bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Rating Scales for Age-Related White Matter Changes (Leukoaraiosis)
Authors: Pantoni Leonardo , Simoni Michela , Pracucci Giovanni , Schmidt Reinhold , Barkhof Frederik , Inzitari Domenico
Published: December 2002

Background and Purpose—

It has been hypothesized that the use of different visual rating scales partly explains the discordant results of studies investigating risk factors and clinical correlates of age-related cerebral white matter changes (leukoaraiosis). We aimed to compare 6 widely used rating scales for leukoaraiosis and to calculate conversion coefficients of the score of 1 scale in the score of a second scale.

Methods—

Two trained raters evaluated 80 pairs of CT and MRI scans using 2 CT and 4 MRI rating scales for white matter changes. Correlations among the scales were evaluated and regression lines were constructed with each of the CT and MRI scale scores as variables.

Results—

A high correlation was observed in all the paired comparisons of the 6 scales (Spearman’s ρ ranging from 0.85 to 0.96,
P
<0.0001). Using regression analysis, we determined numeric parameters to transform the score of 1 scale to the corresponding score for each of the remaining scales and relative confidence intervals. The predictive values of these conversions expressed as
R
2
ranged from 0.75 to 0.92.

Conclusions—

The present findings support the view that a good correlation exists among the considered visual rating scales for white matter changes. With the limitation that conversion parameters are calculated by applying a linear regression to partly nonlinear scales, their use allows comparison of the results of previous studies that used different scales and to pool data from past and ongoing clinical trials.
Oral Citicoline in Acute Ischemic Stroke
Authors: Dávalos Antoni , Castillo José , Álvarez-Sabín José , Secades Julio J. , Mercadal Joan , López Sonia , Cobo Erik , Warach Steven , Sherman David , Clark Wayne M. , Lozano Rafael
Published: December 2002

Background and Purpose—

No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale ≤1, modified Rankin Scale score ≤1, and Barthel Index ≥95 at 3 months using the generalized estimating equations analysis.

Methods—

A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale ≥8, and prior modified Rankin Scale score ≤1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified.

Results—

Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62;
P
=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72;
P
=0.0043). The overall safety of citicoline was similar to placebo.

Conclusions—

Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.
Sudden Deafness and Anterior Inferior Cerebellar Artery Infarction
Authors: Lee Hyung , Sohn Sung-Il , Jung Doo-Kyo , Cho Yong-Won , Lim Jeong-Geung , Yi Sang-Doe , Lee Seong-Ryong , Sohn Chul-Ho , Baloh Robert W.
Published: December 2002

Background and Purpose—

Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery (AICA) is known to be associated with vertigo, nystagmus, facial weakness, and gait ataxia. Few reports have carefully examined the deafness associated with the AICA infarction. Furthermore, previous neurological reports have not emphasized the inner ear as a localization of sudden deafness. The aim of this study was to investigate the incidence of deafness associated with the AICA infarction and the sites predominantly involved in deafness.

Methods—

Over 2 years, we prospectively identified 12 consecutive patients with unilateral AICA infarction diagnosed by brain MRI. Pure-tone audiogram, speech discrimination testing, stapedial reflex testing, and auditory brainstem response were performed to localize the site of lesion in the auditory pathways. Electronystagmography was also performed to evaluate the function of the vestibular system.

Results—

The most common affected site on brain MRI was the middle cerebellar peduncle (n=11). Four patients had vertigo and/or acute auditory symptoms such as hearing loss or tinnitus as an isolated manifestation from 1 day to 2 months before infarction. Audiological testings confirmed sensorineural hearing loss in 11 patients (92%), predominantly cochlear in 6 patients, retrocochlear in 1 patient, and combined on the affected side cochlear and retrocochlear in 4 patients. Electronystagmography demonstrated no response to caloric stimulation in 10 patients (83%).

Conclusions—

In our series, sudden deafness was an important sign for the diagnosis of AICA infarction. Audiological examinations suggest that sudden deafness in AICA infarction is usually due to dysfunction of the cochlea resulting from ischemia to the inner ear.
Direct Percutaneous Transluminal Angioplasty for Acute Middle Cerebral Artery Trunk Occlusion
Authors: Nakano Shinichi , Iseda Tsutomu , Yoneyama Takumi , Kawano Hirokazu , Wakisaka Shinichiro
Published: December 2002

Background and Purpose—

The purpose of this study was to evaluate the safety and efficacy of direct percutaneous transluminal angioplasty (PTA) for patients with acute middle cerebral artery (MCA) trunk occlusion.

Methods—

Over the past 9 years, a total of 70 patients with acute MCA trunk occlusion were treated with intra-arterial reperfusion therapy. In the last 5 years, 34 patients were treated with direct PTA, and subsequent thrombolytic therapy was added if necessary for distal embolization. The other 36 patients, mainly in the first 4 years, were treated with thrombolytic therapy alone and were used as controls. Pretherapeutic neurological status was evaluated with National Institutes of Health Stroke Scale scores. The modified Rankin Scale (mRS) was used to assess clinical outcome at 90 days.

