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

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

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 Summary:

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.


Sponsor: Holger Joswig

Current Primary Outcome: Intracranial pressure (ICP) in mmH20 [ Time Frame: after 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Concentration of CSF-protein phospho-tau [ Time Frame: Day 0, 2, 6 ]
    Concentration of CSF-protein phospho-tau taken from EVD-CSF
  • Concentration of CSF-protein amyloid-ß 40/42 [ Time Frame: Day 0, 2, 6 ]
    Concentration of CSF-protein phospho-tau taken from EVD-CSF
  • Delayed cerebral ischemia [ Time Frame: 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), occurrence of delayed cerebral schema, diagnosed by CT or MRI, is noted (number of patients of cohort).
  • Clinically manifest vasospasm [ Time Frame: 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), 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.
  • Re-bleed [ Time Frame: 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), occurrence of an intracranial re-bleed, diagnosed by CT or MRI, is noted (number of patients of cohort).
  • Surgery for refractory ICP (decompressive hemicraniectomy) [ Time Frame: 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.
  • Necessity of CSF-shunt [ Time Frame: 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 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 exam [ Time Frame: Day 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.



Original Secondary Outcome: Same as current

Information By: Cantonal Hospital of St. Gallen

Dates:
Date Received: April 27, 2014
Date Started: April 2013
Date Completion:
Last Updated: March 7, 2016
Last Verified: March 2016