James Leyden

A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA)

Background and Hypothesis Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4.5 h of ischemic stroke onset. However, tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients. We hypothesized that anterior circulation ischemic stroke patients, selected with ‘dual target’ vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging ‘mismatch’ within 4.5 h of onset, would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone. Study Design EXTEND-IA is an investigator-initiated, phase II, multicenter prospective, randomized, open-label, blinded-endpoint study. Ischemic stroke patients receiving standard 0.9 mg/kg intravenous tissue plasminogen activator within 4.5 h of stroke onset who have good prestroke functional status (modified Rankin Scale <2, no upper age limit) will undergo multimodal computed tomography or magnetic resonance imaging. Patients who also meet dual target imaging criteria: vessel occlusion (internal carotid or middle cerebral artery) and mismatch (perfusion lesion: ischemic core mismatch ratio >1.2, absolute mismatch >10 ml, ischemic core volume <70 ml) will be randomized to either clot retrieval with the Solitaire FR device after full dose intravenous tissue plasminogen activator, or tissue plasminogen activator alone. Study Outcomes The coprimary outcome measure will be reperfusion at 24 h and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Secondary outcomes include modified Rankin Scale at day 90, death, and symptomatic intracranial hemorrhage.

Adelaide Stroke Incidence Study Declining Stroke Rates but Many Preventable Cardioembolic Strokes

Background and Purpose— Stroke incidence rates are in flux worldwide because of evolving risk factor prevalence, risk factor control, and population aging. Adelaide Stroke Incidence Study was performed to determine the incidence of strokes and stroke subtypes in a relatively elderly population of 148 000 people in the Western suburbs of Adelaide. Methods— All suspected strokes were identified and assessed in a 12-month period from 2009 to 2010. Standard definitions for stroke and stroke fatality were used. Ischemic stroke pathogenesis was classified by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Results— There were 318 stroke events recorded in 301 individuals; 238 (75%) were first-in-lifetime events. Crude incidence rates for first-ever strokes were 161 per 100 000 per year overall (95% confidence interval [CI], 141–183), 176 for men (95% CI, 147–201), and 146 for women (95% CI, 120–176). Adjusted to the world population rates were 76 overall (95% CI, 59–94), 91 for men (95% CI, 73–112), and 61 for women (95% CI, 47–78). The 28-day case fatality rate for first-ever stroke was 19% (95% CI, 14–24); the majority were ischemic (84% [95% CI, 78–88]). Intracerebral hemorrhage comprised 11% (8–16), subarachnoid hemorrhage 3% (1–6), and 3% (1–6) were undetermined. Of the 258 ischemic strokes, 42% (95% CI, 36–49) were of cardioembolic pathogenesis. Atrial fibrillation accounted for 36% of all ischemic strokes, of which 85% were inadequately anticoagulated. Conclusions— Stroke incidence in Adelaide has not increased compared with previous Australian studies, despite the aging population. Cardioembolic strokes are becoming a higher proportion of all ischemic strokes.

Clinical Associations and Causes of Convexity Subarachnoid Hemorrhage

Background and Purpose— It has been previously found noted that ≈15% to 20% of subarachnoid hemorrhage (SAH) is nonaneurysmal. Nontraumatic convexity SAH (cSAH) is increasingly recognized. Data concerning incidence and associations are scant. Methods— We identified all SAH-coded cases from South Australian public hospitals between January 2005 and July 2011. Electronic discharge summaries were reviewed, and cases of cSAH were ascertained. Clinical and radiological features were recorded, and pathogenesis was assigned. Results— Of 742 cases with SAH, 41 (6%) cases were cSAH, giving a minimum population annual incidence of 5.1 per million (95% confidence interval, 3.7–7.0). Median age was 70 years (interquartile range, 48–79). Commonest causes were cerebral amyloid angiopathy (39%), reversible cerebral vasoconstriction syndrome (17%), cerebral venous sinus thrombosis (10%), large-vessel stenotic atherosclerosis (10%), and posterior reversible encephalopathy syndrome (5%). No cause was identified in 20% (mostly elderly patients with incomplete evaluation). Most (63%) presented with transient neurological symptoms. Many (49%) were misdiagnosed as transient ischemic attacks and treated inappropriately with antithrombotics. Conclusions— cSAH comprises a significant proportion of SAH. Commonest causes are cerebral amyloid angiopathy in the elderly and reversible cerebral vasoconstriction syndrome in the young, but differential diagnosis is broad. Misdiagnosis is common and leads to potentially harmful treatments.

