bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Perfusion Imaging in Acute Ischemic Stroke Using Continuous Arterial Spin Labeling
Authors: Chalela Julio A. , Alsop David C. , Gonzalez-Atavales Julio B. , Maldjian Joseph A. , Kasner Scott E. , Detre John A.
Published: June 2011

Background and Purpose
—Continuous arterial spin-labeled perfusion MRI (CASL-PI) uses electromagnetically labeled arterial blood water as a diffusible tracer to noninvasively measure cerebral blood flow (CBF). We hypothesized that CASL-PI could detect perfusion deficits and perfusion/diffusion mismatches and predict outcome in acute ischemic stroke.

Methods
—We studied 15 patients with acute ischemic stroke within 24 hours of symptom onset. With the use of a 6-minute imaging protocol, CASL-PI was measured at 1.5 T in 8-mm contiguous supratentorial slices with a 3.75-mm in-plane resolution. Diffusion-weighted images were also obtained. Visual inspection for perfusion deficits, perfusion/diffusion mismatches, and effects of delayed arterial transit was performed. CBF in predetermined vascular territories was quantified by transformation into Talairach space. Regional CBF values were correlated with National Institutes of Health Stroke Scale (NIHSS) score on admission and Rankin Scale (RS) score at 30 days.

Results
—Interpretable CASL-PI images were obtained in all patients. Perfusion deficits were consistent with symptoms and/or diffusion-weighted imaging abnormalities. Eleven patients had hypoperfusion, 3 had normal perfusion, and 1 had relative hyperperfusion. Perfusion/diffusion mismatches were present in 8 patients. Delayed arterial transit effect was present in 7 patients; serial imaging in 2 of them showed that the delayed arterial transit area did not succumb to infarction. CBF in the affected hemisphere correlated with NIHSS and RS scores (
P
=0.037 and
P
=0.003, Spearman rank correlation). The interhemispheric percent difference in middle cerebral artery CBF correlated with NIHSS and RS scores (
P
=0.007 and
P
=0.0002, respectively).

Conclusions
—CASL-PI provides rapid noninvasive multislice imaging in acute ischemic stroke. It depicts perfusion deficits and perfusion/diffusion mismatches and quantifies regional CBF. CASL-PI CBF asymmetries correlate with severity and outcome. Delayed arterial transit effects may indicate collateral flow.
Relationship Between Pattern of Intracranial Artery Abnormalities on Transcranial Doppler and Oxfordshire Community Stroke Project Clinical Classification of Ischemic Stroke
Authors: Mead G. E. , Wardlaw J. M. , Dennis M. S. , Lewis S. C. , Warlow C. P.
Published: June 2011

Background and Purpose
—The Oxfordshire Community Stroke Project (OCSP) devised a simple classification for acute stroke based on clinical features only, which is of value in predicting prognosis. We investigated whether the pattern of intracranial vascular abnormalities is related to the clinical syndrome.

Methods
—Patients with acute ischemic stroke were classified by a stroke physician as having total or partial anterior circulation infarct (TACI or PACI, respectively), lacunar infarct (LACI), or posterior circulation infarct (POCI). Color-coded power transcranial Doppler was done whenever possible. Intracranial arterial velocities were compared in the 4 subtypes of ischemic stroke after adjustment for age and time to transcranial Doppler.

Results
—Middle cerebral artery velocity was abnormal (hyperemia, reduced velocity, occlusion, or focal stenosis) in 38 of 69 TACIs (55%), 50 of 171 PACIs (29%), and 20 of 236 LACIs or POCIs (8%) (
P
<0.001). Velocity in the A1 segment of the anterior cerebral artery was reversed in 12 of 69 TACIs (17%), 20 of 171 PACIs (12%), and 8 of 236 LACIs or POCIs (3%) (
P
<0.001). Basilar artery velocity was abnormal in 8 of 121 POCIs (7%) compared with 5 of 355 (1%) of the other subtypes (
P
=0.005). Vertebral artery velocity was abnormal (reduced velocity, occlusion, stenosis) in 20 of 121 POCIs (17%) compared with 20 of 355 others (6%) (
P
=0.01).

Conclusions
—Intracranial arterial abnormalities were related to OCSP clinical subtype. Therefore, it is possible to stratify patients according to OCSP classification in trials of new treatments in which treatment effectiveness may depend on the underlying pattern of arterial pathology and before any arterial imaging is available.
Plasma Endothelin-1 Levels Neither Increase nor Correlate With Neurological Scores, Stroke Risk Factors, or Outcome in Patients With Ischemic Stroke
Authors: Haapaniemi Elena , Tatlisumak Turgut , Hamel Kathleen , Soinne Lauri , Lanni Carmine , Opgenorth Terry J. , Kaste Markku
Published: June 2011

Background and Purpose
—Endothelins (ETs) are potent vasoconstrictors and may play a role in the pathophysiology of several diseases. Limited and controversial data exist on their role in human ischemic stroke. We planned a prospective, observational, and longitudinal clinical study to test whether ET-1 levels increase in various phases of ischemic stroke and whether the ET-1 levels correlate with neurological scores, stroke etiology, stroke risk factors, or final outcome.

