ABSTRACT
Aim of the study was to investigate whether high-intensity interval cycling performed immediately after resistance training would inhibit muscle strength increase and hypertrophy expected from resistance training per se. Twenty-two young men were assigned into either resistance training (RE; N = 11) or resistance training plus high-intensity interval cycling (REC; N = 11). Lower body muscle strength and rate of force development (RFD), quadriceps cross-sectional area (CSA) and vastus lateralis muscle architecture, muscle fiber type composition and capillarization, and estimated aerobic capacity were evaluated before and after 8 weeks of training (2 times per week). Muscle strength and quadriceps CSA were significantly and similarly increased after both interventions. Fiber CSA increased significantly and similarly after both RE (type I: 13.6 ± 3.7%, type IIA: 17.6 ± 4.4%, type IIX: 23.2 ± 5.7%, P < 0.05) and REC (type I: 10.0 ± 2.7%, type IIA: 14.8 ± 4.3% type IIX: 20.8 ± 6.0%, P < 0.05). In contrast, RFD decreased and fascicle angle increased (P < 0.05) only after REC. Capillary density and estimated aerobic capacity increased (P < 0.05) only after REC. These results suggest that high-intensity interval cycling performed after heavy-resistance exercise may not inhibit resistance exercise-induced muscle strength/hypertrophy after 2 months of training, while it prompts aerobic capacity and muscle capillarization. The addition of high-intensity cycling after heavy-resistance exercise may decrease RFD partly due to muscle architectural changes.
Subject(s)
Muscle Fibers, Skeletal/physiology , Muscle Strength , Quadriceps Muscle/physiology , Resistance Training , Exercise Test , High-Intensity Interval Training , Humans , Hypertrophy , Male , Quadriceps Muscle/diagnostic imaging , Ultrasonography , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Apolipropotein E(apoE) is a plasma protein exhibiting three common isoforms (E2, E3, E4). Its involvement in lipoprotein metabolism may have an impact on stroke occurrence. As results in the literature are inconclusive further studies are needed to elucidate its role. Our objective was to study the role of apoE isoforms and the interplay with environmental risk factors in patients with first ischaemic stroke occurrence in the Greek population. METHODS: Three hundred and twenty-nine patients with first-ever ischaemic stroke were included in our study. Strokes of cardioembolic origin and patients with autoimmune or prothrombotic syndromes were excluded. A control group of 361 subjects with no stroke history were also included in our study. Risk factors (hyperlipidemia, hypertension, diabetes mellitus and smoking) were assessed. ApoE alleles were determined in all subjects participating in the study. RESULTS: Genotype ε3/ε3 was found to have a protective role against stroke occurrence compared with other genotypes (odds ratio 0.674, 95% confidence interval 0.480-0.946) especially in the female patient subgroup. In multivariate analysis after adjustment for age, body mass index (BMI), hypertension, dyslipidemia, diabetes mellitus and smoking, the role of genotype was limited and outweighed by risk factors in both genders. No association between apoE alleles and BMI, cholesterol, triglycerides or high-density lipoprotein plasma levels was noted. CONCLUSIONS: Our study was indicative of a protective role of the ε3/ε3 genotype, especially in female patients. However, risk factors such as age, BMI, hypertension, dyslipidemia, diabetes mellitus and smoking have a strong impact on stroke occurrence and outweigh the protective role of the ε3/ε3 genotype.
