The modified rankin scale to assess disability in myasthenia gravis: Comparing with other tools

Introduction: We explored the modified Rankin scale (mRS) as a tool to quantitate disability in myasthenia gravis (MG). Our aim was to correlate patients' perception of their disability with that of the care provider and determine its relationship with other MG‐related scores. Methods: We evaluated 107 MG patients at 2 neurological centers. Patients were assessed over the telephone before and after clinic visits using the 15‐item Myasthenia Gravis Quality‐of‐Life index (MG‐QOL15) and mRS. At the clinic, patients were assessed using the MG‐QOL15, MG Composite (MGC), and mRS. Results: The MG‐QOL15 correlated with the MGC, mRS, and assessors' scores of patients. Assessors' perception of disease burden was in line with that of the patients' scoring. MG‐QOL15 scores obtained over the telephone were consistent with those obtained in the clinic. Scores were generally higher in patients receiving steroids at >5 mg/day and in those receiving or seeking benefits. Conclusion: The MG‐QOL15 and mRS are useful for estimating disability in MG. Muscle Nerve 50 : 501–507, 2014     

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     

The utility of a single simple question in the evaluation of patients with myasthenia gravis

Introduction: Assessing myasthenia gravis (MG) can be challenging, and multiple scales are available to evaluate disease severity. We evaluated the utility of a single, simple question, as part of the MG evaluation: “What percentage of normal do you feel regarding your MG, 0%–100% normal?” Methods: A retrospective chart review of patients attending the neuromuscular clinic from January 2014 to December 2015 was performed. Responses were correlated with symptoms and signs, the Quantitative Myasthenia Gravis Score (QMGS), the Myasthenia Gravis Impairment Index (MGII), and the 15‐item Myasthenia Gravis Quality of Life scale (MG‐QOL15). Results: The total cohort included 169 patients. The percentage of normal correlated strongly with limb muscle weakness and MG scales, moderately with bulbar and respiratory symptoms, and weakly with ocular manifestations. Discussion: The question, “What percentage of normal do you feel regarding your MG?” is feasible and valid, and can be incorporated easily into routine clinical evaluation. Muscle Nerve 57 : 240–244, 2018     

Translation,cross-cultural adaptation,and validation of the chinese version of the 15-item myasthenia gravis quality of life questionnaire

Introduction: We sought to translate, cross-culturally adapt, and evaluate the internal consistency and validity of the Chinese version of the 15-Item Myasthenia Gravis Quality of Life (MG-QOL15). Methods: Translation and cross-cultural adaptation of the MG-QOL15 were performed. We used Cronbach's α to test internal consistency, one-way analysis of variance to test construct validity, and Pearson or Spearman correlations to test discriminant and concurrent validity. Results: We enrolled 168 outpatients. Internal consistency was excellent (Cronbach's α = 0.928). The MG-QOL15 discriminated MG severity as stratified by the MG Composite (MGC; P < 0.001) and Osserman class (P = 0.01). Concurrent validity was low to moderate with the subscales of the 36-item Short Form (−0.31 to ∼−0.59), MGC (r = 0.46), and Myasthenia Gravis Activities of Daily Living profile (r = 0.54). Discussion: The Chinese MG-QOL15 showed comparable construct, discriminant and concurrent validity, and internal consistency with to the original version. Muscle Nerve 59 :95–99, 2019     

International clinimetric evaluation of the MG‐QOL15, resulting in slight revision and subsequent validation of the MG‐QOL15r

Introduction: The MG‐QOL15 is a validated, health‐related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze its clinimetric properties. Methods: We first performed Rasch analysis on >1,300 15‐item Myasthenia Gravis Quality of Life scale (MG‐QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG‐QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on >1,300 MG‐QOL15r scales. Results: The MGQOL15r performed slightly better than the MG‐QOL15. The 3‐response option MG‐QOL15r demonstrated better clinimetric properties than the 4‐ or 5‐option scales. Relative distributions of item and person location estimates showed good coverage of disease severity. Conclusions: The MG‐QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG‐QOL15. Muscle Nerve 54 : 1015–1022, 2016     

Translation and validation of the 15‐item Myasthenia Gravis Quality of life scale in Dutch

