Table 1.

Clinical findings in neuromuscular immune-related adverse events

Clinical findings in NMD induced by ICIs	Myasthenia gravis	Myositis	Guillain-Barré syndrome
	Frequency of symptoms
Ocular weakness (ptosis/double vision)	+++	+++	+ In cranial nerve affection
Facial weakness	++	++	+
Bulbar symptoms (dysarthria/dysphagia)	+++	++ 50% of the cases	+/++
Extremity weakness	+ Symmetrical proximal	++ Symmetrical proximal	++ Mostly symmetrical proximal or distal
Dropped head	++	+++ 70% of the cases	(+)
Limb girdle weakness	+/++	++	+
Pain	(+)	+++ 70% of the cases	Possible in sensory involvement
Respiratory failure	Frequent due to diaphragm involvement or aspiration
Reflexes	Normal	May be reduced according to paresis	Reduced or absent
Cardiac pathology	Rare in isolated MG, 10% overlapping myositis-myocarditis	++ 25%-35% myocarditis, arrhythmia	Possible with autonomic involvement

	Additional findings
Laboratory findings: CK	Normal, elevated in myositis overlap	Markedly (fivefold to 10-fold) elevated (including troponin) up to 100×, rarely normala	Normal
Cerebrospinal fluid	Normal	Normal	Cytoalbuminary dissociation
Antibody status	May be positive for AChR, often negative or very low titres	Negative	Negative
Red flags	Fluctuation of symptoms, no pain	At onset: 20% fever, pain	Concurrent sensory impairment/paraesthesia, autonomic involvement: consider leptomeningeal carcinomatosis as a differential diagnosis
Indicative neurophysiology	Pathologic decrement in affected muscle group, but may also be absent	Pathologic fibrillation, myogenic muscle potentials,b in doubt consider EMG in paraspinal muscles also	Demyelination (missing or prolonged F-wave latency, temporal dispersion, possible conduction block)
Optional additional investigation in doubtful cases	Response to pyridostigmine or ice pack on eyes	Only necessary in very rare cases: imaging muscle abnormalities (MRI, PET)c	MRI spinal cord or brainstem
Therapy response	Usually rapid and effective if treated early with -glucocorticoids, in myositis correlating with fast CK decline; careful consideration of therapy escalation if unresponsive to glucocorticoids (IVIG/plasma exchange, see Figure 1)
Outcome	Usually favourable, however fatal outcome is possible, mortality primarily defined by cardiac and pulmonary complication

(+) rare; + sometimes; ++ often; +++ very often.

AChR, acetylcholine receptor; CK, creatine kinase; EMG, electromyography; ICIs, immune checkpoint inhibitors; IVIG, intravenous immunoglobulins; MG, myasthenia gravis; MRI, magnetic resonance imaging; NMD, neuromuscular disease; PET, positron emission tomography.

^aNormal in case of oculobulbar predominance (resembles MG).

^bEarly recruiting, short-duration, low-amplitude motor unit potentials.

^cMay show muscular T2 gadolinium enhancement or increased [¹⁸F]2-fluoro-2-deoxy-D-glucose uptake.