Intravenous thrombolysis for patients with in-hospital stroke onset: propensity-matched analysis from the Safe Implementation of Treatments in Stroke-East registry.

BACKGROUND AND PURPOSE: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry. METHODS: We compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months, (iii) functional independence defined as an mRS score of 0-2 at 3 months and (iv) 3-month mortality. RESULTS: Out of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P > 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60-140) vs. 65 (IQR, 47-95) min, P < 0.001] and door-to-imaging [40 (IQR, 20-90) vs. 24 (IQR, 15-35) min, P < 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273). CONCLUSIONS: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS.

Benefit of thrombolysis for stroke is maintained around the clock: results from the SITS-EAST Registry.

BACKGROUND AND PURPOSE: The outcome of thrombolysis for early morning and sleep time strokes may be worse because of uncertainty of stroke onset time or differences in logistics. The aim of the study was to analyze if stroke outcome after intravenous thrombolysis differs depending on time of day when the stroke occurs. METHODS: The data collected in the Safe Implementation of Treatments in Stroke - Eastern Europe (SITS-EAST) Registry between September 2000 and December 2011 were used. Strokes were categorized as night-time 00:00-07:59, day-time 08:00-15:59 and evening-time 16:00-23:59 and were compared in terms of several outcome measures. All results were adjusted for baseline differences. RESULTS: A total of 8878 patients were enrolled: 18% had night-time, 54% day-time and 28% evening-time strokes. Onset-to-treatment time in patients with night-time strokes was 10 min longer than in day-time and evening-time strokes (P < 0.001). Symptomatic intracerebral hemorrhage by ECASS II definition occurred in 5.6%, 5.6% and 5.3% (adjusted P = 0.41) of the night-time, day-time and evening-time stroke patients, respectively; by SITS definition it occurred in 2.5%, 1.9% and 1.3% (adjusted P = 0.013) and by NINDS definition in 7.8%, 7.6% and 7.5% (adjusted P = 0.74). Patients with night-time, day-time and evening-time strokes achieved modified Rankin Scale score 0-1 in 33%, 31%, 31% (adjusted P = 0.34) and 0-2 in 52%, 51%, 50% (adjusted P = 0.23), and 13%, 15%, 16% respectively of patients died (adjusted P = 0.17) by 3 months. CONCLUSIONS: The time when stroke occurs (day versus evening versus night) does not affect the outcome after thrombolysis despite the fact that patients with night-time strokes have worse time management.

Transcranial Doppler in brain death confirmation in clinical practice.

PURPOSE: Transcranial Doppler (TCD) can be used as a confirmatory test in brain death. The aim was to present the usefulness of TCD in brain death confirmation. MATERIALS AND METHODS: Forty-four patients with severe brain lesions leading to brain death were treated over a 4-year period. After the clinical diagnosis of brain death was made, the appropriate confirmatory test was chosen according to patient condition, taking into consideration the restrictions of the test protocol. Due to the inconclusive test results, some patients underwent repeat testing. RESULTS: Among 44 patients, 19 had neurotrauma, 11 massive aneurysmal subarachnoidal hemorrhages, 1 arteriovenous subarachnoidal and parenchymal hemorrhage, 12 hypertensive parenchymal hemorrhages, and 1 ischemic stroke. As a primary test, TCD was used in 30, brain scintigraphy in 2, multislice CT angiography (CTA) in 10, and cerebral angiography in 2 patients, and the diagnosis was confirmed in 26, 3, 9 and 2 patients, respectively. Due to inconclusive results CTA was repeated in five patients. In patients in whom TCD was applied, the time to confirm the diagnosis was the shortest, and in most (61 %) cerebral circulatory arrest was confirmed within 2 hours of clinical diagnosis. CONCLUSION: TCD is a favorable confirmatory test for cerebral circulatory arrest in brain death diagnosis.

Perception of stroke in Croatia--knowledge of stroke signs and risk factors amongst neurological outpatients.

