Clinical trial NCT02129010: The Pathogenesis of Terson Syndrome and the Role of CSF Tau / Amyloid-ß 40 and 42 in Patients With Aneurysmatic Subarachnoid Hemorrhage
Official title: The Pathogenesis of Terson Syndrome and the Role of CSF Tau / Amyloid-ß 40 and 42 in Patients With Aneurysmatic Subarachnoid Hemorrhage
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Subarachnoid Hemorrhage
Terson Syndrome
CSF-proteines
Keywords: subarachnoid hemorrhage
terson syndrome
CSF-proteines
phospho-tau
beta-amyloid
Lead sponsor: Cantonal Hospital of St. Gallen
Sponsor class: OTHER
Collaborators: name: Innogenetics N.V., Belgium
First posted: 2014-05-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with aneurysmatic subarachnoid hemorrhage requiring CSF-diversion and/or intracranial pressure monitoring

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intracranial pressure (ICP) in mmH20
timeFrame: after insertion of EVD or ICP-probe (between day 0 and 3)
Secondary outcomes:
measure: Concentration of CSF-protein phospho-tau
timeFrame: Day 0, 2, 6
measure: Concentration of CSF-protein amyloid-ß 40/42
timeFrame: Day 0, 2, 6
measure: Delayed cerebral ischemia
timeFrame: Daily for the duration of hospital stay, an expected average of 3 to 5 weeks
measure: Clinically manifest vasospasm
timeFrame: Daily for the duration of hospital stay, an expected average of 3 to 5 weeks
measure: Re-bleed
timeFrame: Daily for the duration of hospital stay, an expected average of 3 to 5 weeks
measure: Surgery for refractory ICP (decompressive hemicraniectomy)
timeFrame: Daily for the duration of hospital stay, an expected average of 3 to 5 weeks
measure: Necessity of CSF-shunt
timeFrame: Daily for the duration of hospital stay, an expected average of 3 to 5 weeks
measure: Opthalmologic exam
timeFrame: Day 0 to 3; before discharge if initial exam negative
Other outcomes:
measure: Glasgow-Outcome-Scale-Extended (GOSE)
timeFrame: initial, 3, 6, 12 months after SAH
measure: Life quality (Euro-Qol-5)
timeFrame: initial, 3, 6, 12 months after SAH
measure: Neuropsychological deficits
timeFrame: On day 14 and at 3 and 12 months
Locations:
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
Study officials:
affiliation: Cantonal Hospital St. Gallen, Dept. of Neurosurgery
name: Holger Joswig, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joswig H, Fournier JY, Hildebrandt G, Stienen MN. Sentinel Headache: A Warning Sign Preceding Every Fourth Aneurysmal Subarachnoid Hemorrhage. AJNR Am J Neuroradiol. 2015 Sep;36(9):E62-3. doi: 10.3174/ajnr.A4467. Epub 2015 Jul 16. No abstract available.