Varicella-zoster virus reactivation is frequently detected in HIV-infected individuals presenting with stroke.

Infections are an underappreciated cause of stroke, particularly in young and immunocompromised individuals. Varicella-zoster virus (VZV) reactivation, particularly ophthalmic zoster, has been linked to increased risk of stroke but diagnosing VZV-associated cerebral vasculopathy is challenging as neither a recent zoster rash, nor detectable levels of VZV DNA are universally present at stroke presentation. Detection of VZV IgG in cerebrospinal fluid (CSF-VZVG) presents a promising alternative, but requires evaluation of individual blood-CSF dynamics, particularly in the setting of chronic inflammatory states such as HIV infection. Consequently, its use has not been broadly adopted as simple diagnostic algorithms are not available. In this study looking at young adults presenting with acute stroke, we used an algorithm that includes testing for both VZV nucleic acids and CSF-VZVG which was corrected for blood-CSF barrier dynamics and poly-specific immune activation. We found that 13 of 35 (37%), including 7 with a positive CSF VZV PCR, young HIV-infected adults presenting with stroke, 3 of 34 (9%) young HIV-uninfected adults presenting with stroke, and 1 of 18 (6%) HIV-infected nonstroke controls demonstrated evidence of central nervous system reactivation of VZV.

Viral protein R polymorphisms in the pathogenesis of HIV-associated acute ischaemic stroke: a case-control study.

HIV-1 viral proteins have been implicated in endothelial dysfunction, which is a major determinant of ischaemic stroke risk in HIV-infected individuals. Polymorphisms in HIV-1 viral protein R (Vpr) may alter its potential to promote endothelial dysfunction, by modifying its effects on viral replication, reactivation of latent cells, upregulation of pro-inflammatory cytokines and infection of macrophages. We analysed Vpr polymorphisms and their association with acute ischaemic stroke by comparing Vpr signature amino acids between 54 HIV-infected individuals with acute ischaemic stroke, and 80 age-matched HIV-infected non-stroke controls. Isoleucine at position 22 and serine at position 41 were associated with ischaemic stroke in HIV. Individuals with stroke had lower CD4 counts and CD4 nadirs than controls. These polymorphisms are unique to individuals with stroke compared to South African subtype C and the control group consensus sequences. Signature Vpr polymorphisms are associated with acute ischaemic stroke in HIV. These may increase stroke risk by promoting endothelial dysfunction and susceptibility to opportunistic infections. Therapeutic targeting of HIV-1 viral proteins may present an additional mechanism of decreasing stroke risk in HIV-infected individuals.

Impact of Low Ankle-Brachial Index on the Risk of Recurrent Vascular Events.

Background and Purpose- Low ankle-brachial index (ABI) identifies a stroke subgroup with high risk of recurrent stroke, cardiovascular events, and death. However, limited data exist on the relationship between low ABI and stroke in low and middle-income countries. Therefore, we evaluated the prevalence of ABI ≤0.90 (which is diagnostic of peripheral artery disease) in nonembolic stroke patients or transient ischemic attack and assessed the correlation of low ABI with stroke risk, factors, and recurrent vascular events and death. Methods- Patients ≥45 years with acute transient ischemic attack or minor ischemic strokes were recruited consecutively from over 17 low-income and middle-income countries (Latin America [1543 patients], Middle East [1041 patients], North Africa [834 patients], and South Africa [217 patients]). The ABI measurement was performed at a single visit. Stroke recurrence and risk of new vascular events were assessed after 24 months of follow-up. Results- Among 3487 enrolled patients, abnormal ABI (<0.9) was present in 22.3 %. Patients with an ABI of ≤0.9 were more likely ( P<0.05) to be male, older, and have a history of peripheral artery disease, hypertension, and diabetes mellitus. During 2-year follow-up, the rate of major cardiovascular event was higher in patients with ABI <0.9 than those with ABI ≥0.9 (Kaplan-Meier estimates, 22.5%; 95% CI, 19.6-25.8 versus 13.7%; 21.4-15.1; P<0.001), and when ABI was categorized into 4 groups (≤0.6; 95% CI, 0.6-0.9; 0.9-1; 1-1.4), the rate of major cardiovascular event was higher in those with ABI ≤0.6 than the other groups (Kaplan-Meier estimates, 32.6%; 95% CI, 21.0-48.3 for ABI≤0.6 versus 21.7%; 95% CI, 18.8-25.0 for ABI 0.6-0.9 versus 14.3%; 95% CI, 12.4-16.6 for ABI 0.9-1 versus 13.3%; 95% CI, 11.6-15.2 for ABI 1-1.4; P<0.001). Conclusions- Among patients with nonembolic ischemic stroke or transient ischemic attack, those with low ABI had a higher rate of vascular events and death in this population. Screening for ABI in stroke patients may help identify patients at high risk of future events.

