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.

Thymectomy lowers the myasthenia gravis biomarker miR-150-5p.

OBJECTIVE: The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels. METHODS: Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18-65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II-IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+). RESULTS: Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p ≤ 0.001). CONCLUSIONS: Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.

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.

High-resistance strength training does not affect nerve cross sectional area - An ultrasound study.

OBJECTIVE: The aim was to study the effect of high-resistance strength training on peripheral nerve morphology, by examining properties of peripheral nerves as well as distal and proximal muscle thickness with ultrasound, comparing healthy individuals who perform and do not perform high-resistance strength training. METHODS: Neuromuscular ultrasound was used to examine cross sectional area (CSA) of the median and musculocutaneous nerves, and muscle thickness of the abductor pollicis brevis muscle, biceps brachii muscle, quadriceps muscle and extensor digitorum brevis muscle, in 44 healthy individuals, of whom 22 performed regular high-resistance strength training. RESULTS: No difference in nerve CSA was found between trained and untrained individuals although trained individuals had thicker biceps brachii muscles. The CSA of the median nerve in the forearm correlated with participants' height and was significantly larger in men than women. CONCLUSIONS: In this cohort, CSA of the median and musculocutaneous nerves was not affected by strength training, whereas gender had a prominent effect both on CSA and muscle thickness. SIGNIFICANCE: This is the first study to examine the effect of high-resistance strength training on peripheral nerves with neuromuscular ultrasound.

Compound Motor Action Potential: Electrophysiological Marker for Muscle Training.

PURPOSE: The compound motor action potential (CMAP) represents the summated action potentials of all stimulated motor endplates and potentially reflects muscle hypertrophy and increased muscle contractions. Since electrophysiological biomarkers for high-resistance strength training are lacking, the authors evaluated whether the CMAP of distal and proximal muscles differs between healthy men and women who perform and do not perform high-resistance muscle training. METHODS: Motor neurography was performed with stimulation of the median nerve (recording of abductor pollicis brevis muscle), peroneal nerve (recording of extensor digitorum brevis muscle), femoral nerve (recording of rectus femoris muscle) and musculocutaneous nerve (recording of biceps brachii muscle), and isometric muscle strength, measured with a hand-held dynamometer, were performed on 83 healthy subjects (52 women). RESULTS: Trained women had 25% higher CMAP amplitude in the rectus femoris muscle than untrained women (P < 0.001), whereas CMAP amplitude in the trained male cohort was 25% higher in the biceps (P = 0.005) compared with untrained men. In the trained group, CMAP amplitude in the biceps correlated with isometric muscle strength (R = 0.30; P = 0.046). CONCLUSIONS: The authors' propose the CMAP as an objective neurophysiological parameter for proximal muscle status and training effects in future interventional studies of patients with neuromuscular disorders.