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The authors have developed an MG activities of daily living (ADL) profile (MG-ADL)-a simple eight-question survey of MG symptoms. In 254 consecutive encounters with established MG patients, the authors compared scores from the MG-ADL to the quantitative MG score (QMG)-a standardized, reliable scale used in clinical trials. The mean MG-ADL score was 4.89+/-3.63. The mean QMG score was 10.80+/-5.70. Pearson's correlation coefficient was 0.583 (p < 0.001). The MG-ADL is an easy-to-administer survey of MG that correlates well with the QMG and can serve as a secondary efficacy measurement in clinical trials.
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MG-ADL: STILL A RELEVANT OUTCOME MEASURE
SRIKANTH MUPPIDI, MD,
1
GIL I. WOLFE, MD,
1
MARK CONAWAY, PhD,
2
and TED M. BURNS, MD
3
and the MG COMPOSITE AND MG-QOL15 STUDY GROUP
1
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
2
Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia 22908, USA
3
Department of Neurology, University of Virginia, Charlottesville, Virginia, USA
Accepted 15 April 2011
ABSTRACT: Introduction: The aim of this analysis was to
examine the performance of the Myasthenia Gravis–specific
Activities of Daily Living scale (MG-ADL) during a multicenter
scale validation study. Methods: Consecutive MG patients were
assessed with several MG outcome measures, including the
MG-ADL. Statistical tests included descriptive analysis, Pearson
correlation, and sensitivity/specificity. Results: Eighty-seven
patients completed the MG-ADL, MG Composite (MGC), and
MG 15-item Quality of Life scale (MG-QOL15) on the first visit,
and 76 returned for the second visit. At the first visit, there was
a strong positive correlation between MG-ADL and MGC (r¼
0.85, P<0.0001) and MG-QOL15 (r¼0.76, P<0.0001). Cor-
relation of the delta MG-ADL score and physician impression of
change between the visits was strong (r¼0.70, P<0.0001). A
2-point improvement in the MG-ADL best predicted clinical
improvement. Test–retest analysis demonstrated a high reliabil-
ity coefficient. Conclusions: The MG-ADL correlates strongly
with newer, validated MG outcome measures. A 2-point
improvement in the MG-ADL indicates clinical improvement.
The MG-ADL is useful as a research tool and in routine clinical
management.
Muscle Nerve 44: 727–731, 2011
Multiple outcome measures have been developed
for evaluating the clinical status of patients with
myasthenia gravis (MG).
1
These outcome measures
differ in ease of use, ease of interpretation, what is
being measured, how it is being measured, and
who interprets and reports the symptoms and
impairments (i.e., patient-reported vs. physician-
reported).
1–11
The Myasthenia Gravis–specific
Activities of Daily Living scale (MG-ADL) was devel-
oped in the late 1990s to assess the status of symp-
toms and activities in MG.
11
It is an 8-item, patient-
reported questionnaire that can be completed in
2–3 minutes with no need for specialized equip-
ment or training (Table 1).
We recently studied and validated two new MG
outcome measures, the MG Composite (MGC) and
MG 15-item Quality of Life (MG-QOL15) scales, in
a prospective, multicenter study.
1,3
As part of this
scale validation study, several centers collected MG-
ADL data. In this analysis, we evaluate the perform-
ance of the MG-ADL.
METHODS
A multicenter, scale validation observational study
was recently completed in patients with MG to
assess the validity and reliability of the MGC and
MG-QOL15. The uniform entry criteria for all cen-
ters were as follows: (1) patients were at least 17
years of age with a diagnosis of MG based on clini-
cal, serological, and electrodiagnostic testing; and
(2) the treating physician scheduled the patient to
be seen for follow-up within 6 months. The study
protocol did not mandate any changes in treat-
ment or management; this was left to the discre-
tion of the treating physician.
3
Briefly, consecutive
MG patients were enrolled at 11 centers. Prior to
the study, investigators at the centers were asked to
perform either the MG-ADL or the MG Manual
Motor Test, in addition to other measures
included in the study. Patients at five centers com-
pleted the MG-ADL and other outcome measures
at two consecutive visits. At both visits, demo-
graphic data and disease features, including
antibody status, duration of MG, and MG Founda-
tion of America (MGFA) class, were also docu-
mented. A neuromuscular-trained neurologist
documented the physician impression of change at
the second visit using a 7-point scale: markedly
improved; moderately improved; slightly improved;
unchanged; slightly worsened; moderately wors-
ened; or markedly worsened. The study protocol
did not provide guidance or instruction on the
care of the patients. The protocol was approved by
the institutional review board at each study center,
and informed consent was obtained from all
subjects.