Methods
—We measured plasma ET-1 levels with a sandwich-enzyme immunoassay method in 101 consecutive patients with ischemic stroke on admission and 1 week, 1 month, and 3 months after stroke and in 101 sex- and age-matched control subjects. At each sampling, the patients underwent a complete neurological evaluation. All stroke risk factors were recorded, an array of laboratory tests were performed, and the subtype of ischemic stroke was determined. The patients were contacted 3 years later for prognostic determination.

Results
—ET-1 levels in patients (2.4±1.3 pg/mL on admission, 2.2±1.4 pg/mL at 1 week, 2.1±1.4 pg/mL at 1 month, and 2.1±1.2 pg/mL at 3 months) were not different from those of the control subjects (2.2±0.9 pg/mL) at any time point. No correlation was found between the ET-1 levels and stroke etiology, stroke risk factors, stroke recurrence risk, age, sex, or neurological scores, except that ET-1 levels correlated with the use of warfarin and with body mass index.

Conclusions
—Plasma ET-1 levels were normal in patients with ischemic stroke. Our findings cannot exclude a role of ETs in the pathophysiology of ischemic stroke because plasma levels might not accurately reflect intracerebral concentrations, but they also do not support the occurrence of a major plasma ET-1 level increase at any phase of stroke. Our patient population is the largest ever reported in whom ET-1 levels were measured, but it consisted of mild and moderately ill patients with stroke due to the study design, of which the aim was long-term observation, which excludes severely ill patients.
Stiffness of Carotid Artery Wall Material and Blood Pressure in Humans
Authors: Safar M. E. , Blacher J. , Mourad J. J. , London G. M.
Published: June 2011

Background and Purpose
—Because epidemiological studies show that increased pulse pressure and carotid wall–material stiffness are predictors of cardiovascular mortality independent of age, atherosclerosis, and conventional risk factors, the relationships between carotid wall stiffness and blood pressure are important to the optimization of cardiovascular prevention.

Summary of Review
—In middle-aged hypertensive patients, mean and pulse pressures are increased, and systolic and diastolic pressures are increased to the same degree as mean pressure. Carotid hypertrophy is associated with normal wall stress, but no increased stiffness of wall material has been reported. With age, the normal wall stress is associated with a larger diameter and a stiffer material of carotid but not peripheral arteries. The stiffer wall involves calcifications, large amounts of collagen, and fragmentation and rupture of elastic tissue, which results in increased pulse-wave velocity and alterations of amplitude and timing of wave reflections and thus causes a disproportionate increase in systolic and pulse pressure. During this period, acutely administered nitrates in elderly subjects are able to reduce selectively systolic and pulse pressures without altering diastolic and mean blood pressure and composition of the carotid wall.

Conclusions
—New therapeutic approaches acting mainly on the wall of large arteries are needed to treat hypertension in elderly patients and prevent stroke and myocardial infarction. These drugs could either selectively lower pulse pressure through changes in wave reflections (as nitrates do) or decrease arterial wall stiffness through modification of the composition of material (such as compounds that act on collagen cross-linking).
Unilateral Leptomeningeal Enhancement After Carotid Stent Insertion Detected by Magnetic Resonance Imaging
Authors: Wilkinson Iain D. , Griffiths Paul D. , Hoggard Nigel , Cleveland Trevor J. , Gaines Peter A. , Venables Graham S.
Published: June 2011

Background and Purpose
—Percutaneous transluminal angioplasty combined with vascular stenting is currently being assessed in the treatment of patients with symptomatic, severe carotid stenosis. The immediate cerebral hemodynamic effects resulting from stenting are not fully understood. This article describes a novel finding: abnormal leptomeningeal enhancement after stenting shown by MRI.

Methods
—Fourteen patients with symptomatic severe carotid bifurcation stenosis underwent MRI within 4 hours before and within 3 hours after attempted carotid stenting. Twelve patients were successfully stented. Part of the MR investigation consisted of the acquisition of T1-weighted images before and after administration of the contrast agent Gd-DTPA, both before and after the procedure.

Results
—All 12 patients who underwent successful stenting did not have abnormal enhancement of the leptomeninges before stenting but developed unilateral enhancement following intervention but before the second injection of contrast agent. No contrast enhancement was detected in the 2 patients who had the angiographic procedure but were not stented.

Conclusions
—These findings suggest that abnormal changes to the leptomeningeal vasculature occur during carotid stenting which are not associated with sudden development of neurological symptoms. The anatomic distribution of the enhancement suggests that it is a consequence of the sudden change in brain hemodynamics secondary to the improvement in carotid flow after stenting.
Nitric Oxide–Related Brain Damage in Acute Ischemic Stroke
Authors: Castillo José , Rama Ramón , Dávalos Antoni
Published: June 2011

Background and Purpose
—The neurotoxic and neuroprotective role of nitric oxide (NO) in experimental cerebral ischemia has generated considerable debate. The aim of this study was to analyze the relationship between NO metabolite (NO-m) concentrations in cerebrospinal fluid (CSF) and clinical and neuroimaging parameters of brain injury in patients with acute ischemic stroke.

Methods
—We studied 102 patients and 24 control subjects who were included in a larger previous study conducted to analyze risk factors of progressing stroke. NO generation was calculated by quantifying nitrates and nitrites with a colorimetric assay in CSF samples obtained within the first 24 hours from symptoms onset. Early neurological deterioration was defined as a fall of 1 or more points in Canadian Stroke Scale score between admission and 48 hours after inclusion. Infarct volume was measured on days 4 to 7 by cranial CT.

