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Predicting Secondary Stroke

PREDICTING SECONDARY DETERIORATION IN SUBARACHNOID HAEMORRHAGE

Division of Clinical Neurosciences – School of Medicine, University of Southampton

Principal investigator: Mr Antonio Belli – Senior Lecturer in Neurosurgery

Subarachnoid haemorrhage accounts for 10-15% of all strokes. This occurs when a cerebral vessel ruptures into the space surrounding the brain (subarachnoid space) causing spillage of blood into the cerebrospinal fluid. In about 80% of cases the cause is the rupture of an intracranial aneurysm, which an outpouching of the vessel wall; the remainder are due to bleeding from an arterio-venous malformation (a birth-mark on the surface of the brain) or no cause is found. Between 2% and 10% of the population harbour cerebral aneurysms but these are usually asymptomatic until they rupture.

Subarachnoid haemorrhage occurs in about 10 persons per 100,000 population each year and is more common in women than men. It can occur in any age group (including infants) but its peak is between the ages of 40 and 60 years. Therefore, it tends to affect a younger population than other forms of stroke and carries a disproportionally high toll in terms of productive life-years lost and social burden.

The clinical hallmark of SAH is a severe headache that starts suddenly. Approximately 12% of patients die before receiving medical attention due to the initial bleed or its immediate complications, 40% of hospitalised patients die within one month after the event and more than one third of those who survive have major neurological deficits and will be dependent on others for activities of daily living. The primary cause of this deterioration in hospitalized patient is a phenomenon called cerebral vasospasm. This is a narrowing of the arteries supplying the brain, triggered by the initial damage to the vessel and the spillage of blood around the surface of the brain, which releases chemicals that cause the artery to go into spasm. Vasospasm typically develops 3 to 10 days after the initial bleed and causes a stroke in the part of the brain supplied by that vessel.

There are number of ways of treating vasospasm but the key is to identify this complication before irreparable brain damage occurs. This can be particularly difficult, as many patients who have suffered a subarachnoid haemorrhage are either in a coma or anaesthetised in Neuro Intensive Care; in these cases, the stroke can usually develop undetected for several hours or days. At present the identification of vasospasm in comatose patients relies on investigative techniques that have limited applicability, either because they are majorly invasive or because they can only be repeated once or twice a day.

Mr Belli's group had been working on a novel technique called cerebral microdialysis. This is made of a small catheter (less than 1mm diameter) implanted in the brain and connected to small portable pump. The catheter collects very small samples (15 microlitres) of brain fluid in a continuous fashion. This fluid contains biochemical information on the state of the brain and several markers that indicate when vasospasm is developing. In essence, it could be likened to an on-line biochemical laboratory attached to the brain.

The team had collected information showing that these markers relate to early damage secondary to vasospasm, and their initial studies and those of other groups had shown that, because microdialysis information is available to clinicians on a continuous basis, vasospasm can be detected as soon as it occurs and can potentially be treated before irreversible damage occurs. However, this also relies on these biomarkers being sensitive (i.e. able to detect changes very early) and specific (i.e. not giving false information leading to patients being treated unnecessarily). For this reason more work on these novel markers was needed in order to improve the diagnostic accuracy of the system before it could be deemed sufficiently reliable for everyday use.

To this end, the WNCT awarded a sum of just over £40,000 from the Smile4Rich Appeal to Mr Belli's team to enable them to complete the analysis of some 2,500 samples from subarachoid haemorrhage patients. If successful, this research would directly benefit patients who have suffered one of the most devastating forms of stroke by reducing mortality and long-term disability.

The results of this analysis have clearly demonstrated the presence of two distinct chemical markers which could be used to predict the risk of secondary stroke. Further work in the form of a full clinical trial will now be needed before the technique can be fully exploited, and it is hoped that funding for this trial will be provided by other agencies.

The Brain Pulse Project