Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.

BACKGROUND: Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. METHODS: In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130-149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306. FINDINGS: 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137-139) in the higher-target group and 127 mm Hg (95% CI 126-128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64-1·03, p=0·08), disabling or fatal stroke (0·81, 0·53-1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68-1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15-0·95, p=0·03). Treatment-related serious adverse events were infrequent. INTERPRETATION: Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial. FUNDING: National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS).

Spontaneous limb movements and posturing secondary to acute basilar artery occlusion: a potentially devastating seizure mimic.

Basilar artery occlusion is a devastating but treatable form of ischaemic stroke with high morbidity and mortality rates. The diagnosis is often challenging due to considerable heterogeneity of clinical signs and symptoms. We report a case of an acute basilar artery occlusion presenting with decreased level of consciousness associated with rhythmic tonic movements of the four extremities, mimicking seizure activity. The patient was treated with intravenous thrombolysis and subsequently gained good recovery. Awareness of this entity is required to recognise this potentially treatable, but otherwise devastating seizure mimic.

Cerebral microbleeds: histopathological correlation of neuroimaging.

BACKGROUND: In recent years, there has been a growing interest in cerebral microbleeds (CMBs) and their role in cerebrovascular disease. A few studies have investigated the histopathological correlation between CMBs and neuroimaging findings. We conducted a systematic review in an attempt to characterize the pathological and radiological correlation. METHODS: A systematic literature search was conducted for studies in which CMBs were characterized histopathologically and correlated with MRI findings. RESULTS: Five studies met the inclusion criteria, with a total of 18 patients. Hemosiderin deposition was reported in 42 CMBs (49%), while 16 CMBs (19%) were described as old hematomas which stained for iron, 13 (15%) had no associated specific pathology, 11 (13%) contained intact erythrocytes, 1 (1%) was due to vascular pseudocalcification, 1 (1%) was a microaneurysm and 1 (1%) was a distended dissected vessel. Lipofibrohyalinosis was the most prominent associated vascular finding. Amyloid angiopathy was present primarily in patients with dementia. CONCLUSIONS: Although histopathological associations have been observed using MRI in patients with CMBs, the findings have yet to be validated and further research is warranted.

Estimación de la prevalencia de riesgo de síndrome de apneas obstructivas del sueño en funcionarios de una Institución de Salud según el cuestionario STOP-Bang / Estimation of the prevalence of risk of obstructive sleep apnea syndrome in workers of a health institution according to the stop-bang questionnaire

INTRODUCCIÓN: En Chile, se estima que 8,5% de los adultos tiene riesgo elevado de síndrome de apnea e hipopnea obstructiva del sueño (SAHOS). OBJETIVO: Estimar el riesgo de SAHOS en funcionarios de la salud. MATERIAL Y MÉTODO: Se consignaron los datos clínicos, antropométricos, presión arterial, cuestionarios STOP-Bang (CSB), índice de Flemons y escalas de Epworth y de Thornton en trabajadores de Clínica Dávila, Santiago, Chile. RESULTADOS: Se evaluaron 1.332 funcionarios, 77,1% mujeres, circunferencia de cuello: 35,7 ± 3,7 cm (26-54), circunferencia de cintura: 89,3 ± 3,7 cm, e índice de masa corporal: 27,5 ± 4,5 (17,5-49,4) kg/m2; 42% tenía sobrepeso y 26% obesidad. El Cuestionario SB los clasificó en tres categorías: Riesgo alto (RA): 43 funcionarios (3,2%), 50 ± 10,5 años; riesgo moderado: 215 (16,1%), 45,6 ± 11,4 años y riesgo bajo: 1.074 (80,6%), 36,2 ± 10,6 años. En hombres, la edad y los puntajes de los cuestionarios de sueño fueron diferentes en las tres categorías de riesgo (p = 0,003 y 0,001). En mujeres, los puntajes de los cuestionarios fueron distintos en los tres grupos de riesgo, no hubo diferencias en la escala de Epworth (p = 0,274), ni en la edad (p = 0,08). La escala Mallampati no permitió predecir el riesgo de SAHOS en ambos sexos. CONCLUSIONES: El cuestionario SB identificó a 9,8% de los hombres con riesgo alto de SAHOS. En los hombres, la edad, cuestionario SB, Flemons, Epworth y Thornton, fueron diferentes en las tres categorías de riesgo de SAHOS. En las mujeres, la edad y escala de Epworth fueron similares en las tres categorías de riesgo.

