[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic transformation of cerebral infarction (HTI) occurs spontaneously but its frequency and risk factors are uncertain with mixed results in previous studies. We aimed to determine the overall frequency of and risk factors for HTI.
We performed a systematic review according to Cochrane Collaboration methods of published reports of HTI with reliable, systematic follow-up with computed tomography or magnetic resonance imaging.
In all, 28 observational studies and 19 randomized controlled trials in stroke were identified that included follow-up imaging data. Problems with inconsistent definitions or small and biased patient populations limited detailed interpretation. The overall frequency of any HTI in untreated patients was 8.5% (95% confidence interval 7%-10%). Severe HTI (i.e., HTI accompanied by neurologic deterioration or parenchymal hematoma formation) occurred in 1.5% (95% confidence interval 0.8%-2.2%). The frequency of HTI increased markedly with increasing use of antithrombotic or thrombolytic drugs. Magnetic resonance imaging detected more HTI than did computed tomography. The published data were generally inadequate to undertake more detailed analysis of risk factors. However, in the 8 studies that did provide the information, HTI was associated with large infarcts, mass effect, hypodensity observed early after the stroke, and age older than 70 years, but not hypertension or cardioembolic stroke.
Severe HTI is uncommon in patients not receiving antithrombotic or thrombolytic agents. The methods used to assess the frequency of and risk factors for HTI, particularly a standard of definitions in future prospective studies, could be improved.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 11/2004; 13(6):235-46. DOI:10.1016/j.jstrokecerebrovasdis.2004.03.003 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study describes the large variations in outcome after stroke between countries that participated in the International Stroke Trial and seeks to define whether they could be explained by variations in case mix or by other factors.
We analyzed data from the 15 116 patients recruited in Argentina, Australia, Italy, the Netherlands, Norway, Poland, Sweden, Switzerland, and the United Kingdom: We compared crude case fatality and the proportion of patients dead or dependent at 6 months; we used logistic regression to adjust for age, sex, atrial fibrillation, systolic blood pressure, level of consciousness, and number of neurological deficits. We used the frequency of prerandomization head CT scan and prescription of aspirin at discharge to indicate quality of care.
The differences in outcome (all treatment groups combined) between the "best" and "worst" countries were very large for death (171 cases per 1000 patients) and for death or dependency (375 cases per 1000 patients). The differences were somewhat smaller after adjustment for case mix (160 and 311 cases per 1000 patients, respectively). Process of care may have accounted for some but not all of the residual variation in outcome.
Adjustment for case mix explained only some of the variation in outcome between countries. The residual differences in outcome were too large to be explained by variations in care and most likely reflect differences in unmeasured baseline factors. These findings demonstrate the need to achieve balance of treatment and control within each country in multinational randomized controlled stroke trials and the need for caution in the interpretation of nonrandomized comparisons of outcome after stroke between countries.
[Show abstract][Hide abstract] ABSTRACT: The relative's questionnaire (RQ) was developed to assess outcome after brain injury. The present study investigated its test-retest reliability when used in a postal survey.
Hospital records were used to identify and contact 288 surviving patients treated for brain injury five to seven years earlier. Patients were sent a copy of the RQ (RQ1) and one month later a second copy (RQ2) was sent to those who returned RQ1.
Two hundred and eleven patients were successfully contacted, of whom 128 (61%) returned RQ1, and 94 of these (73%) returned RQ2. The reliability of items was variable, with most having a kappa value of > 0.6 suggesting 'substantial agreement' or better.
The data presented suggest that the RQ is a reliable instrument in collecting outcome information in brain-injured patients by postal survey. Further research is recommended to test the suitability of the RQ for the use as a telephone interview.
Disability and Rehabilitation 08/2000; 22(10):446-50. · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine how far the difference in published stroke case fatality between the Western General Hospital (WGH), Edinburgh and the Falkirk and District Royal Infirmary (FDRI) for the period 1990-93 can be explained by adjusting more fully for casemix.
The cases were ascertained and followed prospectively at the WGH and retrospectively at the FDRI; casemix correction was performed using a validated logistic regression model.
The WGH is a teaching hospital and the FDRI a district general hospital.
