Organized inpatient (stroke unit) care in very old patients

BACKGROUND AND PURPOSE: It is unclear whether very old patients benefit from organized inpatient (stroke unit) care. The aim of this work was to compare the clinical outcome of patients with first-ever ischemic stroke aged either >or=80 or <80 years who were treated conservatively (without cerebral revascularization) in a university-based stroke unit. PATIENTS AND METHODS: We included 147 (11%) patients >or=80 years and 1241 (89%) patients, <80 years. All patients underwent clinical examination, blood tests, electrocardiography (ECG), brain imaging and cerebrovascular ultrasound. Additional investigations were done at the discretion of the treating physician. The modified Rankin scale (mRS) score was used to assess the 3-month outcome (favorable: mRS, 0-1; poor: mRS, 2-6; death of any cause). RESULTS: Stroke severity did not differ between both groups [median National Institutes of Health Stroke Scale (NIHSS) score, 4]. Younger patients underwent magnetic resonance (MR) imaging of the brain, MR and catheter angiography and echocardiography (p<0.001) more frequently, whereas older patients underwent computed tomography of the brain and 24-hour ECG (p<0.001) more frequently. Stroke prevention included clopidogrel (p<0.001) and heparin (p=0.047) more often in older patients and aspirin (p=0.016) in younger patients. Recurrent ischemic events were similarly frequent in old (7%) and young (5%) patients. Favorable outcome was equally prevalent in old (71%) and young (76%) patients, whereas mortality was higher in older patients (7 and 3%, p=0.007). Admission NIHSS score >or=12 was the only independent predictor of unfavorable outcome (odds ratio, 19.6; 95% confidence interval, 9.7-39.6; p<0.001). CONCLUSION: Our work provides further evidence that also the oldest patients may benefit from conservative stroke unit care.

Increased prevalence of hyperhomocysteinemia in cervical artery dissection causing stroke: a case-control study

BACKGROUND: Spontaneous cervical artery dissection (sCAD) is a nonatherosclerotic vascular disease of unknown etiology. Mild elevation of total plasma homocysteine (tHcy) levels may be a risk factor for sCAD, but the precise mechanism remains unknown. On the other hand, mild hyperhomocysteinemia is also associated with ischemic stroke related to atherothrombotic or small artery disease. We undertook a case-control study to compare the prevalence of mild hyperhomocysteinemia and tHcy levels between patients with a first ischemic stroke due to sCAD and healthy volunteers, as well as patients with a first ischemic stroke due to atherothrombotic or small artery disease. METHODS: Fasting tHcy levels were determined in 346 consecutive patients with a first ischemic stroke due to sCAD (n = 86) and atherothrombotic or small artery disease (n = 260) within 24 h after the onset of symptoms, and in 100 healthy volunteers. RESULTS: Mild hyperhomocysteinemia was more prevalent in patients with sCAD causing ischemic stroke (n = 33, 38%) than in healthy volunteers (n = 23, 23%; p = 0.034), and less prevalent than in patients with ischemic stroke due to atherothrombotic or small artery disease (n = 149, 57%; p = 0.001). Mean fasting tHcy levels of patients with ischemic stroke caused by sCAD showed a trend to be higher (11.4 +/- 3.8 micromol/l) than those of healthy volunteers (10.2 +/- 3.0 micromol/l, p = 0.61), but were lower than those of patients with stroke due to atherothrombotic or small artery disease (13.6 +/- 6.6 micromol/l, p = 0.002). CONCLUSION: Our results suggest that mild hyperhomocysteinemia may be a risk factor for sCAD causing ischemic stroke, but further studies are needed to identify a possible mechanism. This study confirms the association of hyperhomocysteinemia with ischemic stroke due to atherothrombotic or small artery disease.

