Article record

双特异性抗体teclistamab治疗骨髓瘤相关淋巴细胞脉络丛脑膜炎病毒脑膜脑炎患者的联合抗病毒治疗

Combination antiviral treatment for a patient with lymphocytic choriomeningitis virus meningoencephalitis associated with bispecific antibody teclistamab therapy for myeloma.

临床研究耳科IF 26Q1

文献信息

PMID	42987888
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Rea Grace Maamari 查看其他 22 位作者 Tom G S Williams；Cindy Zheng；Berkin Hack；Oliver Tomkins；Prijay Bakrania；Rajeni Thangarajah；Inès Ringue；Nathaniel Storey；Julianne R Brown；Sofia Morfopoulou；Caroline Solas；Nadège Néant；Jake Daddiego；Valentine Okonkwo；Julie Chandra；Tommy Rampling；Catherine F Houlihan；Judith Breuer；Iain Milligan；Sam Douthwaite；Matthew Streetly；Devan Vaghela
作者单位	Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK. 查看其他 13 条单位信息 Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.；Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK.；Pharmacy Department, Guy's and St Thomas' NHS Foundation Trust, London, UK.；Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK; Pharmacy Department, Guy's and St Thomas' NHS Foundation Trust, London, UK.；Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK.；Department of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.；Unité des Virus Émergents, Aix-Marseille Université, Università di Corsica, IRD 190, Inserm 1207, IRBA, Marseille, France; Assistance Publique Hôpitaux de Marseille, Laboratoire de Pharmacocinétique et Toxicologie, Marseille, France.；Virology and Pathogenesis Group, UK Health Security Agency, Porton Down, Salisbury, UK.；Department of Neuroradiology, Guy's and St Thomas' NHS Foundation Trust, London, UK.；Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK; Rare and Imported Pathogens Laboratory, UK Health Security Agency, Porton Down, UK; National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, London, UK.；Rare and Imported Pathogens Laboratory, UK Health Security Agency, Porton Down, UK; Institute of Infection, Immunity and Transplantation, University College London, London, UK; Department of Virology, University College London Hospitals NHS Foundation Trust, London, UK; Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.；Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK; Department of Microbiology, Virology and Infection Prevention and Control, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.；Department of Infection, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address: devan.vaghela1@nhs.net.
期刊	The Lancet. Infectious diseases
SCI 分区	Q1
IF	26
研究类型	临床研究 · 临床
所属专科	耳科

中文摘要

背景： 淋巴细胞脉络丛脑膜炎病毒（LCMV）是人类脑膜脑炎的罕见病因。尽管LCMV是一种全球分布的啮齿动物人畜共患病，但自20世纪50年代以来，已发表文献中未见英国人类病例报告，且检测很少进行。LCMV脑膜脑炎在免疫功能正常者中呈自限性，但免疫功能受损宿主的感染会导致严重疾病。方法：我们报告一例接受teclistamab治疗的复发性多发性骨髓瘤患者出现LCMV脑膜脑炎的表现。结果：患者表现为5个月进行性神经系统症状史，包括听力下降、共济失调、头痛和体重减轻。脑脊液（CSF）分析显示淋巴细胞性细胞增多、蛋白浓度显著升高和低糖。广泛的微生物学和自身免疫学检查均为阴性，经验性抗菌和抗结核治疗未能阻止临床恶化。CSF宏基因组下一代测序鉴定出LCMV，随后发现家鼠暴露史。开始使用利巴韦林、瑞德西韦和莫努匹韦联合抗病毒治疗。莫努匹韦后来被法匹拉韦替代，法匹拉韦给药由血清和CSF治疗药物监测指导。患者神经系统持续改善，2个月内CSF和血液中LCMV清除。抗病毒治疗持续6个月。患者恢复功能独立并重返工作，仅遗留轻度残余症状。结论：除报告一例接受teclistamab治疗患者中LCMV感染的新发情况外，本病例还强调LCMV在英国的存在以及宏基因组下一代测序在未确诊脑炎病原体鉴定中的效用。最后，本病例为持续性LCMV感染的联合抗病毒治疗提供了初步证据。

英文摘要

Lymphocytic choriomeningitis virus (LCMV) is a rare cause of meningoencephalitis in humans. Although LCMV is a rodent zoonosis with a global distribution, no UK cases in humans have been reported in published literature since the 1950s, and testing is rarely performed. LCMV meningoencephalitis is self-limiting in people who are immunocompetent, but infection in hosts who are immunocompromised causes severe disease. We report a presentation of LCMV meningoencephalitis in a patient with relapsed multiple myeloma receiving teclistamab. The patient presented with a 5-month history of progressive neurological symptoms, including hearing loss, ataxia, headache, and weight loss. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, markedly elevated protein concentration, and hypoglycorrhachia. Extensive microbiological and autoimmune investigations were negative, and empirical antimicrobial and antituberculosis therapies did not prevent clinical deterioration. Metagenomic next-generation sequencing of CSF identified LCMV, and a history of domestic rodent exposure was subsequently identified. Combination antiviral therapy with ribavirin, remdesivir, and molnupiravir was initiated. Molnupiravir was later substituted for favipiravir, and favipiravir dosing was guided by serum and CSF therapeutic drug monitoring. The patient showed sustained neurological improvement, with clearance of LCMV from CSF and blood within 2 months. Antiviral therapy continued for 6 months. The patient regained functional independence and returned to work, with only mild residual symptoms. In addition to reporting a novel occurrence of LCMV infection in a patient on teclistamab, the case highlights the presence of LCMV in the UK and the utility of metagenomic next-generation sequencing for pathogen identification in undiagnosed encephalitis. Finally, the case provides preliminary evidence supporting combination antiviral therapy in persistent LCMV infection.