bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser-Doppler Scanning of Local Cerebral Blood Flow and Reserve Capacity and Testing of Motor and Memory Functions in a Chronic 2-Vessel Occlusion Model in Rats
Authors: Ulrich Peter T. , Kroppenstedt Stefan , Heimann Axel , Kempski Oliver
Published: June 2011

Background and Purpose
—An animal model of incomplete forebrain ischemia resembling human hemodynamic insufficiency was established. The model allows examination of acute and chronic changes of local cerebral blood flow (lCBF) and reserve capacity in correlation with behavioral parameters.

Methods
—Anesthetized male Wistar-Kyoto rats underwent bilateral carotid occlusion (BCO). Laser-Doppler scanning of lCBF at baseline conditions and after acetazolamide was done 30 minutes after BCO, motor and memory function tests were administered after 1 and 2 days, and both investigations were repeated after 1, 2, 4, and 6 weeks. A sham-operated and a control group without any vessel manipulation served as controls.

Results
—lCBF dropped within 60 minutes after surgery by 62% (
P
<0.001) in 10 animals surviving BCO (BCO
survival
) and by 69% in 5 rats that died within 9 days (BCO
lethal
). Acetazolamide increased lCBF to 142.33% in controls, to 136.66% in sham-operated rats (both significant), and to 104.80% in BCO
survival
(not significant), and it decreased flow by 23.1% in BCO
lethal
rats (
P
<0.001). Baseline lCBF normalized within 4 weeks. Total motor function scores were significantly reduced from 9 points preoperatively to 5.80±0.65 in BCO
lethal
and 6.68±0.54 points in BCO
survival
rats 1 day after occlusion. Memory retention function remained impaired after BCO, as did the acetazolamide response, which correlated with motor score and was inversely related to maze exploration time.

Conclusions
—This model allows long-term follow-up of cerebral function, lCBF, and reserve capacity in a pathophysiological setting similar to hemodynamic insufficiency in humans.
Poor Recovery of Mitochondrial Redox State in CA1 After Transient Forebrain Ischemia in Gerbils
Authors: Shiino Akihiko , Matsuda Masayuki , Handa Jyoji , Chance Britton
Published: June 2011

Background and Purpose
—Several investigations have detected evidence of apoptosis in delayed neuronal death, but controversy prevails regarding this point. Recent studies have implicated mitochondria in apoptotic events. To explore relationships between delayed neuronal death and dysfunction of the respiratory chain, we analyzed mitochondrial redox changes in the gerbil hippocampus.

Methods
—We assessed the mitochondrial redox state in gerbil hippocampus before, during, and at various time points after 5 minutes of forebrain ischemia. The redox state was examined with a low-temperature fluorometer. Fluorescence signals of flavoprotein and NADH were measured, and their fluorescence ratio was calculated as a mitochondrial redox ratio (MRR) equal to flavoprotein/(flavoprotein+NADH).

Results
—Ischemia increased NADH and decreased flavoprotein signals in all hippocampal areas, but reduction in MRR was greater in CA1 than in other areas of the hippocampus. Immediately after recirculation, MRR recovery was delayed in the CA1 and the dentate gyrus, and the reduction in MRR persisted in CA1.

Conclusions
—These results suggest that during ischemia CA1 experiences more pronounced hypoxia (state V) than less vulnerable regions. Persistent MRR reduction in CA1 is attributed to dysfunction of the electron transport system, and this phenomenon may be importantly involved in apoptosis.
Long-Term Risk of First Recurrent Stroke in the Perth Community Stroke Study
Authors: Hankey Graeme J. , Jamrozik Konrad , Broadhurst Robyn J. , Forbes Susanne , Burvill Peter W. , Anderson Craig S. , Stewart-Wynne Edward G.
Published: June 2011

Background and Purpose
—Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia.

Methods
—Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event.

Results
—Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived >2 days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4).

Conclusions
—Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.
Factor V Leiden Mutation Is a Risk Factor for Cerebral Venous Thrombosis
Authors: Lüdemann Peter , Nabavi Darius G. , Junker Ralf , Wolff Endrik , Papke Karsten , Buchner Helmut , Assmann Gerd , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Different coagulation disorders have been associated with cerebral venous thrombosis (CVT). Until now, fewer than 50 patients have been reported with CVT and the factor V Leiden (FVL) mutation. Although the prevalence of FVL-positive patients with CVT ranged from 10% to 25%, it was as low as 0.5% to 3% in the control groups. Most other studies had not systematically searched for concomitant risk factors or previous thromboembolic events. To better define the relevance of the FVL mutation in conjunction with additional risk factors in CVT, we conducted the present case-control study.

Methods
—Fifty-five patients with CVT were compared with 272 healthy controls. A standardized interview regarding established risk factors for venous thrombosis and the patients’ and their families’ histories for thromboembolic events was performed. The presence of the FVL mutation was determined by polymerase chain reaction on DNA obtained from peripheral blood leukocytes.

Results
—Of 55 patients, 8 (14.5%) were heterozygous for the FVL mutation compared with 17 of 272 controls (6.25%). The relative risk for the presence of FVL was 2.55 (95% confidence interval, 1.04 to 6.26;
P
=0.04). Additional risk factors for CVT were frequently found in both the presence and absence of FVL. Recurrence of venous thromboembolic events was more frequent in patients with the FVL mutation (5 of 8 patients, 62.5%) than in those without this anomaly (8 of 47 patients, 17%;
P
<0.005).