INTRODUCTION: In Chile, it is estimated that 8.5% of adults are at high risk of Obstructive Sleep Apnea (OSA). OBJECTIVE: To estimate the risk of OSA in health workers. MATERIAL AND METHOD: clinical and anthropometric data, blood pressure, STOP-Bang (CSB) questionnaires, Flemons index and Epworth and Thornton scales were assessed in workers from Clínica Dávila, Santiago, Chile. RESULTS: 1,332 workers were evaluated, 77.1% women, neck circumference: 35.7 ± 3.7 cm (26-54), waist circumference: 89.3 ± 3.7 cm, and body mass index: 27.5 ± 4.5 (17.5-49.4) kg/m2; 42% were overweight and 26% obese. The SB Questionnaire classified them into three risk categories: High risk (HR): 43 workers (3.2%), 50 ± 10.5 years-old; moderate risk: 215 (16.1%), 45.6 ± 11.4 years-old and low risk: 1,074 (80.6%), 36.2 ± 10.6 years-old. In men, age and sleep questionnaire scores were different in the three risk categories (p = 0.003 and 0.001). In women, the sleep questionnaire scores were different in the three risk groups, there were no differences in the Epworth scale (p = 0.274), nor in age (p = 0.08). The Mallampati scale did not allow predict OSA risk in both sexes. CONCLUSIONS: The SB questionnaire identified 9.8% of the men with high risk of OSA. In men, age, SB questionnaire, Flemons index, Epworth and Thornton scale, were different in the three OSA risk categories. In women, the age and Epworth scale were similar in the different risk categories.

Diffuse vacuolization (spongiosis) and arteriolosclerosis in the frontal white matter occurs in vascular dementia.

OBJECTIVE: To examine quantitatively white-matter changes at different sites in patients with definite vascular dementia and Alzheimer's disease. DESIGN: Prospective clinical and neuropathological series. SETTING: University Hospital clinics (Helsinki, Finland and London, Ontario). SUBJECTS: Twenty-two patients with a clinical and neuropathological diagnosis of vascular dementia and 20 patients with Alzheimer's disease. MEASURES: The frequencies of focal white-matter lesions, arteriolosclerosis, and cerebral amyloid angiopathy were assessed. Validated ratings and cell counts were done in the subcortical U-fiber, centrum semiovale, and periventricular areas of the frontal white matter. Degrees of abnormality (none, mild, moderate, severe) were rated for spongiosis (vacuolization of white matter), état criblé (widening of perivascular spaces), myelin loss, oligodendrocyte density, axonal loss, and overall. Densities of oligodendrocytes and astrocytes (cells per square millimeter) were determined. RESULTS: Patients with vascular dementia showed focal white-matter lesions and arteriolosclerosis more often than patients with Alzheimer's disease. The patients with vascular dementia also had significantly greater spongiosis (P<.001), état criblé (P=.004), myelin loss (P<.005) and overall white-matter abnormality (P<.001). Arteriolosclerosis was found in association with spongiosis but not with état criblé. Cerebral amyloid angiopathy did not appear to be related to any of the white-matter changes in patients with either vascular dementia or Alzheimer's disease. The U-fiber area showed fewer changes, and the periventricular area tended to be most affected. CONCLUSION: In addition to focal infarcts, patients with vascular dementia showed widespread diffuse changes, including spongiosis and arteriolosclerosis, along with état criblé and myelin loss. White-matter changes in patients with Alzheimer's disease could not be related to infarction. Pathologic changes in small blood vessels are associated with diffuse white-matter changes and may have a distinct role in the genesis of vascular dementia.

Lack of relationship between leukoaraiosis and carotid artery disease. The North American Symptomatic Carotid Endarterectomy Trial.

