bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient Focal Neurological Deficits During Pregnancy in Carriers of Inherited Thrombophilia
Authors: Kupferminc Michael J. , Yair Daniel , Bornstein Natan M. , Lessing Joseph B. , Eldor Amiram
Published: June 2011

Background and Purpose
—The aim of our study was to investigate the association of transient ischemic cerebrovascular events during pregnancy and inherited thrombophilias.

Methods
—The study group comprised previously healthy pregnant women who had their first ischemic event during pregnancy (n=12). The control group included 24 healthy women matched with the study women for age, ethnicity, and smoking status. All women were evaluated for factor V Leiden mutation, methylenetetrahydrofolate reductase C677T gene mutation, the G20210A mutation in the prothrombin gene, and deficiencies of plasma proteins C and S and antithrombin III.

Results
—Inherited thrombophilia was detected in 83% of women with transient neurological manifestations compared with 17% of the control group (
P
<0.001).

Conclusions
—Transient cerebrovascular ischemic events during pregnancy are associated with a high rate of inherited thrombophilias. Pregnant women with focal neurological symptoms should be evaluated for thrombophilia.
Increased Sympathetic Nervous Activity in Patients With Nontraumatic Subarachnoid Hemorrhage
Authors: Naredi S. , Lambert G. , Edén E. , Zäll S. , Runnerstam M. , Rydenhag B. , Friberg P.
Published: June 2011

Background and Purpose
—Activation of the sympathetic nervous system, which leads to elevation of circulating catecholamines, is implicated in the genesis of cerebral vasospasm and cardiac aberrations after subarachnoid hemorrhage. To this juncture, sympathetic nervous testing has relied on indirect methods only.

Methods
—We used an isotope dilution technique to estimate the magnitude and time course of sympathoadrenal activation in 18 subarachnoid patients.

Results
—Compared with 2 different control groups, the patients with subarachnoid hemorrhage exhibited an approximately 3-fold increase in total-body norepinephrine spillover into plasma within 48 hours after insult (3.2±0.3 and 4.2±0.7 versus 10.2±1.4 nmol/L;
P
<0.05 versus both). This sympathetic activation persisted throughout the 7- to 10-day examination period and was normalized at the 6-month follow-up visit.

Conclusions
—The present study has established that massive sympathetic nervous activation occurs in patients after subarachnoid hemorrhage. This overactivation may relate to the well-known cardiac complications described in subarachnoid hemorrhage.
Benefit of Echocontrast-Enhanced Transcranial Color-Coded Duplex Ultrasound in the Assessment of Intracranial Collateral Pathways
Authors: Droste Dirk W. , Jürgens Rasmus , Weber Sepp , Tietje Ralf , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Although clinically important, proper assessment of intracranial arterial collateral pathways by transcranial color-coded duplex sonography (TCCD) in patients with internal carotid artery (ICA) high-grade stenosis or occlusion is occasionally made difficult by an insufficient temporal bone window, an unfavorable insonation angle, or low flow velocity or volume. In these cases, echocontrast could be helpful to increase the diagnostic confidence or to make the diagnosis at all.

Methods
—We investigated 50 temporal windows of 44 patients with ipsilateral high-grade (≥70%) ICA stenosis or occlusion and insufficient native transtemporal insonation conditions before and after the application of the echo enhancer Levovist with an infusion pump.

Results
—Compared with the precontrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography (
P
<0.0001) and for longer lumen segments to be displayed on color mode (
P
<0.0001). Also, collateral flow via the anterior and posterior communicating artery could be demonstrated in 25 and 32 scans, respectively, compared with only 1 demonstration of each collateral pathway before the application of contrast medium (both
P
<0.0001). Similarly, with the help of contrast medium, flow velocity in the middle cerebral artery could be measured in 45 cases compared with only 26 cases before contrast was applied (
P
<0.0001).

Conclusions
—In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful in the assessment of intracranial collateral pathways recruited downstream to ICA stenoses and occlusions.
Acute Carotid Occlusion Alters the Activation Flow Coupling Response to Forepaw Stimulation in a Rat Model
Authors: Ances Beau M. , Greenberg Joel H. , Detre John A.
Published: June 2011

Background and Purpose
—To determine whether the hemodynamic response to functional stimulation is sensitive to proximal arterial occlusion, we measured the activation flow coupling response in a rat model of acute reversible vascular occlusion.

Methods
—In α-chloralose–anesthetized rats (n=18), laser Doppler measurements were made through a thinned skull over the somatosensory cortex in response to electrical forepaw stimulation. Signal-averaged responses to 4 and 8 seconds of electrical forepaw stimulation were obtained before, during, and shortly after acute unilateral or bilateral carotid occlusion produced with the use of a surgically placed snare.

Results
—Baseline cerebral blood flow was significantly decreased over the forepaw region of the somatosensory cortex after both occlusion of the carotid contralateral to the stimulated forepaw and bilateral occlusion compared with preocclusion (
P
<0.05). Postocclusion and ipsilateral occlusion led to a nonsignificant increase in baseline cerebral blood flow compared with preocclusion. Contralateral carotid occlusion and bilateral occlusion significantly prolonged the temporal characteristics of the flow response, especially the delay to peak (
P
<0.05), compared with preocclusion, whereas ipsilateral carotid occlusion significantly shortened the delay to peak (
P
<0.05). Only contralateral carotid occlusion produced a significant reduction in the peak amplitude of the flow response compared with preocclusion (
P
<0.05).

