bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychological Impairment in Stroke, Carotid Stenosis, and Peripheral Vascular Disease
Authors: Rao Rahul , Jackson Steven , Howard Robert
Published: June 2011

Background and Purpose
—An increasing body of literature suggests a role for clinically “silent” cerebrovascular disease in the pathogenesis of cognitive impairment. Such pathology commonly occurs in the absence of stroke. The main aim of the study was to examine neuropsychological impairment associated with cerebrovascular and peripheral vascular disease (PVD) and to compare cognitive deficits with a nonvascular control group. The main hypothesis was that older people with both transient ischemic attack (TIA) and PVD would demonstrate greater cognitive impairment than controls.

Methods
—A battery of neuropsychological tests was administered to 4 groups of community residents older than 65 years. The groups comprised 25 patients with carotid stenosis and TIA, 25 nonamputees with PVD, 25 patients with stroke, and 25 matched (with the stroke group) controls.

Results
—Stroke patients showed greater impairment than controls in all tests. PVD patients did not perform significantly worse (
P
<0.05 after Bonferroni correction) than control subjects on any of the neuropsychological tests. However, 25% of PVD patients had scores lying within the bottom 5% of control group scores for attention, calculation, and 1 test of frontal lobe function. TIA patients were more impaired in general intellectual impairment and frontal lobe function than controls. Frontal lobe impairment, suicidal thinking, and age were all independent predictors of global cognitive impairment in the TIA group. Frontal lobe impairment was the only predictor of global cognitive impairment in the PVD group.

Conclusions
—TIA and PVD patients showed similar patterns of neuropsychological impairment, but TIA may result in more prolonged cognitive impairment, particularly in frontal lobe function. This group may be at increased risk of vascular dementia as well as impulsivity and suicide.
Vascular Effects of Lipopolysaccharide Are Enhanced in Interleukin-10–Deficient Mice
Authors: Gunnett Carol A. , Berg Daniel J. , Faraci Frank M.
Published: June 2011

Background and Purpose
—The role in blood vessels of interleukin-10 (IL-10), a potent anti-inflammatory cytokine, is not known. Using mice with targeted deletion of the gene for IL-10 (IL-10
−/−
), we examined the hypothesis that IL-10 is a major modulator of the vascular effects of lipopolysaccharide (LPS).

Methods
—We examined in vitro responses of carotid arteries obtained from wild-type (129/SvEv or C57BL/6; IL-10
+/+
) and IL-10–deficient mice 6 hours after injection of a relatively low dose of LPS (10 μg).

Results
—Contraction of the carotid artery in response to U46619 was impaired in IL-10–deficient mice treated with LPS compared with LPS-treated controls. After LPS, U46619 (0.03 and 0.1 μg/mL) contracted the carotid artery by 0.11±0.02 (mean±SEM) and 0.38±0.03 g in wild-type (n=10) and 0.03±0.01 and 0.19±0.03 g in IL-10–deficient (n=8) mice (
P
<0.05 versus control). Aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), had no significant effect on contraction of the carotid artery from LPS-treated control mice but restored contraction of the carotid artery in response to U46619 in IL-10–deficient mice to levels seen in wild-type mice. Similar findings were obtained when phenylephrine was used as a vasoconstricting agent. These findings indicate that LPS produces much greater impairment of contractile responses of the carotid artery in IL-10–deficient mice than in control mice. Impaired contractile function was eliminated by aminoguanidine, suggesting that expression of iNOS is enhanced in arteries from IL-10–deficient mice. In carotid arteries from animals injected with LPS, reverse transcription–polymerase chain reaction (RT-PCR) products for iNOS were found more frequently in IL-10–deficient mice than in wild-type mice. RT-PCR products for iNOS were not present in arteries from vehicle-treated animals (IL-10–deficient or wild-type mice).

Conclusions
—This is the first evidence that endogenous IL-10 is a major determinant of the effects of LPS on vascular tone. The results suggest that impaired constrictor responses of the carotid artery after LPS in IL-10–deficient mice are mediated by enhanced expression of iNOS.
Cerebrovascular Dynamics of Autoregulation and Hypoperfusion
Authors: Zaharchuk Greg , Mandeville Joseph B. , Bogdanov Alexei A. , Weissleder Ralph , Rosen Bruce R. , Marota John J. A.
Published: June 2011

Background and Purpose
—To determine how cerebral blood flow (CBF), total and microvascular cerebral blood volume (CBV), and blood oxygenation level–dependent (BOLD) contrast change during autoregulation and hypotension using hemodynamic MRI.