Results
—Median NO-m concentrations [quartiles] were 2.1 [1.0, 4.5] μmol/mL in patients and 1.0 [1.0, 1.0] μmol/mL in control subjects (
P
<0.0001). In 45 patients with subsequent early neurological deterioration, NO-m levels in CSF were significantly higher than in those with stable stroke (4.0 [1.7, 7.8] versus in 1.6 [1.0, 2.5] μmol/mL,
P
<0.0001). There was a moderate correlation between NO-m and infarct volume (coefficient 0.39,
P
<0.001). NO-m concentrations >5.0 μmol/mL were significantly associated with early neurological worsening (OR 5.7, 95% CI 1.2 to 27.4;
P
=0.030) independent of other important factors related to progressing stroke, such as CSF glutamate levels.

Conclusions
—Our clinical findings suggest an important role of NO generation in acute ischemic stroke. Increased NO-m in CSF are associated with a greater brain injury and early neurological deterioration.
Reduced Vasomotor Reactivity in Cerebral Microangiopathy
Authors: Terborg Christoph , Gora Felix , Weiller Cornelius , Röther Joachim
Published: June 2011

Background and Purpose
—Reduction of cerebral blood flow and vasomotor reactivity (VMR) are thought to play an important role in the pathogenesis of cerebral microangiopathy. The aim of our study was to determine whether near-infrared spectroscopy (NIRS) can detect a reduced VMR in patients with microangiopathy, whether NIRS reactivities correlate with VMR assessed by transcranial Doppler sonography (TCD), and whether the differing extents of patients’ microangiopathy demonstrated on MRI or CT can be distinguished by both noninvasive techniques.

Methods
—We compared the VMR of 46 patients with cerebral microangiopathy with 13 age-matched control subjects. Patients were classified with the Erkinjuntti scale. We monitored cerebral blood flow velocity (CBFV) in both middle cerebral arteries by TCD, changes in concentration of oxyhemoglobin (Hb
o
2
), deoxyhemoglobin (Hb) and blood volume (HbT) by NIRS, mean arterial blood pressure, and end-tidal CO
2
(Et
co
2
) during normocapnia and hypercapnia. VMRs were calculated as percent change of CBFV (NCR) and as absolute change in concentration of HbO
2
, Hb, and HbT per 1% increase in Et
co
2
(CR-HbO
2
, CR-Hb, CR-HbT).

Results
—NCR and NIRS reactivities were significantly reduced in patients with cerebral microangiopathy. CR-HbO
2
and CR-Hb showed a close correlation with NCR, and NCR and NIRS reactivities were related to the severity of cerebral microangiopathy according to the Erkinjuntti scale. Validity of NCR and NIRS reactivities were similar.

Conclusions
—VMR is reduced in patients with cerebral microangiopathy and can be noninvasively assessed in basal arteries (with TCD) and brain parenchyma (with NIRS). Reduction of CO
2
-induced VMR, as measured by NIRS and TCD, may indicate the severity of microangiopathy.
Postischemic Attenuation of Cerebral Artery Reactivity Is Increased in the Presence of Tissue Plasminogen Activator
Authors: Cipolla Marilyn J. , Lessov Nikola , Clark Wayne M.
Published: June 2011

Background and Purpose
—We investigated the combined effect of tissue plasminogen activator and ischemia on middle cerebral artery (MCA) reactivity to determine whether abnormal MCA function after 2 hours of ischemia was worse in arteries perfused with recombinant tissue plasminogen activator (rtPA).

Methods
—The intraluminal suture model of focal cerebral ischemia was used to induce 2 hours of ischemia in rats, after which occluded MCAs were removed and studied in vitro with an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were either nonischemic (control; n=8), nonischemic and perfused with 400 μg/mL rtPA (rtPA; n=5), ischemic (ISC; n=6), or ischemic and perfused with 400 μg/mL rtPA (ISC-rtPA; n=6). After a 1-hour equilibration at 75 mm Hg, TMP was increased to 125 mm Hg and lumen diameter was recorded at each pressure. Reactivity to acetylcholine (ACh, 0.1 to 10.0 μmol/L) and serotonin (0.01 to 10 μmol/L) was then determined.

Results
—Control arteries responded myogenically to pressure and increased the amount of tone from 18.5±3.8% at 75 mm Hg to 24.8±3.0% at 125 mm Hg (
P
<0.05), which decreased diameter from 241±7 to 232±6 μm. In contrast, all other groups decreased tone at 125 mm Hg, which demonstrated a loss of myogenicity. The percent tone in each group at 75 versus 125 mm Hg was rtPA, 16.0±4.5% versus 11.8±3.8%; ISC, 23.5±4.5% versus 13.5±3.1%; and ISC-rtPA, 23.5±4.2% versus 12.3±3.2% (
P
<0.05 for all). The percent increase in lumen diameter at each concentration of ACh was diminished in all groups compared with control; ISC-rtPA arteries responded the least, which suggests an additive effect of rtPA in ischemic arteries. The percent increase in lumen diameter at 10
−5
mol/L ACh was 23±4% for control versus 15±2% for rtPA; 17±3% for ISC arteries (
P
<0.05), and 8±2% for ISC-rtPA arteries (
P
<0.01). Sensitivity to serotonin was equally diminished in all groups compared with control: EC
50
(μmol/L) was 0.06±0.01 for control, 0.17±0.02 for rtPA, 0.22±0.07 for ISC, and 0.16±0.04 for ISC-rtPA (
P
<0.05).

