Vinpocetine for acute ischaemic stroke.

BACKGROUND: Vasoactive and neuroprotective drugs such as vinpocetine are used to treat stroke in some countries. OBJECTIVES: To assess the effect of vinpocetine in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched February 2007), MEDLINE (1966 to February 2007) and Scopus (1960 to February 2007). We also searched the Internet Stroke Center Stroke Trials Registry, Google Scholar, the science-specific search engine Scirus and Wanfang Data, the leading information provider in China. We contacted researchers in the field and four pharmaceutical companies that manufacture vinpocetine. Searches were complete to February 2007. SELECTION CRITERIA: Unconfounded randomised trials of vinpocetine compared with placebo, or any other reference treatment, in people with acute ischaemic stroke. We included trials if treatment started no later than 14 days after stroke onset. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria. One review author extracted the data, which was then checked by the second review author. We assessed trial quality. The primary outcome measure was death or dependency. MAIN RESULTS: We included two trials, involving a total of 70 participants. Data for 63 participants were reported in the two trials combined. The rate of death or dependency did not differ between the treatment and placebo groups at one and three months. The 95% confidence intervals for the outcome measures were wide and included the possibility of both significant benefit and significant harm. No adverse effects were reported. AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the effect of vinpocetine on survival or dependency in patients with acute ischaemic stroke.

Mannitol for acute stroke.

BACKGROUND: Mannitol is an osmotic agent and a free radical scavenger which might decrease oedema and tissue damage in stroke. OBJECTIVES: To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischaemic stroke or intracerebral haemorrhage (ICH). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (searched December 2006), MEDLINE (1966 to January 2007), the Chinese Stroke Trials Register (searched November 2006), the China Biological Medicine Database (searched December 2006) and the Latin-American database LILACS (1982 to December 2006). We also searched the database of Masters and PhD degree theses at Sao Paulo University (searched January 2007), and neurology and neurosurgery conference proceedings in Brazil from 1965 to 2006. In an effort to identify further published, ongoing and unpublished studies we searched reference lists and contacted authors of published trials. SELECTION CRITERIA: We included randomised controlled trials comparing mannitol with placebo or open control in patients with acute ischaemic stroke or non-traumatic intracerebral haemorrhage. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality, extracted data, and performed the data analysis. MAIN RESULTS: Three small trials, involving 226 participants, were included. One trial included patients with presumed ischaemic stroke without computerised tomography (CT) verification, and the other two trials included patients with CT-verified ICH. Data on the primary outcome measure (death and dependency) were not available in any of the trials. Death and disability could be calculated in the larger ICH trial without differences between the mannitol and control groups. Case fatality was not reported in the trial of ischaemic stroke. Case fatality did not differ between the mannitol and control groups in the ICH trials. Adverse events were either not found or not reported. The change in clinical condition was reported in two trials, and the proportion of those with worsening or not improving condition did not differ significantly between mannitol-treated patients and controls. Based on these three trials neither beneficial nor harmful effects of mannitol could be proved. Although no statistically significant differences were found between the mannitol-treated and control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms as possibilities. AUTHORS' CONCLUSIONS: There is currently not enough evidence to support the routine use of mannitol in acute stroke patients. Further trials are needed to confirm or refute whether mannitol is beneficial in acute stroke.

Rate of buthionine sulfoximine entry into brain and xenotransplanted human gliomas.

