Determination of systemic inflammatory biomarkers in multiple sclerosis.

Background: Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system. We aimed to investigate serum and cerebrospinal fluid levels of different laboratory inflammatory biomarkers in patients with MS. Methods: A total of 120 subjects participated in the study, 60 of whom were diagnosed with MS, 30 with the final diagnosis of non-inflammatory diseases of the central nervous system (CNS), and 30 healthy subjects representing the control group. Regarding the progression of radiological findings after 2 years from the initial diagnosis, the MS group was divided into stationary radiological findings (n=30) and radiologically proven disease progression (n=30). In all patients, we analyzed levels of laboratory inflammatory biomarkers: C reactive protein (CRP), Neutrophil-to-lymphocyte ratio (NLR), Growth differentiation factor 15 (GDF15) in serum samples, and neurofilaments (NFs) in cerebrospinal fluid (CSF). NFs and GDF15 were analyzed initially, while CRP and NLR values were analyzed initially and after two years. Results: We found statistically lower GDF15 values and initial CRP values in the MS group regarding the group with non-inflammatory diseases of the CNS (p<0.0001). On the other side, we determined a significant elevation of laboratory markers CRP and NLR, initially and after a two-year period, in the MS subgroup with the progression of magnetic resonance imaging (MRI) findings (p<0.0001 and p=0.050, respectively). Also, we found a positive correlation between CRP and NFs (r=0.243, p=0.04), as well as a positive correlation between CRP and GDF15 in patients with MS (r=0.769, p<0.0001). Conclusions: We found a significant elevation of laboratory markers of systemic inflammation, CRP, and NLR in MS patients who developed disease progression based on MRI findings. There is a need for further studies to validate current parameters to be considered as useful markers of MS activity and disability.

Heat-not-burn tobacco products and cardiovascular risk reduction: A systematic review of randomized controlled trials.

BACKGROUND: Heat-not-burn (HNB) technology by the U.S. Food and Drug Administration has been classified as a modified risk tobacco product, which can be a better option for those populations who cannot give up the habit of smoking. The outlook on the effects of these products is quite controversial in the scientific world. OBJECTIVE: To present the effect of HNB tobacco products on the cardiovascular system, with reference to the existence of possible benefits of the technology. METHODS: The literature search was conducted in PubMed/Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases, with reliance on a well-defined guiding research statement. Quality appraisal was performed using the CASP checklist for randomized controlled trials. RESULTS: The search of three databases identified 167 records, and after selection process, 25 randomized controlled trials were eligible for our study's criteria. Twenty studies investigated the effects of HNB products on biomarkers of clinical relevance. Five studies evaluated other functional heart parameters rather than biomarkers. CONCLUSION: With HNB tobacco products, significant reductions were found in biomarkers of exposure and biological effect related to pathways involved in cardiovascular disease, including inflammation, oxidative stress, lipid metabolism, platelet function, and endothelial dysfunction.

Patients with neuropathic pain from lumbosacral radiculopathy demonstrate similar pressure pain thresholds and conditioned pain modulation to those with fibromyalgia.

OBJECTIVE: The purpose of the study was to evaluate pain thresholds, impairment of the endogenous pain modulatory system, and self-reported cognitive-emotional and central sensitization-related symptoms among three subject groups: a rarely studied patient cohort with neuropathic pain from lumbosacral radiculopathy (NPLSR), patients with fibromyalgia (FM) and healthy controls (HC). METHODS: Patient-reported pain-related symptomology was evaluated with psychometricallyvalidated questionnaires. Pressure pain threshold (PPT), heat pain threshold (HPT), and cold pain threshold (CPT) were assessed in the low back and contralateral forearm. Conditioned pain modulation (CPM) was evaluated with a recently introduced methodology that accounts for a standard error of measurement. RESULTS: Compared to the HC subjects, the FM and NPLSR subjects had significantly lower pain thresholds and more CPM impairment. No significant differences in PPT and CPM were observed between the FM and NPLSR groups. Significant group differences were found in self-reported symptoms of depression, anxiety, stress, and central sensitization. Self-reported symptom severity increased in a stair-step fashion, with the HC group scoring lowest and FM group scoring highest. CONCLUSION: The NPLSR group manifested CPM dysfunction and pressure hyperalgesia at similar levels to the FM group, indicating that these two chronic pain syndromes, likely based on different pathophysiological mechanisms, in fact share some common pain processing features. However, though both patient groups demonstrated similarities in pain processing, self-reported cognitive-emotional and central sensitization-related symptom severity was significantly higher in the FM cohort, which distinguished them from the chronic NPLSR cohort.