Conclusions
—These results demonstrate that both ischemia and rtPA perfusion diminish cerebral artery reactivity and that the combination may produce an additive effect. This impaired reactivity may contribute to reperfusion-induced injury during or after thrombolysis by altering upstream cerebrovascular resistance.
In Vivo Gene Transfer of Endothelial Nitric Oxide Synthase to Carotid Arteries From Hypercholesterolemic Rabbits Enhances Endothelium-Dependent Relaxations
Authors: Sato Jun’ichi , Mohácsi Tibor , Noel Audra , Jost Corey , Gloviczki Peter , Mozes Geza , Katusic Zvonimir S. , O’Brien Timothy
Published: June 2011

Background and Purpose
—Hypercholesterolemia is associated with abnormal endothelium-dependent vasorelaxation due to decreased nitric oxide bioavailability. Our aim was to examine the effect of adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) to the hypercholesterolemic rabbit carotid artery in vivo. In addition, we examined whether adenovirus-mediated gene transfer was associated with vascular dysfunction.

Methods
—Rabbits were fed a 1% cholesterol diet for 4 weeks followed by a 0.5% cholesterol diet for 6 weeks. Vascular reactivity was assessed in nontransduced carotid arteries from chow- and cholesterol-fed animals. In addition, carotid arteries were surgically isolated, and 2 separate doses of adenoviral vectors encoding eNOS or β-galactosidase (AdβGal) on the contralateral side were delivered to the lumen (1×10
10
and 5×10
10
pfu/mL).

Results
—Abnormal acetylcholine-mediated endothelium-dependent vasorelaxation was detected in the carotid artery from cholesterol-fed animals, whereas responses to calcium ionophore A23187 and diethylamine NONOate were normal. Vascular reactivity was similar in nontransduced and AdβGal-transduced hypercholesterolemic vessels. In vessels transduced with eNOS, transgene expression was demonstrated by immunostaining in both the endothelium and the adventitia and by Western blot analysis. High-dose but not low-dose eNOS gene transfer enhanced endothelium-dependent relaxation in vessels from cholesterol-fed rabbits.

Conclusions
—Adenovirus-mediated gene transfer of eNOS to carotid arteries of cholesterol-fed animals improves endothelium-dependent relaxation when an optimal viral titer is administered.
Home or Hospital for Stroke Rehabilitation? Results of a Randomized Controlled Trial
Authors: Anderson Craig , Mhurchu Cliona Ni , Rubenach Sally , Clark Michael , Spencer Carol , Winsor Adrian
Published: June 2011

Background and Purpose
—The goal of the present study was to examine the resource and economic implications of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke.

Methods
—A cost minimization analysis in conjunction with a randomized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide, South Australia, between 1997 and 1998. Eighty-six hospitalized patients with acute stroke who required rehabilitation were randomized to receive both early hospital discharge and home-based rehabilitation, or conventional in-hospital rehabilitation and community care. Direct and indirect costs related to stroke rehabilitation were calculated, including hospital bed days, home-based intervention program, community services, and personal expenses during the 6 months after randomization.

Results
—The mean cost per patient was lower for patients randomized to the early hospital discharge and home-based rehabilitation ($8040) compared with those who received conventional care ($10 054). This cost saving was not statistically significant (
P
=0.14). However, sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50% less than those used in the main analysis. Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient’s level of disability after adjustment for age, comorbidity, and the presence or absence of a caregiver.

Conclusions
—The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke. Limitation of the provision of such services to patients with mild disability is likely to be most cost effective.
Economic Evaluation in Stroke Research
Authors: Evers Silvia M. A. A. , Ament André J. H. A. , Blaauw Gerhard
Published: June 2011

Background and Purpose
—The purpose of this review is to provide insight into the quality of economic evaluation in the field of cerebrovascular diseases (CVD) on the basis of a systematic analysis.

Methods
—A literature search was performed using several sources. Trial-based full economic evaluation studies, were included in this review. The quality of the studies was independently assessed by 2 reviewers using a checklist.

Results
—Twenty-three articles were found to comply with our inclusion and exclusion criteria. Only a few studies mentioned the perspective of the study, and in these cases it was always the societal perspective. The majority of the studies were cost-minimization and cost-effectiveness analyses based on cohort studies. All studies included healthcare costs, and in some instances patient and family costs were considered. Costs were usually measured by tariffs. Clinical end points and mortality were used to measure effects. Cost and effect measurements were based on hospital records.

Conclusions
—Only a few full economic evaluations have been undertaken in the domain of CVD. In most of the studies, the technical execution and methodology were limited.
Arterial Pulsatility as an Index of Cerebral Microangiopathy in Diabetes
Authors: Lee Kyung Y. , Sohn Young H. , Baik Jong S. , Kim Gyung W. , Kim Jin-Soo
Published: June 2011

Background and Purpose
—This study was designed to evaluate cerebral hemodynamic changes related to diabetes mellitus (DM) with transcranial Doppler ultrasonography (TCD).

