Stroke in the tropics

Similar to northern developed countries, cerebrovascular disease is a leading cause of morbidity and mortality in tropical countries. The epidemiology of stroke in the tropics is different from one tropical region to another and from the tropics to northern latitudes. In tropical regions, stroke is due to the conventional mechanisms encountered in other latitudes, as well as unusual causative mechanisms unique to the tropics. In tropical regions, infectious causes of stroke and nonatherosclerotic mechanisms are more common than in nontropical areas. Our current knowledge of stroke in the tropics is limited by the financial restrictions existing in such regions limiting health care delivery and epidemiological research.     

Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS)

BACKGROUND: Individuals with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While acetylsalicylic acid (ASA, aspirin) is proven and accepted as standard therapy in these patients, recent trials demonstrate that a combination of ASA and dipyridamole (DP) or clopidogrel may be superior to ASA. Blocking the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may also reduce recurrent stroke. The ongoing PRoFESS (Prevention Regimen for Effectively Avoiding Second Strokes) trial is designed to evaluate whether ASA + extended-release DP compared to clopidogrel, and whether telmisartan in addition to usual care in individuals after a stroke, will reduce the risk of further strokes. METHODS: PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. Patients > or = 50 years presenting with an ischemic stroke < 120 days who were stable were randomized. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. The most important secondary outcome is the composite of stroke, myocardial infarction or vascular death. Other secondary outcomes include this composite + congestive heart failure, new-onset diabetes, other designated occlusive vascular events (pulmonary embolism, deep-vein thrombosis, peripheral arterial occlusion, transient ischemic attack, cerebral venous thrombosis or retinal vascular accident not classified as stroke), any death, stroke subtype by TOAST criteria and Mini Mental State Examination score. Safety is evaluated by assessing the risk of major hemorrhagic events. The comparison between ASA + DP and clopidogrel is based on an initial assessment of noninferiority, followed by evaluation of superiority, while for telmisartan, we will assess its superiority over placebo. RESULTS: With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke. The mean age was 66.1 +/- 8.6 years, and 36.0% of the patients were females. The median time from qualifying event to randomization was 15 days with 39.9% of patients randomized within 10 days. According to the TOAST criteria, 28.5% of the strokes were due to large-vessel disease, 52.1% to small-vessel disease, 1.8% to cardioembolism, and 2.0% to other determined etiologies and 15.5% were of undetermined etiology. CONCLUSIONS: PRoFESS is the largest secondary stroke prevention trial to date and will directly compare two antiplatelet regimens as well as the benefit of telmisartan versus placebo.     

Stroke in Asia

The epidemic of cardiovascular disease across most of Asia is at a different stage from that in the West; the incidence and prevalence of stroke are increasing steadily, associated with nutritional changes and aging of the population. Epidemiologic data, crucial in combating stroke, have been relatively sparse in Asian populations, but a few international collaborative studies on stroke have been in progress for several years. Through these, we now know that ischemic stroke is actually the most frequent type of cerebrovascular accident in Asia, although hemorrhagic stroke remains more common in Asia than in the West. Also, the percentage of ischemic stroke attributable to intracranial vascular disease is much higher than in the West. In Japan and a few other countries, stroke rates are declining; however, increasing rates in most other countries make primary prevention of critical importance in minimizing the severe impact of this epidemic in Asia.     

