Cerebrospinal fluid (CSF) biomarkers in patients with vasospasm secondary to subarachnoid haemorrhage
Dr Alexios Adamides
Aneurysmal subarachnoid haemorrhage (aSAH) involves leakage of blood into the subarachnoid space which is secondary to the rupture of an aneurysm. In Australia, the incidence of aSAH is estimated at 10.3 cases per 100,000 persons per year. It has also been predicted that 450,000 to 1.4 million people may harbour unruptured aneurysms with over 2200 of these leading to an aneurysmal bleed very year. The outcome for patients with aneurysmal SAH is generally very poor as it is associated with a high mortality rate and an increased loss of productive years in patients younger than 65 years of age.
Cerebral vasospasm (CV) is a common complication after aSAH. Of the 2200 Australian patients suffering an aneurysmal bleed every year, approximately one third of these people will be affected by symptomatic CV, which can lead to the development of additional focal neurologic deficits causing secondary strokes and ultimately death. The precise mechanisms contributing to the development and progression of CV remain unknown, although factors such as vascular inflammation, smoking and hypertension have been implicated as influencing factors. Data generated from laboratory based studies are providing evidence that molecular regulatory processes may also contribute to the formation and rupture of aneurysms. However, as there are no established and reliable physiological biomarkers that may be used in diagnosis, progression of CV and ultimately, outcome prediction. There is an urgent need to identify potentially important molecules that can allow for the early detection and treatment of CV.
The aim of this on-going to study is to comprehensively screen cerebrospinal fluid (CSF) samples from SAH patients with / without CV and determine if there is a distinct set of biomarkers between patients who develop CV to those who do not develop vasospasm. Identification of a 'signature' following the development and progression of CV, will potentially allow for tailoring the subsequent clinical management a patient in the future.
We have established a comprehensive databse of biochemical, clinical and radiological data linked to CSF samples that have been collected. Our initial proteomics analysis has identified a number of proteins that may have predictive as well as therapeutic value. A pilot miRNA study of CSF samples identified 4 miRNA being differentially expressed between SAH patients who develop CV to those that do not develop CV. This is now being expanded into a larger study to validate the initial findings.
Professor Andrew Kaye, Neurosurgeon
Dr Stanley Stylli, Post-Doctoral Scientist
Associate Professor James Ziogas (University of Melbourne),
John T Reid Charitable Trusts
Friends of The Royal Melbourne Hospital Neuroscience Foundation
1. miRNA expression profiling of cerebrospinal fluid in patients with anuerysmal subarachnoid hemorrhage. Stylli SS, Adamides AA, Koldej RM, Luwor RB, Ritchie DS, Ziogas J, Kaye AH. J Neurosurg. 2016 Apr 29, 109. PMID: 27128592 DOI: 10.3171/2016.1.JNS151454
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