Buthionine sulfoximine (BSO) is an inhibitor of glutathione synthesis and can be used to potentiate the effects of chemotherapeutic alkylating agents and radiotherapy. We examined the rates of influx and efflux of [35S]BSO administered to athymic mice with and without xenografted D-54MG human gliomas. Three analytic approaches were applied to the experimental data to obtain values of the blood-to-tissue influx constant, K1, of BSO. Multiple time point experiments in tumor-bearing mice were analyzed with a two-compartment model and nonlinear fitting routines, and by graphical analysis which assumed no backflux of BSO from tissue to blood. A third approach used single time point data in nontumor-bearing mice and assumed no backflux. Calculated values of the K1 of BSO ranged from 0.23 to 1.35 microliters/g/min in tumor-free cortex, and from 5.3 to 6.3 microliters/g/min in the D-54MG gliomas. The tissue-to-blood efflux constant, k2, was zero in both cortex and tumor, suggesting that BSO entered cells and was trapped once it crossed the blood-brain barrier. Estimates of plasma vascular space (Vp) ranged from 2 to 20 microliters/g in cortex, and from 103 to 169 microliters/g in tumor. Another set of experiments, done in normal mice with different doses of BSO, suggested that BSO competes for neutral amino acid transport sites at the blood-brain barrier, but that the capacity of the carrier-mediated transport system is low and saturates at administered doses of about 0.5 mmol/kg (corresponding to plasma concentrations of about 12 mumol/ml). The rate of entry into brain was proportional to the octanol/water partition coefficient and molecular weight of BSO, which also supports passive diffusion as the means of entry. Consequently, although the rate of BSO entry into D-54MG gliomas was between 4 and 30 times higher than the rate of entry into tumor-free cortex, the results of these experiments suggest that most of the BSO that enters brain tumors in the doses commonly used in experimental situations will cross capillaries by passive diffusion.

The effect of an amino acid-lowering diet on the rate of melphalan entry into brain and xenotransplanted glioma.

Melphalan (L-phenylalanine mustard, L-PAM, alkeran; molecular weight, 305,000) is transported across tumor cell membranes and the blood-brain barrier by the large neutral amino acid (LNAA) transport system. Normally, plasma LNAA levels are high enough and the affinity low enough that this system does not transport much melphalan into the brain. However, plasma amino acids can be reduced by fasting and protein-free diet. We used this method to reduce competition and to increase melphalan transport into brain tumors. In nude mice fasted for 12 h and then fed a protein-free diet for 2 and 6 h, mean plasma LNAA levels were 46% and 42% of control values. Nude mice with xenotransplanted D-54MG human gliomas were used to study tissue distribution and uptake kinetics of [3H]melphalan in a control group and a diet group (after a 12-h fast and 2 h of a 0% protein diet). The K1 (blood-to-tissue transfer constant) of melphalan, determined by graphical analysis and by nonlinear fitting to a 2-compartment model, was higher in the diet group in all tumor regions except the necrotic center of subcutaneous tumors; the increase was significant in the tumor periphery of brain and s.c. tumors. The ratio of K1s (diet to control) varied from 1.2 to 1.3 in brain tumors, 1.9 to 2.1 in subcutaneous tumors, and 1.8 to 3.1 in tumor-free brain. The apparent [3H]melphalan distribution space was significantly higher in the tumor periphery of both brain and subcutaneous tumors of the 15- and 30-min diet group. We also measured blood-brain barrier transport of [alpha-14C]aminoisobutyric acid and blood flow (with [131I]iodoantipyrine): the K1 of [alpha-14C]aminoisobutyric acid was 28.1 +/- 6.6 (SE) in brain tumors and 24.3 +/- 8.9 microliters/g/min in subcutaneous tumors. Blood flow was 58.2 --> 3.9 in brain tumors and 5.2 +/- 0.4 ml/100 g/min in subcutaneous tumors. Fasting, when combined with a protein-free diet, reduces plasma amino acid levels and thereby reduces competition between melphalan and LNAAs. This may increase the amount of melphalan that can enter a brain tumor without increasing the administered drug dose and suggests a therapeutic manipulation that can be used to increase the delivery of melphalan.

Cochrane report: A systematic review of mannitol therapy for acute ischemic stroke and cerebral parenchymal hemorrhage.

