Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome

BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is frequent in stroke patients. Risk factors, treatment response, short-term and long-term outcome of SDB in stroke patients are poorly known. METHODS: We prospectively studied 152 patients (mean age 56+/-13 years) with acute ischemic stroke. Cardiovascular risk factors, Epworth sleepiness score (ESS), stroke severity/etiology, and time of stroke onset were assessed. The apnea-hypopnea index (AHI) was determined 3+/-2 days after stroke onset and 6 months later (subacute phase). Continuous positive airway pressure (CPAP) treatment was started acutely in patients with SDB (AHI > or =15 or AHI > or =10+ESS >10). CPAP compliance, incidence of vascular events, and stroke outcome were assessed 60+/-16 months later (chronic phase). RESULTS: Initial AHI was 18+/-16 (> or =10 in 58%, > or =30 in 17% of patients) and decreased in the subacute phase (P<0.001). Age, diabetes, and nighttime stroke onset were independent predictors of AHI (r2=0.34). In patients with AHI > or =30, age, male gender, body mass index, diabetes, hypertension, coronary heart disease, ESS, and macroangiopathic etiology of stroke were significantly higher/more common than in patients with AHI <10. Long-term incidence of vascular events and stroke outcome were similar in both groups. CPAP was started in 51% and continued chronically in 15% of SDB pts. Long-term stroke mortality was associated with initial AHI, age, hypertension, diabetes, and coronary heart disease. CONCLUSIONS: SDB is common particularly in elderly stroke male patients with diabetes, nighttime stroke onset, and macroangiopathy as cause of stroke; it improves after the acute phase, is associated with an increased poststroke mortality, and can be treated with CPAP in a small percentage of patients.

Intracardiac devices for stroke prevention

Stroke is a significant cause of serious disability and death worldwide. A substantial proportion of strokes are related to an underlying cardiac embolic source, most commonly in association with atrial arrhythmias (fibrillation/flutter). Atrial fibrillation is considered a major risk factor for stroke. Although long-term prophylactic oral anticoagulation has been shown to be very effective in reducing stroke in patients with atrial fibrillation, it has a number of major limitations and is not feasible in all patients. In such cases, the use of percutaneously (transvenous) implanted left atrial appendage occlusive devices or surgical appendage obliteration is being explored. Similarly, the presence of a patent foramen ovale, especially in the presence of an atrial septal aneurysm, is now recognized as an important potential mediator of paradoxical cardiogenic embolism. Percutaneous patent foramen ovale closure is becoming increasingly established as a safe and effective means of preventing recurrent strokes in the presence of a patent foramen ovale. In this account, the authors discuss the intracardiac devices and techniques available and the relative merits of their use for stroke prevention.

Estimating the number of motor units using random sums with independently thinned terms

The problem of estimating the numbers of motor units N in a muscle is embedded in a general stochastic model using the notion of thinning from point process theory. In the paper a new moment type estimator for the numbers of motor units in a muscle is denned, which is derived using random sums with independently thinned terms. Asymptotic normality of the estimator is shown and its practical value is demonstrated with bootstrap and approximative confidence intervals for a data set from a 31-year-old healthy right-handed, female volunteer. Moreover simulation results are presented and Monte-Carlo based quantiles, means, and variances are calculated for N in{300,600,1000}.

Neuropsychological problems after paediatric stroke: two year follow-up of Swiss children

AIM: The aim of this study was to obtain information about neurological and cognitive outcome for a population-based group of children after paediatric ischaemic stroke. METHODS: Data from the Swiss neuropaediatric stroke registry (SNPSR), from 1.1.2000 to 1.7.2002, including children (AIS 1) and neonates (AIS 2). At 18-24 months after a stroke, a follow-up examination was performed including a history, neurological and neuropsychological assessment. RESULTS: 33/48 children (22 AIS 1, 11 AIS 2) participated in the study. Neurological outcome was good in 16/33. After childhood stroke mean IQ levels were normal (94), but 6 children had IQ < 85 (50-82) and neuropsychological problems were present in 75%. Performance IQ (93) was reduced compared to verbal IQ (101, p = 0.121) due to problems in the domain of processing speed (89.5); auditory short-term memory was especially affected. Effects on school career were common. Outcome was worse in children after right-sided infarction. Children suffering from stroke in mid-childhood had the best prognosis. There was no clear relationship between outcome and localisation of the lesion. After neonatal stroke 7/11 children showed normal development and epilepsy indicated a worse prognosis in the remaining 4. CONCLUSION: After paediatric stroke neuropsychological problems are present in about 75% of children. Younger age at stroke as well as an emergence of epilepsy were predictors for worse prognosis.

