Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, Sahlgrenska University Hospital, 41345, Gothenburg, Sweden.
Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden.
Fluids Barriers CNS. 2023 Oct 25;20(1):77. doi: 10.1186/s12987-023-00475-8.
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.
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.
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 R = 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.
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.
神经化学变化与特发性正常压力脑积水（iNPH）患者分流术后结局的关系尚不清楚，iNPH 是一种可治疗的痴呆和步态障碍。我们使用基线脑室脑脊液来探讨一系列反映病理生理过程的生物标志物与分流术后结局的相关性。
对 119 例连续 iNPH 患者，使用 iNPH 量表在分流术前和术后评估其结局。在手术期间收集脑室脑脊液，并对星形胶质细胞增生、轴突、淀粉样蛋白和 tau 病理学以及突触功能障碍的生物标志物进行分析：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）、神经丝轻链（NfL）、β 淀粉样蛋白 38（Aβ38）、Aβ40、Aβ42、β 淀粉样蛋白 42/40 比值（Aβ42/40）、可溶性淀粉样前体蛋白 alfa（sAPPα）、sAPPβ、总 tau（T-tau）、磷酸化 tau（P-tau）、生长相关蛋白 43（GAP43）和神经颗粒蛋白。
与无改善的患者相比，改善的患者（68%）神经颗粒蛋白浓度更高（中位数 365ng/L（IQR 186-544）比 330（205-456）；p=0.046）。校正年龄、性别和血管危险因素（包括神经颗粒蛋白、T-tau 和 GFAP）后，线性回归模型的调整 R2=0.06，p=0.047。Aβ42/40 比值在所有样本中呈双峰分布，在改善和未改善的亚组中也是如此，但对结局预测没有贡献。与高 Aβ 比值亚组相比，低 Aβ 比值亚组的术前 MMSE 评分较低（中位数 25，IQR 23-28）（p=0.028）。T-Tau x Aβ40/42 比值和 P-tau x Aβ40/42 比值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。
术前脑室脑脊液中神经颗粒蛋白（一种突触后标志物）水平较高，可能预示着术后结局良好。一系列脑室脑脊液生物标志物的浓度仅解释了结局变异性的 6%。淀粉样蛋白或 tau 病理学的证据并不影响结局。