Changes in the first anti-seizure medication prescribed for children and adolescents with epilepsy in a tertiary clinical center in Serbia over two decades.

OBJECTIVES: We assessed the prevalence of the use of new anti-seizure medications and valproate in the female population over two decades. MATERIALS AND METHODS: We conducted a retrospective observational cross-sectional study of medical records of children and adolescents (4 - 19 years old) with newly diagnosed epilepsy in a tertiary clinical center in Serbia from 1997 to 1999 and 2017 to 2019. RESULTS: The statistical analysis revealed significant changes in the treatment of generalized and focal seizures and all etiologies of epilepsy. Valproate use in the adolescent girl population decreased significantly from 2017 to 2019. CONCLUSION: The prescription pattern of the initial anti-seizure medication changed significantly over the two decades. The results correspond to current guidelines and recommendations.

Which precocial rodent species is more suitable as the experimental model of microgravity influence on prenatal musculosketal development on international space station?

The International Space Station (ISS) has the possibility to perform experiments regarding rodent reproduction in microgravity. The musculoskeletal system at birth in precocial rodent species more resembles the human than that of altricial rodent species. For precocial rodent species with body weight ≤ 500 g (limit of ISS) determined were: adult body mass, newborn body mass, head-body length, tail length, existing variants (wild, domesticated, laboratory), single/group housing, dry food consumption/24 h, water intake/24 h, basal metabolic rate mlO2/g/h, environmental temperature, sand baths, urine output ml/24 h, fecal output g/24 h, size of fecal droplet, hair length, life span, length of oestrus cycle, duration of pregnancy, building nest, litter size, stage of musculoskeletal maturity at birth, and the duration of weaning. Characteristics were obtained by searching SCOPUS as well as the World Wide Web with key words for each of the species in English, Latin and, local language name. These characteristics were compared in order to find most appropriate species. Twelve precocial rodent species were identified. There is not enough data for Common yellow-toothed cavy, and Eastern spiny mouse. Inappropriate species were: Gundis, Dassie rat are a more demanding species for appropriate tending, litter size is small; Octodon degus requires sand baths as well as a nest during the first two weeks after delivery; muscle maturity of Spiny mouse at birth (myotubular stage), does not correspond to the human (late histochemical stage); Chinchilla requires separately housing, daily sand baths, has upper limit of weight. Possibility of keeping Southern mountain cavy as pet animal, short estrus, large litter size, absence of the need for nest and sand baths, makes this species the most promising candidates for experiments on ISS. If an experiment is planned with exposing gravid animals before term of the birth, then they might be kept together in the existing Rodent Habitat (USA). If an experiment with birth in microgravity is planned on ISS, the existing habitats do not provide conditions for such an experiment. It is necessary to develop habitats for separate keeping of pregnant animals to enable the following: 1. undisturbed delivery 2. prevent the possibility of hurting the newborns 3. ensure adequate post-partum maternal care and nursing.

Clinical Characteristics of Patients with Acute Ischemic Stroke Previously Vaccinated Against COVID-19.

