Department of Neurology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Department of Neurology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
J Neurol. 2018 Mar;265(3):586-596. doi: 10.1007/s00415-018-8749-3. Epub 2018 Jan 22.
To report pitfalls in the clinical diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.
We retrospectively reviewed the clinical information of 221 patients with clinically suspected autoimmune neurological disorders who underwent testing for autoantibodies against neuronal cell-surface antigens between January 1, 2007 and September 10, 2017. Forty-one patients met the diagnostic criteria for probable anti-NMDAR encephalitis (probable criteria), but one was excluded because neither serum nor CSF was examined at the active stage. Thus, in 220 patients, sensitivity and specificity of the probable criteria were assessed.
NMDAR-antibodies were detected in 34 of 40 patients (85%) with the probable criteria; however, 2 of the 6 antibody-negative patients had ovarian teratoma. The median age at onset was higher in antibody-negative patients than those with antibodies (49 vs. 27 years, p = 0.015). The age at onset was associated with the probability of antibody detection (p = 0.014); the probability was less than 50% in patients aged 50 years or older. NMDAR-antibodies were also detected in 5 of 180 patients who did not fulfill the probable criteria; these patients presented with isolated epileptic syndrome (n = 2), atypical demyelinating syndrome (n = 2; one with aquaporin 4 antibodies), and autoimmune post-herpes simplex encephalitis (post-HSE) (n = 1). Sensitivity and specificity of the probable criteria was 87.2 and 96.7%, respectively.
The probable criteria are valid, but the diversity of clinical phenotype should be taken into account in diagnosing anti-NMDAR encephalitis particularly in patients aged 50 years or older, or with isolated epileptic syndrome, atypical demyelinating syndrome, or post-HSE.
报告抗 N-甲基-D-天冬氨酸受体（NMDAR）脑炎临床诊断中的陷阱。
我们回顾性分析了 2007 年 1 月 1 日至 2017 年 9 月 10 日期间接受神经元细胞表面抗原自身抗体检测的 221 例临床疑似自身免疫性神经疾病患者的临床资料。41 例符合抗 NMDAR 脑炎的可能诊断标准（可能标准），但由于在活动期未检测血清和脑脊液，有 1 例被排除。因此，我们评估了 220 例患者可能标准的敏感性和特异性。
在 40 例可能标准的患者中，34 例（85%）检测到 NMDAR 抗体；然而，6 例抗体阴性患者中有 2 例患有卵巢畸胎瘤。抗体阴性患者的发病年龄高于抗体阳性患者（49 岁比 27 岁，p=0.015）。发病年龄与抗体检测的可能性相关（p=0.014）；50 岁以上患者的可能性小于 50%。180 例不符合可能标准的患者中也检测到 NMDAR 抗体；这些患者表现为孤立性癫痫综合征（n=2）、非典型脱髓鞘综合征（n=2；1 例伴有水通道蛋白 4 抗体）和自身免疫性单纯疱疹病毒脑炎（HSVE）后（n=1）。可能标准的敏感性和特异性分别为 87.2%和 96.7%。
可能标准是有效的，但在诊断抗 NMDAR 脑炎时，应考虑到临床表型的多样性，特别是在 50 岁或以上的患者中，或有孤立性癫痫综合征、非典型脱髓鞘综合征或 HSVE 后。
