bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Benefit of Early Recanalization Sustained at 3 Months?
Authors: Labiche Lise A. , Al-Senani Fahmi , Wojner Anne W. , Grotta James C. , Malkoff Marc , Alexandrov Andrei V.
Published: March 2003

Background and Purpose—

Early arterial recanalization can lead to dramatic recovery (DR) during intravenous tissue plasminogen activator (tPA) therapy. However, it remains unclear whether this clinical recovery is sustained 3 months after stroke.

Methods—

We studied consecutive patients treated with intravenous tPA (0.9 mg/kg within 3 hours) who had M1 or proximal M2 middle cerebral artery occlusion on pretreatment transcranial Doppler according to previously validated criteria. Patients were continuously monitored for 2 hours after tPA bolus to determine complete, partial, or no early recanalization with the Thrombolysis in Brain Ischemia (TIBI) flow grading system. A neurologist obtained the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores independently of transcranial Doppler results. DR was defined as a total NIHSS score of 0 to 3 points, and early recovery (ER) was defined improvement by ≥10 points at 2 hours after tPA bolus. Good long-term outcome was defined as an NIHSS score of 0 to 2 or an mRS score of 0 to 1 at 3 months.

Results—

Fifty-four patients with proximal middle cerebral artery occlusion had a median prebolus NIHSS score of 16 (range, 6 to 28; 90% with ≥10 points). The tPA bolus was given at 130±32 minutes (median, 120 minutes; 57% treated within the first 2 hours). DR+ER was observed in 50% of patients with early complete recanalization (n=18), 17% with partial recanalization (n=18), and 0% with no early recanalization (n=18) (
P
=0.025). Overall, DR+ER was observed in 12 patients (22%), and 9 (75%) had good outcome at 3 months in terms of NIHSS (
P
=0.009) and mRS (
P
=0.006) scores compared with non-DR and non-ER patients. If early recanalization was complete, 50% of these patients had good outcome at 3 months, and 78% with DR+ER sustained early clinical benefit. If recanalization was partial, 44% had good long-term outcome, and 66% of patients with DR+ER sustained the benefit. If no early recanalization occurred, 22% had good long-term outcome despite the lack of DR within 2 hours of tPA bolus (
P
=0.046). Mortality was 11%, 11%, and 39% in patients with complete, partial, and no early recanalization, respectively (
P
=0.025). Reasons for not sustaining DR in patients with early recanalization were subsequent symptomatic intracranial hemorrhage and recurrent ischemic stroke.

Conclusions—

DR or ER after recanalization within 2 hours after tPA bolus was sustained at 3 months in most patients (75%) in our study. Complete or partial early recanalization leads to better outcome at 3 months after stroke. Fewer patients achieve good long-term outcome without early recanalization.
Promoter Polymorphism in the Endotoxin Receptor (CD14) Is Associated With Increased Carotid Atherosclerosis Only in Smokers
Authors: Risley Paul , Jerrard-Dunne Paula , Sitzer Matthias , Buehler Alexandra , von Kegler Stefan , Markus Hugh S.
Published: March 2003

Background and Purpose—

The risk of atherosclerosis from endotoxemia is increased in smokers. Endotoxin is a potent mediator of inflammation, and smokers have elevated plasma levels of endotoxin. The endotoxin receptor CD14 can enhance the endotoxin-neutralization capacity of plasma. A functional polymorphism in the promoter region of the CD14 gene (CD14 −159C/T) was studied to determine its impact on common carotid artery (CCA) intima-media thickness (IMT) and any interactions with environmental inflammatory stimuli.

Methods—

A community population (n=992; aged 50 to 65 years) underwent genotypic examination for the CD14 −159 polymorphism by restriction fragment length polymorphism analysis.

Results—

The
CC
genotype was associated with increased CCA IMT. The age- and sex-adjusted odds ratio for IMT above the 75th percentile was 1.63 (95% CI, 1.19 to 2.24;
P
=0.002) and 1.70 (95% CI, 1.18 to 2.44;
P
=0.004) after additional adjustment for conventional risk factors. This gene effect was found only in current smokers and ex-smokers. Multivariate analysis in this group (n=503) increased the odds ratio to 2.02 (95% CI, 1.23 to 3.34;
P
=0.006). No significant interactions were found in nonsmokers or with alcohol consumption.

Conclusions—

The CD14 −159 polymorphism is associated with increased CCA IMT in smokers from a general population. CD14 may modulate the inflammatory effects of smoking in atherogenesis.
Neuroprotective Effect of SolCD39, a Novel Platelet Aggregation Inhibitor, on Transient Middle Cerebral Artery Occlusion in Rats
Authors: Belayev Ludmila , Khoutorova Larissa , Deisher Theresa A. , Belayev Andrey , Busto Raul , Zhang Yongbo , Zhao Weizhao , Ginsberg Myron D.
Published: March 2003

Background and Purpose—

SolCD39 is a soluble form of recombinant human ecto-ATP/ADPase (NTPDase1) and represents a new class of antithrombotic agents. SolCD39 blocks and reverses platelet activation, preventing recruitment of additional platelets into a growing thrombus. The purpose of this study was to examine the effect of solCD39 on neurological deficit, infarct size, and extent of edema after transient middle cerebral artery occlusion (MCAO) in rats.

Methods—

Physiologically controlled Sprague-Dawley rats underwent 2-hour MCAO by retrograde insertion of an intraluminal suture coated with poly-
l
-lysine. The agent (solCD39) was administered intravenously before MCAO or at 1-hour or 3-hour recirculation. Other groups received vehicle (Tris-buffered saline) or human albumin (as a “positive” neuroprotective control; 25%, 0.5% of body weight) at 1-hour recirculation. Neurological status was evaluated during occlusion (at 60 minutes) and daily for 3 days after MCAO. Brains were perfusion-fixed at 72 hours, and infarct volumes and brain swelling were determined.

