Sokolov Elisaveta, Karschnia Philipp, Benjamin Reuben, Hadden Robert D M, Elwes Robert C D, Drummond Lee, Amin Devyani, Paiva Vitor, Pennisi Alex, Herlopian Aline, Frigault Matthew, Sanderson Robin, Inam Shafqat, Cole Andrew J, Dietrich Jorg
Department of Neurology, Harvard University, Cambridge, Massachusetts, USA.
Department of Neurosurgery, Ludwig Maximilians University Munich, Munchen, Bayern, Germany.
BMJ Neurol Open. 2020 Jun 18;2(1):e000054. doi: 10.1136/bmjno-2020-000054. eCollection 2020.
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.
We aimed to characterise language dysfunction and define electroencephalographic signatures after CAR-T cell therapy.
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).
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.
Language dysfunction after CAR-T cell therapy is associated with generalised EEG abnormalities.
嵌合抗原受体修饰的T细胞（CAR-T）已成为复发/难治性血液系统恶性肿瘤中一种有前景的免疫治疗方法。更广泛的应用受到独特毒性的限制，尤其是神经毒性（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，可能有助于深入了解语言功能障碍。
我们旨在描述CAR-T细胞治疗后的语言功能障碍特征并确定脑电图特征。
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。该队列包括一部分接受研究性CD19导向的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）的患者。
16例（84%）患者在CAR-T细胞输注后14天内出现语言功能障碍。10例（50%）患者有轻度找词困难，10例（50%）有明显的失语症且找词困难严重；后者均与脑电图上的广泛性节律性δ活动或广泛性周期性放电有关。
CAR-T细胞治疗后的语言功能障碍与广泛性脑电图异常有关。
