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Published in: Journal of Neurology 2/2021

01-02-2021 | Guillain-Barré Syndrome | Original Communication

Polyradiculoneuropathy induced by immune checkpoint inhibitors: a case series and review of the literature

Authors: Kensuke Okada, Morinobu Seki, Hiroshi Yaguchi, Kenichi Sakuta, Taiji Mukai, Satoshi Yamada, Koichi Oki, Jin Nakahara, Shigeaki Suzuki

Published in: Journal of Neurology | Issue 2/2021

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Abstract

Objective

The purpose of the present study is to report the clinical characteristics of polyradiculoneuropathy induced by immune checkpoint inhibitors (ICIs).

Methods

We retrospectively reviewed lists of all inpatients with neurological immune-related adverse events (irAEs) treated at the neurology departments of three hospitals in January 2017 and December 2019. We also performed a review of the previous case reports with polyradiculoneuropathy induced by ICI therapy.

Results

We had 4 patients with polyradiculoneuropathy following ICI therapy. We comprehensively reviewed our 4 patients and 32 previous case reports. There were 28 men and 8 women with a mean onset age of 61 years. ICI monotherapy was performed in 27 patients, whereas the combination of ICIs was administered in 9 patients. All patients except 2 showed limb weakness, which was observed symmetrically and predominantly in the legs rather than the arms. Bulbar involvement was observed in 7 patients. The laboratory findings were demyelination in electrophysiological studies and elevated protein with lymphocytes in the cerebrospinal fluid. Disease severity was ranked on the Hughes functional scale; 17 patients were grade 4 or greater. The treatment responses to corticosteroid and intravenous methylprednisolone were favorable. Intravenous immunoglobulin was also used in combination with steroids. Seven patients died, including 4 who on mechanical ventilation.

