Wagner Judith N, Kalev Ognian, Sonnberger Michael, Krehan Ingomar, von Oertzen Tim J
Department of Neurology 1, Kepler University Hospital, Linz, Austria.
Department of Neuropathology, Kepler University Hospital, Linz, Austria.
Front Neurol. 2018 Jun 8;9:434. doi: 10.3389/fneur.2018.00434. eCollection 2018.
The differential diagnosis of autoimmune and infectious encephalitis is notoriously difficult. For this study, we compare the presenting clinical symptoms and paraclinical test results of autoimmune and infectious encephalitis patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has recently been published. We test these Graus criteria on our cohort for diagnostic sensitivity and specificity within the first week of presentation. We included all patients seen at our department within a 10-year-period who were diagnosed with encephalitis. The discharge diagnoses served as the reference standard for testing the clinical algorithm for two conditions: use of all the clinical information available on a patient during the first week of hospital admission assuming undefined autoantibody status and microbiological test results (C1) vs. consideration of all the information available on a patient, including the results of serological and microbiological testing (C2). Eighty-four patients (33 autoimmune, 51 infectious encephalitis) were included in the study. Fifty-one (17 autoimmune, 34 infectious) had a definite clinical diagnosis. The two groups differed significantly for the presence of headache, fever, epileptic seizures, and CSF cell-count at presentation. Application of the clinical algorithm resulted in a low sensitivity (58%) and very low specificity (8%) for the diagnosis of possible autoimmune encephalitis. The latter increased considerably in the subgroups of probable and definite autoimmune encephalitis. Whereas the sensitivity of the individual diagnostic categories was clearly time-dependent, the specificity rested foremost on the knowledge of the results of microbiological testing. Anti-CASPR2- and -LGI1-associated autoimmune encephalitis and tick-borne virus encephalitis presented particular diagnostic pitfalls. We define clinical symptoms and paraclinical test results which prove valuable for the differentiation between infectious and autoimmune encephalitis. Sensitivity and specificity of the clinical algorithm clearly depended on the amount of time passed after hospital admission and knowledge of microbiological test results. Accepting this limitation for the acute setting, the algorithm remains a valuable diagnostic aid for antibody-negative autoimmune encephalitis or in resource-poor settings. The initiation of immune therapy however should not be delayed if an autoimmune etiology is considered likely, even if the diagnostic criteria of the algorithm are not (yet) fulfilled.
自身免疫性脑炎和感染性脑炎的鉴别诊断极具难度。在本研究中，我们比较了自身免疫性脑炎和感染性脑炎患者的初始临床症状及辅助检查结果。近期已发布了一种用于诊断自身免疫性脑炎的临床算法。我们在队列中对这些格劳斯标准进行测试，以评估其在发病第一周内诊断的敏感性和特异性。我们纳入了在10年期间于我院就诊且被诊断为脑炎的所有患者。出院诊断作为检验两种情况临床算法的参考标准：一种是假定自身抗体状态不明且考虑微生物检测结果，使用患者入院第一周可获取的所有临床信息（C1）；另一种是考虑患者可获取的所有信息，包括血清学和微生物检测结果（C2）。本研究共纳入84例患者（33例自身免疫性脑炎，51例感染性脑炎）。51例（17例自身免疫性脑炎，34例感染性脑炎）有明确的临床诊断。两组在发病时头痛、发热、癫痫发作及脑脊液细胞计数方面存在显著差异。应用该临床算法诊断可能的自身免疫性脑炎时敏感性较低（58%），特异性极低（8%）。在可能的和明确的自身免疫性脑炎亚组中，后者显著提高。虽然各个诊断类别的敏感性明显与时间相关，但特异性主要取决于微生物检测结果的知晓情况。抗接触蛋白相关蛋白2（CASPR2）和富含亮氨酸胶质瘤失活蛋白1（LGI1）相关的自身免疫性脑炎以及蜱传病毒性脑炎存在特殊的诊断陷阱。我们明确了对于区分感染性脑炎和自身免疫性脑炎有价值的临床症状和辅助检查结果。临床算法的敏感性和特异性明显取决于入院后经过的时间以及微生物检测结果的知晓情况。尽管在急性情况下存在这一局限性，但该算法对于抗体阴性的自身免疫性脑炎或资源匮乏地区仍是一种有价值的诊断辅助工具。然而，如果认为自身免疫病因很可能存在，即便该算法的诊断标准尚未满足，免疫治疗的启动也不应延迟。
