致命性神经精神性系统性红斑狼疮中神经代谢物异常的组织病理学关联
The histopathologic associates of neurometabolite abnormalities in fatal neuropsychiatric systemic lupus erythematosus.
作者信息
Brooks William M, Sibbitt Wilmer L, Kornfeld Mario, Jung Rex E, Bankhurst Arthur D, Roldan Carlos A
机构信息
University of Kansas Medical Center, Kansas City, USA.
出版信息
Arthritis Rheum. 2010 Jul;62(7):2055-63. doi: 10.1002/art.27458.
OBJECTIVE
To determine the histopathologic basis of altered brain neurometabolites in neuropsychiatric systemic lupus erythematosus (NPSLE).
METHODS
Brain neurometabolite concentrations in a 20-voxel area of the brain were determined premortem by magnetic resonance spectroscopy (MRS) in 7 individuals with NPSLE. Absolute concentrations of neurometabolite for N-acetylaspartate (NAA), choline, creatine, and lactate were measured. After the death of the patients, histopathologic changes were determined at autopsy of the brain and were matched voxel-by-voxel with the neurometabolites.
RESULTS
The mean +/- SD absolute concentrations of NAA (9.15 +/- 1.78 mM in patients versus 12.2 +/- 0.8 mM in controls; P < 0.01) and creatine (6.43 +/- 0.16 mM in patients versus 6.90 +/- 0.60 mM in controls; P < 0.003) were significantly reduced and the concentration of choline (2.51 +/- 0.42 mM in patients versus 1.92 +/- 0.32 mM in controls; P < 0.04) was significantly elevated in NPSLE patients as compared with controls. Widespread heterogeneous changes in the histologic features of the 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 histopathologic changes in the brain: 1) elevated choline levels were independently associated with gliosis, vasculopathy, and edema (r = 0.75, P < 0.004 in the multivariate model); 2) reduced creatine levels with reduced neuronal-axonal density and gliosis (r = 0.72, P < 0.002 in the multivariate model); 3) reduced NAA levels with reduced neuronal-axonal density (r = 0.66, P < 0.001 in the multivariate model); and 4) the presence of lactate with necrosis, microhemorrhages, and edema (r = 0.996, P < 0.0001 in the multivariate model).
CONCLUSION
Altered neurometabolites in NPSLE patients, as determined by MRS, are a grave prognostic sign, indicating serious underlying histologic brain injury.
目的
确定神经精神性系统性红斑狼疮（NPSLE）患者脑神经元代谢物改变的组织病理学基础。
方法
对7例NPSLE患者在生前通过磁共振波谱（MRS）测定脑内20个体素区域的脑神经元代谢物浓度。测量N-乙酰天门冬氨酸（NAA）、胆碱、肌酸和乳酸的神经元代谢物绝对浓度。患者死亡后，对脑进行尸检以确定组织病理学变化，并将其与神经元代谢物逐体素匹配。
结果
与对照组相比，NPSLE患者的NAA平均±标准差绝对浓度（患者为9.15±1.78 mM，对照组为12.2±0.8 mM；P<0.01）和肌酸（患者为6.43±0.16 mM，对照组为6.90±0.60 mM；P<0.003）显著降低，胆碱浓度（患者为2.51±0.42 mM，对照组为1.92±0.32 mM；P<0.04）显著升高。脑的组织学特征存在广泛的异质性变化，包括微梗死、微出血、单纯性血管病、伴有血小板和纤维蛋白血栓的血栓性血管病、处于不同消退状态的神经元坏死、轴突和神经元数量减少、纤维间液泡和间隙形成、少突胶质细胞数量减少、反应性小胶质细胞和星形胶质细胞、富含脂质的巨噬细胞以及囊肿形成。神经元代谢物异常与脑的潜在组织病理学变化密切相关：1）胆碱水平升高与胶质增生、血管病和水肿独立相关（多变量模型中r=0.75，P<0.004）；2）肌酸水平降低与神经元-轴突密度降低和胶质增生相关（多变量模型中r=0.72，P<0.002）；3）NAA水平降低与神经元-轴突密度降低相关（多变量模型中r=0.66，P<0.001）；4）乳酸的存在与坏死、微出血和水肿相关（多变量模型中r=0.996，P<0.0001）。
结论
通过MRS测定，NPSLE患者神经元代谢物改变是一个严重的预后指标，表明存在严重的潜在脑组织结构损伤。
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