Conclusion

Polyradiculoneuropathy induced by ICIs has a distinct subset of neurological irAEs and requires early recognition.
Literature
1.
go back to reference Bot I, Blank CU, Boogerd W, Brandsma D (2013) Neurological immune-related adverse events of ipilimumab. Pract Neurol 13:278–280CrossRef Bot I, Blank CU, Boogerd W, Brandsma D (2013) Neurological immune-related adverse events of ipilimumab. Pract Neurol 13:278–280CrossRef
2.
go back to reference Cafuir L, Lawson D, Desai N, Kesner V, Voloschin A (2018) Inflammatory demyelinating polyneuropathy versus leptomeningeal disease following Ipilimumab. J Immunother Cancer 6:11CrossRef Cafuir L, Lawson D, Desai N, Kesner V, Voloschin A (2018) Inflammatory demyelinating polyneuropathy versus leptomeningeal disease following Ipilimumab. J Immunother Cancer 6:11CrossRef
3.
go back to reference Chen X, Haggiagi A, Tzatha E, DeAngelis LM, Santomasso B (2019) Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy. Clin Neurophysiol 130:1440–1445CrossRef Chen X, Haggiagi A, Tzatha E, DeAngelis LM, Santomasso B (2019) Electrophysiological findings in immune checkpoint inhibitor-related peripheral neuropathy. Clin Neurophysiol 130:1440–1445CrossRef
4.
go back to reference Cuzzubbo S, Javeri F, Tissier M, Roumi A, Barlog C, Doridam J, Lebbe C, Belin C, Ursu R, Carpentier AF (2017) Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer 73:1–8CrossRef Cuzzubbo S, Javeri F, Tissier M, Roumi A, Barlog C, Doridam J, Lebbe C, Belin C, Ursu R, Carpentier AF (2017) Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer 73:1–8CrossRef
5.
go back to reference de Maleissye MF, Nicolas G, Saiag P (2016) Pembrolizumab-induced demyelinating polyradiculoneuropathy. N Engl J Med 375:296–297CrossRef de Maleissye MF, Nicolas G, Saiag P (2016) Pembrolizumab-induced demyelinating polyradiculoneuropathy. N Engl J Med 375:296–297CrossRef
6.
go back to reference Dubey D, David WS, Amato AA, Reynolds KL, Clement NF, Chute DF, Cohen JV, Lawrence DP, Mooradian MJ, Sullivan RJ, Guidon AC (2019) Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology 93:e1093–e1103CrossRef Dubey D, David WS, Amato AA, Reynolds KL, Clement NF, Chute DF, Cohen JV, Lawrence DP, Mooradian MJ, Sullivan RJ, Guidon AC (2019) Varied phenotypes and management of immune checkpoint inhibitor-associated neuropathies. Neurology 93:e1093–e1103CrossRef
7.
go back to reference Fukumoto Y, Kuwahara M, Kawai S, Nakahama K, Kusunoki S (2017) Acute demyelinating polyneuropathy induced by nivolumab. J Neurol Neurosurg Psychiatry 381:534 Fukumoto Y, Kuwahara M, Kawai S, Nakahama K, Kusunoki S (2017) Acute demyelinating polyneuropathy induced by nivolumab. J Neurol Neurosurg Psychiatry 381:534
8.
go back to reference Garcia CA, El-Ali A, Rath TJ, Contis LC, Gorantla V, Drappatz J, Davar D (2018) Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. J Immunother Cancer 6:83CrossRef Garcia CA, El-Ali A, Rath TJ, Contis LC, Gorantla V, Drappatz J, Davar D (2018) Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. J Immunother Cancer 6:83CrossRef
9.
go back to reference Gaudy-Marqueste C, Monestier S, Franques J, Cantais E, Richard MA, Grob JJ (2013) A severe case of ipilimumab-induced Guillain–Barre syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis. J Immunother 36:77–78CrossRef Gaudy-Marqueste C, Monestier S, Franques J, Cantais E, Richard MA, Grob JJ (2013) A severe case of ipilimumab-induced Guillain–Barre syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis. J Immunother 36:77–78CrossRef
10.
go back to reference Gu Y, Menzies AM, Long GV, Fernando SL, Herkes G (2017) Immune mediated neuropathy following checkpoint immunotherapy. J Clin Neurosci 45:14–17CrossRef Gu Y, Menzies AM, Long GV, Fernando SL, Herkes G (2017) Immune mediated neuropathy following checkpoint immunotherapy. J Clin Neurosci 45:14–17CrossRef
11.
go back to reference Jacob A, Unnikrishnan DC, Mathew A, Thyagarajan B, Patel S (2016) A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use. J Cancer Res Clin Oncol 142:1869–1870CrossRef Jacob A, Unnikrishnan DC, Mathew A, Thyagarajan B, Patel S (2016) A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use. J Cancer Res Clin Oncol 142:1869–1870CrossRef