BACKGROUND AND PURPOSE: The aim of this hospital-based survey was to determine baseline stroke knowledge in Croatian population attending the outpatient services at the Department of Neurology. METHODS: A multiple choice questionnaire was designed, divided into three sections: (i) demographic data, (ii) knowledge of stroke risk factors and stroke signs and (iii) actions the patients would undertake if confronted with risk of stroke and information resources regarding health. RESULTS: The analysis included 720 respondents (54.9% women). The respondents most frequently indicated stroke symptoms as following: speech disorder 82%, paresthesiae on one side of the body 71%, weakness of arm or leg 55%, unsteady gait 55%, malaise 53%, monocular loss of vision 44%. The risk factors most frequently identified were hypertension 64%, stress 61%, smoking 59%, elevated lipids 53%, obesity 52%, coagulation disorder 47%, alcoholism 45%, low-physical activity 42%, elderly age 39%, cardiac diseases 38%, weather changes 34%, drugs 33% and diabetes 32%. If confronted with stroke signs 37% of respondents would consult the general practitioner and 31% would call 911 or go to a neurologist. Amongst patients with a risk factor, only diabetics were aware that their risk factor might cause stroke (P < 0.001). Respondents with lowest education had the least knowledge regarding stroke signs (P < 0.01). DISCUSSION: The results of this study indicate that respondents showed a fair knowledge about stroke signs and risk factors for stroke. The results of our study will help to create and plan programmes for improvement of public health in Croatia.

Distinguishing Parkinson's disease and essential tremor with transcranial sonography.

OBJECTIVES: Until today there is no reliable test that can clearly distinguish Parkinson's disease (PD) from the essential tremor (ET). Our aim was to determine the usefulness of the transcranial sonography (TCS) in the differential diagnosis of the PD and ET as well as the interobserver reliability for this method. METHODS: Transcranial sonography of substantia nigra and clinical examination were performed on 80 PD patients, 30 ET patients, and 80 matched controls by two independent physicians. RESULTS: Bilateral SN hyperechogenicity over the margin of 0.20 cm(2) was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET. Interobserver agreement for this method was significant (Student's t-test, P = 1.000). CONCLUSIONS: Substantia nigra hyperechogenicity on TCS is a highly specific finding of PD, where in healthy individuals or in ET patients, it might correspond to an increased risk of developing PD later in life or might also be because of the impairment of nearby area of nucleus ruber in ET patients, as suggested by positron emission tomography studies. TCS may serve as a practical and sufficiently sensitive neuroimaging tool in PD diagnoses and in distinguishing it from ET; its repeatability and accuracy might add to its practical value.

Pineal gland cyst evaluated by transcranial sonography.

Transcranial sonography (TCS) has never been used in the evaluation of morphology of pineal gland. The aim of the study was to assess the possibility of TCS to distinguish normal from cystic pineal gland and to correlate its size with magnetic resonance imaging (MRI) at the first examination and during follow-up. Sixty patients with previously made MRI of the brain were evaluated by two independent observers using TCS, blinded to the results of the MRI. Inappropriate bone window limited TCS examination in seven patients. All 14 pineal gland cysts (PGC) seen on MRI were detected by both observers using TCS. Control group consisted of 39 healthy examinees. No statistically significant difference has been found between: PGC size measured by first and second observer by TCS (P = 0.425), PGC size measured by TCS and MRI (first observer, P = 0.353; second observer, P = 0.425), size of the pineal gland measured by TCS and MRI in control group (first observer, P = 0.497; second observer, P = 0.370) or interobserver variability in control group (P = 0.373). The MRI and TCS follow-up of ten patients after six months did not show any difference in size of PGC. TCS can be used as a method in detection, measurement and follow-up of PGC.

Presynaptic vesicles, exocytosis, membrane fusion and basic physical forces.

The theoretical hypothesis is presented trying to explain the vesicle release from presynaptic nerve ending and membrane fusion. This theoretical concept implies only essential physical forces such as electrostatic force and surface tension force. Transmembrane resting potential of approximately -70 to -80 mV means that the intracellular fluid is electronegative in comparison with extracellular one. In this concept it is supposed that the inner and outer lipid layer of the membrane also have different electrostatic charges. Presynaptic vesicles are made from cell membrane by endocytic process through which the vesicle loses the contact with cell membrane. Also, during the endocytic process, the inner lipid layer of the cell membrane becomes the outer lipid layer of presynaptic vesicle and vice versa. During the resting phase, equally charged lipid layers of presynaptic vesicle and cell membrane repel each other, but during the action potential, differently charged lipid layers strongly attract each other, bringing the presynaptic vesicle and cell membrane in close contact. Immediately thereafter, the surface tension forces open the pore and fuse both membranes trying to minimize the area of the contact between water fluids (extra and intracellular fluid) and lipid fluids (lipid membrane bilayer). Since only fundamental physical forces are involved in this process, it could be very fast, effective and almost inexhaustible. Similar mechanisms could be responsible for all exocytic processes and all membrane fusion processes in the cells.

Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study.