OBJECTIVE: Leukoaraiosis (LA) (white matter changes) is frequently observed on computed tomographic scans of the brain of elderly patients at risk of stroke. A localized vascular-ischemic cause has been suggested for its underlying mechanism. Our aim was to assess whether high-grade carotid stenosis is associated with LA. DESIGN/SETTING: Patients enrolled in the North American Symptomatic Carotid Endareterectomy Trial (also known as NASCET) were evaluated for LA using a recently proposed grading scale. Ordinal regression analysis was used to assess the association between the severity of carotid artery stenosis and the extent of LA observed on computed tomographic scans. The patients' brain hemisphere was selected as the unit of analysis. RESULTS: Of the 2394 brain hemispheres contributed to the analyses, 352 (14.7%) had signs of LA. After controlling for known stroke risk factors in the ordinal regression analysis, only the history of stroke and increasing age were significantly related to LA. Severity of stenosis was observed to be unrelated (odds ratio [severe vs mild stenosis] = 1.08; 95% confidence interval, 0.73-1.62; P = .952) as were a history of hypertension and a history of myocardial infarction. CONCLUSION: Leukoaraiosis is not associated with severe carotid artery stenosis.

The risk of stroke in patients with first-ever retinal vs hemispheric transient ischemic attacks and high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND: The prognosis of amaurosis fugax has been considered to be favorable compared with that of hemispheric transient ischemic attacks. However, this has remained uncertain for patients with significant carotid stenosis as the assessment of progression of the disease has been confounded when patients undergo carotid endarterectomy. In the North American Symptomatic Carotid Endarterectomy Trial, patients with high-grade (70% to 99%) carotid stenosis were randomized to receive either medical or surgical treatment, thus making an unconfounded analysis possible. METHOD: We identified 129 medically treated patients with high-grade carotid stenosis who had their first-ever transient ischemic attack as the entry event into the trial. Fifty-nine patients with retinal transient ischemic attacks (RTIAs) were compared with 70 patients with hemispheric transient ischemic attacks (HTIAs). RESULTS: Patients with HTIAs were older, with a higher prevalence of most risk factors for stroke. Average time of delay from the onset of transient ischemic attacks to medical treatment was longer for patients with RTIAs than for patients with HTIAs (48.5 vs 15.2 days). Kaplan-Meier estimates of the risk of ipsilateral stroke at 2 years were 16.6% +/- 5.6% for patients with RTIAs and 43.5% +/- 6.7% for patients with HTIAs (P = .002 for the difference in risk between RTIAs and HTIAs). From corresponding Cox's proportional hazards regression analyses, the risk of ipsilateral stroke ranged from 11.2% to 28.9% for patients with RTIAs and from 37.4% to 96.3% for patients with HTIAs across stenoses, spanning 75% to 95%. Overall, the relative risk of ipsilateral stroke (HTIAs compared with RTIAs) was 3.23 (95% confidence interval, 1.47 to 7.12), regardless of the degree of high-grade stenosis. CONCLUSION: To our knowledge, this study is the first report on the expected outcome for medically treated patients with high-grade (70% to 99%) carotid stenosis in whom the first-ever event was either an RTIA or HTIA. The presence of RTIAs carries a considerable risk of ipsilateral strokes, particularly at higher degrees of stenosis. However, in comparison with HTIAs, patients with RTIAs still have a better prognosis.

Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses.