Four hundred and thirty seven patients with a verified acute stroke at the WGH; 471 patients assigned a cerebrovascular disease discharge diagnostic code at the FDRI.
Thirty day case fatality.
About half of the difference in the two hospitals' published stroke case fatality could be accounted for by variation in measured casemix. The residual difference in adjusted case fatality might have been due to differences in the structure of stroke care or simply to remaining differences in casemix. Full investigation of the cause was prevented by the destruction of the deceased patients records.
Comparisons of routinely collected stroke outcomes will remain difficult to interpret unless casemix is properly accounted for and deceased patients' records stored for several years.
[Show abstract][Hide abstract] ABSTRACT: The aim of this project was to determine whether histological features of 'active' plaque as described in the coronary circulation following acute myocardial infarction were similar in the carotid circulation, and whether these factors could be detected ultrasonically.
Endarterectomy specimens were prospectively collected, and examined histologically and assessed by two observers for ulceration, inflammation, size of necrotic core, thickness of fibrous cap, haemorrhage and luminal thrombosis. Ultrasound of the plaque obtained preoperatively was similarly coded (blind to pathology) and compared with the pathology.
In 42 endarterectomy specimens, there was a highly significant relationship between a thin fibrous cap and a large necrotic core (P<0.002), irregular plaque contour (P<0.05) and ulceration (P<0.01) and between a large necrotic core (P<0.002) and ulceration and inflammation (P<0.05). Increasing amounts of necrosis were associated with more surface thrombosis (P<0.02). Ultrasound detected the thickness of the fibrous cap and 'any necrosis or haemorrhage' with some reliability (kappas are 0.53 and 0.5, respectively), but not ulceration, necrosis or haemorrhage on their own.
Features corresponding to active atheromatous plaque are similar in the carotid and coronary arteries, and some of these, namely lucent areas in the plaque (corresponding to necrosis or haemorrhage) and the thickness of the fibrous cap, can be determined reliably with ultrasound.
European Journal of Ultrasound 06/2000; 11(2):77-86. DOI:10.1016/S0929-8266(99)00076-2
[Show abstract][Hide abstract] ABSTRACT: To evaluate alternative methods of determining Glasgow Outcome Scale scores, a postal survey was made of 288 general practitioners and 128 relatives of patients who had sustained acute brain injuries 5-7 years previously. The Glasgow Outcome Scale score from the general practitioner and relative were compared with that calculated from questionnaire information by an experienced rater. There was poor agreement between general practitioner and rater (K = 0.17) and relative and rater (K = 0.35) scores. Both general practitioners and relatives indicated more favourable outcomes than the rater, with a higher level of agreement (K = 0.61) between them. When Glasgow Outcome Scale scores are used, the methods employed should be valid and reliable; failure to ensure this may be responsible for a considerable proportion of variability in reported studies of brain injury outcome.
Scandinavian Journal of Rehabilitation Medicine 04/2000; 32(1):25-7. DOI:10.1080/003655000750045703
[Show abstract][Hide abstract] ABSTRACT: Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulant therapy could have a significant impact on patient survival, disability and recurrence of stroke.
The objective of this review was to assess the effect of anticoagulant therapy in the early treatment of patients with acute ischaemic stroke.
We searched the Cochrane Stroke Group trials register (most recent search: March 1999) and consulted MedStrategy (1995). We also contacted drug companies.
Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke.
Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data.
Twenty-one trials involving 23,427 patients were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on eight trials (22,450 patients) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio 1.05, 95% confidence intervals 0.98-1.12). Similarly, based on five trials (21, 846 patients), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow-up (odds ratio 0.99, 95% confidence intervals 0.94-1.05). Although anticoagulant therapy was associated with about 9 fewer recurrent ischaemic strokes per 1000 patients treated, it was also associated with a similar sized 9 per 1000 increase in symptomatic intracranial haemorrhages. Similarly, anticoagulants avoided about 4 pulmonary emboli per 1000, but this benefit was offset by an extra 9 major extracranial haemorrhages per 1000. Sensitivity analyses did not identify a particular type of anticoagulant regimen or patient characteristic associated with net benefit.
Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke.