Conclusions
—Our study confirms the FVL mutation as the most relevant hereditary risk factor for CVT. Coexisting risk factors are usually involved in the initiation of CVT. Patients with the FVL mutation are at an increased risk for recurrent venous thrombosis.
Thrombolysis With Intravenous rtPA in a Series of 100 Cases of Acute Carotid Territory Stroke
Authors: Trouillas Paul , Nighoghossian Norbert , Derex Laurent , Adeleine Patrice , Honnorat Jerôme , Neuschwander Philippe , Riche Georges , Getenet Jean-Claude , Li Wei , Froment Jean-Claude , Turjman Francis , Malicier Daniel , Fournier Gerard , Gabry André Louis , Ledoux Xavier , Berthezène Yves , Ffrench Patrick , Dechavanne Marc
Published: June 2011

Background and Purpose
—Although new, large, double-blind, randomized studies are needed to establish the efficiency of intravenous thrombolysis, open trials of sufficient size may also provide novel data concerning specific outcomes after thrombolysis.

Methods
—An open study of intravenous rtPA in 100 patients with internal carotid artery (ICA) territory strokes between 20 and 81 years of age, with a baseline Scandinavian Stroke Scale (SSS) score of <48 at entry was conducted. Inclusion time was within 7 hours after stroke onset. rtPA (0.8 mg/kg) was infused for 90 minutes, with an initial 10% bolus. Heparin was given according to 3 consecutive protocols. The SSS evaluation was done on days 0, 1, 7, 30, and 90. CT scan was performed before treatment, on days 1 and 7. Etiological investigations included echocardiography and carotid Doppler sonography and/or angiography. Outcome at 1 year was documented by SSS score, the modified Rankin Scale (mRS) score, and a 10-point invalidity scale. Multivariate logistic regression was used to identify predictors of poor versus good outcome.

Results
—At day 90, 45 patients (45%) had a good result, defined as complete regression or slight neurological sequelae (mRS score of 0–1), 18 patients had a moderate outcome (mRS 2–3), and 31 patients had serious neurological sequelae (mRS 4–5). Six patients died, 2 with intracerebral hematoma after immediate heparin. Five of 11 patients (45.5%) treated between 6 and 7 hours had a good result. The overall intracerebral hematoma rate was 7%. Higher values of fibrin degradation products at 2 hours were observed in the subgroup with intracerebral hematomas. Significant predictors of poor outcome on multivariate logistic regression analysis were baseline SSS score of <15 (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.07 to 10.74;
P
=0.04), indistinction between white and gray matter on CT scan (OR, 6.59; 95% CI, 2.19 to 19.79;
P
=0.0008), and proximal internal carotid thrombosis (OR, 3.29; 95% CI, 0.99 to 10.95;
P
=0.05).

Conclusions
—Our study confirms the safety of intravenous rtPA at a dose of 0.8 mg/kg and suggests efficacy for this drug even within 7 hours. Outcome and hematoma rates were at least as favorable as for trials of therapy with a 3-hour time window. Subgroups with a poor prognosis include low baseline neurological score, baseline CT changes, and proximal ICA thrombosis. However, approximately 30% of patients with each of these characteristics show a good outcome, so their inclusion in future routine rtPA protocols is still justified.
Ataxic Hemiparesis
Authors: Gorman Mark J. , Dafer Rima , Levine Steven R.
Published: June 2011

Background and Purpose
—Ataxic hemiparesis is a well-recognized lacunar syndrome involving homolateral ataxia with accompanying corticospinal tract impairment. Despite 30 years of clinical experience there continues to be some doubt as to the defining clinical characteristics, precise neuroanatomic localization of the syndrome, and etiologic mechanisms.

Methods
—We now present 45 new cases that have been analyzed for clinico-radiologic correlation and etiology. Also, all published cases from the English literature known to the authors are reviewed.

Results
—We found that the clinical syndrome of ataxic hemiparesis accurately predicts a small deep infarction, generally in the pons or internal capsule. Sensory loss is highly associated with a capsular localization. We found that 47% of the cases were attributed to small-vessel disease, 11% to cardioembolism, and only 7% to artery-to-artery embolism (all in the basilar artery); 1 case was attributed to thrombocytosis, 1 to multiple sclerosis, and the rest either had negative or incomplete evaluation. Approximately two thirds of the infarctions occurred in patients with neuroimaging evidence of other ischemic brain lesions.

Conclusions
—Ataxic hemiparesis is a distinct clinical syndrome that accurately predicts a small deep infarction, most commonly in the pons or internal capsule. Only sensory loss accurately predicts a capsular localization. Etiology in nearly half of the cases can be attributed to small-vessel disease. Furthermore, ataxic hemiparesis appears to be a good marker for generalized asymptomatic cerebrovascular disease.
Stroke Patterns of Internal Carotid Artery Dissection in 40 Patients
Authors: Lucas Christian , Moulin Thierry , Deplanque Dominique , Tatu Laurent , Chavot Didier
Published: June 2011

Background and Purpose
—Internal carotid artery dissection (ICAD) is a frequent cause of ischemic stroke in young patients. Whether cerebral ischemia is of embolic or hemodynamic origin remains to be determined. Heparin is often administered in ICAD; however, a drug trial can hardly be conducted because of the low recurrence rate after the acute stage. Therefore, the best therapeutic approach should be determined on the basis of the presumed mechanism of cerebral ischemia. One way to approach the mechanism of stroke in ICAD is to determine stroke patterns. We postulated that most cortical and large subcortical infarcts (≥15 mm) are of embolic origin and that small subcortical infarcts (<15 mm) and junctional infarcts are not. The aim of our study was to determine the stroke patterns in 40 consecutive patients with ICAD.