Test–retest reproducibility of the MG-ADL was
performed on 26 patients in a separate study at
the University of Virginia. The MG-ADL was com-
pleted by each patient during the first clinic visit.
Patients were asked to complete a second MG-ADL
at home within 2–4 days of the clinic visit and
return it in a self-addressed, stamped envelope. We
did not call patients to remind them to complete
the scale or assist them during the completion of
the second MG-ADL. The 2–4-day time period was
chosen to minimize the likelihood that the patient
would recall answers from the first MG-ADL and to
minimize the likelihood the disease would have
changed significantly. The protocol was approved
Abbreviations: AChR-Ab, acetylcholine receptor antibodies; MG, myas-
thenia gravis; MG-ADL, Myasthenia Gravis–specific Activities of Daily Living
scale; MGC, MG Composite scale; MGFA, Myasthenia Gravis Foundation
of America; MG-QOL15, 15-item Myasthenia Gravis Quality of Life scale;
MuSK-Ab, muscle-specific tyrosine kinase antibodies; QMG, Quantitative
Myasthenia Gravis scale; ROC, receiver operating characteristic
Correspondence to: T. M. Burns; e-mail: tmb8r@virginia.edu
V
C2011 Wiley Periodicals, Inc.
Published online 15 October 2011 in Wiley Online Library
(wileyonlinelibrary.com). DOI 10.1002/mus.22140
Key words: MG outcome measures, MG scales, MG-ADL, MGC and MG-
QOL15, myasthenia gravis
MG-ADL MUSCLE & NERVE November 2011 727
by the institutional review board at the University
of Virginia, and informed consent was obtained
from all subjects.
We analyzed the correlations between the MG-
ADL, MGC, and MG-QOL15 at both visits and also
the change in scores between the visits. Both Pear-
son and Spearman correlation analyses were used;
however, only the Pearson correlation is reported
here, as there was no significant difference
between these correlation parameters. Receiver
operating characteristic (ROC) curve and sensitiv-
ity/specificity analyses were performed based on
the physician impression of change and the MG-
QOL15 score at the second visit. SAS version 9.2
(SAS Institute, Inc., Cary, North Carolina) software
was used for statistical analysis.
RESULTS
A total of 87 patients were enrolled from the five
participating centers. Seventy-six patients returned
for the second visit. The mean duration between
visits was 129 days (range 25–198 days). The mean
age was 58.1 years, and 49% were women. The
MGFA classifications at visit 1 were as follows: class
I, 18% (16 of 87); class IIa, 22% (20 of 87); class
IIb, 9% (8 of 87); class IIIa, 25% (22 of 87); class
IIIb, 6% (6 of 87); and class IV, 4% (4 of 87).
Eleven patients were in remission. Seventy-four
patients were seropositive for acetylcholine recep-
tor antibodies (AChR-Ab), 4 for muscle-specific ty-
rosine kinase antibodies (MuSK-Ab), and 7 were
seronegative. Antibody status was unknown in 2
patients. At visit 1, 73 patients were established fol-
low-up patients, 8 patients were new clinic patients,
and 6 patients were hospitalized.
Absolute scores and change in scores for the
MG-ADL, MGC, and MG-QOL15 for the first and
second visits are presented in Table 2.
Pearson correlations were performed between
the MG-ADL, MGC, and MG-QOL15 scores at each
visit and on the change in scores between visits
(Table 3). All of these values revealed robust posi-
tive correlations between the MG-ADL and the
other two MG scales (P<0.0001). Correlation
coefficients for the change in scores were also high
(P<0.0001). A high correlation also existed
between the MG-ADL, MGC, MG-QOL15, and phy-
sician impression of change (P<0.0001; Table 4).
Of note, in only 1 of 76 patients seen in follow-up
was the change in MG-ADL score and the physi-
cian impression of change discordant.
Based on previously published data,
3
parallel
improvements in physician impression of change
Table 1. MG Activities of Daily Living (MG-ADL) Profile.
