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Recurrent stroke is a major cause of morbidity and mortality among stroke survivors. With improved survival after first ischemic stroke, stroke recurrence may account for a greater share of the future annual cost of stroke-related health care. Despite advances in stroke prevention strategies and treatments, stroke recurrence is still the major threat to any stroke survivor. This review discusses antithrombotic therapy in secondary stroke prevention which has a major impact in clinical practice.

These are evidence based guidelines for the management of patients with carotid stenosis, developed and endorsed by Croatian Society of Neurovascular Disorders, Croatian Society of Neurology, Croatian Society of Ultrasound in Medicine and Biology, Croatian Society for Radiology, Croatian Society of Vascular Surgery and Croatian Society of Neurosurgery. They consist of recommendations for noninvasive screening of patients with carotid stenosis, best medical treatment and interventions such as carotid endarterectomy and stent placement based on international randomized clinical trials.

Atherosclerosis is chronic, progressive disease of the arterial wall with onset decades prior to its clinical manifestations. Carotid intima-media thickness (IMT) measurement by ultrasound is an important tool for evaluation of early stages of atherosclerosis. Also, carotid intima-media thickness can be used for assessment of therapeutic effect of various regimens. Carotid IMT is sensitive marker of atherosclerosis. The causal relationship between carotid IMT and the clinical endpoint has been established on the basis of epidemiological studies and clinical trials. The strength of carotid IMT as a marker of atherosclerosis is enhanced by the fact that it may yield pathophysiological information at an early stage of atherogenic process.

Background: The biological roles of gangliosides/glycosphingolipids (GSL) have been extensively studied and their involvement in key cellular events as well as their particularly important functions in animal brain tissue are well known. The idea that there are alterations in glycosphingolipid metabolism in Alzheimer's disease (AD) arose from biochemical studies of brain gangliosides pattern. Changes in content and composition of gangliosides and other membrane lipids in AD brain regions were documented by several groups, including ours. Observed specific alterations of ganglioside pattern in AD brains were mostly discussed as a consequence of: (a) neuronal cell degeneration, demyelination and gliosis ; (b) accelerated lysosomal degradation of gangliosides. Increased expression of lysosomal hydrolases in neuronal populations affected by amyloid pathology was indeed documented by other groups. This finding was explained as a proof for up-regulation of endosomal-lysosomal system in AD and was proposed to be an early marker of metabolic dysfunction related to primary AD etiopathogenesis. Methods and Results: A speculation that alteration of ganglioside metabolism/catabolism occurs also in nonneural tissue in AD was further studied by our group. In our study the activity of several enzymes involved in ganglioside and sulfatide catabolism (b– galactosidase, b-hexosaminidase, b-hexosaminidase A and arylsulfatase A) was analyzed in leukocytes and skin fibroblasts derived from individuals with AD and Down's syndrome (DS). Our results showed statistically significant increase in b– galactosidase activity in AD and DS leukocytes in comparison with age-matched control leukocytes. Also, increased activity of b– galactosidase and b– hexosaminidase was observed in AD and fetal DS skin fibroblast cell line and age-matched controls obtained from commercial sources as well as in several DS and age-matched control skin fibroblast cultures established in our laboratory. Conclusions: Obtained results indicated that acceleration of at least some lysosomal catabolic pathways of gangliosides is present in AD and DS nonneural cells (leukocytes and skin fibroblasts). These findings raised several interesting questions: first, whether detected changes of glycosphingolipid metabolism in peripheral cells may present as peripheral biochemical markers in AD ; second, is there a change in transcriptional regulation of analyzed enzymes in AD ; third, are there mutations in genes coding for GSL biosynthetic/catabolic enzymes which may contribute to complex AD pathogenesis ; fourth, which other (epigenetic) events modify and cause altered enzyme activities in both AD and DS.

During the last decade Croatia was faced with war and population migration that entailed socioeconomic changes, modification of lifesryle, risk factors and health care, thus influencing the incidence and outcome of stroke. Data on patients admitted to Universiry Department of Neurology in the years 1990 and 1999 were compared to estimate the incidence and prevalence of stroke and stroke subrypes, risk factors and outcome. In 1999, the number of stroke patients was almost twofold that recorded in 1990 and stroke patients were by 5 years younger In 1999, there were more first-ever strokes (the incidence of crude first stroke inereased by 57%), whereas the number of recurrent strokes increased in men and decreased in women. The proportion of ischemic stroke and subarachnoid hemorrhage did not significantly change, whereas parenchymatous hemorrhage inereased in women. Hypertension was more common (83% ver.sus 62%), whereas the prevalence of other risk factors did not change significantly Patients were more often discharged for home care instead of rehabilitation center care. Mortality decreased in men and inereased in women, whereas case fataliry and crude mortality decreased leading to an increaseđ stroke burden.