Results—

Pretreatment with solCD39 significantly improved the neurological score at 72 hours compared with the vehicle group (4.4±0.6 versus 7.6±0.6, respectively;
P
=0.008). Cortical infarct areas were significantly reduced at multiple levels by pretreatment with solCD39. Total striatal infarct area was also significantly reduced compared with vehicle by both solCD39 pretreatment (48% mean reduction) and solCD39 treatment at 3-hour recirculation (51% mean reduction). Treatment with SolCD39 significantly reduced total infarct volume (corrected for brain swelling) by an average of 71% to 72% when administered either before ischemia or at 3 hours of recirculation compared with vehicle. Treatment with albumin significantly reduced neurological score and total, cortical, and subcortical infarction at multiple levels, as expected.

Conclusions—

Treatment with SolCD39, administered either before or at 3 hours after MCAO, improves neurological score and reduces infarct size compared with vehicle. A pharmacological agent of this type appears to have potential for the treatment of focal ischemic stroke.
Cerebral Vascular Abnormalities in a Murine Model of Hereditary Hemorrhagic Telangiectasia
Authors: Satomi Junichiro , Mount Richard J. , Toporsian Mourad , Paterson Andrew D. , Wallace M. Christopher , Harrison Robert V. , Letarte Michelle
Published: March 2003

Background and Purpose—

Hereditary hemorrhagic telangiectasia type 1 (HHT1) is an autosomal dominant vascular dysplasia caused by mutations in the endoglin gene and characterized by dilated vessels and arteriovenous malformations (AVMs). To understand the etiology of this disorder, we evaluated the cerebral vasculature of endoglin heterozygous (
Eng
+/−
) mice, which represent the only animal model of HHT1.

Methods—

The cerebral vasculature of
Eng
+/−
and
Eng
+/+
mice from C57BL/6 (B6) and 129/Ola (129) strains with a differential susceptibility to HHT1 was studied with corrosion casting. Casts were observed by scanning electron microscopy to detect malformations and evaluate arterial diameters and orientation of endothelial nuclei. Measurements were taken to assess relative constriction at arteriolar branching points and downstream relative dilatation.

Results—

Three of 10
Eng
+/−
mice demonstrated abnormal vascular findings including AVMs, while none of 15
Eng
+/+
mice did. The incidence of relative constriction at arteriolar branching points was significantly less in both
Eng
+/−
groups than in their
Eng
+/+
counterparts. The occurrence of relative dilatation was significantly greater in B6-
Eng
+/−
than in B6-
Eng
+/+
mice. Endothelial nuclei were significantly rounder and deviated more from the direction of blood flow in
Eng
+/−
than in
Eng
+/+
mice.

Conclusions—

Eng
+/−
mice showed significant structural alterations in cerebral blood vessels, indicating that the level of endoglin on endothelium is critical for maintenance of normal vasculature. Since endoglin haploinsufficiency is associated with HHT1, such changes in arteriolar structures might occur in HHT1 patients and predispose them to AVMs and their sequelae.
Hospital-Based Study of the Care and Cost of Acute Ischemic Stroke in Japan
Authors: Yoneda Yukihiro , Uehara Toshiyuki , Yamasaki Hiroshi , Kita Yasushi , Tabuchi Masayasu , Mori Etsuro
Published: March 2003

Background and Purpose—

To evaluate the current status of care and cost of acute ischemic stroke in Japan, we performed a hospital-based analysis at a tertiary emergency hospital with a 24-hour neurology-neurosurgery team and care unit.

Methods—

During the 12-month period of October 2000 to September 2001, we collected data on 179 patients consecutively hospitalized with acute ischemic stroke within 7 days of onset. We examined demographic data, in-hospital care, length of hospital stay, outcome at discharge, and hospital costs. The medical cost data were collected from official hospital medical cost charts, which calculated direct medical costs for beds, staff, examinations, medications, and rehabilitation.

Results—

The mean age was 70 years, and 69% were male. Hospital arrival was within 3 hours of onset in 30% of the patients. A history of stroke was present in 37%. The mean initial National Institutes of Health Stroke Scale score was 8.3 points (median, 6 points). Using the Trial of Org 10172 in Acute Stroke Treatment classification, 25% were lacunar, 27% were atherothrombotic, 33% were cardioembolic, and 15% were of unknown origin. All patients underwent neuroimaging studies during hospitalization; 96% and 92% underwent CT and MRI with MR angiography, respectively. Antithrombotic medications were given in 94%, none of whom received thrombolysis. A newly licensed neuroprotective agent, edaravone, was given in 16%. More than half of the patients (55%) were initially admitted to the neurological intensive care unit. Overall, 64% received in-hospital rehabilitation. Mean length of stay was 33 days. In-hospital mortality rate was 3%. On the modified Rankin Scale (mRS), 63% were independent (mRS, 0 to 2) and 34% were dependent (mRS, 3 to 5) at discharge. Two thirds of the patients (65%) went directly back home. The mean hospital cost per patient was $6887 ($209/d), of which 69% was attributable to the costs for beds and staff, 12% for medications, 7% for rehabilitation, 6% for imaging studies, 5% for laboratory examinations, and 1% for other costs.

