Guillem Lluïsa, Alia-Ramos Pedro, Gonzalez-Diaz Aida, Ardanuy Carmen, Boix-Palop Lucia, Van den Eynde Eva, Cabellos Carmen
Infectious Diseases Department, Department of Clinical Sciences, Hospital Universitari de Bellvitge-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, L'Hospitalet de Llobregat, 08907, Spain.
Clinical Biochemistry Department, Hospital Universitari de Bellvitge, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08907, Spain.
Sci Rep. 2025 May 6;15(1):15854. doi: 10.1038/s41598-025-99883-z.
Cerebrovascular complications are frequent in pneumococcal meningitis and are associated with poor functional outcomes. Among these complications, the incidence of cerebral vasculitis (CV) has been increasingly reported, but neither its pathogenesis nor its relationship with cortisone treatment have been conclusively established. We wanted to describe cerebrospinal fluid (CSF) metalloprotease (MMP) levels, which are linked to cerebral damage and vasculitis (MMP-2, MMP-9, and the antagonist TIMP-1), and differences in microbiological serotypes or virulence factors that could be associated to the development of this complication. A prospective multicenter cohort study was performed from January 2019 to August 2022. All adult patients diagnosed with pneumococcal meningitis and for whom CSF samples from the initial lumbar puncture were available were included and followed up for six months after discharge. Streptococcus pneumoniae strains isolated from CSF or blood were assessed including whole genome sequencing and CSF levels of MMP-2, MMP-9, and TIMP-1 were measured. CV developed in three of 21 patients (14.3%). The serotypes of those who developed CV were 3, 9 N, and 35 F, with no microbiological differences with respect to the non-CV group. The CV group had higher CSF levels of MMP-9 (13.2 vs. 9.8 ng/L) and TIMP-1 (699 vs. 318 ng/L), but lower CSF levels of MMP-2 (5689 vs. 10,484 ng/L) compared with the non-CV group. Although no patients with CV died, they had worse clinical outcomes than the non-CV group. CV is a frequent complication of pneumococcal meningitis that may be associated with worse outcomes. No differences in microbiological serotypes or virulence factors were detected. Further analyses should be carried out to confirm whether CSF MMP levels may be markers of CV development.
脑血管并发症在肺炎球菌性脑膜炎中很常见，且与功能预后不良相关。在这些并发症中，脑血管炎（CV）的发病率报告日益增多，但其发病机制及其与皮质激素治疗的关系尚未最终明确。我们想描述与脑损伤和血管炎相关的脑脊液（CSF）金属蛋白酶（MMP）水平（MMP-2、MMP-9和拮抗剂TIMP-1），以及可能与该并发症发生相关的微生物血清型或毒力因子的差异。2019年1月至2022年8月进行了一项前瞻性多中心队列研究。纳入所有诊断为肺炎球菌性脑膜炎且有初始腰椎穿刺脑脊液样本的成年患者，并在出院后随访6个月。对从脑脊液或血液中分离出的肺炎链球菌菌株进行评估，包括全基因组测序，并测量脑脊液中MMP-2、MMP-9和TIMP-1的水平。21例患者中有3例（14.3%）发生了CV。发生CV的患者血清型为3、9N和35F，与非CV组在微生物学上无差异。与非CV组相比，CV组脑脊液中MMP-9水平较高（13.2对9.8 ng/L）和TIMP-1水平较高（699对318 ng/L），但MMP-2脑脊液水平较低（5689对10484 ng/L）。虽然CV患者无死亡，但他们的临床结局比非CV组差。CV是肺炎球菌性脑膜炎的常见并发症，可能与更差的结局相关。未检测到微生物血清型或毒力因子的差异。应进行进一步分析以确认脑脊液MMP水平是否可能是CV发生的标志物。
