新冠后持续神经精神症状患者的神经元和神经胶质代谢异常：一项脑质子磁共振波谱研究。
Neuronal and Glial Metabolite Abnormalities in Participants With Persistent Neuropsychiatric Symptoms After COVID-19: A Brain Proton Magnetic Resonance Spectroscopy Study.
机构信息
Department of Diagnostic Radiology and Nuclear Medicine, School of Medicine, University of Maryland.
Department of Neurology, School of Medicine, Johns Hopkins University.
出版信息
J Infect Dis. 2023 Nov 28;228(11):1559-1570. doi: 10.1093/infdis/jiad309.
BACKGROUND
The aim of this study was to determine whether neurometabolite abnormalities indicating neuroinflammation and neuronal injury are detectable in individuals post-coronavirus disease 2019 (COVID-19) with persistent neuropsychiatric symptoms.
METHODS
All participants were studied with proton magnetic resonance spectroscopy at 3 T to assess neurometabolite concentrations (point-resolved spectroscopy, relaxation time/echo time = 3000/30 ms) in frontal white matter (FWM) and anterior cingulate cortex-gray matter (ACC-GM). Participants also completed the National Institutes of Health Toolbox cognition and motor batteries and selected modules from the Patient-Reported Outcomes Measurement Information System.
RESULTS
Fifty-four participants were evaluated: 29 post-COVID-19 (mean ± SD age, 42.4 ± 12.3 years; approximately 8 months from COVID-19 diagnosis; 19 women) and 25 controls (age, 44.1 ± 12.3 years; 14 women). When compared with controls, the post-COVID-19 group had lower total N-acetyl compounds (tNAA; ACC-GM: -5.0%, P = .015; FWM: -4.4%, P = .13), FWM glutamate + glutamine (-9.5%, P = .001), and ACC-GM myo-inositol (-6.2%, P = .024). Additionally, only hospitalized patients post-COVID-19 showed age-related increases in myo-inositol, choline compounds, and total creatine (interaction P = .029 to <.001). Across all participants, lower FWM tNAA and higher ACC-GM myo-inositol predicted poorer performance on several cognitive measures (P = .001-.009), while lower ACC-GM tNAA predicted lower endurance on the 2-minute walk (P = .005).
CONCLUSIONS
In participants post-COVID-19 with persistent neuropsychiatric symptoms, the lower-than-normal tNAA and glutamate + glutamine indicate neuronal injury, while the lower-than-normal myo-inositol reflects glial dysfunction, possibly related to mitochondrial dysfunction and oxidative stress in Post-COVID participants with persistent neuropsychiatric symptoms.
背景
本研究旨在确定患有持续性神经精神症状的新冠肺炎（COVID-19）患者是否存在提示神经炎症和神经元损伤的神经代谢物异常。
方法
所有参与者均在 3T 磁共振上进行质子磁共振波谱检查，以评估额白质（FWM）和前扣带回皮质-灰质（ACC-GM）的神经代谢物浓度（点分辨光谱，弛豫时间/回波时间=3000/30ms）。参与者还完成了美国国立卫生研究院认知和运动功能测试工具箱以及患者报告结局测量信息系统的选定模块。
结果
共评估了 54 名参与者：29 名新冠肺炎后（平均年龄±标准差，42.4±12.3 岁；距 COVID-19 诊断约 8 个月；19 名女性）和 25 名对照组（年龄，44.1±12.3 岁；14 名女性）。与对照组相比，新冠肺炎后组的总 N-乙酰化合物（tNAA；ACC-GM：-5.0%，P=0.015；FWM：-4.4%，P=0.13）、FWM 谷氨酸+谷氨酰胺（-9.5%，P=0.001）和 ACC-GM 肌醇（-6.2%，P=0.024）水平降低。此外，仅新冠肺炎后住院患者的 ACC-GM 肌醇、胆碱化合物和总肌酸与年龄呈正相关（交互 P=0.029 至 <0.001）。在所有参与者中，FWM tNAA 降低和 ACC-GM 肌醇升高与多项认知测量结果较差相关（P=0.001-0.009），而 ACC-GM tNAA 降低与 2 分钟步行耐力降低相关（P=0.005）。
结论
在患有持续性神经精神症状的新冠肺炎后患者中，低于正常的 tNAA 和谷氨酸+谷氨酰胺表明神经元损伤，而低于正常的肌醇则反映了神经胶质功能障碍，可能与持续性神经精神症状的 COVID-19 患者中的线粒体功能障碍和氧化应激有关。
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