BACKGROUND: Aspirin therapy reduces stroke by about 25% for persons with atherosclerotic vascular disease, but the effect in those without clinically apparent vascular disease is distinctly different. OBJECTIVE: To define the effect of aspirin use on stroke and other major vascular events when given for primary prevention to persons without clinically recognized vascular disease. DATA SOURCES AND EXTRACTION: Systematic review of randomized clinical trials and large prospective observational cohort studies examining the relation between aspirin use and stroke in persons at low intrinsic risk. Studies were identified by a computerized search of the English-language literature. DATA SYNTHESIS: Five randomized trials of primary prevention included 52 251 participants randomized to aspirin doses ranging from 75 to 650 mg/d; the mean overall stroke rate was 0.3% per year during an average follow-up of 4.6 years. Meta-analysis revealed no significant effect on stroke (relative risk = 1.08; 95% confidence interval, 0.95-1.24) contrasting with a decrease in myocardial infarction (relative risk = 0.74; 95% confidence interval, 0.68-0.82). The lack of reduction of stroke by aspirin for primary prevention was incompatible with its protective effect against stroke in patients with manifest vascular disease (P = .001). Intracranial hemorrhage was increased by the regular use of aspirin (relative risk = 1.35; P = .03), similarly for both primary and secondary prevention. In 4 large observational studies, self-selected use of aspirin was consistently associated with higher rates of stroke. CONCLUSIONS: The effect of aspirin therapy on stroke differs between individuals based on the presence or absence of overt vascular disease, in contrast with the consistent reduction in myocardial infarction by aspirin therapy observed in all populations. We hypothesize that the effect of aspirin therapy on stroke for persons with major risk factors for vascular disease may be intermediate between a substantial decrease for those with manifest vascular disease and a possible small increase for healthy persons due to accentuated intracranial hemorrhage. When aspirin is given for primary prevention of vascular events, available data support using 75 to 81 mg/d.

Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage.

OBJECTIVE: To characterize the rates of recurrent intracranial hemorrhage (ICH), ischemic stroke, and death in survivors of primary ICH. METHODS: Systematic review of studies reporting recurrent stroke in survivors of primary ICH, identified at index ICH and followed forward. Studies were identified by computerized search of the literature and review of reference lists. RESULTS: Ten studies published between 1982 and 2000 reporting 1,880 survivors of ICH, followed for a total of 6,326 patient-years (mean follow-up, 3.4 patient-years), were included. The aggregate rate of all stroke from five studies was 4.3% per patient-year (95% CI, 3.5% to 5.4%). The rate in the three population-based studies was higher than in the two hospital-based studies, 6.2% versus 4.0% per patient-year (p = 0.04). About three fourths of recurrent strokes were ICH. Considering all 10 studies, a total of 147 patients had a recurrent ICH, an aggregate rate of 2.3% per patient-year (95% CI, 1.9% to 2.7%). Based on data from four studies, patients with a primary lobar ICH had a higher rate of recurrent ICH than those with a deep, hemispheric ICH (4.4% versus 2.1% per patient-year; p = 0.002). The aggregate rates of subsequent ischemic stroke and mortality were 1.1% per patient-year (95% CI, 0.8% to 1.7%) and 8.8% per patient-year (95% CI, 5.2% to 11.0%). CONCLUSIONS: Recurrent stroke among survivors of primary ICH occurs at a rate of about 4% per patient-year, and most are recurrent ICH. Survivors of ICH have a higher risk of recurrent ICH than of ischemic stroke, and this has implications for the use of antithrombotic agents in these patients.

Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

BACKGROUND: Atrial fibrillation (AF) carries an increased risk of stroke; antiplatelet agents are proven effective for stroke prevention in other settings. OBJECTIVES: The objective of this review was to determine the efficacy and safety of antiplatelet therapy for prevention of stroke in patients with chronic non-valvular AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Register of Trials, MEDLINE database (June 1999), and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. SELECTION CRITERIA: All randomized trials comparing antiplatelet therapies to placebo in patients with non-valvular AF and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of two trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Among 1680 participants without prior stroke/TIA, randomized to aspirin (N = 838) or placebo in two trials, aspirin was associated with nonsignificantly lower risks of ischemic stroke (OR = 0.71, CI 95% 0. 46 - 1.10), all stroke (OR = 0.70, CI 95% 0.45 - 1.08) all disabling/fatal stroke (OR =0.88, CI 95% 0.48 - 1.58) and the constellation of stroke, MI or vascular death (OR = 0.76, CI 95% 0. 54 - 1.05 ). Considering all randomized participants including those with prior stroke or TIA, reductions in these events by aspirin were consistently smaller and marginally statistically significant: ischemic stroke (OR = 0.77, CI 95% 0.60-1.00), all stroke (OR = 0.76, CI 95% 0.61 - 0.93), all disabling/fatal stroke (OR = 0.87, CI 95% 0.64 - 1.19) and the combined outcome (OR = 0.79, CI 95% 0.64 - 0. 99). No increase in major hemorrhage was seen, but the number of hemorrhagic events was small. REVIEWER'S CONCLUSIONS: Considering all randomized data, aspirin modestly (by about 20%) reduces stroke and major vascular events in nonvalvular AF. For primary prevention among AF patients with an average stroke rate of 4.5%/year, about 10 strokes would be prevented yearly for every 1000 given aspirin.