Conclusions
—These findings suggest that temporal characteristics of functional activation responses are sensitive to alterations in the proximal arterial supply and, conversely, that functional activation studies must be interpreted with consideration of proximal arterial disease.
σ
1
-Receptor Ligand 4-Phenyl-1-(4-Phenylbutyl)-Piperidine Affords Neuroprotection From Focal Ischemia With Prolonged Reperfusion
Authors: Harukuni Izumi , Bhardwaj Anish , Shaivitz Amanda B. , DeVries A. Courtney , London Edythe D. , Hurn Patricia D. , Traystman Richard J. , Kirsch Jeffrey R.
Published: June 2011

Background and Purpose
—We previously showed that the intravenous administration of the potent ς
1
-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine (PPBP) provides neuroprotection against transient focal cerebral ischemia and that the protection depends on treatment duration. We tested the hypothesis that PPBP would provide neuroprotection in a model of transient focal ischemia and 7 days of reperfusion in the rat as assessed with neurobehavioral outcome and infarction volume.

Methods
—Under the controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) with the intraluminal suture occlusion technique. We used laser Doppler flowmetry to assess MCAO. At 60 minutes after the onset of ischemia, rats were randomly assigned to 1 of 4 treatment groups in a blinded fashion and received a continuous intravenous infusion of control saline or 0.1, 1, or 10 μmol · kg
−1
· h
−1
PPBP for 24 hours. Neurobehavioral evaluation was performed at baseline (3 to 4 days before MCAO) and at 3 and 7 days of reperfusion. Infarction volume was assessed with triphenyltetrazolium chloride staining on day 7 of reperfusion in all rats.

Results
—Triphenyltetrazolium chloride–determined infarction volume of ipsilateral cortex was smaller in rats treated with 10 μmol · kg
−1
· h
−1
PPBP (n=15, 68±12 mm
3
, 18±3% of contralateral structure,
P
<0.05) (mean±SEM) compared with corresponding rats treated with saline (n=15, 114±11 mm
3
, 31±3% of contralateral structure). PPBP did not provide significant neuroprotection in the caudoputamen complex. Although MCAO was associated with several alterations in behavior, the treatment with PPBP had no effect on behavioral outcomes.

Conclusions
—The data demonstrate that the potent ς
1
-receptor ligand PPBP decreases cortical infarction volume without altering neurobehavior after transient focal ischemia and prolonged reperfusion in the rat.
Combined Diffusion-Weighted and Perfusion-Weighted Flow Heterogeneity Magnetic Resonance Imaging in Acute Stroke
Authors: Østergaard Leif , Sorensen A. Gregory , Chesler David A. , Weisskoff Robert M. , Koroshetz Walter J. , Wu Ona , Gyldensted Carsten , Rosen Bruce R.
Published: June 2011

Background and Purpose
—The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size.

Methods
—Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning.

Results
—In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients.

Conclusions
—Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.
Reproducibility Validation Study Comparing Analog and Digital Imaging Technologies for the Measurement of Intima-Media Thickness
Authors: Baldassarre Damiano , Tremoli Elena , Amato Mauro , Veglia Fabrizio , Bondioli Alighiero , Sirtori Cesare R.
Published: June 2011

Background and Purpose
—New advances in B-mode imaging technologies have led to improved quality in the detection of minute changes in the surface of intima-media thickness (IMT) and plaques. The new digital systems, with increased numbers of imaging channels, multiple frequency probes, and increased microprocessing speeds, now generate images comparable to those of the analog predecessors. Can these digital systems have reproducibility comparable to that of a pure analog system? We compared the Biosound 2000II (analog) system with the Esaote AU4 (digital) system.

Methods
—Twenty-two subjects were chosen who had varying degrees of IMT on the far wall of the common carotid artery. Common carotid IMT was determined twice: the first time with the analog system and the second time with the digital system. With each system, replicate scans were made within 2 weeks.

Results
—The intramethod agreement was high with the analog system, with a bias between readings of −0.010±0.033 mm, mean absolute difference of 0.027±0.020 mm, repeatability coefficient of 0.067, and correlation coefficient of 0.97. The digital system provided the highest reproducibility with a bias between readings of 0.002±0.016 mm, mean absolute difference of 0.012±0.011 mm, repeatability coefficient of 0.033, and correlation coefficient of 0.99. When the analog and digital systems were compared, the bias between readings was −0.011±0.024 mm with good agreement between the 2 systems; the repeatability coefficient was 0.047, with all points within ±2 SDs of the mean difference. The mean absolute difference between the 2 measurements was 0.018±0.015 mm with a correlation coefficient of 0.98.