Conclusions—

Despite the single hospital-based analysis, this study provided current, precise data on short-term inpatient care and costs of acute ischemic stroke in Japan. Because stroke often carries a permanent dependence, long-term cost-effective stroke care should be established.
l
-Arginine Improves Diminished Cerebral CO
2
Reactivity in Patients
Authors: Zimmermann C. , Haberl R.L.
Published: March 2003

Background and Purpose—

There is experimental evidence that
l
-arginine restores diminished CO
2
reactivity after mild traumatic brain injury in rats. This effect is believed to be mediated by
l
-arginine–derived nitric oxide, which is a permissive substrate for CO
2
reactivity. To clarify whether these findings can be transferred to the clinical situation and have beneficial effects in patients, we studied the effects of
l
-arginine on CO
2
reactivity of the cerebral vessels in patients with impaired vasomotor reactivity (VMR) and compared them with patients with normal VMR.

Methods—

Twenty-two patients with cardiovascular risk factors and VMR <50% with no extracranial or intracranial stenoses were examined by bilateral transcranial Doppler sonography of the right and left middle cerebral arteries and compared with 20 age- and risk-matched patients with normal VMR (>50%). VMR was tested by 1-minute hyperventilation, followed by a 3-minute inhalation of 5% CO
2
. Examinations were performed before and after infusion of 30 g
l
-arginine over 30 minutes. The 22 patients with reduced VMR (<50%) were compared with 20 patients with normal VMR (>50%).

Results—

Initial mean VMR of the 42 patients was 50±12%. There was no difference between the right- and the left-side VMR. In the 22 patients with reduced VMR in the first examination (42±8%), VMR increased significantly after infusion of
l
-arginine (52±14%,
P
=0.005). In contrast, values did not change after infusion of
l
-arginine in the 20 patients with normal VMR (59±8% before versus 59±13% after
l
-arginine). There was a negative correlation of initial CO
2
vasoreactivity and the percentage of VMR increase after infusion of
l
-arginine.

Conclusions—

Our data support the hypothesis that in humans
l
-arginine is able to improve impaired CO
2
reactivity of the cerebral vessels. This effect can be found in patients at cardiovascular risk with impaired VMR and might have therapeutic implications in the future.
Dipyridamole Enhances NO/cGMP-Mediated Vasodilator-Stimulated Phosphoprotein Phosphorylation and Signaling in Human Platelets
Authors: Aktas Barsom , Utz Andrea , Hoenig-Liedl Petra , Walter Ulrich , Geiger Joerg
Published: March 2003

Background and Purpose—

Dipyridamole and in particular dipyridamole in combination with low-dose aspirin are very effective in preventing recurrent stroke. However, the mechanism(s) underlying this dipyridamole effect have not been elucidated. Since dipyridamole inhibits the cGMP-specific phosphodiesterase type V in vitro, we hypothesized and tested whether therapeutically relevant dipyridamole concentrations enhance NO/cGMP-mediated effects in intact human platelets studied ex vivo.

Methods—

Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), an established marker of NO/cGMP effects in human platelets, was quantified by phosphorylation-specific antibodies and Western blots. Serotonin secretion and thromboxane synthase activity were determined by fluorometric quantification of derivatized serotonin and synthase products, respectively.

Results—

Endothelium-derived factors such as NO and prostaglandin I
2
are known to elevate both cGMP and cAMP levels with concomitant platelet inhibition and VASP phosphorylation. In our in vitro experiments, therapeutically relevant concentrations (3.5 μmol/L) of dipyridamole amplified only cGMP-mediated VASP phosphorylation due to the NO donor sodium nitroprusside, but not cAMP-mediated effects. Furthermore, thromboxane synthase activity and serotonin secretion, events important for initial platelet activation, were inhibited by sodium nitroprusside, an effect also enhanced by dipyridamole, demonstrating the functional relevance of these observations. Finally, the ex vivo enhancement of NO/cGMP effects was also observed with platelets obtained from healthy volunteers treated with extended-release dipyridamole.

Conclusions—

Under therapeutically relevant conditions, dipyridamole enhances platelet inhibition by amplifying the signaling of the NO donor sodium nitroprusside. These data support the concept that enhancement of endothelium-dependent NO/cGMP-mediated signaling may be an important in vivo component of dipyridamole action.
Serial FLAIR Imaging After Gd-DTPA Contrast
Authors: Rumpel Helmut , Chan Ling Ling
Published: March 2003

Background—

Most MRI protocols for stroke trials comprise 2 successive fluid-attenuated inversion-recovery (FLAIR) imaging acquisitions in which the first scan is done pre–Gd-DTPA contrast while the second is within the contrast clearance window.

Summary of Report—

A 68-year-old male was diagnosed as having hyperacute right middle cerebral artery infarct and a subacute chronic small left occipital cortical infarct. The latter turned from hypointense to strikingly hyperintense on the second FLAIR image, resembling the picture of an acute-on-chronic infarction or hemorrhage. However, the second DWI and CT refuted either of these.

Conclusions—

Image contrast using FLAIR in acute stroke trial imaging may also be affected by T1 effects of Gd-DTPA in chronic infarcts.
Use of a Field-to-Stroke Center Helicopter Transport Program to Extend Thrombolytic Therapy to Rural Residents
Authors: Silliman Scott L. , Quinn Barbara , Huggett Vicki , Merino José G.
Published: March 2003

Background and Purpose—

Giving stroke victims who reside outside communities with hospitals that can administer tissue plasminogen activator (rtPA) access to thrombolytic therapy is a challenge. Helicopter transport to a stroke center is a potential way to make rtPA available to these communities. We examined the experience of the Shands-Jacksonville Acute Stroke Transport Program, a field-to-stroke center helicopter transport program that serves rural counties in the northeastern Florida/southeastern Georgia region.

Methods—

Prospectively collected data of 111 consecutive helicopter transports to Shands-Jacksonville, from an 11-county region, over a 3-year period were reviewed.