BACKGROUND: Mannitol was reported to decrease cerebral edema associated with tissue damage and is used to treat acute stroke in many countries. SUMMARY OF REVIEW: We tested whether there is any evidence from unconfounded randomized clinical trials that treatment with mannitol reduces short- and long-term case fatality and dependency if administered after ischemic stroke or cerebral parenchymal hemorrhage. Trials were identified by the standard search strategy of the Cochrane Collaboration Stroke Review Group. A supplementary MEDLINE search was performed, and the Chinese Stroke Trials Register and the Latin-American databank LILACS were checked. A search was performed of master's and PhD degree theses in the databank of Sao Paulo University and in abstracts of medical congresses on neurology and neurosurgery during 1965-1997 in Brazil. Investigators were contacted for unpublished information. Only truly randomized unconfounded clinical trials were eligible for inclusion. Two of the reviewers independently extracted data from the trials. Data synthesis and analysis was performed with the use of the Cochrane Review Manager software (RevMan version 4.0.4). CONCLUSIONS: Only 1 trial fulfilled the inclusion criteria. The number of included patients was small, and the follow-up was short. Case fatality, the proportion of dependent patients, and side effects were not reported and were not available from the investigators. As a result of lack of appropriate randomized trials, currently no conclusion can be drawn on the effects of mannitol in acute stroke. The routine use of mannitol in all patients with acute stroke is not supported by evidence from randomized controlled clinical trials.

Cerebral ischaemia produced by homologous blood clot emboli in rabbit.

In 40 rabbits cerebral ischaemia was induced by autologous blood clot emboli injected into the middle cerebral artery. Autologous blood clot formed spontaneously (within 2 h) in a catheter fixed in the internal carotid artery. The effects of embolization were investigated on arterial blood pressure, respiration, local cerebral blood flow, locally available O2 (aO2), steady (DC) potentials and EEG. After embolization the blood pressure and the frequency of respiration decreased transiently. On the embolized side the local cerebral blood flow, aO2, the frequency and amplitude of the EEG diminished markedly and the DC potentials shifted to negative. Similar but less marked and short-lasting changes could be seen on the contralateral side. Pathological examination of the brains revealed extensive infarction with haemorrhagic components. The technique is a promising method for inducing stroke experimentally and offers various ways for its thorough investigation.

Beneficial vascular and metabolic effects of cobalt-ATP in spontaneously hypertensive rabbits with diffuse chronic cerebral ischaemia.

The in vivo effects of adenosine triphosphate (ATP) have not been investigated in cerebrovascular diseases. The use of the long-acting cobalt-ATP complex (Co-ATP) permits us to observe the effects of ATP without the influence of its metabolites. This study was designed to compare the effects of intravenous Co-ATP on the cerebral blood flow (CBF), polarographically detected oxygen currents (O2a), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose in 13 normotensive (NT) rabbits to those in 14 stroke-prone spontaneously hypertensive (HT) animals. CBF was measured by the hydrogen and heat clearance methods. In response to Co-ATP, MABP decreased and CBF increased significantly in both groups. The decrease in MABP was more marked in HT rabbits, while CBF response was 25% smaller than in NT animals. The ratio of O2a to CBF diminished moderately and simultaneously with the CBF increase in NT rabbits. In HT rabbits, the decrease in O2a/CBF was larger and began when CBF response reached its maximum. We suggest that despite the restricted CBF response, long-acting ATP should still be taken into consideration as a supplementary treatment of hypertensive encephalopathy because of its beneficial effects on cerebral metabolism and hypertension.

Experimental focal cerebral ischaemia in rabbits.

A highly reproducible form of experimental embolization of the intracranial arteries is presented in rabbits. The injection of a silver or gold ball into the internal carotid artery caused occlusion predominantly of the middle cerebral artery and/or its branches. At the moment when embolization took place, the characteristic signs of acute cerebral ischaemia occurred in the electroencephalogram, local cerebral blood flow and steady (DC) potentials. Several hours after the ball had been injected the extent of the focal lesions became recognizable on sections stained for myelin. The procedure is simple, rapid, inexpensive and practically always successful. The extent of the lesion may be influenced by the change of both the ball size and the posture of animals. Moreover, the site of occlusion is easily discernible both on radiographs and to the naked eye.