Methods
—The patients (26 women and 14 men; mean age, 42.8 years) had a total of 65 ICADs. Seventeen patients were free of any vascular risk factor. CT scans, MRI scans, and angiographic features were analyzed by observers who were blinded to the clinical findings.

Results
—We found 34 cortical infarcts, 25 large subcortical infarcts, 1 small subcortical infarct, and 5 junctional infarcts.

Conclusions
—Most infarcts related to ICAD are cortical infarcts or large subcortical infarcts; small subcortical infarcts and junctional infarcts are infrequent. Therefore, these findings suggest that most infarcts occurring in carotid artery dissection (CAD) are probably embolic rather than hemodynamic in origin. According to this presumed mechanism, anticoagulation seems a logical treatment at the early stage of CAD.
Diffusion-Weighted Magnetic Resonance Imaging in a Case of Cerebral Venous Thrombosis
Authors: Corvol J. C. , Oppenheim C. , Manaï R. , Logak M. , Dormont D. , Samson Y. , Marsault C. , Rancurel G.
Published: June 2011

Background
—Diffusion-weighted imaging (DWI) is the most sensitive MR sequence in acute arterial ischemic stroke but has not yet been evaluated in venous cerebral ischemia. We describe a patient with DWI performed at the acute phase of a venous ischemic stroke.

Case Description
—A rapid cerebral MRI including DWI and fast fluid-attenuated inversion recovery (FLAIR) sequences was performed at the acute phase of a venous stroke confirmed by conventional angiography. DWI showed a slight decrease in apparent diffusion coefficient values 3 hours after onset (0.53±0.07×10
−3
mm
2
/s) and was normal 48 hours later (0.064±0.15×10
−3
mm
2
/s). Fast FLAIR sequences showed large left frontoparietal hyperintensities. The lack of a clear decrease in apparent diffusion coefficient values associated with marked FLAIR abnormalities may suggest prominent or early associated vasogenic edema. Physiopathological differences between arterial and venous ischemia may explain the different type of DWI FLAIR abnormalities during the acute phase as well as the better recovery of neurological deficit in venous stroke than in arterial ischemic stroke.

Conclusions
—In the context of an acute stroke, the contrast between marked FLAIR and subtle DWI abnormalities on MRI may reflect the venous mechanism of cerebral ischemia.
Assessment of Burden in Partners of Stroke Patients With the Sense of Competence Questionnaire
Authors: Reimer W. J. M. Scholte op , de Haan R. J. , Pijnenborg J. M. A. , Limburg M. , van den Bos G. A. M.
Published: June 2011

Background and Purpose
—The burden of caregiving can be harmful to both carers’ and patients’ functional health, but a specific instrument to assess the burden of caregiving as experienced by carers of stroke patients is not yet available. The Sense of Competence Questionnaire (SCQ), reliable and valid among caregivers of dementia patients, was evaluated on its metric properties in a population of partners of stroke patients.

Methods
—As part of a multicenter study on quality of care, SCQ burden scores of partners and functional health of patients were assessed 6 months after stroke (group A; n=166). In this study group, the reliability in terms of homogeneity, the construct validity, and the clinical validity of the SCQ were evaluated. The test-retest reliability was assessed in a separate group (group B; n=47). The feasibility was examined in both study groups.

Results
—The reliability of the total SCQ score was good (Chronbach’s α coefficient=0.83; intraclass correlation coefficient=0.93). Statistical support for construct validity was shown by principal-components analysis. Clinical validity was supported by the association between higher SCQ burden scores and patients’ impaired functional health: cognitive function (
P
=.03), disability (
P
=.10), handicap (
P
<.01), and quality of life (
P
=.02).

Conclusions
—The SCQ is a reliable and valid instrument for assessing burden of caregiving as experienced by partners of stroke patients. It is suitable for use in cross-sectional stroke studies and may help to identify partners at risk for high levels of burden and caregiving-related problems.
Leisure-Time Physical Activity and Ischemic Stroke Risk
Authors: Sacco Ralph L. , Gan Robert , Boden-Albala Bernadette , Lin I-Feng , Kargman Douglas E. , Hauser W. Allen , Shea Steven , Paik Myunghee C.
Published: June 2011

Background and Purpose
—Physical activity reduces the risk of premature death and cardiovascular disease, but the relationship to stroke is less well studied. The objective of this study was to investigate the association between leisure-time physical activity and ischemic stroke in an urban, elderly, multiethnic population.

Methods
—The Northern Manhattan Stroke Study is a population-based incidence and case-control study. Case subjects had first ischemic stroke, and control subjects were derived through random-digit dialing with 1:2 matching for age, sex, and race/ethnicity. Physical activity was recorded through a standardized in-person interview regarding the frequency and duration of 14 activities over the 2 prior weeks. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals after adjustment for medical and socioeconomic confounders.

Results
—Over 30 months, 369 case subjects and 678 control subjects were enrolled. Mean age was 69.9±12 years; 57% were women, 18% whites, 30% blacks, and 52% Hispanics. Leisure-time physical activity was significantly protective for stroke after adjustment for cardiac disease, peripheral vascular disease, hypertension, diabetes, smoking, alcohol use, obesity, medical reasons for limited activity, education, and season of enrollment (OR=0.37; 95% confidence interval=0.25 to 0.55). The protective effect of physical activity was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. A dose-response relationship was shown for both intensity (light-moderate activity OR=0.39; heavy OR=0.23) and duration (<2 h/wk OR=0.42; 2 to <5 h/wk OR=0.35; ≥5 h/wk OR=0.31) of physical activity.