Results—

Eighty-five patients (76%) had a cerebrovascular event. Forty-seven patients (42%) had an ischemic stroke, 19 (17%) had a transient ischemic attack, and 19 (17%) had a hemorrhagic stroke. Thrombolytic therapy was administered to 18 ischemic stroke patients (38%), with 15 being treated intravenously. Three patients who arrived beyond the 3-hour window were treated intra-arterially. Average field-to-hospital distance for all patients was 29.4 miles (range, 11 to 90 miles). Most patients (n=65) arrived within 135 minutes from symptom onset.

Conclusions—

A helicopter-based transport system can link a rural region to a stroke center and promote access to thrombolytic therapy.
Midazolam Challenge Reinduces Neurological Deficits After Transient Ischemic Attack
Authors: Lazar Ronald M. , Fitzsimmons Brian-Fred , Marshall Randolph S. , Mohr J.P. , Berman Mitchell F.
Published: March 2003

Background and Purpose—

A transient ischemic attack (TIA) in the brain is classically considered a syndrome lasting <24 hours. Having previously shown that an experimental challenge with the GABA
A
agonist midazolam in recovered stroke patients can reinduce the acute clinical state, we determined whether TIA patients would demonstrate a similar effect.

Methods—

Four right-handed patients participated: 3 with clinical TIA presumed to have affected the left hemisphere within the previous 24 to 72 hours and no evidence of a new lesion on diffusion-weighted and fluid-attenuated inversion recovery imaging, and 1 patient with an asymptomatic temporal arteriovenous malformation. The TIA duration ranged from 30 minutes to 3 hours. Each patient underwent baseline testing for motor function and aphasia, after which intravenous midazolam was delivered until mild drowsiness was detected. Patients were tested during the peak drug effect and again after 2 hours when sedation had dissipated.

Results—

No patient showed weakness or aphasia at baseline. After administration of midazolam, all 3 TIA patients demonstrated re-emergence of features that characterized their recent transient neurological syndromes (right-sided weakness and/or aphasia) but no left-sided findings. The arteriovenous malformation patient who had never been symptomatic showed no drug effect. Two hours later, all TIA patients returned to their normal clinical state.

Conclusions—

Patients who had suffered recent transient cerebral ischemic episodes and were neurologically intact with negative diffusion-weighted imaging showed re-emergence of prior focal deficits after administration of a benzodiazepine in a dose that produces light sedation. These findings suggest that presumed TIA may produce neuronal dysfunction beyond the symptomatic period.
Quality Improvement and Tissue-Type Plasminogen Activator for Acute Ischemic Stroke
Authors: Katzan Irene L. , Hammer Maxim D. , Furlan Anthony J. , Hixson Eric D. , Nadzam Deborah M.
Published: March 2003

Background and Purpose—

A systematic audit of intravenous tissue-type plasminogen activator (tPA) use and stroke outcomes in Cleveland, Ohio, during 1997–1998 demonstrated higher rates of symptomatic intracranial hemorrhage (ICH) than reported in the National Institute of Neurological Disorders and Stroke (NINDS) trial. We now report updated results of intravenous tPA use in the Cleveland Clinic Health System (CCHS).

Methods—

A stroke quality improvement program was initiated in the 9-hospital CCHS in 1999. A retrospective chart review for all stroke patients with primary
International Classification of Diseases, Ninth Revision, Clinical Modification
diagnosis codes 434 and 436 admitted to the 9 hospitals from June 1999 to June 2000 was used to determine outcomes of patients treated with intravenous tPA.

Results—

Intravenous tPA was given to 18.8% of patients arriving within 3 hours of symptom onset. Protocol deviations occurred in 19.1% of patients given intravenous tPA. The symptomatic ICH rate was 6.4%.

Conclusions—

Since 1997, intravenous tPA use has increased, while the rates of symptomatic ICH and protocol deviations have decreased in the CCHS. The CCHS symptomatic ICH rate is now similar to that reported in the NINDS trial. These improvements occurred after initiation of a stroke quality improvement program.
Telemedicine for Acute Stroke
Authors: LaMonte Marian P. , Bahouth Mona N. , Hu Peter , Pathan Mohammed Y. , Yarbrough Karen L. , Gunawardane Ruwani , Crarey Patrick , Page Wesley
Published: March 2003

Background and Purpose—

Telemedicine is emerging as a potential timesaving, efficient means for evaluating patients experiencing acute stroke. In areas where local stroke care specialists are not available, telemedicine can link an emergency department physician with a specialist in a stroke treatment center. This consultation provides an opportunity for administration of thrombolytic drugs within the short therapeutic time window associated with ischemic stroke. Here, we describe our stroke treatment center experiences and report safe administration of recombinant tissue plasminogen activator (rtPA) during telemedicine consultation.

Methods—

The University of Maryland Medical Center uses a triplexed integrated services digital network line providing a 30–frames-per-second video link to St Mary’s Hospital >100 miles away. The system uses a pan, tilt, and zoom camera with remote site control, allowing 2-way, real-time, audiovisual communication and CT image transfer. We retrospectively reviewed all acute stroke consultations provided to St Mary’s Hospital between 1999 and 2001.

Results—

We reviewed 50 consultations. Of the 50, 23 were attempted through telemedicine linkage, and 27 were by traditional telephone conversation, followed by transfer. Of the 23 telemedicine consultations, 2 were aborted because of technical difficulties. Of the patients evaluated by traditional means, 1 of 27 (3.8%) received intravenous rtPA; 5 of 21 (23.8%) received rtPA after telemedicine consultation. No patients experienced complications.