Methods
—Using arterial spin labeling and steady-state susceptibility contrast, we measured CBF and changes in both total and microvascular CBV during hemorrhagic hypotension in the rat (n=9).

Results
—We observed CBF autoregulation for mean arterial blood pressure (MABP) between 50 and 140 mm Hg, at which average CBF was 1.27±0.44 mL · g
−1
· min
−1
(mean±SD). During autoregulation, total and microvascular CBV changes were small and not significantly different from CBF changes. Consistent with this, no significant BOLD changes were observed. For MABP between 10 and 40 mm Hg, total CBV in the striatum increased slightly (+7±12%,
P
<0.05) whereas microvascular CBV decreased (−15±17%,
P
<0.01); on the cortical surface, total CBV increases were larger (+21±18%,
P
<0.01) and microvascular CBV was unchanged (3±22%,
P
>0.05). With severe hypotension, both total and microvascular CBV decreased significantly. Over the entire range of graded global hypoperfusion, there were increases in the CBV/CBF ratio.

Conclusions
—Parenchymal CBV changes are smaller than those of previous reports but are consistent with the small arteriolar fraction of total blood volume. Such measurements allow a framework for understanding effective compensatory vasodilation during autoregulation and volume-flow relationships during hypoperfusion.
A Deletion Polymorphism of α
2
-Macroglobulin Gene and Cerebral Amyloid Angiopathy
Authors: Yamada Masahito , Sodeyama Nobuyuki , Itoh Yoshinori , Suematsu Naomi , Otomo Eiichi , Matsushita Masaaki , Mizusawa Hidehiro
Published: June 2011

Background and Purpose
—α
2
-Macroglobulin may be implicated in amyloid β protein deposition. A deletion in the exon 18 splice acceptor of the α
2
-macroglobulin gene (
A2M
) has been reported to be associated with risk for Alzheimer’s disease (AD). In search of genetic risk factors for cerebral amyloid angiopathy (CAA), we investigated association of the
A2M
deletion polymorphism with CAA.

Methods
—The association between the severity of CAA and
A2M
deletion polymorphism was investigated in 178 autopsy cases of the elderly including 68 patients with AD.

Results
—There was no significant difference in the severity of CAA between individuals with the
A2M
deletion allele and those without in the AD, non-AD, or total cases. Status for the ε4 allele of the apolipoprotein E gene did not influence the results.

Conclusions
—Our results suggest that the
A2M
deletion polymorphism may not be a definitive risk factor of CAA in the elderly, although further study with larger samples is necessary to confirm this.
Impaired Cerebrovascular Reactivity as a Risk Marker for First-Ever Lacunar Infarction
Authors: Molina Carlos , Sabín José Alvarez , Montaner Joan , Rovira Alex , Abilleira Sonia , Codina Agustín
Published: June 2011

Background and Purpose
—Functional assessment of small arteries and arterioles could provide valuable information regarding the extent of diffuse arteriolosclerosis in patients with small-vessel disease. Therefore we attempted to clarify the role of cerebrovascular reactivity (CVR) as a risk marker for first-ever symptomatic lacunar infarction.

Methods
—Forty-six patients with lacunar infarction and 46 sex- and age-matched control subjects were prospectively evaluated. Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. CVR was examined by calculating the percent increase in mean flow velocity occurring after 15 mg/kg acetazolamide administration (Diamox test).

Results
—CVR was significantly (
P
<0.0001, Student’s
t
test) lower in cases (50.0±12.7%) as compared with control subjects (65.2±12.4%). A multiple logistic regression analysis identified male sex (odds ratio [OR] 2.3,
P
=0.02), age (OR 3.6,
P
<0.005), and the presence of lacunar infarction on magnetic resonance imaging (OR 5.3,
P
<0.001) as significant and independent factors associated with a reduction of CVR. Moreover, a cut-point of 55.6% (sensitivity 67%, specificity 82%) was established as the threshold value for distinguishing between pathological and normal CVR. CVR was significantly (
P
=0.02) lower in patients with multiple (46.38±12.6%) than with single (54.83±11.58%) lacunar infarction. In addition, a trend of negative correlation was found between CVR and the number of lacunar infarctions (
r
=−0.26,
P
=0.08). In the multiple logistic model, history of hypertension (OR 7.24; 95% confidence interval 2.95 to 17.79) and CVR (OR 0.8; 95% confidence interval 0.81 to 0.93) emerge as significant and independent predictors of first-ever lacunar infarction.