Introduction: The 15‐item Myasthenia Gravis Quality of Life (MG‐QOL15) scale has been developed to assess the health‐related quality of life of patients with myasthenia gravis (MG). The aim of this study was to translate the original English version into Dutch and to test the test–retest reliability and construct validity. Methods: Fifty patients with MG were included. Test–retest reliability and internal consistency were assessed using the intraclass correlation coefficient (ICC) and the Cronbach α. Construct validity was assessed by testing 5 predefined hypotheses. Results: A good test–retest reliability was confirmed with an ICC of 0.866. The Cronbach α was 0.93. The predefined hypotheses were confirmed in 80% of cases, which points to good construct validity. Discussion: The Dutch MG‐QOL15 has good test–retest reliability and good construct validity. It can be used for research in a Dutch‐speaking population. It is also suitable for monitoring individual patients in clinical practice. Muscle Nerve 57 : 206–211, 2018     

Association between musk antibody concentrations and the myasthenia gravis composite score in 3 patients: A marker of relapse?

Introduction: Muscle-specific tyrosine kinase (MuSK) autoantibody related myasthenia gravis is characterized by bulbar and respiratory manifestations, a poor response to anticholinergics, and a generally good response to plasma exchange and rituximab. It is not known if MuSK-antibody (Ab) levels could be used to predict the clinical course Methods: Three patients for whom frequent long-term monitoring of MuSK-Ab levels and the Myasthenia Gravis Composite (MGC) scores were performed are described. Results: A close relationship existed between the MuSK-Ab concentrations and the MGC score. Furthermore, a rise in Ab concentration preceded a more serious clinical relapse in all patients Conclusions: These findings suggest that MuSK-Ab concentrations may be a useful biomarker for the long-term monitoring of MuSK myasthenia gravis, particularly while in clinical remission. This may allow preemptive escalation of therapy to prevent clinical relapse, and conversely permitting greater weaning of unnecessary immunosuppression. Muscle Nerve, 2019     

Construction of an efficient evaluative instrument for Myasthenia Gravis: The MG composite

We assessed the performance of items from the Quantitative Myasthenia Gravis (QMG), MMT (Manual Muscle Test), and MG‐ADL (Myasthenia Gravis – Activities of Daily Living) scales, using data from two recently completed treatment trials of generalized MG. Items were selected that were relevant to manifestations of MG, meaningful to both the physician and the patient, and responsive to clinical change. After the 10 items were chosen, they were weighted based on input from MG experts from around the world, considering factors such as quality of life, disease severity, risk, prognosis, validity, and reliability. The MG Composite is easy to administer, takes less than 5 minutes to complete, and requires no equipment. Weighting of the response options of the 10 items should result in ordinal scores that better represent MG status and are more responsive to meaningful clinical change. To better determine its suitability for clinical use and for treatment trials, the MG Composite will be tested prospectively at several academic medical centers and will be used as a secondary measure of efficacy in pending clinical trials of MG. Muscle Nerve 38: 1553–1562, 2008     

Effects of napping on neuromuscular fatigue in myasthenia gravis

Introduction: The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Methods: Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results: Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Conclusions: Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Muscle Nerve 48:816–818, 2013     

Myasthenia gravis with muscle‐specific tyrosine kinase antibodies: A narrative review

Growing evidence provides new insights about myasthenia gravis (MG) with antibodies against muscle‐specific tyrosine kinase (MuSK‐MG), including its pathogenesis, clinical and electrophysiological manifestations, and treatment. Data now support the presence of both presynaptic and postsynaptic dysfunction in MuSK‐MG. This is 1 of many key differences between MuSK‐MG and acetylcholine receptor antibody‐MG (AChR‐MG), especially as it pertains to potential therapeutic implications. In comparison to AChR‐MG, MuSK‐MG is generally more refractory to treatment. However, because MuSK‐MG is better understood and more readily recognized today, there are more reports of a relatively benign course. The most effective immunotherapies for MuSK‐MG are corticosteroids, plasmapheresis, and rituximab. With appropriate therapy, most patients with MuSK‐MG achieve minimal manifestation status or better on the postintervention status outlined by the Myasthenia Gravis Foundation of America. A minority of patients remain refractory to treatment, and optimal management for this group remains a considerable challenge. Muscle Nerve 58 : 344–358, 2018     

Translation and validation of the arabic version of the revised 15‐item myasthenia gravis quality‐of‐life questionnaire

