急性横贯性脊髓炎（ATM）：43例新冠病毒相关急性横贯性脊髓炎患者及3例接种ChAdOx1 nCoV-19疫苗（AZD1222）后发生的急性横贯性脊髓炎严重不良事件的临床回顾
Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222).
作者信息
Román Gustavo C, Gracia Fernando, Torres Antonio, Palacios Alexis, Gracia Karla, Harris Diógenes
机构信息
Department of Neurology, Neurological Institute, Houston Methodist Hospital, Houston, TX, United States.
Weill Cornell College of Medicine, Cornell University, New York, NY, United States.
出版信息
Front Immunol. 2021 Apr 26;12:653786. doi: 10.3389/fimmu.2021.653786. eCollection 2021.
INTRODUCTION
Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic.
CASE-FINDING METHODS: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222).
RESULTS
All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN).
CONCLUSIONS
We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.
引言
虽然急性横贯性脊髓炎（ATM）是一种罕见的神经系统疾病（每年每百万人口中有1.34 - 4.6例），但在新冠疫情期间出现了与新冠病毒相关的ATM病例。
病例发现方法
我们报告了一名来自巴拿马的感染新冠病毒并发ATM的患者，并对2020年3月至2021年1月期间来自21个国家的43例与新冠病毒相关的ATM患者进行了全面的临床回顾。此外，在新冠疫苗ChAdOx1 nCoV - 19（AZD1222）的临床试验中，有3例ATM被报告为严重不良事件。
结果
所有患者均具有ATM的典型特征，因脊髓病变导致急性起病的瘫痪、感觉平面及括约肌功能障碍，影像学检查证实了这一点。患者中有23名男性（53%）和20名女性（47%），年龄在21岁至73岁之间（平均年龄49岁），29岁和58岁出现两个高峰，不包括3例儿科病例。主要临床表现为四肢瘫（58%）和截瘫（42%）。40例患者有MRI报告；局限性ATM病变累及≤3个脊髓节段（12例，30%），位于颈椎（5例）和胸段脊髓水平（7例）；28例（70%）为纵向广泛的ATM（LEATM），累及≥4个脊髓节段（颈胸段18例，胸腰段 - 骶段10例）。8例患者发生急性播散性脑脊髓炎（ADEM），主要为女性（67%），年龄在27岁至64岁之间。3例ATM患者还因视神经脊髓炎（MNO）导致失明，另外2例还患有急性运动轴索性神经病（AMAN）。
结论
我们发现ATM是新冠病毒意外常见的神经系统并发症。大多数病例（68%）有10天至6周的潜伏期，这可能表明是宿主对病毒反应介导的感染后神经系统并发症。32%的病例潜伏期较短（15小时至5天），提示新冠病毒有直接嗜神经作用。考虑到本报告中全球新冠病毒相关ATM病例的发病率为0.5/百万，在AZD1222疫苗试验的11636名参与者中有3例报告的ATM不良事件发生率极高。ATM的发病机制尚不清楚，但可以想象，新冠病毒抗原——可能也存在于AZD1222新冠疫苗或其黑猩猩腺病毒佐剂中——可能诱导导致脊髓炎的免疫机制。
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