Grade 0 1 2 3
Score
(0, 1, 2, 3)
1. Talking Normal Intermittent
slurring of nasal speech
Constant slurring or nasal,
but can be understood
Difficult to understand
speech
2. Chewing Normal Fatigue with solid food Fatigue with soft food Gastric tube
3. Swallowing Normal Rare episode of choking Frequent choking
necessitating
changes in diet
Gastric tube
4. Breathing Normal Shortness of
breath with exertion
Shortness of breath at rest Ventilator dependence
5. Impairment of ability
to brush
teeth or comb hair
None Extra effort, but no rest
periods needed
Rest periods needed Cannot do one
of these functions
6. Impairment of ability
to arise
from a chair
None Mild, sometimes
uses arms
Moderate, always
uses arms
Severe, requires
assistance
7. Double vision None Occurs, but not daily Daily, but not constant Constant
8. Eyelid droop None Occurs, but not daily Daily, but not constant Constant
MG-ADL score (items
1–8)
Tab le 2 . Descriptive data for MG-ADL, MGC, and
MG-QOL15 for both visits and physician impression of
change at second visit.
NMean SD Median
First visit
MG-ADL 87 4.89 3.54 5
MGC 87 8.89 6.87 8
MG-QOL15 total 87 20.8 15.27 20.0
Second visit
MG-ADL 76 3.59 3.3 3
MGC 76 6.26 5.8 5
MG-QOL15 total 76 15.14 13.88 9
Change in scores (visit 2-visit 1)
MG-ADL 76 1.22 3.0 1.0
MGC 76 2.61 6.25 0.5
MG-QOL15 total 76 5.32 11.7 1.5
Physician impression of change 76 0.69 2.1 0
728 MG-ADL MUSCLE & NERVE November 2011
and in the MG-QOL15 were thought to be the best
indicators of clinical improvement. Figure 1 dem-
onstrates the ROC curve for the MG-ADL using
this indicator as the ‘‘gold standard’’ for clinical
improvement. The ROC area under the curve was
0.90, suggesting high accuracy. Sensitivity/specific-
ity analysis performed with various cut-off points
for the change in MG-ADL suggested that a 2-point
reduction in the scale best predicted improvement
in MG clinical status (Table 5).
Test–Retest Reproducibility of MG-ADL. A total of
26 patients completed the MG-ADL during the
clinic visit, and 20 repeated the MG-ADL at home
within 1 week. The mean MG-ADL score was 3.6
(SD: 63.2) at the clinic visit for the 20 patients
who returned the second MG-ADL; mean MG-ADL
was 7.3 (SD: 63.2) for the 6 patients who did not
return the second MG-ADL. The test–retest reli-
ability coefficient was 93.7%, with a lower 95% con-
fidence interval at 87.3%. The MG-ADL scores
were within 2 points 85% of the time (17 of 20
instances) and never differed by >3 points.
Responsiveness of MG-ADL. The mean improve-
ment in ADL score in patients who improved
based on the gold standard (improvement in MG-
QOL15 score plus improvement in physician
impression of change score) was 3.88 (SD: 62.72).
The standardized mean response was 3.88/2.72 ¼
1.43. The effect size was 1.21 (mean change in
MG-ADL in patients who improved divided by the
SD from the test–retest data ¼3.88/3.2). Both of
these findings indicate excellent responsiveness of
MG-ADL in patients who improved between the
first and second visits.
DISCUSSION
The MG-ADL was designed to assess relevant symp-
toms and the functional performance of daily activ-
ities that are sometimes impaired by MG. The 8
items in the scale were derived from symptom-
based components of the original 13-item QMG.
12
In the original description, the MG-ADL was found
to have good correlation with the QMG and was
recommended as a secondary endpoint in clinical
trials.
11
Since then, it has been widely applied to
both routine practice and clinical research. The
inclusion of the MG-ADL in our multicenter scale
validation study of the MGC and MG-QOL15 pro-
vided an opportunity to further study its perform-
ance. Our analysis suggests that a 2-point improve-
ment in MG-ADL score optimally indicates clinical
improvement and has acceptable reliability. The
correlation between the change in MG-ADL and
the physician assessment of global change also sug-
gested that the MG-ADL possesses excellent
responsiveness to clinical change. The correlations
Table 3 . Correlation coefficients between MG-ADL, MGC, and MG-QOL15.
MG-ADL vs.
MGC
MG-ADL vs.
MG-QOL15
MGC vs.
