bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Year Follow-Up in Acute Stroke Patients Treated With rtPA in Clinical Routine
Authors: Schmülling Susanne , Grond Martin , Rudolf Jobst , Heiss Wolf-Dieter
Published: June 2011

Background and Purpose
—A recent placebo-controlled study provided evidence of a sustained benefit at 1 year from systemic thrombolysis in patients with acute ischemic stroke. The scope of the present study is to determine whether comparable results may be attained in everyday practice if current management guidelines are closely met.

Methods
—Between March 1996 and July 1998, 150 consecutive patients with acute ischemic stroke were treated with systemic thrombolysis using alteplase, strictly in accordance with American Heart Association (AHA) guidelines. The patients were followed up for 12 months after treatment.

Results
—Baseline characteristics and complication rates were comparable to those of the National Institute of Neurological Disorders and Stroke (NINDS) study, except for a somewhat younger age (mean 63 years) and lower National Institutes of Health Stroke Scale score (median 11). At 1 year, 41% of our patients showed minimal or no disability (Rankin scale score of 0 or 1), comparable to 41% in the NINDS rtPA group. The overall rate of recurrent stroke was 6.6% and the transient ischemic attack rate 3.3% at 1 year. Six patients (4%) died after the first 3 months, none of them due to recurrent stroke, and 5 had already been severely disabled at 3 months.

Conclusions
—These observations further encourage the routine use of rtPA for the treatment of acute ischemic stroke in strict accordance with the AHA guidelines.
Perioperative and Late Stroke Rates of Carotid Endarterectomy Contralateral to Carotid Artery Occlusion
Authors: AbuRahma Ali F. , Robinson Patrick , Holt Steven M. , Herzog Thomas A. , Mowery Nathan T.
Published: June 2011

Background and Purpose
—Several previous studies have reported the benefits of carotid endarterectomy (CEA) contralateral to carotid occlusion with mixed results, but none of these were randomized except for the North American Symptomatic Carotid Endarterectomy Trial. The purpose of this study was to analyze the results of surgery in patients with contralateral carotid artery occlusion in a randomized trial in which randomization was done according to the method of closure.

Methods
—In 399 CEAs (357 patients) that were randomized into primary closure versus patching, 49 had contralateral occlusion. Strokes were designated as ipsilateral if they arose from the same CEA side and contralateral if they arose from the occluded side. A Kaplan-Meier analysis was used to estimate perioperative strokes and stroke-free survival in patients with contralateral occlusion (group A) versus those without contralateral occlusion (group B).

Results
—Demographic characteristics and mean follow-up for both groups were similar (group A, 40 months; group B, 33 months). Group A had a higher incidence of contralateral transient ischemic attacks (TIAs) (12.2% versus 0.9%;
P
<0.0001), contralateral strokes (2% versus 0%;
P
=0.025), and combined contralateral TIAs/strokes (14.3% versus 0.9%;
P
<0.0001). The rates for perioperative and all strokes (operative and late) were 2% and 4.1% (2% ipsilateral and 2% contralateral strokes) for group A and 2.9% and 3.4% (all ipsilateral) for group B (
P
=0.60 and 0.85, respectively). The rates for perioperative and all TIAs were 0% and 14.3% for group A versus 2.6% and 6.3% for group B (
P
=0.918 and
P
=0.08, respectively). The rates for perioperative and all neurological events (TIA and stroke) were 2% and 18.4% for group A and 5.4% and 9.7% for group B (
P
=0.27 and 0.113, respectively). The cumulative stroke-free survival rates at 5 years were 84% for group A and 77% for group B (
P
>0.1). The cumulative stroke-free survival rates at 5 years for symptomatic and asymptomatic patients in group A and group B were also similar. The perioperative and late deaths were similar for both groups (group A, 8%; group B, 14%).

Conclusions
—Group A had a higher incidence of contralateral TIAs and strokes than group B; however, the perioperative and all late stroke rates and survival rates of CEA were comparable in patients with and without contralateral occlusion.
Trends in Stroke Incidence and Acute Case Fatality in a Japanese Rural Area
Authors: Morikawa Yuko , Nakagawa Hideaki , Naruse Yuchi , Nishijo Muneko , Miura Katsuyuki , Tabata Masaji , Hirokawa Wataru , Kagamimori Sadanobu , Honda Machiko , Yoshita Katsushi , Hayashi Koich
Published: June 2011

Background and Purpose
—Stroke mortality in Japan has significantly declined during recent decades. To determine the cause of this decrease, we studied the trends in stroke incidence and case fatality within 28 days after stroke in a rural area in Japan.

Methods
—We used a population-based registry during 1977–1991 in Oyabe, a rural area in the central part of Japan. The average population aged 25 years and older numbered 32 859 persons. Changes in age-standardized stroke incidence rate were calculated and compared between the 3 periods 1977–1981, 1982–1986, and 1987–1991. The 28-day case fatality rate was evaluated and also compared between the 3 periods by onset year.