Methods
—We measured the flow velocities and the Gosling pulsatility index (PI) of the middle cerebral artery (MCA), extracranial internal carotid artery (ICA), and basilar artery (BA) in 56 stroke-free, normotensive patients with type 2 DM and 70 age- and gender-matched healthy volunteers. Patients were divided into 2 groups according to the presence of microvascular complications such as retinopathy, nephropathy, and neuropathy.

Results
—Patients showed slightly lower hematocrit and higher serum fibrinogen levels than control subjects, but other clinical profiles, including stroke risk factors except for diabetes, were comparable between patients and controls. The flow velocity of the ICA but not the MCA and BA in patients regardless of the complication was significantly higher than that in controls. The PIs of the MCA and ICA were significantly higher in patients with complication than those without complication, as well as in controls. The PI of the BA was also significantly higher, even in patients without complication, than in controls. The PIs of the MCA and ICA but not the BA were closely correlated with the duration of DM (
r
2
=0.46 and 0.34, respectively).

Conclusions
—This study defines TCD findings of diabetes-related cerebral hemodynamic changes and suggests that the PI reflects microangiopathic changes of cerebral vessels.
Transcranial Doppler Ultrasound Criteria for Recanalization After Thrombolysis for Middle Cerebral Artery Stroke
Authors: Burgin W. Scott , Malkoff Marc , Felberg Robert A. , Demchuk Andrew M. , Christou Ioannis , Grotta James C. , Alexandrov Andrei V.
Published: June 2011

Background and Purpose
—Transcranial Doppler (TCD) can demonstrate arterial occlusion and subsequent recanalization in acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA). Limited data exist to assess the accuracy of recanalization by TCD criteria.

Methods
—In patients with acute middle cerebral artery (MCA) occlusion treated with intravenous tPA, we compared posttreatment TCD with angiography (digital subtraction or magnetic resonance). On TCD, complete occlusion was defined by absent or minimal signals, partial occlusion by blunted or dampened signals, and recanalization by normal or stenotic signals. Angiography was evaluated with the Thrombolysis In Myocardial Ischemia (TIMI) grading scale.

Results
—Twenty-five patients were studied (age 61±18 years, 16 men and 9 women). TCD was performed at 12±16 hours and angiography at 41±57 hours after stroke onset, with 52% of studies performed within 3 hours of each other. Recanalization on TCD had the following accuracy parameters compared with angiography: sensitivity 91%, specificity 93%, positive predictive value (PPV) 91%, and negative predictive value (NPV) 93%. To predict partial occlusion (TIMI grade II), TCD had sensitivity of 100%, specificity of 76%, PPV of 44%, and NPV of 100%. TCD predicted the presence of complete occlusion on angiography (TIMI grade 0 or I) with sensitivity of 50%, specificity of 100%, PPV of 100%, and NPV of 75%. TCD flow signals correlated with angiographic patency (χ
2
=24.2,
P
<0.001).

Conclusions
—Complete MCA recanalization on TCD accurately predicts angiographic findings. Although a return to normal flow dynamics on TCD was associated with complete angiographic resumption of flow, partial signal improvement on TCD corresponded with persistent occlusion on angiography.
Hypertonic Mannitol Loading of NF-κB Transcription Factor Decoys in Human Brain Microvascular Endothelial Cells Blocks Upregulation of ICAM-1
Authors: Hess David C. , Howard Eugene , Cheng Charles , Carroll James , Hill W. David
Published: June 2011

Background and Purpose
—An acute inflammatory response exacerbates tissue injury during acute ischemic stroke. The transcription factor nuclear factor (NF)-κB plays a key role in endothelial cell activation and the inflammatory response. Targeted genetic disruption of NF-κB activation in cerebral endothelial cells may be protective in stroke. We determined whether a NF-κB transcription factor decoy (TFD) could block intercellular adhesion molecule (ICAM)-1 upregulation, an indicator of endothelial cell activation.

Methods
—We modeled ischemia-reperfusion in vitro by exposing cultured human brain microvascular endothelial cells (HBMEC) to tumor necrosis factor (TNF)-α and conditions of hypoxia-reoxygenation (H/R). Mannitol was used to load phosphothiorated oligonucleotides containing 3 copies of the κB binding sequences (TFDs) into cultured HBMEC. An NF-κB TFD, a mutated NF-κB TFD, and a scrambled TFD were studied for their effect on ICAM-1 mRNA levels and surface ICAM-1 by ELISA.

Results
—Hyperosmolar loading with mannitol permitted rapid transfection of TFD into endothelial cell nuclei. The NF-κB TFD but not the mutated or scrambled TFD competed with a κB sequence for binding to nuclear extracts from HBMEC exposed to TNF-α. The NF-κB TFD blocked the TNF-α–induced and H/R-induced increase in ICAM-1 mRNA levels and the upregulation of surface ICAM-1.

Conclusions
—Mannitol delivers phosphothiorated oligonucleotides into cultured HBMEC. An NF-κB decoy blocks both TNF-α–induced and H/R-induced ICAM-1 upregulation in HBMEC. Targeted genetic disruption of endothelial NF-κB activation may be of benefit in acute ischemic stroke.
Treatment-Induced Cortical Reorganization After Stroke in Humans
Authors: Liepert Joachim , Bauder Heike , Miltner Wolfgang H. R. , Taub Edward , Weiller Cornelius
Published: June 2011

Background and Purpose
—Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment.