Results—

There were no significant differences in pretherapeutic National Institutes of Health Stroke Scale score and duration of ischemia between the 2 groups. The rate of partial or complete recanalization in the PTA group was 91.2%, whereas that in the thrombolysis-alone group was 63.9% (
P
<0.01). The incidence of large parenchymal hematoma with neurological deterioration in the PTA group was 2.9%, while that in the thrombolysis-alone group was 19.4% (
P
=0.03). Although direct PTA did not improve the rate of favorable outcome (mRS score 0 or 1; 41.7% for the thrombolysis-alone group versus 52.9% for the PTA group;
P
=0.48), outcome in terms of independence (mRS score 0, 1, 2) was significantly better in the PTA group (73.5%) than in the thrombolysis-alone group (50.0%;
P
=0.04).

Conclusions—

Although definitive conclusions on the comparative merits of these 2 therapies cannot be drawn because of an open trial, direct PTA may be an effective alternative option to intra-arterial thrombolysis for acute MCA trunk occlusion.
Simvastatin Increases Endothelial Nitric Oxide Synthase and Ameliorates Cerebral Vasospasm Resulting From Subarachnoid Hemorrhage
Authors: McGirt Matthew J. , Lynch John R. , Parra Augusto , Sheng Huaxin , Pearlstein Robert D. , Laskowitz Daniel T. , Pelligrino Dale A. , Warner David S.
Published: December 2002

Background and Purpose—

Endothelial nitric oxide synthase (eNOS) activity is decreased after subarachnoid hemorrhage (SAH). Simvastatin increases eNOS activity. We hypothesized that simvastatin would increase eNOS protein and ameliorate SAH-induced cerebral vasospasm.

Methods—

Mice were treated with subcutaneous simvastatin or vehicle for 14 days and then subjected to endovascular perforation of the right anterior cerebral artery or sham surgery. Three days later, neurological deficits were scored (5 to 27; 27=normal), and middle cerebral artery diameter and eNOS protein were measured. The study was repeated, but simvastatin treatment was started after SAH or sham surgery.

Results—

In SAH mice, simvastatin pretreatment increased middle cerebral artery diameter (SAH-simvastatin=74±22 μm, SAH-vehicle=52±18 μm,
P
=0.03; sham-simvastatin=102±8 μm, sham-vehicle=105±6 μm). Pretreatment reduced neurological deficits (SAH-simvastatin=25±2, SAH-vehicle=20±2,
P
=0.005; sham-simvastatin and sham-vehicle=27±0). Simvastatin pretreatment also increased eNOS protein. Simvastatin posttreatment caused a modest increase in middle cerebral artery diameter in SAH mice (SAH-simvastatin=56±12 μm, SAH-vehicle=45±4 μm,
P
=0.03; sham-simvastatin=92±13 μm, sham-vehicle=99±10 μm) and reduced neurological deficits (SAH-simvastatin=21±1, SAH-vehicle=19±2,
P
=0.009). Simvastatin posttreatment did not significantly increase eNOS protein.

Conclusions—

Simvastatin treatment before or after SAH attenuated cerebral vasospasm and neurological deficits in mice. The mechanism may be attributable in part to eNOS upregulation.
Analysis of the Safety and Efficacy of Intra-Arterial Thrombolytic Therapy in Ischemic Stroke
Authors: Lisboa Rejane C. , Jovanovic Borko D. , Alberts Mark J.
Published: December 2002

Background and Purpose—

Intra-arterial thrombolytic therapy (IAT) may be a treatment option for patients with ischemic stroke. We analyzed the safety and efficacy of IAT on the basis of published data.

Methods—

We searched computerized databases for studies using IAT in ≥10 patients with ischemic stroke. Some studies had control patients for comparison. Data were collected on age, stroke territory, time to treatment, medication, site of arterial occlusion and recanalization on angiogram, outcomes, and symptomatic intracranial hemorrhage (SICH).

Results—

The analysis included 27 studies with 852 patients who received IAT and 100 control subjects. There were more favorable outcomes in the IAT than in the control group (41.5% versus 23%,
P
=0.002), with a lower mortality rate for IAT (IAT, 27.2%; control group, 40%,
P
=0.004). The IAT group had an odds ratio of 2.4 (95% CI, 1.45 to 3.85) for favorable outcome. SICH was more frequent in the IAT group compared with the control group (9.5% versus 3%,
P
=0.046). The subgroup of patients receiving a combination of intravenous thrombolytic therapy and IAT had more favorable outcomes than the IAT alone subgroup, but this trend did not reach statistical significance (53.6% versus 41.5%,
P
=0.1). Among the patients treated with IAT, those who had supratentorial strokes were more likely to have favorable outcomes than those with infratentorial strokes (42.2% versus 25.6%;
P
=0.001; odds ratio, 2.0; 95% CI, 1.33 to 3.0).

Conclusions—

IAT for ischemic stroke appears efficacious but carries an increased risk of SICH. Further prospective studies are needed to prove the safety and efficacy of IAT in stroke.
Stroke in the Young in the Northern Manhattan Stroke Study
Authors: Jacobs Bradley S. , Boden-Albala Bernadette , Lin I-Feng , Sacco Ralph L.
Published: December 2002

Background and Purpose—

Stroke and stroke subtype incidence in young black and Hispanic populations have not been well studied. The purpose of this study was to determine stroke incidence rates in these populations and to compare rates among various race-ethnic, sex, and age groups.

Methods—

A population-based incidence study identified all cases of first stroke in Northern Manhattan from 1993 to 1997. Stroke and stroke subtype incidence rates were calculated for younger (20 to 44 years of age) and older (≥45 years of age) adults. The relative risk (RR) of stroke in blacks and Hispanics compared with whites was calculated. Stroke subtypes, infarct subtypes, and case fatality rates were compared in the young and old and in different race-ethnic groups and sexes.

