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

Completed
Conditions
Terson Syndrome
CSF-proteines
Subarachnoid Hemorrhage
Registration Number
NCT02129010
Lead Sponsor
Holger Joswig
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
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

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Intracranial pressure (ICP) in mmH20after insertion of EVD or ICP-probe (between day 0 and 3)

Initial ICP is measured in mmH20 after insertion of EVD with a riser tube or after insertion of an ICP-probe.

Secondary Outcome Measures
NameTimeMethod
Delayed cerebral ischemiaDaily for the duration of hospital stay, an expected average of 3 to 5 weeks

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).

Clinically manifest vasospasmDaily for the duration of hospital stay, an expected average of 3 to 5 weeks

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.

Concentration of CSF-protein phospho-tauDay 0, 2, 6

Concentration of CSF-protein phospho-tau taken from EVD-CSF

Re-bleedDaily for the duration of hospital stay, an expected average of 3 to 5 weeks

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).

Concentration of CSF-protein amyloid-ß 40/42Day 0, 2, 6

Concentration of CSF-protein phospho-tau taken from EVD-CSF

Necessity of CSF-shuntDaily for the duration of hospital stay, an expected average of 3 to 5 weeks

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.

Opthalmologic examDay 0 to 3; before discharge if initial exam negative

Occurrence of Terson syndrome is assessed by fundoscopy with chemically dilated pupils (number of patients of cohort).

Intraocular pressure (mmHg) is measured.

Surgery for refractory ICP (decompressive hemicraniectomy)Daily for the duration of hospital stay, an expected average of 3 to 5 weeks

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.

Trial Locations

Locations (1)

Cantonal Hospital St. Gallen

🇨🇭

St. Gallen, Switzerland

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