This study was designed to evaluate the effect of stabilized oral reduced nicotinamide adenine dinucleotide (NADH) on cognitive functioning in patients with Alzheimer's disease (AD). NADH is a coenzyme that plays a key role in cellular energy production and stimulates dopamine production. In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD. The present trial was a randomized, placebo-controlled, matched-pairs, double-blind, 6-month clinical study. Patients with probable AD (n = 26) were randomized to receive either stabilized oral NADH (10 mg/day) or placebo. Twelve pairs of subjects were matched for age and baseline total score on the Mattis Dementia Rating Scale (MDRS) and the Mini Mental State Examination. After 6 months of treatment, subjects treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning. There were no differences between groups in measures of attention, memory, or in clinician ratings of dementia severity (Clinical Dementia Rating). Consistent with earlier studies, the present findings support NADH as a treatment for AD.

Measurement of blood flow through AV-fistulae by means of Doppler sonography in regularly haemodialysed patients.

In regularly dialyzed patients a variety of pathological events can negatively influence haemodynamics and blood flow through arterio-venous fistula, leading to inadequate blood flow through the dialyzer or disturbances in hemodynamics of the whole body. It therefore appears important to quantify flow velocity and volume flow through the arteriovenous fistula in such cases. We used a Vasoview computer controlled system for noninvasive vascular diagnostics based on B-scan "real-time" ultrasound for imaging the structure of tissue, combined with pulsed Doppler ultrasound for determination of hemodynamics. Thirty patients (16 males and 14 females, aged 45 +/- 10 years; range 23 to 61 years), with different periods spent on hemodialysis (5.5 +/- 3.1 years, range 1 to 11 years) were included in this study. The average systolic, diastolic and mean blood volume flows were 2131.8 +/- 565.8, 972.0 +/- 309.6 and 728.4 +/- 287.4 ml/min, respectively. The mean blood volume flow was calculated by integration of the area under curve of blood flow in one heart cycle on the Doppler signal. It is calculated by the apparatus and displayed on the screen during measurement. The average blood vessel diameter was 9.1 +/- 1.3 mm (mu +/- omega). The results revealed a marked inter-individual variation in volume flow through arteriovenous fistulae of dialyzed uremics (range 240.0 to 1200.0 ml/min). Doppler ultrasound thus appears to be a valuable method for determination of blood flow through arteriovenous fistula of dialyzed uremics as well as for detection of hemodynamics disturbances of interest, such as turbulent blood flow.

A correlation of 5-hydroxytriptamine and cerebral vasoreactivity in patients with migraine.

Cerebral haemodynamics and the level of serum 5-hydroxytriptamine (5-HT) were analysed in 21 migraine patients (8 with and 13 without aura) during the headache-free period as well as the attack. Cerebral vasoreactivity was evaluated by acetazolamide test and Transcranial Doppler ultrasonography (TCD). TCD findings were within normal ranges in the majority of migraine patients. Patients with migraine without aura had higher blood flow velocities (BFV) than patients with aura. Comparison of BVF and pulsatility index (PI) data patterns in migraine with and in migraine without aura during the attack revealed differences indicating cerebral hypoperfusion. It was noticed that systolic BFV decreased in migraine with aura on the headache side while PI increased. In migraine without aura, both systolic BFV and PI increased. 5-HT findings were heterogeneous. Reduction of cerebral vasoreactivity was observed especially in migraine with aura. Our results suggest different pathogenic mechanisms between migraine with and without aura, supporting the neurogenic inflammation theory.

Transcranial Doppler sonography for post-traumatic stress disorder.

Transcranial Doppler sonography (TCD) was used to examine the mean speed of blood circulation in 50 patients suffering from post-traumatic stress disorder (PTSD). The sonography was repeated 6 months after successful psychiatric treatment. Doppler sonography of Willis's circle blood vessels and vertebrobasilar flow was performed on healthy controls as well. All of the subjects in both groups were 20 to 43 years old and had not suffered from other diseases. Vasospasm of Willis's circle blood vessels was discovered in 62% of PTSD patients, which decreased to 22% after treatment. In the control group, it occurred in 8% of subjects. TCD examination of vertebrobasilar system blood vessels did not identify significant differences in blood circulation mean speed between controls and PTSD patients, regardless of whether they had or had not been treated. This research proved the value of TCD in discovering Willis's circle blood vessel vasospasm in PTSD patients, which suggests the inclusion of TCD in diagnosing PTSD. The value of TCD was affirmed in controlling treatment success, because after 6 months of psychiatric treatment, there were significantly fewer patients with Willis's circle blood vessel vasospasm.

Haemodynamic changes in patients with whiplash injury measured by transcranial Doppler sonography (TCD).