Subject(s)
Apolipoprotein E3/genetics , Brain Ischemia/genetics , Stroke/genetics , Aged , Female , Genotype , Greece , Humans , Male , Middle Aged , Polymorphism, Genetic , Protective Factors , Risk Factors , Sex FactorsABSTRACT
BACKGROUND AND PURPOSE: Ankle-brachial blood pressure index (ABI) is a clinical tool to identify the presence of peripheral artery disease. There is a scarcity of data associating ABI with long-term outcome in patients with IS. The association between ABI and long-term outcome in patients with first-ever acute IS was assessed. METHODS: Ankle-brachial blood pressure index was assessed in all consecutive patients with a first-ever acute IS admitted at Alexandra University hospital (Athens, Greece) between January 2005 and December 2010. ABI was considered normal when > 0.90 and ≤ 1.30. The Kaplan-Meier product limit method was used to estimate the probability of 5-year composite cardiovascular event-free (defined as recurrent stroke, myocardial infarction or cardiovascular death) and overall survival. A multivariate analysis was performed to assess whether ABI is an independent predictor of 5-year mortality and dependence. RESULTS: Amongst 653 patients, 129 (19.8%) with ABI ≤ 0.9 were identified. Five-year cumulative composite cardiovascular event-free and overall survival rates were better in normal ABI stroke patients (log-rank test: 7.22, P = 0.007 and 23.40, P < 0.001, respectively). There was no difference in 5-year risk of stroke recurrence between low and normal ABI groups (hazard ratio, HR = 1.23, 95% CI 0.68-2.23). In multivariate Cox regression analysis, independent predictors of 5-year mortality included age (HR = 2.55 per 10 years, 95% CI 1.86-3.48, P < 0.001), the National Institutes of Health Stroke Scale (per point increase HR = 1.12, 95% CI 1.08-1.16, P < 0.001), and low ABI (HR = 2.22, 95% CI 1.22-4.03, P = 0.009). Age (HR = 1.21 per 10 years, 95% CI 1.01-1.45, P = 0.04) and low ABI (HR = 1.72, 95% CI 1.11-2.67, P = 0.01) were independent predictors of the composite cardiovascular end-point. CONCLUSIONS: Low ABI in patients with acute IS is associated with increased 5-year cardiovascular event risk and mortality. However, ABI does not appear to predict long-term stroke recurrence.
Subject(s)
Ankle Brachial Index/statistics & numerical data , Brain Ischemia/epidemiology , Stroke/epidemiology , Adult , Aged , Aged, 80 and over , Brain Ischemia/mortality , Disease-Free Survival , Female , Greece/epidemiology , Humans , Male , Middle Aged , Recurrence , Stroke/mortality , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.
Subject(s)
Brain Ischemia/etiology , Stroke/etiology , Adolescent , Adult , Brain Ischemia/epidemiology , Europe/epidemiology , Female , Humans , Male , Middle Aged , Stroke/epidemiology , Young AdultABSTRACT
BACKGROUND/AIMS: Glycogen storage disease type II (GSD-II) is a lysosomal disorder caused by acid α glucosidase (GAA) deficiency. The infantile form is easier to recognize compared with the milder adult form that may manifest as myopathy without specific clinical characteristics. The aim of this study is to highlight frequent diagnostic errors in adult GSD-II patients. CASE REPORTS: We report four patients with confirmed GSD-II who were at first diagnosed with hypothyroid myopathy, connective tissue disorder, an underlying liver disease and muscular dystrophy, respectively. CONCLUSION: Internists but even neurologists with low suspicion may misdiagnose GSD-II. The early respiratory involvement and the characteristic laboratory abnormalities in a myopathic patient should include GAA deficiency in the differential diagnosis especially in the era of enzyme replacement therapy.
Subject(s)
Diagnostic Errors , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/physiopathology , Adult , Connective Tissue Diseases/diagnosis , Female , Humans , Hypothyroidism/diagnosis , Liver Diseases/diagnosis , Muscular Diseases/diagnosis , Muscular Dystrophies/diagnosisABSTRACT
Pompe disease is an inherited metabolic disorder caused by α-glycosidase deficiency. The adult onset form is mainly characterized by progressive proximal muscle weakness and respiratory dysfunction. The aim of the present study is to evaluate body composition in adult patients before and after enzyme replacement therapy (ERT). Body composition was examined at baseline by means of dual x-ray absorptiometry (DXA) in nine adult patients and after different time periods in six of them who received ERT. Total BMD (bone mineral density) was initially mildly decreased in two patients, while femoral neck BMD was decreased in five patients. On the other hand fat mass was increased in the majority of patients, while body mass index (BMI) was high in four. ERT administration did not seem to induce obvious BMD changes in any patient. Conclusively, the greater femoral neck BMD involvement may be attributed to the lower mechanical load applied by the selectively weakened muscles, whereas the increased fat mass may be the result of metabolic and nutritional derangement.
