Tseng Pao-Hui, Huang Li-Chuan, Huang Xiang-Ling, Huang Bor-Ren, Lin Shinn-Zong, Tsai Sheng-Tzung, Huang Hsin-Yi
Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation.
Department of Nursing, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation.
Int J Surg. 2024 Nov 1;110(11):6962-6971. doi: 10.1097/JS9.0000000000002038.
Blood-brain barrier (BBB) breakdown is associated with neurodegeneration and cognitive impairment. Cerebral small vessel disease (CSVD) is also common in idiopathic normal pressure hydrocephalus (iNPH). Biomarkers in the cerebrospinal fluid (CSF) may reflect the severity of neuropathological damage and indicate a relationship between BBB integrity and iNPH and its surgical outcome. The authors investigated the association of CSVD and comorbidity-related CSF biomarkers with shunt outcomes in iNPH.
This prospective cohort study recruited 53 patients with iNPH, who were subgrouped by CSVD severity. CSF proteins were analyzed, including soluble platelet-derived growth factor receptor-β (sPDGFR-β), Alzheimer's disease biomarkers, neurofilament light chain (NfL), and triggering receptor expressed on myeloid cells 2 (Trem2). We assessed symptom improvement, investigated its association with biomarkers levels, calculated protein cutoffs for surgical outcomes using receiver operating characteristic (ROC) curves, and compared model predictions using different proteins through hierarchical regression analysis.
Among patients with iNPH, 74% had comorbid CSVD. Patients with severe CSVD exhibited significantly higher sPDGFR-β levels ( P =0.019) and better postoperative performance (β=0.332, t=2.174, P =0.039; r =0.573, P =0.001). Analysis of the predictive potential of the biomarkers showed that sPDGFR-β was predictive of surgical outcomes (area under curve=0.82, sensitivity=66.8%, specificity=94.7%). A Comparison of the models revealed a greater effect of sPDGFR-β (Adjusted R 2 =0.247, ∆R 2 =0.160, ∆F(1, 37)=8.238, P =0.007) on cognitive improvement.
This study highlighted the relevance of CSF biomarkers in assessing CSVD severity and predicting iNPH surgical outcomes. CSF shunt surgery may provide an alternative treatment for neurodegenerative diseases with BBB breakdown and dysfunctional CSF clearance.
血脑屏障（BBB）破坏与神经退行性变和认知障碍相关。脑小血管疾病（CSVD）在特发性正常压力脑积水（iNPH）中也很常见。脑脊液（CSF）中的生物标志物可能反映神经病理损伤的严重程度，并表明BBB完整性与iNPH及其手术结果之间的关系。作者研究了CSVD和合并症相关的脑脊液生物标志物与iNPH分流结果的关联。
这项前瞻性队列研究招募了53例iNPH患者，根据CSVD严重程度进行亚组划分。分析了脑脊液蛋白，包括可溶性血小板衍生生长因子受体-β（sPDGFR-β）、阿尔茨海默病生物标志物、神经丝轻链（NfL）和髓样细胞上表达的触发受体2（Trem2）。我们评估了症状改善情况，研究其与生物标志物水平的关联，使用受试者工作特征（ROC）曲线计算手术结果的蛋白临界值，并通过分层回归分析比较不同蛋白的模型预测。
在iNPH患者中，74%合并CSVD。重度CSVD患者的sPDGFR-β水平显著更高（P =0.019），术后表现更好（β=0.332，t=2.174，P =0.039；r =0.573，P =0.001）。对生物标志物预测潜力的分析表明，sPDGFR-β可预测手术结果（曲线下面积=0.82，敏感性=66.8%，特异性=94.7%）。模型比较显示，sPDGFR-β对认知改善的影响更大（调整后R²=0.247，∆R²=0.160，∆F(1, 37)=8.238，P =0.007）。
本研究强调了脑脊液生物标志物在评估CSVD严重程度和预测iNPH手术结果方面的相关性。脑脊液分流手术可能为伴有BBB破坏和脑脊液清除功能障碍的神经退行性疾病提供一种替代治疗方法。