Conclusions
—These data suggest that impaired CVR is a risk marker for first-ever lacunar infarction.
Echocontrast-Enhanced Ultrasound of Extracranial Internal Carotid Artery High-Grade Stenosis and Occlusion
Authors: Droste Dirk W. , Jürgens Rasmus , Nabavi Darius G. , Schuierer Georg , Weber Sepp , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Proper assessment of extracranial internal carotid artery high-grade stenosis and occlusion by extracranial color-coded duplex sonography (ECCD) is occasionally made difficult by shadowing, an unfavorable insonation angle, low flow velocity or volume, or a deep insonation depth. In these cases, echocontrast could be helpful to quantify the degree of stenosis and to diagnose occlusion.

Methods
—We investigated 17 arteries with poor precontrast investigation conditions and suspected high-grade stenosis or occlusion by contrast-enhanced ECCD.

Results
—Compared with the precontrast scans, echocontrast allowed for significantly more segments to be evaluated by pulsed Doppler sonography (
P
<0.001) and for longer lumen segments to be displayed on color mode (
P
<0.001). Because it was now possible to place the sample volume right into the jet of the stenosis, the maximal flow velocity registered increased in all patients with stenosis.

Conclusions
—Echocontrast-enhanced ECCD of the carotid arteries is helpful for stenosis classification in a small group of preselected patients with poor original examination conditions.
Serial Study of Apparent Diffusion Coefficient and Anisotropy in Patients With Acute Stroke
Authors: Yang Qing , Tress Brian M. , Barber P. Alan , Desmond Patricia M. , Darby David G. , Gerraty Richard P. , Li Ting , Davis Stephen M.
Published: June 2011

Background and Purpose
—We sought to characterize the evolution of apparent diffusion coefficient (ADC) and apparent diffusion anisotropy (ADA) in acute stroke and to evaluate their roles in predicting stroke evolution and outcome.

Methods
—We studied 26 stroke patients acutely (<24 hours), subacutely (3 to 5 days), and at outcome (3 months). Ratios of the ADC and ADA within a region of infarction and the normal contralateral region were evaluated and compared with the Canadian Neurological Scale, Barthel Index, and Rankin Scale.

Results
—Heterogeneity in ADC and ADA evolution was observed not only between patients but also within individual lesions. Three patterns of ADA evolution were observed: (1) elevated ADA acutely and subacutely; (2) elevated ADA acutely and reduced ADA subacutely; and (3) reduced ADA acutely and subacutely. At outcome, reduced ADA with elevated ADC was observed generally. We identified 3 phases of diffusion abnormalities: (1) reduced ADC and elevated ADA; (2) reduced ADC and reduced ADA; and (3) elevated ADC and reduced ADA. The ADA ratios within 12 hours correlated with the acute Canadian Neurological Scale (
r
=0.46,
P
=0.06), subacute Canadian Neurological Scale (
r
=0.55,
P
=0.02), outcome Barthel Index (
r
=0.62,
P
=0.01), and Rankin Scale (
r
=−0.77,
P
<0.0005) scores.

Conclusions
—Combined ADC and ADA provide differential patterns of stroke evolution. Early ADA changes reflect cellular alterations in acute ischemia and may provide a potential marker to predict stroke outcome.
Blockade of Central Angiotensin AT
1
Receptors Improves Neurological Outcome and Reduces Expression of AP-1 Transcription Factors After Focal Brain Ischemia in Rats
Authors: Dai Wen-Jie , Funk Alexandra , Herdegen Thomas , Unger Thomas , Culman Juraj
Published: June 2011

Background and Purpose
—Angiotensin-converting enzyme inhibitors have been shown to protect against stroke in hypertensive rats and to improve neurological outcome after cerebral ischemia in normotensive rats. The present study was designated to test the hypothesis that blockade of brain AT
1
receptors improves the recovery from focal cerebral ischemia and reduces expression of AP-1 transcription factors c-Fos and c-Jun, which have been associated with programmed cell death and neurodegeneration.