Curing capability of halogen and LED light curing units in deep class II cavities in extracted human molars

Class II cavities were prepared in extracted lower molars filled and cured in three 2-mm increments using a metal matrix. Three composites (Spectrum TPH A4, Ceram X mono M7 and Tetric Ceram A4) were cured with both the SmartLite PS LED LCU and the Spectrum 800 continuous cure halogen LCU using curing cycles of 10, 20 and 40 seconds. Each increment was cured before adding the next. After a seven-day incubation period, the composite specimens were removed from the teeth, embedded in self-curing resin and ground to half the orofacial width. Knoop microhardness was determined 100, 200, 500, 1000, 1500, 2500, 3500, 4500 and 5500 microm from the occlusal surface at a distance of 150 microm and 1000 microm from the metal matrix. The total degree of polymerization of a composite specimen for any given curing time and curing light was determined by calculating the area under the hardness curve. Hardness values 150 microm from the metal matrix never reached maximum values and were generally lower than those 1000 microm from the matrix. The hardest composite was usually encountered between 200 microm and 1000 microm from the occlusal surface. For every composite-curing time combination, there was an increase in microhardness at the top of each increment (measurements at 500, 2500 and 4500 microm) and a decrease towards the bottom of each increment (measurements at 1500, 3500 and 5500 microm). Longer curing times were usually combined with harder composite samples. Spectrum TPH composite was the only composite showing a satisfactory degree of polymerization for all three curing times and both LCUs. Multiple linear regression showed that only the curing time (p < 0.001) and composite material (p < 0.001) had a significant association with the degree of polymerization. The degree of polymerization achieved by the LED LCU was not significantly different from that achieved by the halogen LCU (p = 0.54).

Design of custom-shaped vascularized tissues using microtissue spheroids as minimal building units

Tissue engineering strategies are gathering clinical momentum in regenerative medicine and are expected to provide excellent opportunities for therapy for difficult-to-treat human pathologies. Being aware of the requirement to produce larger artificial tissue implants for clinical applications, we used microtissues, produced using gravity-enforced self-assembly of monodispersed primary cells, as minimal tissue units to generate scaffold-free vascularized artificial macrotissues in custom-shaped agarose molds. Mouse myoblast, pig and human articular-derived chondrocytes, and human myofibroblast (HMF)-composed microtissues (microm3 scale) were amalgamated to form coherent macrotissue patches (mm3 scale) of a desired shape. Macrotissues, assembled from the human umbilical vein endothelial cell (HUVEC)-coated HMF microtissues, developed a vascular system, which functionally connected to the chicken embryo's vasculature after implantation. The design of scaffold-free vascularized macrotissues is a first step toward the scale-up and production of artificial tissue implants for future tissue engineering initiatives.

Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis

BACKGROUND: We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator (tPA) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage (ICH). METHODS AND RESULTS: Prospectively collected, population-based data for 341 consecutive acute stroke patients (62% men; mean age, 66 years) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerland (3 academic and 5 community) between January 2001 and November 2004 were retrospectively analyzed. The primary outcome measure was neurological deterioration > or = 4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke (defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans, in the absence of ICH) or by ICH. Early recurrent ischemic stroke was diagnosed in 2 patients (0.59%; 95% confidence interval, 0.07% to 2.10%) and symptomatic ICH in 15 patients (4.40%; 95% confidence interval, 2.48% to 7.15%). Both recurrent ischemic strokes occurred during thrombolysis, whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion. CONCLUSIONS: Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis, with a different temporal pattern compared with that of symptomatic ICH.

Effects of somatosensory stimulation on use-dependent plasticity in chronic stroke

BACKGROUND AND PURPOSE: There is a need to develop strategies to enhance the beneficial effects of motor training, including use-dependent plasticity (UDP), in neurorehabilitation. Peripheral nerve stimulation (PNS) modulates motor cortical excitability in healthy humans and could influence training effects in stroke patients. METHODS: We compared the ability of PNS applied to the (1) arm, (2) leg, and (3) idle time to influence training effects in the paretic hand in 7 chronic stroke patients. The end point measure was the magnitude of UDP. RESULTS: UDP was more prominent with arm stimulation (increased by 22.8%) than with idle time (by 2.9%) or leg stimulation (by 6.4%). CONCLUSIONS: PNS applied to the paretic limb paired with motor training enhances training effects on cortical plasticity in stroke patients.