Results—

Over 4 years, 74 cases of first stroke in young patients were discovered (47% women, 12% black, 80% Hispanic, 8% white). The stroke incidence rates (cases per 100 000 persons per year) in the young were 23 overall, 10 for infarct, 7 for intracerebral hemorrhage (ICH), and 6 for subarachnoid hemorrhage. The RR of stroke in the young was greatest for blacks (2.4; 95% CI, 0.8 to 6.7) and Hispanics (2.5; 95% CI, 1.1 to 5.8) compared with whites. ICH was more frequent in men with a RR of 3.7 (95% CI, 1.4 to 10.1). Case fatality rates at 30 days were higher in blacks (38%) and Hispanics (16%) compared with whites (0%).

Conclusions—

Young blacks and Hispanics have greater stroke incidences than young whites.
Association of Obesity and Central Fat Distribution With Carotid Artery Wall Thickening in Middle-Aged Women
Authors: De Michele Mario , Panico Salvatore , Iannuzzi Arcangelo , Celentano Egidio , Ciardullo Anna V. , Galasso Rocco , Sacchetti Lucia , Zarrilli Federica , Bond M. Gene , Rubba Paolo
Published: December 2002

Background and Purpose—

The association between obesity and atherosclerotic disease is controversial. In the present analysis, we evaluated whether common carotid intima-media thickness (IMT) and area, 2 markers of preclinical atherosclerosis, were increased in obese subjects.

Methods—

More than 5000 middle-aged women (n=5062; age, 30 to 69 years) living in the area of Naples, Southern Italy, were recruited for a prospective, currently ongoing study on the etiology of cardiovascular disease and cancer in the female population (the Progetto ATENA study). A subsample of 310 participants underwent high-resolution B-mode ultrasound examination, and the IMTs, intima-media areas, and lumen diameters of common carotid arteries were measured with a semiautomated computerized program. Subjects were divided into 3 groups on the basis of the recently published obesity guidelines for body mass index (BMI), a marker of general obesity, and tertiles of waist-to-hip ratio (WHR), a marker of regional obesity.

Results—

Women with a BMI ≥30 kg/m
2
showed higher systolic and diastolic blood pressures, triglycerides, and fasting glucose and insulin, as well as lower high-density lipoprotein concentrations, than subjects with lower BMI. A gradual increase in common carotid IMT and intima-media area was observed when lean women (0.94±0.01 mm and 19.8±0.5 mm
2
, respectively) were compared with overweight (0.98±0.01 mm and 21.0±0.4 mm
2
) and obese (1.02±0.02 mm and 22.6±0.8 mm
2
,
P
<0.005 for linear trend) individuals. Similarly, women in the highest tertile of WHR (>0.85) had adverse risk factor profiles and thicker carotid intima-media complex than those in the first 2 tertiles (
P
<0.01 and
P
<0.05 for IMT and intima-media area, respectively). In multivariate analyses, BMI and WHR were significant predictors of carotid wall thickness, independently of other traditional and nontraditional cardiovascular risk factors (age, blood pressure, lipid abnormalities, fasting insulin).

Conclusions—

The present results indicate a graded and independent association between general and abdominal obesity—reflected by high BMI and WHR—and carotid artery wall thickening in a population of middle-aged women.
Chlamydia pneumoniae
in Carotid Artery Atherosclerosis
Authors: Prager Manfred , Türel Zeynep , Speidl Walter S. , Zorn Gerlinde , Kaun Christoph , Niessner Alexander , Heinze Georg , Huk Igor , Maurer Gerald , Huber Kurt , Wojta Johann
Published: December 2002

Background and Purpose—

There is growing clinical and experimental evidence that infections with
Chlamydia pneumoniae
might contribute to the development and progression of atherosclerosis. However, studies detecting the pathogen in atherosclerotic lesions examined either only atherosclerotic vessels or control vessels without atherosclerosis obtained from a different group of individuals. We analyzed atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins, and circulating leukocytes from the same individual patients for the presence of
C pneumoniae
.

Methods—

From each of 46 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis, these samples were analyzed by nested polymerase chain reaction for
C pneumoniae
–specific DNA. Furthermore, we determined IgA and IgG titers specific for the pathogen and plasma levels of C-reactive protein in these patients.

Results—

C pneumoniae
DNA was detected in 86.9% of the leukocytes and in 82.6% of the atherosclerotic plaques but in only 6.5% of the saphenous veins. In 85% of patients who also had leukocytes positive for
C pneumoniae
, the atherosclerotic plaques were positive and the saphenous veins were negative. The presence of
C pneumoniae
–specific DNA in leukocytes significantly coincided with the presence of the respective DNA in the plaques of the carotid arteries (
P
=0.0002). No association between the presence of
C pneumoniae
and specific IgA or IgG levels was seen. C-reactive protein levels were significantly higher in patients with chlamydia-positive atherosclerotic plaques and with positive leukocytes than in patients with negative plaques of the carotid arteries or negative leukocytes, respectively (
P
<0.01,
P
<0.05).