Results
—The total number of strokes was 2068. The age-standardized incidence rate of all strokes decreased during the 15-year period, from 605 to 417 per 100 000 in men and from 476 to 329 per 100 000 in women. A marked decline was found during 1977–1986 but was not apparent during 1987–1991. Moreover, there was an increase in the group aged 75 years and older. The 28-day case fatality rates for all strokes improved from 18.0% to 14.2% in men and from 26.8% to 19.1% in women during the observation period.

Conclusions
—These data indicate that declines in the stroke incidence and the 28- day case fatality have been associated with a marked decrease in stroke-related mortality in Japan.
Orthostatic Tolerance, Cerebral Oxygenation, and Blood Velocity in Humans With Sympathetic Failure
Authors: Harms M.P.M. , Colier W.N.J.M. , Wieling W. , Lenders J.W.M. , Secher N.H. , van Lieshout J.J.
Published: June 2011

Background and Purpose
—Patients with orthostatic hypotension due to sympathetic failure become symptomatic when standing, although their capability to maintain cerebral blood flow is reported to be preserved. We tested the hypothesis that in patients with sympathetic failure, orthostatic symptoms reflect reduced cerebral perfusion with insufficient oxygen supply.

Methods
—This study addressed the relationship between orthostatic tolerance, mean cerebral artery blood velocity (V
mean
, determined by transcranial Doppler ultrasonography), oxygenation (oxyhemoglobin [O
2
Hb], determined by near-infrared spectroscopy), and mean arterial pressure at brain level (MAP
MCA
, determined by finger arterial pressure monitoring [Finapres]) in 9 patients (aged 37 to 70 years; 4 women) and their age- and sex-matched controls during 5 minutes of standing.

Results
—Supine MAP
MCA
(108±14 versus 86±14 mm Hg) and V
mean
(84±21 versus 62±13 cm · s
−1
) were higher in the patients. After 5 minutes of standing, MAP
MCA
was lower in the patients (31±14 versus 72±14 mm Hg), as was V
mean
(51±8 versus 59±9 cm · s
−1
), with a larger reduction in O
2
Hb (−11.6±4 versus −6.7±4.5 μmol · L
−1
). Four patients terminated standing after 1 to 3.5 minutes. In these symptomatic patients, the orthostatic fall in V
mean
was greater (45±6 versus 64±10 cm · s
−1
), and the orthostatic decrease in O
2
Hb (−12.0±3.3 versus −7.6±3.9 μmol · L
−1
) tended to be larger. The reduction in MAP
MCA
was larger after 10 seconds of standing, and MAP
MCA
was lower after 1 minute (25±8 versus 40±6 mm Hg).

Conclusions
—In patients with sympathetic failure, the orthostatic reduction in cerebral blood velocity and oxygenation is larger. Patients who become symptomatic within 5 minutes of standing are characterized by a pronounced orthostatic fall in blood pressure, cerebral blood velocity, and oxygenation manifest within the first 10 seconds of standing.
Genetic Variants of Platelet Glycoprotein Receptors and Risk of Stroke in Young Women
Authors: Reiner Alexander P. , Kumar Prasanna N. , Schwartz Stephen M. , Longstreth W. T. , Pearce Rachel M. , Rosendaal Frits R. , Psaty Bruce M. , Siscovick David S.
Published: June 2011

Background and Purpose
—A number of studies have examined the relationship between genetic platelet glycoprotein variants and early-onset atherothrombotic disease, particularly acute myocardial infarction. Data on the association of these genetic susceptibility markers with ischemic stroke are more limited, and their role in hemorrhagic stroke has not been previously examined.

Methods
—We performed genotype analysis for 5 common diallelic platelet glycoprotein polymorphisms in a population-based study of 78 white women aged <45 years with arterial stroke (36 ischemic cases and 42 hemorrhagic cases) and 346 demographically similar control subjects.

Results
—The 807T variant of glycoprotein Ia was associated with a 2-fold increased risk of ischemic stroke (age-adjusted odds ratio [OR]=2.24; 95% CI=0.99 to 5.06). The Met
145
allele of glycoprotein Ibα was associated with a trend toward an increased risk of ischemic stroke that was more pronounced in the homozygous state (OR=10.36), but the CI is extremely wide because of the small numbers of subjects (95% CI=1.43 to 79.34). Homozygosity for the Ser
843
allele of the glycoprotein IIb was associated with an ≈5-fold increased risk of ischemic stroke among subgroups of women who carried a diagnosis of hypertension or diabetes (OR=4.51; 95% CI=1.01 to 20.13) or had elevated plasma homocysteine levels (OR=5.94; 95% CI=1.53 to 23.05). The genotype distributions for all 5 platelet glycoprotein polymorphisms were similar among hemorrhagic stroke cases and controls.

