bluuebunny/crossref_metadata_2025 huggingface dataset:
Time Course of Symptoms in Extracranial Carotid Artery Dissections
Authors: Biousse Valérie , D’Anglejan-Chatillon Jacques , Touboul Pierre-Jean , Amarenco Pierre , Bousser Marie-Germaine
Published: June 2011

Background and Purpose
Cerebral infarction is the most frequent and severe manifestation of extracranial internal carotid artery dissection. However, few data exist on the precise time course of symptoms preceding the onset of stroke.

Methods
We studied 80 consecutive patients (29 retrospectively, 51 prospectively) with angiographically diagnosed extracranial internal carotid artery dissection and, during a 6-month follow-up, recorded the time elapsed between the onset of the first symptoms and the onset of any ischemic event (transient ischemic attack or stroke). We compared patients with and without ischemic events, with and without completed stroke, and, among patients who had local signs at onset, those with and without subsequent ischemic events.

Results
Cerebral or retinal infarction occurred in 42 patients. It was inaugural in 9 patients. In the 33 others, the time interval between the first symptoms (local signs and/or transient ischemic attacks) and the onset of stroke ranged from a few minutes to 31 days; it was ≤7 days in 82% of the patients. No significant difference in the baseline characteristics of the patients or in the angiographic pattern of dissection was found based on the presence or absence of ischemic signs or of completed stroke.

Conclusions
In carotid artery dissections, completed stroke usually occurs in the first few days after the onset of the first symptoms, whether local or ischemic, but it can occur as much as 1 month later. This suggests that any potential preventive treatment should be initiated as early as possible after the onset of the first symptoms but might also be worth initiating even 1 month later.
Safety, Tolerability, and Pharmacokinetics of the
N
-Methyl-
d
-Aspartate Antagonist Dextrorphan in Patients With Acute Stroke
Authors: Albers G.W. , Atkinson R.P. , Kelley R.E. , Rosenbaum D.M.
Published: June 2011

Background and Purpose
Dextrorphan hydrochloride is a noncompetitive
N
-methyl-
d
-aspartate antagonist that is neuroprotective in experimental models of focal brain ischemia. The purpose of this study was to determine the maximum loading dose and maintenance infusion of dextrorphan hydrochloride that are well tolerated in patients with an acute stroke.

Methods
An intravenous infusion of dextrorphan or placebo was begun within 48 hours of onset of a mild-to-moderate hemispheric stroke. Initially, patients were treated with either placebo (n=15) or dextrorphan (n=22) using a 1-hour loading dose (60 to 150 mg) followed by a 23-hour ascending-dose maintenance infusion (maximum total dose, 3310 mg). Subsequently, 29 patients were treated with dextrorphan in an open trial using a 1-hour loading dose (145 to 260 mg) followed by an 11-hour constant rate (30 to 70 mg/h) infusion.

Results
Transient and reversible adverse effects, including nystagmus, nausea, vomiting, somnolence, hallucinations, and agitation, commonly occurred in dextrorphan-treated patients. Loading-dose escalation was stopped because of rapid-onset, reversible, symptomatic hypotension in 7 of 21 patients treated with doses of 200 to 260 mg/h. At the highest rates of maintenance infusion (>90 mg/h), 3 patients developed deep stupor or apnea. The maximum tolerated loading dose was 180 mg/h, and the maximum tolerated maintenance infusion was 70 mg/h. Maximum plasma levels of 750 to 1000 ng/mL were obtained in 9 patients. There was no difference in neurological outcome at 48 hours between the dextrorphan-treated and placebo-treated patients.

Conclusions
The highest doses of dextrorphan administered were associated with serious adverse experiences in some patients. Lower doses (loading doses of 145 to 180 mg, maintenance infusions of 50 to 70 mg/h) were better tolerated and rapidly produced potentially neuroprotective plasma concentrations of dextrorphan. These doses were associated with well-defined pharmacological effects compatible with
N
-methyl-
d
-aspartate receptor antagonism.
Nitric Oxide Synthase Inhibition and Extracellular Glutamate Concentration After Cerebral Ischemia/Reperfusion
Authors: Zhang Jing , Benveniste Helene , Klitzman Bruce , Piantadosi Claude A.
Published: June 2011

Background and Purpose
Transient cerebral ischemia in rats results in selective loss of neuronal viability, eg, hippocampal CA1 neurons. The neurochemical variables responsible for this selective vulnerability to ischemia/reperfusion (IR) appear to involve excitatory amino acids. In brain IR, excitatory amino acid toxicity may be modulated by endogenous nitric oxide (NO•) gas. To investigate NO• in global brain IR, we measured the effects of NO• synthase (NOS) inhibition on interstitial excitatory amino acids in rats. Changes in postischemic cerebral blood flow and blood-brain barrier function also were evaluated.

Methods
Forebrain ischemia was produced by systemic hypotension and occlusion of both carotid arteries for 15 minutes. Blood flow was restored for 60 minutes by unclamping the carotids and reinfusing with blood. A microdialysis probe was placed into the cortex and hippocampus using a stereotaxic device. Interstitial glutamate concentration was measured during IR with high-performance liquid chromatography. A competitive NOS inhibitor,
N
ω
-nitro-
l
-arginine methyl ester (L-NAME), was given intraperitoneally 30 minutes before ischemia in doses of 1, 4, and 20 mg/kg. Changes in cerebral blood flow and blood-brain barrier during IR were determined using laser-Doppler flowmetry and microdialysis with sodium fluorescein.