Conclusions
—Leisure-time physical activity was related to a decreased occurrence of ischemic stroke in our elderly, multiethnic, urban subjects. More emphasis on physical activity in stroke prevention campaigns is needed among the elderly.
Natural History of Stenosis From Intracranial Atherosclerosis by Serial Angiography
Authors: Akins Paul T. , Pilgram Thomas K. , Cross DeWitte T. , Moran Christopher J.
Published: June 2011

Background and Purpose
—Knowledge of the natural history of stenoses due to intracranial atherosclerosis may be useful for evaluating possible treatments such as angioplasty.

Methods
—We retrospectively reviewed records over a 7-year period to identify patients with intracranial atherosclerotic stenoses and serial angiograms. Quantitative measurements of stenoses were made in a blinded manner, and clinical outcomes were reviewed.

Results
—We identified 21 patients with 45 intracranial stenoses who underwent repeat angiography at an average interval of 26.7 months. The average stenosis for all intracranial lesions was 43.9% initially and 51.8% on follow-up (
P
=.032). The average stenosis in the intracranial internal carotid artery (ICA) was stable (51.2% versus 52.6%). The average stenosis in the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) progressed from 32.4% to 49.7% (
P
=.037). Based on a minimum 10% change, 20% of intracranial ICA lesions progressed compared with 61% of ACA, MCA, and PCA lesions. Regression occurred in 14% of the intracranial ICA group and 28% of the ACA-MCA-PCA group. Cerebrovascular events were infrequent during this period, with 4 transient ischemic attacks and 1 intracerebral hemorrhage.

Conclusions
—Intracranial atherosclerotic stenoses are dynamic lesions demonstrating both progression and regression.
Medical and Neurological Complications of Ischemic Stroke
Authors: Johnston Karen C. , Li Jiang Y. , Lyden Patrick D. , Hanson Sandra K. , Feasby Thomas E. , Adams Robert J. , Faught R. Edward , Haley E. Clarke
Published: June 2011

Background and Purpose
—Medical and neurological complications after acute ischemic stroke may adversely impact outcome and in some cases may be preventable. Limited data exist regarding the frequency of such complications occurring in the first days after the ictus and the relationship of these complications to outcome. Our objective was to identify the types, severity, and frequency of medical and neurological complications following acute ischemic stroke and to determine their role in mortality and functional outcome.

Methods
—Rates of serious (life-threatening) and nonserious medical and neurological complications and mortality were derived from the placebo limb of the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) database (n=279). Complications were correlated with clinical outcome using logistic regression techniques.

Results
—Of all patients, 95% had at least one complication. The most common serious medical complication was pneumonia (5%), and the most common serious neurological complication was new cerebral infarction or extension of the admission infarction (5%). The 3-month mortality was 14%; 51% of these deaths were attributed primarily to medical complications. Outcome was significantly worse in patients with serious medical complications, after adjustment for baseline imbalances, as measured by the Barthel Index (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.5 to 15.1) and by the Glasgow Outcome Scale (OR, 11.6; 95% CI, 4.3 to 30.9). After death was discounted, serious medical complications were associated with severe disability at 3 months as determined by the Glasgow Outcome Scale (OR, 4.4; 95% CI, 1.3 to 14.8).

Conclusions
—Medical complications that follow ischemic stroke not only influence mortality but may influence functional outcome.
Activation of Cerebellar Climbing Fibers Increases Cerebellar Blood Flow
Authors: Yang Guang , Iadecola Costantino
Published: June 2011

Background
—The mechanisms regulating the cerebellar microcirculation during neural activity are poorly understood. One of the major neural inputs to the cerebellar cortex is the climbing fiber (CF), a pathway that uses excitatory amino acids, including glutamate, as a transmitter. We studied whether CF activation increases cerebellar blood flow (BFcrb) and, if so, we investigated the role of glutamate receptors, nitric oxide (NO) and cGMP, in the response.

Methods
—The CF were activated by harmaline administration (40 mg/kg, IP) in halothane-anesthetized rats with a cranial window placed over the cerebellar vermis. BFcrb was monitored by a laser-Doppler probe, and arterial pressure and blood gases were controlled.

Results
—With Ringer superfusion, harmaline produced sustained increases in BFcrb that peaked 20 minutes after administration (+115±13%; n=6;
P
<.05). The increases in BFcrb were substantially reduced by superfusion with tetrodotoxin (10 μmol/L; −91±5%; n=5;
P
<.05 from Ringer). The response was also attenuated by the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor inhibitor 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxaline (100 μmol/L; −70±6%;
P
<.05; n=5), but not by the
N
-methyl-
d
-aspartate receptor blocker 2-amino-5-phosphonopentanoic acid (500 μmol/L;
P
>.05; n=5). The response was attenuated by the nonselective NO synthase (NOS) inhibitor nitro-
l
-arginine (1 mmol/L; −73±5%; n=6) or by 7-NI (50 mg, IP; −71±5%; n=5), a relatively selective neuronal NOS inhibitor. The soluble guanylyl cyclase inhibitor 1H-
1,2,4
oxadiazolo[4,3-a]quinoxalin-1-one (100 μmol/L) attenuated the response to harmaline (−73±5;
P
<.05; n=6) but not to superfusion with adenosine (
P
>.05; n=5) or 8-bromo–cGMP (
P
>.05; n=5).

