Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke.

BACKGROUND: Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy. METHODS: Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion. RESULTS: Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group. CONCLUSIONS: These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.

Carotid arterial stent placement: results and follow-up in 53 patients.

PURPOSE: To describe the results, complications, and follow-up data after stent placement for occlusive internal carotid arterial disease and to compare the results with those in the literature. MATERIALS AND METHODS: Carotid arterial stent placement was attempted in 57 arteries in 53 patients. Thirty-six (68%) of 53 patients were symptomatic. Forty-two (79%) of 53 patients had one to three clinically important comorbidities and were considered at high risk. All patients underwent pre- and postprocedural independent neurologic examinations. Follow-up consisted of serial duplex ultrasonography and clinical assessment. RESULTS: The immediate technical success rate of stent deployment was 97%. Periprocedurally, three (three [5%] of 57 interventions) transient ischemic attacks and three (three [5%] of 57 interventions) minor strokes occurred. Two deaths occurred in the first 30 days (one myocardial infarction, one renal failure). One ipsilateral major stroke occurred 3 weeks after the procedure. The 30-day ipsilateral major stroke and death rate was 5% (three of 57 interventions). At 30 days, one of three patients with minor stroke had mild residual dysphasia. Treatment remained clinically successful in 48 (96%) of 50 patients. The restenosis rate was 4% (two patients). CONCLUSION: Carotid arterial stent placement in a high-risk population has morbidity and mortality rates comparable to those of carotid endarterectomy in a lower risk population. Carotid arterial stent placement can be performed with a low restenosis rate.

Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study.

BACKGROUND AND PURPOSE: Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke. This study aimed to determine the absolute and relative survival and the independent baseline prognostic factors for death over the next 5 years among all individuals and among 30-day survivors after a first-ever stroke in a population of Perth, Western Australia. METHODS: Between February 1989 and August 1990, all individuals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. RESULTS: Three hundred seventy patients with first-ever stroke were registered, and 362 (98%) were followed up at 5 years, by which time 210 (58%) had died. In the first year after stroke the risk of death was 36.5% (95% CI, 31.5% to 41.4%), which was 10-fold (95% CI, 8.3% to 11.7%) higher than that expected among the general population of the same age and sex. The most common cause of death was the index stroke (64%). Between 1 and 5 years after stroke, the annual risk of death was approximately 10% per year, which was approximately 2-fold greater than expected, and the most common cause of death was cardiovascular disease (41%). The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent claudication (hazard ratio [HR], 1.9; 95% CI, 1.2 to 2.9), urinary incontinence (HR, 2.0; 95% CI, 1. 3 to 3.0), previous transient ischemic attack (HR, 2.4; 95% CI, 1.4 to 4.1), and prestroke Barthel Index <20/20 (HR, 2.0; 95% CI, 1.2 to 3.2). CONCLUSIONS: One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10% per year, which is twice the rate expected among the general population of the same age and sex. The most common cause of death is cardiovascular disease. Long-term survival after stroke may be improved by early, active, and sustained implementation of effective strategies for preventing subsequent cardiovascular events.

Long-term risk of first recurrent stroke in the Perth Community Stroke Study.

BACKGROUND AND PURPOSE: Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia. METHODS: Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. RESULTS: Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived >2 days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4). CONCLUSIONS: Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.

Risk factors for post-stroke depression.

OBJECTIVE: To examine possible risk factors in post-stroke depression (PSD) other than site of lesion in the brain DATA SOURCES: 191 first-ever stroke patients were examined physically shortly after their stroke and examined psychiatrically and physically 4 months post-stroke. SETTING: A geographically defined segment of the metropolitan area of Perth, Western Australia, from which all strokes over a course of 18 months were examined (the Perth Community Stroke Study). MEASURES: Psychiatric Assessment Schedule, Mini Mental State Examination, Barthel Index, Frenchay Activities Index, physical illness and sociodemographic data were collected. Post-stroke depression (PSD) included both major depression and minor depression (dysthymia without the 2-year time stipulation) according to DSM-III (American Psychiatric Association) criteria. Patients depressed at the time of the stroke were excluded. PATIENTS: 191 first-ever stroke patients, 111 M, 80 F, 28% had PSD, 17% major and 11% minor depression. RESULTS: Significant associations with PSD at 4 months were major functional impairment, living in a nursing home, being divorced and having a high pre-stroke alcohol intake (M only). There was no significant association with age, sex, social class, cognitive impairment or pre-stroke physical illness. CONCLUSION: Results favoured the hypothesis that depression in an unselected group of stroke patients is no more common, and of no more specific aetiology, than it is among elderly patients with other physical illness.

Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group.

