The incidence of stroke in Indigenous populations of countries with a Very High Human Development Index: a systematic review protocol

Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations. Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including <10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research. Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this. Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.Anna H. Balabanski, Angela Dos Santos, John A. Woods, Amanda G. Thrift, Timothy J. Kleinig, Astrid Suchy-Dicey, Susanna Ragnhild Siri, Bernadette Boden-Albala, Rita Krishnamurthi, Valery L. Feigin, Dedra Buchwald, Annemarei Ranta, Christina S. Mienna, Carol Zavaleta, Leonid Churilov, Luke Burchill, Deborah Zion, W.T. Longstreth Jr., David L. Tirschwell, Sonia Anand, Mark W. Parsons, Alex Brown, Donald K. Warne, Matire Harwood, and Judith M. Katzenellenboge

Reversible cerebral vasoconstriction, internal carotid artery dissection and renal artery stenosis

Reversible cerebral vasoconstriction is a rare and poorly understood syndrome, without clear diagnostic criteria. It has been described in association with multiple disorders, but has only been reported rarely in the setting of carotid artery dissection and, to our knowledge, never before in association with renal artery stenosis.DK Field, TJ Kleinig, PD Thompson and TE Kimbe

Fulminant leucocytoclastic brainstem vasculitis in a patient with otherwise indolent systemic lupus erythematosus

The spectrum of central nervous system (CNS) vascular pathology in systemic lupus erythematosus (SLE) includes small vessel vasculopathy, thromboembolism, perivascular lymphocytic infiltration and, rarely, overt transmural vasculitis. We present the case of a patient, who experienced three CNS relapses over total disease duration of 26 years, with otherwise indolent disease. The first two relapses were suspicious of vasculitis and the last was proven at autopsy. The short duration between final relapse onset and death in this SLE CNS vasculitis case was, to our knowledge, unique. Histopathological investigation demonstrated multiple confluent areas of haemorrhage in the medulla due to an acute small vessel leucocytoclastic vasculitis.T.J. Kleinig, B. Koszyca, P.C. Blumbergs and P. Thompso

Antithrombotic Treatment of Embolic Stroke of Undetermined Source RE-SPECT ESUS Elderly and Renally Impaired Subgroups

Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120

Stroke incidence and subtypes in Aboriginal people in remote Australia: a healthcare network population-based study

OBJECTIVES: We aimed to compare the incidence, subtypes and aetiology of stroke, and in-hospital death due to stroke, between Aboriginal and non-Aboriginal people in Central Australia, a remote region of Australia where a high proportion Aboriginal people reside (40% of the population). We hypothesised that the rates of stroke, particularly in younger adults, would be greater in the Aboriginal population, compared with the non-Aboriginal population; we aimed to elucidate causes for any identified disparities. DESIGN: A retrospective population-based study of patients hospitalised with stroke within a defined region from 1 January 2011 to 31 December 2014. SETTING: Alice Springs Hospital, the only neuroimaging-capable acute hospital in Central Australia, serving a network of 50 healthcare facilities covering 672 000 km2. PARTICIPANTS: 161 residents (63.4% Aboriginal) of the catchment area admitted to hospital with stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of first-ever stroke, overall (all events) stroke and in-hospital death. RESULTS: Of 121 residents with first-ever stroke, 61% identified as Aboriginal. Median onset-age (54 years) was 17 years younger in Aboriginal patients (p<0.001), and age-standardised stroke incidence was threefold that of non-Aboriginal patients (153 vs 51 per 100 000, incidence rate ratio 3.0, 95% CI 2 to 4). The rate ratios for the overall rate of stroke (first-ever and recurrent) were similar. In Aboriginal patients aged <55 years, the incidence of ischaemic stroke was 14-fold greater (95% CI 4 to 45), and intracerebral haemorrhage 19-fold greater (95% CI 3 to 142) than in non-Aboriginal patients. Crude prevalence of diabetes mellitus (70.3% vs 34.0%, p<0.001) and hypercholesterolaemia (68.9% vs 51.1%, p=0.049) was greater, and age-standardised in-hospital deaths were fivefold greater (35 vs 7 per 100 000, 95% CI 2 to 11) in Aboriginal patients than in non-Aboriginal patients. CONCLUSIONS: Stroke incidence (both subtypes) and in-hospital deaths for remote Aboriginal Australians are dramatically greater than in non-Aboriginal people, especially in patients aged <55 years

Does the intensity of the inflammatory reaction in a bruise depend on its proximity to the site of trauma?

Whole blood was withdrawn by tail vessel puncture from anesthetized adult male Sprague-Dawley rats and 0.1 ml was re-injected subcutaneously at each of two sites on their abdominal wall. In addition, two adjacent sites were injected with 0.1 ml of sterile saline, and two more sites were only punctured using an injecting needle. In the second part of the study anesthetized adult male Sprague-Dawley rats had two sites on the abdominal wall pinched using a small pair of forceps, two adjacent sites received an injection of 0.1 ml of whole blood obtained by tail vessel puncture, and two more sites were both pinched and injected with 0.1 ml of whole blood. At intervals of 3, 6, 12 h, 1, 2, 3, 5, and 7 days the animals were euthanized and the skin of the abdomen was processed for histological assessment. Hemosiderin staining in tissues from the first part of the study was assessed qualitatively by scoring sections as 0, 1, 2, or 3 (representing no staining, mild staining, moderate staining, and intense staining) and semi quantitatively using a Nanozoomer Digital Pathology Scanner (NDP Scan U10074-01, Hamamatsu Photonics K.K., Japan). No inflammatory reaction was observed at the sites subjected to needle puncture only. At the sites of saline injection a mild reaction occurred. At the sites where the blood had been injected an intense inflammatory cell response occurred centrally, but not toward the periphery where blood had tracked. In the second experiment the most intense inflammation was also observed in the sites where there had been a pinch and injection of blood. Again, this was maximal centrally with reduced inflammation peripherally. Perls' staining of hemosiderin was comparable in both models, with iron first observed at day 1 at the region of the injection site. At the sites of injection only, and the sites of injection plus pinch, blood had spread laterally. Hemosiderin staining appeared first and more intensely at the site of injection/trauma. The intensity of the inflammatory response in this animal model of bruising was, therefore, directly related to the proximity to the site of trauma; the appearance and intensity of hemosiderin staining was also influenced by the location within the bruises. This study has shown that histological changes that may be utilized to date bruises may be significantly influenced by the site of the biopsy.Claire Ross, Roger W. Byard, Neil E. I. Langloi