Alan Bryer

International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome

Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology. Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS). The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied. The weight of each symptomatologic compartment has been carefully designed. The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress.

HIV infection and stroke: Current perspectives and future directions

Summary 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: 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: 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 seven 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.

The South African Stroke Risk in General Practice Study

BACKGROUND Incidence of stroke is increasing in sub-Saharan Africa and stroke prevention is an essential component of successful stroke management. General practitioners (GPs) are well placed to manage stroke risk factors. To design appropriate strategies for risk factor reduction we need to know the risk factor prevalence in each of the population groups attending GPs. The aim of this study was to establish the prevalence of stroke risk factors in the South African general practice population. METHOD We conducted a multicentre, observational study of patients attending general practice in South Africa. Two hundred general practices were randomly selected from lists provided by pharmaceutical representatives. Each GP approached 50 consecutive patients aged 30 years and older. Patients completed an information sheet and the GP documented the patients risk factors. The resulting sample is relevant if not necessarily representative in a statistical sense. RESULTS A total of 9 731 questionnaires were returned out of a possible 10,000. The mean age of particpants was 50.7 years. Seventy-six per cent had 1 or more risk factors and 40% had 2 or more risk factors. Hypertension was the commonest risk factor in all population groups (55%) but was highest in black patients (59%). Dyslipidaemia was commonest in whites (37%) and least common in blacks (5%). Diabetes was commonest in Asians (24%) but least common in whites (8%). Risk factors other than smoking increased with age. CONCLUSION This study provides unique data on the prevalence of stroke risk factors in a South African general practice population. Risk factors are common in all population groups, but differ in distribution among the groups. There is considerable opportunity to reduce the burden of stroke in South Africa through GP screening for and treatment of risk factors.

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.

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.

Community-based care of stroke patients in a rural African setting

BACKGROUND To develop a community-based model of stroke care, we assessed discharge planning of stroke patients, available resources and continuity of care between hospital and community in a remote rural setting in South Africa. We sought to determine outcomes, family participation and support needs, and implementation of secondary prevention strategies. METHODS Thirty consecutive stroke patients from the local hospital were assessed clinically (including Barthel index and modified Rankin scores) at time of discharge and re-assessed 3 months after discharge in their homes by a trained field worker using a structured questionnaire. RESULTS Two-thirds of all families received no stroke education before discharge. At discharge, 27 (90%) were either bed- or chair-bound. All patients were discharged into family care as there was no stroke rehabilitation facility available to the community. Of the 30 patients recruited, 20 (66.7%) were alive at 3 months, 9 (30%) had died, and 1 was lost to follow-up. At 3 months, 55% of the remaining cohort were independently mobile compared with 10% at discharge. Of the 20 surviving patients, 13 (65%) were visited by home-based carers. Only 45% reported taking aspirin at 3 months. CONCLUSIONS The 3-month mortality rate was high. Most survivors improved functionally but were left with significant disability. Measures to improve family education and the level of home-based care can be introduced in a model of stroke care attempting to reduce carer strain and reduce the degree of functional disability in rural stroke patients.

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/mm3, 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.

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.