MG severity, and consequently generaliza-tion of our results to patients with ocular MG maynot be possible. Finally, our study was based on rel-evant and validated sleep questionnaires, but wedid not perform overnight polysomnograms to ver-ify these patient-reported sleep disturbances.

In conclusion, patient-reported sleep disturb-ance is frequently found in clinically stable MGpatients. Our study suggests that, in addition towell-known sleep disorder-related factors (e.g., age,male gender, and obesity), other MG-specific fac-tors may be involved. In particular, lack of clinicalremission should be considered to be a risk factorfor poor sleep quality. Our results highlight theimportance of sleep quality, a not well known issuein MG patients. A better understanding of theprevalence and severity of sleep disorders in MGpatients requires further investigation. Our find-ings should be replicated in a large prospectivecohort of MG patients that ensures an adequatetemporal sequence and avoids selection bias.Although we did not perform polysomnography,our results require objective verification with suchstudies. The MG-QOL15 should be used to esti-mate the impact of the disease on the QOL amongMG patients. It may be especially useful to informabout issues not directly related to muscle impair-ment, such as emotional or social well being. TheMG-QOL15 was found to be correlated with PSQIin well-controlled MG patients. In our opinion,HRQOL scales such as MG-QOL15 and SleepQuality scales such as PSQI should be used in theclinical setting to evaluate patients’ perception ofdisease dysfunction and the efficacy of therapy.

We thank the MG patients for participating in this study. Theauthors declare that they have no conflict of interest. We declarethat we have not received funding.

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myasthenia gravis: sleep quality, quality of life, and disease severity

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