Staal Steven L, Ter Horst Liora, Brenner Juliette, van de Beek Diederik, Titulaer Maarten J, Brouwer Matthijs C
Department of Neurology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Neuroscience, the Netherlands; and.
Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200454. doi: 10.1212/NXI.0000000000200454. Epub 2025 Jul 16.
Long-term cognitive impairment is observed in 14%-32% of patients surviving community-acquired bacterial meningitis. We hypothesized that the impairment might be linked to secondary immune activation due to the development of neuronal autoantibodies, similar to postinfectious autoimmune encephalitis after viral encephalitis.
In this cross-sectional observational study, we included adult patients from a prospective, nationwide cohort study of community-acquired bacterial meningitis in the Netherlands, the MeninGene study. The presence of neuronal autoantibodies was evaluated in follow-up serum samples at 7 days, at 3 months, or over a year. Immunohistochemistry on complete rat brain slices was performed for the initial screening. If positive or ambiguous, immunocytochemistry using live primary rat hippocampal neurons and cell-based assays expressing extracellular targets were performed; immunoblots were used for intracellular targets.
In total, 118 patients were included, of whom 24 of 100 (24%) had cognitive impairment and 14 of 109 (13%) had focal neurologic deficits at discharge. Causative pathogens were in 98 patients (83%), in 4 (3%), and other pathogens in 6 (5%); in 10 patients (9%), no causative pathogen was identified. Two of 118 patients (2%) had neuronal autoantibodies in follow-up serum: 1 had leucine-rich glioma inactivated 1 antibodies, and 1 had unspecified antibodies. None of the patients was positive for NMDA receptor antibodies.
There was no clear evidence of postinfectious autoimmune encephalitis after bacterial meningitis. Therefore, acute brain damage caused by the infection itself seems to be the most plausible explanation for long-term cognitive impairment and neurologic disabilities.
在社区获得性细菌性脑膜炎存活患者中，14% - 32%会出现长期认知障碍。我们推测，这种障碍可能与神经元自身抗体产生导致的继发性免疫激活有关，类似于病毒性脑炎后的感染后自身免疫性脑炎。
在这项横断面观察性研究中，我们纳入了来自荷兰一项关于社区获得性细菌性脑膜炎的前瞻性全国队列研究（MeninGene研究）的成年患者。在7天、3个月或1年以上的随访血清样本中评估神经元自身抗体的存在情况。对完整大鼠脑切片进行免疫组织化学用于初步筛查。如果结果为阳性或不明确，则使用原代大鼠海马活神经元进行免疫细胞化学以及进行表达细胞外靶点的基于细胞的检测；对于细胞内靶点则使用免疫印迹法。
总共纳入了118例患者，其中100例中有24例（24%）在出院时有认知障碍，109例中有14例（13%）有局灶性神经功能缺损。98例患者（83%）的致病病原体为 ，4例（3%）为 ，6例（5%）为其他病原体；10例患者（9%）未鉴定出致病病原体。118例患者中有2例（2%）在随访血清中存在神经元自身抗体：1例有富含亮氨酸的胶质瘤失活1抗体，1例有未明确的抗体。所有患者的N - 甲基 - D - 天冬氨酸受体抗体均为阴性。
没有明确证据表明细菌性脑膜炎后存在感染后自身免疫性脑炎。因此，感染本身引起的急性脑损伤似乎是长期认知障碍和神经功能残疾最合理的解释。