The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study: baseline characteristics of the population

BACKGROUND: The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study is an international double-blind, randomized controlled trial designed to investigate the superiority of the specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day), in reducing cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack. Here we describe the baseline characteristics of the population. METHODS AND RESULTS: Parameters recorded at baseline included vital signs, risk factors, medical history, and concomitant treatments, as well as stroke subtype, stroke-associated disability on the modified Rankin scale, and scores on scales for cognitive function and dependency. Eight hundred and two centers in 46 countries recruited a total of 19,119 patients between February 2006 and April 2008. The population is evenly distributed and is not dominated by any one country or region. The mean +/- SD age was 67.2 +/- 7.9 years, 63% were male, and 83% Caucasian; 83% had hypertension, and about half the population smoked or had quit smoking. Ninety percent of the qualifying events were ischemic stroke, 67% of which were classified as atherothrombotic or likely atherothrombotic (pure or coexisting with another cause). Modified Rankin scale scores showed slight or no disability in 83% of the population, while the scores on the Mini-Mental State Examination, Isaacs' Set Test, Zazzo's Cancellation Test, and the instrumental activities of daily living scale showed a good level of cognitive function and autonomy. CONCLUSIONS: The PERFORM study population is homogeneous in terms of demographic and disease characteristics. With 19,119 patients, the PERFORM study is powered to test the superiority of terutroban over aspirin in the secondary prevention of cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Interdisciplinary Cardiovascular and Neurologic Outpatient Rehabilitation in Patients Surviving Transient Ischemic Attack or Stroke With Minor or No Residual Deficits

Objective To evaluate the feasibility and effectiveness of a comprehensive outpatient rehabilitation program combining secondary prevention and neurorehabilitation to improve vascular risk factors, neurologic functions, and health-related quality of life (HRQOL) in patients surviving a transient ischemic attack (TIA) or stroke with minor or no residual deficits. Design Prospective interventional single-center cohort study. Setting University hospital. Participants Consecutive consenting patients having sustained a TIA or stroke with 1 or more vascular risk factors (N=105) were included. Interventions Three-month hospital-based secondary prevention and neurorehabilitation outpatient program with therapeutic and educational sessions twice a week. Patients were evaluated at entry and program end. Main Outcome Measures Impact on vascular risk factors, neurological outcome, and HRQOL. Results A total of 105 patients entered the program and 95 patients completed it. Exercise capacity (P<.000), smoking status (P=.001), systolic (P=.001) and diastolic (P=.008) blood pressure, body mass index (P=.005), low-density lipoprotein cholesterol (P=.03), and triglycerides (P=.001) improved significantly. Furthermore, the 9-Hole-Peg-Test (P<.000), Six-minute Walking Test (P<.000), and One Leg Stand Test (P<.011) values as well as HRQOL improved significantly. The program could be easily integrated into an existing cardiovascular prevention and rehabilitation center and was feasible and highly accepted by patients. Conclusions Comprehensive combined cardiovascular and neurologic outpatient rehabilitation is feasible and effective to improve vascular risk factors, neurologic functions, and HRQOL in patients surviving TIA or stroke with minor or no residual deficits.

Optimal sequence timing of CT angiography and perfusion CT in patients with stroke

OBJECTIVE Standard stroke CT protocols start with non-enhanced CT followed by perfusion-CT (PCT) and end with CTA. We aimed to evaluate the influence of the sequence of PCT and CTA on quantitative perfusion parameters, venous contrast enhancement and examination time to save critical time in the therapeutic window in stroke patients. METHODS AND MATERIALS Stroke CT data sets of 85 patients, 47 patients with CTA before PCT (group A) and 38 with CTA after PCT (group B) were retrospectively analyzed by two experienced neuroradiologists. Parameter maps of cerebral blood flow, cerebral blood volume, time to peak and mean transit time and contrast enhancements (arterial and venous) were compared. RESULTS Both readers rated contrast of brain-supplying arteries to be equal in both groups (p=0.55 (intracranial) and p=0.73 (extracranial)) although the extent of venous superimposition of the ICA was rated higher in group B (p=0.04). Quantitative perfusion parameters did not significantly differ between the groups (all p>0.18), while the extent of venous superimposition of the ICA was rated higher in group B (p=0.04). The time to complete the diagnostic CT examination was significantly shorter for group A (p<0.01). CONCLUSION Performing CTA directly after NECT has no significant effect on PCT parameters and avoids venous preloading in CTA, while examination times were significantly shorter.

