Abstract
Introduction
Myasthenia gravis (MG) Lambert-Eaton (LE) overlap syndrome is a rare condition. Here, we describe the first case of MG-LE overlap syndrome revealed by the anti-programmed cell death 1 inhibitor, nivolumab, in a patient treated for metastatic melanoma.
Case
Three months after receiving nivolumab and 1 month after brain metastasis radiotherapy, our patient developed generalized fatigue with intermittent ptosis and swallowing difficulty suggesting a myasthenic syndrome. Electromyogram findings, anti-acetylcholine receptor, and anti-calcium channel antibodies levels were consistent with an immune-related myasthenic syndrome with specific features for both MG and LE syndromes. Immunotherapy with nivolumab was stopped. Patient was treated with systemic immunosuppressive and anti-cholinesterase drugs, with remarkable improvement of his neurological symptoms. Prolonged partial remission was obtained for his metastatic melanoma without need for a third-line treatment. Two years later, a relapse of hismyasthenic symptoms was observed along with new neurological symptoms related to brain radiation necrosis.
Conclusion
We describe the first case of MG-LE overlap syndrome diagnosed after anti-PD1 immunotherapy for metastatic melanoma, which appeared after radiation therapy and then relapsed after brain radiation necrosis. We hypothesized a role for brain inflammation as a trigger for MG-LE onset. Neuro-muscular junctions disease induced or revealed by checkpoint inhibitors can be challenging and requires long-term follow-up.
Data availability
Supplemental data are available on request from the last author.
References
Johansen A, Christensen SJ, Scheie D et al (2019) Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies: systematic review. Neurology 92:663–674. https://doi.org/10.1212/WNL.0000000000007235
Safa H, Johnson DH, Trinh VA, et al (2019) Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature. J Immunother Cancer 7. https://doi.org/10.1186/s40425-019-0774-y
Nakatani Y, Tanaka N, Enami T et al (2018) Lambert-Eaton myasthenic syndrome caused by nivolumab in a patient with squamous cell lung cancer. Case Rep Neurol 10:346–352. https://doi.org/10.1159/000494078
Oh SJ (2016) Myasthenia gravis Lambert-Eaton overlap syndrome. Muscle Nerve 53:20–26. https://doi.org/10.1002/mus.24921
Vanderlugt CL, Miller SD (2002) Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2:85–95. https://doi.org/10.1038/nri724
Author information
Authors and Affiliations
Contributions
All authors participated actively for the diagnosis and the management of the patient; DA and PC collected data and drafted the initial manuscript; PS supervised writing and revised the manuscript; LMG, SA, DF, and DC revised the manuscript. All authors approved the final version of the manuscript.
Corresponding author
Ethics declarations
Ethics approval
Not applicable.
Consent to participate
The patient gave his written consent to publish his medical data.
Consent for publication
The patient provided his consent to use his medical data for publication.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Duplaine, A., Prot, C., Le-Masson, G. et al. Myasthenia Gravis Lambert-Eaton overlap syndrome induced by nivolumab in a metastatic melanoma patient. Neurol Sci 42, 5377–5378 (2021). https://doi.org/10.1007/s10072-021-05557-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-021-05557-9