免疫检查点抑制剂相关脑炎的特点及其与 HSV-1 和抗 LGI1 脑炎的比较：一项回顾性多中心队列研究。
Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study.
机构信息
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Clinician Scientist Program, Charitéplatz 1, 10117 Berlin, Germany.
SERIO Side Effect Registry Immuno-Oncology, Germany; Department of Dermatology and Allergy, University Hospital, Ludwig-Maximilian Universität Munich, Frauenlobstr. 9-11, 80337 München, Germany.
出版信息
Eur J Cancer. 2022 Nov;175:224-235. doi: 10.1016/j.ejca.2022.08.009. Epub 2022 Sep 22.
AIM
Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis.
METHODS
In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre.
RESULTS
Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p = .007), confusion (83% vs. 43%; p = .02), disorientation (83% vs. 29%; p = .007) and aphasia (43% vs. 0%; p = .007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43).
CONCLUSIONS
ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death.
目的
免疫检查点抑制剂诱导的脑炎（ICI-iE）是免疫检查点抑制剂治疗的一种罕见但危及生命的毒性。我们旨在确定 ICI-iE 的特征，并描述其与单纯疱疹病毒（HSV-1）脑炎和抗亮氨酸丰富胶质瘤失活 1（anti-LGI1）脑炎的区别，因为这两种脑炎是两种替代实体。
方法
在这项回顾性多中心队列研究中，我们收集了 2015 年 1 月至 2021 年 9 月间向免疫肿瘤副作用登记处报告的 ICI-iE 患者，并将其临床特征和结局与在德国神经学转诊中心接受治疗的 46 例连续 HSV-1 或 anti-LGI1 脑炎患者进行比较。
结果
纳入了 30 例 ICI-iE、25 例 HSV-1 脑炎和 21 例 anti-LGI1 脑炎患者。ICI-iE 的临床表现高度多样化，类似于 HSV-1 脑炎，而意识障碍（66% vs. 5%，p=0.007）、意识模糊（83% vs. 43%；p=0.02）、定向障碍（83% vs. 29%；p=0.007）和失语症（43% vs. 0%；p=0.007）在 ICI-iE 中比在 anti-LGI1 脑炎中更为常见。抗神经元抗体（17/18，94%）和 MRI（18/30，60%）在 ICI-iE 中大多为阴性，但几乎所有患者的脑脊液（CSF）均显示细胞增多和/或蛋白水平升高（28/29，97%）。3 例（10%）患者死于 ICI-iE。早期免疫抑制治疗与更好的结局相关（r=0.43）。
结论
ICI-iE 是一种无特异性临床特征的异质性实体。CSF 分析具有最高的诊断价值，因为它可在大多数患者中揭示炎症变化，并排除感染。早期治疗 ICI-iE 对于预防后遗症和死亡至关重要。
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