Valproate treatment normalizes EEG functional connectivity in successfully treated idiopathic generalized epilepsy patients.

AIM: To investigate the effect of chronic VPA treatment of EEG functional connectivity in successfully treated idiopathic generalized epilepsy (IGE) patients. PATIENTS AND METHODS: 19-channel waking, resting-state EEG records of 26 IGE patients were analyzed before treatment (IGE) and after the 90th day of treatment (VPA), in seizure-free condition. Three minutes of artifact-free EEG background activity (without epileptiform potentials) was analyzed for each patient in both conditions. A group of 26 age-matched healthy normative control persons (NC) was analyzed in the same way. All the EEG samples were processed to LORETA (Low Resolution Electromagnetic Tomography) to localize multiple distributed sources of EEG activity. Current source density time series were generated for 33 regions of interest (ROI) in each hemisphere for four frequency bands. Pearson correlation coefficients (R) were computed between all ROIs in each hemisphere, for four bands across the investigated samples. R values corresponded to intrahemispheric, cortico-cortical functional EEG connectivity (EEGfC). Group and condition differences were analyzed by statistical parametric network method. MAIN RESULTS: p<0.05, corrected for multiple comparisons: (1) The untreated IGE group showed increased EEGfC in the delta and theta bands, and decreased EEGfC in the alpha band (as compared to the NC group); (2) VPA treatment normalized EEGfC in the delta, theta and alpha bands; and (3) degree of normalization depended on frequency band and cortical region. CONCLUSIONS: VPA treatment normalizes EEGfC in IGE patients.

Neurophysiology of juvenile myoclonic epilepsy: EEG-based network and graph analysis of the interictal and immediate preictal states.

INTRODUCTION: The neuronal mechanisms of enduring seizure propensity and seizure precipitation in juvenile myoclonic epilepsy (JME) are not known. We investigated these issues, within the framework of the "network concept" of epilepsy. METHODS: Design1: 19, unmedicated JME patients were compared with nineteen, age-, and sex-matched normal control persons (NC). A total of 120s, artifact-free, paroxysm-free, eyes-closed, resting state EEG background activity was analyzed for each person. Design2: interictal and immediate preictal periods of the JME patients were compared in order to explore interictal-preictal network differences. For both comparison designs, statistically significant differences of EEG functional connectivity (EEGfC), nodal and global graph parameters were evaluated. MAIN RESULTS: Design1: maximum abnormalities were: increased delta, theta, alpha1 EEGfC and decreased alpha2 and beta EEGfC in the JME group as compared to the NC group, mainly among cortical areas that are involved in sensory-motor integration. Nodal degree and efficiency of three, medial, basal frontal nodes were greater in JME than in NC, in the alpha1 band. Design2: preictal delta EEGfC showed further increase in the above-mentioned areas, as compared to the interictal state. DISCUSSION: Increased EEGfC indicates a hypercoupled state among the specified cortical areas. This interictal abnormality further increases in the preictal state. Nodal graph statistics indicates abnormal neuronal dynamics in the cortical area that is the ictal onset zone in JME. SIGNIFICANCE: Interictal and preictal neuronal dysfunction has been described in terms of network dynamics and topography in JME patients. Forthcoming investigations of seizure precipitation and therapeutic drug effects are encouraged on this basis.

Remission of benign epilepsy with rolandic spikes: an EEG-based connectivity study at the onset of the disease and at remission.

