Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a promising immunotherapeutic approach in relapsed/refractory haematolgical malignancies. Broader application is limited by unique toxicities, notably, neurotoxicity (NTX). Language dysfunction is among the most frequent symptoms of NTX, the underlying mechanisms of which remain to be elucidated. Electroencephalogram (EEG) is an important tool to monitor for NTX and may provide insights into language dysfunction. Aim We aimed to characterise language dysfunction and define electroencephalographic signatures after CAR-T cell therapy. Methods We reviewed the clinical presentation and EEG findings of 20 adult patients presenting with language dysfunction after CAR-T cell infusion. The cohort included a subset of patients treated with investigational CD19-directed CAR-T cells for non-Hodgkin’s lymphoma (n=17), acute lymphoblastic leukaemia (n=1), follicular lymphoma (n=1) and chronic lymphocytic leukaemia (n=1). Results Language dysfunction presented within 14 days of CAR-T cell infusion in 16 (84%) patients. Ten (50%) patients had mild word-finding difficulties and 10 (50%) had marked dysphasia with profound word-finding difficulties; the latter were all associated with generalised rhythmic delta activity or generalised periodic discharges on EEG. Conclusions Language dysfunction after CAR-T cell therapy is associated with generalised EEG abnormalities.

中文翻译：

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CAR-T相关神经毒性患者的语言功能障碍相关脑电图发现

嵌合抗原受体修饰的 T 细胞 (CAR-T) 已成为复发/难治性血液恶性肿瘤的一种有前途的免疫治疗方法。更广泛的应用受到独特毒性的限制，特别是神经毒性 (NTX)。语言功能障碍是 NTX 最常见的症状之一，其潜在机制仍有待阐明。脑电图 (EEG) 是监测 NTX 的重要工具，可提供对语言功能障碍的深入了解。目的 我们旨在描述语言功能障碍并定义 CAR-T 细胞治疗后的脑电图特征。方法 我们回顾了 20 例 CAR-T 细胞输注后出现语言功能障碍的成年患者的临床表现和脑电图结果。该队列包括接受研究性 CD19 靶向 CAR-T 细胞治疗非霍奇金淋巴瘤（n=17）、急性淋巴细胞白血病（n=1）、滤泡性淋巴瘤（n=1）和慢性淋巴细胞白血病（n =1)。结果 16 名 (84%) 患者在 CAR-T 细胞输注后 14 天内出现语言功能障碍。10 名 (50%) 患者有轻度找词困难，10 名 (50%) 患者有明显的言语困难并伴有严重的找词困难；后者都与脑电图上的广义节律性δ活动或广义周期性放电有关。结论 CAR-T 细胞治疗后的语言功能障碍与全身脑电图异常有关。结果 16 名 (84%) 患者在 CAR-T 细胞输注后 14 天内出现语言功能障碍。10 名 (50%) 患者有轻度找词困难，10 名 (50%) 患者有明显的言语困难并伴有严重的找词困难；后者都与脑电图上的广义节律性δ活动或广义周期性放电有关。结论 CAR-T 细胞治疗后的语言功能障碍与全身脑电图异常有关。结果 16 名 (84%) 患者在 CAR-T 细胞输注后 14 天内出现语言功能障碍。10 名 (50%) 患者有轻度找词困难，10 名 (50%) 患者有明显的言语困难并伴有严重的找词困难；后者都与脑电图上的广义节律性δ活动或广义周期性放电有关。结论 CAR-T 细胞治疗后的语言功能障碍与全身脑电图异常有关。