Acute stroke chameleons in a university hospital : Risk factors, circumstances, and outcomes.

OBJECTIVE: To identify risk factors, circumstances, and outcomes for individuals with acute ischemic stroke (AIS) chameleons (AIS-C) arriving in the emergency department of a university hospital. METHODS: We retrospectively reviewed all patients with AIS from the prospectively constructed Acute Stroke Registry and Analysis of Lausanne during 8.25 years. AIS-C were defined as a failure to suspect stroke or as incorrect exclusion of stroke diagnosis. They were compared with patients diagnosed correctly at the time of admission. RESULTS: Forty-seven of 2,200 AIS were missed (2.1%). These AIS-C were either very mild or very severe strokes. Multivariate analysis showed a younger age in patients with AIS-C (odds ratio [OR] per year 0.98, p < 0.01), less prestroke statin treatment (OR 0.29, p = 0.04), and lower diastolic admission blood pressure (OR 0.98 p = 0.04). They showed less eye deviation (OR 0.21, p = 0.04) and more cerebellar strokes (OR 3.78, p < 0.01). AIS-C were misdiagnosed as other neurologic (42.6% of cases) or nonneurologic (17.0%) disease, as unexplained decreased level of consciousness (21.3%), and as concomitantly present disease (19.1%). At 12 months, patients with AIS-C had less favorable outcomes (adjusted OR 0.21, p < 0.01) and higher mortality (adjusted OR 4.37, p < 0.01). CONCLUSIONS: AIS are missed in patients with younger age with a lower cerebrovascular risk profile and may be masked by other acute conditions. Patients with chameleons present more often with milder strokes or coma, fewer focal signs and cerebellar strokes, and have higher disability and mortality rates at 12 months. These findings may be used to raise awareness in emergency departments to recognize and treat such patients appropriately.

Clopidogrel Pharmacogenetics, resistance to antiplatelet therapy in ischemic stroke by Epigenome Wide Association Study (EWAS).

Clopidogrel is a widely used antiplatelet drug used in preventing vascular events after suffering a first stoke. Genome-wide association studies (GWAS) has not been able to establish a clear association between polymorphisms and recurrence. Therefore in the present final master project an epigenetic approach is proposed. Using an array based technology, 450.000 CpG sites across all genome were assessed in 48 individuals (21 cases and 21 controls). Looking at differentially methylated levels between cases and controls, 58 CpG sites (DMGs) were found. Although, no clear locus was observed. Looking individually to each 49 genes, two appeared to be important to our study. TRAF3 and ADAMTS2 are gens highly related to platelet aggregation. In orther to confirm these result, a new DNA methylation study will be done in a larger cohort, using Sequenom technology.

Angio-RM das artérias carótidas e vertebrais: análise de diferentes técnicas de volume e diluição de contraste em aparelho de 1,0 t e gradiente de 15 mt/m

OBJETIVO: Avaliar as artérias cervicais (carótidas e vertebrais) por meio da angio-RM, utilizando-se diferentes dosagens e diluições de contraste paramagnético. MATERIAIS E MÉTODOS: Estudo prospectivo em 15 pacientes, com análise de 30 artérias carótidas comuns, 30 artérias carótidas internas, 30 artérias carótidas externas e 30 artérias vertebrais, utilizando-se diferentes volumes e dosagens de contraste paramagnético: grupo I - dose única (14 ml de Gd-DTPA); grupo II -dose dupla (28 ml de Gd-DTPA); grupo III - dose única e diluída a 50%. A injeção de contraste foi realizada com a utilização de bomba injetora e com velocidades de injeção de 2 ml/s (grupo I) e 3 ml/s (grupos II e III). Os segmentos arteriais foram analisados por três examinadores em consenso de forma subjetiva, avaliando-se o grau de visibilidade, intensidade de contrastação e definição de seus contornos. RESULTADOS: Em todos os itens analisados os pacientes do grupo II apresentaram melhor resultado (visibilização total, boa contrastação dos vasos e contornos bem definidos). No grupo I houve boa visibilização das artérias carótidas e vertebrais, porém a intensidade de contraste e a definição dos contornos apresentaram variabilidade qualitativa. O grupo III apresentou os piores resultados, com dificuldade de visibilização, intensidade de contrastação baixa e contornos mal definidos. CONCLUSÃO: Entre os grupos analisados, a técnica utilizando dose dupla de gadolínio é a que permite melhor avaliação das artérias cervicais. A utilização de contraste diluído prejudica a avaliação dos vasos do pescoço.

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

OBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

Quantitative Analysis of Myelin and Axonal Remodeling in the Uninjured Motor Network After Stroke.

Contralesional brain connectivity plasticity was previously reported after stroke. This study aims at disentangling the biological mechanisms underlying connectivity plasticity in the uninjured motor network after an ischemic lesion. In particular, we measured generalized fractional anisotropy (GFA) and magnetization transfer ratio (MTR) to assess whether poststroke connectivity remodeling depends on axonal and/or myelin changes. Diffusion-spectrum imaging and magnetization transfer MRI at 3T were performed in 10 patients in acute phase, at 1 and 6 months after stroke, which was affecting motor cortical and/or subcortical areas. Ten age- and gender-matched healthy volunteers were scanned 1 month apart for longitudinal comparison. Clinical assessment was also performed in patients prior to magnetic resonance imaging (MRI). In the contralesional hemisphere, average measures and tract-based quantitative analysis of GFA and MTR were performed to assess axonal integrity and myelination along motor connections as well as their variations in time. Mean and tract-based measures of MTR and GFA showed significant changes in a number of contralesional motor connections, confirming both axonal and myelin plasticity in our cohort of patients. Moreover, density-derived features (peak height, standard deviation, and skewness) of GFA and MTR along the tracts showed additional correlation with clinical scores than mean values. These findings reveal the interplay between contralateral myelin and axonal remodeling after stroke.