MG-QOL15
Visit 1 0.846 (<0.0001) 0.763 (<0.0001) 0.734 (<0.0001)
Visit 2 0.869 (<0.0001) 0.775 (<0.0001) 0.647 (<0.0001)
Change in scores (second visit-first visit) 0.753 (<0.0001) 0.671 (<0.0001) 0.547 (<0.0001)
Data expressed as Pearson’s R (P-value).
Tab le 4 . Correlation coefficients between MG-ADL, MGC,
MG-QOL15, and physician impression of change.
MG-ADL vs.
physician
impression
of change
MGC vs.
physician
impression
of change
MGQOL 15 vs.
physician
impression
of change
0.703 (<0.0001) 0.770 (<0.0001) 0.554 (<0.0001)
Data expressed as: Pearson’s R (P-value).
FIGURE 1. ROC curve for MG-ADL change with improvement
in physician global impression of change score plus improve-
ment in MG-QOL15 score as the ‘‘gold standard.’ An area under
the curve of 0.90 suggests high accuracy.
MG-ADL MUSCLE & NERVE November 2011 729
between the MG-ADL and both the MGC and MG-
QOL15 were also high.
The construct validity, responsiveness to clinical
improvement, simplicity, and ease-of-use of the
MG-ADL are attractive attributes for use in the
clinic and in clinical trials. In addition to the favor-
able properties observed in this analysis, the MG-
ADL was recently found to be a sensitive outcome
measure of responsiveness to change in a clinical
trial of mycophenolate mofetil in MG.
13,14
Further-
more, because it does not necessarily require face-
to-face contact, the MG-ADL might potentially be
useful as one way to follow patients outside of the
clinic visit (along with, e.g., the MG-QOL15). This
potential additional use of the MG-ADL is sup-
ported by our acceptable test–retest reproducibility
results, which were obtained by having patients
first complete the MG-ADL in the clinic followed
by completion of the second MG-ADL at home
without assistance from any care provider. This
potential remote use of the MG-ADL merits fur-
ther study.
Our analysis demonstrates the validity of the
MG-ADL in a representative sample of the MG
population. In contrast to most clinical trials, our
study included patients seen for MG regardless of
clinical disease severity, many of whom would not
be eligible for clinical trials (e.g., those in remis-
sion). The mean MG-ADL score at first visit in this
study was lower than for some clinical trials,
14
likely because we included mildly affected patients
and patients in remission. Our sample population
is similar in many characteristics, such as for sero-
logical status and MGFA class distribution, to other
reported MG cohorts.
15–17
There are a few limitations to our analysis. Our
multicenter study was primarily designed to assess
the validity of the MGC and MG-QOL15, and ini-
tial power calculations were based on this analysis.
Another limitation stems from the fact that the
MG-ADL and MGC share 4 items, which inflates
the correlations between these two scales. How-
ever, similarly significant correlations were
observed between the MG-ADL and MG-QOL15,
where no test items are shared. Finally, only 5 of
11 centers chose to record MG-ADL scores, and
therefore the sample size was 50% of the original
MGC study.
3
We do not believe this created a sig-
nificant selection bias, however, as all sites enrolled
patients using identical entry criteria.
This project was supported by Myasthenia Gravis Foundation of
America grant (to Ted Burns) and the North and Central Texas
Clinical and Translational Science Initiative KL2RR024983 (to Sri-
kanth Muppidi).
APPENDIX
The MG Composite and MG-QOL15 Study Group
includes: Ted M. Burns (Principal Investigator,
University of Virginia); Mark Conaway (University
of Virginia); Guillermo Solorzano (University of
Virginia); Maria E. Farrugia (Institute of Neurolog-
ical Sciences, Glasgow, UK); Donald B. Sanders
(Duke University); Janice M. Massey (Duke Univer-
sity); Vern C. Juel (Duke University); Lisa D. Hob-
son-Webb (Duke University); Bernadette Tucker-
Lipscomb (Duke University); Carlo Antozzi (Neu-
rological Institute Foundation ‘‘Carlo Besta,’’ Mi-
lan, Italy); Renato Mantegazza (Neurological
Institute Foundation ‘‘Carlo Besta,’’ Milan, Italy);
David Lacomis (University of Pittsburgh); Elliot
Dimberg (Mayo Clinic, Jacksonville); Srikanth
Muppidi (University of Texas Southwestern); Gil I.