Conclusions
—Several inherited platelet glycoprotein variants may be associated with an increased risk of ischemic stroke in young women. These associations seemed to be confined to women with other cardiovascular risk factors. Additional studies involving larger numbers of subjects are needed to confirm these preliminary findings.
Association Between the Glu298Asp Polymorphism in the Endothelial Constitutive Nitric Oxide Synthase Gene and Brain Infarction
Authors: Elbaz Alexis , Poirier Odette , Moulin Thierry , Chédru François , Cambien François , Amarenco Pierre
Published: June 2011

Background and Purpose
—Nitric oxide (NO) synthesized by endothelial constitutive NO synthase (ecNOS) plays a key role in vascular regulation and atherosclerosis. Little is known concerning the role of the ecNOS gene (
NOS3
) as a risk factor for brain infarction (BI). Our aim was to investigate the relation between the Glu298Asp polymorphism in exon 7 of
NOS3
with BI and its subtypes.

Methods
—Patients (n=460; cases) with BI were consecutively recruited and classified into etiological subtypes. Control subjects (n=460; controls) without a history of stroke were recruited among individuals hospitalized at the same institutions and individually matched on age, sex, and center. Genotypes of the polymorphism were determined by polymerase chain reaction.

Results
—The distribution of genotypes was significantly different between cases and controls (
P
=0.008); the
GG
genotype was more frequent in cases (46.1%) than in controls (35.4%; OR, 1.56; 95% CI, 1.19 to 2.04). Among subtypes, the frequency of the
GG
genotype was significantly higher in cases than in controls in the lacunar subtype (OR, 2.00; 95% CI, 1.05 to 3.80); in this group, the relation between BI and LDL level was stronger among carriers of the
GG
genotype than among noncarriers (
P
for interaction, 0.05).

Conclusions
—Homozygosity for the
G
allele of the Glu298Asp polymorphism in
NOS3
was associated with BI, and especially with lacunar stroke. Our findings suggest that genetic susceptibility and LDL cholesterol have a synergistic relation. Although these findings should be replicated in a larger sample of subjects and the functionality of the Glu298Asp polymorphism has not been established, these results may help us to understand the cause of the arteriolopathy underlying lacunae and have future implications in their treatment and prevention.
Stimulated Acoustic Emission Detected by Transcranial Color Doppler Ultrasound
Authors: Pohl Christoph , Tiemann Klaus , Schlosser Thomas , Becher Harald
Published: June 2011

Background and Purpose
—Experimental and clinical data suggest that insonation of echo-contrast agents with high acoustical power produces disintegration of microbubbles, resulting in a pseudo-Doppler phenomenon called stimulated acoustic emission (SAE). The purpose of this study was to investigate whether SAE might be detected by transcranial color Doppler imaging and whether these signals might be used for cerebral tissue perfusion measurements.

Methods
—Nonmoving microbubbles (SHU 563 A) were insonated in vitro through the temporal parts of a human cadaver skull, and contrast signals were detected by velocity-coded color Doppler and power Doppler recordings. Transcranial color as well as power Doppler investigations were performed in 10 healthy volunteers with the echo-contrast agent Levovist (SHU 508 A).

Results
—Color Doppler signals indicating SAE were observed in vitro and in transcranial human investigations. These signals were characterized by a mosaic of color Doppler pixels ranging over the full color scale. Apparent velocity information and spatial distribution of SAE signals changed from image frame to image frame. In the experimental model, the intensity of SAE signals decreased exponentially over time. With an increase of acoustic power, there was a significant increase of the maximum signal intensity (
P
<0.01) and a significantly shortened signal duration (
P
<0.01), consistent with stronger and more rapid disintegration. In humans, SAE signals were clearly detected in cerebral tissue regions. The intensity of SAE signals in those regions (eg, temporal cortex, 3.7±1.2 dB) was ≈8 times lower than the signal enhancement in the major cerebral arteries (eg, in the MCA, 29.5±5.6).

Conclusions
—Echo-contrast specific color Doppler signals known as SAE are detectable by transcranial color and power Doppler sonography. Signals due to SAE might represent tissue perfusion, thereby providing a method for imaging flow with transcranial ultrasound.
MRI Measures of Middle Cerebral Artery Diameter in Conscious Humans During Simulated Orthostasis
Authors: Serrador Jorge M. , Picot Paul A. , Rutt Brian K. , Shoemaker J. Kevin , Bondar Roberta L.
Published: June 2011

Background and Purpose
—The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P
ET
CO
2
) on MCA diameter and CFV.

Methods
—Twelve subjects participated in a CO
2
manipulation protocol and/or an LBNP protocol. In the CO
2
manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO
2
(hypercapnia), or they hyperventilated to ≈25 mm Hg P
ET
CO
2
(hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of −20 and −40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols.

Results
—Compared with normocapnia, hypercapnia produced increases in both P
ET
CO
2
(from 36±3 to 40±4 mm Hg,
P
<0.05) and CFV (from 63±4 to 80±6 cm/s,
P
<0.001) but did not change MCA diameters (from 2.9±0.3 to 2.8±0.3 mm). Hypocapnia produced decreases in both P
ET
CO
2
(24±2 mm Hg,
P
<0.005) and CFV (43±7 cm/s,
P
<0.001) compared with normocapnia, with no change in MCA diameters (from 2.9±0.3 to 2.9±0.4 mm). During −40 mm Hg LBNP, P
ET
CO
2
was not changed, but CFV (55±4 cm/s) was reduced from baseline (58±4 cm/s,
P
<0.05), with no change in MCA diameter.