Conclusions—

Telemedicine consultation provided treatment options not previously available at the remote hospital. Administration of rtPA during telemedicine consultation was feasible and safe, and the system was well received. Lack of reimbursement for telemedicine services will hinder widespread adaptation of this promising technology for remote acute stroke treatment.
Administration of Melatonin After Onset of Ischemia Reduces the Volume of Cerebral Infarction in a Rat Middle Cerebral Artery Occlusion Stroke Model
Authors: Pei Zhong , Pang Shiu Fun , Cheung Raymond Tak Fai
Published: March 2003

Background and Purpose—

In both permanent and transient 3-hour middle cerebral artery occlusion rat stroke models, a single intraperitoneal injection of melatonin at 5 or 15 mg/kg given before ischemia was shown to reduce infarct volume at 72 hours. The present study was conducted to examine the treatment time window when melatonin was commenced after onset of ischemia.

Methods—

Adult male Sprague-Dawley rats were anesthetized to undergo right-sided middle cerebral artery occlusion for 3 hours. A single intraperitoneal injection of vehicle or melatonin at 5 mg/kg was given at 0, 1, or 3 hours after onset of ischemia. Other groups received multiple injections of vehicle or melatonin at 5 mg/kg with the first injection given at 1, 2, or 3 hours after onset of ischemia and the second and third injections at 24 and 48 hours, respectively. Multiple injections of melatonin at 15 mg/kg with the first injection given at 3 hours were also made. The infarct volume was determined at 72 hours.

Results—

A single dose of melatonin at 5 mg/kg given at 0 or 1 but not 3 hours after onset of ischemia reduced the infarct volume. Multiple doses of melatonin at 5 mg/kg also reduced the infarct volume when the first dose was given at 1 or 2 but not 3 hours after onset. Significant hemodynamic effects were not observed.

Conclusions—

Our results indicate that melatonin at 5 mg/kg given as a single injection or multiple injections protects against focal cerebral ischemia when commenced within 2 hours of onset.
Safety and Efficacy of Endovascular Cooling and Rewarming for Induction and Reversal of Hypothermia in Human-Sized Pigs
Authors: Dae Michael W. , Gao Dong Wei , Ursell Philip C. , Stillson Carol A. , Sessler Daniel I.
Published: March 2003

Background and Purpose—

Numerous studies indicate that mild hypothermia provides substantial neuroprotection. However, current systems transfer insufficient heat to rapidly vary core temperature. We thus evaluated the safety and efficacy of endovascular cooling and rewarming for the induction and reversal of hypothermia.

Methods—

In 10 anesthetized pigs (weight, 66±2 kg), a heat-exchange balloon catheter was inserted into the inferior vena cava and used to cool to a core temperature of 32°C and then rewarm to normothermia. Control animals had 38°C saline infused. Venous blood was sampled before, during, and after cooling. Three animals in each group were killed 1 week later, and the lungs and inferior vena cava were removed for gross and microscopic examination. In 5 additional animals, cardiac output was measured during cooling to 32°C.

Results—

Body temperature in the hypothermic animals decreased at a rate of 4.5±0.4°C/h. Animals were subsequently rewarmed to 36.0±0.04°C at 2.5±0.2°C/h. There was no difference in heart rate between hypothermic and control animals, whereas systolic pressure decreased during cooling. Cardiac output was well maintained during cooling. There were no thermal effects on blood elements or blood vessels.

Conclusions—

The endovascular heat-exchange system effectively cooled and rewarmed pigs with large thermal mass without producing any adverse effects on blood elements, blood vessel integrity, or cardiovascular function.
Contrast-Enhanced Three-Dimensional Magnetic Resonance Angiography of Atherosclerotic Internal Carotid Stenosis as the Noninvasive Imaging Modality in Revascularization Decision Making
Authors: Cosottini Mirco , Pingitore Alessandro , Puglioli Michele , Michelassi Maria Chiara , Lupi Giancarlo , Abbruzzese Arturo , Calabrese Rosa , Lombardi Massimo , Parenti Giuliano , Bartolozzi Carlo
Published: March 2003

Background and Purpose—

In patients with severe internal carotid artery stenoses, thromboendarterectomy significantly reduces both ischemic stroke and the risk of more ischemic attacks. Digital subtraction angiography (DSA) is the accepted preoperative test to determine whether a high-grade stenosis is present and requires surgical therapy. However, DSA has a procedural risk of stroke between 0.7% and 1%. An accurate, noninvasive imaging protocol with no risk of severe complications would significantly increase the benefit of surgical treatment. The aims of the study were (1) to evaluate the diagnostic accuracy of contrast-enhanced magnetic resonance angiography (CEMRA) in detecting and grading internal carotid artery stenoses and (2) to assess the misclassification rate of vessels suitable for revascularization by CEMRA.

Methods—

Ninety-two patients with sonographic evidence of neck vessel stenosis were enrolled in the study. All patients were submitted to CEMRA and DSA. CEMRA images were evaluated for the presence of mild, moderate, or severe stenosis and occlusion.

Results—

Sensitivity, specificity, and diagnostic accuracy were 97%, 82%, and 92.5%, respectively. Agreement with DSA was optimal at κ=0.87. The misclassification rate of CEMRA was 3.1% because of its tendency to overestimate the stenosis.

Conclusions—

The high diagnostic accuracy and limited misclassification rate suggest that CEMRA can be considered a powerful tool for the preoperative, noninvasive evaluation of atherosclerotic pathology of carotid arteries.
Occupational Therapy for Stroke Patients
Authors: Steultjens Esther M.J. , Dekker Joost , Bouter Lex M. , van de Nes Jos C.M. , Cup Edith H.C. , van den Ende Cornelia H.M.
Published: March 2003

Background and Purpose—

Occupational therapy (OT) is an important aspect of stroke rehabilitation. The objective of this study was to determine from the available literature whether OT interventions improve outcome for stroke patients.

