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Quality of Life of Myasthenia Gravis Patients in Regard to Epidemiological and Clinical Characteristics of the Disease

Stojanov, Aleksandar MD*; Milošević, Vuk PhD*; Đorđević, Gordana PhD*,†; Stojanov, Jelena MD

doi: 10.1097/NRL.0000000000000238
Original Articles
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Background: Myasthenia gravis (MG) affects overall quality of life (QoL). The aim of the research was to evaluate QoL in patients suffering from MG in regard to epidemiological and clinical factors of the disease.

Methods: The study included 70 patients. The severity of clinical manifestation was estimated using quantitative MG score and MG composite score. Patients were classified by using Myasthenia Gravis Foundation of America Classification. The Questionnaire of Life Quality Specific for Myasthenia Gravis-15 items (MGQOL15) is developed for QoL assessment in patients suffering from MG. In addition to the MGQOL15 revised version (MGQOL15r), a 36-item health survey of the Medical Outcomes Study Short Form (SF36) questionnaire, the Hamilton scales for the assessment of anxiety (HAM-A), and depression (HAM-D) were also used.

Results: MGQOL15r scores are negatively correlated with SF36 scores and positively correlated with scores on HAM-A and HAM-D scales (P<0.001). Patients with longer disease duration and severe clinical manifestation often manifest anxiety, depression, and have poorer QoL (P<0.05). In relation to the presence of the anti-nAchR antibody, statistically significant differences were found in relation to the summed scores on scales for assessing QoL, as well as on a HAM-A scale (P<0.05). Physical workers and unemployed patients had worse scores in relation to retired and administrators/intellectual workers on all scales (P<0.001).

Conclusion: MGQOL15r is a life quality assessment questionnaire that could be used in routine practice in patients with MG. It is much simpler for use in these patients than SF36 and provides relevant data.

*Clinic of Neurology, Clinical Center of Nis

Medical Faculty, University of Nis

Special Psychiatric Hospital “Gornja Toponica,” Nis, Serbia

The authors declare no conflict of interest.

Correspondence to: Aleksandar Stojanov, MD, Ozrenska Street 32, Nis 18000, Serbia. E-mail: astojanov1986@gmail.com.

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BACKGROUND

Chronic acquired myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by muscular fatigue, which often leads to daily variation in muscle weakness and different degree of functional disability in patients.1,2 With the equal representation among young people and the elderly, and twice as higher incidence in females below the age of 50, MG notably affects daily physical engagement, working ability, family functioning, and overall quality of life (QoL).3,4 Symptoms could be more pronounced in the evening or after exercising, and minimal or even absent during the neurological examination. Also, there is clinical and epidemiological diversity among patients. QoL in these patients is affected by the inability to achieve premorbid capacity, despite the implementation of adequate and accessible therapeutic modalities and constant need for health resources.5 Examination of QoL in these patients is very important in order to estimate the individual needs of patients and their requirements, as well as making the therapeutic approach individualized and to provide psychosocial support by appropriate experts.6 Health-related quality of life (HRQoL), measured by self-administered questionnaires, is considered essential in the evaluation of functional status in patients.7 Many studies use a 36-item health survey of the Medical Outcomes Study Short Form (SF36), a questionnaire that covers general parameters for assessing QoL.8 Although very useful, this questionnaire is not wholly suitable for diseases which have special characteristics, such as MG.9 Special questionnaire Questionnaire of Life Quality Specific for Myasthenia Gravis-15 items (MGQOL15) is developed for using in patients suffering from this neuromuscular disease. The previous version of this questionnaire contained 60 questions, which then was reduced to an acceptable number of 15, based on which QoL could be effectively rated.10 The last revised version of the questionnaire (MGQOL15r) was proposed in 2016 by the same authors.11 This questionnaire covers issues related to the impact of disease on physical, psychological, and social aspects. Dysfunction is identified in many life domains. MGQOL15 outperformed SF36, demonstrated a stronger correlation with changes in severity of the disease, and longitudinal construct validity and test-retest reliability.12

We hypothesized that epidemiological and clinical factors could have an impact on the scores obtained on QoL questionnaires. The aim of this research was to evaluate the QoL in patients suffering from MG, with regard to clinical and epidemiological characteristics of the disease.

