The Role of Neurofilament Light (NfL) in Patients With Hydrocephalus

Study Overview
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Brief Summary
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Neurofilament Light Chain Protein (NfL) has been found by many studies as a sensitive biomarker of neuronal damage from several reasons, e.g. neurodegenerative diseases (Alzheimer's disease, Multiple Sclerosis, etc.), inflamation (HIV) or trauma. Its role as biomarker thus offers a possibility to predict and manage diseases associated with neuronal damage. Therefore our aim is to investigate the changes in level of NfL in hydrocephalus and to find its role in management of treatment in hydrocephalus.

Official Title
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The Role of Neurofilament Light (NfL) in Management of Patients With Hydrocephalus: A Pilot Study

Conditions
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Hydrocephalus, Brain Damage, General Anesthetics Toxicity

Intervention / Treatment
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* Diagnostic Test: Lumbar puncture
* Diagnostic Test: External lumbar drainage
* Diagnostic Test: Lumbar infusion test
* Procedure: Ventriculo-peritoneal shunt placement
* Procedure: General Anesthesia
* Procedure: Prechamber puncture
* Procedure: Blood sampling #1
* Procedure: Blood sampling #2
* Procedure: Blood sampling #3
* Procedure: Blood sampling #4 and #5


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In group A: Patients with diagnosed communicating hydrocephalus MMSE > 10 points Absence of any structural laesion on MRI or CT Accepted Informed consent In group B: MMSE > 10 points Absence of any structural laesion on MRI or CT Accepted Informed consent Elective spinal surgery without affecting dural sac and the spinal cord Surgery shorter than 120 minutes of lasting the general anesthesia Exclusion Criteria: Non-communicating hydrocephalus Structural laesion on MRI or CT (tumour, contusion, aneurysm) MMSE < 10 points Life-expectancy shorter than 1 year Pre-existing other type of demetia (m. Alzheimer, vascular dementia) Surgery lasting more than 120 minutes Blood loss more than 500 ml Opening of dural sac (liquororhea) Adverse events during general anestesia: MAP<60 mm Hg more than 5 minutes, arythmia with need for farmacological treatment

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group A<br>Patients with diagnosed hydrocephalus undergoing surgery (VP shunt placement) in general anestezia. Before surgery patients undergo lumbar puncture or external lumbar drainage placement to confirmate the diagnosis and responsivity to VP shunt placement. | Diagnostic Test: Lumbar puncture<br>* Standardized lumbar puncture in L3/4 or L4/5 in diagnosis of hydrocephalus and CSF sampling (sample 1 in NfL level measurement)<br>Diagnostic Test: External lumbar drainage<br>* External lumbar drainage placement for assessing responsivity of external derivation of CSF. It is test of responsivity to ventriculo-peritoneal shunt placement<br>Diagnostic Test: Lumbar infusion test<br>* Diagnostic test accompanying the first lumbar puncture made as i diagnostic test of hydrocephalus. Based on infusion of saline by 90 mL per hour with measurement of CSF pressure each 1 minute and then count of so-called Rout (index).<br>Procedure: Ventriculo-peritoneal shunt placement<br>* Surgical procedure based on implantation a thin catheter into brain lateral ventricle (placed through a burrhole from Kocher point) and connection to prechamber and valve (placed behind the ear under skin) and similar thin catheter pushed under skin of neck, chest and abdomen (where put intraperitoneally).<br>Procedure: General Anesthesia<br>* Standardized combinated general anesthesia with combination of i.v. and inhalated drugs according the protocol. Given by anesthesiologist.<br>Procedure: Prechamber puncture<br>* Puncture of prechamber (place behind the ear under the skin) by thin needle and aspiration of 5 mL of CSF (5 days, 1 month a 2 months after surgery)<br>Procedure: Blood sampling #1<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours prior surgery<br>Procedure: Blood sampling #2<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours after surgery<br>Procedure: Blood sampling #3<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 5 days after surgery<br>Procedure: Blood sampling #4 and #5<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 1 and 2 months after surgery (only in interventional group)<br>|
| Active Comparator: Study group B<br>Patients without diagnosed hydrocephalus undergoing short spinal surgery without affecting dural sac (e.g. anterior cervical discectomy and fusion or lumbar disc herniation or lumbar decompression) in general anestezia. | Procedure: General Anesthesia<br>* Standardized combinated general anesthesia with combination of i.v. and inhalated drugs according the protocol. Given by anesthesiologist.<br>Procedure: Blood sampling #1<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours prior surgery<br>Procedure: Blood sampling #2<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours after surgery<br>Procedure: Blood sampling #3<br>* Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 5 days after surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | To assess the number of patients recruited in a pilot study. Recruitment rate is one of the predictor of feasibility of a study | 6 months | 
| Number of changes in valve settings | To investigate the number of changes in valve settings according the patient's clinical state based on clinical examination, CT examination or telemetrically measured CSF pressure | 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between NfL level and patient's clinical state | To investigate in group A the correlation between the level of NfL get from CSF and blood sampling and observation in changes in patient's clinical state measured by mini-mental state examination (MMSE), 5-meter-walking test and patient's self-assessment questionare | 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydrocephalus, Brain biomarkers, Neurofilament Light Chain, General Anesthesia