Difference between the cerebrovascular effect of purinergic Co-ATP and that of the cholinesterase inhibitor, physostigmine, in vivo.

Development of the cerebrovascular effect of cobalt-ATP was compared to that of physostigmine in 34 anesthetized rabbits. The resting cortical cerebral blood flow (CBF) was estimated from the H2 clearance and the CBF changes by the heat clearance method. Systemic blood pressure, heart and respiratory rate and cerebral electrical activity were recorded simultaneously. In addition, we measured arterial glucose concentration, pH, PaO2 and PaCO2. Both drugs were found to induce a significant increase in CBF. However, the degree of the CBF increase induced by Co-ATP was inversely related, while that induced by physostigmine was directly related to both the baseline level of CBF and the value of PaCO2. We conclude that the cerebrovascular effect of ATP depends mainly on vessel tone, while the effect of physostigmine is related to the level of PaCO2.

Effects of dipyridamole in spontaneously hypertensive rabbits with diffuse chronic cerebral ischemia.

The effect of intravenous dipyridamole (0.7 mg/kg) on cerebral blood flow (CBF), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose was investigated in 14 normotensive and 14 stroke-prone spontaneously hypertensive anesthetized rabbits. CBF was measured by hydrogen and heat clearance. In both groups, MABP decreased (normotensive: -24 mm Hg, hypertensive: -47 mm Hg; ANOVA: P < 0.0001) and CBF increased (normotensive: +59 ml/100 g/min, hypertensive: +72 ml/100 g/min; ANOVA: P < 0.0002). CBF returned to the initial level 21 min later in hypertensive than in normotensive rabbits. Changes in other parameters were insignificant. In additional experiments, 30 mg/kg theophylline entirely prevented the cerebral vasodilator and systemic hypotensive effects of dipyridamole in both normotensive and hypertensive rabbits. We conclude that, in stroke-prone spontaneously hypertensive rabbits, the longer-lasting and larger CBF increase in response to dipyridamole may be attributed to reversible functional changes in the cerebral vasculature resulting from hypertension.

Effect of i.v. dipyridamole on cerebral blood flow, blood pressure, plasma adenosine and cAMP levels in rabbits.

In response to intravenous administration of dipyridamole, the quantitative and temporal changes in plasma adenosine and cyclic AMP (cAMP) levels in relation to the changes in cerebral blood flow (CBF) and mean arterial blood pressure (MABP) have not been studied. Therefore, we investigated simultaneously the changes in CBF (hydrogen and thermal clearance methods), MABP, plasma adenosine (HPLC) and cAMP (radioimmunoassay) levels for 1 h after intravenous injection of 0.7 and 1.4 mg/kg dipyridamole in rabbits. In separate experiments, only plasma adenosine concentrations were measured to determine how and for how long intravenous administration of 0.7 mg/kg dipyridamole is able to inhibit the removal of plasma adenosine. Dipyridamole decreased MABP, increased plasma adenosine and cAMP levels in a dose-dependent manner. The dose-dependency of increases in CBF could not be demonstrated owing to the marked hypotension. The increase in plasma adenosine concentrations was biphasic. The first peak could be detected at the end of the dipyridamole injection. The second peak occurred 20 min after drug administration, simultaneously with the maximal increases in plasma cAMP level and CBF, whereas the maximal fall in MABP developed earlier. Intravenous administration of 0.7 mg/kg dipyridamole inhibited adenosine uptake only by 25%, which lasted less than 10 min. We concluded that intravenously given dipyridamole is responsible only for the initial short-lasting elevation of plasma adenosine concentration, and is able to induce vasodilation without either dipyridamole itself or adenosine necessarily gaining access to the muscular layer.

Screening for depressive symptoms in the acute phase of stroke.

