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Environmental Factors of Importance in Myasthenia Gravis: Emphasis on Physical Activity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Myasthenia Gravis (MG) is an autoimmune disease caused by antibodies directed against proteins at the neuromuscular junction (NMJ). The disturbed neuromuscular transmission induces fatigable weakness in skeletal muscles. The severity of MG ranges from purely ocular symptoms to extensive weakness with, at worst, respiratory failure and need of intensive care. Due to different pathogenic antibodies, as well as varying phenotypes there is a classification into MG subgroups.

As lifestyle disorders are common conditions they occur also in MG patients. It is unknown whether there are any lifestyle factors associated with MG or MG subgroups. However, medication side effects and disability due to disease could contribute to higher risks for lifestyle related diseases. General treatment guidelines are not suitable to MG patients, since various medications are known to affect the disease negatively and as the tolerance and effects of physical activity in MG is unknown.

In this thesis the occurrence of lifestyle related environmental factors in MG patients were investigated. MG epidemiology, subgroup differences and the presence of lifestyle related risks in MG patients were evaluated in Jönköping county in Southern Sweden. The findings were compared to a similar evaluation in a region of Estonia. We found that MG patients in the late-onset disease subgroup had a more disadvantageous pattern of life-style related risk factors, with a higher rate of obesity, smoking and physical inactivity and a lower rate of fish consumption in comparison to matched population controls. Furthermore, we found that despite comparable clinical muscle fatigue status, Estonian MG patients subjectively scored fatigue and disease severity higher than Swedish MG patients. More Estonian patients were physically inactive. The tolerance and effects of physical exercise was further evaluated in two intervention studies, where MG patients with stable disease performed a 12-week-training-program according to general exercise recommendations to healthy adults. We found that physical exercise was well tolerated by the MG patients and that they had a beneficial skeletal muscle response to physical exercise.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. , p. 75
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1439
Keywords [en]
Myasthenia Gravis, MG subgroups, Environmental factors, Lifestyle, Physical activity, Exercise
National Category
Neurology
Research subject
Clinical Neurophysiology
Identifiers
URN: urn:nbn:se:uu:diva-344667ISBN: 978-91-513-0262-1 (print)OAI: oai:DiVA.org:uu-344667DiVA, id: diva2:1188590
Public defence
2018-04-27, Gunnesalen, Psykiatrins hus, Akademiska sjukhuset, ingång 10, Uppsala, 09:00 (English)
Opponent
Supervisors
Funder
Futurum - Academy for Health and Care, Jönköping County Council, SwedenSwedish Research Council
Note

Ytterligare forskningsfinansiärer: Neuroförbundet, Palle Ferbs minnesfond samt Erik, Karin och Gösta Selanders stiftelse

Available from: 2018-04-05 Created: 2018-03-08 Last updated: 2018-04-24
List of papers
1. Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries
Open this publication in new window or tab >>Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries
2017 (English)In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 4, article id e00653Article in journal (Refereed) Published
Abstract [en]

Tntroduction: 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.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
Estonia, fatigue, myasthenia gravis, Sweden
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-322219 (URN)10.1002/brb3.653 (DOI)000399452500009 ()28413704 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Available from: 2017-05-17 Created: 2017-05-17 Last updated: 2018-03-08Bibliographically approved
2. Lifestyle factors and gender-related differences in clinical subgroups of Myasthenia Gravis in southern Sweden
Open this publication in new window or tab >>Lifestyle factors and gender-related differences in clinical subgroups of Myasthenia Gravis in southern Sweden
(English)In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377Article in journal (Refereed) Submitted
Abstract [en]

Background: Based on the need for further regional and global epidemiological knowledge on Myasthenia Gravis (MG) and MG subgroups, we conducted a questionnaire-based epidemiological survey in a medium-sized health care region in southern Sweden. The primary aims were to investigate disease-specific items and lifestyle related factors between MG subgroups and matched population controls.