Methods
—Experiments were carried out in normotensive male Wistar rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion lasting for 90 minutes and followed by reperfusion. The selective AT
1
receptor antagonist irbesartan was infused intracerebroventricularly over a 5-day period before the induction of ischemia at a dose that inhibited brain but not vascular AT
1
receptors. Twenty-four hours after ischemia, neurological outcome was evaluated and expression of c-Fos and c-Jun proteins in the brain was studied immunocytochemically.

Results
—Focal brain ischemia resulted in a strong induction of c-Fos and c-Jun proteins in the cortex, which positively correlated with the degree of neurological deficits. Treatment of rats with irbesartan significantly improved neurological outcome of focal cerebral ischemia when compared with the vehicle-treated group and markedly reduced the expression of c-Fos and c-Jun proteins in the cortex on the ligated side of the brain. Irbesartan pretreatment completely abolished the ischemia-induced c-Fos expression in the hippocampus.

Conclusions
—The present study shows a relationship between c-Fos and c-Jun expression and neurological outcome after focal brain ischemia. Our data indicate that long-term blockade of central AT
1
receptors improves the recovery from brain ischemia and reduces the expression of c-Fos and c-Jun proteins in the brain. Pretreatment with an AT
1
receptor antagonist has beneficial effects after cerebral ischemia.
Copper-Zinc Superoxide Dismutase Prevents the Early Decrease of Apurinic/Apyrimidinic Endonuclease and Subsequent DNA Fragmentation After Transient Focal Cerebral Ischemia in Mice
Authors: Fujimura Miki , Morita-Fujimura Yuiko , Narasimhan Purnima , Copin Jean-Christophe , Kawase Makoto , Chan Pak H.
Published: June 2011

Background and Purpose
—DNA damage and its repair mechanism are thought to be involved in ischemia/reperfusion injury in the brain. We have previously shown that apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, rapidly decreased after transient focal cerebral ischemia (FCI) before the peak of DNA fragmentation. To further investigate the role of reactive oxygen species in APE/Ref-1 expression in vivo, we examined the expression of APE/Ref-1 and DNA damage after FCI in wild-type and transgenic mice overexpressing copper-zinc superoxide dismutase.

Methods
—Transgenic mice overexpressing copper-zinc superoxide dismutase and wild-type littermates were subjected to 60 minutes of transient FCI by intraluminal blockade of the middle cerebral artery. APE/Ref-1 protein expression was analyzed by immunohistochemistry and Western blot analysis. DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase–mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL).

Results
—A similar level of APE/Ref-1 was detected in the control brains from both groups. APE/Ref-1 was significantly reduced 1 hour after transient FCI in both groups, whereas the transgenic mice had less reduction than that seen in wild-type mice 1 and 4 hours after FCI. DNA laddering was detected 24 hours after FCI and was decreased in transgenic mice. Double staining with APE/Ref-1 and TUNEL showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive.

Conclusions
—These results suggest that reactive oxygen species contribute to the early decrease of APE/Ref-1 and thereby exacerbate DNA fragmentation after transient FCI in mice.
Ischemic Stroke Subtypes
Authors: Petty George W. , Brown Robert D. , Whisnant Jack P. , Sicks JoRean D. , O’Fallon W. Michael , Wiebers David O.
Published: June 2011

Background and Purpose
—There is scant population-based information on incidence and risk factors for ischemic stroke subtypes.

Methods
—We identified all 454 residents of Rochester, Minn, with a first ischemic stroke between 1985 and 1989 from the Rochester Epidemiology Project medical records linkage system. We used Stroke Data Bank criteria to assign infarct subtypes after reviewing medical records and brain imaging. We adjusted average annual incidence rates by age and sex to the US 1990 population and compared the age-adjusted frequency of stroke risk factors across ischemic stroke subtypes.

Results
—Age- and sex-adjusted incidence rates (per 100 000 population) were as follows: large-vessel cervical or intracranial atherosclerosis with >50% stenosis, 27; cardioembolic, 40; lacuna, 25; uncertain cause, 52; other or uncommon cause, 4. Sex differences in incidence rates were detected only for atherosclerosis with stenosis (47 [95% CI, 34 to 61] for men; 12 [95% CI, 7 to 17] for women). There was no difference in prior transient ischemic attack and hypertension among subtypes, and diabetes was not more common among patients with lacunar infarction than other common subtypes.