Conclusions—

Our observation of >80% incidence of
C pneumoniae
in atherosclerotic plaques of the carotid artery does not prove causality between an infection with the pathogen and the development of atherosclerosis. It must be emphasized, however, that >90% of apparently healthy saphenous veins were negative for
C pneumoniae
. Given the structural and functional differences between veins and arteries, careful interpretation of our results regarding a possible causative role of
C pneumoniae
seems warranted.
Altered Vascular Function in Fetal Programming of Hypertension
Authors: Lamireau Delphine , Nuyt Anne Monique , Hou Xin , Bernier Sylvie , Beauchamp Martin , Gobeil Fernand , Lahaie Isabelle , Varma Daya R. , Chemtob Sylvain
Published: December 2002

Background and Purpose—

Reduced endothelium-dependent vasorelaxation partly due to loss of nitric oxide (NO) bioavailability occurs in most cases of chronic hypertension. Intrauterine nutritional deprivation has been associated with increased risk for hypertension and stroke, associated with relaxant dysfunction and decreased vascular compliance, but the underlying mechanisms are not known. The present studies were undertaken to investigate whether endothelial dysfunction associated with altered NO-dependent vasodilatation pathways is also observed in a model of in utero programming of hypertension.

Methods—

Pregnant Wistar rats were fed a normal (18%), low (9%), or very low (6%) protein isocaloric diet during gestation. Vasomotor response of resistance cerebral microvessels (<50 μm) was studied in adult offspring of dams fed the 18% and 9% protein diets by a video imaging technique. Endothelial NOS (eNOS), soluble guanylate cyclase (sGC), and K
Ca
channel expression were measured by Western blot. NO synthase (NOS) activity was measured enzymatically as well as in situ by NADPH diaphorase staining.

Results—

Litter size and survival to adulthood were not affected by the diets. Birth weights of offspring of dams fed the 6% diet were markedly lower than those of dams fed the 9% diet, which were marginally lower than those of controls. Systolic blood pressures of adult offspring of mothers in the 6% and 9% groups were comparably greater (156±2 and 155±1 mm Hg, respectively) than that of control offspring (137±1 mm Hg); we therefore focused on the 9% and 18% groups. Cerebral microvessel constriction to thromboxane A
2
mimetic and dilation to carba-prostaglandin I
2
did not differ between diet groups. In contrast, vasorelaxation to the NO-dependent agents substance P and acetylcholine was diminished by 50% in low protein-exposed offspring, but eNOS expression and activity were similar between the 2 diet groups. Vasorelaxant response to the NO donor sodium nitroprusside was also decreased and was associated with reduced (by 50% to 65%) cGMP levels and sGC expression. cGMP analogues caused comparable vasorelaxation in the 2 groups. Expression of K
Ca
(another important mediator of NO action) and relaxation to the K
Ca
opener NS1619 were unchanged by antenatal diet.

Conclusions—

Maternal protein deprivation, which leads to hypertension in the offspring, is associated with diminished NO-dependent relaxation of major organ (cerebral) microvasculature, which seems to be largely attributed to decreased sGC expression and cGMP levels. The study provides an additional explanation for abnormal vasorelaxation in nutrient-deprived subjects in utero.
Selective Blockade of Endothelin-B Receptors Exacerbates Ischemic Brain Damage in the Rat
Authors: Chuquet Julien , Benchenane Karim , Toutain Jérôme , MacKenzie Eric T. , Roussel Simon , Touzani Omar
Published: December 2002

Background and Purpose—

Endothelins act through 2 receptors, namely, ET
A
and ET
B
. In the cerebral circulation, ET
A
mediates marked and prolonged vasoconstriction, and its blockade increases cerebral blood flow (CBF) and reduces ischemic brain damage. However, the role of ET
B
receptors remains unclear. In this study we examined, in rats, the kinetics of expression of ET
B
and the effects of ET
B
blockade on changes in CBF and brain damage after focal cerebral ischemia and
N
-methyl-
d
-aspartate (NMDA)–induced excitotoxic injury.

Methods—

Rats were subjected to transient (60 minutes) focal cerebral ischemia or cortical injection of NMDA. The selective ET
B
antagonist BQ-788 was injected intracerebroventricularly 30 minutes before and 30 minutes after the onset of ischemia. Cortical perfusion was monitored by laser-Doppler flowmetry. The volume of infarction or NMDA-induced cortical lesion was assessed at 24 hours after the insult. The reverse transcription–polymerase chain reaction technique was used to assess ET
B
expression.

Results—

Cerebral ischemia failed to alter the expression of ET
B
mRNA in both acute and chronic stages. Administration of BQ-788 resulted in an increase in infarction volume (178%;
P
<0.05) accompanied by a decrease in residual CBF (−26.7% versus control;
P
<0.01). In these animals we found a positive correlation between the volume of infarction and the severity of the decrease in CBF. NMDA-induced cortical lesions were not affected by the administration of BQ-788.

Conclusions—

Our results suggest that the ET
B
antagonist BQ-788 induces deleterious effects that are mediated by the reduction of residual blood flow after ischemia and argue that the optimal therapeutic strategy in stroke would be to target the use of selective ET
A
antagonists and not mixed ET
A
/ET
B
antagonists.
Isolated and Borderline Isolated Systolic Hypertension Relative to Long-Term Risk and Type of Stroke
Authors: Qureshi Adnan I. , Suri M. Fareed K. , Mohammad Yousef , Guterman Lee R. , Hopkins L. Nelson
Published: December 2002

Background and Purpose—

Although the short-term risks of stroke and types of stroke associated with isolated systolic hypertension (ISH) and borderline isolated systolic hypertension (BISH) have been described, the long-term effects of these hypertensive conditions, particularly in younger individuals, are unclear. We performed this study to evaluate the long-term risks of stroke, type of stroke, and predictors of stroke associated with ISH and BISH and how this risk compares with that for persons with diastolic hypertension and normotension.