Conclusions
—The digital system for IMT evaluation compares well with the more widely used analog system and provides a reliable technology for common carotid IMT measurement that can be applied to clinical trials.
Effect of Short-Term Hyperventilation on Cerebral Blood Flow Autoregulation in Patients With Acute Bacterial Meningitis
Authors: Møller Kirsten , Skinhøj Peter , Knudsen Gitte Moos , Larsen Fin Stolze
Published: June 2011

Background and Purpose
—Cerebral blood flow (CBF) autoregulation is impaired in patients with acute bacterial meningitis: this may be caused by cerebral arteriolar dilatation. We tested the hypothesis that CBF autoregulation is recovered by acute mechanical hyperventilation in 9 adult patients with acute bacterial meningitis.

Methods
—Norepinephrine was infused to increase mean arterial pressure (MAP) 30 mm Hg from baseline. Relative changes in CBF were concomitantly recorded by transcranial Doppler ultrasonography of the middle cerebral artery, measuring mean flow velocity (V
mean
), and by measurement of arterial to jugular oxygen content difference (a-v D
o
2
). The slope of the regression line between MAP and V
mean
was calculated. Measurements were performed during normoventilation and repeated after 30 minutes of mechanical hyperventilation.

Results
—At normoventilation (median Pa
co
2
4.4 kPa, range 3.5 to 4.9), MAP was increased from 68 mm Hg (60 to 101) to 109 mm Hg (95 to 126). V
mean
increased with MAP from 48 cm/s (30 to 61) to 65 cm/s(33 to 86) (
P
<0.01), and a-v D
o
2
decreased from 2.2 mmol/L (1.0 to 2.7) to 1.4 mmol/L (0.8 to 1.8) (
P
<0.05). During hyperventilation (Pa
co
2
3.5 kPa, range 3.3 to 4.1), MAP was increased from 76 mm Hg (58 to 92) to 109 mm Hg (95 to 121). V
mean
increased from 45 cm/s (29 to 55) to 53 cm/s (33 to 78) (
P
<0.01), and a-v D
o
2
decreased from 2.5 mmol/L (1.8 to 3.0) to 1.8 mmol/L (1.2 to 2.4) (
P
<0.05). Four patients recovered autoregulation completely during hyperventilation. The slope of the autoregulation curve decreased during hyperventilation compared with normoventilation (
P
<0.05).

Conclusions
—CBF autoregulation is partially recovered during short-term mechanical hyperventilation in patients with acute bacterial meningitis, indicating that cerebral arteriolar dilation in part accounts for the regulatory impairment of CBF in these patients.
Trials of Thrombolysis in Acute Ischemic Stroke
Authors: Wardlaw J. M. , Sandercock P. A. G. , Warlow C. P. , Lindley R. I.
Published: June 2011

Background and Purpose
—Controversy regarding the risks and benefits of thrombolysis has not been helped by the perception that some trials were “positive” and others “negative” on their primary outcome measure of either “good” or “poor” functional outcome. We wondered whether the definition of good or poor functional outcome might have contributed to this perception, and what effect altering the definition might have on the individual trials and on the systematic review of all the trials combined.

Methods
—We analyzed data on functional outcome, extracted from the randomized trials of thrombolysis in acute ischemic stroke, according to good (modified Rankin scale scores of 0 to 1 versus 2 to 6) and poor (modified Rankin 0 to 2 versus 3 to 6) functional outcome, to determine the effects of thrombolysis.

Results
—Twelve trials (4342 patients, treated up to 6 hours after stroke) contributed to this analysis. Overall, there was no difference in the estimate of treatment effect between the 2 definitions (modified Rankin 0 to 2 versus 3 to 6, and 0 to 1 versus 2 to 6 [ORs 0.83 and 0.79, respectively]). However, the apparent “success” of several individual trials did alter.

Conclusions
—We should not place undue emphasis on the results of individual trials, when a change of a single point on the Rankin scale can make the difference between “success” and “failure.” Overall, by either analysis, there was a significant benefit in patients treated with thrombolysis up to 6 hours after stroke.
Regional Myocardial Perfusion After Experimental Subarachnoid Hemorrhage
Authors: Zaroff Jonathan G. , Rordorf Guy A. , Titus James S. , Newell John B. , Nowak Nicholas J. , Torchiana David F. , Aretz H. Thomas , Picard Michael H.
Published: June 2011

Background and Purpose
—The pathophysiology of cardiac injury after subarachnoid hemorrhage (SAH) remains controversial. Data from animal models suggest that catecholamine-mediated injury is the most likely cause of cardiac injury after SAH. However, researchers also have proposed myocardial ischemia to be the underlying cause, as a result of coronary artery disease, coronary artery spasm, or hypertension and tachycardia. To test the hypothesis that SAH-induced cardiac injury occurs in the absence of myocardial hypoperfusion, we developed an experimental canine model that reproduces the clinical and pathological cardiac lesions of SAH and defines the epicardial and microvascular coronary circulation.

Methods
—Serial ECG, hemodynamic measurements, coronary angiography, regional myocardial blood flow measurements by radiolabeled microspheres, 2D echocardiography, and myocardial contrast echocardiography were performed in 9 dogs with experimental SAH and 5 controls.

Results
—Regional wall motion abnormalities were identified in 8 of 9 SAH dogs and 1 of 5 controls (Fisher’s Exact Test,
P
=0.02) but no evidence was seen of coronary artery disease or spasm by coronary angiography and of significant myocardial hypoperfusion by either regional myocardial blood flow or myocardial contrast echocardiography.