[Show abstract][Hide abstract] ABSTRACT: A new automated method of compliance measurement has been developed which may overcome some of the problems of the manual method. Measurement of craniospinal compliance in brain-injured patients offers the potential for early detection of raised intracranial pressure (ICP) before it rises to levels that may damage brain parenchyma. However, limitations of the existing manual volume pressure techniques have meant few centres routinely perform compliance testing. We report on the results of testing this new method against a manual volume pressure response method (VPR) in 10 patients with hydrocephalus. In this comparison study, 19 pairs of compliance measurements were obtained from 10 patients. The compliance values obtained ranged from 0.141 to 1.407 ml/mmHg. There was a good correlation between the two methods (r2 = 0.8508). The average bias in compliance between the two methods was 0.111 ml/mmHg (95% CL for the bias = 0.0438, 0.1788) with the new method reading higher compliance than the manual method. These results indicate that the new automatic method of compliance measurement correlates well with an independent and classical measurement of compliance, and defines the bias and limits of agreement by which the new method measures craniospinal compliance in patients with hydrocephalus. Further work is needed to validate this device over a wider compliance range, especially at the lower compliance range often found in head injured patients. Studies are also required to determine the normal range of compliance values in the patient populations who undergo ICP monitoring. Research into determining which patient populations may benefit from continuous compliance measurement is warranted.
British Journal of Neurosurgery 01/2000; 13(6):581-6. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using an independent data set, the utility of the Glasgow Head Injury Outcome Prediction Program was investigated in terms of possible frequency of use and reliability of outcome prediction in patients with severe head injury, or haematoma requiring evacuation, or coma lasting 6 hours or more, in whom outcome had been reliably assessed at 6 to 24 months after injury. Predictions were calculated on admission, before evacuation of a haematoma, or 24 hours, 3 days, and 7 days after onset of coma lasting 6 hours or more. Three hundred and twenty four patients provided 426 predictions which were possible in 76%, 97%, 19%, 34%, and 53% of patients on admission, before operation, 24 hours, 3 days, and 7 days respectively. Major reasons for non-feasible predictions were that patients were paralysed/ventilated as part of resuscitation or management. Overall, 75.8% of predictions were correct, 14.6% were pessimistic (outcome better than predicted), and 9.6% optimistic (outcome worse than predicted). Of 197 patients (267 predictions) whose eventual outcome was good or moderate, 84.3% of predictions were correct. For death or vegetative survival (96 patients with 110 predictions), 83.6% of predictions were correct but for severe disability (31 patients with 49 predictions), only 12.2% were correctly predicted. The utility of the Glasgow Head Injury Outcome Prediction Program compares favourably with other outcome prediction algorithms for patients with head injury.
[Show abstract][Hide abstract] ABSTRACT: The most common neuropathological substrates of dementia are Alzheimer's disease, cerebrovascular disease, and dementia with Lewy bodies. A preliminary, retrospective postmortem analysis was performed of the relative burden of each pathology in 25 patients with predominantly Alzheimer's disease-type dementia. Log linear modelling was used to assess the relations between ApoE genotype, Alzheimer's disease, and cerebrovascular disease pathology scores. Sixteen of 18 cases (89%) with a Braak neuritic pathology score </=4 had, in addition, significant cerebrovascular disease, or dementia with Lewy bodies, or both. There was a significant inverse relation between cerebrovascular disease and Braak stage (p=0.015). The frequency of the ApoE-epsilon4 allele was 36.4%. No evidence was found for an association between possession of the ApoE-epsilon4 allele and any one pathological variable over another. In this series most brains from patients with dementia for which Alzheimer's disease is the predominant neuropathological substrate also harboured significant cerebrovascular disease or dementia with Lewy bodies. The data suggest that these diseases are perhaps pathogenetically distinct, yet conspire to produce the dementing phenotype.
[Show abstract][Hide abstract] ABSTRACT: Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity. We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre Acute Stroke Trial-Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors, identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was found to cause an absolute increase of about 3% in case fatality in both "severe" and "mild" strokes; however, there was a 12% reduction in the number of dead or dependent "mild" strokes but a 6% increase in "severe" strokes. The number of patients was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase appears similar in "severe" and "mild" strokes, but the benefit may be greater in "mild" strokes. Thrombolysis may be more effective in patients with "mild" strokes, but more information is required to confirm this hypothesis.
