stroke

stroke Apoplexy or stroke has been recognized at least since the beginning of Western medicine, in ancient Greece. Stroke arises from injury to the brain caused by interruption of the blood supply, rather like a heart attack: in fact stroke is now sometimes called a ‘brain attack’. Over 250 000 people suffer some type of stroke in the UK each year. Stroke now is the third leading cause of death and the most common cause of adult disability.

The most typical manifestations include sudden weakness of the face, arm, or leg, and altered sensation or numbness, on the side of the body opposite the stroke. Language expression and comprehension can be impaired, usually for strokes in the left cerebral hemisphere. A stroke in the occipital lobe, at the back of the hemisphere, can cause blindness in the opposite half of the visual field. Sometimes a stroke in the parietal lobe of the right hemisphere renders the patient unable to attend to the left hand side of objects or even without awareness of the left side of their own body (the so-called neglect syndrome). Most bizarre of all, damage to the right hemisphere can produce anosagnosia — denial by the patient of any deficit at all, despite virtual paralysis of the left arm and leg.

The brain — especially the cerebral cortex, a frequent target of strokes — is divided into distinct regions, functionally specialized for one sense or another, for the control of movement, for aspects of language, etc. The sensory, motor, linguistic, and cognitive deficits caused by small strokes can therefore be extraordinarily specific, and their interpretation by neuropsychologists has been a major source of evidence about the organization of the human brain. But major strokes can have devastating effects, sometimes eliminating consciousness completely, or, perhaps even worse, leaving a conscious mind in a useless body. The French writer Jean-Dominique Bauby gives a unique view of this state in his autobiography — paralysed except for the capacity to blink an eye, he described himself as a ‘butterfly’ trapped inside a ‘diving bell’.

In 1761, Battista Morgagni, Professor of Anatomy in Padua, first clearly attributed strokes to limitation of blood flow to the brain. In 85% of cases this comes from blockage of a blood vessel giving a so-called ischaemic stroke. Most of the remaining 15% are due to sudden bleeding into the substance of the brain to create a haemorrhagic stroke. A small percentage are due to rupture of an artery in the surface of the brain — a subarachnoid haemorrhage.

The brain is metabolically highly active. Although it accounts for only about 2% of the body weight, it uses 20% of the total oxygen intake and has a high demand for the blood sugar, glucose. At least 15% of the blood output from the heart is needed to supply this amount of oxygen and glucose. If this blood flow is interrupted, even for minutes, then brain cells die. The pattern of clinical deficits after strokes (other than subarachnoid haemorrhage) is determined by the particular blood vessel that is primarily affected. Interruption of flow in the left middle cerebral artery, for example, typically leads to specific impairments of language or calculation, while occlusion of the right middle cerebral artery may disturb visual–spatial skills. Subarachnoid haemorrhages lead to changes in pressure on the brain and chemical effects that cause more general deficits.

The most common cause of ischaemic strokes is blocking of a vessel by a so-called embolus, which forms on a pathologically abnormal wall of a larger vessel and then detaches and circulates in the blood. The wall of the larger vessel, particularly in areas of high-flow turbulence and around major bifurcations (e.g. the point at which the internal carotid artery branches off from the aorta), may become thickened and irregular, and calcified atherosclerotic plaques may form. Rupture of these plaques can form a blood clot, fragments of which can be carried along the course of flowing blood to block smaller vessels. Alternatively, platelets that aggregate on the abnormal surface of a plaque, or fragments of the plaque, can themselves act as emboli. Emboli also can be formed in the heart, or, more rarely, can come from elsewhere in the body.

The risk of stroke is determined by both genetic and environmental influences. A number of specific risk factors include: a family history of stroke in first-degree relatives; older age; male sex; hypertension; smoking; diabetes; and heart disease.

Control of risk factors (e.g. giving up smoking, control of hypertension or diabetes, treatment of heart disease) can reduce the risk of stroke in affected individuals. The importance of hypertension has been recognized in a practical way since the time of Galen (c. ad 130–210), who advocated treatment of apoplexy with vigorous blood-letting.

Perhaps half or more of strokes are preceded by neurological symptoms (such as difficulty with speech or with movement of one hand) that last less than 12 hours and reverse completely. However, the risk of a full-blown stroke following these transient ischaemic attacks (TIAs) is similar to the risk that a stroke leaving persistent deficits will be followed by another (approximately 12% overall risk over 12 months). The precise risks vary substantially, however, depending on the underlying cause and the particular blood vessel involved.

Acute treatment of smaller ischaemic strokes is generally based on use of drugs that limit platelet aggregation, such as aspirin. Patients with occlusion of relatively large vessels, who reach medical care within the first few hours after the onset of deficits, may benefit from infusion of thrombolytic agents (clot-busters) such as tissue plasminogen activator (tPA) that can dissolve emboli and restore blood flow in the ischaemic area. This may benefit particularly the tissue at the outside of the core of the damage, in the so-called ischaemic penumbra, where the function of brain tissue is not irreversibly impaired.

Patients who survive their strokes without massive neurological deficits always show significant functional improvement. This occurs most rapidly over the first month after the stroke, but can continue for two years or more. The degree of recovery depends not only on the size of a stroke but also on its location. For example, small ischaemic strokes in the basal ganglia — nuclei deep in the cerebral hemispheres, involved in the control of movement — have a much better prognosis than strokes in the posterior limb of the internal capsule (see brain), which contains major nerve fibres running between the cerebral cortex and the rest of the brain.

Recovery is often complicated by less well-understood consequences of stroke, which illustrate the complex interconnectedness of brain functions. Alfred Brodal, the famous Danish neuroanatomist, observed in 1973 after his own small, ‘pure motor’ stroke that, in addition to difficulties moving one half of his body, he suffered from a ‘loss of powers of concentration, reduced short-term memory, increased fatigue, reduced initiative, [and] incontinence of movements of emotional expression’. Depression can also be a major problem. In part this is a consequence of the patient's perception of the new disability. Sir Peter Medawar, Nobel Laureate in Medicine, describes this well in personal reflections on his own stroke entitled Memoirs of a Thinking Radish (1986). Strokes can have direct effects on the balance of neurotransmitters in the brain that are responsible for mood.

Current experimental strategies for treatment in stroke are focusing simultaneously on several areas: safer and more effective ways of delivering thrombolytic therapy to patients, with particular attention to the possibility of rapid, on-the-spot treatment; neuroprotective agents, designed to guard the surrounding area of brain from the effects of neurotransmitters released by dying neurons following the initial damage of the stroke; and other experimental drugs, directed at limiting damage from the breakdown of nerve cell membranes and highly reactive oxygen radicals that are generated in the damaged tissue.

An intriguing possibility is that cells derived from bone marrow (stem cells) could be implanted surgically into areas of brain damaged by stroke, where they may be able to differentiate into new neurons that could take over functions of those that have been damaged.

Paul M. Matthews

Bibliography

Bauby, J.- D. (1998). The diving-bell and the butterfly. Fourth Estate, London.
Kapur, N. (1997). Injured brains of medical minds. Oxford University Press.
Porter, R. (1999). The greatest benefit to mankind. Fontain Press, London.

See also apoplexy; brain; language and the brain; paralysis.