Introduction: We sought to translate, culturally adapt, and assess the Arabic version of the 15‐item myasthenia gravis quality‐of‐life revised scale (MGQOL15R). Methods: We assessed reliability with Cronbach α; reproducibility with intraclass correlation coefficient (ICC); validity with Spearman correlations for myasthenia gravis (MG)‐specific activities of daily living (MG‐ADL), MG composite (MGC) score, and MG manual muscle test (MG‐MMT) and with MGQOL15R in patients with different disease severity through the Kruskal–Wallis test; and sensitivity to change with Wilcoxon signed‐rank test. Results: In 65 enrolled patients, the mean MGQOL15R score was 10.84 ± 8.11 (α = 0.94, ICC = 0.95). The correlation coefficients between MGQOL15R and MGC, MG‐ADL, and MG‐MMT scores were 0.75, 0.75, and 0.74, respectively (P < 0.001). MGQOL15R scores were significantly higher (worse) in patients with more severe disease at baseline and significantly lower (better) in improved patients at follow‐up. Discussion: The Arabic version of MGQOL15R is valid, reliable, stable, and sensitive to changes. Muscle Nerve 57 : 581–585, 2018     

Rituximab treatment of myasthenia gravis: A systematic review

Rituximab is a chimeric mouse/human anti‐CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle‐specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P < 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20⁺ B‐cells were observed up to 20 and 16 weeks, respectively, after 4 weekly infusions. Muscle Nerve 56 : 185–196, 2017     

Validation of the besta neurological institute rating scale for myasthenia gravis

Introduction: We validated the scale for myasthenia gravis (MG) developed at the Neurological Institute Foundation of Milan (INCB‐MG scale). Methods: A total of 174 patients were evaluated with the INCB‐MG and compared with the MG Composite (MGC) as the gold standard. Dimensionality, reliability, and validity of the INCB‐MG scale were studied by principal component factor analysis, Cronbach alpha, and Pearson correlation coefficients; interobserver reliability was calculated by the weighted Cohen K coefficient. Results: Generalized and bulbar INCB‐MG subscales were unidimensional with excellent consistency; the INCB‐MG and MGC scales were strongly correlated. Fatigability assessment was correlated with the INCB‐MG generalized, bulbar, and respiratory subscales. Conclusions: The INCB‐MG scale is a reliable tool to assess MG and is strongly correlated with the MGC. The INCB‐MG scale is a valid tool for every day practice and should be further investigated for its application in clinical trials. Muscle Nerve 53 : 32–37, 2016     

Mycophenolate mofetil in AChR‐antibody‐positive myasthenia gravis: Outcomes in 102 patients

Two recent randomized, controlled trials failed to demonstrate a benefit of mycophenolate mofetil (MMF) over prednisone in the treatment of myasthenia gravis (MG). We reviewed our experience with MMF in MG to determine whether these trials may have been unsuccessful because of their short duration and the unpredicted benefit of prednisone. We reviewed outcomes and prednisone dosage for all our acetylcholine‐receptor (AChR)‐antibody positive MG patients treated with MMF alone or with prednisone for at least 3 months. The percentage of patients with a desirable outcome (MG‐specific Manual Muscle Test score <4 or Myasthenia Gravis Foundation of America post‐invention status of minimal manifestations or better) began to increase after 6 months; 80% of those followed for >24 months had a desirable outcome. Prednisone dose decreased after 12 months; after 25 months, 54.5% of patients took no prednisone and 75% took <7.5 mg/day. This retrospective analysis provides class IV evidence that MMF begins to improve AChR‐positive MG after 6 months, both with prednisone and as monotherapy. Muscle Nerve 41: 593–598, 2010     

Correlating serum micrornas and clinical parameters in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a debilitating neurologic disorder with poor survival rates and no clear biomarkers for disease diagnosis and prognosis. Methods: We compared serum microRNA (miRNA) expression from patients with ALS with healthy controls and patients with multiple sclerosis and Alzheimer disease. We also correlated miRNA expression in cross‐sectional and longitudinal cohorts of ALS patients with clinical parameters. Results: We identified 7 miRNAs (miR‐192‐5p, miR‐192‐3p, miR‐1, miR‐133a‐3p, miR‐133b, miR‐144‐5p, miR‐19a‐3p) that were upregulated and 6 miRNAs (miR‐320c, miR‐320a, let‐7d‐3p, miR‐425‐5p, miR‐320b, miR‐139‐5p) that were downregulated in patients with ALS compared with healthy controls, patients with Alzheimer disease, and patients with multiple sclerosis. Changes in 4 miRNAs (miR‐136‐3p, miR‐30b‐5p, miR‐331‐3p, miR‐496) correlated positively and change in 1 miRNA (miR‐2110) correlated negatively with changes in clinical parameters in longitudinal analysis. Discussion: Our findings identified serum miRNAs that can serve as biomarkers for ALS diagnosis and progression. Muscle Nerve 58 : 261–269, 2018     