OBJECTIVES: To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. DESIGN: Randomized, double-blind, placebo-controlled trial with 3-month follow-up. PARTICIPANTS: A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. INTERVENTION: Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. MAIN OUTCOME MEASURE: Combined death and disability score (Barthel index <60) 3 months after the stroke. RESULTS: Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2%[12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (P=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). CONCLUSION: The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.

A population-based assessment of the impact and burden of caregiving for long-term stroke survivors.

BACKGROUND AND PURPOSE: Little attention has been focused on the demands on caregivers in stroke outcome research. A major aim of this study was to identify factors in patients associated with emotional distress in caregivers 1 year after stroke. METHODS: One-year stroke survivors with residual handicap (defined by the Oxford Handicap Scale) and their chief caregivers were interviewed as part of the follow-up activities for patients (n = 492) registered with the Perth Community Stroke Study. We assessed emotional distress in caregivers using the Hospital Anxiety and Depression Scale and the 28-item General Health Questionnaire. Appropriate sections of the Social Behaviour Assessment Schedule were used to assess the patient's behavior and the impact on the caregiver's life. Other aspects of the patient's functional state were assessed with the Barthel Index, the Mini-Mental State Examination, the Frenchay Activities Index, and the Psychiatric Assessment Schedule (at 4 months after stroke). RESULTS: Of 241 patients who survived to 1 year after stroke and were living outside of an institution, 103 patients (43%; 95% confidence interval, 37% to 49%) were handicapped. Eighty-four patient/caregiver units were assessed from this latter group. Almost all caregivers reported adverse effects on their emotional health, social activities, and leisure time, and more than half reported adverse effects on family relationships. Forty-six caregivers (55%) showed evidence of emotional distress on either of the two screening instruments, particularly if they were caregiving for patients with dementia and/or abnormal behavior. There was no significant relationship between emotional illness among caregivers and the degree of patients' physical disability. CONCLUSIONS: In this population, the high level of emotional distress among caregivers of stroke patients suggests that many caregivers have unmet needs. Community services need to focus attention on the neuropsychological aspects of stroke patients and the social functioning of caregivers who support them.

Screening instruments for depression and anxiety following stroke: experience in the Perth community stroke study.

Evaluation of the relative efficacy of three screening instruments for depression and anxiety in a group of stroke patients was undertaken as part of the Perth community stroke study. Data are presented on the sensitivity and specificity of the Hospital Anxiety and Depression Scale (HAPS), the Geriatric Depression Scale and the General Health Questionnaire (GHQ) (28-item version) in screening patients 4 months after stroke for depressive and anxiety disorders diagnosed according to DSM-III criteria. The GHQ-28 and GDS but not the HADS depression, were shown to be satisfactory screening instruments for depression, with the GHQ-28 having an overall superiority. The performance of all 3 scales for screening post-stroke anxiety disorders was less satisfactory. The HADS anxiety had the best level of sensitivity, but the specificity and positive predictive values were low and the misclassification rate high.

Prevalence of depression after stroke: the Perth Community Stroke Study.

BACKGROUND: The Perth Community Stroke Study (PCSS) was a population-based study of the incidence, cause, and outcome of acute stroke. METHOD: Subjects from the study were assessed initially, by examination and interview, and at four- and 12-month follow-ups to determine differences in prevalence of depression between the sexes and between patients with first-ever and recurrent strokes. RESULTS: The prevalence of depressive illness four months after stroke in 294 patients from the PCSS was 23% (18-28%), 15% (11-19%) major depression and 8% (5-11%) minor depression. There were no significant differences between the sexes or between patients with first-ever and recurrent strokes. With a non-hierarchic approach to diagnosis of those with depression, 26% of men and 39% of women had an associated anxiety disorder, mainly agoraphobia. Nine per cent of male and 13% of female patients interviewed had evidence of depression at the time of the stroke. Twelve months after stroke 56% of the men were still depressed (40% major and 16% minor), as were 30% of the women (12% major and 18% minor). CONCLUSION: The prevalence of depression after stroke was comparable with that reported from other studies, and considerably less than that reported from in-patient and rehabilitation units.

Anxiety disorders after stroke: results from the Perth Community Stroke Study.