Journal of Neurology 12/1999; 246(11):1059-62. · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic
stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes
between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity.
We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre
Acute Stroke Trial–Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors,
identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those
with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency
at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was
found to cause an absolute increase of about 3% in case fatality in both “severe” and “mild” strokes; however, there was a
12% reduction in the number of dead or dependent “mild” strokes but a 6% increase in “severe” strokes. The number of patients
was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase
appears similar in “severe” and “mild” strokes, but the benefit may be greater in “mild” strokes. Thrombolysis may be more
effective in patients with “mild” strokes, but more information is required to confirm this hypothesis.
Journal of Neurology 11/1999; 246(11):1059-1062. DOI:10.1007/s004150050512 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many of the important clinical decisions we make on a daily basis in stroke medicine are not supported by adequate evidence. This leads to variations in practice. If practice influences outcome, this must be regarded as unacceptable since it implies that many patients are receiving sub-optimal treatment. Where the advantages of certain treatment policies over others are only moderate, large randomised clinical trials provide the most reliable evidence of effectiveness. However, only a tiny proportion of patients with stroke are randomised in trials. Instead, the majority are exposed to treatments allocated haphazardly, rather than randomly, which serves only to delay the emergence of evidence concerning the relative merits of alternative treatment approaches. We suggest that we might increase the proportion of patients who contribute to advancing our knowledge by developing 'families' of trials. A 'family' would comprise a series of randomised trials into which patients with stroke may be enrolled either simultaneously or sequentially into one or more of the trials which would share common systems for randomisation and follow-up. Such a system would facilitate large, simple, randomised trials, reduce research costs, increase the generalisability of trial results and allow clinicians and patients to contribute to advancing our knowledge whenever they are uncertain about the best treatment. In this article, we discuss the advantages of this approach, some of the problems and their potential solutions.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Prediction of patient outcome can be useful as an aid to clinical decision making, to explore possible biological mechanisms, and as part of the clinical audit process. Many studies have constructed predictive models for survival after traumatic brain injury, but these have often used expensive, time consuming, or highly specialised measurements. The aim of this study was to develop a simple easy to use model involving only variables which are rapidly and easily clinically achievable in routine practice.
All consecutive patients admitted to a regional trauma centre with moderate or severe head injury were enrolled in the study. Basic demographic, injury, and CT characteristics were recorded. Patient survival at 1 year was used to construct a simple predictive model which was then validated on a very similar patient group.
372 patients were included in the study, of whom 365 (98%) were followed up for survival at 1 year. Multiple logistic regression resulted in a model containing age (p<0.001), Glasgow coma scale score (p<0.001), injury severity score (p<0.001), pupil reactivity (p=0.004), and presence of haematoma on CT (p=0.004) as independently significant predictors of survival. The model was validated on an independent set of 520 patients, showing good discrimination and adequate calibration, but with a tendency to be pessimistic about very severely injured patients. It is presented as an easy to use nomogram.
All five variables have previously been shown to be related to survival. All variables in the model are clinically simple and easy to measure rapidly in a centre with access to 24 hour CT, resulting in a model that is both well validated and clinically useful.
[Show abstract][Hide abstract] ABSTRACT: Secondary intracranial hypertension has been linked to leukocytosis. We examined our data bank containing physiologic recordings and outcome data of severely head injured patients to investigate the relationship between delayed increases in intracranial pressure (ICP), defined as occurring after a 12-hr period of normal ICP values, and leukocytosis.
A retrospective study of observational data.
Regional neurosurgical unit and intensive care unit.
Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five patients fulfilled selection criteria for delayed increases in ICP (group 1). Twenty-nine patients with increased ICP with no preceding or intervening periods of normal ICP were selected as a comparison group (group 2).
Comparison of 12-month outcome revealed that 11% of group 1 patients died, with 49% remaining severely disabled, in contrast to group 2, where 35% of patients died and 14% were left severely disabled (p = .021). The pattern of outcome was independent of monitoring time, or injury severity. Regression modeling was performed for prediction of delayed increase in ICP. Of 46 patients with an initial increase then decrease in leukocyte count in the first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of the 11 patients without this pattern p = .01 1).