OBJECTIVES: The aim of this study was to examine the clinical characteristics of patients with acute ischemic stroke which were previously vaccinated against Coronavirus Disease 2019 (COVID-19) and determine whether the vaccine had impact on outcome. MATERIALS AND METHODS: In this observational cohort study we analyzed the clinical characteristics of 58 patients with ischemic stroke, previously vaccinated against COVID-19. We analyzed demographic characteristics, risk factors, type of stroke and outcome. We also compared outcome of those patients with outcome in stroke patients hospitalized in the same period but not vaccinated, patients hospitalized during the pandemic, before vaccination began, and stroke patients hospitalized before the pandemic. Further, we compared mortality rate with mortality rate in patients who had acute ischemic stroke and COVID-19 simultaneously. RESULTS: The mean age of the patients was 71.0 years, most were male (58.6%), mostly with risk factors for stroke. In the largest number of patients, 17 (29.3%), the etiopathogenetic mechanism of stroke was atherosclerosis of the large arteries. Mortality in vaccinated patients was identical to mortality in stroke patients before pandemic, without significant difference from mortality in unvaccinated patients (13.8% versus 8.6%; p= 0.23). The mean NIHSS and mRS score at discharge for all examined groups were without significant difference. A significant difference in mortality was found between COVID-19 positive and COVID-19 negative stroke patients (37.8% versus 18.1%; p=0.001). CONCLUSIONS: There are no significant differences in clinical characteristics of stroke in vaccinated compared to unvaccinated patients. We did not find a connection between vaccination and stroke.

Cognitive impairment and depression after acute myocardial infarction: associations with ejection fraction and demographic characteristics.

Cognitive impairment and depression are often associated with acute myocardial infarction, however, the risk factors for their occurrence after myocardial infarction are still unclear. To determine the effect of reduced ejection fraction and demographic characteristics on the occurrence of cognitive impairment and depression after myocardial infarction. In the prospective study, the final sample consisted of 82 patients. Based on the value of the ejection fraction, the patients were divided into those with a value of < 40% and those having a value of ≥ 40%. Demographic data (age, gender, education), and data on comorbidities, were collected from the patients' medical history. The instruments of studies were: Mini-mental test and Beck depression inventory. The occurrence of cognitive impairment and depression was not, to a significant degree, associated with the level of ejection fraction. In contrast, demographics have shown positive predictive effects. Among demographic characteristics, the age of the patient proved to be a significant predictor for the occurrence of cognitive impairment (p = 0.004). The probability of cognitive impairment increases 1.16 times for each year of life. Significant depression predictor was female gender (p = 0.014). The probability of depression was 3.5 times greater for female gender. Cognitive impairment after acute myocardial infarction is more common in older patients, and depression in more common in women.

Outcome after intravenous thrombolysis in embolic stroke of undetermined source compared to cardioembolic stroke.

BACKGROUND: It is assumed that most cases of embolic stroke of undetermined source (ESUS) are of cardioembolic origin. The data about outcome after the treatment with intravenous thrombolysis (IVT) for this type of acute ischemic stroke (AIS) are limited. We aimed to compare clinical characteristics and outcomes after IVT for AIS between patients with ESUS and cardioembolic stroke (CS). METHODS: This study was a single center retrospective analysis of stroke patients treated with IVT. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish stroke etiology subtype at 3 months, while ESUS was considered a subset of stroke of undetermined etiology, defined according to 2014 international criteria. Functional outcome was assessed at 3 months and defined as excellent (modified Rankin scale 0-1) and favorable (modified Rankin scale 0-2). RESULTS: Total of 394 patients were treated with IVT; 113 had a cardioembolism, 88 had undetermined stroke subtype, of which 62 met the ESUS criteria. Patients with ESUS were on average younger (63.7 years versus 69.7 years, p = 0.001), had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission (12 versus 15, p = 0.002) and lower prevalence of antiplatelets use (27.4% versus 42.5%, p = 0.04) compared with CS patients. Favorable outcome was more likely in ESUS patients, at discharge (48.4% versus 24.0%, p = 0.002) and after 3 months (71.0% versus 37.2%, p < 0.001). Hemorrhagic transformation was less frequent (17.7% versus 33.6%, p = 0.03) in ESUS patients. Independent predictors of 3­month favorable outcome were ESUS, the absence of leukoaraiosis on computed tomography (CT) and absence of diabetes as a risk factor. CONCLUSION: Patients with ESUS had better outcome after IVT than patients with CS, which can be attributed to younger age and milder strokes in these patients.

PREDICTORS OF EARLY-ONSET DEPRESSION AFTER FIRST-EVER STROKE.

