Implementation of tailored exercise programs for MG patients in a gym setting: a pragmatic feasibility case study.

Although supervised aerobic and resistance training in a hospital setting was proven safe and beneficial for well-controlled myasthenia gravis (MG) patients, implementation of similar programs in the community has not been studied. We conducted a pragmatic open-label study at a large gym in Uppsala, Sweden. Seven patients with generalized MG were recruited to participate in an individualized, tailored exercise program, based on individual baseline status and personal goals, with a personal trainer. All patients completed the entire training period. The individually tailored exercise program was implemented safely and effectively, with all patients improving in aerobic capacity, muscle strength, and balance. Our pragmatic open-label case study suggests that well-controlled patients with generalized MG can extend their physical exercise to personal training in the gym. This is an essential step towards reducing the barriers to implementing exercise procols and increasing the availability of these interventions to MG patients.

Enrichment of serum IgG4 in MuSK myasthenia gravis patients.

Muscle-specific kinase (MuSK) myasthenia gravis (MG) is a neuromuscular autoimmune disease belonging to a growing group of IgG4 autoimmune diseases (IgG4-AIDs), in which the majority of pathogenic autoantibodies are of the IgG4 subclass. The more prevalent form of MG with acetylcholine receptor (AChR) antibodies is caused by IgG1-3 autoantibodies. A dominant role for IgG4 in autoimmune disease is intriguing due to its anti-inflammatory characteristics. It is unclear why MuSK autoantibodies are predominantly IgG4. We hypothesized that MuSK MG patients have a general predisposition to generate IgG4 responses, therefore resulting in high levels of circulating IgG4. To investigate this, we quantified serum Ig isotypes and IgG subclasses using nephelometric and turbidimetric assays in MuSK MG and AChR MG patients not under influence of immunosuppressive treatment. Absolute serum IgG1 was increased in both MuSK and AChR MG patients compared to healthy donors. In addition, only MuSK MG patients on average had significantly increased and enriched serum IgG4. Although more MuSK MG patients had elevated serum IgG4, for most the IgG4 serum levels fell within the normal range. Correlation analyses suggest MuSK-specific antibodies do not solely explain the variation in IgG4 levels. In conclusion, although serum IgG4 levels are slightly increased, the levels do not support ubiquitous IgG4 responses in MuSK MG patients as the underlying cause of dominant IgG4 MuSK antibodies.

Cancer in myasthenia gravis subtypes in relation to immunosuppressive treatment and acetylcholine receptor antibodies: A Swedish nationwide register study.

BACKGROUND AND PURPOSE: The potentially increased risk of extrathymic cancers in myasthenia gravis (MG) remains uncertain. We present the occurrence of extrathymic cancer diagnoses in different MG subgroups. METHODS: We conducted a nationwide Swedish register-based cohort study, including patients who had their first MG diagnosis or first prescription of acetylcholine esterase inhibitors between the years 2006 and 2018. Timing and subtypes of cancer diagnosis in relation to MG as well as corticosteroid-sparing immunosuppressants (CSISs) were identified from national patient, cancer and drug registers. RESULTS: In the study population of 2812 MG patients, 92 had juvenile MG (3%), 632 had early-onset MG (23%), 1968 had late-onset MG (LOMG; 70%) and 120 patients had thymoma-associated MG (TAMG; 4%). Extrathymic cancers were observed in 630 patients (22.4%). Skin cancer and cancer in the male genital organs were most common (N = 138, respectively), followed by cancers in the female genital organs (N = 103), digestive organs (N = 90) and breast (N = 80). Patients with TAMG (29.2%) and LOMG (28.4%) had the highest occurrence of extrathymic cancer. Cancer frequency was comparable between acetylcholine receptor antibody seropositive and seronegative patients. Two or more CSIS prescriptions significantly increased the frequency of cancer, especially cancers in the digestive organs (p = 0.0026), male genital organs (p = 0.0037) and skin (p < 0.0001). CONCLUSIONS: Most extrathymic cancer types in MG were observed in TAMG and LOMG patients, and there was a clear correlation between CSIS exposure and cancer risk. This study sheds light on extrathymic cancers also in non-thymoma MG.

Mortality rates and causes of death in Swedish Myasthenia Gravis patients.