Methods—

We used the 20-year follow-up data for 12 344 adults aged 25 to 74 years who participated in the First National Health and Nutrition Examination Survey Follow-Up Study to determine the aforementioned risks. Blood pressure (BP) measurements of the participants were obtained during baseline evaluation. ISH was defined as systolic BP ≥160 mm Hg and diastolic BP <90 mm Hg. BISH was defined as systolic BP between 140 and 159 mm Hg and diastolic BP <90 mm Hg. Diastolic hypertension was defined as a diastolic BP ≥90 mm Hg. Normotension was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Incidence of stroke overall and incidence of ischemic stroke and intracerebral hemorrhage were determined from a review of hospital records and death certificates. Relative risk (RR) of stroke and stroke type in association with each hypertensive category was determined by Cox proportional hazards analysis after adjustment for potential confounding variables.

Results—

Among the 12 344 participants, hypertension was categorized as ISH (n=493), BISH (n=1241), and diastolic hypertension (n=3954). Normotension was observed in 6656 persons. After adjustment for differences in age, sex, education, serum cholesterol level, body mass index, diabetes mellitus, and cigarette smoking, a significantly higher RR for all strokes was observed in participants with ISH (RR, 2.7; 95% CI, 2.0 to 3.4) and BISH (RR, 1.4; 95% CI, 1.1 to 1.8) than those with normotension. The risk was significantly higher for ischemic stroke or intracerebral hemorrhage in persons with ISH and BISH. Among the 1734 persons with either ISH or BISH, the risk of stroke was independently associated with older age, diabetes mellitus, and systolic BP ≥180 mm Hg.

Conclusions—

Increased risks for stroke, ischemic stroke, and intracerebral hemorrhage were observed in patients with BISH, similar to those associated with ISH and diastolic hypertension. Future clinical trials are required to evaluate the effect of antihypertensive treatment in younger patients with BISH and ISH.
Effects of Nonpeptide V
1
Vasopressin Receptor Antagonist SR-49059 on Infarction Volume and Recovery of Function in a Focal Embolic Stroke Model
Authors: Shuaib Ashfaq , Xu Wang Chen , Yang Tao , Noor Raza
Published: December 2002

Background and Purpose—

Cerebral edema develops very early after the onset of focal cerebral ischemia and may be a major factor in early disability after an acute ischemic stroke. There have been very limited studies on the usefulness of antiedemic agents as neuroprotective agents in the setting of focal cerebral ischemia. We tested the neuroprotective effects of a new potent nonpeptide vasopressin receptor V
1
antagonist, SR-49059, in a focal embolic stroke model in rats.

Methods—

Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA). Infarction volume was measured at 48 hours after the MCA occlusion. Neurological deficits, ischemic brain edema, seizure activity, and mortality and hemorrhage rates were also documented.

Results—

Treatment with SR-49059 (2 mg/kg), initiated immediately after MCA occlusion, significantly reduced infarction volume (
P
<0.05) measured at 48 hours after the arterial occlusion. In animals in which the treatment was delayed for 1 hour after MCA occlusion, infarction volume was also reduced significantly (
P
<0.05). Infarction volume in the rats that received the drug at 3 or 6 hours after MCA occlusion was not different from that in the vehicle-treated group. Treatment with SR-49059, when started early after the arterial occlusion, also reduced neurological deficits and ischemic brain edema. Injection of drug at a higher dose (30 mg/kg) also reduced infarction volume and improved functional recovery but was not superior to the lower dose (2 mg/kg) when the drug was administrated at 1 hour after MCA occlusion.

Conclusions—

Our data show that the selective vasopressin receptor antagonist SR-49059 is a potent neuroprotective agent when used early after onset of arterial occlusion in an embolic focal ischemia model in rats. Further studies are needed in stroke models to better understand its neuroprotective properties when used alone or in combination with thrombolysis.
Different Mechanisms of Secondary Neuronal Damage in Thalamic Nuclei After Focal Cerebral Ischemia in Rats
Authors: Dihné Marcel , Grommes Christian , Lutzenburg Michael , Witte Otto W. , Block Frank
Published: December 2002

Background and Purpose—

After focal cerebral ischemia, depending on its localization and extent, secondary neuronal damage may occur that is remote from the initial lesion. In this study differences in secondary damage of the ventroposterior thalamic nucleus (VPN) and the reticular thalamic nucleus (RTN) were investigated with the use of different ischemia models.

Methods—

Transient middle cerebral artery occlusion (MCAO) leads to cortical infarction, including parts of the basal ganglia such as the globus pallidus, and to widespread edema. Photothrombotic ischemia generates pure cortical infarcts sparing the basal ganglia and with only minor edema. Neuronal degeneration was quantified within the ipsilateral RTN and VPN 14 days after ischemia. Glial reactions were studied with the use of immunohistochemistry.

Results—

MCAO resulted in delayed neuronal cell loss of the ipsilateral VPN and RTN. Glial activation occurred in both nuclei beginning after 24 hours. Photothrombotic ischemia resulted in delayed neuronal cell loss only within the VPN. Even 2 weeks after photothrombotic ischemia, glial activation could only be seen within the VPN.