Conclusions
—Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in P
ET
CO
2
.
Hypertonic Saline Worsens Infarct Volume After Transient Focal Ischemia in Rats
Authors: Bhardwaj Anish , Harukuni Izumi , Murphy Stephanie J. , Alkayed Nabil J. , Crain Barbara J. , Koehler Raymond C. , Hurn Patricia D. , Traystman Richard J.
Published: June 2011

Background and Purpose
—Hypertonic saline (HS) has been advocated as a hyperosmolar agent for the treatment of cerebral edema, especially after traumatic brain injury. We tested the hypothesis that continuous intravenous HS administered during reperfusion from transient focal cerebral ischemia attenuates infarct volume.

Methods
—Halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. At the onset of reperfusion, rats received a 10-mL/kg intravenous bolus of 0.9% saline (SAL, n=8) or 7.5% SAL (chloride:acetate 50:50, n=8) followed by a continuous infusion for 22 hours. In a second series of experiments, ischemic damage was determined in cohorts treated with equivolumetric 3% saline (n=8) or 20% mannitol (n=8). In a third series, regional cerebral blood flow was measured ([
14
C]iodoantipyrine autoradiography) at 6 hours of reperfusion in 7.5%-SAL–treated (n=5) or SAL-treated (n=5) animals.

Results
—In SAL rats, serum Na
+
was 137±3 and 138±2 mEq/L (mean±SEM) at baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na
+
was 136±2 and 154±2 mEq/L at baseline and reperfusion, respectively. Physiological variables and reduction in laser-Doppler signal during MCAO and early reperfusion were not different between the 2 treatment groups. Cortical infarct volume was larger in 7.5%-SAL–treated rats (121±14 mm
3
; 30±3% of contralateral cortex;
P
<0.05) than in SAL (64±15 mm
3
; 16±4% of contralateral cortex). Striatal infarct volume was unchanged by HS therapy. Ipsilateral cortical tissue volume was increased relative to the contralateral side (by 26±5% with SAL; by 41±5% with 7.5% SAL). In contrast, ischemic damage was unaffected by 3%-SAL or 20%-mannitol treatment compared with SAL. Regional cerebral blood flow during reperfusion was heterogeneous in all animals, but there was no evidence of postischemic hypoperfusion or blood flow maldistribution in 7.5%-SAL–treated animals.

Conclusions
—These data demonstrate that hypernatremia resulting from postischemic HS infusion worsens cortical infarct volume in transient focal cerebral ischemia. The deleterious effect is not linked to exacerbation of delayed hypoperfusion during early reperfusion (6 hours); however, blood flow defects at later recovery time points remain to be excluded. These results may have implications for HS therapy in clinical ischemic stroke.
Facial Palsy in Cerebral Venous Thrombosis
Authors: Straub J. , Magistris M. R. , Delavelle J. , Landis T.
Published: June 2011

Background
—Cranial nerve palsy in cerebral sinovenous thrombosis (CVT) is rare, its pathophysiology remains unclear, and data from electrophysiological examinations in such patients are missing.

Case Description
—We report the case of a 17-year-old woman with familial protein S deficiency who was admitted with extensive multiple CVT. Two weeks after onset of symptoms, she developed isolated right peripheral facial palsy, and MR venography showed segmental occlusion of the ipsilateral transverse sinus. Complete recovery of facial palsy occurred concomitant with recanalization of the transverse sinus. Facial neurography, including transcranial magnetic stimulation of the facial nerve and related motor cortex, ruled out a coincidental idiopathic palsy and revealed conduction block proximal to the facial canal.

Conclusions
—Facial palsy in our patient was caused by transient neurapraxia in the intracranial segment of the nerve. We suggest that elevated venous transmural pressure in the nerve’s satellite vein, which belongs to the affected drainage territory of the transverse sinus, might have caused venous blood-brain barrier dysfunction in the intrinsic vascular system of the nerve, with leakage of fluids and ions into the endoneurial space and thus an increase in interstitial resistance.
Thienopyridines or Aspirin to Prevent Stroke and Other Serious Vascular Events in Patients at High Risk of Vascular Disease?
Authors: Hankey Graeme J. , Sudlow Cathie L. M. , Dunbabin David W.
Published: June 2011

Background and Purpose
—Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety.

Methods
—We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash.

Results
—In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0.98; 2
P
=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for ≈2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by ≈2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia.

Conclusions
—The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.
Intracranial Hemorrhage Associated With Thrombolytic Therapy for Elderly Patients With Acute Myocardial Infarction
Authors: Brass Lawrence M. , Lichtman Judith H. , Wang Yun , Gurwitz Jerry H. , Radford Martha J. , Krumholz Harlan M.
Published: June 2011

Background and Purpose
—Intracranial hemorrhage is a serious complication of thrombolytic therapy for acute myocardial infarction, especially among the elderly, but little information exists on estimating risk. Better estimation of risk in individual patients may allow for withholding or using alternate therapies among those at highest risk.