Efficacious treatment of acute stroke is a major challenge in modern medicine. Therapeutic neuroprotection acting towards minimization of ischemic neuronal injury in penumbral tissue in the regions of reduced cerebral blood flow seems to be an appealing concept in the treatment of acute stroke and brain trauma. The `ischemic cascade', a complex mechanism of metabolic events initiated by brain ischemia, offers many pathways by which the neuroprotective agents may act. Time to treatment remains a major limiting factor for many potential neuroprotective agents. Although the exact therapeutic window is not known, evidence from many animal models and clinical research suggest that neuroprotective therapy can only be efficacious if administered very early after the onset of ischemia. Various neuroprotective agents have been tested in many clinical stroke trials during the past 20 years. Large phase III clinical trials of several classes of neuroprotectants (mainly NMDA receptor antagonists, free radical scavengers, and calcium channel blockers) have recently failed to demonstrate efficacy of neuroprotection. After initial disappointment, the active research continues and some new exciting neuroprotective models emerge on the horizon.

The majority of biochemical disorders in neural and non-neural tissues in Alzheimer's disease (AD) has consequences on cell membrane structure and function. Previous studies showed significant quantitative and qualitative changes of gangliosides (GG) in AD brains explained mostly as the result of: (a) neuronal cell loss and glial response, but also (b) possible disorder/acceleration of GG degradation. As GG are incorporated in all types of cell membranes, the hypothesis of this study was that similar metabolic disorder of GG may exist in non-neural tissues in AD. The study was performed on available peripheral tissues: skin fibroblasts derived from individuals with neuropathologically confirmed diagnosis of AD and individuals with Down's syndrome (DS) in comparison with age-matched control fibroblasts ; leukocytes and serum from individuals with clinical diagnosis of dementia of Alzheimer's type (DAT, N=19) and DS (N=21) in comparison with age -matched controls (N=26). The results showed: (1) statistically significant increase in beta-galactosidase activity in DAT and DS leukocytes and skin fibroblasts, while there were no significant changes in activities of several other lysosomal enzymes of GG degradation ; (2) metabolic labelling with 1-14C-D-galactose showed increase in total radioactivity incorporation in glycosphingolipid fraction of almost all DS and AD cultures of skin fibroblasts ; also, metabolic turnover of glycosphingolipids was greater in fetal Down than in age-matched control fibroblasts ; (3) there were no changes in composition and content of serum gangliosides in DAT and DS samples in comparison with control samples. In conclusion, the results of this study indicate probable disorder of GG metabolism (accelerated ganglioside degradation) in analyzed AD and DS non-neural tissues, and are challenging for our further investigation and understanding of glycosphingolipid metabolism in mentioned diseases.

As a part of the community-based Northern Manhattan Stroke Study, 611 patients with first cerebral infarction were prospectively followed to detect the 1-year stroke recurrence. Baseline risk factors evaluated included age, gender, hypertension, diabetes, smoking, alcohol consuption, serum cholesterol, myocardial infarction, congestive heart failure (CHF), atrial fibrillation, and NIH stroke scale (NIHSS). Life tables were used to estimate the 1-year stroke recurrence risk, and a logistic multiple regression model to calculate relative risks and 95 percent CI one year after initial stroke. Among 94 (15 percent) patients with identified recurrence, 19 percent died within 1 year from recurrent stroke. The life table cumulative risk of recurrent stroke was 3 percent at day 30, 10 percent at 1 year, 14 percent at 2 years, and 18 percent at 3 years. The 1-year cumulative risk of recurrence did not significantly differ according to age or gender. The 1 year recurrence risk was significantly different for the baseline NIH stroke scale (NIHSS less than 3.5 percent, 3-8, 14 percent ; NIH over 8, 7 percent ; p=0.019) and CHF (yes 17 percent, no 19 percent ; p=0.041). The logistic multiple regression model revealed age over 60 years, CHF, and alcohol consuption of over 2 drinks/(day to be independent predictors of 1 year stroke recurrence (age over 60 RR 2.9, 95 percent CI 1.1-8.2 ; CHF RR 2.7, 1.3-5.5, alcohol over 2/day RR 3.1 CI 1.2-8.1). Our data suggest a different pattern of risk factors for stroke recurrence than that for initial stroke. The patients who have ačready suffered first stroke should also be considered a target population for education, improvement of compliance with medical therapies, and modification of hazardous behaviours.

The majority of biochemical disorders in neural and non-neural tissues in Alzheimer's disease (AD) has consequences on cell membrane structure and function. Previous studies showed significant quantitative and qualitative changes of gangliosides (GG) in AD brains explained mostly as the result of neuronal cell loss and glial response, but also possible disorder/acceleration of GG degradation. As GG are incorporated in all types of cell membranes, the hypothesis of this study was that similar metabolic disorder of GG may exist in non-neural tissues in AD. The study was performed on available periperal tissues: skin fibroblasts derived from individuals with neuropathologically confirmed diagnosis of AD and individuals with Down's syndrome (DS) in comparison with age-matched control fibroblasts; leukocytes and serum from individuals with clinical diagnosis of dementia of the Alzheimer's type (DAT, N=19) and DS (N=21) in comparison with age-matched controls (C, N=26). The results showed: (1) statistically significant increase in beta-galactosidase activity in DAT and DS leukocytes and skin fibroblasts, while there were no significant changes in activities of several other lysosomal enzymes of GG degradation; (2) metabolic labelling with 14C-galactose showed increase in total radioactivity incorporation in glycosphingolipid fraction of almost all DS and AD cultures of skin fibroblasts; also, metabolic turnover of glycosphingolipids was greater in fetal Down than in age-matched control fibroblasts; (3) no changes in composition and content of serum gangliosides in DAT and DS samples in comparison with control samples. In conclusion, the results of this study indicate probable disorder of GG metabolism (accelerated ganglioside degradation) in analyzed AD and DS non-neural tissues, and are challenging for our further investigation and understanding of glycosphingolipid metabolism in mentioned diseases.

