Evolution of neurodegeneration in patients with normal pressure hydrocephalus: a monocentric follow up study.

Leonard L Klemke, Katharina Müller-Schmitz, Aschwin Kolman, Rüdiger J Seitz
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Abstract

Background: The aim of this study was to examine in patients with idiopathic and neurodegenerative normal pressure hydrocephalus (NPH) if motor and cognitive performance as well as changes in biomarkers in cerebrospinal fluid (CSF) evolve differently.

Methods: 41 patients with a typical clinical and MR-/CT-morphological presentation of NPH divided into an Alzheimer-negative (AD-, n = 25) and an Alzheimer-positive (AD+, n = 16) group according to neurodegenerative biomarkers (S100 protein, neuron-specific enolase, β-amyloid 1-42, Tau protein, phospho-Tau, protein-level and CSF pressure) in CSF. Follow-up of cognitive and gait functions before and after a spinal tap of 40-50 ml CSF of up to 49 months. Clinical, motor, neuropsychological and CSF biomarkers were analyzed using a repeated multifactorial analysis of variance (ANOVA) with post-hoc testing.

Results: Gait and neuropsychological performance and CSF biomarkers evolved differently between the AD- and AD+ patients. In particular, the AD+ patients benefited from the spinal tap regarding short-term memory. In contrast, gait parameters worsened over time in the AD+ patients, although they showed a relevant improvement after the first tap.

Conclusions: The results substantiate the recently reported association between a tap-responsive NPH and CSF changes of Alzheimer disease. Furthermore, they suggest that the AD changes in CSF manifest in an age-related fashion in AD- patients presenting with NPH.

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常压脑积水患者神经退行性变的演变:一项单中心随访研究。
背景:本研究的目的是检查特发性和神经退行性正常压力脑积水(NPH)患者的运动和认知表现以及脑脊液(CSF)中生物标志物的变化是否有不同的演变。方法:41例具有典型临床和MR-CT形态表现的NPH患者分为阿尔茨海默病阴性(AD- = 25)和阿尔茨海默病阳性(AD+ = 16) 根据CSF中的神经退行性生物标志物(S100蛋白、神经元特异性烯醇化酶、β-淀粉样蛋白1-42、Tau蛋白、磷酸化Tau、蛋白水平和CSF压力)分组。对40-50 ml CSF脊髓穿刺前后的认知和步态功能进行长达49个月的随访。临床、运动、神经心理学和CSF生物标志物使用重复多因素方差分析(ANOVA)和事后检验进行分析。结果:AD和AD+患者的步态、神经心理表现和CSF生物标志物的进化不同。特别是,AD+患者受益于关于短期记忆的脊椎穿刺。相比之下,AD+患者的步态参数随着时间的推移而恶化,尽管他们在第一次敲击后表现出了相关的改善。结论:研究结果证实了最近报道的敲击反应性NPH与阿尔茨海默病CSF变化之间的相关性。此外,他们认为,在伴有NPH的AD患者中,CSF中的AD变化以年龄相关的方式表现出来。
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