Depressive symptoms can often be observed after stroke. We prospectively evaluated patients at a stroke unit in order to determine the occurrence and severity of depressive symptoms in the acute phase of stroke in 82 patients 7 +/- 2 days after admission to the stroke unit. Severity of stroke was evaluated by the Scandinavian and Orgogozo scales and the Barthel index. Severity of depressive symptoms was measured by the 13-item Beck scale. Mean age of the patients was 65.8 years. No gender difference was observed in the severity of stroke or depressive symptoms. DSM-IV criteria of adjustment disorder with depressed mood were fulfilled by 27% of the patients. In this group, stroke was significantly more severe by the Barthel, Orgogozo, and Scandinavian scales (p < 0.001). Whereas Beck score was at least 10 in 19.5%, severe depressive symptoms (Beck score > or = 15) occurred in less than 5% of patients with acute stroke. Those who could not walk by themselves or who were aphasic had significantly higher mean Beck scores (6.3 +/- 5.1 vs 2.4 +/- 3.1, p < 0.001, and 7.0 +/- 5.8 vs 3.4 +/- 3.9, p = 0.002). Significant correlation was found between the severity of stroke and that of the depressive symptoms (r = -0.56, -0.58, and -0.54 for the Scandinavian, Orgogozo, and Barthel scales, p < 0.001).

Screening for depressive symptoms among post-stroke outpatients in Eastern Hungary.

Patients were consecutively enrolled in a cross-sectional study to determine the severity of depressive symptoms and the rate of treated depression in a patient population returning to a stroke outpatient service during a 10-week period for a regular check-up examination after their stroke. Of the 143 stroke patients, 119 fulfilled the inclusion criteria. The 13-item Beck Depression Inventory was used to screen for depressive symptoms. The score was at least 5 in 53%, 10 or above in 26%, and 15 or above in 11% of patients. Severity of depressive symptoms did not depend on gender, age, time elapsed from stroke, or the site of the cerebral lesion. Most patients with considerable depressive symptoms did not receive antidepressant medication at the time of the screening.

Cations of cisternal cerebrospinal fluid in humans and the effect of different doses of nimodipine on CSF calcium after stroke.

Cisternal samples of cerebrospinal fluid (CSF) were analyzed for protein, albumin, sodium (Na), potassium (K), and calcium (Ca) content in 21 control subjects and 64 patients who had experienced acute stroke. A second cisternal CSF sample was taken in 37 of the stroke patients after 2-3 weeks treatment with the calcium antagonist nimodipine. Increased permeability of the blood-brain barrier was reflected by the significantly higher CSF/serum ratio of albumin in stroke patients than in control subjects (0.0046 vs. 0.0028,p = 0.0012). Serum and CSF concentrations of Na, K, and Ca did not differ between control subjects and stroke patients. In control subjects and in stroke patients, concentration of calcium in cisternal CSF ([Ca]) was smaller than values reported by others in lumbar samples. In stroke patients, the pH of CSF was lower than that of simultaneously taken blood (7.38 vs. 7.44, p < 0.001). No differences between stroke patients and control subjects were found for the cisternal CSF/serum ratios of Na (1.0 and 0.99), K (0.61 and 0.63), and Ca (0.25 and 0.24). When patients and controls were pooled together, CSF total [Ca] correlated weakly with serum total [Ca] (Spearman r = 0.28, p = 0.014) and with serum ionized [Ca] (Spearman r = 0.27, p = 0.016). After 2-3 weeks of nimodipine treatment, CSF [Ca] was significantly lower in the subgroup treated with 60 mg nimodipine four times daily (240 mg/d) than with 30 mg four times daily. A nimodipine dosage of 30 mg four times daily (120 mg/d) did not affect CSF [Ca]. A 240 mg daily dosage, but not a 120 mg daily dosage, of nimodipine may affect the Ca transport system in humans at the choroid plexus.

Cerebral effects of a single dose of intravenous vinpocetine in chronic stroke patients: a PET study.