Results
Glutamate in the dialysate during IR increased transiently 10-fold and returned to baseline levels by 30 minutes of reperfusion. Animals treated with L-NAME 30 minutes before ischemia also showed increases in glutamate concentration during ischemia, but glutamate remained elevated during reperfusion. The increase in glutamate concentration during reperfusion caused by L-NAME was prevented by
l
-arginine. The administration of
l
-arginine and L-NAME together decreased extracellular glutamate concentration during ischemia. Cerebral blood flow decreased to about 5% of baseline values during ischemia but increased approximately fourfold relative to control values on reperfusion. The hyperemic responses after ischemia were not different between IR groups treated with or without L-NAME. Brain ischemia increased the permeability of the blood-brain barrier to fluorescein; however, this change was attenuated by L-NAME administration at 20 mg/kg.

Conclusions
NOS inhibition did not attenuate extracellular glutamate accumulation during ischemia and increased its concentration on reperfusion. The elevated glutamate concentration after IR in L-NAME–treated rats did not appear to be due to either a decrease in cerebral blood flow response after ischemia or increases in local blood-brain barrier permeability. For the most part, the blood-brain barrier was spared in the immediate postischemic period by L-NAME treatment. These data suggest that NO• production may oppose synaptic excitatory amino acid accumulation and presumably excitotoxicity during IR.
Stroke Incidence, Case Fatality, and Mortality in the WHO MONICA Project
Authors: Thorvaldsen Per , Asplund Kjell , Kuulasmaa Kari , Rajakangas Anna-Maija , Schroll Marianne
Published: June 2011

Background and Purpose
This report compares stroke incidence, case fatality, and mortality rates during the first years of the WHO MONICA Project in 16 European and 2 Asian populations.

Methods
In the stroke component of the WHO MONICA Project, stroke registers were established with uniform and standardized rules for case ascertainment and validation of events.

Results
A total of 13 597 stroke events were registered from 1985 through 1987 in a total background population of 2.9 million people aged 35 to 64 years. Age-standardized stroke incidence rates per 100 000 varied from 101 to 285 in men and from 47 to 198 in women. The combined stroke attack rates for first and recurrent events were approximately 20% higher than incidence rates in most populations and varied to the same extent. Stroke incidence rates were very high among the population of Finnish men tested. The incidence of stroke was, in general, higher among populations in eastern than in western Europe. It was also relatively high in the Chinese population studied, particularly among women. The case-fatality rates at 28 days varied from 15% to 49% among men and from 18% to 57% among women. In half of the populations studied, there were only minor differences between official stroke mortality rates and rates measured on the basis of fatal events registered and validated for the WHO MONICA stroke study.

Conclusions
The WHO MONICA Project provides a unique opportunity to perform cross-sectional and longitudinal comparisons of stroke epidemiology in many populations. The present data show how large differences in stroke incidence and case-fatality rates contribute to the more than threefold differences in stroke mortality rates among populations.
The Impact of Alcohol and Hypertension on Stroke Incidence in a General Japanese Population
Authors: Kiyohara Yutaka , Kato Isao , Iwamoto Hiromitsu , Nakayama Keizo , Fujishima Masatoshi
Published: June 2011

Background and Purpose
The relationship between alcohol intake and stroke has been inconsistent in previous studies. We examined the separate and combined effects of drinking habits and hypertension on stroke incidence in a prospective survey of a general Japanese population.

Methods
A total of 1621 stroke-free Hisayama residents aged 40 years or older were classified by their alcohol intake into nondrinkers, light drinkers (<34 g of ethanol per day), and heavy drinkers (≥34 g of ethanol per day) and followed up prospectively for 26 years from 1961.

Results
During the follow-up period, cerebral infarction developed in 244 subjects and cerebral hemorrhage in 60. For men, the incidence of cerebral hemorrhage increased significantly with rising alcohol consumption. In contrast, the incidence of cerebral infarction was slightly lower in light drinkers than in nondrinkers, while it increased significantly in heavy drinkers compared with light drinkers. Female drinkers had a lower incidence of cerebral infarction but a slightly higher incidence of cerebral hemorrhage than nondrinkers, as did male light drinkers. Among the hypertensive subjects, the age- and sex-adjusted relative risk of cerebral hemorrhage was significantly elevated in heavy drinkers versus abstainers (3.13; 95% confidence interval [CI], 1.08 to 9.10), but the increase was not significant for light drinkers. In contrast, the relative risk did not significantly increase for normotensive light and heavy drinkers. Compared with hypertensive light drinkers, the relative risk of cerebral infarction significantly increased in hypertensive heavy drinkers (1.96; 95% CI, 1.08 to 3.57) but remained unchanged in normotensive heavy drinkers. Significant associations between alcohol intake and stroke were substantially the same even after controlling for other risk factors in multivariate analysis.

Conclusions
Among hypertensive individuals, heavy alcohol consumption leads to a significant increase in the risk of cerebral hemorrhage, suggesting a synergistic effect of alcohol and hypertension, while light alcohol consumption significantly reduces the risk of cerebral infarction.
Recent Infection as a Risk Factor for Cerebrovascular Ischemia
Authors: Grau Armin J. , Buggle Florian , Heindl Silke , Steichen-Wiehn Christianne , Banerjee Tomas , Maiwald Matthias , Rohlfs Marion , Suhr Helge , Fiehn Walter , Becher Heiko , Hacke Werner
Published: June 2011

Background and Purpose
Previous infection is discussed as a risk factor for ischemic stroke in children and younger adults. We tested the hypothesis that the role of recent infection in cerebrovascular ischemia is not restricted to younger patients and investigated which infections are mainly relevant in this respect.