The aim of this study was to determine the relationship between plasma fibrinogen levels in patients with HITS and those without HITS. A total of 50 patients with a cardiac disease (recent myocardial infarction, myocardiopathy, atrial fibrillation, prosthetic heart valve, valvular stenosis or mural thrombi) was investigated. Plasma fibrinogen levels were determined in all patients and simultaneous TCD monitoring of both middle cerebral arteries was performed over 60 minutes. The patients were categorised into two groups: emboli positive and emboli negative, and according to weather they had or had not a prior neurological event. HITS were detected in 22 (44 percent) patients. The mean plasma fibrinogen level in emboli positive patients was significantly higher (3.66 g/L) than in emboli negative patients (3.14 g/L), (p less than 0.05). HITS can be detected in a large proportion of patients with cardiac diseases. Elevated plasma fibrinogen levels might be added to the list of risk factors for stroke and may serve as a predictor of future vascular events.

The purpose of this study was to determine the role of vertebral artery (VA) hyoplasia in the pathogenesis of migraine. We studied the extracranial part of VA in 59 migraine patients (17 with and 42 without aura) using color Doppler. In migraine with aura, 29 percent of patients had hypoplastic VA, and in migraine without aura 7 percent. In migraine with aura, mean diameter of the right VA was 2.7 +/- 0.7 mm, and of the left 3.3 +/- 0.7 mm; in migraine without aura mean diameter was 3.1 +/-0.5 mm on the right, and 3.3 +/-0.6 on the left. In migraine with aura, mean mean systolic blood flow velocity was 55 +/-16 cm/s on the right, 60+/-17 cm/s on the left, in migraine without aura 57+/-18 cm/s on the right, 57+/-18 on the left. We observed higher frequency of hypoplastic VA in migraine with aura, suggesting that hypoplasia of VA may be an additional factor which can lead to hyoperfusion in the posterior circulation during the aura phase.

Obrađena je skupina od 33 bolesnika do 40 godina s ishemijskom cerebrovaskularnom bolešću u kojih je učinjena cerebralna angiografska obrada metodom po Seldingeru. Najčešće se od velikih ispada nalazila aplazija prednje cerebralne arterije, u jednom slučaju istodobno aplazija prednje i srednje cerebralne arterije, u jednom intrakranijska okluzija unutarnje karotidne arterije. Zatim se učestalo viđala hipoplazija vertebralnih arterija. Nađena su i 2 venska angioma, te varijacije stražnje cerebralne i stražnje zajedničke arterije. Razvitkom ultrasonografskih ekstrakranijskih prikaza kao i transkranijske dupleks sonografije smanjuje se u ishemijskoj bolesti broj kandidata za angiografiju.

A group of 83 patients with symptomatic and asymptomatic carotid atherosclerotic lesions were analysed. The morphology of carotid plaques was determined using color Doppler flow imaging. In each patient, the history of stroke and putative risk factors such as age, sex, hypertension, obesity, cigarette smoking, use of oral contraceptives, diabetes and alcohol consumption was collected. The risk factors were correlated with plaque morphology. In soft plaques, the most common risk factors are elevated cholesterol, low HDL-cholesterol and cigarette smoking ; in heterogeneous plaques, the most common risk factor is low HDL-cholesterol ; in fibrous plaques, the most common risk factors are elevated cholesterol and cigarette smoking ; in calcified plaques, the presence of cigarette smoking, hypertension, elevated cholesterol and low HDL-cholesterol are equally important and in case of hemorrhage into plaque, the most important factor is hypertension. A significant correlation was found between the severity of carotid atherosclerotic lesions and stroke. The patients with stroke had significantly more soft and heterogeneous plaques.

Cilj ovog ispitivanja bio je procijeniti prevalenciju i zvučna obilježja mikroembolijskih signala pomoću transkranijskog doplera u bolesnika sa srčanom bolešću. Ukupno 103 bolesnika podijeljeno je u 5 skupina. Embolijski signali otkriveni su u 39 % bolesnika. Prevalencija embolijskih signala je bila najviša u bolesnika sa umjetnim srčanim zaliscima, "miješanoj skupini", bolesnika sa ne-reumtskom fibrilacijom atrija, valvularnom stenozom i miokardiopatijom. TIA i moždani udar bili su češći u bolesnika s detektiranim moždanim embolusima. Bolesnici sa srčanom bolešću mogli bi imati veći rizik za nastanak moždanog udara.