The effects of vinpocetine (Cavinton) on the cerebral glucose metabolism of chronic stroke patients are studied with positron emission tomography. The regional and global cerebral metabolic rates of glucose (CMRglu) and the kinetic constants related to them are quantified before and after single-dose intravenous vinpocetine treatment. These measurements are completed with transcranial Doppler sonography and single photon emission computed tomography to explore the possible mechanisms underlying the resulting changes in glucose uptake and metabolism in the brain. The authors' findings indicate that a single-dose vinpocetine treatment, although it does not affect significantly the regional or global metabolic rates of glucose, improves significantly the transport of glucose (both uptake and release) through the blood-brain barrier in the whole brain, the entire contralateral hemisphere, and in the brain tissue around the infarct area of the symptomatic hemisphere. These changes are in accord with increased blood flow in the entire contralateral hemisphere as well as decreased blood flow velocity and increased peripheral vessel resistance in the entire symptomatic hemisphere.

Vinpocetine for acute ischaemic stroke.

BACKGROUND: Vasoactive and neuroprotective drugs are used to treat stroke in some countries. OBJECTIVES: The objective of this review was to assess the effect of vinpocetine in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched: August 1999) and Medline. We contacted researchers in the field and drug companies. SELECTION CRITERIA: Unconfounded randomised trials of vinpocetine compared with placebo, or any other reference treatment, in people with acute stroke. Trials were included if treatment started no later than 14 days after stroke onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. One reviewer extracted the data that was then checked by the second reviewer. Trial quality was assessed. MAIN RESULTS: One trial involving 40 patients was included. Data for 33 patients were reported. No deaths occurred in the trial and no significant difference in dependency was shown between the treatment and placebo groups. No adverse effects were reported. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the effect of vinpocetine on survival or dependency of patients with acute stroke.

Mannitol for acute stroke.

BACKGROUND: Mannitol is an osmotic agent and a free radical scavenger so it might decrease oedema and tissue damage in stroke. OBJECTIVES: To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischaemic stroke or cerebral parenchymal haemorrhage. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Trials Register. In addition to this, supplementary MEDLINE searches were performed. The Chinese Stroke Trials Register was checked and the Latin-American databank LILACS was searched with the search term MANNITOL and its variations in the Portuguese and Spanish languages. A search was performed of Masters and Ph.D. degree theses in the databank of Sao Paulo University, and in abstracts of medical congresses on neurology and neurosurgery from 1965 to 1997 in Brazil. SELECTION CRITERIA: Truly randomised unconfounded clinical trials comparing the effect of mannitol with placebo or open control in patients with acute ischaemic stroke or parenchymal haemorrhage were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials to be included in the review. After reaching an agreement on which trials to include, two of the reviewers extracted data from the trials and performed the data analysis. Accuracy of data extraction was checked by comparing the results. Included trials were tabulated for methodological quality including the method of randomisation and blinding, and stating if CT was performed, if patients were lost to follow-up and if intention-to-treat analysis was performed. Data synthesis and analysis was performed using the Cochrane Review Manager software. MAIN RESULTS: Only one trial fulfilled the inclusion criteria. The number of included patients was small (36 treated and 41 controls) and the follow up was short. Neither beneficial nor harmful effects of mannitol could be proved. Case fatality, the proportion of dependent patients at the end of the follow up and side effects were not reported and were not available from the investigators. The planned outcome analyses and sensitivity analyses could not be performed due to lack of appropriate trials. REVIEWER'S CONCLUSIONS: There is currently not enough evidence to decide whether the routine use of mannitol in acute stroke would result in any beneficial or harmful effect. The routine use of mannitol in all patients with acute stroke is not supported by any evidence from randomised controlled clinical trials. Further trials are needed to confirm or refute the routine use of mannitol in acute stroke.

Characteristics of 4 stroke scales for the detection of changes in clinical signs in the acute phase of stroke.

