Division of Neurology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Division of Respiratory Disease, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Medicine (Baltimore). 2022 Oct 21;101(42):e31029. doi: 10.1097/MD.0000000000031029.
Acute encephalopathy is a severe neurological complication of coronavirus disease 2019 (COVID-19). Most cases of acute encephalopathy associated with COVID-19 occur within several weeks of COVID-19 onset. We describe a case series of 6 patients who developed delayed encephalopathy (DE) after COVID-19.
We evaluated patients who recovered from COVID-19 and showed acute disturbance of consciousness or focal neurological deficits without recurrence of pneumonitis. Six patients, 2 females and 4 males, with ages ranging from 65 to 83 years were included. Durations of hospitalization due to COVID-19 were between 25 and 44 days. The severity of COVID-19 was moderate in 5 and severe in 1 patient. Patients were rehospitalized for acute disturbance of consciousness concomitant with postural tremor and, abnormal behavior, hemiplegia, aphasia, or apraxia between 34 and 67 days after the onset of COVID-19. Chest computed tomography showed no exacerbation of pneumonitis. Brain magnetic resonance imaging showed no specific findings except in 1 patient with an acute lacunar infarction. Electroencephalogram demonstrated diffuse slowing in all patients. Repeat electroencephalogram after recovery from encephalopathy demonstrated normal in all patients. One of the 6 patients had cerebrospinal fluid (CSF) pleocytosis. CSF protein levels were elevated in all patients, ranging from 51 to 115 mg/dL. CSF interleukin-6 levels ranged from 2.9 to 10.9 pg/mL. The immunoglobulin index was 0.39 to 0.44. Qlim(alb) < QAlb indicating dysfunction of the blood-brain barrier was observed in all patients. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction of CSF was negative in all patients. Neuronal autoantibodies were absent in serum and CSF.
Immunotherapy including steroid pulses was administered to 3 patients; however, symptoms of encephalopathy resolved within several days in all patients, regardless of treatment with immunotherapy, and their consciousness levels were recovered fully. Notably, postural tremor remained for 2 weeks to 7 months.
In our patients, DE after COVID-19 was characterized by symptoms of acute encephalopathy accompanied with tremor in the absence of worsening pneumonitis after the fourth week of COVID-19 onset. Our findings indicate blood-brain barrier dysfunction may contribute to the pathogenesis of DE after COVID-19.
急性脑病是 2019 年冠状病毒病（COVID-19）的一种严重神经系统并发症。大多数与 COVID-19 相关的急性脑病发生在 COVID-19 发病后的数周内。我们描述了 6 例 COVID-19 后发生迟发性脑病（DE）的病例系列。
我们评估了从 COVID-19 中康复且出现急性意识障碍或局灶性神经功能缺损但无肺炎复发的患者。6 名患者为女性 2 例，男性 4 例，年龄 65-83 岁。COVID-19 住院时间为 25-44 天。5 例患者的 COVID-19 严重程度为中度，1 例为重度。患者在 COVID-19 发病后 34-67 天因急性意识障碍伴有体位性震颤、异常行为、偏瘫、失语或失用症再次住院。胸部计算机断层扫描显示肺炎无恶化。脑磁共振成像除 1 例急性腔隙性梗死患者外无特异性发现。所有患者脑电图均显示弥漫性减慢。所有患者在脑病恢复后复查脑电图均正常。6 例患者中有 1 例脑脊液（CSF）白细胞增多。所有患者 CSF 蛋白水平升高，范围为 51-115mg/dL。CSF 白细胞介素-6 水平为 2.9-10.9pg/mL。免疫球蛋白指数为 0.39-0.44。所有患者均存在 Qlim(alb)<QAlb，表明血脑屏障功能障碍。所有患者 CSF 严重急性呼吸综合征冠状病毒 2 逆转录聚合酶链反应均为阴性。血清和 CSF 中均未检测到神经元自身抗体。
3 例患者接受免疫治疗，包括类固醇冲击治疗；然而，所有患者的脑病症状均在数天内缓解，无论是否接受免疫治疗，且意识水平完全恢复。值得注意的是，体位性震颤持续 2 周至 7 个月。
在我们的患者中，COVID-19 后 DE 的特征是急性脑病症状伴有震颤，在 COVID-19 发病后第 4 周无肺炎恶化。我们的发现表明，血脑屏障功能障碍可能导致 COVID-19 后 DE 的发病机制。