Conclusions
—Activation of the CF system increases BFcrb. The response depends on activation of glutamate receptors and is in large part mediated by NO via stimulation of soluble guanylyl cyclase. Glutamate receptors NO and cGMP are important factors in the mechanisms of functional hyperemia in cerebellar cortex.
Posterior Circulation Infarcts in Patients With Vertebrobasilar Dolichoectasia
Authors: Passero Stefano , Filosomi Giuseppe
Published: June 2011

Background and Purpose
—Vertebrobasilar dolichoectasia (VBD) may produce symptoms by direct compression of cranial nerves or the brain stem, by obstructive hydrocephalus, or by ischemia in the vertebrobasilar arterial territory. This study was undertaken to examine and characterize clinical and imaging findings in patients with stroke associated with VBD and compare these data with those for patients with VBD who did not have a stroke.

Methods
—We studied 40 consecutive stroke patients with associated VBD. All were evaluated by CT scan (n=9), MRI (n=6), or both (n=25). The diameter of the basilar artery (BA), height of bifurcation, and transverse position were evaluated. Clinical and imaging findings were compared with those found in a group of 40 VBD patients without stroke.

Results
—More than half of the patients (24 of 40) had infratentorial infarcts, located mainly in the midpons. Sixteen patients had supratentorial lesions localized in the thalamus (n=8) or in the superficial arterial territory of the posterior cerebral artery (PCA; n=8). The diameter and height of the bifurcation of the BA were correlated with the location of the lesion (PCA territory versus BA territory), in that severe ectasia and vertical elongation of the BA were significantly more often observed in patients with infarcts in PCA territory than in patients with infarcts in territories supplied by branches of the BA. Comparison of VBD patients with and without stroke showed that the incidence of arterial hypertension and the degree of ectasia and lateral displacement of the BA were not significantly different in the two groups. Patients with stroke more often had atherosclerotic changes of the posterior circulation (
P
=.0006) and a higher degree of vertical elongation of the BA (
P
=.025).

Conclusions
—In patients with VBD, superimposed atheromatous changes of the posterior circulation may have an important role in precipitating ischemia. However, other factors related to the severity of the dolichoectasia also favor ischemia and in some cases are the only factors responsible.
High-Resolution Emboli Detection and Differentiation by Characteristic Postembolic Spectral Patterns
Authors: Ries Fernand , Tiemann Klaus , Pohl Christoph , Bauer Christian , Mundo Martin , Becher Harald
Published: June 2011

Background and Purpose
—High-intensity transient signals (HITS) detected by transcranial Doppler ultrasonography correspond to microemboli in intracranial arteries. The purpose of this study was to develop new diagnostic criteria for the differentiation of these microembolic signals from artifact, based on a high-resolution analysis of Doppler power spectra in an in vitro model.

Methods
—Two hundred seventy-six formed emboli, consisting of different biological and nonbiological materials and as air bubbles, were injected into a flow phantom with artificial blood vessels and perfused in a steady or a pulsatile way. Embolic passage was assessed with a modified 2.5-MHz pulsed Duplex machine and a commercial 2-MHz Doppler system. Embolic HITS were analyzed using internationally accepted criteria for the audiovisual characteristics of HITS. Doppler spectra changes associated with HITS were evaluated by means of a specially developed high-resolution analysis of Doppler raw data.

Results
—Seventy-seven percent of all embolic events could be identified using conventional audiovisual criteria for embolic HITS. Analysis of Doppler spectra showed that all injected emboli generated high-amplitude signals with a minimum of at least 3 dB above background level. In addition, using high-resolution processing, specific changes in Doppler spectral patterns could be identified after all embolic HITS caused by solid particles. These postembolic spectral patterns were always characterized by a Doppler frequency shift decreasing in time and resembling the letter lambda (λ). Duration and appearance of the postembolic spectral patterns were mainly influenced by the size and velocity of the embolus. Similar phenomena could not be found in case of embolism by either small air bubbles or in case of provoked artifact registration. Using a commercial Doppler system specific, we documented postembolic spectral patterns in 47% of injected emboli.

Conclusions
—In this study, highly specific changes in Doppler spectral patterns associated with microembolic HITS could be characterized, resulting in further criteria for the differentiation between microembolic signals and artifact in Doppler emboli detection. The sensitivity of the detection of these signals can be increased by high-resolution analysis of raw Doppler data.
A New Noninvasive Technique for Imaging Atherosclerotic Plaque in the Aortic Arch of Stroke Patients by Transcutaneous Real-Time B-Mode Ultrasonography
Authors: Weinberger Jesse , Azhar Salman , Danisi Fabio , Hayes Richard , Goldman Martin
Published: June 2011

Background and Purpose
—Aortic arch atherosclerotic plaque is a probable source of atheroembolic stroke. Transesophageal echocardiography (TEE) has been used to image the aorta of patients with stroke to identify atherosclerotic plaque. TEE is moderately invasive and does not always visualize plaques present in the distal ascending aorta and proximal aortic arch.

Methods
—In the current study, transcutaneous B-mode ultrasonography was performed to image the aortic arch through a lateral supraclavicular window, and the results were compared with those of TEE in 20 patients. The aorta was subdivided into the proximal ascending (PAsc), distal ascending (DAsc), proximal aortic arch (PAA), and distal aortic arch (DAA) to be certain the plaques identified by each technique were the same. Plaques were characterized as simple (<4 mm thick) or complex (>4 mm thick).