Stroke: working toward a prioritized world agenda.

BACKGROUND AND PURPOSE: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. METHODS: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. RESULTS: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent "silo" mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a "Brain Health" concept that enables promotion of preventive measures. CONCLUSIONS: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.

Stroke: working toward a prioritized world agenda.

BACKGROUND AND PURPOSE: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. METHODS: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. RESULTS: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e.g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. CONCLUSIONS: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.

Stroke in patients with human immunodeficiency virus infection.

OBJECTIVE: To report the nature of stroke in patients infected with human immunodeficiency virus (HIV) in a region with high HIV seroprevalence and describe HIV associated vasculopathy. METHODS: Patients with first ever stroke, infected with HIV and prospectively included in the stroke register of the Groote Schuur Hospital/University of Cape Town stroke unit were identified and reviewed. RESULTS: Between 2000 and 2006, 67 of the 1087 (6.1%) stroke patients were HIV infected. Of these, 91% (n = 61) were younger than 46 years. Cerebral infarction occurred in 96% (n = 64) of the HIV positive patients and intracerebral haemorrhage in 4% (n = 3). HIV infected young stroke patients did not demonstrate hypertension, diabetes, hyperlipidaemia or smoking as significant risk factors for ischaemic stroke. Infection as a risk factor for stroke was significantly more common in HIV positive patients (p = 0.018, OR 6.4, CI 3.1 to 13.2). In 52 (81%) patients with ischaemic stroke, an aetiology was determined. Primary aetiologies comprised infectious meningitides/vasculitides in 18 (28%) patients, coagulopathy in 12 (19%) patients and cardioembolism in nine (14%) patients. Multiple aetiologies were present in seven (11%) patients with ischaemic stroke. HIV associated vasculopathy was identified in 13 (20%) patients. The HIV associated vasculopathy manifested either extracranially (seven patients) as total or significant carotid occlusion or intracranially (six patients) as medium vessel occlusion, with or without fusiform aneurysmal dilation, stenosis and vessel calibre variation. CONCLUSION: Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients. In our cohort, 20% of patients demonstrated evidence of an HIV associated vasculopathy.

Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian families.

BACKGROUND: To date, 43 types of Spinocerebellar Ataxias (SCAs) have been identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG repeat tract within the corresponding gene. Ethnic and geographic differences are evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the clinical phenotype and molecular genetics of the SCAs are available from the African continent. Established studies mostly concern the South African populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7 mutation in South Africa (SA) has been found almost exclusively in families of indigenous Black African ethnic origin. OBJECTIVE: To present the results of the first clinical description of seven Zambian families presenting with autosomal dominant SCA, as well as the downstream molecular genetic analysis of a subset of these families. METHODS: The study was undertaken at the University Teaching Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia Rating Scale derived from the modified international ataxia rating scale. Molecular genetic testing for 5 types of SCA (SCA1, SCA2, SCA3, SCA6 and SCA7) was performed at the National Health Laboratory Service at Groote Schuur Hospital and the Division of Human Genetics, University of Cape Town, SA. The clinical and radiological features were evaluated in seven families with autosomal dominant cerebellar ataxia. Molecular genetic analysis was completed on individuals representing three of the seven families. RESULTS: All affected families were ethnic Zambians from various tribes, originating from three different regions of the country (Eastern, Western and Central province). Thirty-four individuals from four families had phenotypic features of SCA7. SCA7 was confirmed by molecular testing in 10 individuals from 3 of these families. The age of onset of the disease varied from 12 to 59 years. The most prominent phenotypic features in these families were gait and limb ataxia, dysarthria, visual loss, ptosis, ophthalmoparesis/ophthalmoplegia, pyramidal tract signs, and dementia. Affected members of the SCA7 families had progressive macular degeneration and cerebellar atrophy. All families displayed marked anticipation of age at onset and rate of symptom progression. The pathogenic SCA7 CAG repeat ranges varied from 47 to 56 repeats. Three additional families were found to have clinical phenotypes associated with autosomal dominant SCA, however, DNA was not available for molecular confirmation. The age of onset of the disease in these families varied from 19 to 53 years. The most common clinical picture in these families included a combination of cerebellar symptoms with slow saccadic eye movements, peripheral neuropathy, dementia and tremor. CONCLUSION: SCA is prevalent in ethnic Zambian families. The SCA7 families in this report had similar clinical presentations to families described in other African countries. In all families, the disease had an autosomal dominant pattern of inheritance across multiple generations. All families displayed anticipation of both age of onset and the rate of disease progression. Further clinical and molecular investigations of the inherited ataxias in a larger cohort of patients is important to understand the natural history and origin of SCAs in the Zambian population.