Southern Buenos Aires stroke project

BACKGROUND: Ethnic differences and vascular risk factors are the major determinants of stroke subtypes. Nevertheless, specific data from undeveloped countries is difficult to obtain. Natives from South America may have a higher frequency of penetrating small vessel disease and hemorrhagic stroke. However, there are few studies in South America supporting these findings. OBJECTIVE: We analyze demographic, ethnic, risk factors, clinical characteristics, and stroke subtypes in all patients with acute stroke admitted to our hospital. METHODS: We studied all consecutive acute stroke patients admitted to the Ramos Mejia Hospital in Buenos Aires from 1997 to 1999. Our hospital serves a determined population of Southern Buenos Aires. Data were collected prospectively on patients' admission in a form especially designed for this study including vascular risk factors, clinical features, epidemiological characteristics, and neuroradiological findings. Stroke subtypes were determined according to the TOAST classification. RESULTS: Among 361 acute stroke patients, 31% had hemorrhagic stroke. It was more frequent among Natives (34%) than Caucasians (27%) (P<0.002). Ischemic stroke subtypes were as follows: 105 (42%) patients had lacunar, 31 (12%) atherosclerotic stroke, 53 (21%) cardioembolic infarction, and 16 (6%) other causes of stroke. Forty-five (18%) patients were classified as undetermined. Small vessel disease was higher among Caucasians (35%) than Natives (24%). CONCLUSIONS: Penetrating artery disease (42%) and intracranial hemorrhage (31%) were the most common stroke subtypes, being more frequent than reported in the literature. Natives had significantly higher frequency of hemorrhagic stroke than Caucasians.     

Burden of stroke in black populations in sub-Saharan Africa

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.     

Tropical myeloneuropathies — a new aetiology

Tropical myeloneuropathies are a group of neurological disorders known to occur in subtropical and tropical regions. Many aetiologies have been postulated and investigated over the past 100 years, but no single cause has been found. Recent studies suggest that human T-cell lymphotropic virus HTLV-I is the causative agent of one of these tropical myeloneuropathies, endemic tropical spastic paraparesis, and of a related disorder in southern Japan called HTLV-I-associated myelopathy. Endemic tropical spastic paraparesis is now being reported from geographical and climatic regions that were previously thought to be free of these disorders.     

Intracerebral Hemorrhage in a Young Urban Population: Etiologies and Outcomes in Patients 50 and Younger

Goal: There is limited research on intracerebral hemorrhage in young urban populations. There is reduced access to healthcare and a high prevalence of multiple comorbidities in this vulnerable population. We studied the etiologies and outcomes of spontaneous intracerebral hemorrhage in an urban North Philadelphia cohort aged 50 years old and younger. Materials and methods: A retrospective chart review of subjects 50 years old and younger who presented with spontaneous intracerebral hemorrhage at Temple University Hospital was conducted. A novel scoring system was used to classify the cause of each intracerebral hemorrhage. This system was used to assign a degree of likelihood that hypertension, amyloid angiopathy, tumor, oral anticoagulants, vascular malformations, infrequent causes, or cryptogenic etiologies were present. Aneurysmal subarachnoid hemorrhage was excluded. The prevalence of each risk factor and outcomes were analyzed. Findings: Of the 110 patients in the study, the most common etiology was hypertension (82.7%). There was no statistically significant difference in mortality between patients with multiple possible etiologies for their hemorrhage. Vascular malformations and cavernomas were rare (5.5%). Conclusions: Hypertension was the most common cause of intracerebral hemorrhage in a young urban population. The presence of multiple possible etiologies does not correlate with a worse prognosis of mortality. There is a need for further research into hemorrhagic stroke in young populations.     

Tropical neuropathies

This article reviews the more common peripheral neuropathies that are restricted to or occur with greater frequency in tropical or subtropical countries. Familiarity with them is desirable for all neurologists so that they can be recognized if they present in temperate countries. Once diagnosed they may require referral for specialist management at a centre for tropical diseases. Together, they constitute an important and variegated group of disorders. Received: 23 April 1997 Accepted: 24 April 1997     

Ischemic stroke in young adults: an overview of etiological aspects

Stroke affects mainly people aged over 65 years, and atherosclerosis predominates as the main etiopathogenic factor in ischemic stroke (IS). On the other hand, cardiac embolism and arterial dissection are the most frequent causes of IS in patients aged less than 45 years. However, inappropriate control of traditional vascular risk factors in young people may be causing a significant increase of atherosclerosis-related IS in this population. Furthermore, a variety of etiologies, many of them uncommon, must be investigated. In endemic regions, neurocysticercosis and Chagas' disease deserve consideration. Undetermined cause has been still reported in as many as one third of young stroke patients.     