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METHODS

The study included 70 adult patients, who were treated at the Clinic of Neurology, Nis, from January 2017 to 2018. MG was diagnosed on the basis of the patient’s history, physical examination, a prostigmin test, repetitive nerve stimulation test results, and the exclusion of other possible causes of symptoms. Data on the epidemiological and clinical characteristics of the disease were collected (sex, current age, disease duration, data on employment status, presence or absence of pathologically altered thymus and conducted thymectomy, and presence or absence of anti-nAchr antibodies). The actual severity of clinical manifestation was estimated using quantitative MG score (QMG)13 and MG composite score.14 Patients were then classified by type and severity of clinical complaints using the system, proposed by the Myasthenia Gravis Foundation of America (MGFA) classification.

The study excluded patients on artificial ventilation that belong to the group V according to the MGFA classification system. Patients with other chronic diseases that could affect QoL (diabetes, asthma, and malignancy—with an exception of malignant thymoma, hypertension, heart failure, renal, and hepatic insufficiency) were also excluded. A small number of patients with positive anti-MUSK antibodies were excluded from the study, mostly due to an insufficient number of patients with the presence of these antibodies. Only patients with positive anti-nAchR antibodies and seronegative patients regarding both of the examined antibodies were taken into consideration.

The MGQOL15r questionnaire consists of 15 questions, each ranging from 0 to 4.11 The maximum score is 60 and represents the biggest impact on the HRQoL in these patients. There are 4 dimensions in this questionnaire: mobility (8 items), symptoms (3 items), general contentment (2 items), and emotional well-being (2 items). The approval was obtained from the corresponding author who created the original version of this questionnaire for use and translation into the Serbian language. MGQOL15r was translated and cross-culturally adapted using the standard recognized methodology,15 which means that the questionnaire was first translated into Serbian twice. The 2 independent translations were discussed by the translators and by 2 neurologists resulting in the first version, which was translated back into English by 2 translators. These 2 translations were compared with the original questionnaire, resulting in the second Serbian version. After minor corrections, the third and final Serbian version of the MGQOL15r was constructed.

SF36 measures 8 general health dimensions: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health and also total score was measured. The scores for each of the 8 domains and total score were converted to 0 to 100 scale, with a higher score representing better health. In addition to the MGQOL15r and the SF36 questionnaire, the Hamilton scales for the assessment of anxiety (HAM-A) and depression (HAM-D) were also used.16,17 All subjects gave their written informed consent for participating in the study. Questionnaires were assigned to patients only after carrying out a clinical examination and collecting epidemiological data.

All data were statistically processed by IBM SPSS statistical software (version 21) for Windows operative system. P-values of <0.05 were regarded as statistically significant. Numerical data are presented as means±SD. The Mann-Whitney test was used to compare continuous variables between 2 groups, and the Kruskal-Wallis test was used to compare more than 2 groups. Correlations were assessed using the Pearson correlation coefficients or the Spearman correlation coefficients.

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RESULTS

The study included 70 patients whose epidemiological and clinical characteristics are listed in Table 1. The results obtained for all subjects on the scales for MGQOL15r and SF36 are presented in Table 2 and Figure 1. The highest scores on the MGQOL15r scales were obtained in response to question 2 (regarding the problem of vision) and 8 (regarding personal independence). On SF36 domains, the disease mostly affected physical functioning, whereas the least affected dimension of health was recorded on a scale that measures physical pain.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

FIGURE 1

FIGURE 1

MGQOL15r scores are negatively correlated with SF36 scores (P<0.001) and with scores of its domains (P<0.05). Also, this score positively correlates with scores on HAM-A and HAM-D, indicating the role that depression and anxiety have on the QoL in these patients (P<0.001).