Post-stroke depression (PSD) is a severe and frequent stroke complication and one of the crucial factors for the outcome of rehabilitation and life quality after stroke. However, mood disorders frequently remain unnoticed and therefore untreated. The aim of the study was to examine all the potential risk factors and determine the independent predictors of early-onset depression after first-ever stroke, which would help identify high-risk patients, establish early diagnosis and timely treatment that would improve the course and prognosis of this disorder. This prospective study included 60 patients treated for their first-ever stroke; there were 30 patients diagnosed with depression and 30 patients without depression. The study included collection and analysis of all socio-demographic and clinical risk factors for PSD. Testing was performed two weeks after stroke. Depression was diagnosed according to the Mini International Neuropsychiatry Interview, DSM-IV diagnostic criteria, and depression severity was quantified by the Hamilton Depression Rating Scale. Cognitive impairment was assessed by the Mini Mental State Examination. Neurological deficit was assessed by the US National Institute of Health Stroke Scale. Our results showed that the independent predictors of early-onset depression after stroke were previous depressive episodes, cognitive dysfunction, and more severe neurological deficit.

Evaluation of Symptoms of Depression and Anxiety in Adolescents with Epilepsy in a Tertiary-Level Medical Center in Serbia.

BACKGROUNDS: Even though epilepsy is the most common neurological disorder in adolescence; studies of adolescents with epilepsy are scarce. OBJECTIVE: To evaluate whether adolescents with epilepsy are more likely to develop anxiety and depressive symptoms than their healthy peers and to determine the relationship of depression and anxiety scores to epilepsy-related variables. SETTINGS AND DESIGN: Cross-sectional observational study. METHODS AND PROCEDURES: Ninety adolescents with epilepsy aged 13-19 years were compared with healthy controls using the Beck Depression Inventory II (BDI II) and the Stait Trait Anxiety Inventory (STAI) for assessment of depressive and anxiety symptoms. Within the study group, epilepsy-related variables were also determined using the stated measures. STATISTICAL ANALYSIS USED: The independent sample t-test, One-Way ANOVA, Pearson's correlation coefficient. OUTCOMES AND RESULTS: 23.3% of the study group and 8.3% of the control group had mild to moderate depression. The mean BDI II score was significantly higher in the group of adolescents with epilepsy. Comparing the STAI scores, results on both STAI scales were higher in the study group. Regarding the epilepsy-related variables, a high frequency of seizures, symptomatic etiology and polytherapy showed strong associations with high depression and anxiety scores. CONCLUSION AND IMPLICATIONS: Symptoms of depression and anxiety are not uncommon among adolescents with epilepsy. BDI II and STAI may be used as screening tools to provide useful information to clinicians when assessing adolescents' mental status.

Patients with Acute Lacunar Infarction Have Benefit from Intravenous Thrombolysis.

INTRODUCTION: Usefulness of intravenous thrombolysis in patients with acute lacunar cerebral infarction is questionable. The aim of this study was to evaluate the efficacy and safety of intravenous thrombolysis in patients with lacunar infarction in comparison with patients with nonlacunar infarction as well as with patients with lacunar infarction who were not treated with intravenous thrombolysis. MATERIALS AND METHODS: In the first part of the study, among patients with acute ischemic stroke treated with intravenous thrombolysis, characteristics and outcomes of 46 patients with lacunar and 221 patients with nonlacunar infarction were compared. In the second part, 46 patients with lacunar infarction treated with intravenous thrombolysis were compared with 45 lacunar infarction patients who were not treated with intravenous thrombolysis. RESULTS: Patients with lacunar infarction had a lower National Institutes of Health Stroke Scale score (9.2 versus 13.9, P < .001), a greater Alberta Stroke Program Early computed tomography (CT) score (9.7 versus 9.2, P = .002), a lower prevalence of atrial fibrillation (6.5% versus 41.2%, P < .001), and significantly more frequently an excellent outcome after 3 months (76.1% versus 36.2%, P < .001) compared with patients with nonlacunar infarction. Among patients with lacunar infarction, an excellent outcome at discharge was significantly more frequent in the intravenous thrombolysis group (41.3% versus 15.6%, P = .01), and the length of hospitalization was significantly shorter (9.5 days versus 14.3 days, P = .002). There was no hemorrhagic transformation among patients with lacunar infarction treated with intravenous thrombolysis. CONCLUSION: Intravenous thrombolysis has proven to be effective and safe in patients with lacunar infarction and should always be applied if there are no absolute contraindications.