Conclusions
—The age-adjusted incidence rate of stroke due to stenosis of the large cervicocephalic vessels is nearly 4 times higher for men than for women. There is no association between preceding transient ischemic attack and stroke mechanism. Diabetes and hypertension are not more common among patients with lacunae. Age- and sex-adjusted incidence rates for ischemic stroke subtypes in this population can be compared with similarly determined rates from other populations.
Different Risk Factors for Different Stroke Subtypes
Authors: Leppälä Jaana M. , Virtamo Jarmo , Fogelholm Rainer , Albanes Demetrius , Heinonen Olli P.
Published: June 2011

Background and Purpose
—Blood pressure is an important risk factor for stroke, but the roles of serum total and HDL cholesterol, α-tocopherol, and β-carotene are poorly established. We studied these factors in relation to stroke subtypes.

Methods
—Male smokers (n=28 519) aged 50 to 69 years without a history of stroke participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a controlled trial to test the effect of α-tocopherol and β-carotene supplementation on cancer. From 1985 to 1993, a total of 1057 men suffered from primary stroke: 85 had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke.

Results
—Systolic blood pressure ≥160 mm Hg increased the risk of all stroke subtypes 2.5 to 4-fold. Serum total cholesterol was inversely associated with the risk of intracerebral hemorrhage, whereas the risk of cerebral infarction was raised at concentrations ≥7.0 mmol/L. The risks of subarachnoid hemorrhage and cerebral infarction were lowered with serum HDL cholesterol levels ≥0.85 mmol/L. Pretrial high serum α-tocopherol decreased the risk of intracerebral hemorrhage by half and cerebral infarction by one third, whereas high serum β-carotene doubled the risk of subarachnoid hemorrhage and decreased that of cerebral infarction by one fifth.

Conclusions
—The risk factor profiles of stroke subtypes differ, reflecting different etiopathology. Because reducing atherosclerotic diseases, including ischemic stroke, by lowering high serum cholesterol is one of the main targets in public health care, further studies are needed to distinguish subjects with risk of hemorrhagic stroke. The performance of antioxidants needs confirmation from clinical trials.
A Randomized Efficacy Trial of Citicoline in Patients With Acute Ischemic Stroke
Authors: Clark Wayne M. , Williams Benjamin J. , Selzer Kenneth A. , Zweifler Richard M. , Sabounjian LuAnn A. , Gammans Richard E.
Published: June 2011

Background and Purpose
—Citicoline (cytidine-5′-diphosphocholine; CDP-choline) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects.

Methods
—The current trial was a 33-center, randomized, double-blind, efficacy trial in 394 patients comparing placebo (n=127) with citicoline (n=267) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up period. Patients with acute (24 hours) ischemic strokes clinically assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale (NIHSS) ≥5 were enrolled.

Results
—Mean time to treatment was 12 hours, and mean age was 71 for placebo and 70 for citicoline. Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS <8 (34% vs 22%;
P
<0.01). The incidence and type of side effects were similar between the groups. The planned primary analysis (logistic regression: 5 categories Barthel) failed the proportional odds assumption and was rendered unreliable. There were no between-group differences seen on the planned secondary assessment analyses at 90 days, including the Barthel Index ≥95 at 12 weeks (last observation carried forward: placebo 40%; citicoline 40%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS ≥8 found that citicoline-treated patients were more likely to have a full recovery (Barthel ≥95): placebo 21%; citicoline 33%;
P
=0.05; whereas no difference was seen in patients with baseline NIHSS<8 (placebo 77%; citicoline 69%;
P
>0.1.

Conclusions
—The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial. Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit.
Absence of Response to Early Transcranial Magnetic Stimulation in Ischemic Stroke Patients
Authors: Pennisi Giovanni , Rapisarda Giuseppe , Bella Rita , Calabrese Vittorio , Maertens de Noordhout Alain , Delwaide Paul Jean
Published: June 2011

Background and Purpose
—Transcranial magnetic stimulation (TMS) has been proposed as a prognostic tool in stroke patients. Most of the previous studies agree in considering the presence of motor-evoked potentials (MEPs) in the first days after a stroke as an indicator of good outcome. In the present study, we have assessed the prognostic value of the absence of response to early TMS on hand motor recovery in stroke patients with complete hand palsy at onset due to ischemia in the area of the middle cerebral artery.