Results
—In the PAsc, 8 simple plaques were identified with TEE but not with B-mode. In the DAsc, 1 complex plaque was identified with both techniques, and B-mode identified 1 additional complex and 1 simple plaque. In the PAA, 6 simple and 5 complex plaques were identified by both techniques, and TEE identified 1 additional complex plaque. In the DAA, TEE identified 2 simple and 2 complex plaques; B-mode identified 3 complex plaques.

Conclusions
—B-mode imaging compared favorably with TEE in identification of plaques in the aortic arch and distal ascending aorta, although it could not identify simple plaques in the proximal ascending. B-mode could visualize plaques not seen by TEE in the distal ascending aorta. B-mode ultrasonography is complementary to TEE in performance of a comprehensive assessment of plaque in the aortic arch and provides a noninvasive method for sequential studies of plaques that can be visualized.
Antioxidants Inhibit ATP-Sensitive Potassium Channels in Cerebral Arterioles
Authors: Wei Enoch P. , Kontos Hermes A. , Beckman Joseph S.
Published: June 2011

Background and Purpose
—Hydrogen peroxide and peroxynitrite are capable of generating hydroxyl radical and are commonly suspected as sources of this radical in tissues. It would be useful to distinguish the source of hydroxyl radical in pathophysiological conditions and to clarify the mechanisms by which antioxidants modify vascular actions of oxidants.

Methods
—We investigated the effect of three antioxidants—dimethylsulfoxide (DMSO), salicylate, and
l
-cysteine—on the cerebral arteriolar dilation caused by topical application of hydrogen peroxide and peroxynitrite in anesthetized cats equipped with cranial windows. We also tested the effect of these antioxidants on the vasodilation caused by pinacidil and cromakalim, two known openers of ATP-sensitive potassium channels.

Results
—DMSO was more effective in inhibiting dilation from hydrogen peroxide, whereas salicylate and
l
-cysteine were more effective in inhibiting dilation from peroxynitrite. All three antioxidants inhibited dilation in concentrations that were remarkably low (<1 mmol/L). All three antioxidants inhibited vasodilation from two known potassium channel openers, pinacidil and cromakalim. Their effect was specific because they did not affect dilation from adenosine or nitroprusside.

Conclusions
—The findings show that antioxidants block ATP-sensitive potassium channels in cerebral arterioles. This appears to be the mechanism by which antioxidants inhibit the dilation from hydrogen peroxide and peroxynitrite and not through scavenging of a common intermediate, ie, hydroxyl radical. The differences between effectiveness in inhibiting dilation from hydrogen peroxide and peroxynitrite by various antioxidants suggest that hydrogen peroxide and peroxynitrite act at two different sites, one in a water-soluble environment and the other in a lipid-soluble environment.
Potassium Channel Activators Protect the
N
-Methyl-
d
-Aspartate–Induced Cerebral Vascular Dilation After Combined Hypoxia and Ischemia in Piglets
Authors: Veltkamp Roland , Domoki Ferenc , Bari Ferenc , Busija David W.
Published: June 2011

Background and Purpose
—Cerebral arteriolar dilation to
N
-methyl-
d
-aspartate (NMDA) is a neuronally mediated multistep process that is sensitive to cerebral hypoxia and ischemia (H/I). We tested the hypothesis that topical pretreatment with the selective potassium channel agonists NS1619 and aprikalim preserves the vascular response to NMDA after consecutive H/I.

Methods
—Pial arteriolar diameters were measured in anesthetized piglets with the use of a closed cranial window and intravital microscopy. Arteriolar responses to NMDA (10
−5
, 5×10
−5
, and 10
−4
mol/L) were recorded before and 1 hour after 10 minutes of hypoxia (8.5% O
2
in N
2
) plus 10 minutes of ischemia (H/I). Ischemia was induced by increasing intracranial pressure. Subgroups were topically pretreated with 10
−5
mol/L NS1619, 10
−6
mol/L aprikalim, 10
−6
mol/L calcitonin gene–related peptide (CGRP), or 10
−5
mol/L papaverine. We also examined the effects of H/I on vascular responses to kainate (10
−4
mol/L) to assess specificity of neuronal injury.

Results
—Arteriolar responses to NMDA were significantly attenuated after H/I. Baseline compared with post-H/I arteriolar diameters were 9±4% versus 3±2% at 10
−5
mol/L, 22±4% versus 4±2% at 5×10
−5
mol/L, and 33±4% versus 7±2% at 10
−4
mol/L (mean±SE; all
P
<.05, n=7). Pretreatment with NS1619 and aprikalim preserved the arteriolar responses to NMDA after H/I. For NS1619 (n=6), values were as follows: 9±2% versus 6±4% at 10
−5
mol/L, 19±6% versus 21±5% at 5×10
−5
mol/L, and 35±3% versus 31±5% at 10
−4
mol/L. For aprikalim (n=7), values were as follows: 6±2% versus 8±2% at 10
−5
mol/L, 22±6% versus 15±3% at 5×10
−5
mol/L, and 41±5% versus 32±6% at 10
−4
mol/L. In contrast, piglets pretreated with CGRP (n=6) or papaverine (n=5) showed no preservation of the vascular response to NMDA after H/I, although these compounds dilated the arterioles to an extent similar to that with NS1619/aprikalim. Kainate-induced arteriolar dilation (n=6) was largely preserved after H/I compared with preischemic responses.

