Archie Cochrane's challenge: can periodically updated reviews of all randomised controlled trials relevant to neurology and neurosurgery be produced?
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Humans↗
Biomedical subjects
P A Sandercock
Publications and source records attributed to P A Sandercock.
Uses of heparin. Withhold in acute ischaemic stroke.
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Acute Disease↗
Serial imaging of the carotid bifurcation and cerebrovascular reserve after carotid endarterectomy.
A radioisotopic method of quantifying mean cerebral transit time was used to assess the immediate effects of carotid endarterectomy on cerebrovascular reserve (CVR) in 69 patients. In addition, serial postoperative data were acquired on CVR, clinical status and non-invasive imaging of the internal carotid arteries in 56 patients over a period of 6-48 (median 24) months. Twenty-one patients (30 per cent) had preoperative evidence of impaired CVR in the symptomatic hemisphere. Within 4 days of surgery, however, reserve had returned to normal in 17 of the 21 patients. During follow-up, four of the 56 patients developed recurrent stenosis (> 50 per cent) or occlusion of the artery operated on but only two of these had impairment of CVR and none was symptomatic. Three patients suffered recurrent transient ischaemic attacks (TIAs) but none had recurrent internal carotid artery disease or impaired CVR. One patient suffered a TIA in the territory of the non-operated artery during follow-up in association with disease progression and CVR impairment. However, the TIA preceded recognition of either of these changes. Twelve other patients had (or developed) stenosis (> 50 per cent) in the non-operated artery during follow-up but none was symptomatic or developed impairment of CVR. Although assessment of CVR provided useful information on the frequency of haemodynamic compromise before carotid endarterectomy and on the natural history of disease progression, neither serial assessment of reserve nor non-invasive imaging of the carotid bifurcation influenced clinical practice during follow-up.
Blood Flow Velocity↗
Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials.
A formal statistical overview of all truly randomised trials was undertaken to determine whether antithrombotic therapy is effective and safe in the early treatment of patients with acute stroke. There were 15 completed randomised controlled trials of the value of early antithrombotic treatment in patients with acute stroke. The regimes tested in acute presumed or confirmed ischaemic stroke were: heparin, 10 trials with 1047 patients: oral anticoagulants, one trial with 51 patients: antiplatelet therapy, three trials with 103 patients. Heparin was tested in one trial with 46 patients with acute haemorrhagic stroke. Outcome measures were deep venous thrombosis (confirmed by I125 scanning or venography), pulmonary embolism, death from all causes, haemorrhagic transformation of cerebral infarction, level of disability in survivors. In patients with acute ischaemic stroke, allocation to heparin was associated with a highly significant 81% (SD 8, 2p < 0.00001) reduction in deep venous thrombosis detected by I125 fibrinogen scanning or venogram. Only three trials systematically identified pulmonary emboli, which occurred in 6/106 (5.7%) allocated control vs 3/132 (2.3%) allocated heparin, a non-significant 58% reduction (SD 45.7, 2p > 0.1). There were relatively few deaths in the trials in patients with presumed ischaemic stroke: 94/485 (19.4%) among patients allocated to the control group vs 79/497 (15.9%) among patients who were allocated heparin. The observed 18% (SD 16) reduction in the odds of death was not statistically significant. The least biased estimated of the effect of treatment on haemorrhagic transformation of the cerebral infarct (HTI) comes from trials where all patients were scanned at the end of treatment, irrespective of clinical deterioration; using this analysis, haemorrhagic transformation occurred in 7/102 (6.9%) control vs 8/106 (7.5%) treated, a non-significant 12% increase (SD 56, 2p > 0.1). These data cannot exclude the possibility that heparin substantially increases the risks of HTI. No data on disability in survivors could be obtained. Early heparin treatment might be associated with substantial reductions in deep venous thrombosis (and probably also pulmonary embolism) and possibly a one fifth reduction in mortality (equivalent to the avoidance of 20-40 early deaths per thousand patients treated.) However, the data were wholly inadequate on safety, particularly on the risk of haemorrhagic transformation of the infarct and on the hazards of heparin therapy in patients with known intracerebral haemorrhage. The trials of oral anticoagulants (15 deaths among 57 patients) and antiplatelet therapy (two deaths among 103 patients) were too small to be informative. Much larger randomized trials-comparing aspirin, heparin and the combination of both drugs against control-in patients with acute ischaemic stroke are justified (and several are now planned or underway).