Methods
—To quantify the risk and identify predictors of intracranial hemorrhage associated with thrombolytic therapy, we performed a retrospective cohort study using data from medical charts. The study involved nearly all acute-care hospitals in the United States. All Medicare patients discharged with a principal diagnosis of acute myocardial infarction during a 9-month period in 1994 to 1995 were included. The main outcome measure was intracranial hemorrhage among those treated with thrombolytic therapy.

Results
—The rate of intracranial hemorrhage was 1.43% (455 of 31 732). In a logistic model, age ≥75 years, female, black race, prior stroke, blood pressure ≥160 mm Hg, tissue plasminogen activator (versus other thrombolytic agent), excessive anticoagulation (international normalized ratio ≥4 or prothrombin time ≥24), and below median weight (≤65 kg for women; ≤80 kg for men) were independent predictors. A risk stratification scale was developed on the basis of these factors: with none or 1 of the factors (n=6651), the rate of intracranial hemorrhage was 0.69%; with 2 factors (n=10 509), 1.02%; with 3 factors (n=9074), 1.63%; with 4 factors (n=4298), 2.49%; and with ≥5 factors (n=1071), 4.11% (Mantel-Haenszel;
P
<0.001).

Conclusions
—The rate of intracranial hemorrhage in older patients after treatment with thrombolytic therapy exceeds 1%. Readily available factors can identify elderly patients with acute myocardial infarction at high and low risk for intracranial hemorrhage associated with thrombolytic therapy.
Fluoxetine in Early Poststroke Depression
Authors: Wiart L. , Petit H. , Joseph P. A. , Mazaux J. M. , Barat M.
Published: June 2011

Background and Purpose
—Early poststroke depression (PSD) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients. This trial was designed to study the efficacy and tolerance of fluoxetine (FLX) in the treatment of early PSD.

Methods
—This was a multicenter, double-blind, placebo-controlled study. Recent hemiplegic patients (<3 months) suffering from major depressive disorder (determined by International Classification of Diseases, 10th Revision, and Montgomery-Asberg Depression Rating Scale [MADRS] >19) were randomized to receive either 20 mg/d fluoxetine (FLX) or placebo for 6 weeks. Patients were evaluated by use of the Motricity Index, Mini-Mental State Examination, Functional Independence Measure, and MADRS. Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 (baseline) and days 15, 30, and 45 (end point).

Results
—Of 121 patients screened, 31 were included in the study, 16 in the FLX group and 15 in the placebo group. There were no significant differences in baseline characteristics among the 2 groups. The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point (11.8±6.7 [mean±SD] versus 18.7±10.0, respectively;
P
=0.05). FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate (62.5% versus 33.3%, respectively) and greater mean decrease of MADRS (16.6 versus 8.4, respectively;
P
=0.02). There were no differences in motor, cognitive, or functional improvement and no significant side effects after FLX treatment, except for a patient with a moderate and transient increase of transaminases.

Conclusions
—FLX is an efficacious and well-tolerated treatment for early PSD. Further research is needed to evaluate the efficacy and safety of long-term treatment in this population.
Sex Differences and Similarities in the Management and Outcome of Stroke Patients
Authors: Holroyd-Leduc Jayna M. , Kapral Moira K. , Austin Peter C. , Tu Jack V.
Published: June 2011

Background and Purpose
—Previous studies have documented sex differences in the management and outcome of patients with cardiovascular disease. However, little data exist on whether similar sex differences exist in stroke patients. We conducted a study to determine whether sex differences exist in patients with acute stroke admitted to Ontario hospitals.

Methods
—Using linked administrative databases, we performed a population-based cohort study. The databases contained information on all 44 832 patients discharged from acute-care hospitals in Ontario between April 1993 and March 1996 with a most responsible diagnosis of acute stroke. The main outcomes measured consisted of sex differences in comorbidities, the use of rehabilitative services, the use of antiplatelet therapy and anticoagulants (in elderly stroke survivors aged ≥65 years only), discharge destination, and mortality.

Results
—Male stroke patients were more likely than female stroke patients to have a history of ischemic heart disease (18.1% versus 15.3%, respectively;
P
<0.001) and diabetes mellitus (20.1% versus 18.7%, respectively;
P
<0.001), whereas female patients were more likely than male patients to have hypertension (33.8% versus 30.0%, respectively;
P
<0.001) and atrial fibrillation (12.9% versus 10.2%, respectively;
P
<0.001). There were no sex differences in the usage of in-hospital rehabilitative services. The overall 90-day postdischarge use of aspirin and ticlopidine was similar in stroke survivors aged 65 to 84 years. However, among stroke survivors aged ≥85 years, men were more likely than women to receive aspirin (36.0% versus 30.7%, respectively;
P
<0.001) and ticlopidine (9.2% versus 6.8%, respectively;
P
=0.007). Use of warfarin was similar for the two sexes. Men were more likely than women to be discharged home (50.6% versus 40.9%, respectively;
P
<0.001) and less likely to be discharged to chronic care facilities (16.8% versus 25.2%, respectively;
P
<0.001). The risk of death 1 year after stroke was somewhat lower in women than men (adjusted odds ratio 0.939, 95% CI 0.899 to 0.980;
P
=0.004). The mortality differences were greatest among elderly stroke patients.