Methods—

An extensive search in MEDLINE, CINAHL, EMBASE, AMED, and SCISEARCH was performed. Studies with controlled and uncontrolled designs were included. Seven intervention categories were distinguished and separately analyzed. If a quantitative approach (meta-analysis) of data analysis was not appropriate, a qualitative approach (best-evidence synthesis), based on the type of design, methodological quality, and significant findings of outcome and/or process measures, was performed.

Results—

Thirty-two studies were included in this review, of which 18 were randomized controlled trials. Ten randomized controlled trials had a high methodological quality. For the comprehensive OT intervention, the pooled standardized mean difference for primary activities of daily living (ADL) (0.46; CI, 0.04 to 0.88), extended ADL (0.32; CI, 0.00 to 0.64), and social participation (0.33; CI, 0.03 to 0.62) favored treatment. For the training of skills intervention, some evidence for improvement in primary ADL was found. Insufficient evidence was found to indicate that the provision of splints is effective in decreasing muscle tone.

Conclusions—

This review identified small but significant effect sizes for the efficacy of comprehensive OT on primary ADL, extended ADL, and social participation. These results correspond to the outcome of a systematic review of intensified rehabilitation for stroke patients. The amount of evidence with respect to specific interventions, however, is limited. More research is needed to enable evidence-based OT for stroke patients.
Long-Term Mortality in Cerebrovascular Disease
Authors: Bravata Dawn M. , Ho Shih-Yieh , Brass Lawrence M. , Concato John , Scinto Jeanne , Meehan Thomas P.
Published: March 2003

Background and Purpose—

Stroke is the third leading cause of death in the United States, yet data are limited about the temporal pattern of mortality among patients with cerebrovascular disease. The objectives of this study were to identify predictors of 6-month mortality and to evaluate 5-year mortality in patients with cerebrovascular disease.

Methods—

Our population included fee-for-service Medicare beneficiaries aged ≥65 years who were discharged with an acute ischemic stroke, transient ischemic attack (TIA), or carotid stenosis (
International Classification of Diseases, Ninth Revision, Clinical Modification
codes 433 to 436) from Connecticut acute care hospitals in 1995. This cohort was followed through 2000 by means of part A Medicare claims and Social Security Administration mortality data.

Results—

Among 5123 patients, 4781 survived their hospitalization and were followed for an average of 3.4 years; 670 (14.0%) died within 6 months of discharge, and 2517 (52.6%) died within 5 years. Predictors of 6-month mortality included older age, male sex, increasing comorbidity, discharge not to home, and prior admission within a year of the index hospitalization. The annual mortality rates for year 1 after discharge differed depending on the discharge diagnosis of the index hospitalization: carotid stenosis, 10.6%; TIA, 14.8%; and acute ischemic stroke, 26.4%. The 5-year cumulative mortality rates were as follows: carotid stenosis, 38.3%; TIA, 49.6%; and acute ischemic stroke, 60.0%.

Conclusions—

Mortality after acute ischemic stroke, TIA, and carotid stenosis is substantial. Rates and patterns of mortality differ according to patients’ discharge diagnoses.
Decreased Cerebrospinal Fluid Apolipoprotein E After Subarachnoid Hemorrhage
Authors: Kay Andrew , Petzold Axel , Kerr Mary , Keir Geoff , Thompson Ed , Nicoll James
Published: March 2003

Background and Purpose—

The apolipoprotein E (
APOE
) ε4 allele has been associated with unfavorable outcome after subarachnoid hemorrhage (SAH), suggesting that apoE plays an important role in the response of the brain to SAH. We determined the concentration of apoE in the cerebrospinal fluid (CSF) of patients with SAH and a control group to test the hypothesis that alterations in CSF apoE reflect the response of the brain to SAH and are correlated with the severity of injury and outcome.

Methods—

ApoE and S100B (a marker of brain injury) were measured by ELISA in CSF from a non–brain-injured control group and patients with SAH. The severity of SAH was determined from the Glasgow Coma Scale, and the clinical outcome was determined from the Glasgow Outcome Scale.

Results—

In contrast to increased CSF concentration of S100B, CSF apoE concentration was significantly lower in patients after SAH than in control subjects (Mann-Whitney test,
P
<0.0001). SAH patients with more severe injury and less favorable outcome had lower CSF apoE concentration than did patients with milder injury and better clinical outcome (Fisher exact test,
P
=0.02).

Conclusions—

The concentration of apoE in the CSF decreases after SAH, despite the likely leakage of plasma apoE into the CSF. We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury, where, in view of previous data, it may have a protective role.
Relationship Between Process and Outcome in Stroke Care
Authors: McNaughton Harry , McPherson Kathryn , Taylor William , Weatherall Mark
Published: March 2003

Background and Purpose—

Better processes in stroke care are assumed to lead to better stroke outcomes. We sought to test whether current measures of stroke process are related to measures of stroke outcome.

Methods—

This was a prospective study of consecutive patients with acute stroke admitted to each of the 3 general hospitals in 1 region who were followed up for 12 months after hospital discharge. Process was measured by use of the Royal College of Physicians Stroke Audit Package, and outcomes were measured with a range of disability, health status, handicap, and independence measures, as well as mortality.

Results—

One hundred eighty-one patients were recruited. There was evidence for a relationship between some process variables and outcomes at hospital discharge, but the relationships were generally weak. None of the process variables remained in regression models of functional outcomes at 12 months. The hospital with the best process scores had the worst case mix-adjusted outcomes.