Acute Disease↗
Interobserver reliability of a clinical classification of acute cerebral infarction.
BACKGROUND AND PURPOSE: The Oxfordshire Community Stroke Project (OCSP) clinical classification of subtypes of cerebral infarction (total and partial anterior circulation infarction, lacunar infarction, and posterior circulation infarction) can be used to predict early mortality, functional outcome, and whether the infarct was likely due to large- or small-vessel occlusion. The OCSP classification was originally developed and tested by neurologists as part of a community-based study of first-ever stroke, in which some cases were seen after the acute phase. We examined the interobserver reliability of the classification when used in everyday clinical practice in patients seen during the acute phase of stroke shortly after admission to the hospital. METHODS: Two clinicians independently assessed consecutive patients admitted to the hospital with an acute stroke and recorded both the neurological features and their opinion of the subtype of infarct. RESULTS: Eighty-five patients were assessed. Interobserver agreement for the classification was moderate to good (kappa = 0.54; 95% confidence interval, 0.39 to 0.68). Differences in the assessment of the commonly elicited neurological signs explained many of the disagreements: interobserver agreement was good for some signs (hemiparesis [kappa = 0.77], dysphasia [kappa = 0.70]), moderate for some (hemianopia [kappa = 0.39]), and poor for others (sensory loss [kappa = 0.15]). CONCLUSIONS: The classification was simple and practicable (and could be widely used in routine clinical practice, randomized controlled trials, and audit), and interobserver reliability was satisfactory.
Acute Disease↗
Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project.
BACKGROUND AND PURPOSE: There have been relatively few community-based studies of long-term prognosis after acute stroke. This study aimed to provide precise estimates of the absolute and relative risks of dying in an unselected cohort of patients with a first-ever stroke. METHODS: Six hundred seventy-five patients were registered by a community-based stroke register (the Oxfordshire Community Stroke Project) and prospectively followed up for up to 6.5 years. Their relative risk of death was calculated using age- and sex-specific mortality rates for Oxfordshire. RESULTS: During the first 30 days, 129 (19%) patients died. Patients who survived at least 30 days after a first-ever stroke thereafter had an average annual risk of death of 9.1%, 2.3-fold the risk in people from the general population. Although the absolute (about 15%) and relative (about threefold) risks of death were highest in these 30-day survivors over the first year after the stroke, they were at increased risk of dying over the next few years (range of relative risk for individual years, 1.1-2.9). Predictably, older patients had a worse absolute survival but, relative to the general population, stroke also increased the relative risk of dying in younger patients. During the first 30 days stroke accounts for most deaths; after this time nonstroke cardiovascular disease becomes increasingly important and is the most common cause of death after the first year. CONCLUSIONS: These data highlight the importance of long-term secondary prevention of vascular events in stroke patients, targeted as much at the cardiovascular as at the cerebrovascular circulation.
Age Factors↗
Patterns of vascular pathology in acute, first-ever cerebral infarction.
This was a preliminary study to see whether patterns of vascular pathology correlated with a simple clinical classification of acute cerebral infarction. Thirty-two patients with acute, first-ever hemispheric cerebral infarction were prospectively studied clinically together with an extra- and transcranial Doppler ultrasound. All 14 patients with the triad of ipsilateral motor/sensory deficit, homonymous hemianopia and higher cortical dysfunction (Total Anterior Circulation Infarction, [TACI]) had occlusion of the symptomatic middle cerebral artery and/or internal carotid artery, or a severe middle cerebral artery stenosis. Three patients with lacunar infarction had no evidence of major vessel occlusion. Eleven of thirteen patients with Partial Anterior Circulation, Infarction (PACI) I (i.e. only one or two clinical features of the TACI triad) had patent symptomatic major vessels, with indirect evidence to suggest distal branch occlusion(s) of the middle cerebral artery in six. The remaining two PACI patients had major vessel occlusions. Two patients were not clinically classifiable, but both had significant vascular pathology on ultrasound. The findings of this preliminary study therefore suggest that a simple clinical classification was generally capable of predicting patterns of vascular pathology in patients with acute cerebral infarction, which could have implications for the selection of patients for clinical trials of thrombolytic therapy.