BACKGROUND: The prevalence of anxiety disorders in 294 patients who survived to four months in the Perth Community Stroke Study (Perth, Australia), and a follow-up of these patients at 12 months, are presented. METHOD: Diagnoses are described both in the usual DSM hierarchic format and by a non-hierarchic approach. Adoption of the hierarchic approach alone greatly underestimates the prevalence of anxiety disorders. RESULTS: Most cases were of agoraphobia, and the remainder were generalised anxiety disorder. The prevalence of anxiety disorders alone was 5% in men and 19% in women; in community controls, it was 5% in men and 8% in women. Adopting a non-hierarchic approach to diagnosis gave a prevalence of 12% in men and 28% in women. When those who showed evidence of anxiety disorder before stroke were subtracted, the latter prevalence was 9% in men and 20% in women. CONCLUSION: One-third of the men and half of the women with post-stroke anxiety disorders showed evidence of either depression or an anxiety disorder at the time of the stroke. At 12 month follow-up of 49 patients with agoraphobia by a non-hierarchic approach, 51% had recovered, and equal proportions of the remainder had died or still had agoraphobia. The only major difference in outcome between those with anxiety disorder alone and those with comorbid depression was the greater mortality in the latter.

Predicting survival for 1 year among different subtypes of stroke. Results from the Perth Community Stroke Study.

BACKGROUND AND PURPOSE: Few studies have evaluated the factors influencing or predicting long-term survival after stroke in an unselected series of patients in whom the underlying cerebrovascular pathology is clearly defined. Moreover, the relative importance of risk factors for stroke, including sociodemographic and premorbid variables, has not been described in detail. METHODS: The study cohort consisted of 492 patients with stroke who were registered with a population-based study of acute cerebrovascular disease undertaken in Perth, Western Australia, during an 18-month period in 1989 and 1990. Objective evidence of the pathological basis of the stroke was obtained in 86% of cases, and all deaths among patients during a follow-up of 1 year were reviewed. RESULTS: One hundred twenty patients (24%) died within 28 days of the onset of stroke. Among the different subtypes of stroke, the 1-year case fatality (mean, 38%) varied from 6% and 16% for boundary zone infarction and lacunar infarction, respectively, to 42% and 46% for subarachnoid hemorrhage and primary intracerebral hemorrhage, respectively. Using Cox proportional-hazards analysis, a predictive model was developed on 321 patients with acute stroke (test sample). The best model contained five baseline variables that were independent predictors of death within 1 year: coma (relative risk [RR], 3.0; 95% confidence interval [CI], 1.1 to 8.4), urinary incontinence (RR, 3.9; 95% CI, 1.4 to 10.6), cardiac failure (RR, 6.5; 95% CI, 2.8 to 15.1), severe paresis (RR, 4.9; 95% CI, 1.6 to 15.5), and atrial fibrillation (RR, 2.0; 95% CI, 1.1 to 3.5). The sensitivity, specificity, and negative predictive value of this model for predicting death were 90%, 83%, and 95%, respectively. When applied to a second randomly selected validation sample of 171 events, sensitivity was 94%, specificity 62%, and negative predictive value 92%, indicating stability of the model. CONCLUSIONS: Although the case fatality, timing, and cause of death vary considerably among the different pathological subtypes of stroke, simple clinical measures that reflect the severity of the neurological deficit and associated cardiac disease at onset independently predict death by 1 year and may help to direct management.

Validation of a clinical classification for subtypes of acute cerebral infarction.

The validity of a clinical classification system was assessed for subtypes of cerebral infarction for use in clinical trials of putative stroke therapies and clinical decision making in a population based stroke register (n = 536) compiled in Perth, Western Australia in 1989-90. The Perth Community Stroke Project (PCSS) used definitions and methodology similar to the Oxfordshire Community Stroke Project (OCSP) where the classification system was developed. In the PCSS, 421 cases of cerebral infarction and primary intracerebral haemorrhage (PICH), confirmed by brain imaging or necropsy, were classified into the subtypes total anterior circulation syndrome (TACS), partial anterior circulation syndrome (PACS), lacunar syndrome (LACS), and posterior circulation syndrome (POCS). In this relatively unselected population, relying exclusively on LACS for a diagnosis of PICH had a very low sensitivity (6%) and positive predictive value (3%). Comparison of the frequencies and outcomes (at one year after the onset of symptoms) for each subgroup of first ever cerebral infarction in the PCSS (n = 248) with the OCSP (n = 543) registers showed uniformity only for LACI. For example, there were 27% of cases of TACI in the PCSS compared with 17% in the OCSP (difference = 10%; 95% confidence interval (95% CI) 4% to 16%) and 15% of cases in the PCSS compared with 24% in the OCSP were POCI (difference = 9%; 95% CI 3% to 15%). Case fatalities and long-term handicap across the subgroups were not significantly different between studies, but the frequencies of recurrent stroke were significantly greater for POCI in the OCSP compared with the PCSS. Although this classification system defines subtypes of stroke with different outcomes, simple clinical measures-level of consciousness, paresis, disability, and incontinence at onset-are more powerful predictors of death or dependency at one year. It is concluded that simple clinical measures that reflect the severity of the neurological deficit should complement this classification system in clinical trials and practice.

Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome.

In a population based register of stroke (n = 536) compiled in Perth, Western Australia during an 18 month period in 1989-90, 60 cases (11%) of primary intracerebral haemorrhage were identified among 56 persons (52% men). The mean age of these patients was 68 (range 23-93) and 46 (77%) events were first ever strokes. The crude annual incidence was 35 per 100,000, with a peak in the eighth decade, and a male predominance. Deep and lobar haemorrhages each accounted for almost one third of all cases. The clinical presentations included sudden coma (12%), headache (8%), seizures (8%), and pure sensory-motor stroke (3%). Primary intracerebral haemorrhage was the first presentation of leukaemia in two cases (both fatal) and it followed an alcoholic binge in four cases. 55% had a history of hypertension. 16 (27%) patients, half of whom had a history of hypertension, were taking antiplatelet agents, and one patient was taking warfarin. There were only two confirmed cases of amyloid angiopathy. The overall 28 day case fatality was 35%, but this varied from 100% for haemorrhages in the brainstem to 22% for those in the basal ganglionic or thalamic region. Other predictors of early death were intraventricular extension of blood, volume of haematoma, mass effect, and coma and severe paresis at onset. Although based on small numbers, these data confirm the heterogeneous nature of primary intracerebral haemorrhage, but they also suggest a different clinical spectrum of this type of stroke in the community compared with the experience of specialist neurological units.

Mechanism of stroke complicating cardiopulmonary bypass surgery.

BACKGROUND: Stroke is a devastating complication of cardiopulmonary bypass (CPB) surgery which occurs in 1 to 5% of cases. Strategies to reduce its incidence require a knowledge of the underlying pathology and aetiology. AIMS: To determine the incidence, pathology and aetiology of stroke complicating CPB. METHODS: Prospective review of clinical, operative and cranial CT scan findings in all cases of stroke complicating CPB procedures in our institution over an 18 month period. RESULTS: Twenty-one (1.6%, 95% CI 0.9-2.3%) cases of stroke were identified from 1336 CPB procedures. Cranial CT scan, performed in all but one patient, was normal in three patients or consistent with ischaemic stroke in 17 patients. There were no cases of haemorrhagic infarction or intracerebral haemorrhage. It was difficult to differentiate embolic and borderzone infarcts in two cases. After considering the clinical, operative and CT scan features together, 12 (57%, 95% CI 36-78%) of the cases were felt to be embolic in origin and nine (43%, 95% CI 22-64%) due to hypoperfusion in a borderzone. CONCLUSIONS: This study demonstrates that stroke remains an important complication of CPB procedures with an incidence in our series of 1.6%. The pathologic type of stroke is predominantly ischaemic in nature due to either cerebral embolism or borderzone infarction. Strategies for stroke prevention in patients undergoing CPB should be targeted primarily at these two mechanisms.

Stroke incidence and case fatality in Australasia. A comparison of the Auckland and Perth population-based stroke registers.

BACKGROUND AND PURPOSE: Population-based studies are crucial for identifying explanations for the decline in mortality from stroke and for generating strategies for public health policy. However, the present particular methodological difficulties, and comparability between them is generally poor. In this article we compare the incidence and case fatality of stroke as assessed by two independent well-designed incidence studies. METHODS: Two registers of acute cerebrovascular events were compiled in the geographically defined metropolitan areas of Auckland, New Zealand (population 945,369), during 1991-1992 for 12 months and Perth, Australia (population 138,708), during 1989-1990 for 18 months. The protocols for each register included prospective ascertainment of cases using multiple overlapping sources and the application of standardized definitions and criteria for stroke and case fatality. RESULTS: In Auckland, 1803 events occurred in 1761 residents, 73% of which were first-ever strokes. The corresponding figures for Perth were 536 events in 492 residents, 69% of which were first-ever strokes. Both studies identified a substantial proportion of nonfatal strokes managed solely outside the hospital system: 28% in Auckland and 22% in Perth of all patients registered. The age-standardized annual incidence of stroke (all events) was 27% higher among men in Perth compared with Auckland (odds ratio, 1.27; P = .016); women tended to have higher rates in Auckland, although these differences were not statistically significant. In both centers approximately a quarter of all patients died within the first month after a stroke. There were significant differences in the prevalence of hypertension among first-ever strokes. CONCLUSIONS: These two studies emphasize the importance of identifying all patients with stroke, both hospitalized and nonhospitalized, in order to measure the incidence of stroke accurately. The incidence and case fatality of stroke were remarkably similar in Auckland and Perth in the early 1990s. However, there are differences in the sex-specific rates that correspond to differences in the pattern of risk factors.