Wolfe (University of Texas Southwestern); Mazen
M. Dimachkie (University of Kansas); Richard J.
Barohn (University of Kansas); Mamatha Pasnoor
(University of Kansas); April L. McVey (University
of Kansas); Laura Herbelin (University of Kansas);
Tahseen Mozaffar (University of California, Irvine);
Vinh Q. Dang (University of California, Irvine);
Sandhya Rao (University of California, Irvine);
Robert Pascuzzi (Indiana University); Riley Snook
(Indiana University); and Anthony A. Amato (Brig-
ham and Women’s Hospital and Harvard Medical
School).
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change in score
Sensitivity
(n¼26)
Specificity
(n¼50)
19671
27782
36290
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MG-ADL MUSCLE & NERVE November 2011 731
... 15 Long-term tolerability and improvements to clinical outcomes have also been shown in an interim analysis of the REGAIN open-label extension (OLE; NCT02301624). 19 The MG activities of daily living profile (MG-ADL) 20 and the quantitative MG scale (QMG) 21 are validated, MG-specific outcome measures, each of which comprise four domains representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. The MG-ADL and QMG were key, prospectively defined efficacy measures used to assess patient outcomes in REGAIN and the OLE. ...
... It comprises four domains, representing ocular (two items), bulbar (three items), respiratory (one item), and limb (two items) muscle groups, which assess visual, oral, breathing, and limb motor abilities, respectively. 20 Each item is scored from 0 to 3, with a maximum total score of 24. The QMG is an objective, physician-reported, 13-item measure of muscle strength that comprises four domains, representing ocular (three ocular and facial muscle items), bulbar (two swallowing and speech items), respiratory (one forced vital capacity item), and gross motor (seven limb and axial motor items) muscle groups. ...
... The scores for all domains of the MG-ADL and QMG were recorded throughout REGAIN and its OLE. Assessments were performed weekly from week 1 to week 3 and then at weeks 4,8,12,16,20,26,40, and 52 in year 1, then every 6 months afterward and at each patient's endof-study visit. The MG-ADL and QMG total and domain scores from REGAIN and the completed OLE are reported here. ...
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... Muscle Nerve 60: [14][15][16][17][18][19][20][21][22][23][24]2019 Generalized myasthenia gravis (gMG) is a chronic, rare autoimmune disorder that is characterized by severe muscle weakness. 1 Autoantibodies to the acetylcholine receptor are present in 73%-88% of patients with gMG. ...
... Validated MG assessments of activities of daily living, muscle strength, functional ability, and quality of life were used to evaluate the long-term efficacy of eculizumab. These assessments consisted of the MG-ADL scale, 24 the Quantitative MG scale (QMG), 25 the MG Composite scale (MGC), 26 and the 15-item MG Quality of Life questionnaire (MG-QOL15). 27 MG-ADL, QMG, MGC, and MG-QOL15 assessments were performed on day 1. ...
... We adopted a policy of close follow-up with a battery of internationally validated scales for MG and with standardized quality of life scales and questionnaires [38][39][40][41][42][43][44] (see Supplementary appendix). The study visits took place before or during IVIG infusion but before starting prednisone (visit 1), as well as at 4 weeks (visit 5) and 6 weeks (visit 7) after starting prednisone. ...
... We used a battery of scales validated for use in MG [38][39][40][41][42][43][44] . Both the objective scales for physical examination (QMC and MG-composite scale) and the patient-reported scales on treatment response (activities of daily living; ADLs) have shown sufficient sensitivity to detect improvement and exacerbation. ...
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Corticosteroids may produce a paradoxical worsening of myasthenia gravis (MG) symptoms within the first weeks of treatment. We therefore wanted to assess the hypothesis that a prior infusion of intravenous immunoglobulin (IVIG) may have a protective effect. Our primary objectives were to show that the coadministration of immunoglobulins and glucocorticoids is safe and effective for controlling myasthenic symptoms, and to compare the exacerbation rate with this approach and historical practice without IVIG. We recruited 45 patients with generalized MG who required corticosteroids for the first time and we gave all IVIG before starting the full doses of prednisone. Monitoring was performed with validated scales, questionnaires, and blood tests over a 6-week period. Only 4.4% had severe adverse effects related to IVIG and 86.7% improved clinically. Notably, only 2.2% had a paradoxical symptom exacerbation in the first weeks of starting prednisone, which was statistically lower than the 42% reported in a historical series. We conclude that adjuvant therapy with IVIG when starting prednisone for the first time in patients with generalized MG is safe and effective. Given that the rate of paradoxical worsening was lower than that previously reported, the addition of IVIG may have a protective effect against such exacerbations.