In regard to the actual age of the patient, there was no statistically significant correlation between the test scales. As far as the duration of the disease is concerned, there was a significant correlation, in the sense that patients in whom the disease lasts for a long period often manifest anxiety, depression, and have poorer HRQoL assessed on SF36 and MGQOL15r (P<0.05). An impact on the QoL, anxiety, and depression is evident in regard to the degree of MGFA classification (poorer QoL estimated at SF36 and MGQOL15r, and more depression and anxiety) which is represented in Figure 2. A correlation is also recorded on all examined scales in regard to the estimated severity of the disease using QMG and MG composite score scales (Table 3). Significantly higher scores were obtained in patients with generalized and bulbar symptomatology than in patients with a pure ocular form of the disease (Fig. 3).

FIGURE 2

FIGURE 2

TABLE 3

TABLE 3

FIGURE 3

FIGURE 3

On SF36 scales, the only statistically significant difference between sexes was observed on the scale for physical functioning, that was worse for female (P<0.05). There was no difference in MGQOL15r in the total sum score, but the answers to questions 11 and 14 (P<0.05) were statistically significantly worse for females. There was no difference in overall scores on any implemented scale. In relation to the time of onset (early or late) on the SF36 questionnaire, physical health was estimated to be statistically significantly worse in the group with a later onset (P<0.05). There was no difference in other SF36 domains, and they were not observed in either total scores on examined scales. Patients with pathologic changes of thymus and conducted thymectomy compared with those in whom pathologic changes of thymus have not been found, had no statistically significant difference in the investigated scores. In relation to the presence of the anti-nAchR antibody, statistically significant differences were found in relation to the summed scores on both scales for assessing QoL, as well as on a HAM-A scale (Table 4). Almost all subscales on the SF36 questionnaire (except those for the assessment of pain) showed a statistically significant difference, in the sense that the values obtained in patients with antibodies showed worse results (P<0.05). As for employment, physical workers and unemployed patients had worse scores in relation to retired and administrators/intellectual workers on all scales (Table 5).

TABLE 4

TABLE 4

TABLE 5

TABLE 5

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DISCUSSION

The patients’ QoL is related both to the influence of the disease and to the factors that are independent of the disease itself (level of education, employment, and family requirements). MG as a chronic fluctuating illness can lead to limitation of daily activities on multiple levels. SF36 is an example of a generic questionnaire that is often used to assess the HRQoL in patients with MG, but contains some parts that are not characteristic for this disease (pain), and does not contain questions about the frequent symptoms of MG (visual problems, swallowing, speaking, etc).18 It was estimated that priority should be given to specific HRQoL questionnaires.3 In our research, in addition to the SF36 questionnaire, we used a more specific version, designed only to assess the HRQoL in patients suffering from MG (MGQOL15r). It was translated into Serbian for the needs of this research and has been transculturally adapted so it can be used in further daily clinical work in our language area. As an advantage of this questionnaire, it is necessary to emphasize the easy application and comprehension by the patient, which can lead to the possibility of routine use in everyday clinical practice.

By using both questionnaires, our research points out the role of the disease severity, anxiety, and depression, as well as the duration of the disease on estimated HRQoL of these patients. Previous studies have shown a link between the severity of the disease and the impact on the HRQoL of those affected, especially on the physical aspects.19 Padua and colleagues showed in their study that HRQoL was also impaired in patients in stable remission due to therapeutic treatments, meaning that constant need for medication may be a burden to these patients, so reduced HRQoL is a consequence of a chronic illness which requires constant therapeutic interventions, the use of health resources, and the avoidance of provocative factors that can lead to exacerbation. Basta et al20 recorded a significant influence of the disease both on physical and mental aspects by using SF36 questionnaire on patients in Serbia. This research showed a clear correlation between estimated anxiety and depression with HRQoL, but without a clear correlation with the duration of the disease. The results of other studies showed that the physical component is more affected than the mental one, which may be due to the adequate psychosocial support that these patients receive in developed countries.21 The relationship between depression and sleep disorders with poor HRQoL was also recorded.22 Patients with MG, compared with healthy controls, showed more significant physical and cognitive fatigue.23 The study conducted by Winter et al24 showed that HRQoL correlates with the severity of muscle weakness and fatigue. The disease has a significant impact on the physical, psychological, and social well-being of the individual. All of these results confirmed the significant role of the disease in daily functioning and fulfillment of social tasks. Some studies do not show a clear correlation between the MGFA classification and the impact on HRQoL, but in these studies, there is a clear correlation between the degrees of current clinical manifestation, depression, and anxiety with scores on scales that assess the QoL.25