Methods
We performed a case-control study with 197 patients aged 18 to 80 years with acute cerebrovascular ischemia and 197 randomly selected control subjects matched for sex, age, and area of residence.

Results
Infection within 1 week before ictus or examination was significantly more common among patients (38 of 197) than control subjects (10 of 197; odds ratio [OR], 4.5; 95% confidence interval [CI], 2.1 to 9.7). Patients more often had febrile and subfebrile infections (≥37.5°C) than control subjects (29 of 197 versus 5 of 197; OR, 7.0; 95% CI, 2.5 to 20). Respiratory tract infections were most common in both groups. Bacterial infections dominated among patients but not among control subjects. Infection increased the risk for cerebrovascular ischemia in all age groups; this reached significance for patients aged 51 to 60 and 61 to 70 years. The profile of vascular risk factors was similar in patients with and patients without previous infection. Infection remained a significant risk factor when previous stroke, hypertension, diabetes mellitus, coronary heart disease, and current smoking were included as covariates in a logistic model (OR, 4.6; 95% CI, 1.9 to 11.3).

Conclusions
Recent infection, primarily of bacterial origin, may be a risk factor for cerebrovascular ischemia in older as well as younger patients.
Early Predictors of Death and Disability After Acute Cerebral Ischemic Event
Authors: Hénon H. , Godefroy O. , Leys D. , Mounier-Vehier F. , Lucas C. , Rondepierre P. , Duhamel A. , Pruvo J. P.
Published: June 2011

Background and Purpose
Many clinical trials are currently being conducted to evaluate the ability of neuroprotectors and thrombolytic agents to improve survival and functional outcome after ischemic stroke. Such trials require early predictors of survival and disability for ethical and methodological reasons. The aim of the study was to determine which variables, of those easily assessable during the first 24 hours after stroke onset, would be predictors of 8-day mortality rate and 3-month clinical outcome.

Methods
One hundred fifty-two consecutive patients with an acute ischemic event were evaluated within 24 hours after symptom onset. We determined (1) the 8-day mortality rate and (2) the 3-month functional outcome (Glasgow Outcome Scale). The following potential predictors of outcome were tested by means of a stepwise logistic regression analysis: age, sex, body mass index, atrial fibrillation, previous stroke, existence of headache, Orgogozo score, level of consciousness, swallowing disturbances, hemianopia, pulse rate, mean blood pressure, hematocrit, glycemia, and computed tomographic scan data (cerebral atrophy score, hyperdense middle cerebral artery sign, number of silent infarcts, leukoaraiosis score).

Results
The multivariate analysis revealed that the 8-day mortality rate depended only on the level of consciousness at admission (
P
=.0001); death or dependence at month 3 (scores 3 to 5 on the Glasgow Outcome Scale) depended on the severity of the clinical deficits (
P
=.0001), previous stroke (
P
=.0018), and age (
P
=.0237).

Conclusions
In future drug trials, the distribution of patients between “active treatment” and “placebo” groups should be balanced regarding the severity of clinical deficits, history of stroke, and age.
Spontaneous Middle Cerebral Artery Reperfusion in Ischemic Stroke
Authors: Zanette Elietta Maria , Roberti Cinzia , Mancini Giovanni , Pozzilli Carlo , Bragoni Maura , Toni Danilo
Published: June 2011

Background and Purpose
The aim of this study was to investigate by means of transcranial Doppler (TCD) ultrasonography how many spontaneous reperfusions of the middle cerebral artery (MCA) occurred during the first week after onset of acute ischemic stroke in the carotid territory.

Methods
TCD examination, computed tomographic scan, and arterial digital angiography were performed in 56 patients with acute ischemic stroke within 6 hours of the onset of symptoms. The TCD examination was repeated within 24 hours, 48 hours, and 7 days after stroke; a further TCD examination was performed within 3 to 9 months in 27 patients.

Results
At 6 hours, 33 patients presented abnormal TCD findings in the symptomatic MCA (16 “no flows” and 17 asymmetries). Of these, 4 patients (3 no flows and 1 asymmetry) died before the 7-day follow-up was completed, whereas of the 29 remaining patients undergoing all the TCD control examinations, only 14 presented permanently abnormal TCD findings (7 asymmetries and 7 no flows). These data are consistent with an MCA reperfusion occurring at any level of the MCA, although most frequently in the distal part, and in the majority of cases during the first 48 hours. One patient who showed MCA asymmetrical flow velocity at the day-7 TCD examination was normal at the TCD follow-up at 3 to 9 months.

Conclusions
TCD examination offers an easy and reliable way of monitoring MCA reopening and might be useful to identify subgroups of patients who may benefit most from pharmacological reperfusion.
A Photothrombotic ‘Ring’ Model of Rat Stroke-in-Evolution Displaying Putative Penumbral Inversion
Authors: Wester Per , Watson Brant D. , Prado Ricardo , Dietrich W. Dalton
Published: June 2011

Background and Purpose
To facilitate reproducible and rigorous study of a tissue zone at risk of encroaching ischemic damage, we propose a new model in which the potentially compromised tissue lies within rather than perifocal to an ischemic locus. The perimeter of the “zone at risk” is defined by a photothrombotically produced cortical lesion in the shape of a toroid (or “ring”).