Association between Apolipoproteins AI and B and Ultrasound Indicators of Carotid Atherosclerosis.

BACKGROUND: Apolipoproteins A-I and B (apoA-I and apoB) may be better indicators of the risk of cardiovascular and cerebrovascular diseases than conventional risk factors (RFs). The onset of ischemic stroke (IS) may be preceded by the development of atherosclerotic changes in carotid arteries, which can be detected by ultrasound. Only a certain % of patients with IS have an (underlying) carotid etiology. OBJECTIVE: The aim of our study was to determine the association between ultrasound indicators of carotid atherosclerosis and the presence of apolipoproteins and other biomarkers in patients with IS. METHODS: The study included 120 patients with clinically first, non-cardioembolic ischemic stroke in the carotid circulation. For all patients the following data were recorded: risk factors (hypertension, diabetes, hyperlipoproteinemia, smoking, obesity, metabolic syndrome, (MetS) hyperhomocysteinemia and inflammation), and levels of blood pressure, glucose, glycosylated hemoglobin, lipids, apoA-I and apoB apolipoproteins, body mass index, homocysteine, and C-reactive protein (CRP). Carotid duplex ultrasound was used to measure carotid intima media thickness (cIMT) and determine the presence of an unstable (hypoechogenic) plaque. RESULTS: The most significant associations were found between cIMT and older age (ß=0.230; p=0.006), lower concentrations of apoA-I (ß=-0.244; p=0.008) and a higher apoB/apoA-I ratio (ß=0.247; p=0.007). The presence of a hypoechogenic plaque was most significantly associated with increased concentrations of apoB (OR=2.29; 95% CI=4.9-173.5; p<0.0001), the presence of MetS (OR=9.2; 95% CI=2.9-29.2; p<0.0001) and elevated CRP (OR=2.7; 95% CI=1.1-6.9; p = 0.046). CONCLUSION: Among RFs and their biomarkers, apoA-I, apoB and the apoB/apoA-I ratio showed strong association with ultrasound indicators of carotid atherosclerosis in IS patients.

The Wnt/ß-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity.

BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/ß-catenin signalling pathway (WßcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WßcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS: The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS: Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION: CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

1h Post-load Blood Glucose in the Identification of Proatherogenic Cardiometabolic Profile in Obesity.

BACKGROUND AND AIM: Current data show that 1h oral glucose tolerance test (OGTT) blood glucose (1h-BG) might identify persons at increased risk of developing type 2 diabetes and cardiovascular diseases more precisely than fasting blood glucose (FBG) and 2h OGTT blood glucose (2h-BG). The aim of study was to determine whether is justified to use 1h-BG over traditional blood glucose measurements, in cardiometabolic profiling of obese individuals. METHOD: Cross-sectional study enrolled 60 obese individuals without previous history of diabetes and other cardiometabolic disorders. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS: All three parameters significantly directly correlated with age, body mass index, waist circumference, erythrocyte sedimentation rate, C-reactive protein, triglycerides and glycated hemoglobin. FBG and 1h-BG significantly directly correlated with alanine transaminase, gammaglutamyltransferase and total cholesterol. FBG significantly directly correlated with fibrinogen and aspartate transaminase, 1h-BG with systolic blood pressure and 2h-BG with diastolic blood pressure. None of parameters significantly correlated with gender, total white blood cell count, uric acid, 25-hydroxyvitamin D, high density lipoprotein cholesterol, low density lipoprotein cholesterol, serum adiponectin and albuminuria. Differences in correlation coefficients were not statistically significant. Individuals with 1h-BG >8.6 mmol/l had much more proatherogenic cardiometabolic profile, as well as higher incidence of dysglycemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) than ones with 1h-BG <8.6 mmol/l, but all differences were driven by the average value of glycemia. There were no statistically significant differences in ability of predicting MetS, NAFLD and pathologically increased carotid artery intima media thickness among analyzed glucose metabolism parameters. CONCLUSION: 1h-BG is not superior to FBG and 2h-BG in the identification of proatherogenic cardiometabolic profile in obesity.