PURPOSE: The neuronal mechanisms of remission of epilepsy are not known. Based on the principles of the "network theory of epilepsy" we postulated the existence of abnormal cortico-cortical interactions at the onset of epilepsy (Hypothesis-1), and postulated that remission is associated with the decrease or disappearance of the abnormal quantitative EEG findings (Hypothesis-2). METHODS: Four children with benign epilepsy with rolandic sharp waves (BERS) were investigated. 21-channel EEG was recorded at the onset of the disease (Setting No. 1) and in remission (Setting No. 2). Local EEG synchronization was estimated by LORETA (low resolution electromagnetic tomography). Remote EEG synchronization (intra-hemispheric, cortico-cortical EEG functional connectivity, EEGfC) was computed by the LSC (LORETA Source Correlation) method, among 23 regions of interest (ROI) in both hemispheres. Both local and remote EEG synchronization were evaluated in very narrow frequency bands of 1Hz bandwidth (VNB), from 1 to 25Hz. RESULTS: Individual results were presented. Abnormal but topographically very dissimilar LORETA and LSC findings were found at the onset of the disease. The disappearance of the initial abnormalities was found in Setting No. 2. An unforeseen finding was the presence of abnormal EEGfC results in Setting No. 2. DISCUSSION: The authors confirmed both hypotheses. The dissimilarity of the initial abnormalities is in accord with the network concept of epilepsy and the etiology of BERS. The disappearance of the initial abnormalities reflects "normalization" of network dynamics while the emergence of new EEGfC abnormalities is interpreted as "compensation". CONCLUSION: EEG-based local and remote connectivity (EEGfC) are appropriate tools to describe network dynamics in the active state of BERS and in remission.

EEG-LORETA endophenotypes of the common idiopathic generalized epilepsy syndromes.

OBJECTIVE: We tested the hypothesis that the cortical areas with abnormal local EEG synchronization are dissimilar in the three common idiopathic generalized epilepsy (IGE) phenotypes: IGE patients with absence seizures (ABS), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures exclusively (EGTCS). PATIENTS AND METHODS: Groups of unmedicated ABS, JME and EGTCS patients were investigated. Waking EEG background activity (without any epileptiform potentials) was analyzed by a source localization method, LORETA (Low Resolution Electromagnetic Tomography). Each patient group was compared to a separate, age-matched group of healthy control persons. Voxel-based, normalized broad-band (delta, theta, alpha, and beta) and very narrow band (VNB, 1Hz bandwidth, from 1 to 25Hz) LORETA activity (=current source density, A/m(2)) were computed for each person. Group comparison included subtraction (average patient data minus average control data) and group statistics (multiple t-tests, where Bonferroni-corrected p<0.05 values were accepted as statistically significant). RESULTS: Statistically not significant main findings were: overall increased delta and theta broad band activity in the ABS and JME groups; decrease of alpha and beta activity in the EGTCS group. Statistically significant main findings were as follows. JME group: bilaterally increased theta activity in posterior (temporal, parietal, and occipital) cortical areas; bilaterally increased activity in the medial and basal prefrontal area in the 8Hz VNB; bilaterally decreased activity in the precuneus, posterior cingulate and superior parietal lobule in the 11Hz and 21-22Hz VNBs. ABS group: bilaterally increased theta activity emerged in the basal prefrontal and medial temporal limbic areas. Decreased activity was found at 19-21Hz in the right postcentral gyrus and parts of the right superior and medial temporal gyri. EGTCS group: decreased activity was found in the frontal cortex and the postcentral gyrus at 10-11Hz, increased activity in the right parahippocampal gyrus at 16-18Hz. DISCUSSION: Increased theta activity in the posterior parts of the cortex is the endophenotype for JME. Increased theta activity in the fronto-temporal limbic areas is the endophenotype for ABS. Statistically not significant findings might indicate diffuse biochemical abnormality of the cortex in JME and ABS. SIGNIFICANCE: EEG-LORETA endophenotypes may correspond to the selective propensity to generate absence and myoclonic seizures in the ABS and JME syndromes.

EEG background activity is abnormal in the temporal and inferior parietal cortex in benign rolandic epilepsy of childhood: a LORETA study.