Conclusions
—(1) Vascular responses of cerebral arterioles to NMDA after H/I are preserved by pretreatment with NS1619 or aprikalim, indicating a neuroprotective effect. (2) CGRP and papaverine do not preserve the vascular response to NMDA despite causing vasodilation similar to that with NS1619 or aprikalim. This suggests that activation of potassium channels on neurons accounts for the protective effect of potassium channel agonists. (3) Preserved arteriolar dilation to kainate suggests largely intact functioning of neuronal nitric oxide synthase after H/I.
Postischemic Application of Lipid Peroxidation Inhibitor U-101033E Reduces Neuronal Damage After Global Cerebral Ischemia in Rats
Authors: Soehle Martin , Heimann Axel , Kempski Oliver
Published: June 2011

Background and Purpose
—The lipid peroxidation inhibitor U-101033E was examined for effects on cerebral blood flow (CBF), cortical tissue hemoglobin oxygen saturation (HbS
o
2
), and neuronal damage.

Methods
—Fifteen minutes of global cerebral ischemia was induced by two-vessel occlusion and hypobaric hypotension. Wistar rats (n=25) were randomized to receive vehicle (n=9) or 40 mg/kg U-101033E (n=9) intraperitoneally during 2 hours of reperfusion. A sham group (n=7) had neither ischemia nor therapy. Histology was evaluated 7 days after ischemia.

Results
—During late hyperperfusion (at 17 minutes), vehicle-treated animals had a higher (
P
=0.044) cortical tissue HbS
o
2
(72.0±1.4%) than did U-101033E–treated animals (65.8±2.5%). Neuronal counts in the superficial cortex layer found after 7 days correlated negatively with rCBF (
r
=−0.76;
P
<0.001) or cortical tissue HbS
o
2
(
r
=−0.56;
P
=0.028) assessed during the late hyperperfusion phase. U-101033E reduced neuronal damage in hippocampal CA1 from 64.3±9.2% to 31.2±8.4% (
P
=0.020), as well as in the superficial cortical layer from 53.5±14.6% to 12.8±11.7% (
P
=0.046). While animals in the vehicle group had reduced counts in all four examined cortex layers (
P
<0.05 versus sham group), there was significant cortical neuron loss in the U-101033E group in only one of four areas. U-101033E had no effect on resting CBF or CO
2
reactivity.

Conclusions
—Postischemic application of U-101033E protects hippocampal CA1 and cortical neurons after 15 minutes of global cerebral ischemia. The results indicate that free radical–induced lipid peroxidation contributes to reperfusion injury, a process that can be inhibited by antioxidants such as U-101033E.
Cerebral Hypoperfusion During Acute Kawasaki Disease
Authors: Ichiyama Takashi , Nishikawa Miki , Hayashi Takashi , Koga Mayumi , Tashiro Norimichi , Furukawa Susumu
Published: June 2011

Background and Purpose
—Kawasaki disease is a febrile disease of children notable for systemic vasculitis. There have been many previous reports of various complications, including disorders of the central nervous system. We evaluated cerebral perfusion during the acute stage in patients with Kawasaki disease.

Methods
—Single-photon emission-computed tomography (SPECT) with
99m
Tc-hexamethylpropyleneamine oxime was performed in 21 children with acute stage Kawasaki disease. Follow-up SPECT and MRI were performed about 1 month after the first SPECT in patients who exhibited abnormal SPECT findings during the acute stage.

Results
—In 6 of 21 children SPECT imaging demonstrated localized cerebral hypoperfusion without abnormal neurological findings or clinical symptoms, and the follow-up SPECT and MRI approximately 1 month after the first SPECT revealed no abnormalities.

Conclusions
—Some patients with Kawasaki disease have transient localized cerebral hypoperfusion at the acute stage.
Impaired Glucose Tolerance and the Likelihood of Nonfatal Stroke and Myocardial Infarction
Authors: Qureshi Adnan I. , Giles Wayne H. , Croft Janet B.
Published: June 2011

Background and Purpose
—Although diabetes mellitus (DM) is known to increase the risk of cardiovascular disease (CVD), the effect of impaired glucose tolerance (IGT) on the risk remains unclear. We determined whether IGT was associated with an increased likelihood for stroke and myocardial infarction in a nationally representative sample of US adults.

Methods
—We evaluated the association between IGT (defined as a fasting glucose level of <140 mg/dL and a plasma glucose level of between 140 and 200 mg/dL 2 hours after administration of 75 grams of an oral glucose load) and DM (defined as the current use of insulin or an oral hypoglycemic medication, a fasting plasma glucose level of >140 mg/dL, or a plasma glucose level of >200 mg/dL 2 hours after administration of an oral glucose load) with a self-reported physician diagnosis of stroke and myocardial infarction in 6547 adults aged 40 to 74 years participating in the Third National Health and Nutrition Examination Survey. Multivariate logistic regression analyses were used to investigate these relationships.

Results
—IGT and DM were observed in 1494 and 1532 adults, respectively. After adjustment for differences in age, gender, race/ethnicity, education, hypertension, cholesterol, body mass index, and cigarette smoking, IGT was not associated with stroke (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.5 to 1.6) or myocardial infarction (OR, 1.1; 95% CI, 0.7 to 1.6). DM was associated with both stroke (OR, 1.6; 95% CI, 1.0 to 2.6) and myocardial infarction (OR, 1.9; 95% CI, 1.3 to 2.8).

