. 2020 Nov 3;12:139–167. doi: 10.2147/EB.S277760

Table 3.

Summary of Cases – Neuromuscular

Author Year Ref	Age M/F	Cancer Type	ICI Name	Cycles and Duration Before Symptoms	Neuro-Ophthalmic Diagnosis	Concomitant Myositis, CK Levels (IU/L)	Ophthalmic Presentation	Treatment	ICI Continued/Held/Terminated	Neuro-Ophthalmic Outcome	Follow-up Period (Months)
Algaeed 2018⁵¹	73M	Melanoma	Pembrolizumab	NR cycles: then 3 weeks	MG	N	OS: ptosis	IVIg 2 g/kg daily, prednisone 60 mg daily, plasmapheresis 5 exchanges	NR	Improvement	5 weeks
Alnahhas 2016⁵²	84M	Melanoma	Pembrolizumab	2 cycles: then 2 months	MG	N	OU: ptosis, ophthalmoplegia	Prednisone 60 mg daily, pyridostigmine 60 mg TID, and IVIg 0.4 g/kg/day for 5 days	Terminated	Death (hypercapnic respiratory failure)	3 days
Becquart 2019⁶³	75F	Melanoma	Nivolumab	3 cycles (6 weeks)	MG	N	OU: diplopia, ptosis	Prostigmine 3 mg daily	Continued	Improvement, continued prostigmine	21
Chang 2017⁷⁴	75M	Transitional cell carcinoma of bladder and ureter	Nivolumab	2 doses: then 3 weeks	MG	N	OU: diplopia, ptosis	Pyridostigmine 90 mg QID, and IVIg 0.4 g/kg daily over 5 days	Terminated	Improvement in 6 days, death (unknown cause) 10 days	10 days
Chen 2017⁸⁵	57M	NSCLC	Nivolumab and ipilimumab	1 cycle ipilimumab, 2 cycles nivolumab: then 2 weeks	MG	Y, 2682	OD: ptosis	IV prednisolone 2 mg/kg daily for 5 days followed by 1 mg/kg daily for 2 days, po pyridostigmine 60 mg TID	Terminated	Improvement, death (pneumonia) 1 week	1 week
Chen 2017⁹²	65M	NSCLC	Nivolumab	3 cycles: then 5 days	MG	Y, CK NR	OU: ptosis	Methylprednisolone 1 mg/kg daily and pyridostigmine 60 mg po BID	Terminated	Death (hypercapnic respiratory failure)	3 weeks
Cooper 2017⁹³	68F	NSCLC	Nivolumab	5 cycles: then 1 month	MG exacerbation	N	OU: diplopia, ophthalmoplegia	Pyridostigmine and prednisone at 60 mg daily, 5 exchanges of plasmapheresis	Terminated	Minimal improvement, hospice care	18 days
Crusz 2018⁹⁴	78M	Melanoma	Pembrolizumab	2 doses: then 6 days	MG	Y, 1109	OD: ptosis	IVIg, pyridostigmine, later mycophenolate + PLEX, later rituximab 1 g infusion	Terminated	Resolution	4
Dhenin 2019⁹⁵	79F	Lung adenocarcinoma	Pembrolizumab	6 doses (22 weeks), then 3 months	MG	N	OU: ptosis	Pyridostigmine 60 mg, five times daily, IV methylprednisolone 80 mg daily	Completed	Resolution	3
Earl 2017⁹⁶	74M	Melanoma	Pembrolizumab	2 doses: then 12 days	MG exacerbation	N	OD: impaired adduction, OU: ptosis, ophthalmoplegia	IVIg 2 g/kg total, prednisone 80 mg daily, mycophenolate 1500 mg BID, pyridostigmine 120 mg TID, plasmapheresis	Terminated	Minimal improvement, death (unknown cause)	NR
Fazel 2019⁵³	78F	Melanoma	Ipilimumab and nivolumab	1 cycle: then 5 days	MG	Y (systemic myositis), CK NR	OU: diplopia, ptosis	IV methylprednisolone 1000 mg daily for 3 days, IVIg 2 g/kg daily for 2 days	Continued	Worsened, hospice care	8 days