Methods
—We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy.

Results
—Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recruitment of adjacent brain areas. In follow-up examinations up to 6 months after treatment, motor performance remained at a high level, whereas the cortical area sizes in the 2 hemispheres became almost identical, representing a return of the balance of excitability between the 2 hemispheres toward a normal condition.

Conclusions
—This is the first demonstration in humans of a long-term alteration in brain function associated with a therapy-induced improvement in the rehabilitation of movement after neurological injury.
Effect of Intravenous Nimodipine on Blood Pressure and Outcome After Acute Stroke
Authors: Ahmed Niaz , Näsman Per , Wahlgren Nils Gunnar
Published: June 2011

Background and Purpose
—The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction.

Methods
—Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed.

Results
—Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (β=0.49,
P
=0.048). Patients with a DBP reduction of ≥20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10.16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome.

Conclusions
—DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.
Preferred Technique for Blood Flow Volume Measurement in Cerebrovascular Disease
Authors: Ho Stella S. Y. , Metreweli Constantine
Published: June 2011

Background and Purpose
—A noninvasive reliable technique that can reveal cerebral blood flow volume could be a valuable tool in screening programs for stroke prevention. In diagnostic ultrasonography, spectral Doppler imaging (SDI) is popular among sonologists and vascular technologists to estimate blood flow volume despite its documented inaccuracy and the availability of the more accurate technique of color velocity imaging (CVI). The aim of the present study was to demonstrate the discrepancy of blood flow volume estimation with CVI and SDI with use of an “internal” standard.

Methods
—The common, internal, and external carotid arteries of 50 healthy subjects (22 men, 28 women, age range 19 to 54 years) were examined with CVI and SDI. The total blood flow volume of the internal and external carotid arteries was then compared with the ipsilateral common carotid artery flow. An accurate technique would demonstrate no difference. The difference (expressed as a percent inconsistency) was therefore a measure of the accuracy of the method.

Results
—The mean±SD inconsistency was found to be 10.6±8.3% for CVI and 27.9±14.3% for SDI. The difference in inconsistency between CVI and SDI in measurement of carotid blood flow volume was statistically significant (
P
<0.01).

Conclusions
—CVI is more accurate than SDI in the determination of blood flow volume in the carotid arteries. For noninvasive clinical estimation of cerebrovascular blood flow volume, CVI quantification should be the preferred technique.
Brain Tissue Sodium Is a Ticking Clock Telling Time After Arterial Occlusion in Rat Focal Cerebral Ischemia
Authors: Wang Yang , Hu Weixing , Perez-Trepichio Alejandro D. , Ng Thian C. , Furlan Anthony J. , Majors Anthony W. , Jones Stephen C.
Published: June 2011

Background and Purpose
—Many patients with acute stroke are excluded from receiving thrombolysis agents within the necessary time limit (3 or 6 hours from stroke onset) because they or their family members are unable provide the time of stroke onset. Brain tissue sodium concentration ([Na
+
]) increases gradually and incessantly during the initial hours of experimental focal cerebral ischemia but only in severely damaged brain regions. We propose that this steady increase in [Na
+
] can be used to estimate the time after arterial occlusion in the rat middle cerebral artery occlusion model of ischemic stroke.

Methods
—Sixteen anesthetized Sprague-Dawley rats underwent permanent middle cerebral artery occlusion combined with bilateral common artery occlusion. After 100 to 450 minutes, diffusion-weighted MRI was used to generate apparent diffusion coefficient (ADC) maps, cerebral blood flow (CBF) was determined with
14
C-iodoantipyrine (in a subset of 7 animals), and the brain was frozen. Autoradiographic CBF sections and punch samples for Na
+
analysis were obtained from the brain at the same level of the MR image. Severely at risk regions were identified with an ADC of <520 μm
2
/s and, in the subset, with both ADC of <520 μm
2
/s and CBF of <40 mL · 100 g
−1
· min
−1
.

Results
—Both CBF and the ADC dropped quickly and remained stable in the initial hours after ischemic onset. Linear regression revealed strong linearity between [Na
+
] and time after onset, with a slope of 0.95 or 1.00 (mEq/kg DW)/min, with both ADC and ADC-plus-CBF criteria, respectively. The 95% CIs at 180 and 360 minutes were between 41 and 52 minutes.

Conclusions
—The time after ischemic onset can be estimated with this 2-step process. First, ADC and CBF are used to identify severely endangered regions. Second, the [Na
+
] in these regions is used to estimate time after onset. The favorable 95% CIs at the time limits for thrombolytic therapy and the availability of measurements of ADC, CBF, and [Na
+
] in humans through the use of MRI suggest that this time-estimation scheme could be used to assess the appropriateness of thrombolysis for patients who do not know when the stroke occurred.
Endovascular Treatment of Dural Sinus Thrombosis With Rheolytic Thrombectomy and Intra-Arterial Thrombolysis
Authors: Chow Kira , Gobin Y. Pierre , Saver Jeffrey , Kidwell Chelsea , Dong Paul , Viñuela Fernando
Published: June 2011

Background and Purpose
—Cerebral venous thrombosis is a rare entity that can be difficult to manage. Intrasinus thrombolysis is an increasingly applied intervention, but this modality carries an increased risk of hemorrhage. We describe for the first time an option with a potentially lower incidence of intracranial bleeding, the combination of the AngioJet rheolytic thrombectomy catheter with intra-arterial thrombolysis, in 2 patients with extensive dural sinus thromboses, preexisting intracranial hemorrhage, and severe progressive neurological deficits despite heparin therapy.