INTRODUCTION: Benign rolandic epilepsy of childhood (BERS) is an epilepsy syndrome with presumably genetic-developmental etiology. The pathological basis of this syndrome is completely unknown. We postulated that a developmental abnormality presumably results in abnormal EEG background activity findings. PATIENTS AND METHODS: 20 children with typical BERS and an age- and sex-matched group of healthy control children underwent EEG recording and analysis. 60×2 s epochs of waking EEG background activity (without epileptiform potentials and artifacts) were analyzed in the 1-25 Hz frequency range, in very narrow bands (VNB, 1 Hz bandwidth). LORETA (Low Resolution Electromagnetic Tomography) localized multiple distributed sources of EEG background activity in the Talairach space. LORETA activity (current source density) was computed for 2394 voxels and 25 VNBs. Normalized LORETA data were processed to voxel-wise comparison between the BERS and control groups. Bonferroni-corrected p<0.05 Student's t-values were accepted as statistically significant. RESULTS: Increased LORETA activity was found in the BERS group (as compared to the controls) in the left and right temporal lobes (fusiform gyri, posterior parts of the superior, middle and inferior temporal gyri) and in the angular gyri in the parietal lobes, in the 4-6 Hz VNBs, mainly at 5 Hz. DISCUSSION: (1) Areas of abnormal LORETA activity exactly correspond to the temporal and parietal cortical areas that are major components of the Mirsky attention model and also the perisylvian speech network. Thus the LORETA findings may correspond to impaired attention and speech in BERS patients. (2) The LORETA findings may contribute to delineating the epileptic network in BERS. SIGNIFICANCE: The novel findings may contribute to investigating neuropsychological disturbances and organization of the epileptic network in BERS.

EEG functional connectivity of the intrahemispheric cortico-cortical network of idiopathic generalized epilepsy.

AIMS: Intrahemispheric, cortico-cortical EEG functional connectivity (fC) was investigated in untreated patients with idiopathic generalized epilepsy (IGE) in this explorative study. PATIENTS AND METHODS: Group comparison was carried out between 19, drug-naive IGE patients and 19, matched healthy persons. 90×2s of 19 channels waking, interictal background EEG signal (without epileptiform potentials) were processed to the LORETA (low resolution electromagnetic tomography) software to compute current source density for 2394 voxels representing parcels of the cerebral cortex for 25 very narrow bands of 1Hz bandwidth (VNBs) from 1 to 25Hz. EEG fC was investigated among the already localized sources. Pearson correlation coefficients (R) were computed among the 33 regions of interest (ROI) within the left and within the right hemisphere, separately. Group differences were computed by means of t-statistics. Corrected p<0.05 differences were accepted as statistically significant. MAIN RESULTS: (1) The anatomical patterns of the fC differences showed great frequency-dependency. (2) Hemispheric asymmetry was prominent within most VNBs. (3) Decreased fC in the IGE group was found across all VNBs in the 1-6Hz frequency range as compared to mixed patterns comprising both increased and decreased fC at >6Hz frequencies. (4) In the 5-25Hz range, decreased fC dominated in the anterior, increased fC in the posterior parts of the cortex. (5) The results delineated an anterior and a posterior network. DISCUSSION: (1) Decreased fC in the 1-6Hz band might indicate some relationship to yet hidden structure network abnormalities. (2) The anatomical patterns of fC indicate frequency-dependent, pathological coupling and decoupling processes in the interictal state. (3) The two networks might help to understand seizure liability and seizure precipitation in IGE. SIGNIFICANCE: This is the first study to explore EEG fC in the interictal condition of IGE patients. The importance of EEG frequencies in evaluating fC in IGE was demonstrated and starting points for further research were given.

Quantitative EEG abnormalities in persons with "pure" epileptic predisposition without epilepsy: a low resolution electromagnetic tomography (LORETA) study.