A smaller number of studies deal with the HRQoL of these patients by comparing them to the clinical characteristics of the diseased—the presence of antibodies, disease duration, the pathology of the thymus, etc.26 In a survey conducted by Boldingh et al,27 generalized forms of the disease, female sex, and treatment with secondary immunosuppressive agents were associated with lower scores on scales used for assessing HRQoL, but the age of onset, the pathologically altered thymus and the presence of antibodies were not found to influence the HRQoL. In our study, females had poorer results in self-evaluation of depression, based on the question that is an integral part of MGQOL15r. Also, there was no difference in the total scores of MGQOL15r and SF36 among the sexes, nor in the estimated anxiety and depression on the Hamilton scales. In relation to that, it should be noted that the original research which presents MGQOL15r scoring system only took into account the total score. A study on patients in Serbia conducted by Basta et al20 suggested that there was no difference between the sexes, neither among the groups of patients who had been subjected to thymectomy nor among those who were not. Differences between the sexes were not observed in studies performed in other populations.28 We observed that SF36 had poorer physical functioning in females and in those in whom the disease started later, which was also the result of the researchers in Germany.29 These differences were not reflected in the total scores on any of the scales used. What we must not ignore are increased social demands, the role in the family, and hormonal variability, especially expressed in women in the generative period, when the largest number of women has first symptoms of MG.30 In our research, there was a difference in terms of poor physical functioning in patients in whom the disease started later, but also with no difference in the sum score on questionnaires used. As for the patients who were thymectomized due to the pathologically altered thymus and those who were not, there was no significant difference between these groups, which is consistent with the results of previous studies.28 A statistically significant difference was observed between the group with anti-nAchR antibodies and seronegative patients, which was not the case in previously performed trials.26 This could be a consequence of a small number of patients in the seronegative group and the fact that anti-MUSK patients being treated in our center were not taken into consideration due to their insufficient number. As far as employment is concerned, sickness and physical weaknesses also limit the ability of patients to engage in business, especially with physical work. It often happens that this disease is the cause of unemployment or premature retirement. In previous research, intellectual work engagement significantly correlates with better scores on certain scales of HRQoL, like in our study.20,31 The fact that the group of unemployed comprised a great number of patients with physical weakness and more severe clinical manifestations of the disease should be taken into consideration. The beneficial effect of the working environment and social occupation is never negligible. However, since it is a disease in which muscle fatigue is the main symptom, it is not unusual that physically active patients have the worst scores on all investigated scales. Research in the Chinese population showed clearly better physical functioning in students than in retired or workers involved in both physical and intellectual work.28

It should be noted that therapeutic treatment and the dose of drugs in many studies correlated with the results obtained on tests that assess the QoL. Thus, research conducted by Japanese researchers has shown that higher scores on the MGQOL15 questionnaire were obtained in patients with higher doses of oral corticosteroid preparations.32 Also, marital status and level of education could have an impact on QoL. These aspects have not been examined in our research and could be examined in future studies on our population. A limitation of our research is a relatively small patient population, meaning it could affect the power of statistical analysis.

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CONCLUSIONS

Patients with severe clinical manifestations and longer duration of the disease, as well as those with anxiety and depression, have poorer QoL. Also, patients with the bulbar manifestation of the disease showed lower scores on the QoL questionnaire. The time of the disease onset, sex, and the presence of pathologically altered thymus do not correlate significantly with the degree of QoL impairment, which is significantly lower in patients with positive anti-nAchr antibodies. Significant impact on QoL was obtained in the group of physical workers and unemployed patients. MGQOL15r is a life quality assessment questionnaire that could be used in routine practice in patients with MG. MGQOL15r is much simpler for use in these patients than SF36 and provides relevant data.

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Keywords:

myasthenia gravis; quality of life; MGQOL15r

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