Diurnal and day‐to‐day variation of isometric muscle strength in myasthenia gravis

Introduction: In patients with myasthenia gravis (MG), muscle strength is expected to decrease gradually during the day due to physical activities. Methods: Isometric muscle strength at the shoulder, knee, and ankle was determined in 10 MG patients (MGFA class II–IV) who were receiving usual medical treatment and in 10 control subjects. To determine diurnal and day‐to‐day variation, muscle strength was measured 4 times during day 1 and once at day 2. Results: Knee extension strength decreased during the day in both patients and controls. Neither diurnal nor day‐to‐day variation of muscle strength was higher in patients compared with controls. Conclusions: Patients with mild to moderate MG did not have increased variation of isometric muscle strength during the day or from day‐to‐day compared with controls. This suggests that isometric muscle performance can be determined with high reproducibility in similar groups of MG patients without regard to time of day. Muscle Nerve 53 : 67–72, 2016     

Muscle strength and fatigue in patients with generalized myasthenia gravis

Myasthenia gravis (MG) is characterized by fatigue and fluctuating muscle weakness resulting from impaired neuromuscular transmission (NMT). The objective of this study was to quantify, by direct measurement of muscle force, the strength and fatigue of patients with MG. A maximal voluntary isometric contraction protocol of shoulder abductors was used in conjunction with conventional fatigue and disease‐severity instruments. Results from patients with (D‐MG) and without (ND‐MG) decrement on repetitive nerve stimulation (RNS) of the spinal accessory and axillary nerves were compared with healthy controls. Patients with MG reported greater fatigue than controls. Muscle strength was lowest in the D‐MG group, followed by the ND‐MG group and controls. Normalized shoulder abduction fatigue and recovery values did not differ between the D‐MG and ND‐MG groups or controls. The RNS decrement appears to relate best to disease severity and muscle weakness but not to objective measures of fatigue in this population. Muscle Nerve, 2009     

Muscle strength and fatigue in newly diagnosed patients with myasthenia gravis

Introduction: Dynamometry is increasingly used as an objective measurement of muscle strength in neurological diseases. No study has applied dynamometry in untreated newly diagnosed patients with myasthenia gravis (MG). Methods: Isometric muscle strength at the shoulder, knee, and ankle was determined in 21 MG patients before and after initial anti‐myasthenic treatment. Isometric strength was compared with MG evaluation scales. Results: Muscle strength was reduced for knee extensors and shoulder abductors but normal for ankle extensors. Isometric muscle strength did not correlate significantly with manual muscle testing (MG Composite). Dynamometry revealed improved muscle strength of up to 50% (median 17%; range ‐1.8–49.8) despite no change in the MG Composite score. Conclusions: Dynamometry appears to be a more sensitive method of identifying changes in limb strength than MG evaluation scales. This supports the use of dynamometry in MG patients, especially for evaluation of the effect of anti‐myasthenic treatment. Muscle Nerve 54 : 709–714, 2016     

Single fiber EMG and repetitive stimulation of the same muscle in myasthenia gravis

We performed RNS and SFEMG studies of the same muscle in 46 patients with myasthenia gravis. Maximum decrement to 3–5-Hz stimulation before and after maximum voluntary exercise, percentage of action potential pairs with increased jitter and blocking, and mean MCD in each study were compared. A significant decrement (> 10% decrease in CMAP area or amplitude between the first and fourth response) was never found without increased jitter and impulse blocking on SFEMG. Increased jitter, blocking, and mean MCD were each correlated with maximum decrement (r > 0.61, P < 0.0001). We conclude that decrement to RNS and impulse blocking on SFEMG result from the same physiologic phenomenon, and that SFEMG is more sensitive at detecting disordered neuromuscular transmission given its ability to detect impulse blocking at levels below the resolution of RNS and increased neuromuscular jitter when there is not blocking. © 1994 John Wiley & Sons, Inc.     

Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis

Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis (MG). In 22 patients we compared the validity and interobserver reliability of two scoring methods commonly used as main endpoints in clinical trials, i.e., the Myasthenic Muscle Score (MMS) ranging from 0 to 100 (normal) and the Quantified Myasthenia Gravis Strength Score (QMGSS) ranging from 0 (normal) to 39. Each score is correlated more with functional scale and less with the patient's self-evaluation. Using intraclass correlation we found strong agreement between observers for both the MMS (r = 0.906) and the QMGSS (r = 0.905). The correlation between MMS and QGMSS was high (r = 0.87). The reliability of neither score depended on any specific item, since the removal of individual items did not significantly alter the intraclass correlation coefficient (ranging from 0.86 to 0.93).     

Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis

Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility. © 1993 John Wiley & Sons, Inc.     

