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.

Quantitative and qualitative evaluation tool in planning stroke treatment strategies: the "Safe implementation of treatments in stroke Monitoring Study (SITS MOST)" registry.

A decade ago, stroke was the first leading cause of morbidity and mortality in Croatia. Nowadays, we record reduction in stroke incidence, as well as stroke consequences-invalidity and mortality. These are due to long-term planned actions in the field of public health as well as actions performed by professional organizations. Today, we can be satisfied with improvement in that field, but there are still things we can improve, at the first place improvement of the emergency medicine network due to Croatian-specific topographical characteristics to reduce onset-to-door time. In this paper, we evaluated results from 11 Croatian hospitals in the period 11/2005-11/2012. To find out about the past and present state in applying thrombolytic therapy in Croatia and to plan further actions in light of new studies and efforts in Europe and in the world, all with the aim of improvement in stroke prevention and acute treatment resulting in reduction of stroke morbidity, mortality and symptomatic intracerebral hemorrhage as well as better functional outcome. Our results have shown that we improved stroke treatment in the last decade, but further actions should be performed to raise public stroke awareness and to improve emergency medicine network as well as in hospital protocols.

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.

[Vertebrobasilar transient ischemic attacks in young and middle aged patients].

A complex clinical, neurological, laboratory, ultrasound and neuroimaging examination of 70 patients, aged 31-59 years, suffering from vertebrobasilar transient ischemic attack (TIA) was carried out in order to determine clinical and pathogenetic peculiarities of the disease in young and middle aged patients. The hemodynamically significant atherosclerotic lesion of the large cerebral arteries (LCA) as a cause of TIA was observed more rarely in the young and middle age groups than in elderly and aged people. Heart valves lesion was the main cause of cerebral cardioembolism in young and middle aged patients with TIA. A greater number of cases with other established causes of the disease (dissections, kinking of vertebral arteries, hemorheological microocclusion) were revealed. An undetermined pathogenesis of the disease mostly due to the inability to choose the main pathogenetic mechanism out of other potential mechanisms, e.g., the association of arterial hypertension with kinking, the hypoplasia or anomaly of the entrance of vertebral artery into the transverse channel, was observed in these groups more often than in elderly and aged people. The clinical picture of TIA in young and middle aged patients with hemodynamically significant atherosclerotic lesion of LCA had the highest similarity with that in elderly and aged ones. In case of cardioembolic pathogenesis, it was characterized by the markedly less severe signs of the disease and in case of the disease due to isolated arterial hypertension--by the lower rate of vascular white matter abnormalities on neuroimaging. A relatively higher rate of symptoms attributed to the manifestation of hypertensive crisis during the attack was observed in young and middle aged patients with TIA due to isolated arterial hypertension comparing with other pathogenetic variants of the disease. The clinical picture of TIA due to other established causes was depended on the main pathogenetic mechanism of the disease.

Aortic arch dissection presenting with hemodynamic spectrum of aortic regurgitation on transcranial Doppler.

The diagnosis of aortic dissection is frequently missed at the time of hospital admittance. Neurological presentations are rare, and neuro-sonography is rarely used. We describe a patient with atypical clinical presentation of aortic arch dissection in whom neuro-sonological investigations showed a "cathedral like" haemodynamic spectrum of aortic regurgitation, directing the investigation towards the diagnosis.

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.

Teaching of neuroepidemiology in Europe: time for action.

Many epidemiological and clinical studies in Europe, especially in Eastern Europe and countries in transition, are of poor methodological quality because of lack of background knowledge in clinical epidemiology methods and study designs. The only way to improve the quality of epidemiological studies is to provide adequate undergraduate and/or postgraduate education for the health professionals and allied health professions. To facilitate this process, the European Federation of Neurological Societies (EFNS) Task Force on teaching of clinical epidemiology in Europe was set up in October 2000. Based on analyses of the current teaching and research activities in neuroepidemiology in Europe, this paper describes the Task Force recommendations aimed to improve these activities.

