How is the severity of myasthenia gravis (MG) scored?

Myasthenia Gravis Severity Scoring

Myasthenia gravis severity is scored using the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, the Quantitative Myasthenia Gravis Score (QMGS), and the MG Composite (MGC) score, with the MGFA classification serving as the primary framework for clinical decision-making and the QMGS providing validated quantitative assessment. 1

Primary Scoring Systems

MGFA Clinical Classification (Gold Standard)

The MGFA classification stratifies disease severity into distinct categories that directly guide treatment decisions 1:

• Class 1: Ocular symptoms and findings only (ptosis, diplopia, extraocular movement abnormalities) 1, 2
• Class 2: Mild generalized weakness affecting limb, axial, or oropharyngeal muscles, with some interference with activities of daily living 1
• Class 3: Moderate generalized weakness with significant limitation of self-care activities 1
• Class 4: Severe generalized weakness requiring aids for walking or self-care 1
• Class 5: Myasthenic crisis requiring intubation or mechanical ventilation 1

This classification is critical because treatment intensity escalates dramatically between grades—Grade 2 patients may continue immunotherapy with close monitoring, while Grade 3-4 patients require permanent discontinuation of certain therapies, ICU admission, and aggressive immunosuppression 1.

Quantitative Myasthenia Gravis Score (QMGS)

The QMGS is a validated 13-item physician-administered assessment that objectively quantifies muscle weakness 3, 4:

• Score range: 0-39 points, with higher scores indicating greater severity 3
• Strong correlation with MGFA classification (r² = 0.54, P < 0.0001), quality of life measures (rs = 0.41), and electrophysiological jitter (rs = 0.40) 3
• Clinical utility: Mean baseline scores typically range from 12-15 points in generalized MG, with improvement of 3-4 points at 3 months and 6-8 points at 6 months representing meaningful treatment response 4

The QMGS is particularly valuable because it provides objective, reproducible measurements that correlate with both clinical severity and patient-reported outcomes, making it the preferred primary endpoint in clinical trials 3.

MG Composite Score (MGC)

The MGC is a 10-item scale combining physician assessment and patient-reported symptoms 4, 5:

• Score range: 0-50 points 4
• Strong correlation with QMGS (r > 0.70) and moderate correlation with acetylcholine receptor antibody titers 4
• Baseline values: Mean scores of 15-16 in generalized MG, improving to 10-11 at 3 months and 6-7 at 6 months with treatment 4

Complementary Assessment Tools

MG-Activities of Daily Living (MG-ADL)

Patient-reported 8-item scale assessing functional impact on daily activities, with scores ranging 0-24 5. This correlates moderately with physician-assessed measures (r = 0.56-0.74) and captures the patient perspective on disease burden 5.

MG Symptoms PRO

The most comprehensive patient-reported outcome measure, uniquely capturing physical fatigue in addition to muscle weakness fatigability across ocular, bulbar, and respiratory domains 5, 6:

• Muscle Weakness Fatigability scale: Clinically meaningful improvement defined as ≥16.67-point reduction 6
• Physical Fatigue scale: Meaningful improvement ≥20.00-point reduction 6
• Bulbar Muscle Weakness scale: Meaningful improvement ≥20.00-point reduction 6

This instrument provides the broadest coverage of the MG severity continuum and complements physician-assessed measures by capturing symptoms like physical fatigue that are not adequately reflected in QMGS or MGC 5, 6.

Critical Severity Indicators Requiring Immediate Action

Certain clinical features mandate urgent escalation regardless of formal scoring 1, 7:

• Any dysphagia, facial weakness, or dysarthria (bulbar involvement) 1, 7
• Respiratory muscle weakness with declining negative inspiratory force (NIF) or vital capacity (VC) 1, 7
• Neck weakness preventing head support 7
• Rapidly progressive symptoms of any type 1

These features indicate Grade 3-4 disease requiring ICU-level monitoring, permanent discontinuation of certain immunotherapies, and immediate initiation of IVIG (2 g/kg over 5 days) or plasmapheresis 1.

Practical Scoring Approach

For initial assessment: Use MGFA classification to determine treatment urgency and intensity, supplemented by QMGS for objective baseline measurement 1, 3.

For monitoring treatment response: Serial QMGS and MGC measurements at 3-month intervals, with meaningful improvement defined as 3-4 point reduction in QMGS or achievement of minimal manifestation status 4, 8.

For comprehensive evaluation: Combine physician-assessed measures (QMGS, MGC) with patient-reported outcomes (MG-ADL, MG Symptoms PRO) to capture both objective severity and functional impact 4, 5.

Important Caveats

Baseline severity matters: Absolute score changes may underestimate treatment response in patients with moderate-to-severe disease at baseline, where relative improvement percentages provide complementary information 8. The consistency between absolute and relative criteria is only moderate in severe patients (Kappa ≤0.639) 8.

Ocular manifestations are distinct: Ocular muscle weakness may reflect a different facet of MG severity and does not fit well into the overall severity continuum with other muscle groups 5. Fifty percent of patients presenting with isolated ocular symptoms (MGFA Class 1) will progress to generalized disease within 2 years 1.

Antibody titers don't correlate with severity: While AChR-positive patients have slightly higher QMGS scores (14.2 vs 12.0, P = 0.008), antibody titers themselves show no correlation with disease severity scores 3, 4.