A population-based follow-up study of maximal muscle strength and mobility in patients with myasthenia gravis.

It is uncertain whether residual muscle weakness in myasthenia gravis (MG) can improve, and whether it reflects deficits and disability. In a population-based follow-up study of 107 patients with MG and 50 healthy controls, maximal shoulder, knee and ankle strength was measured using isometric dynamometry and related to the quantitative MG (QMG), the MG Composite (MGC), the MG-activities of daily living (MG-ADL), the MG quality of life 15-items (QOL15) and a 400 m walk test (400MWT). During a mean follow-up of 4.6 (±0.04) years, patients improved 10.8% (P < 0.001) in isometric shoulder strength, whereas their isometric knee strength did not improve (3.2%, P = 0.151). Higher age, longer disease duration and greater baseline impairment had no negative impact. Change in isometric shoulder and knee strength did not correlate with changes in the QMG, the MG-ADL or the QOL15. Change in isometric knee strength correlated with change in the 400MWT (r = -0.357), and the 400MWT correlated with changes in the QMG (r = 0.439), the MG-ADL legs subitem (r = 0.419) and the QOL15 (r = 0.310). Overall, muscle strength improved over time, and the MG clinical scales were related to impaired mobility and muscle strength. Change in residual muscle weakness was unrelated to disability (MG-ADL) and quality of life (QOL15).

Oral function in patients with myasthenia gravis.

Myasthenia Gravis (MG) is characterised by muscle weakness and increased fatigability. The aim of this pilot study was to investigate if patients with MG demonstrate different functional chewing patterns and report more complaints related to mastication as compared with healthy controls. Twelve patients (median 60 years Q1-Q3: 46-70) with generalised MG and nine healthy controls (median 57 years Q1-Q3: 55-63) participated. All participants underwent dental and oral examination and were asked to fill in a questionnaire concerning oral health. Static maximum bite force was measured with a bite force transducer, electromyography in the masseter, temporalis, and suprahyoid muscles were recorded, and jaw movement was tracked, during a 5-minute gum chewing test. The patients had more oral complaints (oral health impact profile total score 22.6 vs 7.5 P < 0.01) and had lower peak bite force than controls (18.8kgf (11.1;26.4) (95% CI) vs 29.5 kgf (21.6; 37.4) (P = 0.04)). In contrast, fatigability of the masticatory muscles, as defined by number of chewing cycles during the gum-chewing test, did not differ between patients and controls (P = 0.10). In conclusion, patients had more oral complaints and lower bite force than controls, but did not show significantly different functional chewing patterns. Future studies should aim at integrating measurement of peak force into functional tests. Attention should be given to oral complaints of patients with MG.

Gender differences in clinical outcomes in myasthenia gravis: A prospective cohort study.

INTRODUCTION/AIMS: It is uncertain whether clinical outcomes differ between male and female patients with myasthenia gravis (MG) while receiving standard clinical care. METHODS: In a prospective cohort study of 107 patients with MG receiving standard of care from 2012 to 2019, the Quantitative MG (QMG), the MG Composite (MGC), the MG Activities of Daily Living (MG-ADL), and the MG Quality of Life 15-Items (QOL15) were determined. Clinical outcomes were analyzed in relation to gender. RESULTS: Mean follow-up time was 4.8 (±0.4) y, and 70 patients completed all follow-up assessments. Patients improved on all clinical scores: QMG -1.8 (P < .001), MGC -1.5 (P < .001), MG-ADL -1.3 (P < .001), and QOL15 -3.0 (P < .001). Females improved less than males on the QMG (P = .01), MGC (P < .001), MG-ADL (P = .006), and QOL15 (P < .001) independent of potential confounders. Males had moderate to strong correlations between changes in all clinical scales (r range 0.52 to 0.73), whereas females had weak correlations between changes in the QMG and MG-ADL (r = 0.13), the QMG and QOL15 (r = 0.27), the MGC and MG-ADL (r = 0.21), the MGC and QOL15 (r = 0.00), and the MG-ADL and QOL15 (r = 0.31). DISCUSSION: Females improved less compared to males on objective and patient-reported outcomes. Moreover, females improved more on objective measures than on patient-reported outcomes. These gender differences should receive attention in clinical care and in the design of future trials.

Overactive bladder in patients with myasthenia gravis-A cross-sectional population-based study.

BACKGROUND: In myasthenia gravis (MG), first-line treatment for MG is acetylcholinesterase inhibitors which alleviates symptoms, but concomitantly may cause autonomic adverse effects. AIMS OF THE STUDY: In this study, we evaluated if symptoms of overactive bladder (OAB) are more frequent among MG patients than healthy controls. METHODS: Eighty-three MG patients and 50 healthy sex- and age-matched controls were included and answered the questionnaire "International Consultation on Incontinence Questionnaire Overactive Bladder Module" (ICIQ-OAB), including questions about polyuria, nocturia, urgency, and stress incontinence. Clinical severity of MG was determined based on three standardized clinical evaluations. RESULTS: Compared to control subjects, MG patients had a higher total OAB score (median 5 [range 0-12] versus 3 [0; 7]) (p < 0.005) with higher scores concerning all four items. Also, MG patients had a higher bother score (10 [0-40] versus 5 [0-40]) (p < 0.05). Patients receiving a daily dose of pyridostigmine of more than 300 mg had a higher OAB score than other patients. CONCLUSIONS: Myasthenia gravis patients have more bothering symptoms of OAB than healthy controls, related to the daily dose of pyridostigmine. To minimize adverse effects in patients with symptoms of OAB, the pyridostigmine dose should be as low as possible.