Methods: All MG patients (n=70) in Jönköping County were invited to participate in a survey, using a standardized disease-specific questionnaire, previously developed by an expert group. This questionnaire contains three parts, including demographic and disease-specific data, lifestyle and health-related aspects as well as co-morbidity and mental fatigue. The patients were clinically evaluated. Four hundred age- and gender matched randomly selected population controls excluding MG were invited to answer the non-disease-specific part of the questionnaire. Statistical tests included student t-test (for parametric data) or Mann–Whitney U test (for nonparametric data) and Chi-square test and Fisher’s exact test for evaluations between MG subgroups. In the case-control analysis conditional logistic regression was used to estimate the adjusted Odds Ratios.

Results: Forty of the 70 identified MG patients and 188 of the 400 age-and gender matched population controls participated in the study (response rate 57.1%). 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) group, time to diagnosis was longer and bulbar weakness was the dominant symptom (65%). EOMG patients had higher fatigue compared to LOMG. Compared to their matched population controls, LOMG patients were obese more often, ate ess fish, smoked more, had a lower educational level and were employed as manual laborers more often. 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: These findings highlight lifestyle and gender related differences between the EOMG and LOMG subgroups and between MG patients and population controls. Importantly, these lifestyle issues such as cardiovascular risk factors and physical inactivity, as well as mental health problems should be addressed intensively in the clinical follow-up of MG patients.

Keywords
Myasthenia Gravis, late onset MG, early onset MG, lifestyle, fatigue
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-344665 (URN)
Funder
Swedish Research Council, VR-523-2014-2048Futurum - Academy for Health and Care, Jönköping County Council, Sweden, 488501
Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-03-08
3. Physical exercise in Myasthenia Gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study
Open this publication in new window or tab >>Physical exercise in Myasthenia Gravis is safe and improves neuromuscular parameters and physical performance-based measures: A pilot study
Show others...
2017 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 56, no 2, p. 207-214Article in journal (Refereed) Published
Abstract [en]

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 as well as 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 safely can be applied to well-regulated MG patients.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-314678 (URN)10.1002/mus.25493 (DOI)000406875000009 ()27935072 (PubMedID)
Funder
Swedish Research Council, 2014-02048Futurum - Academy for Health and Care, Jönköping County Council, Sweden, 520281, 520411Swedish Society of Medicine, SLS-499271
Available from: 2017-02-04 Created: 2017-02-04 Last updated: 2018-03-08Bibliographically approved
4. The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study
Open this publication in new window or tab >>The impact of physical exercise on neuromuscular function in Myasthenia gravis patients: A single-subject design study
Show others...
2018 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 97, no 31, article id e11510Article in journal (Refereed) Published
Abstract [en]

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 life-style 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 high-resistance strength training. After the training program, parameters of the proximal leg muscle rectus femoris improved: compound motor action potential (from 4.5 ± 2.6 to 5.3 ± 2.8 mV, p=0.016), isometric muscle force (from 25.2 ± 4.4 to 30.2 ± 3.8 kg; p=0.014) and ultrasound muscle thickness (from 19.6 ± 5.6 to 23.0 ± 3.9 mm, p=0.0098) all increased. Further, physical performance-based measures improved, including the 30-Second Chair Stand Test (median change +2, p=0.0039) as well as the clinical MG composite score (from 3[2-5] to 2 [0-4], p=0.043). These findings indicate that MG patients can improve their functional muscle status as a result of aerobic and high-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.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
Myasthenia Gravis, physical exercise, neuromuscular, CMAP, resistance training
National Category
Neurology Physiotherapy Sport and Fitness Sciences
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-344666 (URN)10.1097/MD.0000000000011510 (DOI)000442259200025 ()30075515 (PubMedID)
Funder
Swedish Research Council, VR-523-2014-2048
Note

Title in thesis list of papers: The impact of physical exercise on functional muscle measures in Myasthenia Gravis patients – a single subject design study

Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-10-30Bibliographically approved

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