Acute Disease↗
Recent developments in secondary prevention of stroke.
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Aspirin↗
Why test antiplatelet therapy in acute ischaemic stroke and how can this be done?
Stroke is a major public health problem, yet there is no treatment of proven value for widespread use in the acute phase of the illness. This paper outlines the rationale for using antiplatelet therapy in acute ischaemic stroke and why it appears to be one of the most promising agents for testing in very large scale clinical trials.
Acute Disease↗
Investigation of acute stroke: what is the most effective strategy?
Techniques of investigation of acute stroke syndromes have progressed rapidly in recent years, outpacing developments in effective stroke treatment. The clinician is thus faced with a variety of tests, each with different cost implications and each altering management to a greater or lesser extent. This review will concentrate on the basic tests which should be performed for all strokes (full blood count, ESR, biochemical screen, blood glucose, cholesterol, syphilis serology, chest X-ray and electrocardiogram). Additional tests may be required in selected cases: CT scan to diagnose 'non-stroke' lesions, to exclude cerebral haemorrhage if anti-haemostatic therapy is planned, and to detect strokes which may require emergency intervention (such as cerebellar stroke with hydrocephalus); echocardiography to detect cardiac sources of emboli; and in a few cases lumbar puncture and specialized haematological tests. Other tests, which are currently research tools, may be suitable for widespread use in the future including NMR, SPECT and PET scanning.
Acute Disease↗
Are hypertension or cardiac embolism likely causes of lacunar infarction?
We tested the hypothesis that hypertension is more common and cardiac embolism less common in patients with lacunar infarction than in patients with other types of cerebral infarction. We studied risk factor profiles in a series of 102 consecutive patients with a lacunar infarct and 202 consecutive patients with a carotid artery-distribution infarct involving the cortex registered in the Oxfordshire Community Stroke Project, a community-based study of first-ever stroke. The two groups did not differ in the prevalence of prestroke hypertension (defined in a number of ways) or in the prevalence of markers of sustained hypertension. The presence of atrial fibrillation and a history of myocardial infarction, particularly during the 6 weeks before the stroke, were significantly more common in the group with carotid-distribution infarcts involving the cortex. There was no significant difference in the prevalence of other accepted risk factors for ischemic stroke, including previous transient ischemic attack, cervical bruit, diabetes mellitus, peripheral vascular disease, or cigarette smoking. Our results suggest that hypertension is no more important in the development of lacunar infarction than it is in the development of other types of ischemic stroke that are presumed to be due to atherosclerotic thromboembolism in a major cerebral artery. Our data support the autopsy evidence that cardioembolic occlusion is an unusual cause of lacunar infarction.
Aged↗
Benign intracranial hypertension associated with danazol.
We describe a case of benign intracranial hypertension (BIH) whose onset coincided with treatment of danazol for menorrhagia. No other causative factors were identified. Headache and visual symptoms occurring in patients treated with danazol therefore require careful assessment, so that visual failure from advanced BIH can be avoided by appropriate treatment.
Adult↗
Migraine or amaurosis fugax? The value of ultrasound.
Episodes of uniocular visual loss in patients with classical migraine may be due to thromboembolism from atheroma in the internal carotid artery. Non-invasive testing may prove very useful in making the correct diagnosis particularly in patients with an approximately 50% pre-test possibility of disease.
Arteriosclerosis↗
Preventing stroke by the modification of risk factors.
Epidemiologic research has revealed the major risk factors in cerebrovascular disease. This review will concentrate on three important risk factors: elevated blood pressure, the most common and important, since it is responsible for up to 70% of all strokes; raised cholesterol; and smoking. These factors are important not only because they increase the risk of stroke, but also because they are amenable to modification by drugs, diet, or other interventions. Strategies to avoid stroke can either 1) try to produce substantial reductions, usually with drugs, in the level of the risk factor in the few individuals in the population with high levels (the "high-risk" approach), or 2) try to produce modest reductions in the level of the risk factor in every individual in the population, usually not with drugs but with lifestyle modification (the "mass" approach). The prevention of stroke could best be achieved through continuing medical efforts to deal with high-risk individuals and through political strategies to encourage a healthier lifestyle in the population as a whole.
Blood Pressure↗
Lone bilateral blindness: a transient ischaemic attack.