Myasthenia Gravis (MG) is an autoimmune disease with several comorbidities, however information on MG mortality remains sparse. We conducted a nationwide register-based study on mortality rates and causes of death among Swedish MG patients. Data was acquired from four Swedish National Board of Health and Welfare registers. A total of 4559 MG patients (2522 women, 55.3%) being alive entering the year 2006, were identified. 1121 patients (562 women, 50.1%) died during 2006-2016. Age- and gender-standardized mortality rate was 1.51 (95% CI 0.40) per 100 patients and did not differ from the Swedish general population. Time from MG diagnosis to death was 8.9 ±â€¯6.8 years. The most common ultimate cause of death was cancer (19.5%), followed by ischemic heart disease (13.3%) and MG (11.3%). When MG was stated as the ultimate cause of death, there was a strikingly higher likelihood of having influenza/pneumonia as a contributing cause of death (OR 2.5, p<0.0001). In conclusion, although we could not confirm a higher mortality rate in Swedish MG patients compared to the general population, and despite modern advancements in treatment, we observed that MG itself was stated as the third most common ultimate cause of death in Swedish MG patients.

Epidemiology of Myasthenia Gravis in Sweden 2006-2016.

INTRODUCTION: Reported incidence and prevalence rates of Myasthenia Gravis (MG) vary widely and are assumed to have increased over the last few decades. We conducted a nationwide register-based study on the current incidence and prevalence of MG and MG subgroups in Sweden. METHODS: Data were acquired from four Swedish Health Registers in order to identify patients with MG. Incidence and prevalence rates were calculated for the years 2006-2016, using population numbers provided by Statistics Sweden. RESULTS: In 2016, the incidence of MG in Sweden was 2.9 per 100,000 inhabitants (95% CI: 2.5-3.2/100,000) and the crude prevalence was 36.1 per 100,000 inhabitants (95% CI: 34.9-37.3). There was a significant increase in Myasthenia Gravis prevalence from 2006 to 2016. Prevalence rates of all MG subgroups but thymoma-associated MG increased over the same period of time. CONCLUSIONS: The incidence and prevalence of Myasthenia Gravis have increased over time in Sweden, and the rates are high in comparison with other countries.

Pattern of Habitual Physical Exercise in Myasthenia Gravis Patients.

BACKGROUND: Notwithstanding the amount of deliberate exercise, the daily patterns of active versus sedentary behavior have a major influence on health outcomes [1]. Patterns of habitual active and sedentary behavior in Myasthenia Gravis (MG) patients, as well as their possible relations to disease activity, are not known. OBJECTIVE: To evaluate baseline patterns of physical and sedentary behavior in MG patients. METHODS: Activity patterns of twenty-seven MG patients were assessed by a Dynaport MoveMonitor (McRoberts) accelerometer, worn for seven consecutive days. The amount of time spent in moderate and vigorous intensity activities, physical activity level (PAL), number of steps/day and sedentary time were assessed and correlations to disease severity were analyzed. The results were compared to general recommendations and published data of healthy individuals and to data of patients with the chronic disorders chronic obstructive pulmonary disease (COPD) and mitochondrial myopathy. RESULTS: MG patients had sedentary behavior during 78±7% of the day. There was neither a correlation between disease severity and number of steps/day (R = -0.15; p = 0.56) nor between disease severity and PAL (R = 0.33; p = 0.26). Nevertheless, the MG patients met the recommendations of daily deliberate exercise (181±158 MET min/day). PAL was lower in MG patients (1.5±0.138) than in healthy individuals (1.67±0.145, p < 0.00001). CONCLUSION: Although a majority of MG patients meet the recommendations of deliberate exercise, their baseline physical activity levels are dominated by sedentary behavior. In comparison with a healthy population, MG patients are less physically active, but the reason for this remains unclear with no correlations between disease severity and physical activity patterns.

Lifestyle factors and disease-specific differences in subgroups of Swedish Myasthenia Gravis.

