Paraneoplastic neurological syndromes (PNS) are the immune-mediated effects of a remote cancer and are characterised by an autoantibody response against antigens expressed by the tumour. Classically, well-characterised ‘onconeuronal’ antibodies target intracellular antigens and hence cannot access their antigens across intact cell membranes. The pathogenic mediators are likely to be neuronal-specific T cells. There is a variable response to immunotherapies and the clinical syndrome helps to direct the search for a specific set of tumours. By contrast, many newly emerging autoantibodies with oncological associations target cell surface epitopes and can exert direct pathogenic effects on both the central and peripheral nervous systems. Patients with these cell-surface directed autoantibodies often clearly respond to immunotherapies. Overall, the clinical, serological and oncological features in an individual patient helps determine the clinical relevance of the syndrome and hence guide its management. We summarise current knowledge and a practical approach to the investigation, diagnosis, treatment and outcomes of patients with suspected PNS.
- paraneoplastic syndrome
- clinical neurology
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Contributors SRI and SB conceived the study and produced the first draft. CU and JH edited the manuscript for intellectual content. All authors approved the final text.
Funding SRI is supported by the Wellcome Trust (104079/Z/14/Z), Medical Research Council(MR/V007173/1), BMA Research Grants - Vera Down grant (2013), Margaret Temple (2017), Epilepsy Research UK (P1201), the Fulbright UK-US commission (MS Society research award) and by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. This research was funded in whole, or in part, by the Wellcome Trust (grant number 104079/Z/14/Z). JH is supported by a public grant overseen by the French National Research Agency (ANR), as part of the second 'Investissements d'Avenir' programme called BETPSY (reference ANR-18-RHUS-0012, https://www.rhu-betpsy.fr/). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. SB has received salary support from the NIHR and is currently supported by the Wellcome Trust. CU is supported by the Friedman Award for Health Scholars (University of British Columbia) and received salary support from the UBC Division of Neurology.
Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, UBC, or Vancouver Coastal Health. The funders had no role in the preparation, review or approval of the manuscript, and decision to submit the manuscript for publication.
Competing interests SRI is a coapplicant and receives royalties on patent application WO/2010/046716 (UK patent number, PCT/GB2009/051441) entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed commercially for the development of assays for LGI1 and other VGKC complex antibodies. SRI and SB are coapplicants on a patent application entitled 'Diagnostic Strategy to Improve Specificity of CASPR2 Antibody Detection' (PCT/GB2019/051257, publication number WO/2019/211633 and UK1807410.4). SRI has received honoraria from UCB, MedImmun, ADC therapeutics and Medlink Neurology, and research support from CSL Behring, UCB and ONO Pharma. CU and JH declare no competing interests with respect to this publication.
Provenance and peer review Commissioned. Externally peer reviewed by Neil Anderson, Auckland, New Zealand.
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