The PRoFESS trial: future impact on secondary stroke prevention

Patients with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While aspirin is accepted as standard therapy in these patients, recent trials demonstrate that a combination of aspirin and extended-release dipyridamole or clopidogrel is superior to aspirin monotherapy. Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers may also reduce recurrent stroke. The ongoing Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is designed to evaluate whether extended-release dipyridamole plus aspirin compared with clopidogrel, and whether telmisartan in addition to usual care, in individuals after a stroke, will reduce the risk of further strokes. PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. Safety is evaluated by assessing the risk of major hemorrhagic and other serious adverse events. With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke.     

Headache associated with ischemic cerebrovascular disease

Headache often accompanies acute ischemic stroke. Observational studies indicate that 15 to 40% of patients with acute ischemic stroke report headache in close temporal relation to the event. The onset headache is more often seen in posterior circulation strokes than in strokes in other vascular territories. Transient ischemic attacks (TIA) can also lead to headache. The pathophysiology of headache associated with acute ischemic stroke includes edema, hemorrhagic transformation, and changes in the trigeminovascular system.     

Magnetic resonance and clinical cerebrovascular disease. An update

MRI is becoming the imaging modality of choice in patients with ischemic cerebrovascular disease although CT is still the test of choice to exclude acute hemorrhagic stroke. We have briefly reviewed characteristic features of ischemic and hemorrhagic cerebrovascular disease as well as vascular anomalies as seen on MRI. In time MRS should provide useful noninvasive metabolic data to complement the anatomical data in patients with cerebrovascular disease.     

Correlation between muscular strength and basal nuclei ischemic/hemorrhagic stroke-induced corticospinal tract injury, as detected by diffusion tensor imaging and tractography

BACKGROUND:Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke,or motor functional recovery.Magnetic resonance,diffusion tensor imaging,and diffusion tensor tractography have all been used to observe features of cerebral white matter fibrous structures.In addition,diffusion tensor tractography is the only non-invasive imaging method to display the corticospinal tract in vivo.OBJECTIVE:To evaluate the impairment degree of corticospinal tract induced by basal nuclei ischemic and hemorrhagic stroke through the use of magnetic resonance,diffusion tensor imaging,and diffusion tensor tractography,and to analyze the correlation to muscular strength.DESIGN,TIME AND SETTING:A retrospective case analysis was performed at the Department of Medical Imaging,Neurology and Neurosurgery,Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between November 2002 and June 2008.PARTICIPANTS:A total of 15 patients with acute or subacute cerebral ischemic stroke and nine with hemorrhagic stroke in the basal nuclei were selected.METHODS:Magnetic resonance,diffusion tensor imaging,and diffusion tensor tractography results and data were analyzed.Fractional anisotropy and directionally encoded color maps were obtained.Three-dimensional tractography of bilateral corticospinal tract was created,and corticospinal tract integrity was graded.Fractional anisotropy of infarct region and corresponding contralateral normal regions were measured,and hematoma volume in hemorrhagic stroke patients was determined.Hand motor function ability was evaluated using Brunstorm criteria.MAIN OUTCOME MEASURES:Fractional anisotropy of infarct region and corresponding contralateral normal regions; hematoma volume in hemorrhagic stroke patients; correlation between muscular strength and corticospinal tract impairment degree in ischemic stroke and hemorrhagic stroke patients before and after treatment.RESULTS:In ischemic stroke patients,the fractional anisotropy value was significantly lower in the infarct area of white matter than in the normal hemisphere(P < 0.01).The impairment degree of corticospinal tract negatively correlated with muscular strength of the corresponding hand(r=-0.97,P < 0.01).The hematoma volume of hemorrhagic stroke patients significantly negatively correlated with Spearman test results for muscular strength of the corresponding hand(r=-0.88,P < 0.01).CONCLUSION:Corticospinal tract impairment severity negatively correlated with muscular strength and motor functional recovery,which suggested that diffusion tensor imaging and diffusion tensor tractography could be used to evaluate corticospinal tract motor function.     

Advanced CT imaging in the evaluation of hemorrhagic stroke

Multidetector computed tomographic (CT) angiography is rapidly becoming a pivotal examination in the initial evaluation of patients with hemorrhagic stroke. This article provides an update of the literature on this dynamic topic, focusing on (1) the utility of CT angiography in the identification of hemorrhagic stroke patients who harbor an underlying vascular etiology and the role of the secondary intracerebral hemorrhage score, as well as (2) the clinical value of the CT angiography spot sign and spot sign score in patients with primary intracerebral hemorrhage.     