Conclusions
—In this experimental model of SAH, a unique form of regional left ventricular dysfunction occurs in the absence of myocardial hypoperfusion. Future studies are justified to determine the cause of cardiac injury after SAH.
Early Exclusive Use of the Affected Forelimb After Moderate Transient Focal Ischemia in Rats
Authors: Bland Sondra T. , Schallert Timothy , Strong Roger , Aronowski Jaroslaw , Grotta James C.
Published: June 2011

Background and Purpose
—Previous work by researchers in our laboratory has shown that in the rat, the exclusive use of the affected forelimb during an early critical period exaggerates lesion volume and retards functional recovery after electrolytic lesions of the forelimb sensorimotor cortex. In the present study, we examined the effects of exclusive use of the affected forelimb after middle cerebral artery occlusion (MCAO).

Methods
—Ischemia of moderate severity was produced in male Long-Evans rats through 45 minutes of occlusion of the left middle cerebral and both common carotid arteries. Exclusive use of either the affected or unaffected forelimb was forced through immobilization of either the ipsilateral (MCAO+ipsi) or contralateral (MCAO+contra) forelimb, respectively, for 10 days in a plaster cast, or the animal was left uncasted (MCAO+nocast). Sham surgeries were performed, and animals were also casted for 10 days or left uncasted. Sensorimotor testing was performed during days 17 to 38. At the end of sensorimotor testing, cognitive performance was tested with use of the Morris water maze. In a separate experiment, temperatures and corticosterone levels were measured during the 10-day period after 45-minute ischemia and casting.

Results
—The MCAO+ipsi group performed worse on sensorimotor tasks than the MCAO+contra, MCAO+nocast, and sham groups. Infarct volume was significantly larger in the MCAO+ipsi group than in the sham and MCAO+contra groups but not in the MCAO+nocast group. No group differences were found with the Morris water maze, and no group differences were found in either temperature or plasma corticosterone level.

Conclusions
—The exclusive use of the affected forelimb immediately after focal ischemia has detrimental effects on sensorimotor function that cannot be attributed to hyperthermia or stress.
Warfarin for Stroke Prevention Still Underused in Atrial Fibrillation
Authors: Cohen Natan , Almoznino-Sarafian Dorit , Alon Irena , Gorelik Oleg , Koopfer Margarita , Chachashvily Shulamit , Shteinshnaider Miriam , Litvinjuk Vladimir , Modai David
Published: June 2011

Background and Purpose
—The value of warfarin in preventing stroke in patients with chronic atrial fibrillation is well established. However, the prevalence of such treatment generally lags behind actual requirements. The aim of this study was to evaluate doctor- and/or patient-related demographic, clinical, and echocardiographic factors that influence decision for warfarin treatment.

Methods
—Between 1990 and 1998, 1027 patients were discharged with chronic or persistent atrial fibrillation. This population was composed of (1) patients with cardiac prosthetic valves (n=48), (2) those with increased bleeding risks (n=152), (3) physically or mentally handicapped patients (n=317), and (4) the remaining 510 patients, the main study group who were subjected to thorough statistical analysis for determining factors influencing warfarin use.

Results
—The respective rates of warfarin use on discharge in the 4 groups were 93.7%, 30.9%, 17.03%, and 59.4% (
P
=0.001); of the latter, an additional 28.7% were discharged on aspirin. In the main study group, warfarin treatment rates increased with each consecutive triennial period (29.7%, 53.6%, and 77.1%, respectively;
P
=0.001). Age >80 years, poor command of Hebrew, and being hospitalized in a given medical department emerged as independent variables negatively influencing warfarin use:
P
=0.0001, OR 0.30 (95% CI 0.17 to 0.55);
P
=0.02, OR 0.59 (95% CI 0.36 to 0.94); and
P
=0.0002, OR 0.26 (95% CI 0.12 to 0.52), respectively. In contrast, past history of stroke and availability of echocardiographic information, regardless of the findings, each increased warfarin use (
P
=0.03, OR 1.95 [95% CI 1.04 to 3.68], and
P
=0.0001, OR 3.52 [95% CI 2.16 to 5.72], respectively).

Conclusions
—Old age, language difficulties, insufficient doctor alertness to warfarin benefit, and patient disability produced reluctance to treat. Warfarin use still lags behind requirements.
Factor V Leiden and Antiphospholipid Antibodies Are Significant Risk Factors for Ischemic Stroke in Children
Authors: Kenet G. , Sadetzki S. , Murad H. , Martinowitz U. , Rosenberg N. , Gitel S. , Rechavi G. , Inbal A.
Published: June 2011

Background and Purpose
—The association between ischemic childhood stroke and thrombophilia has been debated. We studied the prevalence of thrombophilia risk factors in 65 unrelated children with ischemic stroke compared with 145 control subjects.

Methods
—Patients and control subjects were tested for antithrombin protein C and protein S deficiencies, the presence of antiphospholipid antibodies (APLA), factor V Leiden (FVL), G20210A polymorphism of factor II gene (FII G20210A), and C677T polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR).