Conclusions—

The link between stroke process and outcome, through the use of currently available measures of process such as the Royal College of Physicians Stroke Audit Package, is not straightforward. Ongoing work may clarify some of these issues and provide guidance to stroke clinicians on how best to improve existing services.
Plasma Lipid Profile and Incident Ischemic Stroke
Authors: Shahar Eyal , Chambless Lloyd E. , Rosamond Wayne D. , Boland Lori L. , Ballantyne Christie M. , McGovern Paul G. , Sharrett A. Richey
Published: March 2003

Background and Purpose—

The role of circulating lipids and lipoproteins in the pathogenesis of ischemic stroke remains uncertain despite 3 decades of research. We examined this issue in a large population-based cohort.

Methods—

Between 1987 and 1989, 14 175 middle-aged men and women, free of clinical cardiovascular disease, took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study cohort. Baseline measurements included plasma levels of LDL cholesterol, HDL cholesterol, apolipoprotein B, apolipoprotein A-1, and triglycerides and myriad risk factors for cardiovascular disease. The cohort was followed for cardiovascular disease end points.

Results—

Over an average follow-up of 10 years (142 704 person-years at risk), we documented clinical ischemic stroke in 305 participants (161 men and 144 women). After multivariable adjustment for stroke risk factors, categorical and spline regression analyses of the entire sample, as well as the sample of men alone, revealed weak and inconsistent associations between ischemic stroke and each of the 5 lipid factors. Among women, the most consistent findings were decreasing risk of ischemic stroke within the top half of the distribution of HDL cholesterol and increasing risk within the lower range of the triglyceride distribution.

Conclusions—

The relation of circulating cholesterol to ischemic stroke does not resemble its well-known relation to coronary heart disease. Either the pathogenesis of a substantial proportion of ischemic strokes does not involve classic atherosclerotic mechanisms, or the effect of plasma lipids on atherogenesis is substantially different in the intracranial vascular bed.
Aspirin Inhibits p44/42 Mitogen-Activated Protein Kinase and Is Protective Against Hypoxia/Reoxygenation Neuronal Damage
Authors: Vartiainen Nina , Goldsteins Gundars , Keksa-Goldsteine Velta , Chan Pak H. , Koistinaho Jari
Published: March 2003

Background and Purpose—

Acetylsalicylic acid (ASA) is preventive against stroke and protects against focal brain ischemia in rats. We studied the mechanisms of the manner in which ASA provides neuroprotection against hypoxia/reoxygenation (H/R) injury.

Methods—

Spinal cord cultures exposed to 20 hours of hypoxia followed by reoxygenation were treated with a vehicle, ASA or inhibitors of inducible nitric oxide synthase (iNOS), mitogen-activated protein kinases p38 MAPK and ERK1/2, or an
N
-methyl-
d
-aspartic acid (NMDA) receptor antagonist. Cell viability was assessed by LDH release measurement and cell counts. Prostaglandin production was measured by enzyme immunoassay, MAPK signaling by immunoblotting, and DNA binding of nuclear factor-κB (NF-κB) and activating protein-1 (AP-1) by electrophoretic mobility shift assay.

Results—

One to 3 mmol/L ASA inhibited H/R-induced neuronal death when present during H/R but not when administered only for the reoxygenation period. Prostaglandin E
2
production was very low and was not altered by ASA. The AP-1 and NF-κB DNA binding activities increased after H/R. ASA increased the H/R-induced AP-1 binding but had no effect on NF-κB binding. H/R induced a sustained ERK1/2 activation followed by neuronal death, whereas no changes in p38 or c-Jun N-terminal kinase were detected. ASA strongly inhibited this ERK1/2 activation. PD98059, an ERK1/2 inhibitor, was also neuroprotective, prevented H/R-induced ERK1/2 activation, and had no effect on NF-κB binding activity. Inhibition of NMDA receptors, iNOS, or p38 MAPK did not provide neuroprotection.

Conclusions—

Inhibition of the sustained activation of ERK1/2 may partially contribute to neuroprotection achieved by ASA against H/R injury.
Neuroprotective Effect of Granulocyte Colony–Stimulating Factor After Focal Cerebral Ischemia
Authors: Schäbitz W.-R. , Kollmar R. , Schwaninger M. , Juettler E. , Bardutzky J. , Schölzke M.N. , Sommer C. , Schwab S.
Published: March 2003

Background and Purpose—

The potential neuroprotective effect of the granulocyte colony–stimulating factor (G-CSF) after glutamate-induced excitotoxicity in cell culture and after focal cerebral ischemia in rats was studied. We hypothesized the existence of the G-CSF receptor (G-CSFR) as a main G-CSF effector on neurons, and immunohistochemistry, immunoblotting, and polymerase chain reaction were performed. The G-CSFR–mediated action was studied by activation of signal transducer(s) and activator(s) of transcription-3 (STAT3) in the periphery of the infarction.

Methods—

Neuroprotection of various G-CSF concentrations on glutamate-induced excitotoxicity was studied in cell culture. In vivo, ischemia was induced by use of a suture occlusion model of the middle cerebral artery (90-minute occlusion) in the rat. Thirty minutes after the induction of ischemia, the animals (n=12 per group) received G-CSF at 60 μg/kg body wt IV for 90 minutes or vehicle (saline). Infarct volume was calculated on the basis of 2,3,5-triphenyltetrazolium chloride staining 24 hours after ischemia. Expression of the G-CSFR was studied by immunohistochemistry and verified by reverse transcription–polymerase chain reaction and immunoblotting. Expression of STAT3 was determined by immunohistochemistry.

