Bar Mucha Sapir, Rozenberg Ayal, Gutter Kapon Lilach, Gorenshtein Alon, Ganelin-Cohen Esther, Ben Hayun Rachel, Yarovinsky Nataliya, Shelly Shahar
Department of Neurology, Rambam HealthCare Campus, Haifa, Israel.
Neuroimmunology Laboratory, Ruth and Bruce Rapaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Front Immunol. 2024 Nov 18;15:1466704. doi: 10.3389/fimmu.2024.1466704. eCollection 2024.
It is unknown whether delay in diagnosis affects morbidity reportedly in paraneoplastic syndromes (PNS). We aimed to explore various aspects of PNS, including prevalence, clinical characteristics, diagnostic criteria, and treatment outcomes.
We studied n-PNS diagnosis between 2016 to 2023, and included only patients with positive onconeural antibodies, who developed cancer, and exhibited a recognizable PNS phenotype.
We identified 12 patients with positive Abs and co-occurring cancer, most prevalent PNS antibodies included anti-GAD65, anti-Recoverin and anti-Yo. The most common phenotypes were limbic encephalitis (n=5, 42%) and encephalomyelitis (n=4,33%). Cancer preceded neurological presentation in 6 cases. Among the 6 patients who initially presented with n-PNS, median time from neurological presentation to oncologic diagnosis was 73 days, as five of them (83%) were diagnosed with cancer during oncological evaluation prompted by the PNS diagnosis or suspicion. Lymphoma was the most frequent cancer (n=3, 25%), followed by lung cancer (n=2, 17%), and ovarian cancer (n=2, 17%). Among patients who received immunotherapy as n-PNS treatment (n=9, 75%), steroids were a part of the management at 78% (n=7). Another immunotherapy used included plasmapheresis (n=5, 55%) and steroid sparing immunosuppressant (n=2, 29%). Four (33%) patients had short term therapeutic benefit with improvement or stabilization at mRS ≤ 4. Median Disability-adjusted life years (DALYs), as disease burden value, was 13 years. Death occurred in 9 of the 12 patients, with most cases deaths attributed to cancer progression. Compering to the expected median survival by type and stage of tumor, from 9 deceased patients, 56% (n=5) died younger than expected. Median survival was 410 days (range 29-2738 days), and 152 days since the appearance of n-PNS (range 8-1434 days). There were no differences in survival between patients who initially presented with n-PNS versus cancer (p=0.39).
In up to 8 years of follow up, there was no difference in mortality among patients who presented initially n-PNS. There was a significant decline in the quality of life, most face substantial disability and functional impairment long term.
目前尚不清楚诊断延迟是否会影响副肿瘤综合征（PNS）的发病率。我们旨在探讨PNS的各个方面，包括患病率、临床特征、诊断标准和治疗结果。
我们研究了2016年至2023年间的非典型PNS诊断，仅纳入了肿瘤神经抗体阳性、患癌且表现出可识别的PNS表型的患者。
我们确定了12例抗体阳性且同时患癌的患者，最常见的PNS抗体包括抗GAD65、抗恢复蛋白和抗Yo。最常见的表型是边缘叶脑炎（n = 5，42%）和脑脊髓炎（n = 4，33%）。6例患者癌症先于神经症状出现。在最初表现为非典型PNS的6例患者中，从神经症状出现到肿瘤诊断的中位时间为73天，其中5例（83%）在因PNS诊断或怀疑而进行的肿瘤评估期间被诊断出患有癌症。淋巴瘤是最常见的癌症（n = 3，25%），其次是肺癌（n = 2，17%）和卵巢癌（n = 2，17%）。在接受免疫治疗作为非典型PNS治疗的患者中（n = 9，75%），78%（n = 7）的患者治疗中使用了类固醇。使用的其他免疫治疗方法包括血浆置换（n = 5，55%）和类固醇节省型免疫抑制剂（n = 2，29%）。4例（33%）患者有短期治疗获益，改良Rankin量表（mRS）评分≤4且病情改善或稳定。作为疾病负担值的中位伤残调整生命年（DALYs）为13年。12例患者中有9例死亡，大多数病例死于癌症进展。与根据肿瘤类型和分期预期的中位生存期相比，在9例死亡患者中，56%（n = 5）的患者死亡年龄低于预期。中位生存期为410天（范围29 - 2738天），自非典型PNS出现以来为152天（范围8 - 1434天）。最初表现为非典型PNS与最初表现为癌症的患者之间的生存率无差异（p = 0.39）。
在长达8年的随访中，最初表现为非典型PNS的患者死亡率无差异。生活质量显著下降，大多数患者长期面临严重残疾和功能障碍。