12.
go back to reference Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, Liewluck T, Hammack JE, Sandroni P, Finnes H, Mauermann ML (2017) Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol 74:1216–1222CrossRef Kao JC, Liao B, Markovic SN, Klein CJ, Naddaf E, Staff NP, Liewluck T, Hammack JE, Sandroni P, Finnes H, Mauermann ML (2017) Neurological complications associated with anti-programmed death 1 (PD-1) antibodies. JAMA Neurol 74:1216–1222CrossRef
13.
go back to reference Kyriazoglou A, Liontos M, Papadopoulos C, Bilali A, Kostouros E, Pagoni S, Doumas K, Dimopoulos MA, Bamias A (2019) Guillain–Barre syndrome related to Nivolumab: case report of a patient with urothelial cancer and review of the literature. Clin Genitourin Cancer 17:e360–e364CrossRef Kyriazoglou A, Liontos M, Papadopoulos C, Bilali A, Kostouros E, Pagoni S, Doumas K, Dimopoulos MA, Bamias A (2019) Guillain–Barre syndrome related to Nivolumab: case report of a patient with urothelial cancer and review of the literature. Clin Genitourin Cancer 17:e360–e364CrossRef
14.
go back to reference Liao B, Shroff S, Kamiya-Matsuoka C, Tummala S (2014) Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro Oncol 16:589–593CrossRef Liao B, Shroff S, Kamiya-Matsuoka C, Tummala S (2014) Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro Oncol 16:589–593CrossRef
15.
go back to reference Mancone S, Lycan T, Ahmed T, Topaloglu U, Dothard A, Petty WJ, Strowd RE (2018) Severe neurologic complications of immune checkpoint inhibitors: a single-center review. J Neurol 265:1636–1642CrossRef Mancone S, Lycan T, Ahmed T, Topaloglu U, Dothard A, Petty WJ, Strowd RE (2018) Severe neurologic complications of immune checkpoint inhibitors: a single-center review. J Neurol 265:1636–1642CrossRef
16.
go back to reference Nukui T, Nakayama Y, Yamamoto M, Taguchi Y, Dougu N, Konishi H, Hayashi T, Nakatsuji Y (2018) Nivolumab-induced acute demyelinating polyradiculoneuropathy mimicking Guillain–Barre syndrome. J Neurol Sci 390:115–116CrossRef Nukui T, Nakayama Y, Yamamoto M, Taguchi Y, Dougu N, Konishi H, Hayashi T, Nakatsuji Y (2018) Nivolumab-induced acute demyelinating polyradiculoneuropathy mimicking Guillain–Barre syndrome. J Neurol Sci 390:115–116CrossRef
17.
go back to reference Patel AS, Snook RJ, Sehdev A (2019) Chronic inflammatory demyelinating polyradiculoneuropathy secondary to immune checkpoint inhibitors in melanoma patients. Discov Med 28:107–111PubMed Patel AS, Snook RJ, Sehdev A (2019) Chronic inflammatory demyelinating polyradiculoneuropathy secondary to immune checkpoint inhibitors in melanoma patients. Discov Med 28:107–111PubMed
18.
go back to reference Plasma Ex change/Sandoglobulin Guillain–Barré Syndrome Trial Group (1997) Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain–Barre syndrome. Plasma Exchange/Sandoglobulin Guillain–Barre Syndrome Trial Group. Lancet 349:225–230CrossRef Plasma Ex change/Sandoglobulin Guillain–Barré Syndrome Trial Group (1997) Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain–Barre syndrome. Plasma Exchange/Sandoglobulin Guillain–Barre Syndrome Trial Group. Lancet 349:225–230CrossRef
19.
go back to reference Schneiderbauer R, Schneiderbauer M, Wick W, Enk AH, Haenssle HA, Hassel JC (2017) PD-1 antibody-induced Guillain–Barre syndrome in a patient with metastatic melanoma. Acta Derm Venereol 97:395–396CrossRef Schneiderbauer R, Schneiderbauer M, Wick W, Enk AH, Haenssle HA, Hassel JC (2017) PD-1 antibody-induced Guillain–Barre syndrome in a patient with metastatic melanoma. Acta Derm Venereol 97:395–396CrossRef
20.
go back to reference Sepulveda M, Martinez-Hernandez E, Gaba L, Victoria I, Sola-Valls N, Falgas N, Casanova-Molla J, Graus F (2017) Motor polyradiculopathy during pembrolizumab treatment of metastatic melanoma. Muscle Nerve 56:E162–E167CrossRef Sepulveda M, Martinez-Hernandez E, Gaba L, Victoria I, Sola-Valls N, Falgas N, Casanova-Molla J, Graus F (2017) Motor polyradiculopathy during pembrolizumab treatment of metastatic melanoma. Muscle Nerve 56:E162–E167CrossRef
