From the Clinical Neurology Unit (A.M., A.B., G.L.G., M.V., A.V.), Santa Maria Della Misericordia University Hospital; Department of Medicine (DAME) (A.M., G.L.G., M.V.), University of Udine Medical School, Italy; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (S.M.-C., J.H., A.V.), Hospices Civils de Lyon, Hôpital Neurologique; Synatac Team (S.M.-C., J.H., A.V.), NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310; and University Claude Bernard Lyon 1 (S.M.-C., J.H., A.V.), Université de Lyon, France.
Neurology. 2021 Apr 20;96(16):754-766. doi: 10.1212/WNL.0000000000011795. Epub 2021 Mar 2.
To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).
Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, 59%; < 0.001). Anti-programmed cell death protein 1/programmed cell death ligand 1 was more frequent in myasthenic syndromes (50/58, 86%; = 0.005) and less common in meningitis (2/13, 15%; < 0.001) and cranial neuropathies (13/31, 42%; = 0.005). Anti-cytotoxic T-lymphocyte antigen-4 ICIs were more frequent in meningitis (8/13, 62%; < 0.001) and less common in encephalitis (2/56, 4%; = 0.009) and myositis (12/136, 9%; = 0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; = 0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; = 0.003) and less common in encephalitis (19/56, 34%; = 0.001). The highest mortality rate was reached in myasthenic syndromes (28%).
Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.
定义免疫检查点抑制剂（ICI）相关神经免疫不良事件（n-irAEs）的临床特征、处理方法和结局。
根据系统评价和荟萃分析的首选报告项目进行文献系统回顾。
共确定了 694 篇文章。256 篇文章，428 名患者符合纳入标准。与中枢神经系统疾病（109/428，25%）相比，神经肌肉疾病（319/428，75%）的报道更为常见。最常见的 n-irAEs 报告包括肌炎（136/428，32%）、吉兰-巴雷综合征和其他周围神经病（94/428，22%）、肌无力综合征（58/428，14%）、脑炎（56/428，13%）、颅神经病变（31/428，7%）、脑膜炎（13/428，3%）、中枢神经系统脱髓鞘疾病（8/428，2%）和脊髓炎（7/428，2%）。25/428（6%）患者还检测到其他中枢神经系统疾病。与整个样本相比，肌无力综合征的 Ab 阳性率明显更高（33/56，59%；<0.001）。抗程序性细胞死亡蛋白 1/程序性细胞死亡配体 1 在肌无力综合征（50/58，86%；=0.005）中更为常见，而在脑膜炎（2/13，15%；<0.001）和颅神经病变（13/31，42%；=0.005）中则更为少见。抗细胞毒性 T 淋巴细胞抗原-4 ICI 在脑膜炎（8/13，62%；<0.001）中更为常见，而在脑炎（2/56，4%；=0.009）和肌炎（12/136，9%；=0.01）中则较少见。不同 ICI 的联合使用在颅神经病变中更为常见（12/31，39%；=0.005）。黑色素瘤在周围神经病患者中更为常见（64/94，68%；=0.003），而在脑炎患者中则较少见（19/56，34%；=0.001）。肌无力综合征的死亡率最高（28%）。
鉴于未来免疫检查点抑制剂治疗的应用日益增加，这些信息对于帮助神经科医生和肿瘤学家早期诊断和治疗 n-irAEs 可能具有重要价值。