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

OBJECTIVE: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. METHODS: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. RESULTS: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4(+) T-lymphocyte count (92 vs 375 cells/mm(3), p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. CONCLUSIONS: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms.

Arterial ischemic stroke in HIV: Defining and classifying etiology for research studies.

HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.

Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: Design of the NAVIGATE ESUS randomized trial.

BACKGROUND: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. MAIN HYPOTHESIS: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. DESIGN: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. SUMMARY: The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.

High levels of von Willebrand factor and low levels of its cleaving protease, ADAMTS13, are associated with stroke in young HIV-infected patients.

BACKGROUND: Stroke associated with human immunodeficiency virus infection may occur through a variety of mechanisms. Von Willebrand factor is a marker of endothelial dysfunction, and is elevated in human immunodeficiency virus infection. High levels of von Willebrand factor, a protein involved in platelet adhesion and aggregation, and low levels of ADAMTS13, a metalloproteinase that cleaves von Willebrand factor, have been associated with an increased risk of thrombosis. AIM: To investigate the role of von Willebrand factor and ADAMTS13 in the pathogenesis of human immunodeficiency virus-related stroke in young patients. METHODS: A case-control study (n = 100) comprising three participant groups: human immunodeficiency virus-positive antiretroviral therapy-naïve young strokes (n = 20), human immunodeficiency virus-negative young strokes (n = 40), and human immunodeficiency virus-positive antiretroviral therapy-naïve nonstroke controls (n = 40). von Willebrand factor and ADAMTS13 levels were measured in plasma samples collected five- to seven-days poststroke. RESULTS: Human immunodeficiency virus-positive stroke participants had higher von Willebrand factor levels than human immunodeficiency virus-negative strokes (173·5% vs. 135%, P = 0·032). They tended to have higher levels of von Willebrand factor than human immunodeficiency virus-positive nonstroke controls (173·5% vs. 129%, P = 0·061). Human immunodeficiency virus-positive stroke participants had lower levels of ADAMTS13 than human immunodeficiency virus-positive nonstroke controls (0% vs. 23·5% P = 0·018) most likely due to the effect of the acute stroke. However, in the nonstroke group, these levels were significantly reduced compared with population norms. von Willebrand factor levels in all human immunodeficiency virus-positive participants were negatively correlated with CD4 counts. CONCLUSIONS: Stroke in human immunodeficiency virus infection is associated with a prothrombotic state, characterized by elevated von Willebrand factor and low ADAMTS13 levels.

The hereditary adult-onset ataxias in South Africa.

There is little data on the spectrum and frequencies of the autosomal dominant spinocerebellar ataxias (SCAs) from the African continent. We undertook a large prospective population-based study over a 10-year period in South Africa (SA). Affected persons were clinically evaluated, and the molecular analysis for the SCA1, 2, 3, 6 and 7 expansions was undertaken. Of the 54 SA families with dominant ataxia, SCA1 accounted for 40.7%, SCA2 for 13%, SCA3 for 3.7%, SCA6 for 1.9%, SCA7 for 22.2% and 18.5% were negative for all these mutations. The frequency of the SCA1 and SCA7 expansions in SA represents one of the highest frequencies for these expansions reported in any country. In this study, the SCA7 mutations have only been found in SA families of Black ethnic origin.