Conclusions—

Pure cortical infarcts after photothrombotic ischemia, without major edema and without effects on the globus pallidus of the basal ganglia, only lead to secondary VPN damage that is possibly due to retrograde degeneration. MCAO, which results in infarction of cortex and globus pallidus and which causes widespread edema, leads to secondary damage in the VPN and RTN. Thus, additional RTN damage may be due to loss of protective GABAergic input from the globus pallidus to the RTN or due to the extensive edema. Retrograde degeneration is not possible because the RTN, in contrast to the VPN, has no efferents to the cortex.
Brief Comprehensive Quality of Life Assessment After Stroke
Authors: Sturm Jonathan W. , Osborne Richard H. , Dewey Helen M. , Donnan Geoffrey A. , Macdonell Richard A.L. , Thrift Amanda G.
Published: December 2002

Background and Purpose—

Generic utility health-related quality of life instruments are useful in assessing stroke outcome because they facilitate a broader description of the disease and outcomes, allow comparisons between diseases, and can be used in cost-benefit analysis. The aim of this study was to validate the Assessment of Quality of Life (AQoL) instrument in a stroke population.

Methods—

Ninety-three patients recruited from the community-based North East Melbourne Stroke Incidence Study between July 13, 1996, and April 30, 1997, were interviewed 3 months after stroke. Validity of the AQoL was assessed by examining associations between the AQoL and comparator instruments: the Medical Outcomes Short-Form Health Survey (SF-36); London Handicap Scale; Barthel Index; National Institutes of Health Stroke Scale; and Irritability, Depression, Anxiety scale. Sensitivity of the AQoL was assessed by comparing AQoL scores from groups of patients categorized by severity of impairment and disability and with total anterior circulation syndrome (TACS) versus non-TACS. Predictive validity was assessed by examining the association between 3-month AQoL scores and outcomes of death or institutionalization 12 months after stroke.

Results—

Overall AQoL utility scores and individual dimension scores were most highly correlated with relevant scales on the comparator instruments. AQoL scores clearly differentiated between patients in categories of severity of impairment and disability and between patients with TACS and non-TACS. AQoL scores at 3 months after stroke predicted death and institutionalization at 12 months.

Conclusions—

The AQoL demonstrated strong psychometric properties and appears to be a valid and sensitive measure of health-related QoL after stroke.
Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging of the Brain Before and After Coronary Artery Bypass Grafting Surgery
Authors: Restrepo Lucas , Wityk Robert J. , Grega Maura A. , Borowicz Lou , Barker Peter B. , Jacobs Michael A. , Beauchamp Norman J. , Hillis Argye E. , McKhann Guy M.
Published: December 2002

Background and Purpose—

Coronary artery bypass grafting (CABG) is a frequently performed surgical procedure that can be associated with neurological complications. Some studies have demonstrated that new focal brain lesions, detected by MRI, can develop after CABG. Furthermore, it has been suggested that the presence of such new lesions is associated with a decline in neurocognitive test scores. Advanced MRI techniques, including diffusion- (DWI) and perfusion-weighted imaging (PWI), offer important diagnostic advantages over conventional imaging in the assessment of patients undergoing CABG. We sought to determine whether focal PWI and DWI abnormalities could occur after CABG, particularly in patients without any measurable neurological deterioration.

Methods—

Thirteen patients prospectively underwent MRI with DWI and PWI before and after CABG. A battery of neurocognitive tests was administered before and after surgery. Demographic, clinical, and radiographic characteristics of the patients were collected and compared.

Results—

Four patients developed new DWI defects after CABG. The lesions were small, rounded, and multiple (3 of 4 patients). One of these patients was diagnosed with stroke on clinical grounds. The patients with new lesions had a larger neurocognitive decline than their counterparts with stable MRI. Other clinical characteristics of patients with new DWI lesions, including stroke risk factors, were similar to those of patients without MRI changes. No focal perfusion abnormalities were observed on preoperative or postoperative scans.

Conclusions—

Postoperative DWI abnormalities can occur after CABG, even in patients without overt neurological defects. The PWI scans remained unchanged. Larger prospective studies are required to determine whether the new lesions are clearly associated with neurocognitive decline or with specific perioperative stroke risk factors.
Monitoring Disease Progression in CADASIL With Diffusion Magnetic Resonance Imaging
Authors: Molko Nicolas , Pappata Sabina , Mangin Jean-François , Poupon Fabrice , LeBihan Denis , Bousser Marie-Germaine , Chabriat Hugues
Published: December 2002

Background and Purpose—

In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a large increase in water diffusion has been found both inside and outside the cerebral lesions as detected on conventional MRI. The aim of the present study was to assess the sensitivity of diffusion tensor imaging for monitoring the progression of cerebral tissue damage during the course of CADASIL.

Methods—

With the use of diffusion tensor imaging, whole brain trace of the diffusion tensor [Trace(D)] histograms were obtained in 22 CADASIL patients and 12 age-matched controls at baseline, in 14 patients after a mean delay of 21 months, and in 5 controls after a mean delay of 29 months. Parameters derived from these histograms (mean value, peak height, and peak location) were analyzed at baseline and during the follow-up.

Results—

At baseline, all the histogram parameters differed between patients and controls and were found to be significantly correlated with both the Mini-Mental State Examination score and Rankin Scale score in the patient group. The follow-up study showed a decrease in the peak height associated with an increase in the mean value of whole brain Trace(D) histograms in the 14 CADASIL patients scanned twice. The diffusion changes appeared larger in the patients whose Rankin score increased during the study period.