Surrogates of Insulin Sensitivity and Indices of Cardiometabolic Profile in Obesity.

BACKGROUND AND OBJECTIVES: Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. METHOD: This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS: All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. CONCLUSION: The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

Cerebral Vasomotor Reactivity and Apnea Test in Symptomatic and Asymptomatic High-Grade Carotid Stenosis.

INTRODUCTION: Cerebral vasomotor reactivity (VMR) represents an autoregulatory response of the arterial trunks on the specific vasoactive stimuli, most commonly CO2. OBJECTIVE: The aim of this retrospective study was to compare VMR in high-grade symptomatic (SCAS) and asymptomatic carotid stenosis (ACAS), using the apnea test to evaluate the hemodynamic status. METHODS: The study included 50 patients who were hospitalized at the neurology and vascular surgery departments as part of preparation for carotid endarterectomy. We evaluated VMR by calculating the breath holding index (BHI) in 34 patients with SCAS and 16 patients with ACAS, with isolated high-grade carotid stenosis. We evaluated the impact of risk factors and collateral circulation on BHI, as well as the correlation between the degree of carotid stenosis and BHI. RESULTS: A pathological BHI was more frequent in the SCAS group (p<0.01). There was no difference in the range of BHI values between the groups, both ipsilaterally and contralaterally. Only male gender was associated with pathological BHI in both groups (p<0.05). Collateral circulation did not exist in over 60% of all subjects. We confirmed a negative correlation between the degree of carotid stenosis and BHI. CONCLUSION: SCAS and ACAS patients present with different hemodynamics. While ACAS patients have stable hemodynamics, combination of hemodynamic and thromboembolic effects is characteristic of SCAS patients.

Sonothrombolysis: is the story (t)old or just the beginning.

INTRODUCTION: Intravenous administration of recombinant tissue plasminogen activator, fastest and widely feasible treatment in acute ischemic stroke induces arterial recanalization, a prerequisite for neurological recovery. THE THERAPEUTIC ROLE OF ULTRASOUND AND POTENTIAL MECHANISM OF SONOTHROMBOLYSIS: Augmentation of recanalization can be achieved safely in combination with diagnostic transcranial Doppler by delivering mechanical pressure waves to the thrombus and exposing more thrombus surface to circulating drug. The addition of microspheres can further improve thrombolytic effect. CLINICAL TRIALS: International multicenter CLOTBUST trial showed that acute ischemic stroke patients treated with sonothrombolysis had higher rate of arterial recanalization and dramatic clinical recovery without increasing risk of symptomatic intracranial hemorrhage. A microsphere dose-escalation study called TUCSON showed that rates of recanalization and clinical recovery tended to be higher in target groups compared with controls. META-ANALYSIS OF CLINICAL TRIALS OF SONOTHROMBOLYSIS: Cochrane Stroke Group found that sonothrombolysis was likely to reduce death or dependency. A meta-analysis of sonothrombolysis showed that patients who received any form of sonothrombolysis had more than twofold higher likelihood of achieving complete arterial recanalization. PERSPECTIVES FOR SONOTHROMBOLYSIS - OPERATOR-INDEPENDENT DEVICE FOR SONOTHROMBOLYSIS: The collaborative group of the CLOTBUST trial designed multi-transducer assembly to cover conventional windows used for transcranial Doppler examinations. Operator-independent device can be quickly mounted by medical personnel with no prior experience in ultrasound. Sonothrombolysis for acute ischemic stroke is now tested in a pivotal efficacy multi-national trial called CLOTBUSTER. CONCLUSION: Ultrasound is a promising tool to enhance systemic thrombolysis.