High doses of onabotulinumtoxinA in post-stroke spasticity: a retrospective analysis.

We retrospectively evaluated the efficacy and safety of high doses of onabotulinumtoxinA (from 600 to 800 units) in 26 patients affected by upper and/or lower limb post-stroke spasticity. They were assessed before, 30 and 90 days after treatment. We observed a significant muscle tone reduction and a significant functional improvement (assessed with the Disability Assessment Scale). No adverse events were reported. In our retrospective analysis the treatment with high doses of onabotulinumtoxinA showed to be effective and safe.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: effect of Anticoagulation and Its Timing: the RAF Study.

BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Improving the Prediction of Spontaneous and Post-thrombolytic Recanalization in Ischemic Stroke Patients.

BACKGROUND: Endovascular treatment for acute ischemic stroke patients was recently shown to improve recanalization rates and clinical outcome in a well-defined study population. Intravenous thrombolysis (IVT) alone is insufficiently effective to recanalize in certain patients or of little value in others. Accordingly, we aimed at identifying predictors of recanalization in patients treated with or without IVT. METHODS: In the observational Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry, we selected those stroke patients (1) with an arterial occlusion on computed tomography angiography (CTA) imaging, (2) who had an arterial patency assessment at 24 hours (CTA/magnetic resonance angiography/transcranial Doppler), and (3) who were treated with IVT or had no revascularization treatment. Based on 2 separate logistic regression analyses, predictors of spontaneous and post-thrombolytic recanalization were generated. RESULTS: Partial or complete recanalization was achieved in 121 of 210 (58%) thrombolyzed patients. Recanalization was associated with atrial fibrillation (odds ratio , 1.6; 95% confidence interval, 1.2-3.0) and absence of early ischemic changes on CT (1.1, 1.1-1.2) and inversely correlated with the presence of a significant extracranial (EC) stenosis or occlusion (.6, .3-.9). In nonthrombolyzed patients, partial or complete recanalization was significantly less frequent (37%, P < .01). The recanalization was independently associated with a history of hypercholesterolemia (2.6, 1.2-5.6) and the proximal site of the intracranial occlusion (2.5, 1.2-5.4), and inversely correlated with a decreased level of consciousness (.3, .1-.8), and EC (.3, .1-.6) and basilar artery pathology (.1, .0-.6). CONCLUSIONS: Various clinical findings, cardiovascular risk factors, and arterial pathology on acute CTA-based imaging are moderately associated with spontaneous and post-thrombolytic arterial recanalization at 24 hours. If confirmed in other studies, this information may influence patient selection toward the most appropriate revascularization strategy.

Combined T2 -preparation and two-dimensional pencil-beam inner volume selection.

PURPOSE: To improve coronary magnetic resonance angiography (MRA) by combining a two-dimensional (2D) spatially selective radiofrequency (RF) pulse with a T2 -preparation module ("2D-T2 -Prep"). METHODS: An adiabatic T2 -Prep was modified so that the first and last pulses were of differing spatial selectivity. The first RF pulse was replaced by a 2D pulse, such that a pencil-beam volume is excited. The last RF pulse remains nonselective, thus restoring the T2 -prepared pencil-beam, while tipping the (formerly longitudinal) magnetization outside of the pencil-beam into the transverse plane, where it is then spoiled. Thus, only a cylinder of T2 -prepared tissue remains for imaging. Numerical simulations were followed by phantom validation and in vivo coronary MRA, where the technique was quantitatively evaluated. Reduced field-of-view (rFoV) images were similarly studied. RESULTS: In vivo, full field-of-view 2D-T2 -Prep significantly improved vessel sharpness as compared to conventional T2 -Prep, without adversely affecting signal-to-noise (SNR) or contrast-to-noise ratios (CNR). It also reduced respiratory motion artifacts. In rFoV images, the SNR, CNR, and vessel sharpness decreased, although scan time reduction was 60%. CONCLUSION: When compared with conventional T2 -Prep, the 2D-T2 -Prep improves vessel sharpness and decreases respiratory ghosting while preserving both SNR and CNR. It may also acquire rFoV images for accelerated data acquisition.

European Stroke Organisation (ESO) guidelines for the management of temperature in patients with acute ischemic stroke.

BACKGROUND: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke. METHODS: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. RESULTS: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke. CONCLUSIONS: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: an Outcome Analysis.

BACKGROUND AND PURPOSE: Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. METHODS: Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. RESULTS: 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). CONCLUSIONS: Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes.

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications.

OBJECTIVES: The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS: The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS: The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION: In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE: Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke.

OBJECTIVE: We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation. METHODS: The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings. RESULTS: A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use. CONCLUSION: Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.