Safety of influenza vaccination in patients with myasthenia gravis: A population‐based study

Influenza vaccination has been associated with adverse events including Guillain–Barré syndrome. Because the safety of influenza vaccination in patients with myasthenia gravis (MG) has not been established, some clinicians discourage vaccination for these patients. We explored whether the administration of influenza vaccine to patients with MG might increase the risk of myasthenic crisis. Using population‐based healthcare data from Ontario, Canada, from 1992 to 2007, we utilized the self‐matched, case‐series method of detecting adverse events following vaccination. We studied patients with established myasthenia who were hospitalized for MG within 42 weeks of influenza vaccination. We defined the primary risk interval as the 6 weeks following vaccination. Between January 1, 1992 and March 31, 2006, we identified 3667 hospital admissions for MG. No seasonal trend in MG admissions was evident. In 513 instances, hospitalization occurred within 42 weeks following vaccination in patients previously diagnosed with MG. Among these patients, 266 (52%) were men, the median age was 74 years, and 86 (17%) had previously undergone thymectomy. The estimated relative incidence of admission for MG in the primary risk interval compared with the control interval was 0.84 (95% confidence interval 0.65–1.09). We found similar results in stratified analyses according to gender, age, and thymectomy status. Vaccination of patients with MG against influenza was not found to be associated with exacerbations of the disease. Our findings do not support the practice of withholding influenza vaccination in patients with MG. Muscle Nerve, 2009     

A randomized,double‐blind,placebo‐controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis

Introduction: Complement activation at the neuromuscular junction is a primary cause of acetylcholine receptor loss and failure of neuromuscular transmission in myasthenia gravis (MG). Eculizumab, a humanized monoclonal antibody, blocks the formation of terminal complement complex by specifically preventing the enzymatic cleavage of complement 5 (C5). Methods: This study was a randomized, double‐blind, placebo‐controlled, crossover trial involving 14 patients with severe, refractory generalized MG (gMG). Results: Six of 7 patients treated with eculizumab for 16 weeks (86%) achieved the primary endpoint of a 3‐point reduction in the quantitative myasthenia gravis (QMG) score. Examining both treatment periods, the overall change in mean QMG total score was significantly different between eculizumab and placebo (P = 0.0144). After assessing data obtained from all visits, the overall change in mean QMG total score from baseline was found to be significantly different between eculizumab and placebo (P < 0.0001). Eculizumab was well tolerated. Conclusion: The data suggest that eculizumab may have a role in treating severe, refractory MG. Muscle Nerve, 2013     

B‐cell–activating factor is elevated in serum of patients with myasthenia gravis

Introduction: Myasthenia gravis (MG) is a B‐cell–mediated autoimmune disease. B‐cell–activating factor (BAFF) is a major factor in B‐cell development and activation. In this study we investigated serum BAFF levels in MG patients. Methods: We compared the serum BAFF levels of 20 MG patients with gender‐matched healthy controls. We assayed serum concentrations of BAFF and anti‐acetylcholine receptor antibody (AChR) titers. Results: Serum BAFF levels of MG patients with AChR antibodies were significantly higher than those of healthy controls. A significant positive correlation was observed between serum BAFF levels and anti‐AChR antibody titers. BAFF values did not correlate with disease severity. Conclusions: BAFF may play a major role in the pathogenesis of MG, and it may provide a potential target for therapy in patients with MG. Muscle Nerve 54 : 1030–1033, 2016     

Content and release of acetylcholinesterase in skeletal muscle of rats with experimental autoimmune myasthenia gravis

The effects of experimental autoimmune myasthenia gravis (EAMG) on acetylcholinesterase (AChE) were investigated in diaphragms of adult female Lewis rats. Both total AChE activity per muscle and release of enzyme activity during a 3-h incubation in vitro were measured. Two groups of myasthenic animals were used. Acute EAMG was induced by intravenous injection 48 h earlier with a syngeneic monoclonal autoantibody against the nicotinic acetylcholine receptor (AChR) of rat skeletal muscle; age- and weight-matched controls received a monoclonal anti-AChR antibody nonreactive with mammalian muscle. Chronic EAMG was induced by immunization 4 weeks earlier with AChR purified from Torpedo electroplax; controls received only adjuvants. When preparations from rats with acute or chronic EAMG were compared with the appropriate controls, no statistically significant differences in content or release of AChE activity were detected. Neither was there any change in the relative amounts of the various molecular forms of AChE in samples from animals with chronic EAMG. We conclude that the structural and functional changes arising in EAMG are highly specific for the acetylcholine receptor and associated elements of the neuromuscular junction, but have little impact on the biology of AChE.     

Peroneal nerve repetitive nerve stimulation test: Its value in diagnosis of myasthenia gravis and Lambert–Eaton myasthenic syndrome

We have developed a repetitive nerve stimulation (RNS) technique for the peroneal nerve. Normal limits for the decremental responses for the anterior tibialis and extensor digitorum brevis muscles are 6–21% at the low rate of stimulation and 44–70% at the high rate of stimulation. These values exceed the normal limits for other commonly tested muscles. This may be due to the lower safety factor for neuromuscular transmission for the anterior tibialis and extensor digitorum brevis muscles. We present 4 cases in which the peroneal nerve RNS test was crucial for the diagnosis of the limb-girdle form of MG or LEMS. Thus, we conclude that, in a small number of patients with neuromuscular transmission disorders, the peroneal nerve RNS test is needed for confirmation of disease. © 1995 John Wiley & Sons, Inc.