Outcome of stroke with mild or rapidly improving symptoms

BACKGROUND AND PURPOSE: Acute ischemic stroke with mild or rapidly improving symptoms is expected to result in good functional outcome, whether treated or not. Therefore, thrombolysis with its potential risks does not seem to be justified in such patients. However, recent studies indicate that the outcome is not invariably benign. METHODS: We analyzed clinical and radiological data of patients with stroke who presented within 6 hours of stroke onset and did not receive thrombolysis because of mild or rapidly improving symptoms. Univariate and logistic regression analyses were performed to define predictors of clinical outcome. RESULTS: One hundred sixty-two consecutive patients (110 men and 52 women) aged 63+/-13 years were included. The median National Institutes of Health Stroke Scale score on admission was 2 (range, 1 to 14). All patients presented within 6 hours of symptom onset. After 3 months, modified Rankin Scale score was Stroke Scale score >/=10 points increased the odds of unfavorable outcome or death 16.9-fold (95% CI: 1.8 to 159.5; P<0.013), and proximal vessel occlusion increased the odds 7.13-fold (95% CI: 1.1 to 45.5; P<0.038). CONCLUSIONS: Seventy-five percent of patients with mild or rapidly improving symptoms will have a favorable outcome after 3 months. Therefore, a decision against thrombolysis seems to be justified in the majority of patients. However, selected patients, especially those with proximal vessel occlusions and baseline National Institutes of Health Stroke Scale scores >/=10 points, might derive a benefit from thrombolysis.

EFFICIENT EVALUATION OF RANKING PROCEDURES WHEN THE NUMBER OF UNITS IS LARGE WITH APPLICATION TO SNP IDENTIFICATION

Simulation-based assessment is a popular and frequently necessary approach to evaluation of statistical procedures. Sometimes overlooked is the ability to take advantage of underlying mathematical relations and we focus on this aspect. We show how to take advantage of large-sample theory when conducting a simulation using the analysis of genomic data as a motivating example. The approach uses convergence results to provide an approximation to smaller-sample results, results that are available only by simulation. We consider evaluating and comparing a variety of ranking-based methods for identifying the most highly associated SNPs in a genome-wide association study, derive integral equation representations of the pre-posterior distribution of percentiles produced by three ranking methods, and provide examples comparing performance. These results are of interest in their own right and set the framework for a more extensive set of comparisons.

Percutaneous devices for stroke prevention

The most important approaches to prevent cerebral ischemia by catheter technique are patent foramen ovale (PFO) closure in patients with a history of cryptogenic stroke and left atrial appendage (LAA) occlusion in atrial fibrillation (AF) patients. Over the past years, several new devices have been developed for these procedures. Results of randomized trials comparing device therapy, antiplatelet, or anticoagulation therapy are still not available. However, several nonrandomized studies have shown promising results. This article gives a review on the current results and techniques of the most commonly used devices as well as on new developments and approaches to catheter-based stroke prevention.

Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy

BACKGROUND AND PURPOSE: For patients having suffered ischemic stroke, the current diagnostic strategies often fail to detect atrial fibrillation as a potential cause of embolic events. The aim of the study was to identify paroxysmal atrial fibrillation in stroke patients. We hypothesized that patients with frequent atrial premature beats (APBs) recorded in 24-hour ECG will show more often atrial fibrillation when followed by repeated long-term ECG recordings than patients without or infrequent APBs. METHODS: 127 patients with acute ischemic stroke and without known AF were enrolled in a prospective study to detect paroxysmal AF. Patients were stratified according to the number of APBs recorded in a 24-hour ECG (> or =70 APBs versus <70 APBs). Subsequently, they all underwent serial 7-day event-recorder monitoring at 0, 3, and 6 months. RESULTS: Serial extended ECG monitoring identified AF in 26% of patients with frequent APBs but only in 6.5% when APBs were infrequent (P=0.0021). A multivariate analysis showed that the presence of frequent APBs in the initial 24-hour ECG was the only independent predictor of paroxysmal AF during follow-up (odds ratio 6.6, 95% confidence intervals 1.6 to 28.2, P=0.01). CONCLUSIONS: In patients with acute ischemic stroke, frequent APBs (> or = 70/24 hours) are a marker for individuals who are at greater risk to develop or have paroxysmal AF. For such patients, we propose a diagnostic workup with repeated prolonged ECG monitoring to diagnose paroxysmal AF.