Subject(s)
Body Composition , Bone Density , Glycogen Storage Disease Type II/pathology , Absorptiometry, Photon , Adolescent , Adult , Aged , Female , Femur Neck/pathology , Glycogen Storage Disease Type II/prevention & control , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Although hypercoagulability-induced thromboembolism is generally accepted as cause of cerebral ischaemia in thalassemic patients, cardiogenic embolism has been recently suggested as another possible stroke etiology. METHODS: We present four adult ß-thalassemia major patients with manifest cardiac involvement who suffered territorial strokes. RESULTS: In the presence of siderotoxic cardiomyopathy and arrhythmia, we assumed cardiogenic embolism as etiology of stroke and initiated oral anticoagulation as preventive medication. Two of our patients were the first ß-thalassemia major patients who underwent successful thrombolysis with rtPA. CONCLUSIONS: Cardioembolism seems to be the cause of stroke in cases of ß-thalassemia major. Thrombolysis can be applied in the setting of acute brain ischaemia in such high risk patients.
Subject(s)
Anticoagulants/therapeutic use , Brain Ischemia/etiology , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , beta-Thalassemia/complications , Adult , Anti-Arrhythmia Agents/therapeutic use , Aphasia/etiology , Atrial Fibrillation/etiology , Brain Ischemia/diagnostic imaging , Brain Ischemia/drug therapy , Cardiomyopathies/etiology , Cardiomyopathy, Dilated/complications , Chelation Therapy , Combined Modality Therapy , Female , Hemiplegia/etiology , Hemosiderosis/etiology , Humans , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/etiology , Intracranial Embolism/complications , Male , Splenectomy , Tomography, X-Ray Computed , Transfusion Reaction , beta-Thalassemia/drug therapy , beta-Thalassemia/surgery , beta-Thalassemia/therapyABSTRACT
INTRODUCTION: Previous studies on posterior cerebral artery (PCA) strokes focused mainly on topography and underlying pathophysiology. However, there are no data on long-term prognosis and its association with the localization of the infarct. METHODS: All consecutive PCA strokes registered in the Athens Stroke Outcome Project between 01/1998 and 12/2009 were included in the analysis. The New England Posterior Circulation Registry criteria were applied to classify them in relation to topography: (i) pure PCA infarcts, including pure cortical-only and combined cortical/deep PCA infarcts (groups A and B respectively), and (ii) PCA-plus strokes, including cortical-only and combined cortical/deep PCA strokes with ≥1 concomitant infarcts outside PCA territory (groups C and D respectively). Patients were prospectively followed up to 10 years after stroke. RESULTS: Amongst 185 (8.1%) PCA patients that were followed up for 49.6±26.7months, 98 (53%), 24 (13%), 36 (19.5%), and 27 (14.6%) were classified in group A, B, C, and D, respectively. Infections and brain edema with mass effect were more frequently encountered in PCA-plus strokes compared to pure PCA (P<0.05 and <0.01 respectively). At 6 months, 56% of cortical-only PCA patients had no or minor disability, compared to 37%, 36%, and 26% in the other groups (P=0.015). The 10-year probability of death was 55.1% (95%CI: 42.2-68.0) for pure PCA compared to 72.5% (95%CI: 58.8-86.2) for PCA-plus (log-rank 14.2, P=0.001). Long-term mortality was associated with initial neurologic severity and underlying stroke mechanism. CONCLUSIONS: Patients with pure PCA stroke have significantly lower risk of disability and long-term mortality compared to PCA strokes with coincident infarction outside the PCA territory.