Impact of living and socioeconomic characteristics on cardiovascular risk in ischemic stroke patients.

OBJECTIVE: We aimed to stratify the risk of vascular event recurrence in patients with cerebral infarction according to living and socioeconomic characteristics and geographic region. METHOD: The Outcomes in Patients with TIA and Cerebrovascular Disease (OPTIC) study is an international prospective study of patients aged 45 years or older who required secondary prevention of stroke [following either an acute transient ischemic attack, minor ischemic strokes, or recent (less than six-months previous), stable, first-ever, nondisabling ischemic stroke]. A total 3635 patients from 245 centers in 17 countries in four regions (Latin America, Middle East, North Africa, South Africa) were enrolled between 2007 and 2008. The outcome measure was the two-year rate of a composite of major vascular events (vascular death, myocardial infarction and stroke). RESULTS: During the two-year follow-up period, 516 patients experienced at least one major cardiovascular event, resulting in an event rate of 15·6% (95% confidence interval 14·4-16·9%). Event rates varied across geographical region (P < 0·001), ranging from 13·0% in Latin America to 20·7% in North Africa. Unemployment status, living in a rural area, not living in fully serviced accommodation (i.e., house or apartment with its own electricity, toilet and water supply), no health insurance coverage, and low educational level (less than two-years of schooling) were predictors of major vascular events. Major vascular event rates steeply increased with the number of low-quality living/socioeconomic conditions (from 13·4% to 47·9%, adjusted P value for trend <0·001). CONCLUSION: Vascular risk in stroke patients in low- and middle-income countries varies not only with the number of arterial beds involved but also with socioeconomic variables.

Thrombolysis for acute ischemic stroke in South Africa.

BACKGROUND: Stroke is an important cause of death and disability in sub-Saharan Africa. Thrombolysis with recombinant tissue plasminogen activator (tPA) is the only effective therapy for acute ischaemic stroke. Essential requirements for stroke thrombolysis include availability of CT scanning and arrival at hospital within 4.5 hours of symptom onset. However, in developing countries where the prerequisites are met at certain centres, the efficacy and safety of thrombolysis have not been firmly established. AIMS: We aimed to evaluate the early outcomes and safety of stroke thrombolysis in a South African setting. METHOD: We conducted a prospective observational study of all stroke patients receiving tPA for thrombolysis over the period January 2000 to February 2011. The primary outcome measure was the proportion of patients achieving significant early neurological recovery defined as an improvement of four or more points on the NIHSS score at discharge. The safety endpoint was the rate of symptomatic intracranial haemorrhage (SICH) and death. RESULTS: Forty-two patients received thrombolysis over the study period. Sixty-seven percent achieved significant neurological improvement. The majority of patients (53.8%) were discharged home, and by the time of discharge 17 (40.5%) were functionally independent. SICH occurred in 2 (4.8%) patients with an overall mortality rate of 7.1%. CONCLUSIONS: Our findings indicate that the use of thrombolysis in routine clinical practice in a South African setting has similar safety and early efficacy outcomes to developed and other developing countries.

Demographics, socio-economic characteristics, and risk factor prevalence in patients with non-cardioembolic ischaemic stroke in low- and middle-income countries: the OPTIC registry.