Methods
The exposed crania of erythrosin B–injected rats were irradiated with a 514.5-nm laser beam, configured as a 5-mm-diameter ring, to yield a ring-shaped lesion caused by photochemically induced platelet occlusion of cortical vasculature. Developing perfusion deficits in the interior region were revealed by carbon black infusion. Tissue damage and infarct volumes were assessed by light and electron microscopy, and blood-brain barrier integrity was assessed with Evans blue dye and horseradish peroxidase as tracers.

Results
For rats injected with 17 mg/kg erythrosin B and irradiated for 2 minutes with a ring beam intensity of 0.92 W/cm
2
(beam power of 65 mW), carbon black infusion at times up to 4 hours demonstrated a shallow cortical ring lesion encircling a fully patent zone at risk, which by 24 hours evinced an essentially complete perfusion deficit. At times up to 24 hours, the ring lesion was penetrated at the pial surface by distal branches of the middle cerebral and anterior cerebral arteries. Stereotaxically based histopathological assessment showed that by 24 hours the lesion spanned the cortical thickness. Lesion volume increased from 14.5±8.0 mm
3
(mean±SD) (n=8) to 46.2±15.6 mm
3
(n=8) between 4 and 24 hours after irradiation (
P
<.01), but the anteroposterior lesion diameter did not change significantly between 4 hours (6.00±1.03 mm; n=9) and 24 hours (6.75±1.15 mm; n=9).

Conclusions
The present model of slowly developing but inevitable cortical tissue death in a sequestered area should facilitate more precise observations of the evolution of tissue metabolic responses, from the impending onset of ischemia to the threshold of irreversible damage. This system may prove efficient for evaluating treatments intended to salvage a penumbral region.
Neuroprotective Properties of the Novel Antiepileptic Lamotrigine in a Gerbil Model of Global Cerebral Ischemia
Authors: Wiard Robert P. , Dickerson Mary Carroll , Beek Otto , Norton Ronald , Cooper Barrett R.
Published: June 2011

Background and Purpose
Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils.

Methods
The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated.

Results
Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia.

Conclusions
Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia.
Hyperglycemia and Hemorrhagic Transformation of Cerebral Infarcts
Authors: Broderick Joseph P. , Hagen Timothy , Brott Thomas , Tomsick Thomas
Published: June 2011

Background
Identification of factors that predispose to bleeding into ischemic brain could lead to safer use of thrombolytic agents in the setting of ischemic stroke. Recently de Courten-Meyers and colleagues reported that occluding the middle cerebral artery of markedly hyperglycemic cats was associated with 5-fold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Hemorrhage associated with hyperglycemia in cats was much more pronounced with reperfusion than with permanent middle cerebral artery occlusion.

Case Descriptions
We describe two patients with a unique presentation of diffuse hemorrhagic infarction of the caudate and lentiform nuclei associated with initially marked hyperglycemia and the subsequent development of hemichorea.

Conclusions
We hypothesize that the marked hyperglycemia due to poor control of diabetes contributed to the hemorrhagic change of the caudate and lenticular nuclei. Because the hemorrhage in hyperglycemic cats was more pronounced in the setting of reperfusion, hemorrhagic risk associated with hyperglycemia should be investigated, particularly in ongoing thrombolytic treatment trials for acute ischemic stroke. We encourage other acute stroke investigators to prospectively look at the risk of brain hemorrhage in stroke patients with marked hyperglycemia.
Sex Differences in the Management of Patients Hospitalized With Ischemic Cerebrovascular Disease
Authors: Patrick S. J. , Concato J. , Viscoli C. , Chyatte D. , Brass L. M.
Published: June 2011

Background and Purpose
Previous studies suggest that the management of coronary artery disease differs for women compared with men. We examined this issue for ischemic cerebrovascular disease.

Methods
We reviewed the use of angiography and carotid endarterectomy among patients discharged from Connecticut hospitals during 6 years over the past decade. Crude and age-adjusted rates of angiography and endarterectomy were determined for each sex.

Results
Among 22 582 female and 19 729 male patients discharged, the rate of cerebral angiography was 11.8% for men and 7.2% for women; the age-adjusted odds ratio was 0.77 (95% confidence interval [CI], 0.72 to 0.82). The rate of endarterectomy was 10.6% for men and 5.7% for women; the age-adjusted odds ratio was 0.67 (95% CI, 0.62 to 0.72). The distribution of cerebrovascular disease type differed by sex, however, with carotid artery disease representing a larger proportion of men (12.2% [2415/19 729]) than women (6.9% [1554/22 582]) (χ
2
=355.8,
P
<.0001). When restricted to this diagnosis, no sex differences exist (odds ratio for angiography, 1.00 [95% CI, 0.87 to 1.14] and for endarterectomy, 0.93 [95% CI, 0.81 to 1.07]).

