Neurological autoimmunity in patients with non-pulmonary neuroendocrine neoplasms - clinical manifestations and neural autoantibody profiles

Sep 21, 2026

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Paraneoplastic neurological autoimmunity is well characterized in small-cell lung cancer, yet evidence remains limited for other neuroendocrine neoplasms (NENs). This retrospective cohort study identified adults with histopathologically confirmed non-pulmonary NENs, neurological autoimmunity within five years of NEN diagnosis, and neural antibody testing at Mayo Clinic (January 2008 to March 2023), including controls without neurological autoimmunity.

LanguageEnglish

CategoryHealthcare

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Pages13

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Introduction

Methods

Study patients

DOI: 10. 1111/ene.16273 OR I G I NAL ART I C L E Neurological autoimmunity in patients with non-pulmonary neuroendocrine neoplasms: clinical manifestations and neural autoantibody profiles Georgios Mangioris1 | Thorvardur R. Halfdanarson2 | Vanda A. Lennon1,3,4 | Bryce K. Chang3 | Divyanshu Dubey1,3,5 | P. James B. Dyck3 | Eoin P. Flanagan1,3,5 | Andrew McKeon1,3,5 | John R. Mills1 | Sean J. Pittock1,3,5 | Anastasia Zekeridou1,3,5 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA 2Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA 3 Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA 4Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA 5Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota, USA Correspondence Anastasia Zekeridou, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. Email: [zekeridou.anastasia@mayo.edu](zekeridou.anastasia@mayo.edu) Abstract Background and purpose: Paraneoplastic neurological autoimmunity is well described with small-cell lung cancer, but information is limited for other neuroendocrine neoplasms (NENs) . Methods: Adult patients with histopathologically confirmed non-pulmonary NENs, neurological autoimmunity within 5 years of NEN diagnosis, and neural antibody testing performed at the Mayo Clinic Neuroimmunology Laboratory (January 2008 to March 2023) were retrospectively identified. Control sera were available from patients with NENs without neurological autoimmunity (116) . Results: Thirty-four patients were identified (median age 68 years, range 31–87) . The most common primary tumor sites were pancreas (nine), skin (Merkel cell, eight), small bowel/duodenum (seven), and unknown (seven) . Five patients received immune checkpoint inhibitor (ICI) therapy before symptom onset; symptoms preceded cancer diagnosis in 62. 1% of non-ICI-treated patients. The most frequent neurological phenotypes (nonICI-treated) were movement disorders (12; cerebellar ataxia in 10), dysautonomia (six), peripheral neuropathy (eight), encephalitis (four), and neuromuscular junction disorders (four) . Neural antibodies were detected in 55.9% of patients studied (most common specificities: P/Q-type voltage-gated calcium channel [seven], muscle-type acetylcholine receptor [three], anti-neuronal nuclear antibody type 1 [three], and neuronal intermediate filaments [two]), but in only 6.9% of controls. Amongst patients receiving cancer or immunosuppressive therapy, 51. 6% had partial or complete recovery. Outcomes were unfavorable in 48 . 3%(non-ICI-treated) and neural autoantibody positivity was associated with poor neurological outcome. Discussion: Neurological autoimmunity associated with non-pulmonary NENs is often multifocal and can be treatment responsive, underscoring the importance of rapid recognition and early treatment. K E Y WO R D S carcinoid, cerebellar ataxia, encephalitis, myasthenia gravis, paraneoplastic syndromes This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. Eur J Neurol. 2024;31:e16273 . [https://doi.org/10.1111/ene.16273](https://doi.org/10.1111/ene.16273) [wileyonlinelibrary.com/journal/ene](wileyonlinelibrary.com/journal/ene) 1 of 13 INTRODUCTION Paraneoplastic neurological syndromes are rare manifestations of immune responses targeting antigens expressed by a tumor that in normal conditions are nervous-system-restricted. The onset of neurological manifestations usually precedes cancer diagnosis and may lead to earlier cancer dete

FAQs

What is the study’s main objective regarding non-pulmonary NENs?

To describe the clinical phenotypes and neural autoantibody profiles of patients with neurological autoimmunity associated with non-pulmonary NENs.

How were eligible patients and controls identified?

Adults with non-pulmonary NENs and neurological autoimmunity within five years were identified via Mayo Clinic databases and cross-referenced with the Neuroimmunology Laboratory database; control sera came from patients with NENs without neurological autoimmunity.

What proportion of patients had detected neural antibodies, and how did controls compare?

Neural antibodies were detected in 55.9% of studied patients, but only in 6.9% of controls.

Sep 21, 2026

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