Methods—
Four procedures were performed in 2 patients with thromboses in the superior sagittal and transverse sinuses (right in 1 patient and bilateral in 1 patient) and cortical veins. Rheolytic thrombectomy was performed in the sigmoid, transverse, straight, and superior sagittal sinuses; this technique involves the use of the Bernoulli effect to create a vacuum that fragments and aspirates thrombus. For associated persistent cortical vein thromboses, low-dose intra-arterial thrombolysis was used.

Results—
Both patients had excellent angiographic results with sinus reopening after rheolytic thrombectomy and cortical vein reopening after intra-arterial thrombolysis. Follow-up CT showed no change in 1 patient and increased preexisting intracranial hemorrhage in the other. One patient had a negative hypercoagulable workup, and the other patient had probable anti-phospholipid antibody syndrome. At 6 months, both patients had excellent clinical outcome with no neurological deficits except mild short-term memory loss in 1 patient.

Conclusions
—The combination of rheolytic thrombectomy with intra-arterial thrombolysis is a treatment modality that allows accelerated recanalization of occluded dural sinuses and cerebral veins with lower doses of thrombolytic agents.
Critical Appraisal of the Design and Reporting of Studies of Imaging and Measurement of Carotid Stenosis
Authors: Rothwell Peter M. , Pendlebury Sarah T. , Wardlaw Joanna , Warlow Charles P.
Published: June 2011

Background and Purpose
—Several hundred studies have been published over the last few years on imaging and measurement of carotid stenosis. Despite all this research, there is still no consensus about how best to image and measure stenosis. One possible explanation for this is that many of the studies have not been large enough or methodologically sound enough to allow useful conclusions to be drawn. We aimed to assess the design and methods of a random sample of published studies of imaging and measurement of carotid stenosis using 9 simple criteria.

Methods
—A formal literature search was performed for studies of imaging and measurement of carotid stenosis. Two subsets were randomly selected for detailed assessment: 20 studies published before 1991 and 20 published between 1993 and 1997 (some years after the initial publication of the ECST and NASCET trials). The criteria used to assess the selected studies were as follows: prospective rather than retrospective study design; patient selection based on a consecutive series or a random sample; adequate detail of study population; adequate detail of imaging techniques; inclusion of all investigations, ie, patients with poor-quality imaging were not excluded; blinded assessment of images; adequate detail of derivation of measurement of stenosis from images or data; adequate data on the reproducibility of measurements of stenosis; and study powered according to a sample-size calculation.

Results
—There were many basic methodological deficiencies in both subsets of studies, with relatively little evidence of improvement with time. For example, only 33% of studies were prospective, only 45% studied a consecutive or random selection of patients, and only 38% reported any data on the reproducibility of measurements. More than half of the studies satisfied ≤4 of the 9 quality criteria. However, there was considerable variation between studies, with 7 studies satisfying ≥7 criteria and 10 studies satisfying ≤2. No study was based on a sample-size calculation. The number of patients studied was often small, particularly in the more recent studies: median sample size was 100 in the 1970–1990 studies and 58 in the 1993–1997 studies (
P
<0.0001).

Conclusions
—The design and reporting of published studies of imaging and measurement of carotid stenosis are poor and have not improved much in recent years. The majority of published studies are not of a sufficient standard to enable the results to be used to inform clinical practice. The utility of future studies could be improved considerably by better adherence to 9 simple methodological guidelines.
Reperfusion and Metabolic Recovery of Brain Tissue and Clinical Outcome After Ischemic Stroke and Thrombolytic Therapy
Authors: Berrouschot Jörg , Barthel Henryk , Hesse Swen , Knapp Wolfram H. , Schneider Dietmar , von Kummer Rüdiger
Published: June 2011

Background and Purpose
—It is unclear from recent clinical trials whether thrombolytic agents are capable of facilitating reperfusion and metabolic recovery over time or whether a beneficial effect is counteracted by an increase in the risk of brain hemorrhage. We studied the effect of thrombolytic treatment on metabolic recovery after reperfusion and clinical outcome.

Methods
—Patients were prospectively studied with
99m
Tc-ethyl cysteinate dimer single photon emission computed tomography (
99m
Tc-ECD-SPECT) before treatment with recombinant tissue plasminogen activator (rTPA; 0.9 mg/kg IV; n=26) or placebo (n=26) 6 to 8 hours after treatment and at 7±1 days. Activity deficits were graded, compared between the treatment groups, and correlated with clinical outcome and the incidence of brain hemorrhage. Metabolic recovery of ischemic brain tissue was defined as a 25% decrease on the SPECT graded scale.