Conclusions
Overall, women hospitalized for ischemic cerebrovascular disease undergo fewer angiograms and are less likely to have carotid endarterectomy than men. These differences are not found when analysis is restricted to subjects with carotid disease and suggest that part of the difference in management may be due to biological differences between men and women.
Neuronal Necrosis After Middle Cerebral Artery Occlusion in Wistar Rats Progresses at Different Time Intervals in the Caudoputamen and the Cortex
Authors: Garcia Julio H. , Liu Kai-Feng , Ho Khang-Loon
Published: June 2011

Background and Purpose
Most brain lesions that develop after an artery is occluded evolve from an initial stage of “ischemic injury” (probably reversible) to an infarct or an area where most neurons become necrotic. There is scant information on the time that must elapse after the arterial occlusion for neurons to undergo irreversible injury. The objective of these experiments was to chart the time course and the topographic distribution of the neuronal necrosis that follows the occlusion of a large cerebral artery.

Methods
One hundred fifty-one adult rats (including 15 controls) were used in this study. One hundred forty-seven had the right middle cerebral artery occluded for variable periods ranging from 30 minutes to 7 days. After processing the brains for histology, a meticulous structural evaluation of each specimen, including quantitation of necrotic neurons, was followed by a detailed statistical analysis of the neuronal counts.

Results
Few neurons in isolated sites showed morphological signs of necrosis during the initial 4 hours; the first significant increase in the percentage of necrotic neurons (15%) was observed within the territory of the occluded artery after 6 hours (
P
<.05); 12 hours after the arterial occlusion most neurons (65%) had become necrotic (
P
<.0001). Pannecrosis involving neurons, glial cells, and blood vessels was observed at 72 to 96 hours. However, even at this time pannecrosis involved only the preoptic area and the lateral putamen; a few intact neurons remained visible in the cortex, and scattered necrotic neurons could be identified beyond the edges of the “area of pallor,” which does not become clearly demarcated until 4 to 5 days after the arterial occlusion.

Conclusions
There is a predictable progression in the development of neuronal necrosis after a permanent arterial occlusion. Irreversible changes appear first in the caudoputamen and then spread to the cortex. The causes for the progression of the lesion are not known; however, therapeutic interventions that start within the first 1 to 2 hours after the arterial occlusion may alter the histopathologic responses to this form of injury. It remains to be determined whether the extent of the neurological deficit induced by an arterial occlusion correlates with the number of necrotic neurons.
Effect of Nitric Oxide Synthase Inhibition on the Cerebral Vascular Response to Hypercapnia in Primates
Authors: McPherson Robert W. , Kirsch Jeffrey R. , Ghaly Ramsis F. , Traystman Richard J.
Published: June 2011

Background and Purpose
The role of nitric oxide in cerebrovascular response to changes in P
co
2
is unclear. In the present study, we assessed responses at two levels of hypercapnia in a primate model before and after blockade of nitric oxide synthesis.

Methods
We compared the effects of two levels of hypercapnia, defined as P
co
2
of ≈70 mm Hg (high-CO
2
group, n=5) and P
co
2
of ≈50 mm Hg (moderate-CO
2
group, n=6), on increases in regional cerebral blood flow (microspheres) before and after inhibition of nitric oxide synthase with
N
ω
-nitro-
l
-arginine methyl ester (L-NAME; 60 mg · kg
−1
) in isoflurane-anesthetized cynomolgus monkeys (1.0% end-tidal concentration).

Results
Before L-NAME administration, hypercapnia increased flow in all regions (eg, forebrain: high-CO
2
group, 69±10 to 166±15 mL · min
−1
· 100 g
−1
; moderate-CO
2
group, 49±7 to 93±15 mL · min
−1
· 100 g
−1
) and decreased cerebral vascular resistance (high-CO
2
, 1.1±0.1 to 0.4±0.1 mm Hg · mL
−1
· min · 100 g; moderate-CO
2
, 1.4±0.1 to 0.7±0.1 mm Hg · mL
−1
· min · 100 g). During normocapnia, L-NAME decreased cerebral blood flow (high-CO
2
, 37±9%; moderate-CO
2
, 40±6%) and increased cerebral vascular resistance (high-CO
2
, 93±33%; moderate-CO
2
, 88±20%). After L-NAME, hypercapnia still increased blood flow in all regions (eg, forebrain: high-CO
2
, 56±7 to 128±3 mL · min
−1
· 100 g
−1
; moderate-CO
2
, 36±5 to 57±8 mL · min
−1
· 100 g
−1
) and decreased vascular resistance (high-CO
2
, 1.5±0.1 to 0.6±0.1 mm Hg · mL
−1
· min · 100 g; moderate-CO
2
, 2.0±0.3 to 1.2±0.1 mm Hg · mL
−1
· min · 100 g). In both groups L-NAME attenuated hypercapnia hyperemia by approximately 30% in cortex but not in other regions.

Conclusions
Nitric oxide contributes to basal vascular tone but is not a major contributor to the mechanism of hypercapnia-induced cerebral vasodilation, except in cortex, in primates.
Brain Abscess as a Complication of Stroke
Authors: Chen Sien-Tsong , Tang Lok-Ming , Ro Long-Sun
Published: June 2011

Background
Systemic infection is a common complication of stroke. However, brain abscess as a complication of stroke has never been reported.

Case Descriptions
We report two patients, one with a hypertensive intracerebral hemorrhage and the other with nonseptic cerebral infarction. In both patients, brain abscess developed at the stroke lesion site after an infectious complication. After surgical aspiration and antibiotic treatment, one patient recovered and the other died.

