Zeljko Zivanovic

Agenesis of Internal Carotid Artery With Unusual Fetal Collateral Circulation

A 17-YEAR-OLD BOY EXperienced 2 transitory ischemicattacks withdysphasia, right hemiparesis, and visual disturbances. At the age of 2 years, he had undergone surgery to repair a complex congenital heart defect consisting of patent ductus arteriosus,patent foramenovale, and dysplastic pulmonary valve with shunting and pulmonary hypertension. After the surgery, he was regularlyobservedbyhiscardiologists;his physical and mental development were normal. On magnetic resonance angiography the patient’s left internal carotid artery was missing, while the right internal carotid artery was hypoplastic (Figure, A). Computed tomography of the temporal bone showed the carotid canal was hypoplastic on the left side, which is highly suggestive of internal carotid artery agenesis (Figure, B). In the circle of Willis, the fetal type of collateral circulation was present, with the left middle cerebral artery supplied with blood from the basilar artery. Furthermore, the anterior communicating artery and both pericallosal arteries were arising from the anterior cerebral artery on the affected left side, while segment A1 was missing on the right (Figure, C). Aneurysms were not found. Echocardiography revealed no cardiac thrombi. COMMENT

Intravenous thrombolysis in acute ischemic stroke due to occlusion of internal carotid artery – A Serbian Experience with Thrombolysis in Ischemic Stroke (SETIS)

OBJECTIVE The benefit of intravenous thrombolysis in patients with internal carotid artery (ICA) occlusion is still unclear. The aim of this study was to assess the influence on outcome of intravenous thrombolysis in patients with ICA occlusion comparing to those without it. METHODS Data were from the national register of all acute ischemic stroke patients treated with intravenous thrombolysis in Serbia. Patients with nonlacunar anterior circulation infarction were included and were divided into two groups, those with and those without ICA occlusion. We compared the differences in demographic characteristics, risk factors, baseline NIHSS score, early neurological improvement, 3-month functional outcome, complications and death between these two groups. RESULTS Among 521 included patients there were 13.4% with ICA occlusion. Group with ICA occlusion had more males (82.9% vs. 60.5%; p=0.0008), and more severe stroke (baseline NIHSS score 15.3 vs. 13.6; p=0.004). Excellent functional outcome (mRS 0-1) at 3 months was recorded in 32.9% patients with ICA occlusion and in 50.6% patients without (p=0.009), while favorable functional outcome (mRS 0-2) was recorded in 50.0% of patients with ICA occlusion vs. 60.1% without (p=0.14). Death occurred in 12.9% patients with ICA occlusion and in 17.3% patients without it (p=0.40). There was no significant difference in rate of symptomatic ICH between the two groups (1.4% vs. 4.2%; p=0.5). Multivariate logistic regression analysis showed that ICA occlusion was associated with the absence of early neurological improvement (p=0.03; OR 1.78, 95% CI 1.05-3.04). However, the presence of ICA occlusion was not significantly associated with an unfavorable outcome at 3-month (p=0.44; OR 1.24, 95% CI 0.72-2.16) or with death (p=0.18; OR 0.57, 95% CI 0.25-1.29). CONCLUSION The patients with ICA occlusion treated with intravenous thrombolysis have a worse outcome than patients without it.

Recurrent longitudinally extensive transversal myelitis in a patient with Sjögren's syndrome.

