The Pathogenesis of Terson Syndrome and the Role of CSF Tau / Amyloid-ß 40 and 42 in Patients With Aneurysmatic Subarachnoid Hemorrhage

Subarachnoid Hemorrhage Clinical Trial

Official title:

The Pathogenesis of Terson Syndrome and the Role of CSF Tau / Amyloid-ß 40 and 42 in Patients With Aneurysmatic Subarachnoid Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02129010
• Other study ID #: ICPTS-Sma-2012
• Status: Completed
• Phase: N/A
• First received: April 27, 2014
• Last updated: March 7, 2016
• Start date: April 2013
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Cantonal Hospital of St. Gallen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ethikkommission des Kantons St. Gallen (Ethics Committee of the Canton of St. Gallen) Switzerland:
• Study type: Observational

Clinical Trial Summary

Prospective clinical study to investigate the pathogenesis of Terson syndrome and the prognostic value of the CSF-biomarkers tau-protein and amyloid-β 40 and 42 in patients with aneurysmatic subarachnoid hemorrhage. Our two hypotheses are as follows:

1. The incidence of Terson syndrome correlates with the initial intracranial opening pressure (measured with extra ventricular drain)

2. The CSF-biomarkers correlate with the outcome assessed at discharge, 3-, 6- and 12-months postictally using Glasgow-Outcome-Scale-Extended (GOSE) and Euro-Qol-5 as well as with complications related to aneurysmatic subarachnoid hemorrhage such as cerebral vasospasm, delayed cerebral ischemia and re-bleed.

Description:

In this prospective clinical study the pathogenesis of Terson syndrome and the prognostic value of the CSF-biomarkers tau-proteine and amyloid-β 40 and 42 in patients with aneurysmatic subarachnoidal hemorrhage are investigated. Intracranial opening pressure will be measured in patients requiring CSF-diversion for acute hydrocephalus and correlated with the incidence of Terson syndrome tested by an opthalmologic exam (group A: Terson syndrome positive, group B: Terson syndrome negative). CSF samples from external ventricular drainages are obtained at day 0, 2 and 6 and concentration of tau-protein and amyloid-β 40 and 42 are determined and correlated to secondary outcome measures such as delayed cerebral ischemia, clinical vasospasm, re-bleed, necessity for surgical intervention secondary to raised intracranial pressure or CSF-diversion. Outcome in terms of Glasgow-Outcome-Scale-Extended and Euro-Qol-5 will be assessed at 3, 6 and 12 months.

CSF from patients undergoing diagnostic or therapeutic tapping of their internal ventricles for normal pressure hydrocephalus or shunt diagnostics serve as a reference for CSF-biomarkers concentration in healthy individuals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• older than 18 years

• diagnosis of subarachnoid hemorrhage secondary to an intracranial aneurysm

• aneurysmatic subarachnoid hemorrhage must be the principal diagnosis for hospitalization

• an intracranial aneurysm must be confirmed by imaging (Computed tomography, magnet resonance tomography or angiography)

• Patients requiring diagnostic/therapeutic tapping of their internal ventricles for CSF-diversion (shunt) for normal pressure hydrocephalus or shunt diagnostics serve as a control group

• informed consent

Exclusion Criteria:

• younger than 18 years

• other diagnosis such as traumatic or perimesencephalic subarachnoid hemorrhage without an intracranial aneurysm

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• CSF-proteines
• Hemorrhage
• Subarachnoid Hemorrhage
• Syndrome
• Terson Syndrome

Locations

Country	Name	City	State
Switzerland	Cantonal Hospital St. Gallen	St. Gallen

Sponsors (2)

