[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

C H Ren, X Y Yang, Z M Liu, X W Zhuo, X D Han, L F Dai, X J Tian, W X Feng, L Ge, T L Han, C H Chen, F Fang
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Abstract

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

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22例SARS-CoV-2感染相关急性脑病临床特点及近期预后分析
目的:探讨SARS-CoV-2感染相关急性脑病(AE)患者的临床特点及近期预后。方法:回顾性队列研究。回顾性分析北京儿童医院神经内科2022年12月至2023年1月诊断为SARS-CoV-2感染相关AE的22例临床资料、影像学特征及短期随访。根据临床病理特征和影像学表现将患者分为细胞因子风暴组、兴奋性中毒性脑损伤组和未分型脑病组。描述性分析各组患者的临床特点。根据末次随访的改良Rankin量表(mRS)评分将患者分为预后良好组(≤2分)和预后不良组(>2分)。两组比较采用Fisher精确检验或Mann-Whitney U检验。结果:共纳入22例,其中女性12例,男性10例。发病年龄分别为3.3岁(1.7岁,8.6岁)。病史异常11例(50%),家族史异常4例。所有入组患者首发临床症状均为发热,发热后24小时内出现神经系统症状21例(95%)。发病的神经症状包括惊厥(17例)和意识障碍(5例)。病程中出现脑病22例,抽搐20例,言语障碍14例,不自主运动8例,共济失调3例。临床分型:细胞因子风暴组3例,均为急性坏死性脑病(ANE);兴奋毒性组9例,急性脑病伴两相癫痫发作伴晚期弥散减少(AESD) 8例,半痉挛-偏瘫综合征1例;未分型脑病10例。实验室检查显示谷胱甘肽转氨酶升高9例,谷丙转氨酶升高4例,血糖升高3例,d -二聚体升高3例。血清铁蛋白升高3例(5例),血清及脑脊液神经丝轻链蛋白升高5例(9例),血清细胞因子升高7例(18例),脑脊液细胞因子升高7例(8例)。颅内影像学异常18例,其中双侧对称病变3例,AESD呈“亮树样”8例。22例患者均接受对症治疗和免疫治疗(静脉注射免疫球蛋白或糖皮质激素),1例ANE患者接受托珠单抗治疗。随访50 (43,53)d,预后好10例,预后差12例。两组患者在流行病学、临床表现、生化指标、免疫治疗起始时间等方面比较,差异均无统计学意义(P>0.05)。结论:SARS-CoV-2感染也是AE的主要原因。AESD和ANE是常见的AE综合征。因此,及早发现伴有发热、惊厥、意识受损的AE患者,并给予积极治疗至关重要。
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