The daily increasing number of cervical whiplash injuries presents ever-greater requirement for vertebrobasilar diagnostics. A cervical spine injury, which is quite frequent injury, may occur during a fall, or industrial, traffic, sport or war injury. Transcranial Doppler (TCD) sonography with Transcan 3-D EME device and 2 MHz probe was used for the assessment of vertebrobasilar circulation in patients with a whiplash injury of the cervical spine, that occurred mostly in car accident. This study includes 47 patients with clinically verified cervical spine trauma with x-ray evidence of no bone lesion. The patients were examined by TCD within a month, and then six months following the accident. The obtained values were compared to normal blood flow velocities and correlated with the severity of clinical picture. During the first month after the injury, statistically significant disturbances in the vertebrobasilar circulation were recorded, such as the increase in mean blood flow velocities in AVL (68%), AVR (62%) and BA (51%) (mostly as spasam). Six months later, normal findings were obtained in about 50% of the vessels, whereas in rest of the patients vasospasam persisted in one, two or all examined blood vessels. TCD of the vertebrobasilar circulation was found to be a very useful method in the diagnostics and follow-up of patients with a whiplash injury.

Value of color-Doppler imaging in diagnosis of intrabulbar and intraorbital tumors.

Patients with intrabulbar and intraorbital tumours have been investigated by colour Doppler imaging. In the first group there were 20 patients with malignant melanoma of the uvea and in the second group there were 19 patients with cavernous hemangioma. The third group was a control group represented by 20 healthy individuals. In the group of patients with uveal melanoma it has been established that every patient, except one, has a blood flow inside of tumour tissue. Internal blood flow of intraorbital hemangioma was slower than inside the melanoma and the resistance index was lower. Comparison of blood flow in all patients has shown that there is no statistically significant difference between ophthalmic artery, central retinal artery and posterior ciliary arteries except in maximal blood flow in central retinal artery and posterior ciliary arteries.

Influence of prolonged stress on risk factors for cerebrovascular disease.

The main purpose of this study was to analyze the influence of psychological and socio-economic factors on the frequency and characteristics of risk factors for cerebrovascular disease (CVD) among Croatians. A group of 120 war sufferers with signs of post-traumatic stress disorder and adaptation disturbances have been studied, and compared with a control group of 120 persons with no traumatic war experience. The risk factors for CVD were registered using epidemiological, clinical and functional measures, and level of the risk. In a displaced persons group a significant higher rates (p < 0.05) of arterial hypertension (AH), hyperlipidemia and obesity are found, with particularly higher rates of occurrence of AH and hyperlipidemia in younger individuals. Alcoholism was more frequent in the control group. Total risk for stroke was higher in the exposed group. The authors conclude that there is a need for undertaking intensive preventive measures in the risk population exposed to chronic stress and negative socioeconomic life conditions.

Influence of prolonged stress on cerebral hemodynamics.

The author has investigated the impact of psychological and socio-economic factors on cerebral hemodynamics and development of cerebrovascular disease (CVD). A group of 120 war sufferers with signs of post-traumatic stress disorder and adaptation disturbances, and 120 persons of the control group with no traumatic war experience have been studied. The blood flow velocity and various parameters of spectral frequency analysis have been measured, using the method of transcranial doppler sonography (TCD). A greater number of hemodynamical changes has been found in the group of subjects than in the control group (p < 0.05), in which increase of vasospasm is statistically significant probably as a result of predomination of the sympathetic system stimulation and nicotinic effect on the brain blood vessels. Flow disturbances are relatively more frequent in older subjects, which suggests the rapid development of the atherosclerotic process. The results suggest that exposure to prolonged stress and bad socio-economic factors, through different neurobiological mechanisms, increased the risk for stroke.

Transcranial Doppler in smoking relapse prevention strategy.

Nicotine dependence is a progressive, chronic, relapsing disorder. Nicotine is the principal and most potent psychopharmacologically active component of tobacco smoke. Through activation of nicotine receptors in the central nervous system, nicotine can lead to tolerance and dependence. Cessation of smoking is followed by severe pathophysiologic withdrawal and by long-term craving. TCD measurement of cerebral blood flow velocity (BFV) and nicotine dependence degree measured by Fragestrom questionnaire was analyzed in relation to smoking relapse. This study includes 47 participants (25 females and 22 males) included in Breathe Free Plan To Stop Smoking in Non Smoking School in Zagreb. 12 month following the end of treatment participants were divided in three groups: continued abstinence, interrupted abstinence and non abstinence. High nicotine dependence combined with TCD pathological finding significantly discriminated successes and failures, suggesting that smokers with pathological TCD need specific therapeutic approach with more social support, individualized coping skills and cognitive restructuring. Measuring cerebral flow velocity by transcranial Doppler in smokers showed the practical validity in prediction of smoking relapse.