BACKGROUND: There is a paucity of data on patients with stroke/transient ischaemic attack in low- and middle-income countries. We sought to describe the characteristics and management of patients with an ischaemic stroke and recent transient ischaemic attack or minor ischaemic strokes in low- or middle-income countries. METHODS: The Outcomes in Patients with TIA and Cerebrovascular disease registry is an international, prospective study. Patients ≥ 45 years who required secondary prevention of stroke (either following an acute transient ischaemic attack or minor ischaemic strokes (National Institutes of Health Stroke Scale <4) of <24 h duration, or recent (<6 months), stable, first-ever, non-disabling ischaemic stroke) were enrolled in 17 countries in Latin America, the Middle East, and Africa. The main measures of interest were risk factors, comorbidities, and socio-economic variables. RESULTS: Between January 2007 and December 2008, 3635 patients were enrolled in Latin America (n = 1543), the Middle East (n = 1041), North Africa (n = 834), and South Africa (n = 217). Of these, 63% had a stable, first-ever ischaemic stroke (median delay from symptom onset to inclusion, 25 days interquartile range, 7-77); 37% had an acute transient ischaemic attack or minor ischaemic stroke (median delay, two-days; interquartile range, 0-6). Prevalence of diabetes was 46% in the Middle East, 29% in Latin America, 35% in South Africa, and 38% in North Africa; 72% had abdominal obesity (range, 65-78%; adjusted P < 0.001); prevalence of metabolic syndrome was 78% (range, 72-84%, P < 0.001). Abnormal ankle brachial index (<0.9) was present in 22%, peripheral artery disease in 7.6%, and coronary artery disease in 13%. Overall, 24% of patients had no health insurance and 27% had a low educational level. INTERPRETATION: In this study, patients in low- and middle-income countries had a high burden of modifiable risk factors. High rates of low educational level and lack of health insurance in certain regions are potential obstacles to risk factor control. FUNDING: The Outcomes in Patients with TIA and Cerebrovascular disease registry is supported by Sanofi-Aventis, Paris, France.

Early outcomes of thrombolysis for acute ischaemic stroke in a South African tertiary care centre.

BACKGROUND: Stroke is an important cause of death and disability in sub-Saharan Africa. Recombinant tissue plasminogen activator (tPA) thrombolysis is effective in treating acute ischaemic stroke, but may not be a viable option in developing countries. METHODS: We assessed the short-term outcomes and safety of tPA for the treatment of stroke at Groote Schuur Hospital from the year 2000. Patients with a clinical diagnosis of acute stroke with onset of stroke symptoms within 4.5 hours of receiving thrombolysis were included. Exclusion criteria were based on the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial protocol (upper age limit was 75 years). Primary outcomes were the proportion of patients achieving significant early neurological recovery defined as an improvement of 4 or more points on the National Institutes of Health stroke scale (NIHSS) score and functional independence defined as a modified Rankin score of 2 or less at discharge. The primary safety measures were the rates of symptomatic intracranial haemorrhage (SICH) and death. RESULTS: From January 2000 to February 2011 42 patients were thrombolysed, with a mean time to tPA infusion of 160 minutes (standard deviation (SD) 50; range 60 - 270). By discharge the median NIHSS score fell from 14 (interquartile range (IQR) 10.5 - 17) to 7.5 (IQR 1 - 15); 28 (66.7%) achieved significant neurological improvement, and 17 (40.5%) were functionally independent. Two patients (4.8%) suffered SICH and there were 3 (7.1%) deaths. CONCLUSION: Thrombolysis in routine clinical practice in a South African setting has similar safety and early efficacy outcomes to controlled trials and open-label studies in developing and developed countries.

HIV infection and stroke: current perspectives and future directions.

HIV infection can result in stroke via several mechanisms, including opportunistic infection, vasculopathy, cardioembolism, and coagulopathy. However, the occurrence of stroke and HIV infection might often be coincidental. HIV-associated vasculopathy describes various cerebrovascular changes, including stenosis and aneurysm formation, vasculitis, and accelerated atherosclerosis, and might be caused directly or indirectly by HIV infection, although the mechanisms are controversial. HIV and associated infections contribute to chronic inflammation. Combination antiretroviral therapies (cART) are clearly beneficial, but can be atherogenic and could increase stroke risk. cART can prolong life, increasing the size of the ageing population at risk of stroke. Stroke management and prevention should include identification and treatment of the specific cause of stroke and stroke risk factors, and judicious adjustment of the cART regimen. Epidemiological, clinical, biological, and autopsy studies of risk, the pathogenesis of HIV-associated vasculopathy (particularly of arterial endothelial damage), the long-term effects of cART, and ideal stroke treatment in patients with HIV are needed, as are antiretrovirals that are without vascular risk.

