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新型冠状病毒肺炎的神经系统表现及脑脊液病毒检测

Neurologic manifestations of COVID-19 and viral test in cerebrospinal fluid.

作者信息

Cardoso Carla de Oliveira, Rodrigues Sandoval Evandra Strazza, de Oliveira Chagas Lilian Beatriz Moreira, Badra Soraya Jabur, Covas Dimas Tadeu, Haddad Simone Kashima, Figueiredo Luiz Tadeu Moraes

机构信息

Virology Research Center, Department of Internal Medicine, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Advanced Molecular Biology Laboratory, Blood Center of Ribeirão Preto, Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

出版信息

PLoS One. 2025 Mar 19;20(3):e0312621. doi: 10.1371/journal.pone.0312621. eCollection 2025.

Abstract

BACKGROUND

Neurological manifestations are present in about one-third of COVID-19 cases, ranging from mild symptoms, such as anosmia, to more severe forms like demyelinating syndromes. Although direct invasion of the CNS has been demonstrated, the immune- mediated pathway is also described and more accepted. Even in cases where viral detection in CSF is absent, it should not rule out neuroinvasion. There are few prospective studies about neurological manifestations of COVID-19, especially with viral tests in CSF; as well there are still many questions about COVID-19 associated with neurological disease. Thus, we describe clinical and CSF findings of a prospective cohort of patients with nasal positive tests for SARS-CoV-2 and neurological involvement. We also discuss the pathogenic mechanisms related to these manifestations.

METHODS AND FINDINGS

This is a prospective cohort study; 27 patients were evaluated according to clinical presentation, the time interval between COVID-19 diagnosis and onset of neurological alterations, syndromic diagnosis, imaging and CSF findings. Real time polymerase chain reaction for SARS-CoV-2 genome was performed in all CSF samples. 2 RT-PCR in spinal cord fluid resulted positive in 9 (33.3%) cases, five of them had a positive swab nasal test concomitant to neurologic disease. Respiratory signs were described in 12 out 27 patients, five of them with viral detection in CSF. White cell counts in CSF were normal range in the majority of cases, except for 3 occurrences: two patients had elevated CSF WBC counts and viral detection in CSF (10 and 36 cells/mm3) and one also had elevated CSF WBC count but viral detection in CSF was negative (21cells/mm3). The observed neurological signs encompassed a diverse neurologic spectrum, including seizures, paresis, gait abnormalities, headaches, alteration in consciousness and memory or cognitive impairment. Both imaging and CSF alterations exhibited non-specific characteristics. Syndromic diagnoses included stroke, dementia or cognitive impairments, Guillain-Barré Syndrome, encephalitis, encephalomyelitis, acute flaccid palsy and optical neuritis.

CONCLUSIONS

The patients in the present study had COVID-19 and neurologic involvement including a wide range of clinical manifestations. SARS-CoV-2 was detected in one-third of CSF samples, regardless of time interval between COVID-19 diagnosis and the onset of neurological signs. These conditions encompass various pathogenic pathways and the neuroinvasion potential of SARS-CoV-2 should be more studied.

摘要

背景

约三分之一的新冠病毒病(COVID-19)病例存在神经系统表现,范围从嗅觉丧失等轻微症状到脱髓鞘综合征等更严重的形式。尽管已证实新冠病毒可直接侵入中枢神经系统(CNS),但免疫介导途径也有描述且更被认可。即使脑脊液(CSF)中未检测到病毒,也不能排除神经侵袭。关于COVID-19神经系统表现的前瞻性研究很少,尤其是脑脊液病毒检测方面;关于与神经系统疾病相关的COVID-19仍有许多问题。因此,我们描述了一组SARS-CoV-2鼻腔检测呈阳性且有神经系统受累的前瞻性队列患者的临床和脑脊液检查结果。我们还讨论了与这些表现相关的致病机制。

方法和结果

这是一项前瞻性队列研究;根据临床表现、COVID-19诊断与神经系统改变发作之间的时间间隔、综合征诊断、影像学和脑脊液检查结果对27例患者进行了评估。对所有脑脊液样本进行了SARS-CoV-2基因组的实时聚合酶链反应。脊髓液中的2次逆转录聚合酶链反应(RT-PCR)在9例(33.3%)病例中呈阳性,其中5例在神经系统疾病发作时鼻腔拭子检测也呈阳性。27例患者中有12例出现呼吸道症状,其中5例脑脊液中有病毒检测。大多数情况下脑脊液中的白细胞计数在正常范围内,有3例例外:2例患者脑脊液白细胞计数升高且脑脊液中有病毒检测(分别为10和36个细胞/mm³),1例脑脊液白细胞计数也升高但脑脊液病毒检测为阴性(21个细胞/mm³)。观察到的神经系统体征涵盖多种神经系统表现,包括癫痫发作、轻瘫、步态异常、头痛、意识和记忆改变或认知障碍。影像学和脑脊液改变均表现出非特异性特征。综合征诊断包括中风、痴呆或认知障碍、吉兰-巴雷综合征、脑炎、脑脊髓炎、急性弛缓性麻痹和视神经炎。

结论

本研究中的患者患有COVID-19且有神经系统受累,包括广泛的临床表现。无论COVID-19诊断与神经系统体征发作之间的时间间隔如何,三分之一的脑脊液样本中检测到了SARS-CoV-2。这些情况涉及多种致病途径,SARS-CoV-2的神经侵袭潜力应进一步研究。

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