21.
go back to reference Supakornnumporn S, Katirji B (2017) Guillain–Barre syndrome triggered by immune checkpoint inhibitors: a case report and literature review. J Clin Neuromuscul Dis 19:80–83CrossRef Supakornnumporn S, Katirji B (2017) Guillain–Barre syndrome triggered by immune checkpoint inhibitors: a case report and literature review. J Clin Neuromuscul Dis 19:80–83CrossRef
22.
go back to reference Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K, Uhara H, Hasegawa Y, Inomata S, Otani Y, Yokota K, Hirose T, Tanaka R, Suzuki N, Matsui M (2017) Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 89:1127–1134CrossRef Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K, Uhara H, Hasegawa Y, Inomata S, Otani Y, Yokota K, Hirose T, Tanaka R, Suzuki N, Matsui M (2017) Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 89:1127–1134CrossRef
23.
go back to reference Tanaka R, Maruyama H, Tomidokoro Y, Yanagiha K, Hirabayashi T, Ishii A, Okune M, Inoue S, Sekine I, Tamaoka A, Fujimoto M (2016) Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain–Barre syndrome: a case report. Jpn J Clin Oncol 46:875–878CrossRef Tanaka R, Maruyama H, Tomidokoro Y, Yanagiha K, Hirabayashi T, Ishii A, Okune M, Inoue S, Sekine I, Tamaoka A, Fujimoto M (2016) Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain–Barre syndrome: a case report. Jpn J Clin Oncol 46:875–878CrossRef
24.
go back to reference Thaipisuttikul I, Chapman P, Avila EK (2015) Peripheral neuropathy associated with ipilimumab: a report of 2 cases. J Immunother 38:77–79CrossRef Thaipisuttikul I, Chapman P, Avila EK (2015) Peripheral neuropathy associated with ipilimumab: a report of 2 cases. J Immunother 38:77–79CrossRef
25.
go back to reference Wilgenhof S, Neyns B (2011) Anti-CTLA-4 antibody-induced Guillain–Barre syndrome in a melanoma patient. Ann Oncol 22:991–993CrossRef Wilgenhof S, Neyns B (2011) Anti-CTLA-4 antibody-induced Guillain–Barre syndrome in a melanoma patient. Ann Oncol 22:991–993CrossRef
26.
go back to reference Yildirim N, Gonen M, Balgetir F, Er MB (2019) Fatal acute motor axonal neuropathy induced by Nivolumab: a case report and literature review. Clin Genitourin Cancer 17:e1104–e1107CrossRef Yildirim N, Gonen M, Balgetir F, Er MB (2019) Fatal acute motor axonal neuropathy induced by Nivolumab: a case report and literature review. Clin Genitourin Cancer 17:e1104–e1107CrossRef
27.
go back to reference Yuen C, Kamson D, Soliven B, Kramer C, Goldenberg F, Rezania K (2019) Severe relapse of vaccine-induced Guillain–Barre syndrome after treatment with Nivolumab. J Clin Neuromuscul Dis 20:194–199CrossRef Yuen C, Kamson D, Soliven B, Kramer C, Goldenberg F, Rezania K (2019) Severe relapse of vaccine-induced Guillain–Barre syndrome after treatment with Nivolumab. J Clin Neuromuscul Dis 20:194–199CrossRef
28.
go back to reference Zimmer L, Goldinger SM, Hofmann L, Loquai C, Ugurel S, Thomas I, Schmidgen MI, Gutzmer R, Utikal JS, Goppner D, Hassel JC, Meier F, Tietze JK, Forschner A, Weishaupt C, Leverkus M, Wahl R, Dietrich U, Garbe C, Kirchberger MC, Eigentler T, Berking C, Gesierich A, Krackhardt AM, Schadendorf D, Schuler G, Dummer R, Heinzerling LM (2016) Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 60:210–225CrossRef Zimmer L, Goldinger SM, Hofmann L, Loquai C, Ugurel S, Thomas I, Schmidgen MI, Gutzmer R, Utikal JS, Goppner D, Hassel JC, Meier F, Tietze JK, Forschner A, Weishaupt C, Leverkus M, Wahl R, Dietrich U, Garbe C, Kirchberger MC, Eigentler T, Berking C, Gesierich A, Krackhardt AM, Schadendorf D, Schuler G, Dummer R, Heinzerling LM (2016) Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 60:210–225CrossRef
Metadata
Title
Polyradiculoneuropathy induced by immune checkpoint inhibitors: a case series and review of the literature
Authors
Kensuke Okada
Morinobu Seki
Hiroshi Yaguchi
Kenichi Sakuta
Taiji Mukai
Satoshi Yamada
Koichi Oki
Jin Nakahara
Shigeaki Suzuki
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 2/2021
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-020-10213-x

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