Körtvelyessy Peter, Prüss Harald, Thurner Lorenz, Maetzler Walter, Vittore-Welliong Deborah, Schultze-Amberger Jörg, Heinze Hans-Jochen, Reinhold Dirk, Leypoldt Frank, Schreiber Stephan, Bittner Daniel
Department of Neurology, University Hospital Magdeburg, Magdeburg, Germany.
German Center for Neurodegenerative Diseases Magdeburg, Magdeburg, Germany.
Front Neurol. 2018 Sep 19;9:668. doi: 10.3389/fneur.2018.00668. eCollection 2018.
Progranulin (PGRN), Total-Tau (t-tau), and Neurofilament light chain (NfL) are well known biomarkers of neurodegeneration. The objective of the present study was to investigate whether these parameters represent also biomarkers in autoimmune-mediated Encephalitis (AE) and may give us insights into the pathomechanisms of AE. We retrospectively examined the concentration of PGRN in the cerebrospinal fluid (CSF) and serum of 38 patients suffering from AE in acute phase and/or under treatment. This AE cohort comprises patients with autoantibodies against: NMDAR ( = 18 patients), Caspr2 ( = 8), Lgi-1 ( = 10), GABAB(R) ( = 1), and AMPAR ( = 1). Additionally, the concentrations of NfL ( = 25) and t-tau ( = 13) in CSF were measured when possible. Follow up data including MRI were available in 13 patients. Several age-matched cohorts with neurological diseases besides neuroinflammation or neurodegeneration served as control groups. We observed that PGRN was significantly elevated in the CSF of patients with NMDAR-AE in the acute phase, but normalized at follow up under treatment ( < 0.01). In the CSF of other patients with AE PGRN was in the range of the CSF levels of control groups. T-tau was highly elevated in the CSF of patients with temporal FLAIR-signal in the MRI and in patients developing a hippocampal sclerosis. NfL was exceptionally high initially in Patients with AE with a paraneoplastic or parainfectious cause and also normalized under treatment. The normalizations of all biomarkers were mirrored in an improvement on the modified Rankin scale. The data suggest that the concentration of PGRN in CSF might be a biomarker for acute NMDAR-AE. Pathological high t-tau levels may indicate a risk for hippocampal sclerosis. The biomarker properties of NfL remain unclear since the levels decrease under treatment, but it could not predict severity of disease in this small cohort. According to our results, we recommend to measure in clinical practice PGRN and t-tau in the CSF of patients with AE.
颗粒蛋白前体（PGRN）、总tau蛋白（t-tau）和神经丝轻链（NfL）是众所周知的神经退行性变生物标志物。本研究的目的是调查这些参数是否也是自身免疫介导性脑炎（AE）的生物标志物，并能否为我们提供有关AE发病机制的见解。我们回顾性检测了38例急性期和/或治疗期AE患者脑脊液（CSF）和血清中PGRN的浓度。该AE队列包括抗以下自身抗体的患者：N-甲基-D-天冬氨酸受体（NMDAR，18例患者）、接触蛋白相关蛋白2（Caspr2，8例）、富含亮氨酸胶质瘤失活蛋白1（Lgi-1，10例）、γ-氨基丁酸B型受体（GABAB(R)，1例）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR，1例）。此外，尽可能检测了25例患者CSF中NfL的浓度以及13例患者CSF中t-tau的浓度。13例患者可获得包括MRI在内的随访数据。几个除神经炎症或神经退行性变外患有神经系统疾病且年龄匹配的队列作为对照组。我们观察到，急性期NMDAR-AE患者CSF中PGRN显著升高，但治疗后随访时恢复正常（P<0.01）。其他AE患者CSF中PGRN处于对照组CSF水平范围内。MRI显示颞叶液体衰减反转恢复（FLAIR）信号的患者以及发生海马硬化的患者CSF中t-tau高度升高。伴有副肿瘤或副感染病因的AE患者最初NfL异常高，治疗后也恢复正常。所有生物标志物的恢复正常反映在改良Rankin量表评分的改善上。数据表明，CSF中PGRN的浓度可能是急性NMDAR-AE的生物标志物。病理性高t-tau水平可能表明存在海马硬化风险。NfL的生物标志物特性仍不清楚，因为其水平在治疗后降低，但在这个小队列中它无法预测疾病严重程度。根据我们的结果，我们建议在临床实践中检测AE患者CSF中的PGRN和t-tau。