Ischaemic stroke among young people aged 15 to 50 years in Adelaide, South Australia.

Objectives: To report risk factors, aetiology and neuroimaging features among a large series of young Australian patients who were admitted to hospital for a first‐ever occurrence of ischaemic stroke; to analyse the effect of age, sex and ethnicity on the presence of risk factors; and to compare Australian and overseas data.

Determining the Number of Ischemic Strokes Potentially Eligible for Endovascular Thrombectomy: A Population-Based Study

Background and Purpose— Endovascular thrombectomy (ET) is standard-of-care for ischemic stroke patients with large vessel occlusion, but estimates of potentially eligible patients from population-based studies have not been published. Such data are urgently needed to rationally plan hyperacute services. Retrospective analysis determined the incidence of ET-eligible ischemic strokes in a comprehensive population-based stroke study (Adelaide, Australia 2009–2010). Methods— Stroke patients were stratified via a prespecified eligibility algorithm derived from recent ET trials comprising stroke subtype, pathogenesis, severity, premorbid modified Rankin Score, presentation delay, large vessel occlusion, and target mismatch penumbra. Recognizing centers may interpret recent ET trials either loosely or rigidly; 2 eligibility algorithms were applied: restrictive (key criteria modified Rankin Scale score 0–1, presentation delay <3.5 hours, and target mismatch penumbra) and permissive (modified Rankin Scale score 0–3 and presentation delay <5 hours). Results— In a population of 148 027 people, 318 strokes occurred in the 1-year study period (crude attack rate 215 [192–240] per 100 000 person-years). The number of ischemic strokes eligible by restrictive criteria was 17/258 (7%; 95% confidence intervals 4%–10%) and by permissive criteria, an additional 16 were identified, total 33/258 (13%; 95% confidence intervals 9%–18%). Two of 17 patients (and 6/33 permissive patients) had thrombolysis contraindications. Using the restrictive algorithm, there were 11 (95% confidence intervals 4–18) potential ET cases per 100 000 person-years or 22 (95% confidence intervals 13–31) using the permissive algorithm. Conclusions— In this cohort, ≈7% of ischemic strokes were potentially eligible for ET (13% with permissive criteria). In similar populations, the permissive criteria predict that ⩽22 strokes per 100 000 person-years may be eligible for ET.

Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought: A Retrospective Population-Based Study

Background and Purpose— The incidence of cerebral venous thrombosis (CVT) varies between studies, but it is estimated to be between 2 and 5 per million per year. A recent study in the Netherlands with comprehensive ascertainment suggested a much higher incidence. It is uncertain whether these differing estimates reflect the quality of ascertainment or true variation. The purpose of this study was to determine the incidence of CVT in Adelaide, using a novel clinical and radiological methodology. Methods— We retrospectively identified CVT International Classification of Diseases-coded cases from all Adelaide public hospitals from 2005 to 2011. We also searched all neuroimaging studies (259 101) from these hospitals for text variations containing venous thromb. All potential cases were reviewed, and cases of incident CVT ascertained. Associations and outcomes were determined. Results— Of 169 possible cases, 105 cases of CVT were confirmed (59 cases by both coding and neuroimaging, 40 from neuroimaging alone, and 6 from coding alone). In our population of 953 390 adults, this represented an incidence of 15.7 million per year (95% confidence interval, 12.9–19.0), the highest incidence reported. Of these cases, a possible procoagulant predisposition was identified in 48%. Fifty-five of 105 cases occurred in females. Relative risk of CVT in females of reproductive age was insignificantly higher than in males (1.18 [95% confidence interval, 0.94–1.48]). Conclusions— Cerebral venous sinus thrombosis in our study was more common than previously reported, perhaps because of more complete ascertainment. Future CVT incidence studies should include comprehensive capture and review of neuroimaging.