Lead Sponsor	Collaborator
Holger Joswig	Innogenetics N.V., Belgium

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glasgow-Outcome-Scale-Extended (GOSE)	Health outcome is assessed by the study physicians or a study nurse using the Glasgow-Outcome-Scale-Extended (GOSE) with the help of family members if necessary.	initial, 3, 6, 12 months after SAH	No
Other	Life quality (Euro-Qol-5)	Life quality is assessed by the study physicians or a study nurse using the Euro-Qol-5 questionnaire with the help of family members if necessary.	initial, 3, 6, 12 months after SAH	No
Other	Neuropsychological deficits	The Montreal Cognitive Assessment (MoCA) is performed at day 14 days. A neuropsychological assessment by a neuropsychologist will then be performed at 3 and 12 months after SAH and includes a combination of the following tests: Alertness (Testbatterie zur Aufmerksamkeitsprüfung, TAP 2.2), Go/Nogo (TAP 2.2), Geteilte Aufmerksamkeit (TAP 2.2), Deux Barrage (2002), Farbe-Wort-Interferenztest (FWIT, after J.R. Stroop, 1985), Regensburger Wortflüssigkeitstest (RWT (2000)), 5-Punkte-Test (HAMASCH, H5PT-R), Frontal Assessment Battery Bedside (FAB), Verbaler Lern- und Merkfähigkeitstest (VLMT), Rey Complex Figure Test (RCFT (1995)), Tiere-Wörter-Test of the test battery Consortium to Establish A Registry for Alzheimer (CERAD), Boston Naming Test (CERAD), Mini-Mental-Status-Examination (CERAD), Trail-Making-Test A (CERAD) and B (CERAD), S-Wörter-Test (CERAD), Apraxie-Prüfung (Goldenberg). Patients' cognitive status is graded as no (regular), or as minimal, moderate or severely disabled.	On day 14 and at 3 and 12 months	No
Primary	Intracranial pressure (ICP) in mmH20	Initial ICP is measured in mmH20 after insertion of EVD with a riser tube or after insertion of an ICP-probe.	after insertion of EVD or ICP-probe (between day 0 and 3)	No
Secondary	Concentration of CSF-protein phospho-tau	Concentration of CSF-protein phospho-tau taken from EVD-CSF	Day 0, 2, 6	No
Secondary	Concentration of CSF-protein amyloid-ß 40/42	Concentration of CSF-protein phospho-tau taken from EVD-CSF	Day 0, 2, 6	No
Secondary	Delayed cerebral ischemia	For the duration of their hospital stay (which can be expected to be an average of 3 to 5 weeks for SAH patients), occurrence of delayed cerebral schema, diagnosed by CT or MRI, is noted (number of patients of cohort).	Daily for the duration of hospital stay, an expected average of 3 to 5 weeks	No
Secondary	Clinically manifest vasospasm	For the duration of their hospital stay (which can be expected to be an average of 3 to 5 weeks for SAH patients), occurrence of clinically manifest vasospasm is noted (number of patients of cohort). Screening will be performed daily by transcranial doppler and confirmation of diagnosis done by CTA or angiography.	Daily for the duration of hospital stay, an expected average of 3 to 5 weeks	No
Secondary	Re-bleed	For the duration of their hospital stay (which can be expected to be an average of 3 to 5 weeks for SAH patients), occurrence of an intracranial re-bleed, diagnosed by CT or MRI, is noted (number of patients of cohort).	Daily for the duration of hospital stay, an expected average of 3 to 5 weeks	No
Secondary	Surgery for refractory ICP (decompressive hemicraniectomy)	For the duration of their hospital stay (which can be expected to be an average of 3 to 5 weeks for SAH patients), the need for surgery for refractory ICP (decompressive hemicraniectomy) is noted (number of patients of cohort). Indication for surgery is made by the treating staff consultant based on ICP, CPP and clinical status.	Daily for the duration of hospital stay, an expected average of 3 to 5 weeks	No
Secondary	Necessity of CSF-shunt	For the duration of their hospital stay (which can be expected to be an average of 3 to 5 weeks for SAH patients), the need for permanent CSF-diversion is noted (number of patients of cohort). Indication for permanent CSF-diversion (usually a ventriculoperitoneal shunt) is made by the treating staff consultant based on radiographic and clinical signs of hydrocephalus secondary to SAH.	Daily for the duration of hospital stay, an expected average of 3 to 5 weeks	No
Secondary	Opthalmologic exam	Occurrence of Terson syndrome is assessed by fundoscopy with chemically dilated pupils (number of patients of cohort).; Intraocular pressure (mmHg) is measured.	Day 0 to 3; before discharge if initial exam negative	No

External Links

•   Study synopsis