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

BACKGROUND: Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke. OBJECTIVES: The objective of this review was to characterize the efficacy and safety of oral anticoagulation (OAC) with vitamin K antagonists for the primary prevention of stroke in patients with chronic AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Register of Trials (June 1999), MEDLINE database, and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. SELECTION CRITERIA: All randomized controlled trials comparing the value of OAC versus control in patients with non-valvular chronic atrial fibrillation and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of four trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Of 2313 participants without prior cerebral ischemia from five trials, about half (n = 1154) were randomized to adjusted-dose OAC with an estimated mean INRs ranging between 2.0-2.6 during 1.5 years/participant average follow-up. Participant features and study quality were similar between trials. OAC was associated with large, highly statistically significant reductions in ischemic stroke (OR = 0.34, 95% CI 0.23 - 0.52), all stroke (OR = 0.39, 95% CI 0.26 - 0. 59), all disabling or fatal stroke (OR = 0.47, 95% CI 0.28 - 0.80), and the combined endpoint of all stroke, MI or vascular death (OR = 0.56, 95% CI 0.42 - 0.76). The observed rates of intracranial and extracranial hemorrhage not significantly increased by OAC therapy, but confidence intervals were wide. REVIEWER'S CONCLUSIONS: Adjusted-dose OAC (achieved INRs between 2-3) reduces stroke as well as disabling/fatal stroke for patients with nonvalvular AF, and these benefits were not substantially offset by increased bleeding among participants in randomized clinical trials. Limitations include relatively short follow-up and imprecise estimates of bleeding risks from these selected participants. For primary prevention in AF patients who have an average stroke rate of 4%/year, about 25 strokes and about 12 disabling fatal strokes would be prevented yearly for every 1000 given OAC.

Clobazam in partial status epilepticus.

Clobazam is the first and only 1,5-benzodiazepine to be used in the management of epilepsy. The use and effectiveness of oral clobazam in patients with status epilepticus has only been previously described in one study of 16 cases, seven of whom were in complex partial status. We have used clobazam in four patients with EEG-proven partial status epilepticus refractory to standard antiepileptic drugs. In all cases, except one, the seizure activity was controlled within 2 hr of administering clobazam. Our four patients responded promptly to an oral loading of clobazam which was approximately twice the usual daily maintenance dose. The drug was well tolerated and no adverse effects were seen. Clobazam's effectiveness as a first-line agent remains to be studied. Further controlled studies are recommended.

Motor unit involvement in human acute Chagas' disease.

Thirty five patients with acute Chagas' disease who demonstrated parasitaemia at the time of the investigation were submitted to a detailed electromyographical study. With their muscles at rest, 12 patients showed fibrillation potentials and/or positive sharp waves. On volitional contraction, 7 had short duration motor unit potentials (MUPs) and low polyphasic MUPs. On motor and sensory nerve fibers conduction studies, 20 disclosed values below the lower control limit within one or more nerves. Finally, 12 patients produced a muscle decremental response on nerve supramaximal repetitive stimulation. The findings signal that primary muscle involvement, neuropathy and impairement of the neuromuscular transmission, either isolated or combined, may be found in the acute stage of human Chagas' disease.

Carotid endarterectomy for asymptomatic carotid stenosis: a meta-analysis.