Effects of balance strategy training in myasthenia gravis: A case study series

Introduction: Studies of exercise in patients with myasthenia gravis (MG) are sparse. Balance strategy training (BST) multimodal exercise has proven efficacy in adults for enhancing balance and functional mobility. This prospective study aims to determine if BST improves functional ability and balance in people with MG. Methods: Seven individuals with MG participated in a 16‐session workstation intervention. Repeated measures (pre/post‐intervention and 4‐week follow‐up) consisting of quantitative myasthenia gravis score (QMG), 6‐minute walk test (6MWT), timed up and go (TUG) with dual task (TUG_manual and TUG_cognitive), and standing stability on foam with eyes closed (foamEC) were assessed. Results: Most measurements showed sustained improvement at follow‐up. QMG, TUG_cognitive, and foam EC achieved clinically significant improvements (>15%). No adverse effects were reported. Conclusions: BST was effective in improving balance and QMG scores in subjects with MG. A multimodal BST approach is thus suggested to target different aspects of balance and functional mobility. Muscle Nerve 49 : 654–660, 2014     

Thymectomy may not be associated with clinical improvement in MuSK myasthenia gravis

Introduction: A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti–muscle-specific kinase (MuSK)-MG. Methods: The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK-MG. Results: Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12–1.53, P = 0.19). Discussion: Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK-MG patients. Muscle Nerve 59:404–410, 2019     

Correlation between a patient-derived functional questionnaire and abnormal neuromuscular transmission in Myasthenia Gravis patients.

OBJECTIVE: To correlate the patient-derived physical function score, as measured by the disease specific Myasthenia Gravis Questionnaire (MGQ), and the score obtained with commonly used generic 36-item questionnaire, the Short-Form health survey (SF-36), with the degree of abnormal neuromuscular transmission measured by Single-Fibre EMG (SFEMG) and repetitive nerve stimulation (RNS) in Myasthenia Gravis (MG) patients. METHODS: SFEMG and RNS were performed in the deltoid muscle and SFEMG was also performed in the orbicularis oculi muscle in 45 MG patients. The patients were asked to fill out the MGQ, which has been translated and validated into Swedish, and the SF-36. The sum of MGQ items generates a global MGQ score. Items are also divided into 3 muscle specific domains: generalized, bulbar and ocular. RESULTS: The global MGQ score and generalized domain score of MGQ were strongly correlated with the degree of abnormal neuromuscular transmission, as measured by SFEMG in the deltoid muscle. Scores from ocular and bulbar domains of MGQ were not related to neurophysiological findings. Physical composite scores of SF-36 correlated significantly with the abnormal SFEMG findings in the deltoid. CONCLUSIONS: The degree of disturbed neuromuscular transmission in a proximal limb muscle correlates with a patient's subjective experience of generalized myasthenic dysfunction. SIGNIFICANCE: The observed correlation adds a new dimension to neurophysiological examinations in patients with MG.     

Psychometric evaluation of the myasthenia gravis composite using Rasch analysis

Introduction: The MG Composite (MGC) is a validated outcome measure of the clinical manifestations of myasthenia gravis. Methods: We performed Rasch analyses of the MGC to investigate additional properties, including its unidimensionality and the appropriateness of the weights assigned to the response categories for the MGC items. Results: The fit statistics indicated that the 10 items belong together and can be summated for a total score. There was an overall absence of item order distortion between response categories. The Rasch model's expected category response values were compatible with item weights previously assigned. Conclusions: Our analysis suggests that: (1) the score can be summated to estimate an overall disease severity score; (2) the response options of the 10 items are not significantly distorted; and (3) the assigned weights of the response options are appropriate. Muscle Nerve 45: 820–825, 2012