Objective:

To assess the coordination of core EAMG phenotypes and the association of selected exploratory imaging-derived phenotypes with disease severity.

Approach:

• Study Design: Established EAMG in C57BL/6J mice using a two-tier analytical framework aimed at integrating core phenotyping with imaging analyses.

Key Findings:

• EAMG mice exhibited significant neuromuscular and immunological abnormalities.
• Electrophysiological impairment had the strongest association with disease severity (rho = −0.79, P < 0.001).
• Behavioral and immunological measures showed limited stratification capacity within the EAMG group.
• Imaging analyses revealed reduced cardiac ejection fraction, heart rate, iliopsoas FDG uptake, and sagittal spinal angle.
• Iliopsoas FDG uptake was negatively correlated with disease severity (rho = −0.89, P = 0.041).

Interpretation:

EAMG is associated with coordinated electrophysiological, functional, and immunological abnormalities, with imaging analyses identifying additional phenotypes related to disease severity.

Limitations:

• Imaging-derived findings require validation in unselected cohorts.
• Current evaluation strategies may not fully capture the complexity of disease progression.

Conclusion:

The multi-dimensional framework may enhance comprehensive assessment of disease progression in preclinical myasthenia gravis studies.