Stroke outcomes in a socio-economically disadvantaged urban community.

AIMS: To determine survival, disability and functional outcomes of stroke patients following their discharge from an acute stroke unit in an urban community with limited rehabilitative resources. METHODS: Stroke patients were recruited from a district hospital in Cape Town and followed-up for 6 months. Clinical characteristics, demographic and socioeconomic data, and disability and function as measured by modified Rankin Score (mRS), modified Barthel Index (mBI) at recruitment and 3 follow-up visits, were recorded. RESULTS: The study included 196 patients. Median age was 60 (IQR 51-69) years, 135 (68.9%) were female, 57.7% black, 42.3% coloured, and 45 (23%) died within 6 months. At discharge, median mBI score was 7 (IQR 3-12) and median mRS 4 (IQR 3-5). In the multivariate regression models, only function (mBI OR 0.88, 95% confidence interval (CI) 0.79-0.96, p < 0.0001) and disability (mRS OR 2.34, 95%CI 1.20-4.54, p < 0.0001) were independently associated with risk of death. Shack housing was independently associated with moderate or severe disability (odds ratio 3.42, 95% CI 1.22-9.59, p = 0.02). Despite limited rehabilitation resources, 67% of survivors had mild to moderate disability at 6 months. CONCLUSION: Apart from initial stroke severity, risk factors for poor survival were a severe disability category and the presence of impaired swallowing at discharge. Shack housing was independently associated with poor functional outcomes. These findings should be helpful in allocating home-based care and inpatient rehabilitation resources to high-risk groups to improve outcomes.

South African guideline for management of ischaemic stroke and transient ischaemic attack 2010: a guideline from the South African Stroke Society (SASS) and the SASS Writing Committee.

BACKGROUND: Stroke is a leading cause of death and disability in South Africa. An increase in the burden of stroke is predicted as the population is undergoing a rapid epidemiological transition with increased exposure to, and development of, stroke risk factors, together with aging of the population. Objective. The objective was to update the guideline published in 2000, to place the recommendations within the current South African context, and to grade evidence according to the level of scientific rigour. RECOMMENDATIONS: Ideally, all patients with acute stroke should be managed in a dedicated stroke unit. There is ample evidence that protocol-driven multidisciplinary stroke unit care within a hospital improves recovery from stroke. Treatment in a stroke unit has been shown to reduce mortality as well as reduce the likelihood of dependency after stroke. An effective stroke service requires the establishment of a seamless network consisting of acute stroke units, post-acute care and rehabilitation, and further care in the community. Primary preventive measures reduce stroke incidence and should be universally available and actively promoted at all levels of health care in South Africa. Successful care of a stroke patient begins with recognition by the public and health professionals that stroke should be considered an emergency. Avoiding delay should be the major aim of the prehospital phase of acute stroke care. Acute stroke or transient ischaemic attack (TIA) should be treated as a medical emergency and evaluated with minimum delay. General supportive treatment is emphasised and is directed at maintaining homeostasis and the treatment of complications. Intravenous thrombolytic therapy with recombinant tissue plasminogen activator (tPA) is an accepted therapy for acute ischaemic stroke within 4.5 hours of onset of symptoms, but can only be administered at centres with specific resources. Awareness and treatment of the neurological and systemic complications of acute stroke are an integral part of management. Patients with suspected TIA and minor stroke with early spontaneous recovery should be evaluated as soon as possible after an event. Brain imaging is recommended, and non-invasive imaging of the cervicocephalic vessels should be performed urgently and routinely as part of the evaluation. Carotid endarterectomy (CEA) is recommended for patients with severe (70 - 99%) ipsilateral stenosis, and the procedure should be performed as soon as possible after the last ischaemic event - ideally within 2 weeks - in centres with a peri-operative complication rate (all strokes and death) of less than 6%. Survivors of a TIA or stroke have an increased risk of another stroke, which is a major source of increased mortality and morbidity. Secondary prevention strategies are aimed at reducing this risk. Stroke rehabilitation is a goal-orientated process that attempts to obtain maximum function in patients who have had strokes and who suffer from a combination of physical, cognitive and language disabilities.