Conclusions
These two cases demonstrate that brain abscess may occur in a previous hemorrhage or infarction area as a complication of systemic infection. Recognition of the risk is important for early diagnosis and proper treatment of this potentially fatal complication of stroke.
Comparative Correlations of HMPAO SPECT Indices, Neurological Score, and Stroke Subtypes With Clinical Outcome in Acute Carotid Infarcts
Authors: Laloux Patrice , Richelle Fabienne , Jamart Jacques , De Coster Patrick , Laterre Christian
Published: June 2011

Background and Purpose
The prognostic value of single-photon emission computed tomography (SPECT) remains controversial. The aim of this study was to compare the prognostic value of stroke severity, stroke subtypes, and SPECT indices and to determine which predictive factors have an independent effect on clinical outcome.

Methods
We studied 55 consecutive patients with acute (<12 hours) carotid infarct within 36 hours of symptom onset with SPECT. Clinical presentation was assessed by the Canadian Neurological Scale and stroke subtypes. SPECT indices were the degree and size of hypoperfusion and crossed cerebellar diaschisis as assessed by a semiquantitative analysis. Outcome was evaluated by the functional status and mortality (Rankin Scale score at 1 month).

Results
The Rankin Scale score correlated with the degree (
r
=.580;
P
<.00001) and size (
r
=.616;
P
<.00001) of hypoperfusion. The mean degree and size of hypoperfusion were significantly higher in patients with poor outcome. Crossed cerebellar diaschisis had no significant predictive value. Statistical analysis determined threshold values for the Canadian Neurological Scale score and the degree and size of hypoperfusion for the functional status and mortality. The degree and size of hypoperfusion had no higher performance than the Canadian Neurological Scale score. The negative predictive value was excellent for both clinical and SPECT indices. Multivariate analysis selected only the size of hypoperfusion as an independent predictor for the functional status (
P
=.004) and the Canadian Neurological Scale score for mortality (
P
=.009).

Conclusions
SPECT performed within 36 hours of onset predicts clinical outcome, but different clinical and SPECT indices with threshold values should be chosen according to the relevant outcome end point.
Diminished Nocturnal Blood Pressure Decline and Lesion Site in Cerebrovascular Disease
Authors: Yamamoto Yasumasa , Akiguchi Ichiro , Oiwa Kaiyo , Satoi Hitoshi , Kimura Jun
Published: June 2011

Background and Purpose
Many studies have suggested that diminished nocturnal blood pressure decline in hypertensive cardiovascular disease is associated with the extent of hypertensive vascular disease. In our previous observation of cerebrovascular disease, however, we found reduced nocturnal blood pressure decline to be associated not only with the extent of hypertensive vascular disease but also with the specific location of cerebrovascular lesions. The purpose of this study was to elucidate the mechanism of nocturnal blood pressure decline in cerebrovascular disease. Moreover, to clarify whether reduced nocturnal blood pressure decline occurs before cerebrovascular disease, we examined patients with recurring episodes.

Methods
Ambulatory blood pressure monitoring was carried out every 30 minutes in 14 control subjects, 15 hypertensive subjects, 90 patients with cerebrovascular disease (16 single lacunar infarctions, 15 multiple lacunar infarctions, 10 putaminal hemorrhages, 14 thalamic hemorrhages, 11 pontine base infarctions, 15 pontine tegmentum infarctions, 8 pontine hemorrhages, 13 wide cortical infarctions), and 7 patients with recurring stroke episodes. The percentage of nocturnal blood pressure decline and the correlations for systolic blood pressure and heart rate were calculated.

Results
The percentage of nocturnal blood pressure decline was significantly smaller in the groups with multiple lacunar infarction (systolic,
P
<.001; diastolic,
P
<.01), thalamic hemorrhage (
P
<.01,
P
<.05), pontine tegmentum infarction (
P
<.01,
P
<.05), and pontine hemorrhage (both
P
<.05). The correlation between systolic blood pressure and heart rate was not significant for almost all the groups with diminished blood pressure decline.

Conclusions
Diminished nocturnal blood pressure decline in cerebrovascular disease is thought to be caused by specific injury to the central autonomic nervous system such as the striatum, diencephalon, midbrain, and pontine tegmentum and their connecting fibers.
Ischemic Stroke in Young Patients With Activated Protein C Resistance
Authors: Simioni P. , de Ronde H. , Prandoni P. , Saladini M. , Bertina R.M. , Girolami A.
Published: June 2011

Background
A new pathological condition termed “activated protein C (APC) resistance” has recently been reported to be the most common hereditary blood coagulation disorder associated with familial thrombosis. APC resistance is characterized by a poor anticoagulant response to APC in the plasma of patients and is due to a defect of factor V.

Case Descriptions
This report deals with three Italian families with inherited APC resistance in which stroke had occurred at a young age in one of the family members. One of the patients exhibited ischemic stroke at 8 months of age. Although deep vein thrombosis is considered the main clinical manifestation of the defect, its possible association with stroke is discussed. DNA analysis confirmed the presence of the 1691GA mutation in the factor V gene (factor V Leiden) in all patients with a normalized APC sensitivity ratio of less than 0.70. In three cases the APC sensitivity ratios were very low (approximately 1.2), with a normalized APC sensitivity ratio of approximately 0.4. DNA analysis confirmed that these patients were homozygous for the mutation. The clinical history of these patients suggests that homozygosity for the defect is compatible with life and does not seem to be associated with early or more severe thrombophilia compared with homozygous defects of other clotting inhibitors.