Results—

In cell culture, G-CSF exhibited a significant neuroprotective effect after glutamate-induced excitotoxicity (
P
<0.05). A G-CSF concentration of 10 ng/mL was maximally effective, resulting in a nearly complete protection. In vivo, G-CSF reduced infarct volume to 47% (132.0±112.7 mm
3
versus 278.9±91.6 mm
3
[
P
<0.05] in the control group). Immunohistochemistry, Western blotting, and reverse transcription–polymerase chain reaction revealed the existence of G-CSFRs in neurons and glial cells. Animals treated with G-CSF significantly upregulated STAT3 in the periphery of the infarction compared with control animals (
P
<0.05).

Conclusions—

G-CSF achieved a significant neuroprotective effect in cell culture and after intravenous administration after stroke. Increased STAT3 expression in the penumbra of G-CSF–treated rats suggests mediation by G-CSFR.
Interleukin-1 Receptor Antagonist Gene Polymorphisms in Carotid Atherosclerosis
Authors: Worrall Bradford B. , Azhar Salman , Nyquist Paul A. , Ackerman Robert H. , Hamm Theresa L. , DeGraba Thomas J.
Published: March 2003

Background and Purpose—

Inflammation plays an important role in the development of atherosclerosis. The gene for the counterinflammatory cytokine interleukin–1 receptor antagonist (IL-1ra) is polymorphic, and high frequencies of allele 2 have been found to be associated with other inflammatory diseases. This study examined the association of allele and carrier frequencies of the IL-1ra gene with the presence of carotid atherosclerosis and plaque symptomaticity.

Methods—

A total of 328 subjects identified as having carotid atherosclerosis or no atherosclerosis (controls) participated. Blood was obtained for DNA determination.

Results—

Frequency of allele 2 was significantly greater in patients with atherosclerosis compared with nonatherosclerotic subjects. No difference was seen between symptomatic and asymptomatic atherosclerosis patients. Noncarriage of allele 2 was associated with reduced likelihood of atherosclerosis (odds ratio [OR], 0.44; 95% CI, 0.27 to 0.71). The homozygous carrier state for allele 2 was associated with greater likelihood of atherosclerosis (unadjusted OR, 7.30; 95% CI, 2.31 to 22.94; adjusted OR, 13.78; 95% CI, 1.94 to 97.9). A gene-dose effect was detected.

Conclusions—

These data suggest that allele 2 of the IL-1ra gene represents a susceptibility factor in the development of carotid atherosclerosis. Further investigation appears warranted.
Association Between Diabetes and Stroke Subtype on Survival and Functional Outcome 3 Months After Stroke
Authors: Megherbi Salah-Eddine , Milan Chantal , Minier Dominique , Couvreur Grégory , Osseby Guy-Victor , Tilling Kate , Di Carlo Antonio , Inzitari Domenico , Wolfe Charles D.A. , Moreau Thibault , Giroud Maurice
Published: March 2003

Background and Purpose—

Although diabetes is a strong risk factor for stroke, it is still unclear whether stroke subtype, severity, and prognosis are different in diabetic and nondiabetic patients. We sought to evaluate stroke features, prognosis, and functional outcome in patients with diabetes compared with patients without diabetes.

Methods—

In a European Union Concerted Action involving 7 countries and 4537 patients hospitalized for a first-in-a-lifetime stroke, defined according to the Oxfordshire Community Stroke Project criteria, we collected data on demographics, risk factors, clinical presentation, and outcome. We used logistic regression to examine the relationship between diabetes and outcome at 3 months (disability, handicap, and death), controlling for risk factors, clinical presentation, and demographics.

Results—

Overall, diabetes was present in 937 patients (21%). Diabetic patients, compared with those without diabetes, were more likely to have limb weakness (
P
<0.02), dysarthria (
P
<0.001), ischemic stroke (
P
<0.001), and lacunar cerebral infarction (
P
=0.03). At 3 months, the case fatality rates were not higher in the diabetic groups (
P
=0.33). Handicap (Rankin Scale) and disability (Barthel Index) were significantly higher in diabetic patients (
P
=0.005 and
P
=0.016, respectively).

Conclusions—

Stroke in diabetic patients has a specific clinical pattern and a poor prognosis in terms of motor function, which emphasizes the need for early diagnosis and treatment of every case of diabetes.
Levels of Anti-Inflammatory Cytokines and Neurological Worsening in Acute Ischemic Stroke
Authors: Vila Nicolás , Castillo José , Dávalos Antonio , Esteve Anna , Planas Anna M. , Chamorro Ángel
Published: March 2003

Background—

Mechanisms involved in stroke progression are incompletely understood. Ischemic brain injury is characterized by acute local inflammatory response mediated by cytokines. Anti-inflammatory cytokines act in a feedback loop to inhibit continued proinflammatory cytokine production. We assessed the implication of interleukin (IL)-10 and IL-4 in deteriorating ischemic stroke.

Methods—

Two hundred thirty-one patients with ischemic stroke within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale score fell at least 1 point during the first 48 hours after admission. Anti-inflammatory cytokines were determined in plasma obtained on admission.

Results—

Eighty-three patients (35.9%) worsened within the first 48 hours after stroke onset. Significantly lower concentrations of IL-10 were found in patients with neurological worsening (
P
<0.05), but IL-4 levels were similar in patients with or without deterioration. Lower plasma concentrations of IL-10 (<6 pg/mL) were associated with clinical worsening on multivariate analysis (odds ratio=3.1, 95% CI=1.1 to 8.9) independently of hyperthermia, hyperglycemia, or neurological condition on admission. Further analysis disclosed that early worsening was independently associated with lower IL-10 plasma levels in patients with subcortical infarcts or lacunar stroke but not in patients with cortical lesions.

Conclusions—

Anti-inflammatory cytokine IL-10 is associated with the early clinical course of patients with acute ischemic stroke, especially in patients with small vessel disease or subcortical infarctions.