Neuroimmunology Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Nat Rev Clin Oncol. 2019 Sep;16(9):535-548. doi: 10.1038/s41571-019-0194-4.
Paraneoplastic neurological syndromes (PNSs) comprise a group of disorders that can affect any part of the nervous system in patients with cancer and frequently result from autoimmune responses triggered by the ectopic expression of neuronal proteins in cancer cells. These disorders are rare, although the introduction of immune-checkpoint inhibitors (ICIs) into cancer treatment algorithms has renewed interest in PNSs. ICIs are associated with a considerably increased incidence of immunological toxicities compared with traditional anticancer therapies, including neurological immune-related adverse effects (nirAEs) that can manifest as PNSs. Theoretically, the use of ICIs might increase the risk of PNSs, in particular, in patients with the types of cancer that are most frequently associated with these disorders (such as small-cell lung cancer), emphasizing the importance of their prompt diagnosis and treatment to prevent irreversible neurological deficits. To facilitate the recognition of these disorders in the context of immune-checkpoint inhibition, we provide an overview of PNSs, including the main syndromes, types of neuronal autoantibodies and associated immunological mechanisms. We also review the scenarios in which nirAEs fulfil the criteria for PNSs and examine their frequency and clinical presentations. Finally, we provide recommendations for the prevention and management of PNSs that can occur during ICI therapy.
副肿瘤神经系统综合征（PNSs）是一组疾病，可影响癌症患者神经系统的任何部位，通常是由癌细胞中神经元蛋白的异位表达引发的自身免疫反应引起的。这些疾病较为罕见，但免疫检查点抑制剂（ICIs）在癌症治疗方案中的应用，使人们对 PNSs 再次产生兴趣。与传统的抗癌疗法相比，ICI 治疗与更高的免疫毒性发生率相关，包括可能表现为 PNSs 的神经免疫相关不良事件（nirAEs）。从理论上讲，ICI 的使用可能会增加 PNSs 的风险，特别是在与这些疾病最常相关的癌症类型（如小细胞肺癌）患者中，这强调了及时诊断和治疗以预防不可逆的神经功能缺损的重要性。为了在免疫检查点抑制的背景下促进对这些疾病的识别，我们提供了 PNSs 的概述，包括主要的综合征、神经元自身抗体的类型和相关的免疫机制。我们还回顾了 nirAEs 符合 PNSs 标准的情况，并研究了它们的频率和临床表现。最后，我们提供了在 ICI 治疗期间可能发生的 PNSs 的预防和管理建议。