Results
—Of 65 children, 7 had a stroke in the neonatal/perinatal period and therefore were analyzed separately. Thirty-one of the remaining 58 patients with pediatric stroke (53.4%) were found to have at least 1 thrombophilia marker compared with only 25.5% of control subjects. None of the patients or control subjects had protein S or antithrombin III deficiency. The prevalence of protein C deficiency was higher among pediatric stroke patients than among control subjects, but the difference was not statistically significant (OR=7, 95% CI 0.75 to 65.1). Heterozygous FII G20210A and homozygous MTHFR 677T were not associated with an increased risk for stroke (OR=1.29, 95% CI 0.2 to 8.2; and OR=1.06, 95% CI 0.4 to 2.7, respectively). In contrast, the presence of APLA was associated with a >6-fold risk of stroke (OR=6.08, 95% CI 1.5 to 24.3), and the heterozygosity for FVL increased the risk of stroke by almost 5-fold (OR=4.82, 95% CI 1.4 to 16.5). Five patients with pediatric stroke had a combination of ≥2 thrombophilia markers, whereas none of the control subjects had a combination of the markers. Most of the patients with neonatal/perinatal stroke were found to have at least 1 thrombophilia marker.

Conclusions
—These data suggest that the prevalence of thrombophilia markers is increased in children with stroke compared with control subjects and, specifically, that FVL and APLA contribute significantly to stroke occurrence.
Integrin α
IIb
β
3
Inhibitor Preserves Microvascular Patency in Experimental Acute Focal Cerebral Ischemia
Authors: Abumiya Takeo , Fitridge Robert , Mazur Curt , Copeland Brian R. , Koziol James A. , Tschopp Juerg F. , Pierschbacher Michael D. , del Zoppo Gregory J.
Published: June 2011

Background and Purpose
—Platelets become activated and accumulate in brain microvessels of the ischemic microvascular bed after experimental focal cerebral ischemia. The binding of glycoprotein IIb/IIIa (integrin α
IIb
β
3
) on platelets to fibrinogen is the terminal step in platelet adhesion and aggregation. This study tests the hypothesis that inhibition of platelet-fibrin(ogen) interactions may prevent microvascular occlusion after experimental middle cerebral artery occlusion (MCA:O).

Methods
—TP9201 is a novel Arg-Gly-Asp (RGD)-containing integrin α
IIb
β
3
inhibitor. Microvascular patency after 3-hour MCA:O and 1-hour reperfusion within the ischemic and nonischemic basal ganglia was compared in adolescent male baboons who received high-dose TP9201 (group A: IC
80
in heparin, n=4), low-dose TP9201 (group B: IC
30
in heparin, n=4), or no treatment (group C: n=4) before MCA:O.

Results
—After MCA:O, microvascular patency decreased significantly in group C. However, in the ischemic zones of groups A and B compared with group C, patencies were significantly greater in the 4.0- to 7.5-μm-diameter (capillary) and 7.5- to 30.0-μm-diameter vessels (2
P
<0.05). A dose-dependent increase in hemorrhagic transformation was seen in group A (3 of 4 animals) compared with group B (1 of 4 animals), and no hemorrhage was visible in group C (χ
2
analysis for trend,
P
<0.05).

Conclusions
—Platelet activation contributes significantly to ischemic microvascular occlusion. Occlusion formation may be prevented by this RGD–integrin α
IIb
β
3
inhibitor at a dose that does not produce clinically significant parenchymal hemorrhage. The effect of microvascular patency on neuron recovery can now be tested.
Treatment of Cognitive Impairment After Poststroke Depression
Authors: Kimura Mahito , Robinson Robert G. , Kosier James T.
Published: June 2011

Background and Purpose
—Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion. Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy. We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial.

Methods
—Patients with major (n=33) or minor (n=14) depression participated in a double-blind treatment study with nortriptyline or placebo. They were examined for change in depressive mood, measured by the Hamilton Rating Scale for Depression (HAM-D), and change in cognitive impairment, assessed by the Mini-Mental State Examination (MMSE), after treatment with nortriptyline or placebo. Cognitive treatment response, as measured by the MMSE, was compared between patients whose depression did and did not respond to treatment.

Results
—Patients whose poststroke depression remitted (predominantly associated with nortriptyline treatment) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit (predominantly associated with placebo treatment).

Conclusions
—Our findings support the contention that poststroke major depression leads to a “dementia of depression.” Prior studies failed to show an effect of treatment because the effect size was too small. Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke.
Vascular Dementia
Authors: Hébert Réjean , Lindsay Joan , Verreault René , Rockwood Kenneth , Hill Gerry , Dubois Marie-France
Published: June 2011

Background and Purpose
—Very few population-based studies have systematically examined incident vascular dementia (VaD). From the Canadian Study of Health and Aging cohort, incidence rates of VaD were determined and risk factors analyzed.

Methods
—This was a cohort incidence study that followed 8623 subjects presumed to be free of dementia over a 5-year period. The risk factors were examined with a nested prospective case-control study. Exposure was determined by means of a risk factor questionnaire administered to the subject or a proxy at the beginning of the study.

