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

Sponsor

University Hospital Hradec Kralove (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05399602

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hydrocephalus Brain Damage General Anesthetics Toxicity	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	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

May 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study group A 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 Standardized lumbar puncture in L3/4 or L4/5 in diagnosis of hydrocephalus and CSF sampling (sample 1 in NfL level measurement) Diagnostic Test: External lumbar drainage External lumbar drainage placement for assessing responsivity of external derivation of CSF. It is test of responsivity to ventriculo-peritoneal shunt placement Diagnostic Test: Lumbar infusion test 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). Procedure: Ventriculo-peritoneal shunt placement 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). Procedure: General Anesthesia Standardized combinated general anesthesia with combination of i.v. and inhalated drugs according the protocol. Given by anesthesiologist. Procedure: Prechamber puncture 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) Procedure: Blood sampling #1 Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours prior surgery Procedure: Blood sampling #2 Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours after surgery Procedure: Blood sampling #3 Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 5 days after surgery Procedure: Blood sampling #4 and #5 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)
Active Comparator: Study group B 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 Standardized combinated general anesthesia with combination of i.v. and inhalated drugs according the protocol. Given by anesthesiologist. Procedure: Blood sampling #1 Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours prior surgery Procedure: Blood sampling #2 Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours after surgery Procedure: Blood sampling #3 Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 5 days after surgery

Arm

Intervention/Treatment

Experimental: Study group A

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

Standardized lumbar puncture in L3/4 or L4/5 in diagnosis of hydrocephalus and CSF sampling (sample 1 in NfL level measurement)

Diagnostic Test: External lumbar drainage

External lumbar drainage placement for assessing responsivity of external derivation of CSF. It is test of responsivity to ventriculo-peritoneal shunt placement

Diagnostic Test: Lumbar infusion test

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).

Procedure: Ventriculo-peritoneal shunt placement

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).

Procedure: General Anesthesia

Standardized combinated general anesthesia with combination of i.v. and inhalated drugs according the protocol. Given by anesthesiologist.

Procedure: Prechamber puncture

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)

Procedure: Blood sampling #1

Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours prior surgery

Procedure: Blood sampling #2

Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours after surgery

Procedure: Blood sampling #3

Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 5 days after surgery

Procedure: Blood sampling #4 and #5

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)

Active Comparator: Study group B

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

Standardized combinated general anesthesia with combination of i.v. and inhalated drugs according the protocol. Given by anesthesiologist.

Procedure: Blood sampling #1

Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours prior surgery

Procedure: Blood sampling #2

Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 24 hours after surgery

Procedure: Blood sampling #3

Blood sampling to get level of NfL from standarized percutaneous vein puncture by thin needle 5 days after surgery

Outcome Measures

Primary Outcome Measures

Recruitment rate [6 months]
To assess the number of patients recruited in a pilot study. Recruitment rate is one of the predictor of feasibility of a study
Number of changes in valve settings [3 months after surgery]
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

Secondary Outcome Measures

Correlation between NfL level and patient's clinical state [3 months after surgery]
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

Other Outcome Measures

Influence of general anesthesia on the level of NfL [24 hours before procedure (surgery) and 24 hours and 5 days after surgery]
In group B investigate the level of NfL 24 hours before surgery and 24 hours (blood sampling #2) and 5 days after surgery (blood sampling #3) and comparison with standardized NfL level based on literature. Looking for the influence of general anesthesia on brain damage caused and the prepair in predefined time frame.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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