... An interim analysis of the open-label extension of REGAIN found that eculizumab remained effective and well tolerated for up to 3 years of extended treatment (NCT02301624) [14]. During these studies, key efficacy endpoint assessments included the patient-reported MG activities of daily living scale (MG-ADL) [15] and the 15-item MG quality of life questionnaire (MG-QOL15) [16]. ...
Article
Background The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods Attainment of 'minimal symptom expression' was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. 'Minimal symptom expression' was defined as MG-ADL total score of 0-1 or MG-QOL15 total score of 0-3. Results At REGAIN week 26, more eculizumab-treated patients achieved 'minimal symptom expression' versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension,
... Facing the problem of TM consulting for NMD during COVID-19 outbreak, we suggest, as suitable for that, the following scales: ALSFR-R for motor neuron diseases [7], MG-ADL for neuromuscular junction diseases [8], Myo-FRS for myopathies and Nerve-FRS (N-FRS) for neuropathies. ALSFR-R and MG-ADL are disease-specific scales validated for amyotrophic lateral sclerosis and myasthenia gravis, respectively; they appear the most reliable scales for a remote evaluation in these two disorders, as they satisfy the aforementioned prerogatives required in a TM context and in addition, they allow to compare the score obtained by TM with those previously obtained. ...
... 30,31 The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is a validated simple 8-question survey of MG symptoms with scores ranging from 0 to 24 with higher scores indicating more severe disease. 32 MMS is defined as having "no symptoms or functional limitations from MG, but there may be some weakness on examination of some muscles." 26,33 At the same time, QMG score at the visit had to be lower than baseline and lower than 14 to qualify for MMS in this study. ...
Article
Objective To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized myasthenia gravis (MG) patients. Methods This study is a post hoc analysis of data from the randomized trial of thymectomy in myasthenia gravis (MGTX). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone versus prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100mg on alternate-days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone, was compared between the thymectomy plus prednisone and prednisone alone groups. Results MG patients in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, P<0.001) over the 5-year study period. Prednisone associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone. Conclusions Thymectomy benefits MG patients by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone. Trial Registration The trial was registered on clinicaltrials.gov, number NCT00294658 Classification of Evidence: This study provides Class II evidence that for generalized MG patients with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.
... The main outcome measures are the timeweighted average (TWA) quantitative myasthenia gravis score (QMG) [14] and the TWA needed dose of prednisone by assessing in each stage. The myasthenia gravis activities of daily living scale scores (MG-ADL), [15,16] treatment-associated complications, incidence of myasthenic crisis and the mortality over the follow up period are defined as the secondary outcomes. ...
Article
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Background: The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is currently one of the regular treatment in clinic, which is, however, still controversial for non-thymomatous MG. This research will assess the effectiveness and safety of thymectomy plus prednisone compared to prednisone monotherapy for the treatment of non-thymomatous MG systematically. Methods: According to eligibility and ineligibility criteria, 8 databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan-fang Database, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), will be searched to gather the up-to-standard articles from September 2000 to September 2025. Inclusion criteria are as follows: randomized controlled trials of thymectomy plus prednisone for the treatment of non-thymomatous MG. The quantitative myasthenia gravis score (QMG) and the dose of prednisone required will be accepted as the main outcomes. Data synthesis, subgroup analysis, sensitivity analysis, and meta-regression analysis will be conducted using RevMan 5.3 software. We will use Egger or Begg test to evaluate symmetry on a funnel plot which is made to assess reporting bias, and use trial sequential analysis (TSA) to exclude the probability of false positives. Results: This systematic review will measure the QMG and the dose of prednisone required, the myasthenia gravis activities of daily living scale scores (MG-ADL), treatment-associated complications, incidence of myasthenic crisis and other aspects to comprehensively assess the clinical benefits of thymectomy plus prednisone for MG patients without thymoma. Conclusion: The conclusion of this study will achieve convincing evidence to evaluate the effectiveness and safety of thymectomy plus prednisone for the treatment of non-thymomatous MG. Prospero registration number: CRD 42020167735.
Article
Objective: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG). Methods: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment. Results: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05). Conclusions: Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.