Results
—On the basis of 38 476 person-years at risk, the annual incidence rate was estimated to be 2.52 per thousand undemented Canadians (95% CI 2.02 to 3.02). Including an estimation of the probability of VaD among the decedents, this figure rose to 3.79. For the risk factors study, 105 incident cases of VaD according to the NINCDS-AIREN criteria were compared with 802 control subjects. Significant risk factors were: age (OR=1.05), residing in a rural area (2.03), living in an institution (2.33), diabetes (2.15), depression (2.41), apolipoprotein E ε4 (2.34), hypertension for women (2.05), heart problems for men (2.52), taking aspirin (2.33), and occupational exposure to pesticides or fertilizers (2.05). Protective factors were eating shellfish (0.46) and regular exercise for women (0.46). There was no relation with sex, education, or alcohol.

Conclusions
—The study confirmed some previously reported risk factors but also suggested new ones. It raised concerns about the prescription of aspirin and perhaps other factors related to rural life.
Chlamydia pneumoniae
and the Risk of First Ischemic Stroke
Authors: Elkind Mitchell S. V. , Lin I-Feng , Grayston J. T. , Sacco Ralph L.
Published: June 2011

Background and Purpose
—Serological evidence of infection with
Chlamydia pneumoniae
has been associated with cardiovascular disease in multiple epidemiological studies. The data on its association with ischemic stroke are limited. We sought to determine whether chronic
C pneumoniae
infection is associated with ischemic stroke in a multi-ethnic population.

Methods
—The Northern Manhattan Stroke Study contains a population-based, case-control study component. Cases had first ischemic stroke and matched control subjects were derived through random digit dialing. Titers of IgG, IgA, and IgM antibodies specific for
C pneumoniae
were measured with the use of microimmunofluorescence, and titers ≥1:16 were considered positive. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjustment for medical, behavioral, and socioeconomic factors.

Results
—Eighty-nine cases and 89 control subjects were selected. Mean age among cases was 68.5±12.8 years; 53% were women and 15% of the subjects were white, 28% were black, and 54% were Hispanic. Elevated
C pneumoniae
IgA titers were significantly associated with risk of ischemic stroke after adjusting for other stroke risk factors (adjusted OR 4.51, 95% CI 1.44 to 14.06). IgG titers were less strongly associated with stroke risk (adjusted OR 2.59, 95% CI 0.87 to 7.75). The association of IgA with stroke risk was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. There was also a significant continuous increase in risk associated with the log-transformation of the titer for IgA (adjusted OR 1.32, 95% CI 1.05 to 1.66) but not IgG.

Conclusions
—Serological evidence of chronic infection with
C pneumoniae
is associated with risk of ischemic stroke in an urban, multi-ethnic population. IgA titers may be a better marker of this risk than are IgG titers. This association is independent of other vascular disease risk factors. Further prospective epidemiological studies of the effect of this infection on stroke risk are warranted.
Dietary Potassium Intake and Stroke Mortality
Authors: Fang Jing , Madhavan Shantha , Alderman Michael H.
Published: June 2011

Background and Purpose
—An inverse relationship of dietary potassium to stroke mortality in a small community has been previously reported. To further assess this association in a larger sample, we examined data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiological Follow-up Study.

Methods
—We analyzed baseline data during 1971–1975 and follow-up through 1992. Dietary potassium intake, determined by 24-hour dietary recall at baseline, was available for 9866 subjects. Stroke mortality was recorded through 1992 follow-up.

Results
—Mean age and dietary potassium at baseline were 55 years and 2084 mg/d; blacks reported significantly lower potassium intake than whites (1606 versus 2178 mg/24 h). During an average of 16.7 years of follow-up, there were 304 stroke deaths. For men, stratified by tertile of dietary potassium intake, age-adjusted stroke mortality rates per 1000 person-years for the lowest dietary potassium group were significantly higher than for the highest intake group, for both whites (1.94 versus 1.17; relative risk, 1.66; 95% CI, 1.32 to 2.14) and blacks (5.08 versus 1.19; relative risk, 4.27; 95% CI , 1.88 to 9.19). For women, there was no significant difference in stroke mortality between similar levels of potassium intake for either whites (1.61 versus 1.42; relative risk, 1.13; 95% CI, 0.84 to 1.66) or blacks (2.46 versus 3.04; relative risk, 0.80; 95% CI, 0.21 to 2.01). After stratification by hypertensive status, stroke mortality rates were significantly different by tertile of dietary potassium only for hypertensive men. There was no stroke mortality difference by potassium intake among hypertensive women or nonhypertensive men and women. Multivariate analysis, in which we controlled for caloric intake and other baseline cardiovascular risk factors, revealed that only among black men and hypertensive men was lower dietary potassium intake a predictor of stroke mortality.

Conclusions
—The previous finding of an association of increasing dietary potassium intake with decreasing stroke mortality has been detected only among black men and hypertensive men in this study.
Differing Temporal Patterns of Onset in Subgroups of Patients With Intracerebral Hemorrhage
Authors: Passero Stefano , Reale Fabio , Ciacci Giuseppe , Zei Ettore
Published: June 2011

Background and Purpose
—The purpose of this study was to further analyze the temporal patterns of onset of intracerebral hemorrhage (ICH) and to determine whether or not subgroups with specific clinical characteristics exhibit different patterns of onset.