PURPOSE: To evaluate disease-specific differences between Myasthenia Gravis (MG) subgroups and compare patterns of lifestyle between MG patients and population controls. METHODS: All MG patients (n = 70) in Jönköping County, Sweden, were invited to answer a disease-specific questionnaire, containing questions about disease-specific data, lifestyle, comorbidity, and mental fatigue. The patients were clinically evaluated. Four hundred age- and gender-matched population controls were invited to answer the nondisease-specific part of the questionnaire. Disease-specific issues were compared between MG subgroups. Lifestyle-related factors and concomitant conditions were compared to the population controls. RESULTS: Forty MG patients and 188 population controls participated in the study. In the late-onset MG (LOMG; N = 18) subgroup, the male predominance was higher than previously reported. In the early-onset MG (EOMG; N = 17) subgroup, time to diagnosis was longer, fatigue was higher, and bulbar weakness was the dominant symptom (65%). Compared to their matched population controls, LOMG patients were more obese (OR = 13.7, P = 0.015), ate less fish (OR = 4.1, P = 0.012), tended to smoke more (OR = 4.1, P = 0.086), and tended to be employed as manual laborers more often (OR = 2.82, P = 0.083). Mental health problems and sickness benefits were more common among MG patients than in controls, and MG patients were less regularly doing focused physical activity. CONCLUSIONS: It is important to consider disease-specific differences when tailoring the management of individual MG patients. There is a need for improved knowledge on how to apply primary and secondary prevention measures to lifestyle disorders in MG patients without risk of deterioration.

The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study.

There is a need for tailored exercise recommendations to patients with Myasthenia gravis (MG). A few pilot studies have recently shown that physical exercise in accordance with general recommendations to healthy adults can be applied safely to patients with mild MG symptoms. How physical exercise affects muscle parameters and risk factors for lifestyle diseases in patients with MG is, however, only poorly known. We evaluated functional skeletal muscle parameters in 11 MG patients, before and after conducting a 12-week supervised physical therapy regimen of aerobic and resistance strength training. After the training program, parameters of the rectus femoris muscle improved: compound motor action potential (from 4.5 ±â€Š2.6 to 5.3 ±â€Š2.8 mV, P = .016), isometric muscle force (from 25.2 ±â€Š4.4 to 30.2 ±â€Š3.8 kg; P = .014), and ultrasound muscle thickness (from 19.6 ±â€Š5.6 to 23.0 ±â€Š3.9 mm, P = .0098) all increased. Further, physical performance based measures improved, including the 30-Second Chair Stand Test (median change +2, P = .0039) as well as the clinical MG composite score [from 3 (2-5) to 2 (0-4), P = .043]. No improvement in muscle function was observed in the biceps brachii muscle. These findings indicate that MG patients can improve their muscular functions by incorporating aerobic and resistance strength training, especially in proximal leg muscles. This is important knowledge when physical therapy is considered for this patient group, for whom no guidelines on physical exercise currently exist.

Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries.

Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden. METHODS: This cross-sectional study included southern counties in Sweden and Estonia of comparable size. All patients with a confirmed MG diagnosis were asked to answer two questionnaires including demographic and disease-specific data, lifestyle issues, and mental fatigue (Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through the Quantitative Myasthenia Gravis Score (QMG). RESULTS: Thirty-six of 92 identified patients in Estonia and 40 of 70 identified MG patients in Sweden chose to participate in the study. The demographic characteristics and symptoms reported by the patients were similar. QMG score did not differ; however, the Estonian patients scored their current subjective disease severity significantly higher (5.6 ± 2.8) compared to the Swedish patients (3.4 ± 2.3, p = .0005). Estonian patients also had significantly higher FSS scores (5.0 ± 1.7) than Swedish patients (3.5 ± 1.6; p = .001). Swedish patients were more active and performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden, p = .004). CONCLUSIONS: Although, the patients had comparable clinical fatigue, Estonian patients evaluated their health state as being more severe and reported more mental fatigue than Swedish patients. These data indicate large regional differences in disease perception of MG, which is important to consider in international studies.

Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.

This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.

Physical exercise in myasthenia gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study.

INTRODUCTION: Due to the shortage of exercise-related research in Myasthenia Gravis (MG), there are no consensus guidelines on physical exercise for MG patients. METHODS: In this prospective pilot study, 10 MG patients with mild disease performed supervised aerobic and resistance training twice weekly for 12 weeks. The Myasthenia Gravis Composite (MGC) score, compound motor action potential (CMAP), repetitive nerve stimulation, muscle force, physical performance-based measures, serum levels of interleukin-6, muscle enzymes, and immuno-microRNAs miR-150-5p and miR-21-5p were assessed before and after the training period. RESULTS: Physical exercise was well tolerated, and the MGC score was unchanged. Muscle resistance weights and CMAP amplitudes increased for biceps brachii and rectus femoris muscles, and physical performance-based measures improved. Muscle enzymes remained normal, whereas disease-specific microRNAs miR-150-5p and miR-21-5p were reduced after the training period. CONCLUSIONS: We propose that general recommendations regarding physical exercise can be applied safely to well-regulated MG patients. Muscle Nerve 56: 207-214, 2017.