磁共振弥散加权像阴性缺血性卒中临床特征和原因分析

目的探讨静脉溶栓治疗中磁共振成像(magnetic resonance imaging,MRI)弥散加权像(diffusion weighted imaging,DWI)阴性缺血性卒中的临床特征及可能原因。方法回顾性分析长海医院2013年9月-2015年2月单纯静脉溶栓的缺血性卒中患者,根据头颅MRI将患者分为DWI阳性组和DWI阴性组,比较两组患者基线资料、脑血管病危险因素、临床症状和出院时结局的差异。结果入组的119例患者中,DWI阳性94例,阴性25例,DWI阴性率为21%,DWI阳性组和阴性组患者性别、年龄、脑血管病危险因素发生率无显著差异。两组入院时的美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分未见显著差异,出院时DWI阴性组的NIHSS评分中位数为0(0,1),显著低于DWI阳性组NIHSS评分中位数1(0,4)(P=0.02);改良Rankin量表(modified Rankin Scale,m RS)评分中位数为0(0,1),显著低于DWI阳性组m RS评分中位数1(1,3)(P0.001)。DWI阳性组出血转化率(2.1%)和死亡率(1.1%)均较低,而DWI阴性组未见出血转化和死亡病例,两组的出血转化及死亡结局没有显著差异。结论与DWI阳性缺血性卒中相比,DWI阴性缺血性卒中出院时症状较轻,恢复较好。两组溶栓后颅内出血的发生率及死亡率均较低且没有显著差异,静脉溶栓对于DWI阳性及阴性的缺血性卒中都是安全的。     

Changes of protein S100B serum concentration during ischemic and hemorrhagic stroke in relation to the volume of stroke lesion

BACKGROUND AND PURPOSE: Biochemical markers offer a new strategy in the diagnosis, estimation of clinical prognosis and monitoring of treatment in patients with brain damage. At present, two specific brain originated proteins play a major role: S100B protein and neuron-specific enolase (NSE). S100B comes from astrocytes and NSE has been found in neuronal cytoplasm. The aim of this study was to evaluate dynamics of protein S100B level changes in blood in stroke patients. MATERIAL AND METHODS: The material consisted of 67 patients, 53 with ischemic stroke (mean age 67.7) and 14 with hemorrhagic stroke (mean age 66.7). The diagnosis of stroke was made on the basis of clinical symptoms and computed tomography (CT). Plasma concentration of S100B was measured using the immunoluminometric test (Lia-Mat Sangtec 100(R)) on the 1st, 3rd, 7th and 14th day after stroke onset. RESULTS: The highest levels of protein S100B were found in ischemic stroke predominantly on the 3rd day and in hemorrhagic stroke on the 1st day. The concentrations of protein S100B were similar in ischemic and hemorrhagic stroke on the 3rd, 7th and 14th day but they were significantly higher on the 1st day in hemorrhagic stroke. Serum levels of protein S100B after stroke onset have shown a correlation with infarct volume, especially in patients with large or medium stroke. In small stroke lesions, concentrations of protein S100B were under the cut-off level. In hemorrhagic stroke protein S100B levels were higher in patients with midline shift visible in brain CT, but the differences were not significant. CONCLUSIONS: Ischemic and hemorrhagic strokes lead to release of protein S100B into the blood. A good correlation between the release pattern of S100B and volume of vascular lesion has been found. S100B protein is the marker of brain damage during stroke. It is possible to use protein S100B measurements in monitoring the stroke treatment.     

