From the Department of Neurology (C.V.S., M.T., A.M.) and Division of Microbiology (E.T., M.B.) and Neuroimmunology Laboratory (A.M.), Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Neurology. 2021 Dec 7;97(23):e2262-e2268. doi: 10.1212/WNL.0000000000012931. Epub 2021 Oct 11.
Autoimmune encephalitis (AE) cases after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, but the frequency is unknown. We aimed to determine the frequency and diagnostic features of coronavirus disease 2019 (COVID-19)-related AE.
Residual sera from 556 consecutive Mayo Clinic Rochester patients (laboratory cohort) who underwent autoimmune encephalopathy neural immunoglobulin G (IgG) evaluation were tested for total antibodies against the SARS-CoV-2 spike glycoprotein using a Food and Drug Administration-authorized chemiluminescence assay (October 2019-December 2020). Clinical records from patients with a positive SARS-CoV-2 antibody result and available research consent were reviewed. This laboratory cohort was cross-referenced with the Department of Neurology's COVID-19-related consultative experience (encephalopathy cohort, n = 31).
Eighteen of the laboratory cohort (3%) were SARS-CoV-2 antibody positive (April-December 2020). Diagnoses were as follows: AE, 2; postacute sequelae of SARS CoV-2 infection (PASC), 3; toxic-metabolic encephalopathy during COVID-19 pneumonia, 2; diverse non-COVID-19 relatable neurologic diagnoses, 9; unavailable, 2. Five of the encephalopathy cohort had AE (16%, including the 2 laboratory cohort cases that overlapped), representing 0.05% of 10,384 patients diagnosed and cared for with any COVID-19 illness at Mayo Clinic Rochester in 2020. The 5 patients met definite (n = 1), probable (n = 1), or possible (n = 3) AE diagnostic criteria; median symptom onset age was 61 years (range, 46-63); 3 were women. All 5 were neural IgG negative and 4 tested were SARS-CoV-2 PCR/IgG index negative in CSF. Phenotypes (and accompanying MRI and EEG findings) were diverse (delirium [n = 5], seizures [n = 2], rhombencephalitis [n = 1], aphasia [n = 1], and ataxia [n = 1]). No acute disseminated encephalomyelitis cases were encountered. The 3 patients with possible AE had spontaneously resolving syndromes. One with definite limbic encephalitis was immune therapy responsive but had residual mood and memory problems. One patient with probable autoimmune rhombencephalitis died despite immune therapy. The remaining 26 encephalopathy cohort patients had toxic-metabolic diagnoses.
We encountered occasional cases of AE in our 2020 COVID-19 experience. Consistent with sporadic reports and small case series during the COVID-19 pandemic, and prior experience of postinfectious AE, our cases had diverse clinical presentations and were neural IgG and CSF viral particle negative. Application of diagnostic criteria assists in differentiation of AE from toxic-metabolic causes arising in the setting of systemic infection.
有报道称，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染后会出现自身免疫性脑炎（AE）病例，但具体频率尚不清楚。我们旨在确定与 2019 年冠状病毒病（COVID-19）相关的 AE 的发生频率和诊断特征。
对 556 例连续接受梅奥诊所罗切斯特分院自身免疫性脑疾病神经免疫球蛋白 G（IgG）评估的患者的残留血清（实验室队列），使用经食品和药物管理局授权的化学发光测定法（2019 年 10 月至 2020 年 12 月）检测针对 SARS-CoV-2 刺突糖蛋白的总抗体。对 SARS-CoV-2 抗体检测结果阳性且有可用的研究同意书的患者的临床记录进行了回顾。将该实验室队列与神经病学系的 COVID-19 相关咨询经验（脑病队列，n = 31）进行交叉引用。
实验室队列中，有 18 例（3%）SARS-CoV-2 抗体阳性（2020 年 4 月至 12 月）。诊断如下：AE，2 例；SARS-CoV-2 感染后急性后遗症（PASC），3 例；COVID-19 肺炎期间的中毒性代谢性脑病，2 例；非 COVID-19 相关的多种神经诊断，9 例；无法确定诊断，2 例。脑病队列中有 5 例 AE（16%，包括与实验室队列中重叠的 2 例），这代表了 2020 年在梅奥诊所罗切斯特分院接受任何 COVID-19 疾病诊治的 10384 例患者中的 0.05%。这 5 例患者符合明确（n = 1）、可能（n = 1）或可能（n = 3）的 AE 诊断标准；中位症状出现年龄为 61 岁（范围：46-63 岁）；3 例为女性。所有 5 例患者的神经 IgG 均为阴性，4 例患者的脑脊液 SARS-CoV-2 PCR/IgG 指数均为阴性。表型（及伴随的 MRI 和 EEG 发现）多样（谵妄[n = 5]、癫痫发作[n = 2]、脑桥脑炎[n = 1]、失语[n = 1]和共济失调[n = 1]）。未发现急性播散性脑脊髓炎病例。3 例可能的 AE 患者的症状自发缓解。1 例明确的边缘性脑炎患者对免疫治疗有反应，但仍存在情绪和记忆问题。1 例自身免疫性脑桥脑炎患者尽管进行了免疫治疗，但仍死亡。剩余的 26 例脑病队列患者均为中毒性代谢性疾病。
我们在 2020 年 COVID-19 经验中偶尔会遇到 AE 病例。与 COVID-19 大流行期间的零星报告和小病例系列以及先前的感染后 AE 经验一致，我们的病例具有多种临床表现，神经 IgG 和脑脊液病毒粒子均为阴性。应用诊断标准有助于区分 AE 与系统感染时出现的中毒性代谢性病因。