Conclusions—

These results suggest that the measurement of water diffusion over time is a sensitive marker for the progression of tissue damage in the brain. Thus, quantitative diffusion MRI can be used to monitor disease progression in CADASIL and possibly in other types of small-vessel brain disorders.
Carotid Plaque Area
Authors: Spence J. David , Eliasziw Michael , DiCicco Maria , Hackam Daniel G. , Galil Ramzy , Lohmann Tara
Published: December 2002

Background and Purpose—

Carotid plaque area measured by ultrasound (cross-sectional area of longitudinal views of all plaques seen) was studied as a way of identifying patients at increased risk of stroke, myocardial infarction, and vascular death.

Methods—

Patients from an atherosclerosis prevention clinic were followed up annually for up to 5 years (mean, 2.5±1.3 years) with baseline and follow-up measurements recorded. Plaque area progression (or regression) was defined as an increase (or decrease) of ≥0.05 cm
2
from baseline.

Results—

Carotid plaque areas from 1686 patients were categorized into 4 quartile ranges: 0.00 to 0.11 cm
2
(n=422), 0.12 to 0.45 cm
2
(n=424), 0.46 to 1.18 cm
2
(n=421), and 1.19 to 6.73 cm
2
(n=419). The combined 5-year risk of stroke, myocardial infarction, and vascular death increased by quartile of plaque area: 5.6%, 10.7%, 13.9%, and 19.5%, respectively (
P
<0.001) after adjustment for all baseline patient characteristics. A total of 1085 patients had ≥1 annual carotid plaque area measurements: 685 (63.1%) had carotid plaque progression, 306 (28.2%) had plaque regression, and 176 (16.2%) had no change in carotid plaque area over the period of follow-up. The 5-year adjusted risk of combined outcome was 9.4%, 7.6%, and 15.7% for patients with carotid plaque area regression, no change, and progression, respectively (
P
=0.003).

Conclusions—

Carotid plaque area and progression of plaque identified high-risk patients. Plaque measurement may be useful for targeting preventive therapy and evaluating new treatments and response to therapy and may improve cost-effectiveness of secondary preventive treatment.
A Pilot Study of Event-Related Functional Magnetic Resonance Imaging of Monitored Wrist Movements in Patients With Partial Recovery
Authors: Newton J. , Sunderland A. , Butterworth S.E. , Peters A.M. , Peck K.K. , Gowland P.A.
Published: December 2002

Background and Purpose—

Previous functional imaging studies of motor recovery after stroke have investigated cerebral activation during periods of repetitive, often complex, movement. This article reports the use of an event-related approach to study activation associated with isolated simple movements (wrist extension). This allows investigation of the pattern of the motor response and corresponding brain activation on a trial-by-trial basis. Patients with partial recovery can be assessed, and allowance can be made for abnormalities in the shape of hemodynamic responses.

Methods—

Functional MRI at 3 T was performed during a series of isolated, near-isometric wrist extension movements. A visual tracking procedure was used to elicit forces of 10% and 20% of maximum voluntary contraction. Force output from both wrists was monitored continuously. A voxel-wise procedure was used to fit the optimum hemodynamic response functions in each case.

Results—

Three chronic stage patients with partial recovery were successfully scanned and compared with 8 healthy controls. The patients showed well-lateralized motor responses but inaccurate control of force. During movement of the paretic wrist, we observed excessive activation of the ipsilateral primary motor cortex and increased relative activation of the supplementary motor area compared with movement of the nonparetic side. In the primary motor area, hemodynamic responses peaked more quickly on the ipsilateral side in 2 patients for movements of the paretic hand, whereas controls showed the opposite trend.

Conclusions—

An event-related approach can be used to study the relationship between motor responses and cerebral activation in patients with partial recovery. These preliminary findings suggest that excessive activation in ipsilateral motor cortex and secondary motor areas remains evident under these tightly controlled conditions and cannot be ascribed to mirror movements or abnormalities in the timing of the blood oxygen level–dependent (BOLD) response. However, close monitoring of motor responses also makes evident continuing impairment in motor skill, which makes comparison with activation in normal controls difficult.
Multiparametric MRI ISODATA Ischemic Lesion Analysis
Authors: Mitsias Panayiotis D. , Jacobs Michael A. , Hammoud Rabih , Pasnoor Mamatha , Santhakumar Sunitha , Papamitsakis Nikolaos I.H. , Soltanian-Zadeh Hamid , Lu Mei , Chopp Michael , Patel Suresh C.
Published: December 2002

Background and Purpose—

The purpose of this study was to show that the computer segmentation algorithm Iterative Self-Organizing Data Analysis Technique (ISODATA), which integrates multiple MRI parameters (diffusion-weighted imaging [DWI], T2-weighted imaging [T2WI], and T1-weighted imaging [T1WI]) into a single composite image, is capable of defining the ischemic lesion in a time-independent manner equally as well as the MRI techniques considered the best for each phase after stroke onset (ie, perfusion weighted imaging [PWI] and DWI for the acute phase and T2WI for the outcome phase).

Methods—

We measured MRI parameters of PWI, DWI, T2WI, and T1WI from patients at the acute phase (<30 hours) and DWI, T2WI, and T1WI at the outcome phase (3 months) of ischemic stroke. The clinical neurological deficit was graded with the National Institutes of Health Stroke Scale (NIHSS). We compared the ISODATA lesion size with the PWI, DWI, and T2WI lesion sizes measured within the same slice at each phase. The lesion sizes were also correlated with NIHSS score of each phase.

