Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Department of Neurology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Enfermedades Raras, Centro de Investigación Biomédica en Red, Madrid, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Lancet Neurol. 2022 Oct;21(10):899-910. doi: 10.1016/S1474-4422(22)00299-X.
Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers.
In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding.
Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p<0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated.
The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention.
Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation.
抗 N- 甲基-D- 天冬氨酸受体（NMDAR）脑炎与一个鲜为人知的急性期后阶段有关。我们旨在描述该阶段的临床特征、与精神分裂症谱系障碍的相似之处，以及预测认知-精神病学结果并可作为预后生物标志物的因素。
在这项前瞻性队列研究中，患有抗 NMDAR 脑炎的参与者（年龄 12-60 岁）在急性期后阶段三次就诊于巴塞罗那临床医院（西班牙巴塞罗那）：研究入组时（V1）、6 个月时（V2）和 12 个月时（V3），并接受全面的神经精神评估。在年龄匹配的精神分裂症谱系障碍组和年龄、性别匹配的健康对照组中也进行了类似的评估，这些对照组也是从巴塞罗那临床医院招募的。我们使用多级线性混合效应模型分析了组内和组间的纵向随访差异，并进行了调整，以控制组、年龄、性别和社会经济地位等因素的混杂影响。
2017 年 1 月 1 日至 2020 年 9 月 30 日，共招募了 82 名参与者，其中 28 名（34%）患有抗 NMDAR 脑炎，27 名（33%）患有精神分裂症谱系障碍，27 名（33%）为健康参与者。尽管到 V1（疾病发作后中位数 4 个月[IQR 3-7]）时，许多急性阶段的症状已经缓解（急性期 V1 改良 Rankin 量表评分中位数 5[IQR 4-5] vs V1 评分 2[1-2]；p<0·0001），但 25 名（89%）参与者仍存在至少一个认知领域的缺陷。在这一组中，22 个认知域变量中有 15 个（68%）在 V1 时受损，而只有 8 个（36%）在 V3 时改变（p=0·016）。在精神分裂症谱系障碍组中，22 个变量中有 11 个（50%）（均与抗 NMDAR 脑炎患者共有）在 V1 时受损，而在 V3 时没有变化。抗 NMDAR 脑炎的两个急性期特征（即意识下降和治疗前 4 周内无改善）预测了认知域的结果，而 V1 的一项视空间任务（即序列偏差）具有预测学习和记忆结果的潜力。在 V1 时，抗 NMDAR 脑炎和精神分裂症谱系障碍患者的所有精神病症状群均有类似改变，但只有抗 NMDAR 脑炎患者的症状随后改善（p=0·031）。抗 NMDAR 脑炎患者的认知-精神病学改善最大发生在 V1 到 V2 之间。在此期间，如果没有进行脑脊液抗体检测，4 名（14%）抗 NMDAR 脑炎患者将符合精神分裂症的诊断标准。
抗 NMDAR 脑炎急性期后的认知-精神病学症状类似于稳定期精神分裂症，但只有抗 NMDAR 脑炎患者的症状逐渐改善，主要发生在 V1-V2 期间。这些发现对抗 NMDAR 脑炎的临床试验很重要，并表明及时的认知-社会心理康复可能是一种有价值的干预措施。
西班牙卡洛斯三世健康研究所、欧洲神经科学研究资助网络、精神分裂症和情感障碍国家联盟、以及拉卡伊基金会。
