Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Fluids Barriers CNS. 2012 Mar 23;9(1):7. doi: 10.1186/2045-8118-9-7.
Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of dementia and gait disturbance that is typically treated by operative placement of a ventriculoperitoneal shunt. The outcome from shunting is variable, and some evidence suggests that the presence of comorbid Alzheimer's disease (AD) may impact shunt outcome. Evidence also suggests that AD biomarkers in cerebrospinal fluid (CSF) may predict the presence of AD. The aim of this study was to investigate the relationship between the phosphorylated tau/amyloid beta 1-42 (ptau/Aβ1-42) ratio in ventricular CSF and shunt outcome in patients with iNPH.
We conducted a prospective trial with a cohort of 39 patients with suspected iNPH. Patients were clinically and psychometrically assessed prior to and approximately 4 months after ventriculoperitoneal shunting. Lumbar and ventricular CSF obtained intraoperatively, and tissue from intraoperative cortical biopsies were analyzed for AD biomarkers. Outcome measures included performance on clinical symptom scales, supplementary gait measures, and standard psychometric tests. We investigated relationships between the ptau/Aβ1-42 ratio in ventricular CSF and cortical AD pathology, initial clinical features, shunt outcome, and lumbar CSF ptau/Aβ1-42 ratios in the patients in our cohort.
We found that high ptau/Aβ1-42 ratios in ventricular CSF correlated with the presence of cortical AD pathology. At baseline, iNPH patients with ratio values most suggestive of AD presented with better gait performance but poorer cognitive performance. Patients with high ptau/Aβ1-42 ratios also showed a less robust response to shunting on both gait and cognitive measures. Finally, in a subset of 18 patients who also underwent lumbar puncture, ventricular CSF ratios were significantly correlated with lumbar CSF ratios.
Levels of AD biomarkers in CSF correlate with the presence of cortical AD pathology and predict aspects of clinical presentation in iNPH. Moreover, preliminary evidence suggests that CSF biomarkers of AD may prove useful for stratifying shunt prognosis in patients being evaluated and treated for this condition.
特发性正常压力脑积水（iNPH）是一种潜在可逆转的痴呆和步态障碍的原因，通常通过手术放置脑室-腹腔分流管来治疗。分流的结果是可变的，一些证据表明合并阿尔茨海默病（AD）的存在可能会影响分流的结果。证据还表明，脑脊液（CSF）中的 AD 生物标志物可能预测 AD 的存在。本研究的目的是探讨脑室 CSF 中磷酸化 tau/淀粉样β 1-42（ptau/Aβ1-42）比值与 iNPH 患者分流结果之间的关系。
我们进行了一项前瞻性试验，纳入了 39 例疑似 iNPH 的患者。患者在脑室-腹腔分流术前和术后约 4 个月进行临床和心理测量评估。术中获得腰椎和脑室 CSF，并分析术中皮质活检组织中的 AD 生物标志物。评估指标包括临床症状量表、补充步态测量和标准心理测量测试的表现。我们研究了脑室 CSF 中 ptau/Aβ1-42 比值与皮质 AD 病理学、初始临床特征、分流结果以及我们队列中患者的腰椎 CSF ptau/Aβ1-42 比值之间的关系。
我们发现脑室 CSF 中的高 ptau/Aβ1-42 比值与皮质 AD 病理学的存在相关。在基线时，比值最提示 AD 的 iNPH 患者表现出更好的步态表现，但认知表现较差。ptau/Aβ1-42 比值较高的患者在步态和认知测量方面对分流的反应也较弱。最后，在 18 例也接受腰椎穿刺的患者亚组中，脑室 CSF 比值与腰椎 CSF 比值显著相关。
CSF 中的 AD 生物标志物水平与皮质 AD 病理学的存在相关，并预测 iNPH 患者的临床特征。此外，初步证据表明，AD 的 CSF 生物标志物可能有助于对接受评估和治疗该疾病的患者的分流预后进行分层。
