Department of Pulmonary and Infectious Diseases, Nordsjællands Hospital, 3400 Hillerød, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Brain. 2023 Sep 1;146(9):3816-3825. doi: 10.1093/brain/awad089.
Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
临床特征适用于病毒脑膜炎的整个谱是有限的,不良预后的预后因素尚未确定。这项全国性基于人群的前瞻性队列研究包括了丹麦所有 2015 年至 2020 年间疑似和微生物学确诊的病毒性脑膜炎的成年人。使用修正后的泊松回归分析了出院后 30 天不良结局(格拉斯哥结局量表评分 1-4)的预后因素。总共包括了 1066 例病毒性脑膜炎发作,每年每 100000 人中有 4.7 例。病原体为肠道病毒 419/1066(39%)、单纯疱疹病毒 2 型 171/1066(16%)、水痘-带状疱疹病毒 162/1066(15%)、其他病毒 31/1066(3%)和 283/1066(27%)未确定。中位年龄为 33 岁(IQR 27-44),1066 例中有 576/1066(54%)为女性。单纯疱疹病毒 2 型脑膜炎中,131/171(77%)为女性。免疫抑制[162/162(20%)]和带状疱疹[90/149(60%)]在水痘-带状疱疹病毒脑膜炎中很常见。1066 例中有 264/960(28%)存在头痛、颈强直和听觉过敏或畏光三联征。腰椎穿刺的中位时间为 3.0 小时(IQR 1.3-7.1),脑脊液白细胞计数的中位数为 160 个/µl(IQR 60-358)。出院后 30 天,1055 例中有 216/1055(20%)预后不良。以未确定病原体为参照,肠道病毒、单纯疱疹病毒 2 型、水痘-带状疱疹病毒和其他病毒不良结局的调整相对风险分别为 1.34(95%CI 0.95-1.88)、1.55(95%CI 1.00-2.41)、1.51(95%CI 0.98-2.33)和 1.37(95%CI 0.61-3.05)。女性不良结局的调整相对风险为 1.34(95%CI 1.03-1.75)。阿昔洛韦或伐昔洛韦的给药时间与单纯疱疹病毒 2 型或水痘-带状疱疹病毒引起的脑膜炎结局无关。总之,不同病因的病毒性脑膜炎患者的结局相似,包括那些被诊断为病毒性脑膜炎但未确定病原体的患者。女性不良结局的风险增加。早期抗病毒治疗与单纯疱疹病毒 2 型或水痘-带状疱疹病毒引起的脑膜炎结局改善无关。