OBJECTIVE: To assess the value of carotid endarterectomy for prevention of stroke in patients with asymptomatic carotid stenosis. DESIGN: Systematic review and meta-analysis of randomised controlled trials in patients with asymptomatic carotid stenosis in which subjects were allocated to carotid endarterectomy or to medical treatment alone. SUBJECTS: Five trials enrolled 2440 patients with stenosis >/ 50%. MAIN OUTCOME MEASURES: Stroke ipsilateral to the stenosis, all strokes, and perioperative complications (stroke or death). RESULTS: In patients who underwent carotid endarterectomy (n=1215) there was a significant reduction in the odds of ipsilateral stroke plus perioperative stroke or death (odds ratio 0.62; 95% confidence interval 0.44 to 0.86), corresponding to a 2% absolute risk reduction over about 3.1 years. The prevalence of stroke in any location was also reduced (0.68; 0.51 to 0.9) in patients undergoing carotid endarterectomy. During the immediate postoperative period there was an increased prevalence of stroke or death among such patients (4.51; 2.36 to 8.64). CONCLUSION: Carotid endarterectomy in patients with asymptomatic carotid stenosis unequivocally reduces the incidence of ipsilateral stroke, though the absolute benefit is relatively small. Given the modest benefit of surgery for unselected patients with asymptomatic carotid artery stenosis carotid endarterectomy cannot be routinely recommended for these patients pending reliable identification of high risk subgroups, and medical management is a sensible alternative for most patients.

Familial dwarfism and painful muscle spasms.

We report a family with a disorder characterized by limbs and truncal undulating painful muscle spasms, short stature, fine and sparse hair in the scalp, absence of body hair, low implanted ears, big nose, pitched voice, enlarged heart ventricles and increased fasting glucose levels. Symptoms began in childhood and did not progress after the third decade of life. This disorder represents a new clinical phenotype among the several forms of dwarfism associated with neurological manifestations already described in the literature.

Survey of the causes of stroke among Mexican Americans in South Texas.

Management strategies for optimal stroke prevention depend on the cause of threatened stroke. We know relatively little about the etiology of stroke in Mexican Americans, who make up one quarter of the population in Texas. A retrospective case series of 159 consecutive patients hospitalized in San Antonio, Tex, for acute, first-ever stroke compared risk factors, features, and causes of stroke between Mexican Americans and whites. Mexican Americans who had strokes were significantly younger than whites and had diabetes mellitus more often. Intracerebral hemorrhage and lacunar infarcts occurred often in Mexican Americans. Ethnicity appeared to be an independent risk factor for lacunar infarction. Mortality and functional outcome at the time of hospital discharge were similar in Mexican Americans and whites. Intrinsic small-vessel disease causing lacunar infarcts and intracerebral hemorrhage accounts for about one half of strokes in Mexican Americans. Stroke among Mexican Americans in South Texas has a distinctive profile with implications for its prevention.

The Levels of Inflammatory Markers in the Treatment of Stroke study (LIMITS): inflammatory biomarkers as risk predictors after lacunar stroke.

BACKGROUND: Inflammation is increasingly recognised as playing a central role in atherosclerosis, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischaemic stroke is less clear. The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) study will address hypotheses related to the role of inflammatory markers in secondary stroke prevention in an efficient manner using the well-established framework of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (NCT00059306). METHODS: SPS3 is an ongoing Phase III multicentre secondary prevention trial focused on preventing recurrent stroke in patients with small vessel ischaemic stroke, or lacunes. In SPS3, patients are assigned in a factorial design to aspirin vs. aspirin plus clopidogrel, and to usual vs. aggressive blood pressure targets. The purpose of LIMITS is to determine whether serum levels of inflammatory markers - including high-sensitivity C-reactive protein, serum amyloid A, CD40 ligand, and monocyte chemoattractant protein-1 - predict recurrent stroke and other vascular events among lacunar stroke patients. The project will also determine whether these markers predict which people will respond best to dual antiplatelet therapy with clopidogrel and aspirin, as well the relationship to cognitive function. ANALYSIS: plan Multivariable Cox proportional hazard regression modeling will be used to estimate hazard ratios for the effect of marker levels on risk of recurrent stroke and other outcomes after adjusting for additional potential risk factors, including age, gender, ethnicity, treatment arm, and traditional stroke risk factors. Interactions between marker levels and treatment assignment for both arms of the SPS3 study will be assessed. Observations will be censored at the time of last follow-up visit. CONCLUSIONS: LIMITS represents an efficient approach to the identification of novel inflammatory biomarkers for use in risk prediction and treatment selection in patients with small vessel disease.