Conclusions
—In contrast to DM, IGT was not associated with an increased likelihood of prevalent nonfatal stroke or myocardial infarction.
Altered Function of Inward Rectifier Potassium Channels in Cerebrovascular Smooth Muscle After Ischemia/Reperfusion
Authors: Marrelli Sean P. , Johnson T. David , Khorovets Andrei , Childres William F. , Bryan Robert M.
Published: June 2011

Background and Purpose
—Several recent studies have demonstrated that inward rectifier potassium channels (K
ir
s) are located on vascular smooth muscle of cerebral arteries in the rat. Activation of the K
ir
s dilates the arteries by relaxing the vascular smooth muscle. We tested the following hypothesis in the present study: function of inward rectifier potassium channels is altered after ischemia/reperfusion (I/R).

Methods
—Temporary (2-hour) focal ischemia was induced in male Long-Evans rats (3% isoflurane anesthesia) by the intraluminal filament model. After 24 hours of reperfusion, ipsilateral and contralateral middle cerebral arteries (MCAs) were harvested and mounted on micropipettes, pressurized to 85 mm Hg, and luminally perfused.

Results
—Resting diameters for contralateral (control) and ipsilateral (I/R) MCAs were not significantly different (215±4 μm and 211±5 μm [n=6 and n=7], respectively). Activation of the K
ir
s by abluminal administration of 15 mmol/L KCl to the control MCAs dilated the MCA by 34±4% (n=8). Activation of the K
ir
s in I/R MCAs produced a dilation of only 11±3% (n=8;
P
<0.001 compared with control). BaCl
2
(75 μmol/L), a concentration-selective inhibitor of the K
ir
s, significantly attenuated the dilation produced by 15 mmol/L KCl in control MCAs but not in the I/R MCAs. Endothelial-mediated dilations elicited by the luminal administration of uridine triphosphate (10 μmol/L) produced similar dilations in both groups (32±5% for sham [n=4] and 33±2% for I/R [n=4]), indicating that dilator function in general was not altered in I/R vessels.

Conclusions
—We conclude that K
ir
function is altered after I/R. The K
ir
altered function is likely to exacerbate the brain injury occurring after I/R.
Early Intravenous Thrombolysis for Acute Ischemic Stroke in a Community-Based Approach
Authors: Grond Martin , Stenzel Christoph , Schmülling Susanne , Rudolf Jobst , Neveling Michael , Lechleuthner Alex , Schneweis Susanne , Heiss Wolf-Dieter
Published: June 2011

Background and Purpose
—Controlled multicenter studies have demonstrated the efficacy of systemic recombinant tissue-type plasminogen activator (rtPA) treatment in selected cases of acute ischemic stroke. The feasibility of this therapeutic option in clinical practice was assessed in a community-based approach.

Methods
—We offered rtPA treatment to stroke patients in a prospective open-label monocenter study applying inclusion criteria similar to those of the National Institute of Neurological Disorders, and Stroke study. In order to treat patients within 3 hours of symptom onset, a referral system was used by which eligible patients from all over the city of Cologne, Federal Republic of Germany, were rushed to the Department of Neurology of the University Hospital. We present data on the effectiveness of the referral system and the outcome results of the first 100 consecutive patients treated within an 18-month period.

Results
—Of 453 consecutive patients with a presumed diagnosis of acute stroke referred to our department between March 1996 and August 1997, 100 patients (22%) were treated with intravenous thrombolysis, 26% of them within 90 minutes of symptom onset. The average time from stroke onset to arrival at our department was 78 minutes, and from arrival to treatment 48 minutes. After 3 months, 53 patients recovered to fully independent function. The rates of total, symptomatic, and fatal intracerebral hemorrhage were 11%, 5%, and 1%, respectively. Overall mortality was 12%.

Conclusions
—Thrombolysis with rtPA was effectively applied in routine management of stroke patients in a community-based approach with acceptable efforts and without additional costs. Under these circumstances, outcome and complication rates were comparable to those of multicenter trials.
Identification of a Serum Gelatinase Associated With the Occurrence of Cerebral Aneurysms as Pro-Matrix Metalloproteinase-2
Authors: Todor D. Roxanne , Lewis Isabel , Bruno Gerry , Chyatte Douglas
Published: June 2011

Background and Purpose
—Subarachnoid hemorrhage from intracranial aneurysm rupture produces a severe form of stroke. Extracellular matrix remodeling is associated with cerebral aneurysms and may play a role in the formation or rupture of these lesions. We previously reported a 3-fold increase in a 72-kDa serum gelatinase in a subgroup of aneurysm patients. The purpose of the present study was to further characterize and identify this gelatinase.

Methods
—Serum samples were collected from surgical patients with intracranial aneurysms. The following series of experiments was designed to further characterize and identify the predominant serum gelatinase found in the subgroup of patients with increased gelatinase activity. Gelatin zymography was performed on native serum samples and compared with serum that had been pretreated with a known metalloproteinase activator (4-aminophenylmercuric acetate [APMA]). Gelatin zymography was repeated in the presence of a matrix metalloproteinase (MMP) inhibitor (EDTA) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride [PMSF]). Final identification was made by Western blotting with the use of monoclonal antibodies to MMP-2 and MMP-9.

Results
—A consistent gelatinolytic band (72 kDa) was identified in all serum samples (n=60). Pretreatment of the serum by APMA (n=60) lowered the molecular weight of the band to 66 kDa. The band was inhibited by EDTA (n=10) but not PMSF (n=10), thus characterizing the circulating 72-kDa gelatinase as an inactive pro-MMP. Western blotting (n=20) identified the 72-kDa band as MMP-2.

Conclusions
—These findings confirm that the increased gelatinolytic activity observed in vitro in a subset of cerebral aneurysm patients is due to pro-MMP-2.