Subject(s)
Infarction, Posterior Cerebral Artery/mortality , Adolescent , Adult , Aged , Female , Humans , Infarction, Posterior Cerebral Artery/classification , Longitudinal Studies , Male , Middle Aged , Prognosis , Prospective Studies , Registries , Risk Assessment/methods , Risk Factors , Severity of Illness Index , Survivors , Young AdultABSTRACT
OBJECTIVE: The purpose of this study was to investigate the clinical, electrophysiological and pathological features of Churg Strauss syndrome (CSS) neuropathy. METHODS: Biopsies were selected from over 700 sural nerve biopsies. The diagnosis of vasculitis was based on established clinicopathological criteria. Complete laboratory, clinical, electrophysiological and pathological studies were performed in all cases. RESULTS: Nerve biopsies of 9 patients were diagnosed as Churg-Strauss syndrome. The pathological features were vasculitis with predominant axonal degeneration and a varying pattern of myelinated fiber loss. The vasculitic changes were found mainly in small epineural blood vessels. Mononeuritis multiplex and distal symmetrical and asymmetrical sensorimotor neuropathy, were equally frequent. CONCLUSION: We conclude that, Churg-Strauss syndrome complicated frequently with polyneuropathy, and as remission depends on immunosuppressive therapy, it is important to recognize it in the early stage. The diagnosis of polyneuropathy is based on clinical and electrophysiologic studies, but precise histology, immunolohistochemistry and morphometric study of the peripheral nerve biopsy may be decisive in establishing the diagnosis.
Subject(s)
Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/pathology , Polyneuropathies/etiology , Polyneuropathies/pathology , Adult , Aged , Biopsy , Churg-Strauss Syndrome/drug therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Polyneuropathies/drug therapy , Sural Nerve/pathologyABSTRACT
BACKGROUND AND PURPOSE: Data regarding stroke in young adults from Greece is scarce. We aimed to evaluate risk factors, etiology, and outcome in a hospital-based prospective observational study. METHODS: Data from a series of 253 first-ever ischemic stroke patients aged 15-45 were collected over 10 years. Stroke etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Comparisons were done between groups stratified by gender and age. The probability of death or composite vascular events during follow-up was estimated by the Kaplan-Meier method. We used Multivariate Cox proportional hazard analyses to determine the effect of different factors on mortality and occurrence of composite cardiovascular events. RESULTS: Although male patients predominate in our cohort (ratio 1.3:1), females outnumber males significantly at ages under 30. Smoking (59.3%) and dyslipidemia (41.1%) were the most frequent risk factors. Small vessel disease was identified as cause of stroke in 17.4%, whereas cardioembolism caused 13.4% of all strokes. No definite etiology was found in 33.6%, whereas other causes of stroke, including dissection (6.7%), were documented in 26.5%. The probability of 10-year survival was 86.3% (95%CI: 79.1-93.6). The corresponding probability of composite vascular events was 30.4% (95%CI: 19.6-41.2). Stroke severity and heart failure were the main predictors of mortality. At the end of the follow-up period, most patients (92.7% of survivors) were independent. CONCLUSION: There are gender- and age-related differences regarding risk factors and causes of ischemic stroke in young patients. Survival and long-term outcome is generally favorable.
Subject(s)
Brain Ischemia/complications , Stroke/epidemiology , Stroke/etiology , Adolescent , Adult , Age Factors , Cohort Studies , Female , Greece/epidemiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Severity of Illness Index , Sex Factors , Stroke/diagnosis , Stroke/metabolism , Stroke/therapy , Young AdultSubject(s)
Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/epidemiology , Nutritional Status , Adult , Age of Onset , Body Mass Index , Enzyme Replacement Therapy , Fibroblasts/enzymology , Fibroblasts/pathology , Glycogen Storage Disease Type II/drug therapy , Humans , Prognosis , alpha-Glucosidases/therapeutic useABSTRACT
BACKGROUND AND PURPOSE: Arterial hypertension is the major risk factor for intracerebral haemorrhage (ICH) and lacunar infarction (LI) and both types of cerebral lesions originate from pathology of the same deep perforating small arteries. We aimed to evaluate the relationship between vascular risk factors including common carotid artery intima-media thickness (CCA-IMT) with LI versus ICH. METHODS: We prospectively collected data from 159 first ever stroke patients (67 cases with ICH and 92 cases with LI) with documented history of hypertension. All subjects underwent B-mode ultrasonographic measurements of the CCA-IMT. Logistic regression modelling was used to determine the factors (established vascular risk factors, severity and duration of hypertension, concomitant medications and CCA-IMT) that may significantly differentiate LI from ICH. RESULTS: Patients with LI had significantly (p=0.002) larger CCA-IMT values (0.926 mm, 95% CI: 0.881-0.971) than subjects with ICH (0.815 mm, 95% CI: 0.762-0.868) even after adjusting for baseline characteristics and cardiovascular medications. The multivariate logistic regression procedure selected CCA-IMT, diabetes mellitus and hypercholesterolaemia as the only independent factors able to discriminate between LI and ICH. The risk for LI versus ICH increased continuously with increasing CCA-IMT. For each increment of 0.1 mm in CCA-IMT the probability of suffering from LI versus ICH increased by 36.6% (95 % CI: 13%-65.2%, p=0.001) even after adjustment for cardiovascular risk factors. CONCLUSIONS: Increased CCA-IMT values are a factor favouring LI over ICH in hypertensive patients. The measurement of CCA-IMT may be a useful non-invasive diagnostic tool for the risk assessment of LI with respect to ICH in such patients.