Acute stroke treatment in Europe: a questionnaire-based survey on behalf of the EFNS Task Force on acute neurological stroke care.

In 1997 the EFNS Task Force on Acute Neurological Stroke Care published its recommendations for acute stroke care (Brainin et al., 1997), which, in 1999, was followed by a stroke care inventory (Brainin et al., 2000) assessing the development of acute stroke care. In 2000 all 33 members of the EFNS Stroke Scientist Panel were asked to complete a questionnaire on the treatment of acute stroke in their country as of 2000. Data were based either on national surveys or a personal estimate of national practice, together with data from the personal practice of the panel member. Data from 22 countries were received. One of the principal findings is the lack of systematic evidence about practice in a significant number of European countries. Results illustrate that neurologists have a leading role in implementing acute stroke treatment guidelines and in adopting new therapeutic methods in most countries, but there is a wide variation in the application of different therapeutic procedures.

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.

Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease.

Although controversial, data on the genetic polymorphism of apoprotein E (APOE), methylenetetrahydrofolate (MTHFR) and paraoxonase (PON1) genes implicate their role in the development of cerebrovascular disease. The aim of this study was to assess the association of polymorphism of APOE, MTHFR and PON1 genes in 56 stroke and 36 carotid stenosis patients, and in 124 control subjects by PCR-restriction fragment length polymorphism analysis. In the stroke group a significantly different MTHFR genotype distribution (p=0.004, odds ratio for T/T of 17.571), but no significant difference in APOE and PON1 allele and genotype distribution compared to the control was found. The carotid stenosis group exhibited a significantly different APOE allele and genotype distribution (p=0.023, odds ratio APOEepsilon3epsilon4 of 4.24), but no significant difference in the MTHFR and PON1 allele and genotype distribution from the control group. The preliminary results obtained in this study revealed an association of the MTHFR and APOE gene polymorphism with cerebrovascular disease, suggesting a significant risk for stroke in subjects who are homozygous for the T allele and for carotid stenosis in subjects having APOEepsilon3epsilon4 genotype. Additional studies in larger patient groups are needed to confirm these observations.

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.

Carotid artery intima thickness and flow velocity after discontinuation of hormone replacement therapy in postmenopausal women: follow-up study.

AIM: To investigate the effect of discontinuation of hormone replacement therapy on the intima thickness and blood flow velocity of the common carotid artery. METHODS: The thickness of the left common carotid artery intima and maximal systolic blood velocity were measured by real-time and Doppler ultrasonography in 75 healthy postmenopausal women starting sequential combined hormone replacement therapy. The measurements were performed at the start and after 6 and 12 months of the therapy. Thirty two women decided to discontinue the therapy after 6 months, whereas 43 continued. RESULTS: In the group that continued with the hormone replacement therapy, a significant decrease was recorded in the mean baseline values for carotid artery intima thickness and flow velocity at 6 months (0.35+0.11 vs 0.54+0.19 mm and 0.73+0.16 vs 0.87+0.19 m/s, respectively, p?0.001) and 12 months of follow-up (0.36+0.1 mm and 0.72+0.15 m/s vs baseline, respectively, p?0.001). In women who discontinued the therapy, there were significant deviations from the baseline values in the intima thickness (0.36+0.11 vs. 0.59+0.09 mm, p=0.010) and flow velocity (0.75+0.14 vs. 0.85+0.16 m/s, p?0.001) at 6 but not at 12 months of the follow-up (0.55+0.12 mm, and 0.85+0.17 m/s vs baseline; p=0.148 and p=0.965, respectively). CONCLUSION: Decreased flow velocity and reduced intima thickness were directly related to blood vessel wall dilatation after estrogen component of hormone replacement therapy. Discontinuation of the hormone replacement therapy returned the flow velocity and intima thickness to their baseline values.