Patients with delayed increases have a significantly different pattern of outcome. Change in leukocyte count from admission to day 2 is a significant predictor of such a delayed increase.
Critical Care Medicine 02/1999; 27(1):177-81. · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the prognostic value of summary measures of secondary physiological insult in addition to baseline clinical variables for patients with traumatic brain injury.
A series of 110 patients with traumatic brain injury had data on intracranial pressure (ICP), arterial blood pressure (ABP), cerebral perfusion pressure (CPP), arterial O2 saturation (SaO2), temperature in degrees C (Temp), and heart rate in beats/min (HRT) monitored and recorded every minute. Secondary insults were defined according to the Edinburgh University secondary insult grading system. The prognostic value of summary measures of these secondary insults was assessed by adding them to a prognostic model for survival at 1 year after controlling for baseline clinical variables using a previously validated model.
Of the eight secondary insults measured, only ICP added significantly to the prediction of survival in the first 72 hours after injury. The particular type of summary measure did not seem to influence the results. After the addition of ICP to the model, none of the other secondary insult measures could improve the predictive power of the model significantly.
Early intracranial hypertension is confirmed as a sign of poor prognosis in patients with traumatic brain injury, even after controlling for baseline clinical variables. The value or otherwise of treating such secondary insults, however, can only be definitively established in the context of prospective randomised controlled trials. The specific pathophysiological evolution of secondary insults is still the subject of much research, and a clear understanding will be necessary before the development of specific treatments is feasible.
[Show abstract][Hide abstract] ABSTRACT: Objective: Secondary intracranial hypertension has been linked to leukocytosis. We examined our data bank containing physiologic recordings and outcome data of severely head injured patients to investigate the relationship between delayed increases in intracranial pressure (ICP), defined as occurring after a 12-hr period of normal ICP values, and leukocytosis. Design: A retrospective study of observational data. Setting: Regional neurosurgical unit and intensive care unit. Patients: Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five patients fulfilled selection criteria for delayed increases in ICP (group 1). Twenty-nine patients with increased ICP with no preceding or intervening periods of normal ICP were selected as a comparison group (group 2). Measurements and Main Results: Comparison of 12-month outcome revealed that 11% of group 1 patients died, with 49% remaining severely disabled, in contrast to group 2, where 35% of patients died and 14% were left severely disabled (p = .021). The pattern of outcome was independent of monitoring time, or injury severity. Regression modeling was performed for prediction of delayed increase in ICP. Of 46 patients with an initial increase then decrease in leukocyte count in the first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of the 11 patients without this pattern (p = .011). Conclusions: Patients with delayed increases have a significantly different pattern of outcome. Change in leukocyte count from admission to day 2 is a significant predictor of such a delayed increase. (Crit Care Med 1999; 27:177-181)
Critical Care Medicine 01/1999; 27(1):177-181. DOI:10.1097/00003246-199901000-00048 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a need for valid objective tests of neurological improvement or deterioration to more accurately define response or progression in phase II studies of malignant glioma. The Edinburgh Functional Impairment Tests (EFIT) incorporate objective measures of upper and lower limb function, memory and a rating scale for dysphasia. We examined the intra-observer repeatability of the (EFIT) 24 hours apart in 55 patients with brain tumors and stable neurological disease and the inter-rater repeatability in 33 patients in the perioperative period (54 dual assessments). Intra-observer studies of the four subtests, failed to demonstrate any learning effect and showed close agreement. Inter-rater studies were affected by a treatment effect (steroids) and identified slight inter-rater bias for the ten meter walk. Altman-Bland plots showed that the level of agreement was less good in patients with more severe impairment. Correction for the severity of handicap was possible using a simple formulae: (timed tests: [rater 1 - rater 2]/[rater 1 + rater 2], Williams Delayed Recall Test [WDRT] (rater 1 - 2/81). Using this correction, all intra- and inter-rater variance of patients tested within 12 hours were < 0.2. A change of > or = 0.2 for the timed tests and WDRT, and a change in dysphasia score of > or = 2, represent a significant change in impairment using the EFIT. The EFIT should be a useful addition in phase II studies where objectively recording response or time to progression is important.
Journal of Neuro-Oncology 09/1998; 39(1):81-90. DOI:10.1023/A:1005950003774 · 3.07 Impact Factor