Subject(s)
Brain Infarction/etiology , Carotid Artery, Common/pathology , Cerebral Hemorrhage/etiology , Tunica Intima/pathology , Tunica Media/pathology , Biomarkers , Brain/blood supply , Humans , Hypertension/complications , Risk FactorsSubject(s)
Muscular Dystrophies, Limb-Girdle/genetics , Sarcoglycans/genetics , Child , Child, Preschool , Female , Founder Effect , Greece , Humans , Infant , Male , Mutation , Roma/geneticsABSTRACT
BACKGROUND: More than half of patients with documented hypertension surviving cerebrovascular events do not have their blood pressure (BP) controlled, despite the use of antihypertensive medication. Data on the possible reasons for poor BP control in stroke survivors are limited. METHODS: We evaluated prospectively parameters influencing the effectiveness of BP control in hypertensive stroke survivors who were followed up. RESULTS: At 3 months after stroke BP was effectively controlled in only 38.8% of patients. Diabetes mellitus had a negative influence on the effectiveness of antihypertensive medication by reducing significantly the chance of achieving a significant BP reduction, while patients suffering from coronary artery disease had an increased chance of getting their BP under control within 3 months after stroke onset. Diuretic medication was found to be an independent positive predictor for effective antihypertensive control. Combined therapy including diuretics was significantly more effective than antihypertensive monotherapy. CONCLUSIONS: Arterial pressure control in stroke survivors is poor. Risk factor profile, manifest heart disease, and the chosen antihypertensive medication are factors of prognostic relevance for effective BP control.
Subject(s)
Antihypertensive Agents/administration & dosage , Hypertension/drug therapy , Hypertension/mortality , Risk Assessment/methods , Stroke/mortality , Stroke/prevention & control , Aged , Blood Pressure/drug effects , Comorbidity , Female , Germany/epidemiology , Humans , Incidence , Male , Risk Factors , Survival Analysis , Survival RateABSTRACT
BACKGROUND: Chronic axonal polyneuropathy is a well-known clinical sequela of excessive alcohol consumption; however, acute axonal polyneuropathy related to alcohol abuse is less well recognized. OBJECTIVE: To describe alcohol-related acute axonal polyneuropathy in 5 chronic alcoholics who developed ascending flaccid tetraparesis and areflexia within 14 days. METHODS: Case series with clinical, laboratory, electrophysiological, and, in 1 patient, biopsy data. RESULTS: All 5 patients consumed a daily average of 250 g of alcohol, and 4 had lost a substantial amount of weight recently. Additional clinical features included painful paresthesia, myalgia, and glove and stocking-type sensory loss. Repeated cerebrospinal fluid examinations failed to show the marked increase of protein concentration with normal cell count typical of Guillain-Barré syndrome, although the protein level was mildly elevated in 1 patient. Blood laboratory findings were consistent with longstanding alcohol abuse. Compound muscle and sensory nerve action potentials were absent or reduced, while conduction velocities were normal or mildly reduced. Three to 4 weeks after onset, needle electromyography displayed moderate to severe fibrillations and positive sharp waves in addition to normal motor unit potentials, indicating an acute axonal polyneuropathy; this was confirmed by sural nerve biopsy in 1 patient. CONCLUSIONS: Excluding other factors, we assume that in these patients the combination of alcohol abuse and malnutrition caused severe acute axonal polyneuropathy. Its distinction from Guillain-Barré syndrome is important because treatment requires balanced diet, vitamin supplementation, and abstinence from alcohol, while immunotherapy may not be indicated.