Color Doppler flow imaging (CDFI) of the vertebral arteries--the normal appearance, normal values and the proposal for the standards.

In order to assess mean diameters and blood flow velocities (BFV), Color Doppler Flow Imaging (CDFI) of vertebral arteries (VA) was performed. Five hundred and ninety six persons without carotid disease or symptoms related to vertebrobasilar system were analyzed by CDFI of VA. Mean right VA diameter was 3.37 +/- 0.6 mm and left 3.55 +/- 0.61 mm. Women had thinner VA (p < 0.05). Left VA was wider (p < 0.05). Mean right BFV was 48.31 +/- 14.09 cm/s and left 48.93 +/- 13.94 cm/s. Females had higher BFV (p < 0.05). BFV didn't very with age (p > 0.05). The VA hypoplasia was present in 2.34%, asymmetry in 15% (left VA dominant in 64%). Visualisation of V1 and V2 segment was possible in 100% and of the origin in 81.7% on the right, and 80.7% on the left side. CDFI is a reliable method for evaluation of VA. Left VA was wider. Women had thinner VA. Hypoplasia was present in 2.34% and asymmetry in 15%.

Vertebral artery hypoplasia--sex-specific frequencies in 36 parent-offspring pairs.

The major interest in vertebral artery (VA) hypoplasia comes from its possible connection to migraines with aura as well as from the fact that it is one of the risk factors for a stroke. Therefore, the aim of this preliminary study was to investigate the mode of inheritance of VA hypoplasia. Initially, color Doppler of VA was performed in 64 first- and second-degree relatives of 33 probands, and the presence of VA hypoplasia was confirmed according to the already established criteria. Since a higher prevalence of VA hypoplasia (15.6%) in probands'relatives in comparison with 2.34% in the general population of Croatia was indicative of a strong familial predisposition for this condition, an analysis of family data by means of Pearson's chi-square statistics has been performed. In this analysis, the observed sex-specific frequencies of 36 parent-offspring pairs composed only of affected parent and his/her (affected or non-affected) offspring are compared to the frequencies as expected under eight proposed models. For both--autosomal and X-linked monogenetic inheritance--four hypotheses have been chosen, assuming that the individuals having the affected allele (in combination with a healthy one) have 100%, 50%, 40% and 0% chances of developing VA hypoplasia. Out of eight tested models only two--completely dominant and completely recessive X-linked models--were rejected. But, from the six non-rejected models, goodness-of-fit statistics showed that the hypothesis of X-linked inheritance of VA hypoplasia with the "healthy" allele being stronger (60% effect on phenotype)--almost perfectly fit the data (chi2 = 2.0023; df = 7; p = 0.9597). Further research encompassing a more enlarged family sample is needed to confirm the present findings.

[Perioperative complications in carotid endarterectomy with respect to the stage of the cerebrovascular disease]. / Perioperacijske komplikacije karotidnih endarterektomija s obzirom na stadij cerebrovaskularne bolesti.

Records of perioperative complications following 407 consecutive carotid endarterectomies performed in 366 patients in the 18-year period have been presented. The complications are categorized according to the clinical stage of vascular disease, that is, according to the indications for the surgery. Out of the total number, 46 (11.3%) operations were done in the 1st, asymptomatic stage of disease, for the haemodinamically significant stenoses and ulcerated plaques; 173 (42.5%) in the 2nd clinical stage for hemispheral and nonhemispheral transient ishemic attacks (TIA) and reversible neurologic deficits (RIND); 3 (0.7%) in the 3rd stage which is a progressive cerebrovascular stroke and 185 (45.5%) in the 4th clinical stage of the disease, in patients with previous cerebral infarction and a permanent neurologic deficit. The rate of a temporary and permanent neurologic deficit, as well as mortality in the first stage of the disease equals zero. In the second stage of the disease, the rate of a temporary neurologic postoperative morbidity increases to 1.7%, of a permanent neurologic morbidity to 1.2%, while the rate of mortality is 1.2%. In the 3rd and 4th stage, those rates amount to 66.7%, 0% and 33.3%, and 1.1%, 3.8% and 1.6%, respectively. The rates of perioperative morbidity and mortality are in proportion to the scope of preoperative brain dysfunction. Results of this work suggest the necessity of categorization of patients, candidates for carotid endarterectomy, according to the clinical stage of the disease, which will enable a better comparison with other authors' results, give a more reliable view on the efficacy of the surgical treatment and justify the surgeons' attitude towards indications.(ABSTRACT TRUNCATED AT 250 WORDS)