Fellner 2018⁵⁴	68M	Melanoma	Pembrolizumab	2 doses (5 weeks): then 2 weeks	MG	N	OS: ptosis, esophoria	Prednisone 10 mg daily then taper	Held	Resolution	6 weeks
Fukasawa 2017⁵⁵	69F	Lung adenocarcinoma	Nivolumab	3 cycles: then 1 week	MG	N	OU: diplopia, OS: impaired adduction	Methylprednisolone 1 g for 3 days followed by 1 mg/kg daily	NR	Improvement, continued steroids	36 days
Gonzalez 2017⁵⁶	71F	Uterine carcinosarcoma	Pembrolizumab	4 doses	MG	N	OU: diplopia, ptosis, OS: impaired abduction	po pyridostigmine up to 60 mg TID, prednisone 20 mg daily	Held	Resolution (3 weeks), death (cancer progression) 5 months	5
Hasegawa 2017⁵⁷	76F	NSCLC	Nivolumab	2 doses: then 26 days	MG	Y, 6566	OU: diplopia, OS: ptosis	IVIg, PLEX 3 sessions, prednisolone 10 mg daily	Terminated	Improvement	85 days
Hibino 2018⁵⁸	83M	Lung squamous cell carcinoma	Pembrolizumab	2 cycles (on day 38 of treatment)	MG	Y, 4361	OU, ptosis, ophthalmoplegia, diplopia	po pyridostigmine 60 mg TID for 7 days	NR	Improvement	3
Huh 2017⁵⁹	34F	Thymic squamous cell carcinoma	Pembrolizumab	4 cycles	MG	Y, 2125	OU: ptosis, ophthalmoplegia	IVIg for 5 days, IV methylprednisolone 1 g daily for 3 days, prednisolone 1 mg/kg daily, then 5 cycles of plasmapheresis	Terminated	Improvement, ptosis resolved, ophthalmoplegia persisted	6
Johnson 2015⁶⁰	69F	Melanoma	Ipilimumab	3 doses: then several days	MG	N	OU: diplopia, ptosis	Pyridostigmine 30 mg TID, then IV methylprednisolone 2 mg/kg and plasmapheresis, then 40 mg prednisone daily	NR	Improvement	3
Kim 2019⁶¹	76M	NSCLC	Nivolumab	4 doses: then 3 days	MG	Y, 2934	OD: ptosis, diplopia	IV methylprednisolone 1 mg/kg daily for 32 days, pyridostigmine 30 mg TID for 6 days and was increased to 60 mg TID, tapered to po prednisolone 40 mg BID	Completed	Improvement	8
Konstantina 2019⁶²	30F	Type B3 thymoma	Pembrolizumab	1 dose: then 3 days	Myasthenic crisis	Y, CK NR	Unilateral ptosis, diplopia	Corticosteroids and pyridostigmine 400 mg/kg for 5 days, then rituximab 375/m² for 3 weeks	Terminated	Death (septic shock)	54 days
Lara 2019⁶⁴	63F	NSCLC-adenocarcinoma	Pembrolizumab	2 cycles	MG	N	OU: ptosis, EOM palsies	IVIg, high-dose corticosteroid therapy, and pyridostigmine	Terminated	Improvement	NR
Lau 2016⁶⁵	75M	Melanoma	Pembrolizumab	5 weeks	MG	N	OS: ptosis	IV methylprednisolone 1 g daily for 5 days, IVIg 0.5 g/kg daily for 4 days, discharged with prednisone 60 mg daily	Held	Resolution	4
Liao 2014⁶⁶	70F	Melanoma	Ipilimumab	2 cycles: then 1 week	MG	Y, 1200	OU: ptosis	Plasmapheresis daily for 3 days, 125 mg IV methylprednisolone daily	Terminated	Improvement	2 weeks
Liu 2019⁶⁷	73M	Melanoma	Pembrolizumab	2 doses: then <1 week	MG	N	OU: ptosis	IVIg 2 g/kg daily for 5 days, and IV methylprednisolone 1 g daily for 3 days	Terminated	Improvement	6 weeks