Methods
—The daily, weekly, and yearly variations in occurrence of ICH together with the relationship between ICH occurrence and changes in air temperature were evaluated in 1018 patients. Patients were grouped according to the presumed etiology of ICH: hypertensive ICH, secondary ICH, and ICH of undetermined origin. The contribution of demographic and clinical factors to the temporal distributions of ICH was also evaluated.

Results
—Marked differences in seasonal and diurnal patterns of ICH onset were observed in the different groups. The incidence of hypertensive ICH reflected seasonal and circadian changes in blood pressure, whereas the latter did not seem related to the onset of nonhypertensive ICH. The seasonal pattern was more evident in elderly patients with hypertensive ICH than in younger subjects. No significant weekly variations were observed; however, risk was greater on Monday in the working population.

Conclusions
—Our results suggest that the higher incidence of ICH in the colder months is due to the effect of low temperatures on blood pressure and that the clustering of ICH events in the morning is due to the increase in sympathetic tone, and consequent increase in blood pressure, on awakening.
Streptokinase in Acute Ischemic Stroke: An Individual Patient Data Meta-Analysis
Authors: Cornu C. , Boutitie F. , Candelise L. , Boissel J. P. , Donnan G. A. , Hommel M. , Jaillard A. , Lees K. R.
Published: June 2011

Background and Purpose
—Three major randomized controlled trials of streptokinase in acute ischemic stroke were curtailed because of safety concerns. The prospective Thrombolysis in Acute Stroke Pooling Project (TAS-PP) was established to examine the aggregate data to identify factors influencing the effect of streptokinase.

Methods
—Individual patient data from the Australian Streptokinase Trial (ASK), Multicentre Acute Stroke Trial-Europe (MAST-E), Multicentre Acute Stroke Trial-Italy (MAST-I), and Glasgow Trial (Glasgow) were pooled. Multivariate modeling determined the interaction between treatment effect and delay from symptom onset to treatment, predicted baseline risk, age, concomitant aspirin or heparin use, and the presence of early CT signs on the outcomes of 10-day death, death and disability, or death alone at 3 or 6 months.

Results
—Patients’ records were pooled (total 1292 patients; streptokinase, n=653, no streptokinase n=639). The subgroup analysis of treatment effect according to delay from symptoms to inclusion shows only a trend toward a better treatment effect with shorter delay, which is not statistically significant for any outcome. Heavier patients in MAST-E may have had a lower (non significant) risk from the fixed dose of 1.5 million units of streptokinase. Concomitant aspirin increased the excess mortality rates in streptokinase-treated patients (17% without aspirin versus 91% with aspirin,
P
=0.005). The presence of early CT scan signs did not increase the detrimental effect of streptokinase.

Conclusions
—Few factors influenced the response to streptokinase. However, earlier administration, lower doses of streptokinase, and avoidance of concomitant aspirin should be considered if further streptokinase trials in acute stroke are planned.
Delayed Treatment With Nicotinamide (Vitamin B
3
) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats
Authors: Mokudai Toshihiko , Ayoub Issam A. , Sakakibara Yohtaro , Lee E-Jian , Ogilvy Christopher S. , Maynard Kenneth I.
Published: June 2011

Background and Purpose
—We have previously shown that nicotinamide (NAm) acutely reduces brain infarction induced by permanent middle cerebral artery occlusion (MCAo) in rats. In this study, we investigate whether NAm may protect against ischemia/reperfusion injury by improving sensory and motor behavior as well as brain infarction volumes in a model of transient focal cerebral ischemia.

Methods
—Forty-eight male Wistar rats were used, and transient focal cerebral ischemia was induced by MCAo for 2 hours, followed by reperfusion for either 3 or 7 days. Animals were treated with either intraperitoneal saline or NAm (500 mg/kg) 2 hours after the onset of MCAo (ie, on reperfusion). Sensory and motor behavior scores and body weight were obtained daily, and brain infarction volumes were measured on euthanasia.

Results
—Relative to treatment with saline, treatment with NAm (500 mg/kg IP) 2 hours after the onset of transient focal cerebral ischemia in Wistar rats significantly improved sensory (38%,
P
<0.005) and motor (42%,
P
<0.05) neurological behavior and weight gain (7%,
P
<0.05) up to 7 days after MCAo. The cerebral infarct volumes were also reduced 46% (
P
<0.05) at 3 days and 35% (
P
=0.09) at 7 days after MCAo.

Conclusions
—NAm is a robust neuroprotective agent against ischemia/reperfusion-induced brain injury in rats, even when administered up to 2 hours after the onset of stroke. Delayed NAm treatment improved both anatomic and functional indices of brain damage. Further studies are needed to clarify whether multiple doses of NAm will improve the extent and duration of this neuroprotective effect and to determine the mechanism(s) of action underlying the neuroprotection observed. Because NAm is already used clinically in large doses and has few side effects, these results are encouraging for the further examination of the possible use of NAm as a therapeutic neuroprotective agent in the clinical treatment of acute ischemic stroke.
Silent Cerebral Ischemia Detected by Diffusion-Weighted MRI After Carotid Endarterectomy
Authors: Barth Alain , Remonda Luca , Lövblad Karl-Olof , Schroth Gerhard , Seiler Rolf W.
Published: June 2011

Background and Purpose
—Small emboli arising from a friable plaque during carotid endarterectomy (CEA) constitute an important risk of perioperative ischemic complications. To evaluate the incidence and significance of silent cerebral ischemic lesions of embolic origin after CEA, we prospectively examined a series of surgical patients with high-grade carotid stenosis by using diffusion-weighted MRI (DWI). We also tried to correlate postoperative ischemic lesions with the occurrence of sonographic cerebral embolic signals, the presence of plaque ulcerations, and the use of intraoperative shunting.