Article
To explore posttraumatic stress disorder symptoms (PTSD) after respiratory insufficiency in patients with myasthenia gravis (MG). The investigation was made with 134 adult patients with MG, after respiratory insufficiency, between January 2012 and January 2016 and had a return visit after one year. 134 patients finished this study and 69 patients (51.5%) had PTSD. Anxiety (HADS-A ≥ 8, HADS: Hospital Anxiety and Depression Scale) (OR 2.585,95% CI 1.102-6.061, p = 0.029), and depression (HADS-D ≥ 8) (OR 3.200, 95% CI 1.395-7.342, p = 0.006) were associated with greater probabilities of screening positive for PTSD. Gender, age, intubation, yearly income, marriage, inability to work, number of respiratory insufficiency episodes, education level, Mini-mental state examination (MMSE) (>20), ICU stays, having insurance, and MG-activities of daily living (ADL) (<9) were not significant predictors for PTSD. One year after a respiratory insufficiency episode, patients with PTSD experienced worse anxiety (p = 0.035), depressive disorder (p < 0.001), and 36-Item Short-Form Health Survey (SF-36) showed physical functioning (p = 0.042), role-physical (p = 0.013), social functioning (p = 0.040), and emotional-role (p = 0.034). But there were no differences in ADL, bodily pain, general health and vitality. PTSD in patients with MG is common after a respiratory insufficiency episode; anxiety and depression were both associated with greater probabilities of screening positive for PTSD.
Article
Myasthenia gravis (MG) is an autoantibody‐mediated inflammatory disease of the neuromuscular junction. Biomarkers indicating disease activity in MG are warranted. Recently, soluble urokinase plasminogen activator receptor (suPAR) has been reported to be associated with inflammation, tissue damage, disease activity, and prognosis in various diseases, including autoimmune diseases. In this study, serum suPAR levels were measured in 40 patients with anti‐acetylcholine receptor antibody‐positive MG and in 30 controls, and their correlations with clinical variables and severity scale scores were investigated. We identified that serum suPAR levels significantly correlated with MG activities of daily living scale (Spearman’s ρ = 0.45; P = 0.004) and MG Foundation of America classification (Spearman’s ρ = 0.37; P = 0.02) at serum sampling, but not with anti‐acetylcholine receptor antibody titers. In conclusion, serum suPAR levels can be a candidate for a novel biomarker of disease activity in anti‐acetylcholine receptor antibody‐positive MG.
Article
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A multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases. Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG. Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona.
Article
Objective: To test the hypothesis that mycophenolate mofetil (MMF) with prednisone provides better control of myasthenic weakness than prednisone alone in the initial management of generalized myasthenia gravis (MG). Methods: Eighty immunosuppression naïve subjects with mild to moderate generalized, acetylcholine receptor positive MG at 13 centers were randomized to 2.5 g/day MMF plus 20 mg/day prednisone (n = 41) or placebo plus 20 mg/day prednisone (n = 39) and followed in a double-blind fashion for 12 weeks. Subjects over 18 years of age were included if judged to be candidates for immunosuppression; excluded were those with thymoma or severe oropharyngeal or respiratory muscle weakness. The primary measure of efficacy was change in the quantitative MG (QMG) score from baseline to week 12. Study completers could take open-label MMF for an additional 24 weeks, while prednisone was reduced to the minimally effective dosage. Results: The mean change in QMG score was similar in the treated (-4.4 +/- 5.1) and placebo (-3.6 +/- 5.0) groups (p = 0.71). The dosage of prednisone was reduced by a similar amount in both groups during the open-label phase. Subjects tolerated the study drug well, without unexpected adverse events. Conclusions: This study demonstrated no benefit of mycophenolate mofetil (MMF) with 20 mg/day prednisone compared to 20 mg/day of prednisone alone after 12 weeks. This may be due to greater than predicted benefit from the prednisone dosage used, the short duration of the study, or the absence of any benefit of MMF in this population of patients with myasthenia gravis.