Conclusions
—Elderly men are more likely than elderly women to receive aspirin and ticlopidine and equally like to receive warfarin after a stroke. Despite these differences, elderly women have a better 1-year survival after a stroke.
HDL-Cholesterol, Total Cholesterol, and the Risk of Stroke in Middle-Aged British Men
Authors: Wannamethee S. Goya , Shaper A. Gerald , Ebrahim S.
Published: June 2011

Background and Purpose
—The purpose of this study was to examine the relation between serum HDL cholesterol and total cholesterol and risk of stroke.

Methods
—We carried out a prospective study in 7735 men, 40 to 59 years of age, drawn from 1 group practice in each of 24 British towns. Men with history of stroke were excluded (n=52).

Results
—During the mean follow-up period of 16.8 years, there were 343 stroke cases (fatal and nonfatal) in the 7683 men with no history of stroke. Higher levels of HDL cholesterol were associated with a significant decrease in risk of stroke even after adjustment for potential confounders (top fifth versus lowest fifth: adjusted relative risk=0.68, 95% CI 0.46 to 0.99). The inverse relation was seen only for nonfatal strokes (adjusted relative risk=0.59, 95% CI 0.39 to 0.90; top fifth versus lowest fifth). Total cholesterol showed no graded association with fatal strokes, but men with levels ≥8.1 mmol/L (top 5% of the distribution) showed increased risk of nonfatal stroke, although this was not statistically significant after adjustment (adjusted RR=1.46, 95% CI 0.91 to 2.32). The beneficial effects of elevated HDL cholesterol on nonfatal stroke were seen in both smokers and nonsmokers and were more evident in men with hypertension than in normotensives. In hypertensive men, elevated HDL cholesterol (top fifth) was associated with a significant 50% reduction in risk of nonfatal strokes compared with men in the lowest fifth.

Conclusions
—Higher levels of HDL cholesterol were associated with a significant decrease in risk of nonfatal stroke. In contrast, elevated total cholesterol showed a weak positive association with nonfatal strokes. The marked inverse association between HDL cholesterol and stroke seen in hypertensives emphasizes the importance of those modifiable risk factors for stroke known to lower the concentrations of HDL cholesterol.
An Objective Characterization of Atherosclerotic Lesion
Authors: Aly Sayed , Bishop Christopher C.
Published: June 2011

Background and Purpose
—The aim of this study was to evaluate a computer-assisted technique to characterize atherosclerotic plaque.

Methods
—In 9 subjects (7 men, 2 women; mean age 33 years), known anatomic areas (carotid, fat, muscle, iliotibial tract, and tibia) were scanned with an Acuson duplex ultrasound machine with 72 machine settings. The ultrasound images of these anatomic areas were recorded on magneto-optical disks. Echo amplitude statistics were obtained, and the mean pixel value (MPV) was used to assess the level of echogenicity. The ideal settings of this particular scanner for optimal discrimination between these tissues types were identified by the Heuristic Index of Discrimination. With these settings, carotid artery scanning was performed on 17 patients (15 men, 2 women; mean age 65 years), and the image analysis of their ultrasound carotid plaques was compared with their histological findings.

Results
—In this study, discrimination between the selected tissues was found to be optimal when the controls were set at log 40 dB, 0/2/0, and gain of −5 dB. The MPV of the carotid specimens scanned at this setting correlated significantly with the histological findings (Spearman correlation,
P
=0.002).

Conclusions
—Computer-assisted image analysis to give the MPV is a technique that may be used to identify unstable atherosclerotic plaques reliably.
Randomized Controlled Trial of Integrated (Managed) Care Pathway for Stroke Rehabilitation
Authors: Sulch David , Perez Inigo , Melbourn Anne , Kalra Lalit
Published: June 2011

Background and Purpose
—Integrated Care Pathway (ICP) is an organized, goal-defined, and time-managed plan that has the potential of facilitating timely interdisciplinary coordination, improving discharge planning, and reducing length of hospital stay.

Methods
—An ICP for stroke rehabilitation based on evidence of best practice, professional standards, and existing infrastructure was developed. Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were randomized to receive ICP care coordinated by an experienced nurse (n=76) or conventional multidisciplinary care (n=76).

Results
—The age, sex, premorbid functional ability, and stroke characteristics of the 2 groups were comparable. There were no differences in mortality rates (10 [13%] versus 6 [8%]), institutionalization (10 [13%] versus 16 [21%]), or length of hospital stay (50±19 versus 45±23 days) between patients receiving ICP or multidisciplinary care. Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks (median change in Barthel Activities of Daily Living Index 6 versus 2;
P
<0.01) and had higher Quality of Life scores at 12 weeks (65 versus 59;
P
=0.07) and 6 months (72 versus 63;
P
<0.005). There were no significant differences in the mean duration of physiotherapy (42.8±41.2 versus 39.4±36.4 hours) or occupational therapy (8.5±7.5 versus 8.0±7.5 hours) received between the 2 groups.

