Table 6

irNeuromuscular junction disorder

Subtypes:
(Median 9, range 7–9)		Possible symptoms:
(Median 8, range 6–9)		Supportive examination findings:
(Median 8, range 7–9)		Diagnostic criteria: All levels of diagnostic certainty for irNMJ disorder require a supportive history, examination, and timing relative to ICI therapy plus:
(Accuracy median 9, range 5–9; Usability median 8, range 5–9)

  • Myasthenia gravis (MG): seropositive (with MG-specific Abs) and seronegative

  • Other (including Lambert-Eaton myasthenic syndrome (LEMS))

Evaluate for overlapping irMyopathy and myocarditis; classify each disorder separately if present

  • Ptosis, diplopia, blurred vision

  • Dysarthria, dysphagia

  • Neck and/or truncal weakness

  • Proximal or distal weakness, may be asymmetric

  • Fluctuating or fatigable weakness

  • Dyspnea, orthopnea

LEMS:

  • Proximal weakness, areflexia/hyporeflexia, autonomic dysfunction (including dry mouth, orthostatic hypotension, early satiety and constipation)

  • Ptosis, particularly asymmetric and/or fatigable

  • Extraocular muscle weakness referable to >1 cranial nerve

  • Weakness in eye closure, smile, cheek puff, jaw closure, tongue protrusion into the cheek

  • Neck flexion or neck extension weakness (head drop)

  • Limb weakness (proximal>distal)

  • Abnormally reduced pulmonary function testing (NIF/FVC)

  • Muscle bulk and deep tendon reflexes usually normal in MG

  • Sensation normal

LEMS:

  • Proximal weakness

  • Deep tendon reflexes attenuated and may facilitate after brief exercise

  • Signs of autonomic dysfuncti


Definite
Required:

  1. AChR binding or modulating Ab positive or MuSK Ab positive AND

  2. Electrodiagnostic studies showing a primary disorder of neuromuscular transmission


Probable
Required (1 of the following): 

  1. AChR Ab or MuSK Ab positive OR

  2. Electrodiagnostic studies showing a disorder of primary neuromuscular transmission OR

  3. Unequivocal clinical response/improvement with cholinesterase inhibitors

Evaluation may include:
(Median 9, range 7–9)		Possible
Required:

  1. AChR and MuSK Ab negative or not performed OR

  2. Electrodiagnostic studies without disorder of neuromuscular transmission, or not performed* AND

  3. CK normal**


*If EDX performed, no evidence for irritable myopathy on EMG
**If CPK abnormally elevated, and no evidence for MG, consider irMyopathy
Common:

  1. Serum testing: AChR binding and modulating antibody (Ab), CK, troponin, TSH

  2. Electrodiagnostic studies (EMG/NCS) including repetitive nerve stimulation studies, routine sensory and motor conductions, needle EMG with thoracic paraspinal muscle examination

  3. CT chest or MRI mediastinum

  4. EKG

Possible:

  1. P/Q VGCC Ab, MuSK Ab

  2. Single fiber electromyography or concentric jitter studies

  3. Ice pack test

  4. Transthoracic echocardiogram

  5. Complete or bedside pulmonary function tests (NIF/FVC)

  6. Fluoroscopic or clinical swallow evaluation

Uncommon:
1. Edrophonium testing

  • AChR, acetylcholine receptor; CK, creatine kinase; EDX, electrodiagnostic studies; EMG, electromyography; ICI, immune checkpoint inhibitor; MG, myasthenia gravis.