OBJECTIVE: Epileptic predisposition means genetically determined, increased seizure susceptibility. Neurophysiological evaluation of this condition is still lacking. In order to investigate "pure epileptic predisposition" (without epilepsy) in this pilot study the authors prospectively recruited ten persons who displayed generalized tonic-clonic seizures precipitated by 24 or more hours of sleep deprivation but were healthy in any other respects. METHODS: 21-channel EEGs were recorded in the morning, in the waking state, after a night of sufficient sleep in the interictal period. For each person, a total of 120s artifact-free EEG was processed to low resolution electromagnetic tomography (LORETA) analysis. LORETA activity (Ampers/meters squared) was computed for 2394 voxels, 19 active electrodes and 1Hz very narrow bands from 1 to 25Hz. The data were compressed into four frequency bands (delta: 0.5-4.0Hz, theta: 4.5-8.0Hz, alpha: 8.5-12.0Hz, beta: 12.5-25.0Hz) and projected onto the MRI figures of a digitized standard brain atlas. The band-related LORETA results were compared to those of ten, age- and sex-matched healthy persons using independent t-tests. p<0.01 differences were accepted as statistically significant. RESULTS: Statistically significant decrease of alpha activity was found in widespread, medial and lateral parts of the cortex above the level of the basal ganglia. Maximum alpha decrease and statistically significant beta decrease were found in the left precuneus. Statistically not significant differences were delta increase in the medial-basal frontal area and theta increase in the same area and in the basal temporal area. DISCUSSION: The significance of alpha decrease in the patient group remains enigmatic. beta decrease presumably reflects non-specific dysfunction of the cortex. Prefrontal delta and theta increase might have biological meaning despite the lack of statistical significance: these findings are topographically similar to those reported in idiopathic generalized epilepsy in previous investigations. SIGNIFICANCE: Quantitative EEG characteristics of the genetically determined epilepsy predisposition were given in terms of frequency bands and anatomical distribution.

Theta EEG source localization using LORETA in partial epilepsy patients with and without medication.

OBJECTIVE: To investigate and localize the sources of spontaneous, scalp-recorded theta activity in patients with partial epilepsy (PE). METHODS: Nine patients with beginning, untreated PE (Group 1), 31 patients with already treated PE (Group 2), and 14 healthy persons were investigated by means of spectral analysis and LORETA, low resolution electromagnetic tomography (1 Hz very narrow band analysis, age-adjusted, Z-scored values). The frequency of main interest was 4-8 Hz. RESULTS: Group analysis: Group 1 displayed bilateral theta maxima in the temporal theta area (TTA), parietal theta area (PTA), and frontal theta area (FTA). In Group 2, theta activity increased all over the scalp as compared to the normative mean (Z=0) and also to Group 1. Maximum activity was found in the TTA, PTA, and FTA. However, in the PTA and FTA the centers of the abnormality shifted towards the medial cortex. Individual analysis: all the patients showed preferential activation (maximum Z-values) within one of the three theta areas. CONCLUSIONS: EEG activity in the theta band is increased in anatomically meaningful patterns in PE patients, which differs from the anatomical distribution of theta in healthy persons. SIGNIFICANCE: The findings contribute to our understanding of the sources of theta rhythms and the pathophysiology of PE.

The Debrecen Stroke Database: demographic characteristics, risk factors, stroke severity and outcome in 8088 consecutive hospitalised patients with acute cerebrovascular disease.

BACKGROUND: High stroke mortality in central-eastern European countries might be due to higher stroke incidence, more severe strokes or less effective acute care than in countries with lower mortality rate. Hospital databases usually yield more detailed information on risk factors, stroke severity and short-term outcome than population-based registries. PATIENTS AND METHODS: The Debrecen Stroke Database, data of 8088 consecutively hospitalised patients with acute cerebrovascular disease in a single stroke centre in East Hungary between October 1994 and December 2006, is analysed. Risk factors were recorded and stroke severity on admission was scored by the Mathew stroke scale. The modified Glasgow outcome scale was used to describe patient condition at discharge. RESULTS: Mean age was 68+/-13 years, 11.4% had haemorrhagic stroke. The rate of hypertension on admission was 79% in men, and 84% in women, 40.3% of men and 19.8% of women were smokers, and 34% of all patients had a previous cerebrovascular disease in their history. Case fatality was 14.9%, and 43% had some disability at discharge. Outcome at discharge was worse with higher age, higher glucose, higher blood pressure, higher white cell count and erythrocyte sedimentation rate and more severe clinical signs on admission. In multivariate analysis admission blood pressure lost its significance in predicting outcome. CONCLUSIONS: In this large Hungarian stroke unit database hypertension on admission, smoking and previous cerebrovascular disease were more frequent than in most western databases. These findings indicate major opportunities for more efficient stroke prevention in this and probably other eastern European countries.