Loochtan 2015⁶⁸	70M	SCLC	Ipilimumab	Day 16	MG	N	OU: diplopia, ptosis	Prednisone 1 mg/kg daily, followed by 3 sessions of plasmapheresis, prednisone 90 mg daily	Terminated	Death (septic shock, cardiac, ulcers)	22 days
Maeda 2016⁶⁹	79M	Melanoma	Nivolumab	3 doses: day 106	MG exacerbation	Y, 1627	OU: diplopia	None	Held	Resolution (timing NR)	9
Mancano 2018⁷⁰	76F	NSCLC	Nivolumab	2 doses: day 26	Myasthenic crisis	Y, 6566	OS: ptosis	IVIg for 2 days, then immunoadsorption plasmapheresis therapy and IVIg for 5 days, prednisolone 10 mg daily	NR	Improvement	65 days
March 2017⁷¹	63M	NSCLC	Pembrolizumab	1 dose: then 2 weeks	MG	Y, 10,386	OD: ptosis, blurry vision, periorbital edema with mild erythema	Pyridostigmine 120 mg q6 h and prednisone 60 mg daily, methylprednisolone 1 g daily for 9 days, 5 IVIg treatments, 4 plasmapheresis rounds	Terminated	Death (respiratory failure)	12 days
Mitsune 2018⁷²	62M	Neuroendocrine carcinoma of trachea	Nivolumab	2 cycles: day 25	MG exacerbation	Y, 14,229	OU: diplopia, ptosis	IV methylprednisolone 2 mg/kg daily	Terminated	Resolution	60 days
Mohn 2019⁷³	82M	Melanoma	Nivolumab	1 dose: then 8 weeks	MG	Y, 2000	OU: ptosis, ophthalmoplegia	IV methylprednisolone 1000mg daily for 5 days, then IVIg	Terminated	Improvement, death (blood loss) at 8 weeks	8 weeks
Mohn 2019⁷³	87F	Melanoma	Nivolumab	1 dose: then 4 weeks	MG	Y, CK NR	OU: ptosis	Prednisolone 100mg daily	Terminated	Death (cause unknown)	12 days
Montes 2018⁷⁵	74M	Melanoma	Ipilimumab	3 doses: then 1 day	MG	N	OU: diplopia, OD: ophthalmoplegia	High-dose corticosteroids and pyridostigmine	Terminated	Improvement, diplopia persisted, continued steroids	1
Nakatani 2018⁵⁰	73F	Lung squamous cell carcinoma	Nivolumab	25 doses: at 51 weeks	Lambert–Eaton Myasthenic Syndrome	N	OU: photophobia, ptosis	po prednisolone 20 mg daily for 7 days, pyridostigmine and ambenonium, 3,4-DAP	Restarted then terminated	Improvement	16
Nguyen 2017⁷⁶	81M	Melanoma	Pembrolizumab	3 cycles: then 2 weeks	MG	N	OU: ptosis	Prednisolone 25 mg daily then taper	Continued	Resolution	6
Nguyen 2017⁷⁶	86F	Melanoma	Pembrolizumab	2 cycles	MG	N	OU: ptosis	IV methylprednisolone 500 mg daily for 5 days, then po prednisolone taper	Continued	Improvement	3
Onda 2019⁷⁷	73M	Lung adenocarcinoma	Pembrolizumab	Day 23	MG	Y, 7311	OU: diplopia, ptosis, ophthalmoplegia	Prednisolone total 20 mg, methylprednisolone 1g daily for 3 days	NR	Resolution	4
Phua 2020⁷⁸	66M	Lung adenocarcinoma	Durvalumab	5 doses: then 3 days	MG	Y, 499	OU: diplopia, ptosis	Prednisone 60 mg daily, pyridostigmine 120 mg TID, mycophenolate mofetil 1 g BID, IVIg 2 g/kg	Terminated	Improvement	2
Polat 2016⁷⁹	65M	NSCLC	Nivolumab	3 doses: then 3 days	MG	N	OU: blurry vision, diplopia, ptosis	Pyridostigmine 45 mg q6 h for 6 weeks	Completed	Resolution (6 weeks)	4