INTRODUCTION Longitudinally extensive transverse myelitis (LETM) is a transversal myelitis that extends through three or more vertebral segments in length. CASE REPORT A 52-year-old woman was hospitalized due to pain in the lumbar region, difficulty in walking, hypoesthesia of the anogenital area and urinary retention. In the past medical history, two years earlier, the patient had been diagnosed with transversal myelitis confirmed by MRI of the cervical spine and six months earlier, the patient was diagnosed with primary Sjögrens syndrome (SS). During the current hospitalization MRM of the spinal cord revealed extensive inflammatory lesions of almost the whole spinal cord. Lumbar puncture (LP) revealed mild pleocytosis and slightly increased protein level. Isoelectric focusing of cerebrospinal fluid (CSF) and serum proteins was normal. Visual evoked potentials were normal. Serological testing excluded acute viral infections. Corticosteroid therapy was applied with good therapeutic response. Control MRI revealed regression of pathological changes in the spinal cord. CONCLUSION A wide range of disorders can cause LETM, but usually the first line diagnosis is neuromyelitis optica (NMO). Based on the detection of NMO immunoglobulin G in the serum of affected patients, a variety of allied disorders were grouped under the name of NMO spectrum disorders, including recurrent myelitis associated with LETM and myelitis associated with autoimmune disorders such as SS. There have been only a few cases reported in the literature with recurrent LETM associated with non-organ specific autoimmune disorder.

The Wnt/β-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/β-catenin signalling pathway (WβcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WβcSP 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.

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.

Paradoxical emboli--clinical importance of transcranial Doppler for detection of patent foramen ovale.

A patent foramen ovale has been reported to be more frequently detected in cryptogenic stroke, with paradoxical embolism as the major pathogenetic mechanism. The standard procedure for the detection of a patent foramen ovale is transesophageal echocardiography. Transcranial Doppler sonography with bubble test is almost as reliable as transesophageal echocardiography. Seventeen patients with acute ischemic stroke and transient ischemic attacks hospitalized at the Department of Neurology in Novi Sad underwent examinations to detect a patent foramen ovale, which was found in 55.6% of patients with cryptogenic stroke. The average age of these patients was 30.6 years. Transcranial Doppler sonography showed 100% sensitivity and 100% specificity for the prediction of right-to-left shunts proven by transesophageal contrast echocardiography. Both positive and negative predictive values in our group of patients were 1. Transcranial Doppler with bubble test is a reliable method for the detection of a patent foramen ovale, with a high level of sensitivity and specificity which is comparable with transesophageal echocardiography. Moreover, it is cheaper and more comfortable than transesophageal echocardiography, and should be used routinely in neurological practice.

Outcome of intravenous thrombolysis for acute ischemic stroke in patients with and without atrial fibrillation

Introduction. Atrial fibrillation is associated with an increased risk of ischemic stroke. The benefit of intravenous thrombolysis in patients with acute ischemic stroke and atrial fibrillation is still unclear. The aim of the study was to assess and compare the effects of intravenous thrombolysis in stroke patients with and without atrial fibrillation. Material and Methods. We analyzed stroke patients who were treated with intravenous thrombolysis. Patients were divided into two groups according to the presence of atrial fibrillation. Demographic, clinical and radiological characteristics of patients were compared between the two groups. The treatment efficacy was evaluated in relation to the improvement of neurological status after 24 hours, and functional recovery after three months. Binary logistic regression was used to evaluate predictors of outcome. Results. From a total of 188 patients, 39.4% presented with atrial fibrillation. Patients with atrial fibrillation were older (69.4 vs. 62.6 years; p <0.0001), with female predominance (43.2% vs. 28.9%, p = 0.04) and had clinically more severe stroke (National Institutes of Health Stroke Scale, score on admission 15.4 vs. 12.1; p = 0.0001). Significantly more patients without atrial fibrillation (61.4% vs. 43.2%, p = 0.01) had a favorable clinical outcome at three months after stroke. Nevertheless, atrial fibrillation was not an independent predictor of poor outcome at three months after stroke (p=0.66). Conclusion. Acute ischemic stroke patients, with atrial fibrillation, treated with intravenous thrombolysis, had worse outcomes than patients without atrial fibrillation did. However, it is mainly due to older age and a more severe stroke in patients with atrial fibrillation.

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.

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 (β=0.230; p=0.006), lower concentrations of apoA-I (β=-0.244; p=0.008) and a higher apoB/apoA-I ratio (β=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.