Conclusions
—ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit. Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care.
Mutations in the Tropoelastin Gene (ELN) Were Not Found in Patients With Spontaneous Cervical Artery Dissections
Authors: Grond-Ginsbach Caspar , Thomas-Feles Constanze , Werner Inge , Weber Ralf , Wigger Frank , Hausser Ingrid , Brandt Tobias
Published: June 2011

Background and Purpose
—The majority of patients with spontaneous cerebral artery dissection show ultrastructural alterations in dermal collagen and elastic fibers.

Methods
—We studied the gene encoding tropoelastin (ELN) by reverse transcription–polymerase chain reaction and subsequent sequence analysis in 10 patients with abnormalities in their elastic fibers.

Results
—No mutations were found in the whole coding region of the ELN gene. The simultaneous visualization and quantification of ELN splice variants by gene scanning enabled the analysis of the regulation of alternative splicing of ELN mRNA. No differences could be detected between fibroblast cultures of the patients and a control subject.

Conclusions
—Neither mutations in the ELN gene nor dysregulation of its activity appears to be the cause of the connective tissue disorder that is found in most patients with spontaneous dissections.
Serial MRI After Transient Focal Cerebral Ischemia in Rats
Authors: Neumann-Haefelin T. , Kastrup A. , de Crespigny A. , Yenari M. A. , Ringer T. , Sun G. H. , Moseley M. E.
Published: June 2011

Background and Purpose
—With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats.

Methods
—Nineteen Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion of 30 minutes, 60 minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion-weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1-weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as 0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture. Final infarct size was determined histologically at 7 days.

Results
—In the 30-minute ischemia group (and partially also after 60 minutes), DWI abnormalities reversed transiently during the early reperfusion period but recurred after 1 day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI abnormalities no longer reversed, and signal intensity on both DWI and T2-weighted images increased rapidly in the previously ischemic region due to BBB damage (enhancement on postcontrast T1-weighted images) and edema formation. Early BBB damage during reperfusion was found to be predictive of relatively pronounced edema at subacute time points and was probably related to the increased mortality rates in this experimental group (3 of 7).

Conclusions
—Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be mainly complicated by secondary ischemic damage as shown by the delayed recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema becomes a dominant factor with longer occlusion times (2.5 hours).
Brain Stem Stroke Causing Baroreflex Failure and Paroxysmal Hypertension
Authors: Phillips A. M. , Jardine D. L. , Parkin P. J. , Hughes T. , Ikram H.
Published: June 2011

Background
—Paroxysmal neurogenic hypertension has been associated with a variety of diseases affecting the brain stem but has only rarely been reported after brain stem stroke. The mechanism is thought to involve increased sympathetic activity and baroreflex dysfunction. We undertook microneurographic recordings of muscle sympathetic nerve activity (MNSA) during beat-to-beat blood pressure (BP) monitoring to investigate this hypothesis.

Case Description
—We investigated a 75-year-old woman who developed paroxysmal hypertension (BP 220/110 mm Hg) after a large left-sided medullary infarct. The paroxysms were triggered by changes in posture and were accompanied by tachycardia, diaphoresis, and headache. Serum catecholamines were substantially increased (norepinephrine level, 23.9 nmol/L 9 days after stroke; normal level, <3.8 nmol/L), and heart rate variability, measured by spectral analysis, was decreased in both low- and high-frequency domains (0.04 and 0.06 ms
2
, respectively; normal level, 0.14±0.02 ms
2
). MNSA was increased in frequency (61 bursts per minute; normal level, 34±18 bursts per minute), and the burst amplitude was not inversely related to diastolic BP. BP and MNSA responses to cold pressor and isometric handgrip stimuli were intact.

Conclusions
—Extensive unilateral infarction of the brain stem in the region of the nucleus tractus solitarius may result in partial baroreflex dysfunction, increased sympathetic activity, and neurogenic paroxysmal hypertension.
Influence of Raised Plasma Osmolality on Clinical Outcome After Acute Stroke
Authors: Bhalla Ajay , Sankaralingam Suki , Dundas Ruth , Swaminathan R. , Wolfe Charles D. A. , Rudd Anthony G.
Published: June 2011

Background and Purpose
—Abnormal physiological parameters after acute stroke may induce early neurological deterioration. Studies of the effect of dehydration on stroke outcome are limited. We examined the association of raised plasma osmolality on stroke outcome at 3 months and the change of plasma osmolality with hydration during the first week after stroke.

Methods
—Acute stroke patients had their plasma osmolality measured at admission and at days 1, 3, and 7. Maximum plasma osmolality and the area under curve (AUC) were also calculated during the first week. Patients were stratified according to how they were hydrated: orally, intravenously, or both. Outcome included survival at 3 months after stroke. Logistic regression was performed to examine the association between raised plasma osmolality (>296 mOsm/kg) and survival, adjusting for stroke severity. Linear regression was performed to examine the pattern of plasma osmolality across hydration groups.