Methods
—Of a consecutive series of 53 patients undergoing elective CEA for high-grade carotid stenosis, 48 patients with unchanged postoperative neurological status were prospectively studied with DWI of the brain the day before and the day after the operation. The magnetic resonance images were analyzed by 2 neuroradiologists blinded to the clinical result of the operation. Any new hyperintense signal was interpreted as a postoperative ischemic lesion.

Results
—Forty-six (95.8%) of 48 patients had unchanged postoperative brain DWI. In 2 patients (4.2%), a new single asymptomatic hyperintense signal was observed on the side of the operation. Both lesions were small and presumably of embolic origin. They were not related to sonographic embolic signals, plaque ulcerations, or intraoperative shunting.

Conclusions
—These results suggest that the incidence of silent ischemic brain lesions of embolic origin after CEA is low and does not correlate with the occurrence of intraoperative sonographic microemboli. They confirm that CEA is a safe procedure that carries a low risk of postoperative cerebral events.
Vascular Cell Components of the Medullary Arteries in Binswanger’s Disease Brains
Authors: Lin Jin-Xi , Tomimoto Hidekazu , Akiguchi Ichiro , Matsuo Akinori , Wakita Hideaki , Shibasaki Hiroshi , Budka Herbert
Published: June 2011

Background and Purpose
—It has been hypothesized that fibrohyalinosis of the medullary arteries may cause white matter lesions in Binswanger’s disease (BD). However, previous reports have been inconsistent on the pathological alterations of the cellular components, which may vary in terms of vessel sizes. We therefore quantitatively examined vasculopathy in the medullary arteries of a defined caliber in BD brains with a quantitative technique.

Methods
—A total of 20 brains were examined: 10 from patients with BD and 10 from age-matched nonneurological control patients. The alterations in the vascular cell components were examined with quantitative immunohistochemistry and immunoelectron microscopy for collagen and smooth muscle actin.

Results
—The nonneurological control patients showed no white matter lesions. In contrast, the patients with BD invariably had marked white matter lesions, as well as fibrohyalinosis of the medullary arteries. The ratio of the area immunolabeled for collagen type I and type IV to the cross-sectional area was 2-fold higher in the BD patients than in the control patients, regardless of the vessel caliber (
P
<0.005). Although the ratio for smooth muscle actin in the BD brains was increased in arteries of <100 μm (
P
<0.0001), there was no corresponding increase in the arteries of >100 μm. However, in the ultrastructure of these vessels, the cell bodies immunolabeled for smooth muscle actin were hypertrophic and segregated from each other by proliferated fibrils. The basal lamina appeared multilayered, and the endothelial cells were swollen. Collagen type I and type IV immunoreactive fibrils also proliferated in the pericapillary space of the BD brains.

Conclusions
—The proliferation of collagen fibrils in the media and adventitia of the blood vessels in BD brains was not specific to small arteries and arterioles but also occurred in the pericapillary spaces. Pericapillary sclerosis, smooth muscle cell proliferation in the terminal arterioles, and their morphological transformation in the proximal arteries may alter the shear rates and thus cause profound microcirculatory disturbances in BD brains.
Hemostatic Markers in Patients at Risk of Cerebral Ischemia
Authors: Côté Robert , Wolfson Christina , Solymoss Susan , Mackey Ariane , Leclerc Jacques R , Simard Denis , Rouah Fabrice , Bourque France , Léger Barbara
Published: June 2011

Background
—Increased levels of markers of hemostasis may assist in the determination of the extent of carotid occlusive disease and the identification of neurologically intact individuals at increased risk of ischemic events.

Methods
—We conducted a prospective study of 304 subjects, including 82 with a recent (≤7 days) transient ischemic attack (TIA), 157 asymptomatic individuals with a cervical bruit, and 65 control subjects. Baseline evaluation included a neurological assessment, ECG, cervical ultrasonography, and cerebral CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were also determined. Results were analyzed in relation to the degree of carotid disease and the subsequent occurrence of cerebral and cardiac ischemic events.

Results
—Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic events occurred. Survival analyses showed that prothrombin fragment 1.2 (F
1.2
) was a predictor of time to cerebral and cardiac ischemic events in the combined TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81) as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to 2.53). In the TIA group, both F
1.2
(RR, 2.36; 95% CI, 1.19 to 4.68) and severe (≥80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of time to ischemic stroke, myocardial infarction, or vascular death.

Conclusions
—In patients with TIAs and in asymptomatic individuals with cervical bruits, F
1.2
levels were found to be independent predictors of subsequent cerebral and cardiac ischemic events. Our results are consistent with an active role of the coagulation system through upregulation of thrombin in carotid disease progression and in the pathogenesis of ischemic events in patients at risk.