Sciacca 2016⁸⁰	81M	NSCLC	Nivolumab	3 cycles	MG	N	OU: blurry vision, diplopia, ptosis	Prednisone 50 mg daily for 4 weeks	Terminated	Resolution (4 weeks)	1
So 2019⁸¹	55F	Melanoma	Nivolumab	2 doses: then 1 day	Myasthenic crisis	Y, CK NR	OU: ptosis, ophthalmoplegia	IVIg 0.5 g/kg daily for 5 days, 4 cycles of steroid pulse, 2 cycles of PLEX	Terminated	Improvement	6
Takai 2020⁸²	77M	Bladder cancer	Pembrolizumab	1 dose: then 20 days	MG	Y, 8574	OU: diplopia, ptosis	Prednisone 80 mg daily, IVIg at 0.4 g/kg daily for 5 days	Terminated	Death (cardiac arrest)	13 days
Tan 2017⁸³	45M	NSCLC	Nivolumab	1 dose: then 2 weeks	MG	Y, CK NR	OU: ptosis, ophthalmoplegia	Pyridostigmine, methylprednisolone 1 g daily for 3 days, and IVIg 400 mg/kg daily for 5 days	Held for 5 months	Improvement	5
Tedbirt 2019⁸⁴	77M	Melanoma	Pembrolizumab and nivolumab	4 doses	MG	N	OU: ptosis, visual disorders (unspecified)	IVIg 0.4 g/kg daily for 5 days, pyridostigmine 360 mg daily, prednisone 60 mg daily	Held for 5 months	Recurrence of myasthenic syndrome, improvement	29
Thakolwiboon 2019⁸⁶	87M	Urothelial carcinoma	Atezolizumab	2 doses	MG	Y, 1542	OU: diplopia, ptosis	Prednisone 60 mg daily for 1 week, IVIg 0.4 g/kg daily, low-dose pyridostigmine	Terminated	Death (cardiac arrest)	10 days
Tozuka 2018⁸⁷	82M	Pulmonary pleomorphic carcinoma	Pembrolizumab	3 cycles: then 44 days	MG with agranulocytosis	N	OU: diplopia	Pyridostigmine 60 mg TID	Terminated	NR	NR
Veccia 2020⁸⁸	65M	Lung squamous cell carcinoma	Nivolumab	2 doses: day 27	MG	Y, 3844	OU: diplopia, OD: ptosis	IVIg 0.4 mg/kg daily for 5 days, pyridostigmine 60 mg daily for 1 week, IV dexamethasone 8 mg BID, prednisone 1 mg/kg daily	Terminated	Worsened, death	7 weeks
Werner 2019⁸⁹	62M	Melanoma	Nivolumab and ipilimumab	2 doses: then 1 week	MG	N	OD: ptosis	Pyridostigmine 300 mg daily, prednisone 20 mg daily	Held for 6 weeks	Resolution (6 weeks)	2
Wilson 2018⁹¹	57M	Lung adenocarcinoma	Pembrolizumab	4 weeks	MG	N	OU: ptosis, ophthalmoplegia	Corticosteroids and pyridostigmine 400 mg/kg daily for 5 days, followed by rituximab 375 mg/m² for 3 weeks	Terminated	Resolution, death (cancer progression)	6
Wilson 2018⁹¹	62F	Melanoma	Nivolumab and ipilimumab	4 weeks	MG	N	OU: ptosis	Pyridostigmine and corticosteroids	Terminated	Resolution	12
Xing 2020⁹⁰	66M	Lung adenocarcinoma	Sintilimab	2 doses: then 4 days	Myasthenic crisis	Y, 11,919	OU: ptosis, ophthalmoplegia	Pyridostigmine bromide 120 mg BIG, IV methylprednisolone 2 mg/kg daily, IVIg 400 mg/kg daily for 5 days, PLEX	Terminated	Improvement	3

Abbreviations: NSCLC, non-squamous cell lung cancer; OU, both eyes; OD, right eye; OS, left eye; IV, intravenous; po, per os; IVIg, intravenous immunoglobulin; NR, not reported; PLEX, plasma exchange; BID, twice daily; TID, three times daily; QID, four times daily; MG, myasthenia gravis.