Muscle weakness and functional disability in patients with myasthenia gravis.

INTRODUCTION: Muscle weakness and functional disability have not been evaluated in a population-based study of patients with myasthenia gravis (MG). METHODS: All patients with MG in a well-defined catchment area were identified in the Danish National Patient Registry. Of the 175 eligible patients, 90 participated and were studied using MG-specific scales, isometric dynamometry, and functional tests. Fifty age- and sex-matched subjects served as controls. RESULTS: Muscle strength was reduced by 13%, 21%, and 12% for shoulder abduction, knee extension, and ankle extension, respectively (P < 0.05). Chair stand and 400-meter walking were impaired by 24% and 23%, respectively (P < 0.05). Muscle strength and functional performances were related to MG-specific scales. DISCUSSION: MG patients have moderately reduced isometric muscle strength and impaired physical performance. Muscle weakness and functional tests relate closely to MG-specific scales, suggesting that dynamometry and functional tests can be used to monitor MG patients and as efficacy parameters in clinical trials. Muscle Nerve 59:218-223, 2019.

Exercise in myasthenia gravis: A feasibility study of aerobic and resistance training.

INTRODUCTION: It has not been established whether progressive resistance training (PRT) and aerobic training (AT) are feasible and efficient in myasthenia gravis (MG). METHODS: Fifteen subjects with generalized MG (Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV) were randomly assigned to 20 training sessions during 8 weeks of either PRT or AT. Feasibility was evaluated based on adherence, drop-out rate, adverse events, and Quantitative Myasthenia Gravis (QMG) score. RESULTS: Twelve subjects (MGFA II, n = 11; MGFA III, n=1) completed the intervention with a mean adherence of 95 % ± 8. One dropout (PRT) could potentially be related to PRT. Both groups reported adverse events, including bulbar symptoms (n = 2) and increased fatigue (n = 3), but no change in QMG score was observed in either group. The PRT group showed increases in maximal strength and functional capacity. CONCLUSIONS: Eight weeks of moderate to high intensity AT and PRT were feasible for most patients with mild MG. Maximal strength and functional capacity increased in the PRT group. Muscle Nerve 56: 700-709, 2017.

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.

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.

Late-onset Pompe disease is prevalent in unclassified limb-girdle muscular dystrophies.

OBJECTIVE: Late-onset Pompe disease is a rare, but potentially treatable metabolic myopathy, and therefore should not be overlooked. However, it is not unusual that patients go undiagnosed for many years. We hypothesized that patients with late-onset Pompe disease may have been overlooked in a population of patients with unclassified neuromuscular disease. METHODS: We used DBS (dried blood spots) to screen for Pompe disease in the two largest neuromuscular clinics and one of the main respiratory centers in Denmark. We selected patients with unclassified LGDM (limb-girdle muscular dystrophy), idiopathic elevation of creatine kinase, unexplained myopathy on muscle biopsy, unexplained restrictive respiratory insufficiency or unspecified myopathy for screening. RESULTS: 177 patients were found eligible for inclusion, and 103 (58.2%) patients accepted screening. Three patients with Pompe disease were identified with DBS, and subsequent genetic testing revealed known pathogenic mutations in the GAA gene. All three patients were found among 38 patients with unclassified LGMD (8%). CONCLUSION: Our findings indicate that a DBS should be considered early in the diagnostic work-up of patients with an LGMD phenotype, to rule out Pompe disease. Retrospectively, all 3 patients presented with "red flags" more compatible with Pompe disease than LGMD, including; 1) mild non-dystrophic, myopathic features on muscle biopsy, 2) creatine kinase levels below 1000, and 3) disproportionate axial and respiratory muscle involvement in comparison with limb muscle involvement.

The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney.

BACKGROUND: A well-characterized dog model of the X-linked collagen disease Alport syndrome (XLAS) was used to study the effect of progressive glomerular disease on megalin-mediated endocytosis. In XLAS, altered structure and function of the glomerular basement membrane induces a progressive proteinuric nephropathy. METHODS: The investigation was performed in male XLAS dogs and age-matched normal male littermates. The urine profile and megalin-mediated endocytosis in the proximal tubule of six healthy and six XLAS dogs were examined at 2, 4, 6, 8 and 10 months of age using SDS-PAGE, immunoblotting and immunohistochemistry. RESULTS: Gradually increasing urinary excretion of proteins over time and a reduced content of the same proteins in proximal tubule cells were found. Besides the glomerular component of the proteinuria, a significant tubular component was seen, which is due to a progressive change in the uptake of low-molecular-weight (LMW) ligands by megalin. Furthermore, the protein overload present in the lumen of the proximal tubule exceeds the reabsorption capacity of megalin and the co-receptor cubilin and results in a combined low- and high-molecular-weight (HMW) proteinuria. Also, a shift in the distribution of lysosomes was seen in the XLAS dogs suggesting changes in the lysosomal degradation pattern in response to the altered endocytosis. CONCLUSIONS: The present study shows that the increased glomerular permeability and the subsequently altered megalin-mediated and megalin-dependent cubilin-mediated endocytosis lead to a partial LMW proteinuria and partial HMW proteinuria.