Role of Brain Specific Biomarkers in Hydrocephalus
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Comparison of levels of the mentioned biomarkers
研究概览
简要总结
Normal pressure hydrocephalus (NPH) is a neurodegenerative disease of unclear etiology characterized by a clinical trias named after the neurosurgeon Hakim. It includes cognitive impairment (dementia), gait disturbance, and urinary incontinence. These symptoms, which frequently occur in the elderly population, often overlap with the symptoms of "other" neurodegenerative diseases, especially Alzheimer's disease and other (pre)senile dementias. To distinguishing NPH from "other" dementias is crucial in determining whether a patient will benefit from a surgical procedure (ventriculoperitoneal shunt placement) or not. At the same time, the options for assessing the patient's condition's progression and distinguishing between the progression of neurodegeneration in a broader sense or malfunction of the drainage system are very limited. Therefore, the role of a biomarker that could meet these expectations mentioned above is highly desirable.
详细描述
Currently, several biomarkers of nerve tissue damage are being studied, which could potentially serve as sensitive and specific biomarkers in the future. These include Neurofilament Light Chain (NfL), Neuron-Specific Enolase (NSE), S100 protein, and tau protein.
A) Neurofilament Light Chain (NfL) and Neurofilament Heavy Chain (NfH):
Neurofilaments (Nfs) are cylindrical proteins found exclusively in neuronal cytoplasm. Under normal conditions, only low levels of the Neurofilament Light Chain (NfL) are released from axons. Elevated levels of NfL have been observed in response to axonal damage in the central nervous system (CNS) due to inflammatory, neurodegenerative, traumatic, or vascular causes, especially in older individuals. NfL is the most soluble subunit of neurofilaments, making its measurement more reliable than other subunits.
The concentration of NfL in cerebrospinal fluid is higher in patients with neurological disorders compared to healthy controls. Similar findings have been reported regarding NfL levels in serum. The role of NfL as a biomarker has been established in conditions such as multiple sclerosis (MS), Alzheimer's disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), atypical parkinsonian disorders (APD), and traumatic brain injury (TBI). It has also been studied to a lesser extent in Creutzfeldt-Jakob disease and neurological complications of HIV infection, where it reaches very high concentrations in cerebrospinal fluid, as well as in Huntington's disease (HD) and normotensive hydrocephalus (NPH or iNPH). Therefore, its implementation in clinical practice is gaining wider acceptance. There is a stronger correlation observed between NfL levels and ALS compared to NfH, although the role of NfH has not been as extensively established yet.
B) Protein S100:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with diagnosed communicating hydrocephalus
- •mini-mental state examination test > 10 points
- •Absence of any structural lesion on MRI or CT
- •Accepted Informed consent
排除标准
- •Non-communicating hydrocephalus
- •Structural lesion on MRI or CT (tumour, contusion, aneurysm)
- •mini-mental state examination test < 10 points
- •Life-expectancy shorter than 1 year
- •Pre-existing other type of dementia (m. Alzheimer, vascular dementia)
- •Surgery lasting more than 120 minutes
- •Blood loss more than 500 ml
- •Adverse events during general anesthesia: mean arterial pressure < 60 mm Hg more than 5 minutes, arrythmia with need for pharmacological treatment
结局指标
主要结局
Comparison of levels of the mentioned biomarkers
时间窗: 6 month
Comparison of levels of the mentioned biomarkers between patients with clinically proven shunt-responsive and shunt-nonresponsive hydrocephalus
次要结局
- Comparison of levels of the biomarkers during follow-up(6 month)
研究者
Miroslav Cihlo
Principal investigator
University Hospital Hradec Kralove