Zoccarato Marco, Grisold Wolfgang, Grisold Anna, Poretto Valentina, Boso Federica, Giometto Bruno
Neurology Unit O.S.A., Azienda Ospedale-Università di Padova, Padova, Italy.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology Donaueschingenstraße 13 A-1200 Vienna, Vienna, Austria.
Front Neurol. 2021 Oct 1;12:706169. doi: 10.3389/fneur.2021.706169. eCollection 2021.
The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded. The antibodies associated with PNS are commonly classified as onconeural (intracellular) and neuronal surface antibodies (NSAbs). Since 2004, the number of antibodies and the associated tumors has increased. Knowledge has grown on the mechanisms underlying the neuropathies observed in lymphoma, paraproteinemia, and multiple myeloma. Moreover, other unrevealed mechanisms underpin sensorimotor neuropathies and late-stage neuropathies, where patients in advanced stages of cancer-often associated with weight loss-experience some mild sensorimotor neuropathy, without concomitant use of neurotoxic drugs. The spectrum of paraneoplastic neuropathies has increased to encompass motor neuropathies, small fiber neuropathies, and autonomic and nerve hyperexcitability syndromes. In addition, also focal neuropathies, as cranial nerves, plexopathies, and mononeuropathies, are considered in some cases to be of paraneoplastic origin. A key differential diagnosis for paraneoplastic neuropathy, during the course of cancer disease (the rare occurrence of a PNS), is chemotherapy-induced peripheral neuropathy (CIPN). Today, novel complications that also involve the peripheral nervous system are emerging from novel anti-cancer therapies, as targeted and immune checkpoint inhibitor (ICH) treatment. Therapeutic options are categorized into causal and symptomatic. Causal treatments anecdotally mention tumor removal. Immunomodulation is sometimes performed for immune-mediated conditions but is still far from constituting evidence. Symptomatic treatment must always be considered, consisting of both drug therapy (e.g., pain) and attempts to treat disability and neuropathic pain.
2004年，周围神经系统副肿瘤综合征（PNS）欧洲协作网络发布的诊断标准为PNS提供了一个有用的分类，包括副肿瘤性神经病。亚急性感觉神经元病（SSN）是最常观察到的周围性PNS，而其他形式的神经病，如感觉性多发性神经病、感觉运动性多发性神经病、脱髓鞘性神经病、自主神经病以及局灶性神经或神经丛病变，则较为少见。在该标准发布时，主要关注点是肿瘤神经抗体，但此后关于其机制的认识有所扩展。与PNS相关的抗体通常分为肿瘤神经（细胞内）抗体和神经元表面抗体（NSAbs）。自2004年以来，抗体数量及相关肿瘤有所增加。对于淋巴瘤、副蛋白血症和多发性骨髓瘤中观察到的神经病的潜在机制，人们的认识也有所增长。此外，在感觉运动性神经病和晚期神经病中还存在其他未揭示的机制，癌症晚期患者（常伴有体重减轻）在未同时使用神经毒性药物的情况下会出现一些轻度感觉运动性神经病。副肿瘤性神经病的范围已扩大到包括运动神经病、小纤维神经病以及自主神经和神经兴奋性增高综合征。此外，在某些情况下，局灶性神经病，如颅神经病变、神经丛病变和单神经病，也被认为源于副肿瘤。在癌症病程中（PNS罕见），副肿瘤性神经病的一个关键鉴别诊断是化疗引起的周围神经病（CIPN）。如今，新型抗癌疗法，如靶向治疗和免疫检查点抑制剂（ICH）治疗，正引发涉及周围神经系统的新型并发症。治疗选择分为病因治疗和对症治疗。病因治疗偶尔会提及肿瘤切除。免疫调节有时用于免疫介导的疾病，但仍远未构成证据。必须始终考虑对症治疗，包括药物治疗（如疼痛治疗）以及治疗残疾和神经性疼痛的尝试。