Neuroimaging advances and the transformation of acute stroke care

Neuroimaging techniques have transformed the delivery of stroke care. Multimodal computed tomography and magnetic resonance imaging rapidly illustrate the vascular and parenchymal correlates in acute ischemic and hemorrhagic stroke. Optimal selection of thrombolytic candidates and the characterization of ischemic sequelae may be achieved with imaging. The nature and topography of intracerebral hemorrhage may also be defined. Increasing use of multimodal imaging in acute stroke has expanded our current understanding of stroke pathophysiology and streamlined the care of stroke patients from the hyperacute to chronic phases. The integration of neuroimaging techniques in research studies has elucidated pitfalls in the translation of novel therapy into clinical practice. This review explores the impact of neuroimaging advances in stroke and emphasizes the critical role of these modalities in the care of patients with ischemic and hemorrhagic events.     

Stroke in children: genetic and metabolic issues

The study of genetic and metabolic etiologies of pediatric stroke, both vascular and metabolic, allows an understanding of the causes of acute focal neurologic deficits in childhood. Here, the mendelian and mitochondrial genetic causes of pediatric stroke syndromes are reviewed. This approach elucidates the etiology of childhood stroke and illustrates many of the genetic risk factors that are found in adult-onset cerebrovascular disease. Therefore, the study of childhood stroke serves as a model to elucidate the potential risk factors for all stroke. Ultimately this will serve to develop a more rational preventive and therapeutic approach for all cerebrovascular disease.     

既往卒中病史对缺血性脑血管病患者卒中结局的影响研究

目的 探讨中国人群中首发和复发缺血性脑血管病患者的临床特征和卒中结局差异。 方法 本研究基于全国多中心前瞻性中国国家卒中登记研究Ⅲ（the third China national stroke regi stry,CNSR-Ⅲ）,连续纳入2015年8月-2018年3月急性缺血性卒中或TIA患者,收集人口学信息、血 管危险因素、既往用药史及病因分型系统（causative classification system,CCS）等临床资料,记录随 访3个月和1年时卒中结局。卒中结局包括卒中复发（缺血性卒中或出血性卒中）、联合血管事件（卒中、 心肌梗死及血管性死亡事件）、脑血管病源性死亡及不良功能结局（mRS＞2分）。依据患者既往是否 有卒中病史分为有卒中病史组和无卒中病史组,比较两组的临床特征及卒中结局差异,并分析卒中病 史与卒中结局间的关系。 结果 最终纳入15 166例患者,平均年龄62.2±11.3岁,其中女性4802例（31.7%）;有卒中病史患者 3355例,无卒中病史患者11 811例。有卒中病史组患者年龄,冠心病、高血压、脂代谢紊乱、糖尿病、心 房颤动比例,既往用药史比例、入院NIHSS评分、住院期间降糖和降压治疗比例均高于无卒中病史组, 目前吸烟和重度饮酒比例、入院时LDL-C水平及住院期间抗血小板治疗比例低于无卒中病史组,差 异均有统计学意义。两组CCS分型的分布差异有统计学意义,其中有卒中病史组大动脉粥样硬化型和 心源性栓塞型卒中比例高于无卒中病史组。多因素分析结果显示,卒中病史是随访3个月不良功能结 局（校正OR 1.25,95%CI 1.09～1.44,P =0.002）,随访1年卒中复发（校正HR 1.44,95%CI 1.25～1.67, P＜0.001）、联合血管事件（校正HR 1.43,95%CI 1.24～1.64,P＜0.001）、脑血管病源性死亡（校正 HR 1.42,95%CI 1.12～1.80,P =0.004）、不良功能结局（校正OR 1.63,95%CI 1.42～1.88,P＜0.001）的 危险因素。 结论 有无卒中病史的缺血性卒中患者的临床特征及随访结局差异较大,尽管患者进行卒中二级 预防治疗,卒中病史仍然是患者1年卒中复发、联合血管事件、脑血管病源性死亡及不良功能结局的 危险因素。     

Stroke in rural Ecuador: a three-phase, door-to-door survey

The authors carried out a three-phase door-to-door survey in Atahualpa, Ecuador to assess epidemiologic and pathogenetic mechanisms of stroke. They found 10 stroke patients among 1,568 individuals aged > or =15 years (crude prevalence, 638 per 100,000). There was only one incident case (incidence, 64 per 100,000). Six of the 10 patients had hypertensive arteriolopathy (five with ischemic and one with hemorrhagic stroke). Additional work is needed to increase knowledge on stroke in developing countries.