The spectrum of overlapping anti-NMDAR encephalitis and demyelinating syndromes: a systematic review of presentation, diagnosis, management, and outcomes

Anti-NMDAR encephalitis frequently overlaps with demyelinating diseases (MOGAD, NMOSD, MS), creating complex syndromes with diverse presentations and challenging management.
Systematic search of databases including MEDLINE, Google Scholar, Embase, Scopus, Cochrane Library, and Web of Science up to March 2024 for studies on co-existing anti-NMDAR encephalitis and demyelinating syndromes. Data extracted on clinical characteristics, diagnostics, treatments, and outcomes.
Twenty-five studies identified 256 patients (16.2%) with co-existing Anti-NMDAR encephalitis and demyelinating syndromes, primarily MOGAD (94.5%), with fewer cases involving NMOSD or MS. The Anti-NMDAR + MOGAD subgroup exhibited seizures (51–72.7%), psychiatric symptoms (45.5–71.4%), cognitive dysfunction (30.6%), and movement disorders (30.6%). All patients had CSF anti-NMDAR antibodies, with MOG (60%) or AQP4 (25%) antibodies. Use of standardized, cell-based assays and adherence to established criteria are essential to avoid false positives, particularly for MOG. MRI abnormalities were seen in 75% of patients. First-line immunotherapies were effective in 70% of cases; 80% of refractory cases responded to second-line therapies.
Anti-NMDAR encephalitis overlapping with demyelinating diseases is challenging. Tailored treatments based on detailed immune profiles are key to better outcomes.

抗NMDAR脑炎（Anti-NMDAR encephalitis）常与脱髓鞘疾病（包括MOG相关脱髓鞘疾病（MOGAD）、视神经脊髓炎谱系疾病（NMOSD）、多发性硬化（MS））重叠，形成临床表现多样、诊疗颇具挑战的复杂综合征。系统检索截至2024年3月的MEDLINE、Google Scholar、Embase、Scopus、Cochrane图书馆及Web of Science等数据库，搜集有关抗NMDAR脑炎与脱髓鞘综合征共病的研究文献，提取其中的临床特征、诊断方法、治疗方案及转归数据。最终纳入的25项研究共筛选出256例共病患者，占比16.2%，其中以MOGAD相关病例为主（占94.5%），NMOSD或MS相关病例较少。抗NMDAR脑炎合并MOGAD亚组患者的临床表现包括癫痫发作（51.0%~72.7%）、精神症状（45.5%~71.4%）、认知功能障碍（30.6%）及运动障碍（30.6%）。所有患者脑脊液（CSF）中均可检测到抗NMDAR抗体，同时伴MOG抗体（60%）或AQP4抗体（25%）。采用标准化细胞基检测法（cell-based assays）并严格遵循既定诊断标准，对于避免假阳性结果至关重要，尤其针对MOG抗体检测。75%的患者存在磁共振成像（MRI）异常。一线免疫治疗对70%的病例有效；80%的难治性患者可对二线免疫治疗产生应答。抗NMDAR脑炎与脱髓鞘疾病重叠的病例诊疗颇具挑战，基于精准免疫分型的个体化治疗是改善患者预后的关键。