Results—

We included 11 patients; 9 (82%) were women, and 7 (64%) were black. The mean±SD age was 65.5±9.3 years (range, 45 to 82 years). The median NIHSS score was 15 (minimum, 4; maximum, 24)at the acute phase and 3 (minimum, 0; maximum, 22) at the outcome phase. The median time interval from stroke symptom onset to the acute MRI study was 10 hours (range, 6 to 29 hours), and the mean time interval to the outcome study was 93±11 days (range, 72 to 106 days). In the acute phase, the ISODATA lesion size had high correlation with the PWI lesion size (
r
=0.95; 95% CI, 0.89 to 0.98;
P
<0.0001), DWI lesion size (
r
=0.83; 95% CI, 0.66 to 0.92;
P
<0.0001), and T2WI lesion size (
r
=0.67; 95% CI, 0.39 to 0.84;
P
=0.008) and moderate correlation with NIHSS score (
r
=0.59; 95% CI, 0.02 to 0.88;
P
=0.06). In the outcome phase, the ISODATA lesion size had high correlation with the T2WI lesion size (
r
=0.97; 95% CI, 0.94 to 0.99;
P
<0.0001) and NIHSS score (
r
=0.78; 95% CI, 0.34 to 0.94;
P
=0.004).

Conclusions—

The integrated ISODATA method can identify and characterize the ischemic lesion independently of time elapsed since stroke onset. The ISODATA lesion size highly correlates with the PWI and DWI lesion size in the acute phase and with the T2WI lesion size in the outcome phase of ischemic stroke, as well as with the clinical neurological status of the patient.
Spreading and Synchronous Depressions of Cortical Activity in Acutely Injured Human Brain
Authors: Strong Anthony J. , Fabricius Martin , Boutelle Martyn G. , Hibbins Stuart J. , Hopwood Sarah E. , Jones Robina , Parkin Mark C. , Lauritzen Martin
Published: December 2002

Background and Purpose—

Cortical spreading depression (CSD) has been much studied experimentally but never demonstrated unequivocally in human neocortex by direct electrophysiological recording. A similar phenomenon, peri-infarct depolarization, occurs in experimental models of stroke and causes the infarct to enlarge. Our current understanding of the mechanisms of deterioration in the days after major traumatic or ischemic brain injury in humans has not yielded any effective, novel drug treatment. This study sought clear evidence for the occurrence and propagation of CSD in the injured human brain.

Methods—

In 14 patients undergoing neurosurgery after head injury or intracranial hemorrhage, we placed electrocorticographic (ECoG) electrodes near foci of damaged cortical tissue.

Results—

Transient episodes of depressed ECoG activity that propagated across the cortex at rates in the range of 0.6 to 5.0 mm/min were observed in 5 patients; this rate of propagation is characteristic of CSD. We also observed, in 8 of the 14 patients, transient depressions of ECoG amplitude that appeared essentially simultaneous in all recording channels, without clear evidence of spread.

Conclusions—

These results indicate that CSD or similar events occur in the injured human brain and are more frequent than previously suggested. On the basis of these observations, we suggest that the related phenomenon, peri-infarct depolarization, is indeed likely to occur in boundary zones in the ischemic human cerebral cortex.
MOSAIC: Multimodal Stroke Assessment Using Computed Tomography
Authors: Nabavi Darius G. , Kloska Stephan P. , Nam Eun-Mi , Freund Michael , Gaus Christiane G. , Klotz Ernst , Heindel Walter , Ringelstein E. Bernd
Published: December 2002

Background and Purpose—

With new CT technologies, including CT angiography (CTA), perfusion CT (PCT), and multidetector row technique, this method has regained interest for use in acute stroke assessment. We have developed a score system based on Multimodal Stroke Assessment Using CT (MOSAIC), which was evaluated in this prospective study.

Methods—

Forty-four acute stroke patients (mean age, 63.8 years) were enrolled within a mean of 3.0±1.9 hours after symptom onset. The MOSAIC score (0 to 8 points) was generated by results of the 3 sequential CT investigations: (1) presence and amount of early signs of infarction on noncontrast CT (NCCT; 0 to 2 points), (2) stenosis (>50%) or occlusion of the distal internal carotid or middle cerebral artery on CTA (0 to 2 points), and (3) presence and amount of reduced cerebral blood flow on 2 adjacent PCT slices (0 to 4 points). The predictive value of the MOSAIC score was compared with each single CT component with respect to the final size of infarction and the clinical outcome 3 months after stroke by use of the modified Rankin Scale (mRS) and the Barthel Index (BI).

Results—

Among the CT components, PCT showed the best correlation to infarction size (
r
=0.75) and clinical outcome (
r
=0.60 to 0.62) compared with NCCT (
r
=0.43 to 0.58) and CTA (
r
=0.47 to 0.71). The MOSAIC score showed consistently higher correlation factors (
r
=0.67 to 0.78) and higher predictive values (0.73 to 1.0) than all single CT components with respect to outcome measures. A MOSAIC score <4 predicted independence with 89% to 96% likelihood (mRS ≤2, BI ≥90); a MOSAIC score <5 predicted fair outcome with 96% to 100% likelihood (mRS ≤3, BI ≥60).

Conclusions—

The MOSAIC score based on multidetector row CT technology is superior to NCCT, CTA, and PCT in predicting infarction size and clinical outcome in hyperacute stroke.