OBJECTIVES: Detection of minor changes in clinical signs of stroke may be of interest when evaluating treatment interventions. This study analyzes the internal structure of four frequently used stroke scales and compares them for their sensitivity to detect changes in neurologic signs in the first week after acute stroke. METHODS: A cohort of 77 hospitalized acute stroke patients was scored by the Mathew, the National Institutes of Health (NIH), the Scandinavian, and the Orgogozo scales within 48 hours of hospital admission and again 7 days later. RESULTS: Scores on different scales correlated well with each other (range of absolute value of Spearman R, .82-.91; P <.001 in all comparisons). Scales reflected significant changes from entry to reexamination: P = .0013 for the Scandinavian scale (P = .004 for prognostic and P = .009 for long-term items, respectively); P = .00009 for the Orgogozo scale; P = .000007 for the Mathew scale; and P < .000001 for the NIH scale. This difference in sensitivity coincided with the number of factors extracted by principal component analysis: higher sensitivity of a scale was associated with a larger number of factors. Initial scores differed significantly among patients who were discharged, patients who died, and patients who remained hospitalized 7 days after the first examination (Kruskal-Wallis ANOVA, P < .01 for all scales). CONCLUSIONS: There are considerable differences in the internal structure of the different scales as reflected by the different number of factors extracted from the scale items. The application of the NIH scale is recommended for the most sensitive detection of changes in stroke signs.

Preparation and primary evaluation of [11C]CSC as a possible tracer for mapping adenosine A2A receptors by PET.

A 11C labeled selective adenosine A2A antagonist, (E)-8-(3-chlorostyryl)-1,3-dimethyl-7-[11C]methylxanthine [11C]CSC) was prepared by the reaction of (E)-8-(3-chlorostyryl)-1,3-dimethylxanthine and [11C]methyl iodide. The decay-corrected radiochemical yield was 32.3% with a radiochemical purity of 99%, a specific activity of 1.85-5.55 GBq/mumol and a preparation time of 1 h. A primary evaluation of [11C]CSC as a potential tracer for mapping adenosine A2A receptors by positron emission tomography (PET) is also presented. Biodistribution and autoradiographic studies were carried out on Swiss mice and domestic rabbits. In mice the lung showed the highest uptake at 10 min after i.v. injection, followed by the liver, kidney, heart and brain. Inside the brain a high level of radioactivity accumulated in the striatum, in accordance with previous findings on the specific spatial distribution of A2A adenosine receptors and also in the medulla oblongata. Dynamic PET studies on rabbits showed a fast brain uptake of CSC, reaching a maximum in less then 2 min. On the basis of competition experiments with the unlabeled ligand [11C]CSC proves to bind specifically to the appropriate receptor.

Hypoglycemia activates compensatory mechanism of glucose metabolism of brain.

The effect of plasma glucose concentration on the cerebral uptake of [18F]-fluorodeoxy-D-glucose (FDG) was studied in a broad concentration range in a rabbit brain model using dynamic FDG PET measurements. Hypoglycemic and hyperglycemic conditions were maintained by manipulating plasma glucose applying i.v. glucose or insulin load. FDG utilization (K) and cerebral glucose metabolic rate (CGMR) were evaluated in a plasma glucose concentration range between 0.5 mM and 26 mM from the kinetic constant k1, k2, k3 obtained by the Sokoloff model of FDG accumulation. A decreasing set of standard FDG uptake values found with increasing blood glucose concentration was explained by competition between the plasma glucose and the radiopharmacon FDG. A similar trend was observed for the forward kinetic constants k1, and k3 in the entire concentration range studied. The same decreasing tendency of k2 was of a smaller magnitude and was reverted at the lowest glucose concentrations where a pronounced decrease of this backward transport rate constant was detected. Our kinetic data indicate a modulation of the kinetics of carbohydrate metabolism by the blood glucose concentration and report on a special mechanism compensating for the low glucose supply under conditions of extremely low blood glucose level.