08 Feb 07

Several important observations on the causes, prediction and treatment of stroke - the leading cause of death and disability in the developed world - have been published by Oxford University's Stroke Prevention Research Unit in the Department of Clinical Neurology, led by Professor Peter Rothwell.

Researchers in the Unit have found that stroke is more likely to be inherited by women than men. The finding emerged from the most detailed ever large population-based study of the genetic epidemiology of stroke, as part of the Oxford Vascular Study, which is following nearly 100,000 people in Oxfordshire.

Stroke patients with a family history of stroke were two to three times more likely to be female than male, even though the overall occurrence of stroke is very similar in men and women. For some subtypes of stroke, families in which only women were affected were three times as common as families with only men affected. The excess heritability was confined to certain subtypes of ischaemic stroke, the causes of which are currently unclear. 'The observation has allowed us to focus our studies of potential genetic susceptibility to stroke on women and on particular stroke subtypes,' said Professor Rothwell. The findings were published in Lancet Neurology.

On stroke prediction and prevention, the Unit has previously demonstrated that in the days after a transient ischaemic attack (TIA, or 'mini-stroke'), there is a very high risk of major stroke, and that the benefit of preventive treatment falls substantially if delayed. The observations led to major changes in clinical management guidelines around the world. However, many healthcare systems, including the NHS, are unable to see all patients sufficiently quickly. The Unit has therefore devised risk scores to identify those most likely to go on to have a stroke, published in The Lancet in 2005. In a follow-up Lancet paper published this week, the group has refined the score and shown that it is highly predictive of stroke in several independent cohorts of UK and USA patients.

The Unit has also been carrying out a five-year project to determine how effective urgent intervention following TIA or minor strokes is in reducing the early risk of major stroke. The EXPRESS study's methods have just been published in The Lancet and the results will be known in summer 2007.

If stroke cannot be prevented, acute treatment is required to reduce death and severe disability. A major complication of large strokes, which has a very high death rate in young patients, is brain swelling and consequent increased pressure. The Unit has coordinated a pooled analysis of data from three independent ongoing trials of hemicraniectomy, an operation to temporarily remove a large part of the skull overlying the stroke in patients with brain swelling. 'Hemicraniectomy is a simple but novel way of allowing the brain to swell and thereby avoid the increased pressure within the skull that would otherwise usually kill the patient,' said Professor Rothwell. 'However, stroke specialists have been anxious that this treatment might avoid death but result in a very high rate of survival with extremely severe disability.'

The pooled analysis, published in Lancet Neurology, shows that hemicraniectomy reduced mortality from 78 per cent to 29 per cent, with 55 per cent of survivors after hemicraniectomy recovering to have only mild to moderate disability. Professor Rothwell said: 'This is an important result which opens the way for us to treat stroke patients with this very serious complication much more actively, rather than simply awaiting the inevitable.'