STroke imAging pRevention and treatment (START): A longitudinal stroke cohort study: Clinical trials protocol

Rationale Stroke and poststroke depression are common and have a profound and ongoing impact on an individuals quality of life. However, reliable biological correlates of poststroke depression and functional outcome have not been well established in humans. Aims Our aim is to identify biological factors, molecular and imaging, associated with poststroke depression and recovery that may be used to guide more targeted interventions. Design In a longitudinal cohort study of 200 stroke survivors, the START – STroke imAging pRevention and Treatment cohort, we will examine the relationship between gene expression, regulator proteins, depression, and functional outcome. Stroke survivors will be investigated at baseline, 24 h, three-days, three-months, and 12 months poststroke for blood-based biological associates and at days 3–7, three-months, and 12 months for depression and functional outcomes. A sub-group (n = 100), the PrePARE: Prediction and Prevention to Achieve optimal Recovery Endpoints after stroke cohort, will also be investigated for functional and structural changes in putative depression-related brain networks and for additional cognition and activity participation outcomes. Stroke severity, diet, and lifestyle factors that may influence depression will be monitored. The impact of depression on stroke outcomes and participation in previous life activities will be quantified. Study Outcomes Clinical significance lies in the identification of biological factors associated with functional outcome to guide prevention and inform personalized and targeted treatments. Evidence of associations between depression, gene expression and regulator proteins, functional and structural brain changes, lifestyle and functional outcome will provide new insights for mechanism-based models of poststroke depression.

Hemiplegic Shoulder Pain Reduces Quality of Life After Acute Stroke: A Prospective Population-Based Study.

ObjectiveHemiplegic shoulder pain is a common complication of stroke. The primary aim of this study was to determine the association of hemiplegic shoulder pain with health-related quality of life at 12 months after first stroke in a population-based registry. The secondary aim was to identify other factors associated with health-related quality-of-life outcomes. DesignA prospective population-based study in a geographically defined region of Adelaide, South Australia was conducted. Multiple ascertainment methods identified all cases of stroke within a 12-month period. Objective and subjective measures were undertaken at baseline and at 4 and 12 months’ follow-up. Multiple regression analyses identified independent variables (including exposure to shoulder pain and depression, 12-month dependence, access to formal rehabilitation) associated with health-related quality of life, defined by the summary index score derived from EuroQol-5D-3L at 12 months post-stroke. ResultsHemiplegic shoulder pain, depression, increased dependency, stroke severity, and absence of initial rehabilitation were each associated with reduction in quality of life. Age, sex, stroke type, Oxfordshire classification, and discharge destination were not related to quality of life. ConclusionHemiplegic shoulder pain reduces health-related quality of life at 12 months. More effort should be directed towards screening and management of this frequent complication of stroke.

Stroke Epidemiology in an Australian Rural Cohort (SEARCH)

Background Stroke rates in Australia and New Zealand have been declining since 1990 but all studies have been completed in large urban centers. Aim We report the first Australasian stroke incidence study in a rural population. Methods The authors applied the principle of complete ascertainment, used the WHO standard definition of stroke and classified ischemic stroke by the TOAST criteria. Data were collected from five rural centers defined by postcode of residence, over a 2-year period with 12 months of follow up of all cases. Results There were 217 strokes in 215 individuals in a population of 96,036 people, over 2 years, giving a crude attack rate of 113 per 100,000 per year. The 181 first-ever strokes (83% of total), standardized to the WHO world population, occurred at a rate of 50/100,000 (95% CI: 43–58). The 28-day fatality for first-ever strokes was 24% (95% CI: 18–31) and 77% (95% CI: 71–83) were classified as ischemic (140/181), 15% (95% CI: 10–21) intracerebral hemorrhage, 3% (95% CI: 1–6) due to subarachnoid hemorrhage and 5% (95% CI: 2–9) were unknown. A high proportion of first-ever ischemic strokes (44%) were cardioembolic, mostly (77%) due to atrial arrhythmias. Of the 38 with known atrial arrhythmias prior to stroke, only six (16%) were therapeutically anticoagulated. Conclusions This rural companion study of a recent Australian urban stroke incidence study confirms the downward trend of stroke incidence in Australia, and reiterates that inadequate anticoagulation of atrial arrhythmia remains a preventable cause of ischemic stroke.

Cerebral amyloid angiopathy causing cortical microinfarction.

Cerebral amyloid angiopathy as a cause of recurrent small cortical strokes is under-recognised. These patients need haemosiderin-sensitive MRI to make a diagnosis and intensive antiplatelet treatment is dangerous.