Subject(s)
Axons/drug effects , Ethanol/adverse effects , Peripheral Nervous System Diseases/chemically induced , Acute Disease , Adult , Ataxia/etiology , Axons/pathology , Biopsy , Demyelinating Diseases/pathology , Diagnosis, Differential , Female , Humans , Male , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/pathology , Polyradiculoneuropathy/pathology , Severity of Illness IndexABSTRACT
The aim of this prospective observational study was to determine the association of acute blood pressure values with independent factors (demographic, clinical characteristics, early complications) in stroke subgroups of different aetiology. We evaluated data of 346 first-ever acute (<24 h) stroke patients treated in our stroke unit. Casual and 24-h blood pressure (BP) values were measured. Stroke risk factors and stroke severity on admission were documented. Strokes were divided into subgroups of different aetiopathogenic mechanism. Patients were imaged with CT-scan on admission and 5 days later to determine the presence of brain oedema and haemorrhagic transformation. The relationship of different factors to 24-h BP values (24-h BP) was evaluated separately in each stroke subgroup. In large artery atherosclerotic stroke (n=59), history of hypertension and stroke severity correlated with higher 24-h BP respectively. In cardioembolic stroke (n=87), history of hypertension, stroke severity, haemorrhagic transformation and brain oedema were associated with higher 24-h BP, while heart failure with lower 24-h BP. History of hypertension and coronary artery disease was related to higher and lower 24-h BP, respectively, in lacunar stroke (n=75). In patients with infarct of undetermined (n=57) cause 24-h BP were mainly influenced by stroke severity and history of hypertension. An independent association between higher 24-h BP and history of hypertension and cerebral oedema was documented in intracerebral haemorrhage (n=68). In conclusion, different factors influence acute BP values in stroke subtypes of different aetiology. If the clinical significance of these observations is verified, a differentiated approach in acute BP management based on stroke aetiology may be considered.
Subject(s)
Blood Pressure/physiology , Stroke/epidemiology , Stroke/physiopathology , Aged , Aged, 80 and over , Blood Pressure Monitoring, Ambulatory , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Brain Ischemia/etiology , Brain Ischemia/physiopathology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/physiopathology , Circadian Rhythm/physiology , Diastole/physiology , Female , Greece/epidemiology , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Male , Middle Aged , Multivariate Analysis , Patient Admission , Prospective Studies , Risk Factors , Severity of Illness Index , Statistics as Topic , Stroke/diagnosis , Stroke/etiology , Systole/physiology , Time Factors , Tomography, X-Ray ComputedABSTRACT
Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window. Neurological outcome depends on the recanalization time of the occluded vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic fibrinolysis in vitro. We examined the effects of transcranially applied US on recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exposure (0.5 W/cm(2); spatial peak, temporal peak intensity). Transcranial and direct US application in combination with rt-PA significantly (p<0.001) shortened recanalization time, increased perfusion flow and reperfusion rate in comparison with rt-PA-mediated thrombolysis alone. Recanalization rate within 30 min was 90-100% in the US-exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate reperfusion and recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated thrombolysis. Shortening of recanalization time could contribute to optimizing effects of acute thrombolytic stroke therapy.
Subject(s)
Brain Ischemia/physiopathology , Cerebrovascular Circulation/physiology , Plasminogen Activators/therapeutic use , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Ultrasonography, Doppler, Transcranial , Blood Flow Velocity/drug effects , Blood Flow Velocity/physiology , Brain Ischemia/diagnostic imaging , Brain Ischemia/drug therapy , Cerebrovascular Circulation/drug effects , Humans , In Vitro Techniques , Models, Biological , Phantoms, Imaging , Recombinant ProteinsABSTRACT
Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3 min.). Flow rate was significantly higher (p < 0.025) and increased faster in the combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We investigated the blood-brain barrier in rats after 90-min exposure time of the brain with 185-kHz US, but no damage was observed. Results suggest efficacy and safety of the 185-kHz transducer, which is superior to diagnostic US. Such a novel US probe may be able to optimize thrombolytic stroke treatment.