The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus.
The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus.
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DOI：
10.1002/art.27458
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发表时间：
2010-07
影响因子：
--
通讯作者：
Roldan, Carlos A.
中科院分区：
文献类型：
--
作者：
Brooks, William M.;Sibbitt, Wilmer L., Jr.;Kornfeld, Mario;Jung, Rex E.;Bankhurst, Arthur D.;Roldan, Carlos A.
本研究确定了神经精神系统性红斑狼疮（NPSLE）脑神经代谢物改变的组织病理学基础。采用磁共振波谱法（MRS）对7例NPSLE患者的20个脑体素进行了脑神经代谢物浓度的测定。测定N-乙酰天冬氨酸（NAA）、胆碱、Cre和乳酸的绝对神经代谢物浓度。死亡后，在脑尸检时确定组织病理学变化，并逐体素匹配神经代谢物。NAA（对照：12.2± 0.8mM，NPSLE：9.15± 1.78mM; p<0.01）和Cre（对照：6.90±0.60mM，NPSLE：6.43± 0.16mM; p<0.01）的绝对浓度。0.003）显著降低，并且胆碱水平（对照：1.92±0.32mM，NPSLE：2.51± 0.42mM; p<0.04）显著升高。脑内存在广泛的异质性组织学变化，包括微梗死、微血管病变、轻度血管病血栓性血管病伴血小板和纤维蛋白血栓、各种消退状态下的神经元坏死、轴突和神经元数量减少、纤维间空泡和间隙形成、少突胶质细胞、反应性小胶质细胞和星形胶质细胞数量减少、脂质负载巨噬细胞和囊肿形成。神经代谢物异常与潜在的脑组织病理学改变密切相关：1）胆碱升高与神经胶质增生、血管病变和水肿独立相关（多变量模型：r = 0.75，p = 0.004）; 2）Cre减少，神经元轴突密度和神经胶质增生减少（多变量模型：r = 0.72，p = 0.002）; 3）NAA减少，神经元-轴突密度减少（0多变量模型：r = 0.66，p = 0.001），和4）乳酸与坏死，微血管和水肿（多变量模型：r = 0.996，p = 0.0001）。MRS改变的神经代谢物是一个严重的预后迹象，表明严重的潜在组织学脑损伤。
The present study determined the histopathologic basis of altered brain neurometabolites in neuropsychiatric systemic lupus erythematosus (NPSLE). Brain neurometabolite concentrations in 20 voxels of brain were determined pre-mortem by magnetic resonance spectroscopy (MRS) in 7 individuals with NPSLE. Absolute neurometabolite concentrations for N-acetylaspartate (NAA), choline, Cre, and lactate were measured. After death, histopathologic changes were determined at brain autopsy, and matched to neurometabolites voxel by voxel. Absolute concentrations of NAA (Controls: 12.2±0.8 mM, NPSLE: 9.15±1.78 mM; p<0.01) and Cre (Controls: 6.90±0.60mM, NPSLE: 6.43±0.16 mM; p<0. 0.003) were significantly reduced, and levels choline (Controls: 1.92±0.32mM, NPSLE: 2.51±0.42 mM; p<0.04) were significantly elevated. Widespread heterogeneous histological changes in brain were present, including microinfarcts, microhemorrhages, bland angiopathy thrombotic angiopathy with platelet and fibrin thrombi, neuronal necrosis in various states of resolution, reduced numbers of axons and neurons, vacuole and space formation among the fibers, reduced numbers of oligodendrocytes, reactive microglia and astrocytes, lipid-laden macrophages, and cyst formation. Neurometabolite abnormalities were closely associated with underlying brain histopathologic changes: 1) elevated choline was independently associated with gliosis, vasculopathy, and edema (multivariate model: r = 0.75, p = 0.004); 2) reduced Cre with reduced neuronal-axonal density and gliosis (multivariate model: r = 0.72, p = 0.002); 3) reduced NAA with reduced neuronal-axonal density (0multivariate model: r = 0.66, p = 0.001), and 4) lactate with necrosis, microhemorrhages, and edema (multivariate model: r = 0.996, p = 0.0001). Altered neurometabolites by MRS are a grave prognostic sign indicating serious underlying histologic brain injury.
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影响因子：
--
作者：
HOPKINS, P;BELMONT, HM;ABRAMSON, SB
通讯作者：
ABRAMSON, SB
影响因子：
158.5
作者：
FALK, RJ;DALMASSO, AP;MICHAEL, A
通讯作者：
MICHAEL, A
影响因子：
5.7
作者：
Jung, RE;Haier, RJ;Brooks, WM
通讯作者：
Brooks, WM
影响因子：
19.7
作者：
LUYTEN, PR;DENHOLLANDER, JA
通讯作者：
DENHOLLANDER, JA
影响因子：
--
作者：
Chinn, RJS;Wilkinson, ID;Harrison, MJG
通讯作者：
Harrison, MJG