Article
On the experience of long-lasting personal observation of 350 myasthenic patients the author has applied the ‘disability status scale’ (known as Kurtzke or Bronx scale in multiple sclerosis practice) for myasthenia gravis. This system renders the quantitative evaluation of the different parameters possible. There are ten grades of gravity (from 1 to 10) and six functional systems (ocular, facial, bulbar, sceletal, respiratory and other functions).Copyright © 1976 S. Karger AG, Basel
Article
We describe the process whereby a recently developed myasthenia gravis (MG)-specific quality-of-life (QOL) instrument was reduced from 60 items to 15 items while maintaining potential usefulness in the clinic and in prospective treatment trials. In data from a recently completed prospective trial of mycophenolate mofetil (MMF) in MG, the MG-QOL15 correlated as highly as the 60-item MG-QOL for physical and social domains of the 36-item health survey of the Medical Outcomes Study Short Form (SF-36). Correlation coefficients for the MG-QOL15 were similar to the 60-item MG-QOL for the Quantitative Myasthenia Gravis (QMG), MG-specific Manual Muscle Testing (MG-MMT), and the MG-specific Activities of Daily Living (MG-ADL) scores at week 0 and for change in scores from week 0 to week 12 in the MMF trial. Using the physician global impression at week 12 of the trial as the "gold standard," the MG-QOL15 demonstrated high sensitivity. Because the MG-QOL15 instrument can be quickly and easily administered and interpreted, it is a potential QOL measure for treatment trials and the clinical evaluation of patients with MG.
Article
This review illustrates how measurements of clinical status in patients with myasthenia gravis have evolved from clinical descriptions and estimates of mortality rates to more sophisticated evaluative instruments, including numerical rating scales that measure strength, endurance, quality of life, and activities of daily living. The rationale and use of weighting and the importance of patient-reported outcomes are also discussed. The measurement of the steroid-sparing effect of an immunosuppressant is also reviewed.
Article
To study the concurrent and construct validity and test-retest reliability in the practice setting of an outcome measure for myasthenia gravis (MG). Eleven centers participated in the validation study of the Myasthenia Gravis Composite (MGC) scale. Patients with MG were evaluated at 2 consecutive visits. Concurrent and construct validities of the MGC were assessed by evaluating MGC scores in the context of other MG-specific outcome measures. We used numerous potential indicators of clinical improvement to assess the sensitivity and specificity of the MGC for detecting clinical improvement. Test-retest reliability was performed on patients at the University of Virginia. A total of 175 patients with MG were enrolled at 11 sites from July 1, 2008, to January 31, 2009. A total of 151 patients were seen in follow-up. Total MGC scores showed excellent concurrent validity with other MG-specific scales. Analyses of sensitivities and specificities of the MGC revealed that a 3-point improvement in total MGC score was optimal for signifying clinical improvement. A 3-point improvement in the MGC also appears to represent a meaningful improvement to most patients, as indicated by improved 15-item myasthenia gravis quality of life scale (MG-QOL15) scores. The psychometric properties were no better for an individualized subscore made up of the 2 functional domains that the patient identified as most important to treat. The test-retest reliability coefficient of the MGC was 98%, with a lower 95% confidence interval of 97%, indicating excellent test-retest reliability. The Myasthenia Gravis Composite is a reliable and valid instrument for measuring clinical status of patients with myasthenia gravis in the practice setting and in clinical trials.
Article
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.
Article
We determined the strength of correlation among, and responsiveness of, outcome measures used in a multicenter, double-blind, placebo-controlled trial of mycophenolate mofetil in combination with prednisone in myasthenia gravis (MG). The primary efficacy measure was the change from baseline in the Quantitative MG (QMG) score at week 12. Secondary outcome measures included the MG-Activities of Daily Living profile (MG-ADL) and MG Manual Muscle Test (MMT). The measures were collected at baseline and at weeks 4, 8, and 12 in the blinded study and at weeks 16, 20, 28, and 36 in an optional open-label extension. At baseline, the QMG was moderately correlated with the MG-ADL (r=0.55, P<0.0001) and the MMT (r=0.53, P<0.0001), but the correlation between the MG-ADL and the MMT was lower (r=0.30, P=0.007). These findings were similar at weeks 4, 8, and 12. Similar correlations were found among the changes in scores from baseline at weeks 12 and 36. The MMT and MG-ADL appeared to be the most sensitive measures for changes in MG status at weeks 12 and 36. Although a task force has recommended use of the QMG in prospective MG trials, the MMT and MG-ADL appear to be suitable alternatives and offer potential advantages. No special training or equipment is required, and they take less time.
Article
Azathioprine (Aza) has been used alone or in combination with steroids for two groups of myasthenic patients. Positive responses were noted in 75% of patients on Aza alone and in 70% receiving the combined regimen. The clinical course of the two groups differed in terms of respiratory crisis and need for plasma exchange. With an appropriate Aza administration schedule side-effects were not a limiting factor to its use. Aza treatment induced a reduction in anti-AchR-antibody level that was correlated with clinical improvement and greatly decreased the need for steroids.