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.

Application of sequential extraction with supercritical CO(2), subcritical H(2)O, and an H(2)O/CO(2) mixture for estimation of environmentally mobile heavy metal fractions in sediments.

Results from use of a new isolation procedure based on sequential extraction with supercritical CO(2), subcritical H(2)O, and an H(2)O/CO(2) mixture in the same supercritical fluid extractor have been compared with results from the BCR-recommended three-step sequential extraction procedure. The new procedure gives more detailed information about environmentally mobile fractions (water-soluble, bicarbonate-forming), and in less time (5-6 h), than the BCR procedure.

The Mures-Uzhgorod-Debrecen study: a comparison of hospital stroke services in Central-Eastern Europe.

Stroke mortality is extremely high in Central-Eastern European countries. The high rate of risk factors and differences in health care services might be among the factors resulting in high stroke morbidity and mortality in this region. As only few prospectively collected information are available from this region, we decided to evaluate some characteristics of stroke services in neurological departments of a Romanian, a Ukrainian and a Hungarian city in the framework of the Mures-Uzhgorod-Debrecen comparative epidemiological study. We registered demographic data, the absence or presence of the most important risk factors, and clinical signs on admission and at discharge. We recorded the application of various diagnostic methods, stroke treatment and recommendations for secondary prevention. Follow-up is planned after 30 days and after 1 year. The paper summarizes the methodology of this prospective epidemiological study of stroke patients hospitalized in neurological departments in Târgu Mures, Uzhgorod and Debrecen, three Central-Eastern European cities in Romania, Ukraine and Hungary, respectively.

Natural coagulation inhibitor proteins in young patients with cerebral ischemia.

Disturbances of coagulation and fibrinolytic pathways were studied in 53 young patients with cerebral ischemia. Upon admission 26 of 53 patients had abnormality in at least one of the antithrombin-III, protein C, protein S activities or in activated protein C (APC) ratios. Three months after the first examination the majority of the previously detected abnormalities returned to normal values and the most frequent alterations were decrease in protein S activity (3 patients) and APC resistance (3 patients). Conditions resulting in impaired fibrinolysis were frequently detected upon admission. Elevation of plasminogen activator inhibitor-1, lipoprotein (a), and alpha-2-antiplasmin was present in 23, 10, and 4 cases, respectively. It is concluded that abnormalities of coagulation as well as of the fibrinolytic systems are prevalent in the acute phase of cerebral ischemia, however, the results may be significantly influenced by the disease process or the acute phase effect.

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.

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.

[The effect of a single-dose intravenous vinpocetine on brain metabolism in patients with ischemic stroke]. / Egyszeri vinpocetin-infúzió agyi anyagcserére gyakorolt hatásának vizsgálata territoriális típusú ischaemiás stroke-ot szenvedett betegeken.

The effect of a single-dose i.v. infusion of vinpocetine on the cerebral blood flow (CBF) and glucose metabolism of post-stroke patients was studied by measuring the regional and global cerebral metabolic rates of glucose (CMRglu) and the corresponding kinetic constants before and after treatment. Transcranial Doppler (TCD) and single photon emission tomography (SPECT) measurements were also performed. The cerebral glucose metabolism was significantly higher in the contralateral hemisphere than in the affected one before therapy. In the affected hemisphere the regional glucose metabolism was inhomogenous: relatively low values were measured in the stroke region, whereas it was increased in the peristroke region. Although a single-dose vinpocetine treatment did not affect significantly the regional or global metabolic rates of glucose, the glucose transport (both intracellular up-take and release) was strongly affected in the whole brain, in the contralateral hemisphere and in the peri-infarct area of the symptomatic hemisphere. A slightly increased (not significant, N. S.) cerebral blood flow could be observed in the contralateral and a decreased flow (N. S.) in the symptomatic hemisphere.

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.

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.

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.