Conclusions
The cases reported here suggest a possible association of inherited APC resistance with ischemic stroke in young patients. Case-control studies should be performed to assess the true association.
Posterior Cerebral Artery Stenosis With Midbrain Infarction
Authors: Duncan Gary W. , Weindling Steven M.
Published: June 2011

Background
Brain infarction secondary to stenosis of the posterior cerebral artery is uncommon. We report a patient with midbrain infarction and symptoms of both Benedikt’s and pupil-sparing oculomotor palsy syndromes secondary to posterior cerebral artery stenosis.

Case Description
A 51-year-old woman developed diplopia, left ptosis, and right hemiataxia and hyperactive tendon reflexes. Pupils were equal and reactive. Radiological examination revealed stenosis of the posterior cerebral artery and a left-sided midbrain infarct.

Conclusions
Stenosis of the posterior cerebral artery may cause only midbrain infarction and may be responsible for Benedikt’s and pupil-sparing oculomotor palsy syndromes.
Incidence and Causes of Strokes Associated With Pregnancy and Puerperium
Authors: Sharshar T. , Lamy C. , Mas J.L.
Published: June 2011

Background and Purpose
The incidence, causes, and prognosis of nonhemorrhagic strokes and intraparenchymal hemorrhages occurring in association with pregnancy or puerperium are poorly understood.

Methods
We carried out a retrospective (1989 through 1991) and prospective (1992) study in 63 public maternities (348 295 deliveries) of the region of Ile de France (10 660 554 inhabitants) and in the neurology, neurosurgery, and intensive care units of the same geographic area. Records of women who suffered a cerebrovascular event during pregnancy or the first 2 weeks postpartum were reviewed by two study neurologists. Stroke was defined according to the criteria of the World Health Organization.

Results
Thirty-one cases of strokes were identified, including 15 nonhemorrhagic strokes (including strokelike deficits associated with eclampsia) and 16 intraparenchymal hemorrhages, assessed in all cases by CT scan and/or MRI. The incidence of nonhemorrhagic strokes in women who delivered in public maternities of Ile de France was 4.3 per 100 000 deliveries (95% confidence interval, 2.4 to 7.1) and that of intraparenchymal hemorrhage was 4.6 per 100 000 deliveries (95% confidence interval, 2.6 to 7.5). Eclampsia accounted for 47% of cases of nonhemorrhagic strokes. The other causes were extracranial vertebral artery dissection, postpartum cerebral angiopathy, inherited protein S deficiency, and disseminated intravascular coagulation associated with amniotic fluid embolism. The cause remained undetermined in four cases despite extensive investigations. Eclampsia accounted for 44% of intraparenchymal hemorrhages. Another 37% were due to rupture of a vascular malformation. The cause remained undetermined in three cases. There were four maternal deaths (all associated with intraparenchymal hemorrhage), three of them in eclamptic women. Fetal mortality and prematurity were associated with eclampsia.

Conclusions
The incidence of nonhemorrhagic stroke does not seem to be much increased during pregnancy and early puerperium. In contrast to that in the nonpregnant state, the frequency of intraparenchymal hemorrhage in pregnancy appears to be similar to that of nonhemorrhagic strokes, suggesting that pregnancy may increase the risk of cerebral hemorrhage. Eclampsia is the main cause of both nonhemorrhagic stroke and intraparenchymal hemorrhage. Intraparenchymal hemorrhage associated with eclampsia carries a poor prognosis.
Carotid Artery Wall Intima-Media Thickness Is Associated With Insulin-Mediated Glucose Disposal in Men at High and Low Coronary Risk
Authors: Agewall Stefan , Fagerberg Björn , Attvall Stig , Wendelhag Inger , Urbanavicius Vaidotas , Wikstrand John
Published: June 2011

Background and Purpose
The aim of this investigation was to examine the relationship between insulin sensitivity and intima-media thickness in the common carotid artery.

Methods
Ultrasound examinations of the common carotid artery and hyperinsulinemic euglycemic clamp examinations were performed in a group (n=25) of men aged 57 to 77 years at high risk for atherosclerotic disease (hypertension and at least one of the following factors: hypercholesterolemia and/or smoking) and in an age-matched low-risk group (n=23) with no cardiovascular risk factors. Subjects with cardiovascular disease or diabetes mellitus were excluded.

Results
A significant negative relationship between insulin sensitivity index and common carotid maximum intima-media thickness was observed in both the high-risk group (
r
=−.45,
P
<.05) and in the low-risk group (
r
=−.59,
P
<.01).

Conclusions
Our results suggest that an increase in intima-media thickness, as a possible expression of early atherosclerosis, is negatively related to insulin sensitivity.
Outcome in Familial Subarachnoid Hemorrhage
Authors: Bromberg J.E.C. , Rinkel G.J.E. , Algra A. , Limburg M. , van Gijn J.
Published: June 2011

Background and Purpose
The outcome of subarachnoid hemorrhage in patients with familial occurrence of subarachnoid hemorrhage (familial SAH) is an important but neglected factor in balancing the risks of screening for asymptomatic aneurysms and repairing these in unaffected members of such families.

Methods
We studied the outcome of familial SAH in a prospective, hospital-based series of patients with at least one first-degree relative with SAH and compared it with the outcome in a prospectively collected hospital series of patients selected for the absence of SAH in first- and second-degree relatives. Outcome was graded in three categories: independence, dependence, or death. Poor outcome was defined as death or dependence.

