Chang L, Lee P L, Yiannoutsos C T, Ernst T, Marra C M, Richards T, Kolson D, Schifitto G, Jarvik J G, Miller E N, Lenkinski R, Gonzalez G, Navia B A
Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
Neuroimage. 2004 Dec;23(4):1336-47. doi: 10.1016/j.neuroimage.2004.07.067.
Differences in diagnostic criteria and methods have led to mixed results regarding the metabolite pattern of HIV-associated brain injury in relation to neurocognitive impairment. Therefore, a multicenter MRS consortium was formed to evaluate the neurometabolites in HIV patients with or without cognitive impairment.
Proton magnetic resonance spectroscopy (MRS) at short-echo time (30 ms) was assessed in the frontal white matter, basal ganglia, and parietal cortex of 100 HIV patients [61 with AIDS dementia complex (ADC) and 39 neuroasymptomatic (NAS)] and 37 seronegative (SN) controls.
Compared to SN, NAS had higher glial marker myoinositol-to-creatine ratio (MI/Cr) in the white matter (multivariate analyses, adjusted P=0.001), while ADC showed further increased MI/Cr in the white matter and basal ganglia (both P<0.001), and increased choline compounds (Cho)/Cr in white matter (P=0.04) and basal ganglia (P<0.001). Compared to NAS, ADC showed a reduction in the neuronal marker N-acetyl compound (NA)/Cr in the frontal white matter (P=0.007). CSF, but not plasma, viral load correlated with MI/Cr and Cho/Cr in white matter and NAA/Cr in parietal cortex. HIV infection and aging had additive effects on Cho/Cr and MI/Cr in the basal ganglia and white matter.
The results suggest that glial activation occurs during the NAS stages of HIV infection, whereas further inflammatory activity in the basal ganglia and neuronal injury in the white matter is associated with the development of cognitive impairment. Aging may further exacerbate brain metabolites associated with inflammation in HIV patient and thereby increase the risk for cognitive impairment.
诊断标准和方法的差异导致了关于HIV相关脑损伤代谢物模式与神经认知障碍关系的研究结果不一。因此,成立了一个多中心磁共振波谱(MRS)联盟,以评估有或无认知障碍的HIV患者的神经代谢物。
对100例HIV患者[61例患有艾滋病痴呆综合征(ADC)和39例神经无症状(NAS)]以及37例血清学阴性(SN)对照者的额叶白质、基底神经节和顶叶皮质进行短回波时间(30 ms)的质子磁共振波谱(MRS)评估。
与SN相比,NAS在白质中的胶质细胞标志物肌醇与肌酸比值(MI/Cr)更高(多变量分析,校正P = 0.001),而ADC在白质和基底神经节中的MI/Cr进一步升高(均P < 0.001),并且在白质(P = 0.04)和基底神经节(P < 0.001)中的胆碱化合物(Cho)/Cr升高。与NAS相比,ADC在额叶白质中的神经元标志物N - 乙酰化合物(NA)/Cr降低(P = 0.007)。脑脊液而非血浆病毒载量与白质中的MI/Cr和Cho/Cr以及顶叶皮质中的NAA/Cr相关。HIV感染和衰老对基底神经节和白质中的Cho/Cr和MI/Cr有累加效应。
结果表明,在HIV感染的NAS阶段发生胶质细胞激活,而基底神经节中进一步的炎症活动和白质中的神经元损伤与认知障碍的发展相关。衰老可能会进一步加剧HIV患者与炎症相关的脑代谢物,从而增加认知障碍的风险。