Rationale: Myasthenia Gravis (MG) is a chronic autoimmune disease affecting the neuromuscular junction. Although a hallmark of MG is muscle fatigability due to dysfunction of the neuromuscular junction (peripheral fatigue), a large number of MG patients also report symptoms of central or cognitive fatigue. Central fatigue is defined as an experienced lack of energy, physically and/or mentally. In October 2019 we performed a cross-sectional survey study (P15.287) among 420 Dutch MG patients showing a clinically relevant central fatigue rate of 62% on the Checklist Individual Strength-Fatigue subscale (CIS-f). In this prior study, we identified a number of factors associated with fatigue, but these factors cannot fully explain the observed high prevalence of fatigue in MG and very little is known on its biological substrates and pathophysiology.

Objectives: The main objective is to investigate if there are biomarkers for fatigue in MG. The secondary objective is to investigate the muscle origin of these biomarkers.

Study design: This study will be an exploratory study, subdivided in part I and part II (optional).

Study population: Patients with Myasthenia Gravis recruited after previous participation in the cross-sectional fatigue survey study (P15.287).

Intervention:

Phase I:

Visit 1, time: 0

• blood withdrawal
• muscle biopsy (not mandatory for participation)
• QMG
• questionnaires on medication, disease severity, fatigue, depressive symptoms and physical condition

Phase II (optional):

Visit 2, time: 6-12 months after visit 1, after analysis of phase I results.

• blood withdrawal (similar analysis as phase I)
• QMG
• questionnaires on medication, disease severity, fatigue, depressive symptoms and physical condition

Inclusion Criteria:

• Male of female patients aged ≥ 18 years

• Subjects must understand the requirements of the study and provide written informed consent.

• Diagnosis of MG:

  • Clinical signs or symptoms characteristic for MG and
  • A positive serologic test for AChR antibodies

Exclusion Criteria:

A medical history of other active auto-immune disorders for which the patient currently receives a medical treatment, such as thyroid disease or rheumatoid arthritis.

• A medical history of neoplasms within the last year.
• Substance abuse.

Exclusion criteria for muscle biopsy

• The use of anticoagulants therapy.
• Allergy for lidocaine

Patients with Myasthenia Gravis recruited after previous participation in the cross-sectional fatigue survey study (P15.287).