Results
—Patients with metabolic recovery (n=28) had a better chance of being functionally unimpaired 3 months after stroke than patients without recovery (n=24) (OR 4.5, 95% CI 1.09 to 18.89) and had smaller infarcts on follow-up CT (36±38 versus 167±162 mL), regardless of whether metabolic recovery was observed within 6 to 8 hours of treatment or at 7 days. None of the 28 patients with metabolic recovery had a fatal parenchymal hemorrhage versus 5 of 24 patients without recovery (
P
=0.016). Treatment did not affect the incidence of brain tissue metabolic recovery.

Conclusions
—Brain tissue metabolic recovery after ischemic stroke was associated with a beneficial effect on clinical outcome and was not facilitated by treatment with 0.9 mg of intravenous rTPA.
Stroke, a Major and Increasing Risk Factor for Femoral Neck Fracture
Authors: Ramnemark Anna , Nilsson Mikael , Borssén Bengt , Gustafson Yngve
Published: June 2011

Background and Purpose
—Patients with stroke have up to a 4-fold increased risk of hip fracture because of their high incidence of falls and loss of bone mass in the paretic side, ie, hemiosteoporosis. The purpose of this study was to investigate the prevalence of previous stroke among patients with femoral neck fracture.

Methods
—The study included all 568 patients, aged ≥65 years, who underwent surgery for femoral neck fracture in 1980, 1983, 1987, 1993, and 1997 at the orthopedic clinic of Umeå University Hospital, Umeå, Sweden.

Results
—The prevalence of previous strokes ranged from 16.4% to 38.5% (
P
<0.001); this finding is only partly explained by the increased incidence of stroke in the corresponding population, and there was no significant increase in the overall incidence of femoral neck fracture. Fractures occurred 5.4±6.4 years after stroke (median 2.9 years, range 0 to 33 years). In stroke patients with unilateral stroke and persisting paresis at the time of fracture, 62.5% had their fracture on the paretic side (
P
=0.034). Survival was significantly reduced in patients with previous stroke (
P
<0.001). In patients previously independently mobile, 69.2% with no previous stroke and 38.1% with previous stroke were still mobile at discharge from the orthopedic unit (
P
<0.001).

Conclusions
—Attention must be focused on stroke as a major and increasing risk factor for femoral neck fracture and also on the poor postfracture outcome and reduced survival of these patients. Prevention of poststroke fractures is necessary and is aimed at reducing the risk of poststroke fall and preventing the development of hemiosteoporosis.
Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts
Authors: Droste Dirk W. , Silling Karen , Stypmann Jörg , Grude Matthias , Kemény Vendel , Wichter Thomas , Kühne Karsten , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of contrast agents and a Valsalva maneuver (VM) as provocation procedure. Currently, data on the appropriate timing of the VM, the use of a diagnostic time window, and a threshold in contrast agent microbubbles detected are insufficient.

Methods
—Fifty-eight patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with injections of 10 mL of the commercial galactose-based contrast agent Echovist was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 2 seconds after the beginning of contrast injection, (3) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, (4) VM for 5 seconds starting 8 seconds after the beginning of contrast injection, and (5) repetitive short VMs in between 2 and 13 seconds after the beginning of contrast injection. In addition to the single tests, we also tested the sensitivity and specificity of combined results of the tests with VM.

Results
—In 21 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-one patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 16 patients were only positive on at least 1 TCD investigation but negative during TEE. Test 3 was the most appropriate test when combined with the results of 1 of the other tests with VM. The highest sensitivities were achieved with a diagnostic time window of 40 seconds and when the presence of a single microbubble was sufficient for the diagnosis of a shunt.

Conclusions
—TCD performed twice with 2 provocation maneuvers with Echovist is a sensitive method to identify TEE-proven cardiac right-to-left shunts. The VM should be performed for 5 seconds starting at 5 seconds after the beginning of contrast injection.
Assessment of Lacunar Hemorrhage Associated With Hypertensive Stroke by Echo-Planar Gradient-Echo T2*-Weighted MRI
Authors: Kinoshita Toshibumi , Okudera Toshio , Tamura Hajime , Ogawa Toshihide , Hatazawa Jun
Published: June 2011

Background and Purpose
—Echo-planar gradient-echo T2*-weighted MR imaging (GRE-EPI) may detect hypointense lesions representing microhemorrhages with high sensitivity. The aim of this study was to evaluate the effectiveness of GRE-EPI for detecting old lacunar hemorrhages in hypertensive patients with stroke.

Methods
—GRE-EPI was performed with a 1.5-T MRI system in 198 hypertensive patients with stroke (130 patients with hemorrhagic stroke and 68 patients with multiple lacunar stroke) and 66 age-matched healthy elderly individuals.

Results
—Concomitant hypointense foci were found in 84 (66%) patients with hemorrhagic stroke, 46 (68%) patients with multiple lacunar stroke, and 3 (5%) healthy elderly individuals. These hypointense foci were noted in the lentiform nucleus in 61 (47%) patients with hemorrhagic stroke, in the caudate nucleus in 9 (7%) patients, in the thalamus in 54 (42%) patients, in the corticosubcortical region in 57 (44%) patients, in the brain stem in 40 (34%) patients, and in the cerebellum in 32 (25%) patients.

Conclusions
—GRE-EPI is effective for the detection of lacunar hemorrhages induced by hypertension.