背景:特发性正常压力脑积水(iNPH)分流手术后神经化学变化与结果之间的关系,一种可治疗的痴呆和步态障碍,不清楚。我们使用基线心室CSF来探索与结果的关联,分流后,选择反映一系列病理生理过程的生物标志物。
方法:在119例iNPH患者中,在分流手术前后使用iNPH量表量化结果.围手术期收集心室CSF,并分析星形胶质细胞增生的生物标志物,轴突,淀粉样蛋白和tau病理,和突触功能障碍:胶质纤维酸性蛋白(GFAP),几丁质酶-3-样蛋白1(YKL40/CHI3L1),单核细胞趋化蛋白-1(MCP-1)神经丝光(NfL),淀粉样β38(Aβ38),Aβ40,Aβ42,淀粉样蛋白β42/40比例(Aβ42/40),可溶性淀粉样前体蛋白α(sAPPα),sAPPβ,总tau(T-tau),磷酸化tau(P-tau),生长相关蛋白43(GAP43),和神经颗粒素.
结果:与未改善患者相比,改善患者的神经颗粒蛋白浓度更高(68%)(中位数365ng/L(IQR186-544)vs330(205-456);p=0.046)。控制年龄的线性回归模型,性别和血管危险因素,包括神经颗粒素,T-tau,GFAP,结果调整后的R2=0.06,p=0.047。Aβ42/40比率在所有样品中呈双峰分布,以及改善和未改善患者的亚组,但对结局预测没有贡献。与高亚组(26,24-29)相比,低Aβ比率组(中位数25,IQR23-28)的术前MMSE评分较低(p=0.028)。T-TauxAβ40/42比率和P-tauxAβ40/42比率对分流反应预测没有贡献。血管危险因素的患病率并不影响分流反应。
结论:术前心室脑脊液中神经颗粒素水平较高,这是突触后标记,可能预示着良好的术后结局。一组心室CSF生物标志物的浓度仅解释了6%的结果变异性。淀粉样蛋白或tau病理的证据不影响结果。
BACKGROUND: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes.
METHODS: In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin.
RESULTS: The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186-544) vs 330 (205-456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23-28) compared to the high subgroup (26, 24-29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response.
CONCLUSIONS: A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.