Transesophageal echocardiography in cryptogenic stroke and patent foramen ovale: analysis of putative high-risk features from the risk of paradoxical embolism database

BACKGROUND Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), although the pathogenicity of a discovered PFO in the setting of CS is typically unclear. Transesophageal echocardiography features such as PFO size, associated hypermobile septum, and presence of a right-to-left shunt at rest have all been proposed as markers of risk. The association of these transesophageal echocardiography features with other markers of pathogenicity has not been examined. METHODS AND RESULTS We used a recently derived score based on clinical and neuroimaging features to stratify patients with PFO and CS by the probability that their stroke is PFO-attributable. We examined whether high-risk transesophageal echocardiography features are seen more frequently in patients more likely to have had a PFO-attributable stroke (n=637) compared with those less likely to have a PFO-attributable stroke (n=657). Large physiologic shunt size was not more frequently seen among those with probable PFO-attributable strokes (odds ratio [OR], 0.92; P=0.53). The presence of neither a hypermobile septum nor a right-to-left shunt at rest was detected more often in those with a probable PFO-attributable stroke (OR, 0.80; P=0.45; OR, 1.15; P=0.11, respectively). CONCLUSIONS We found no evidence that the proposed transesophageal echocardiography risk markers of large PFO size, hypermobile septum, and presence of right-to-left shunt at rest are associated with clinical features suggesting that a CS is PFO-attributable. Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to CS.

Longitudinal polysomnographic assessment from acute to subacute phase in infratentorial versus supratentorial stroke

Background: Regulation of sleep and sleep-related breathing resides in different brain structures. Vascular lesions can be expected to differ in their consequences on sleep depending on stroke topography. However, studies addressing the differences in sleep and sleep-related breathing depending on stroke topography are scarce. The aim of the present investigation was to compare the sleep and sleep-related breathing of patients with supratentorial versus infratentorial stroke. Methods: This study was part of the prospective multicenter study SAS-CARE-1 (Sleep-Disordered Breathing in Transient Ischemic Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy (SAS-CARE); NCT01097967). We prospectively included 14 patients (13 male, age 66 ± 6 years) with infratentorial lesions and 14 patients (14 male, age 64 ± 7 years) with supratentorial lesions, matched for age and stroke severity. Polysomnography was recorded in all during the acute phase within 9 days after stroke onset and 3 months later. Results: During the acute phase after stroke, patients with infratentorial lesions had significantly more sleep-related breathing disorders than patients with supratentorial lesions with an apnea-hypopnea index >20 observed in 8 (57%) patients with infratentorial stroke and in only 2 (14%) patients with supratentorial stroke. Sleep-related breathing improved from the acute to the subacute phase (3 months), albeit remaining elevated in a significant proportion of subjects. Sleep parameters did not differ between the two patient groups but there was a general improvement of sleep from the acute to the subacute phase which was comparable for both patient groups. Although stroke severity was mild, recovery after 3 months was worse in patients with infratentorial stroke with 12 of 14 patients with supratentorial stroke being symptom free (NIHSS = 0), while this was the case for only 6 of 14 patients with infratentorial stroke. Conclusions: Patients with infratentorial lesions are at an increased risk for sleep-related breathing disorders, which are frequent in this group. Monitoring of sleep-related breathing is therefore especially recommended in patients with infratentorial stroke. Because of the absence of reliable differences in sleep parameters between the two patient groups, polygraphy, with reduced diagnostic costs, rather than polysomnography could be considered. The higher prevalence of sleep-related breathing disorders and the poorer recovery of patients with infratentorial lesions suggest that early treatment interventions should be considered.

Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

Risk of incident stroke in patients with Alzheimer disease or vascular dementia

OBJECTIVE To explore the risk of ischemic stroke, hemorrhagic stroke, or TIA in patients with Alzheimer disease (AD) or vascular dementia (VD). METHODS We conducted a follow-up study with a nested case-control analysis using the UK-based General Practice Research Database. We included patients aged 65 years and older with an incident diagnosis of AD or VD between 1998 and 2008 and a comparison group of dementia-free patients. We estimated incidence rates of ischemic stroke, hemorrhagic stroke, or TIA in patients with AD, VD, or without dementia, and we calculated odds ratios with 95% confidence intervals (CIs) of developing such an outcome in patients with AD or VD, stratified by use of antipsychotic drugs. RESULTS We followed 6,443 cases with AD, 2,302 with VD, and 9,984 dementia-free patients over time and identified 281 cases with incident ischemic stroke, 139 with hemorrhagic stroke, and 379 with TIA. The incidence rates of ischemic stroke for patients with AD, VD, or no dementia were 4.7/1,000 person-years (PYs) (95% CI 3.8-5.9), 12.8/1,000 PYs (95% CI 9.8-16.8), and 5.1/1,000 PYs (95% CI 4.3-5.9), respectively. Compared with dementia-free patients, the odds ratio of developing a TIA for patients with AD treated with atypical antipsychotic drugs was 4.5 (95% CI 2.1-9.2). CONCLUSIONS Patients with VD, but not AD, have a markedly higher risk of developing an ischemic stroke than those without dementia. In patients with AD, but not VD, use of atypical antipsychotic drugs was associated with an increased risk of TIA.

Three-dimensional, task-specific robot therapy of the arm after stroke: a multicentre, parallel-group randomised trial

BACKGROUND: Arm hemiparesis secondary to stroke is common and disabling. We aimed to assess whether robotic training of an affected arm with ARMin--an exoskeleton robot that allows task-specific training in three dimensions-reduces motor impairment more effectively than does conventional therapy. METHODS: In a prospective, multicentre, parallel-group randomised trial, we enrolled patients who had had motor impairment for more than 6 months and moderate-to-severe arm paresis after a cerebrovascular accident who met our eligibility criteria from four centres in Switzerland. Eligible patients were randomly assigned (1:1) to receive robotic or conventional therapy using a centre-stratified randomisation procedure. For both groups, therapy was given for at least 45 min three times a week for 8 weeks (total 24 sessions). The primary outcome was change in score on the arm (upper extremity) section of the Fugl-Meyer assessment (FMA-UE). Assessors tested patients immediately before therapy, after 4 weeks of therapy, at the end of therapy, and 16 weeks and 34 weeks after start of therapy. Assessors were masked to treatment allocation, but patients, therapists, and data analysts were unmasked. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00719433. FINDINGS: Between May 4, 2009, and Sept 3, 2012, 143 individuals were tested for eligibility, of whom 77 were eligible and agreed to participate. 38 patients assigned to robotic therapy and 35 assigned to conventional therapy were included in analyses. Patients assigned to robotic therapy had significantly greater improvements in motor function in the affected arm over the course of the study as measured by FMA-UE than did those assigned to conventional therapy (F=4.1, p=0.041; mean difference in score 0.78 points, 95% CI 0.03-1.53). No serious adverse events related to the study occurred. INTERPRETATION: Neurorehabilitation therapy including task-oriented training with an exoskeleton robot can enhance improvement of motor function in a chronically impaired paretic arm after stroke more effectively than conventional therapy. However, the absolute difference between effects of robotic and conventional therapy in our study was small and of weak significance, which leaves the clinical relevance in question.