Results
—One hundred sixty-seven patients were included. Mean admission (300 mOsm/kg, SD 11.4), maximum (308.1 mOsm/kg, SD 17.1), and AUC (298.3 mOsm/kg, SD 11.7) plasma osmolality were significantly higher in those who died compared with survivors (293.1 mOsm/kg [SD 8.2], 297.7 mOsm/kg [SD 8.7], and 291.7 mOsm/kg [SD 8.1], respectively;
P
<0.0001). Admission plasma osmolality >296 mOsm/kg was significantly associated with mortality (OR 2.4, 95% CI 1.0 to 5.9). In patients hydrated intravenously, there was no significant fall in plasma osmolality compared with patients hydrated orally (
P
=0.68).

Conclusions
—Raised plasma osmolality on admission is associated with stroke mortality, after correcting for case mix. Correction of dehydration after stroke requires a more systematic approach. Trials are required to determine whether correcting dehydration after stroke improves outcome.
Noninvasive Cerebrovascular Assessment of Takayasu Arteritis
Authors: Cantú Carlos , Pineda Carlos , Barinagarrementeria Fernando , Salgado Perla , Gurza Alba , Paola de Pablo  , Espinosa Rolando , Martínez-Lavín Manuel
Published: June 2011

Background and Purpose
—Despite prominent neurological symptoms reported in Takayasu arteritis (TA), a complete evaluation of the cerebral circulation has not been consistently performed. The purpose of this study is to describe MR angiography (MRA), color Doppler flow imaging, and transcranial Doppler (TCD) findings in the extracranial and intracranial cerebral arteries in TA.

Methods
—MRA, color Doppler flow imaging, and TCD were performed in 21 patients with TA. Intima-media thickness was measured in the common carotid artery. The correlation between noninvasive studies and panaorto-arteriography was examined for supraortic vessels. Cerebral angiography findings were compared with the noninvasive methods in 7 patients. Intracranial hemodynamic changes detected by TCD were compared with extracranial circulation lesions assessed by panaorto-arteriography.

Results
—Noninvasive vascular techniques showed at least 1 abnormality in the extracranial and/or intracranial cerebral arteries in 20 of 21 patients (95%). Both MRA and color Doppler flow imaging showed a substantial correlation in the ability to detect obstructive lesions in supra-aortic vessels compared with panaorto-arteriography. High-resolution ultrasonography displayed common carotid artery wall thickening in 5 vessels that were considered normal by arteriography. In 24% of patients, MRA and TCD showed abnormalities consistent with stenosis of the basal cerebral arteries. In 10 patients with severe extracranial circulation involvement (detected by arteriography), TCD displayed intracranial hemodynamic changes consisting of dampened or blunted waveforms with low pulsatility.

Conclusions
—The comprehensive assessment of cerebral circulation in TA patients by noninvasive methods allowed the detection of a high rate of diverse vascular abnormalities in both extracranial and intracranial circulation.
Subacute But Not Acute Generation of Nitric Oxide in Focal Cerebral Ischemia
Authors: Fassbender Klaus , Fatar Marc , Ragoschke Andreas , Picard Martin , Bertsch Thomas , Kuehl Sandra , Hennerici Michael
Published: June 2011

Background and Purpose
—Excessive release of nitric oxide (NO) has been implicated in the pathophysiology of neurodegeneration in ischemic stroke. We compared intracerebral release of indicators of NO generation at the acute and subacute stages of transient focal cerebral ischemia.

Methods
—In vivo microdialysis in the rat striatum was performed at the acute (first hours) and subacute (after 24 or 48 hours) stages of cerebral ischemia or sham operation to monitor intracerebral release of the stable NO metabolites nitrite and nitrate.

Results
—Whereas only a nonsignificant trend toward increased release of these NO metabolites was evidenced in acute cerebral ischemia, a significant NO generation was observed subacutely, 48 hours after induction of cerebral ischemia. Aminoguanidine, a selective inhibitor of inducible NO synthase, suppressed this delayed release of nitrite and nitrate.

Conclusions
—Whereas these observations do not support a major NO generation in acute cerebral ischemia, they indicate an inducible NO synthase–dependent NO generation predominantly at the subacute phase of ischemic neurodegeneration. Therefore, NO generation may play a pathophysiological role in delayed ischemic neurodegeneration.
Feasibility and Safety of Inducing Modest Hypothermia in Awake Patients With Acute Stroke Through Surface Cooling: A Case-Control Study
Authors: Kammersgaard L.P. , Rasmussen B.H. , Jørgensen H.S. , Reith J. , Weber U. , Olsen T.S.
Published: June 2011

Background and Purpose
—Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke.

Methods
—We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the “forced air” method, a surface cooling method that uses a cooling blanket with a flow of cool air (10°C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy.

Results
—Body temperature decreased from t
0
=36.8°C to t
6
=35.5°C (
P
<0.001), and hypothermia was present until 4 hours after therapy (t
0
=36.8°C versus t
10
=36.5°C;
P
=0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (
P
=0.50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (
P
=0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses.

Conclusions
—Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the “forced air” method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke.