Advances in medical therapy and intensive-care technology have increased the life expectancy of MG patients . Within the last 10 years QoL aspects were focused increasingly in studies on MG patients - predominantly in clinical settings with a limited number of patients (see introduction). However, up to now, scant information has emerged from population-based, non-clinical studies regarding MG patients' circumstances of life, experiences with health care and QoL. Therefore, our study focused on impairments, therapeutic course, use of the health care system, use of complementary and alternative medicine, QoL and its determinants among German MG patients.
Before discussing results, several limitations of the study have to be considered.
The cooperation with the German MG self-help organization was established to address as many MG patients as possible. However, it remains unclear whether this specific, organized patient population represents the "common German MG patient".
Data used in this study were extracted from a questionnaire. On the one hand it contained well known standardizes instruments as the SF-36. On the other hand descriptions of many aspects provided by patients are based on unstandardized, pre-determined questions (e.g. presence of MG related problems).
Unfortunately, the SF-36 is a non-disease-specific QoL tool. However, by that means, a comparison to the normative German population was possible. At the time of designing the study no MG-specific QoL tools were available.
As a result of the anonymous design it was not possible to assess patients' exact clinical status of MG according to the MGFA Classification  or to check patients' reports with medical records. Due to the large sample size, clinical assessments of each MG patient in the whole country would have required intensive use of trained neurologists; such a procedure was impossible to implement. To obtain more information on the validity of the results, perhaps future studies should examine a portion of MG patients in order to compare assessments by experts with patients' self-reported answers. Additionally, data could be biased by the selection-bias because probably only very motivated patients took part in the survey. On the other hand, a recall-bias has to be discussed (e.g. concerning length of disease duration).
In the following sections QoL and its determinants are discussed in the context of the international literature.
Results manifested reduced QoL in MG patients compared with a German normative cohort. Compared with normative data, Paul et al. found lower scores in seven of the eight domains of the SF-36 in MG patients (n = 27). The mean ratings concerning mental health were nearly identical to those of our study . Padua et al. investigated 46 MG patients, most of them participated during periods of worsening symptoms [26, 30]. The researchers found that the QoL of their patients was lowered in all scales of the SF-36, however .
Determinants of QoL in MG
In our study, stepwise linear regression analysis revealed that illness stability, impairments, comorbid diseases (e.g. depression), and employment were determinants of QoL. Similar determinants of QoL were found in another German study by Winter et al. : disease severity, depression, older age and increased body-mass-index (n = 37). These specific aspects are discussed more deeply in the following sections.
Disease severity - therapy
International literature also reveals a significant relationship between MG severity groups, QoL and disability profiles [35, 36]. In which way a stable or less severe disease level can be achieved? The most critical time concerning progression of MG encompasses the first 2 to 3 years after onset with an implication for early treatment. After that period, MG tends to stabilize or improve [3, 44]. Spontaneous remissions even have been reported . Mantegazza et al. reported the factors associated with complete, stable remission as being age at onset below 40 years, thymectomy, thymic hyperplasia, and female sex . Bachmann et al. showed that patients with generalized MG who underwent thymectomy had significantly greater rates of remission and improvement compared with conservative treatment. Furthermore, they had a significantly greater survival .
Rates of progression of ocular MG to generalized symptoms were reported as being 49%-69% [44, 46]. However, the risk of generalization can be minimized by up to 75% through treatment of patients with corticosteroids or azathioprine . It has to be considered that long-term immunosuppression and thymectomy have been suspected of causing increased illness in elderly patients . Thus, elderly patients require heightened attention from healthcare professionals.
Due to the problems that (1) conventional therapy for MG though does offer treatment but no complete cure and (2) immunosuppressants are linked to severe side effects, the additional therapeutic use of CAM should be considered. Our study has demonstrated the high acceptance of CAM by MG patients. However, it remains unclear whether the use of any particular CAM method results in a measurable improvement of MG-related problems. Specific literature addressing this problem is not yet available. Therefore, MG patients should be discouraged from spending a substantial amount of money on CAM.
Impairments by MG - reduced muscle strength
Reduced muscle strength seems to be an important independent predictor for both physical and mental health.
MG patients often develop a behavioral pattern of advance planning because they have to preserve their muscle strength . They have been described as sometimes avoiding social contacts due to their muscular impairments . However, declines in recreational activities and social interaction are associated with decreased life satisfaction . Among our patients, mobility was limited mainly by muscle weakness at rest or after physical strain, or by weakness of the upper limbs or walking difficulties. Paul et al. reported similar results in a smaller cohort with generalized MG .
Rostedt et al. raised the question if different types of regional muscle involvement, i.e. bulbar, ocular or generalized, in MG patients influence the mental aspects of quality of life. Bulbar and generalized involvement seems to result in an impairment of mental aspects of quality of life, whereas ocular involvement does not so .
Muscular weakness can be treated by drugs. The dose of acetylcholine esterase inhibitors should be well adjusted to muscular weakness. The often-practiced self-adjustment of acetylcholine esterase inhibitor's dose by patients should be supported and not strictly prohibited by physicians . However, patients clearly have to be informed about potential adverse events, including possible cholinergic crisis . Another approach could be encouraging MG patients to use more physical therapy. Through physical training, improvement of muscle force was reported in patients with mild MG ; that improvement plus optimization of gait could enhance mobility. However, little is known about the effects of physiotherapeutic methods among myasthenic patients. In one case, an exacerbation of MG during therapeutic electric stimulation was even reported .
However, in addition to mobility problems, decreased ability to communicate should be considered also . Facial expression disorders, speech difficulties, and swallowing difficulties impair verbal and non-verbal communication . Logopedic methods could ease patients' faciopharyngeal symptoms and speech difficulties, thus improving these areas. However, systematic research concerning that issue is missing.
Comorbid diseases - mental conditions
Comorbid diseases such as depression represent another factor that influences patients' daily activities in the presented study.
All chronic diseases, including MG, may have psychiatric consequences in terms of coping and QoL. However, there are very few and partly confusing data on the prevalence and aetiology of psychiatric symptoms (e.g. depression or anxiety) in MG patients [52–54]. Depression is associated with lowered QoL in a number of chronic illnesses and might result from poor physical health along with limited activity .
Patients in our study showed a high rate of depression. Whether depression occurred as a result of MG or was present before the onset of MG was not determinable from our data.
We agree with Paul et al., who proposed that emotional health should remain a clinical focus . Doering et al. stated that psychotherapeutic techniques may be helpful for MG patients who have psychiatric symptoms but not necessarily for MG patients in general . Prospective, randomized, controlled pharmaco/psychotherapy studies are needed to better direct the management of patients and, thus, improve quality of life during the course of the illness .
Despite being impaired by MG, about 30% of our patients were employed. However, working conditions do not seem to be ideal for those patients. Work-related capabilities are limited mainly by physical impairments. Occupational goals cannot be achieved, and sometimes long terms of unemployment have to be borne . In our results, employment was associated with a higher QoL. However, it is not obvious whether patients who have a better state of health and thus a less impaired QoL are capable of working in the first place or whether employment itself increases QoL. The latter thesis is conceivable because employment increased QoL in patients with cancer, osteoarthritis, and spinal cord injury . For that reason, adequate therapy and adjustments in the workplace are important to keep MG patients in the working environment with such positive consequences as improved health and increased net income. While at work, individuals are stimulated by physical and mental activities and social contacts. In addition, MG patients, especially young ones which face a long job as well as disease period, should be given counseling regarding future job possibilities.
Financial burden of MG
Last but not least, despite the burden of MG on QoL also the financial burden has to be considered. Total annual costs for MG from the societal perspective in Germany were estimated by Schepelmann et al.: EUR 14,950 (95% CI 10,470-21,730) per patient. The main components of costs were the expenditures of health insurance and the loss of productivity of patients and their caregivers. Disease severity of MG and assistance in activities of the daily life were independent cost-driving factors .
However, there are not only costs that have to be covered by the health care system but also by the patient itself. Despite living under a healthcare system that covers neurological therapies, German MG patients incurred additional expenses due to MG (in our study about 50 EURO per month; in some cases up to 500 EURO). Such expenses involved mainly medications, housekeeping assistance, and transportation. Therefore, specific changes in the healthcare system are needed to ease burden and symptoms of MG and the related financial burden for the patient as well as the health care system.