Results
Of 29 patients with familial SAH, 52% had a poor outcome, whereas only 37% of 125 patients with sporadic SAH had a poor outcome. The crude relative risk for poor outcome in familial SAH was 1.4 (95% confidence interval [CI], 0.9 to 2.1;
P
=.14); the odds ratio adjusted for age and sex was 2.5 (95% CI, 1.0 to 6.0;
P
=.04). This risk is probably an underestimation due to our strict patient selection criteria.

Conclusions
Patients with familial SAH have a greater risk of poor outcome than patients with sporadic SAH. This adds to the factors in favor of screening unaffected first-degree relatives of patients with familial SAH.
A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Intravenous Magnesium Sulfate in Acute Stroke
Authors: Muir Keith W. , Lees Kennedy R.
Published: June 2011

Background and Purpose
Magnesium ions act as endogenous vasodilators of the cerebral circulation and act pharmacologically as noncompetitive antagonists of the
N
-methyl-
d
-aspartate receptor by virtue of their role as endogenous voltage-sensitive blockers of the ion channel. The preclinical efficacy of magnesium has been demonstrated in standard models of stroke.

Methods
Sixty patients were randomized to magnesium sulfate (8 mmol IV over 15 minutes and 65 mmol over 24 hours) or placebo within 12 hours of clinically diagnosed middle cerebral artery stroke. Pulse, blood pressure, and serum magnesium levels were monitored. Primary outcome was death or significant functional impairment (Barthel Index score <60) at 3 months.

Results
Magnesium was well tolerated, with no significant adverse effects and no change in blood pressure or pulse rate. Laboratory and electrocardiographic variables did not differ significantly between placebo- and magnesium-treated groups. Serum magnesium rose from 0.76 mmol/L to 1.42 mmol/L over 24 hours and remained significantly higher than in the placebo group at 48 hours. Thirty percent of magnesium-treated and 40% of placebo-treated patients were dead or disabled (Barthel Index score <60) at 3 months (
P
=.42). There was a decrease in the number of early deaths in the magnesium-treated group (
P
=.066, log-rank test).

Conclusions
Magnesium sulfate is well tolerated after acute stroke and has no deleterious hemodynamic effects at this dose. Further trials are required to determine efficacy.
Recurrence of Bleeding in Patients With Primary Intracerebral Hemorrhage
Authors: Passero Stefano , Burgalassi Laura , D’Andrea Paolo , Battistini Noé
Published: June 2011

Background and Purpose
Rebleeding in patients with primary intracerebral hemorrhage is considered uncommon, but there are no precise data to support this opinion. The purpose of this study was to assess the incidence and predictors of recurrent bleeding in survivors of primary intracerebral hemorrhage.

Methods
As part of a prospective study, 112 survivors of a first primary intracerebral hemorrhage were followed up for a mean period of 84.1 months after their discharge. To ascertain risk factors that may influence rebleeding, several demographic, medical history, clinical, and laboratory variables were collected and analyzed.

Results
Twenty-four percent (27/112) of survivors experienced one or more rebleedings during the follow-up period, in 8 cases (30%) in the first year of follow-up; in the others recurrence occurred later, up to 11.5 years. Rebleeding had a high mortality rate: 70% of patients died as a consequence of their second or third hemorrhage. Univariate and multivariate analyses showed that lobar location of the first hemorrhage was the only significant predictor of rebleeding. Patients with rebleeding were more frequently older, more often had a history of previous transient ischemic attack or ischemic stroke, and less often had hyperlipidemia than patients without rebleeding, although these correlations did not reach statistical significance. During follow-up, poor control of arterial hypertension was found in 7% of hypertensive patients without rebleeding and in 47% of hypertensive patients with rebleeding.

Conclusions
Our study showed that rebleeding after a first primary intracerebral hemorrhage is not as uncommon as is usually believed. The risk of rebleeding seems to be particularly high after hemorrhage at the junction of the gray and white matter, a site regarded as typical of hemorrhages due to amyloid angiopathy, and when arterial hypertension is poorly controlled.
Cerebral Venous Thrombosis in Adults
Authors: Daif Abdulkader , Awada Adnan , Al-Rajeh Saad , Abduljabbar Mohammed , Al Tahan Abdul Rahman , Obeid Tahir , Malibary Tajuddin
Published: June 2011

Background and Purpose
We undertook this study to determine the frequency, clinical patterns, and etiologies of cerebral venous thrombosis in a Middle Eastern country.

Methods
Records of all adult patients admitted with an angiographically documented diagnosis of cerebral venous thrombosis from 1985 through 1994 in two major hospitals of Riyadh, Saudi Arabia, were reviewed.

Results
Forty patients (20 men, 20 women) aged 16 to 40 years were identified. Hospital frequency was 7 per 100 000 patients, and the relative frequency against arterial strokes was 1:62.5. Nineteen cases (47%) had a clinical picture of pseudotumor cerebri. Behçet’s disease was the cause in 10 cases (25%). Other causes included antiphospholipid antibodies in 4, protein S deficiency in 3, intracranial tumors in 3, systemic lupus erythematosus in 3, infections in 3, antithrombin III deficiency in 2, postpartum in 1, and oral contraceptives in 1.

Conclusions
Cerebral venous thrombosis in adults is not uncommon in Saudi Arabia. Behçet’s disease is the single most common etiology. Infection is no longer an important cause, whereas “new” coagulation disorders are common. Patients with a pseudotumor cerebri syndrome should undergo angiography or brain MRI before being labeled idiopathic.