In the Oxfordshire Community Stroke Project 14 patients were notified with lone bilateral blindness, defined as rapid onset of dimming or loss of vision over all of both visual fields simultaneously, lasting under 24 hours, without associated symptoms of focal cerebral ischaemia, epilepsy, or reduction in consciousness. The age of these patients was close to that of the 184 patients who presented with transient ischaemic attacks and they had a similar high prevalence of vascular risk factors. During a mean follow-up of 2.4 years, 5 of the 14 had a first-ever stroke (0.31 expected). In view of their 16 times (95% CI 7-39 times) excess risk of stroke such patients should be included, for practical purposes, under the diagnostic heading of transient ischaemic attack.
Aged↗
Predisposing factors for cerebral infarction: the Oxfordshire community stroke project.
The frequency of known causative factors of cerebral infarction was studied in 244 cases of first ever stroke due to cerebral infarction proved by computed tomography or at necropsy who were registered in the first two years of a prospective community based study. Risk factors for cerebral infarction were present in 196 (80%) cases; hypertension in 126 (52%); ischaemic heart disease in 92 (38%); peripheral vascular disease in 60 (25%); a cardiac lesion that was a major potential source of embolism to the brain in 50 (20%); transient ischaemic attacks in 35 (14%); cervical arterial bruit in 33 (14%); and diabetes mellitus in 24 (10%). Thirty one patients (13%) were in atrial fibrillation. Of the 48 patients who were free of risk factors or a major potential cardiac source of embolism at the time of the stroke, 18 were found to have hypertension after the stroke and 10 to have non-atheromatous non-embolic conditions (migrainous cerebral infarction (three), arteritis (two), inflammatory bowel disease (one), arterial trauma (one), autoimmune disease (one), carcinoma of the thyroid (one), and major operation (one). In 20 patients no causative factors could be identified. In this unselected series of patients with first ever stroke due to cerebral infarction most of the strokes were presumed to be due to either atheromatous arterial disease or embolism from the heart, and only 4% (95% confidence interval 2 to 7%) were probably due to non-atheromatous non-embolic causes. This has implications for research into strokes and allocation of public health expenditure.
Aged↗
A prospective audit of the use and costs of myelography in a regional neuroscience unit.
A consecutive series of 397 myelograms performed in 385 patients over a six month period at the Mersey Regional Neurosciences Unit is reported. The reasons for performing the myelogram were to identify the cause of a radicular lesion in 54% of patients, a chronic spinal cord lesion in 30%, an acute cord lesion in 9%, suspected disease at the level of the foramen magnum 6%, and for a variety of other conditions in 8%. For the 385 patients undergoing a myelogram in the study period, the median interval from admission to request, request to myelography and from myelography to discharge was nought, one and three days respectively. The proportion of patients submitted to myelography by individual consultants ranged from 7% to 28%. There was a two-fold variation in the delays in the time to requesting and performing myelograms. There was room for improvement in the clinical information supplied on the myelography request form. The role of ancillary investigations and their effect on myelography was unclear. Only 16 of the patients with suspected cord disease had visual evoked responses performed before myelography. Five of them had myelography after an abnormal result. The estimated annual direct cost of myelography in the unit was at least 486,000 pounds. Reorganisation might have yielded hypothetical "savings" of between 30,000 pounds (6%) and 155,000 pounds (32%), though in practical terms these "savings" represented resources which might have been freed for use in other higher priority clinical problems within the unit, rather than true reductions in monetary cost.
Myelography↗
A comparison of risk factors and prognosis for transient ischemic attacks and minor ischemic strokes. The Oxfordshire Community Stroke Project.
In a community-based study of transient ischemic attack and stroke, we identified 184 cases of transient ischemic attack and 213 cases of first-ever minor ischemic stroke. A comparison of age, sex, and prevalence of coexistent vascular diseases and risk factors revealed no major differences between the two groups. The risk of further stroke and of further stroke and/or death was greater in patients with minor ischemic stroke although the difference was significant only for the latter. The apparent differences in prognosis could largely be accounted for by the favorable prognosis of patients with amaurosis fugax among those with transient ischemic attack. Although for some purposes it may be useful to distinguish transient ischemic attacks from minor ischemic strokes, the similarity of the two groups suggests that in many situations, including in clinical trials of treatments for the secondary prevention of strokes, the arbitrary distinction between them could be dispensed with.
Adult↗