Methods
—Fifteen patients submitted to TMS within 48 hours of stroke onset (defined as day 1) and again after 1 year. They were also evaluated clinically on day 1 by a scale derived from the Medical Research Council (MRC) and by the National Institutes of Health (NIH) stroke scale; they were reevaluated by the same scales and by Barthel Index on day 365.

Results
—On day 1, all the patients had complete hand palsy and no response to TMS; their NIH scores showed great variability. After 1 year, 6 of 15 patients regained small and prolonged MEPs, together with a very poor and not functionally useful motor recovery. NIH scores were significantly improved. Barthel Index scores showed large interindividual differences and were not correlated with MRC scores.

Conclusions
—We conclude that in patients with complete hand palsy, the absence of response to TMS in the first hours is predictive of absent or very poor, not useful, hand motor recovery.
Delayed Treatment With AM-36, a Novel Neuroprotective Agent, Reduces Neuronal Damage After Endothelin-1–Induced Middle Cerebral Artery Occlusion in Conscious Rats
Authors: Callaway Jennifer K. , Knight Melissa J. , Watkins Dianne J. , Beart Philip M. , Jarrott Bevyn
Published: June 2011

Background and Purpose
—AM-36 is a novel arylalkylpiperazine with combined antioxidant and Na
+
channel blocking actions. Individually, these properties have been shown to confer neuroprotection in a variety of in vitro and in vivo animal models of stroke. Preliminary studies have shown that AM-36 is neuroprotective in vivo. The purpose of the present study was to assess the neuroprotective and behavioral outcome after delayed administration of AM-36 in an endothelin-1–induced, middle cerebral artery model of cerebral ischemia in conscious rats.

Methods
—Conscious male hooded Wistar rats were subjected to middle cerebral artery occlusion by perivascular microinjection of endothelin-1 via a previously implanted cannula. AM-36 (6 mg/kg IP) or vehicle was administered intraperitoneally 30, 60, or 180 minutes after middle cerebral artery occlusion. Functional outcome was determined 24, 48, and 72 hours after stroke by neurological deficit score, motor performance, and sensory hemineglect tests. Rats were killed at 72 hours, and infarct area and volume were determined by histology and computerized image analysis.

Results
—Endothelin-1–induced middle cerebral artery occlusion resulted in marked functional deficits and neuronal damage. AM-36 significantly reduced cortical damage when administration was delayed until 30, 60, or 180 minutes after stroke. Interestingly, neuronal damage was time-dependently reduced, with the greatest protection found when AM-36 was administered 180 minutes after stroke. Striatal damage was significantly reduced after treatment with AM-36 at 180 minutes after stroke. Functional outcome paralleled histopathology. Rota-rod performance, sensory hemineglect, and neurological deficit scores returned to preischemia levels in AM-36–treated rats by 72 hours after stroke when administration was delayed by 180 minutes after stroke.

Conclusions
—AM-36 potently protects against both neuronal damage and functional deficits even when administered up to 180 minutes after induction of stroke. In fact, the greatest protection was found when administration was delayed by 180 minutes after stroke. The possible mechanisms of action of AM-36 are discussed. The present findings suggest that AM-36 may have great promise in the acute treatment of human stroke.
Chlamydia pneumoniae
but Not Cytomegalovirus Antibodies Are Associated With Future Risk of Stroke and Cardiovascular Disease
Authors: Fagerberg Björn , Gnarpe Judy , Gnarpe Håkan , Agewall Stefan , Wikstrand John
Published: June 2011

Background and Purpose
—Several cross-sectional and prospective studies have indicated that high titers of antibodies to
Chlamydia pneumoniae
and cytomegalovirus (CMV) are associated with coronary heart disease. The aim of the present study was to examine whether elevated titers of antibodies to these pathogens are predictive of not only coronary but also cerebrovascular disease.

Methods
—Serum titers of antibodies to
C pneumoniae
(IgM, IgG, IgA, IgG immune complex) and CMV (IgG) were determined at baseline (n=130) and after 3.5 years (n=111) in a total sample of 152 men. All individuals had treated hypertension and at least 1 additional risk factor for cardiovascular disease (hypercholesterolemia, smoking, or diabetes mellitus) and constituted 93% of a randomly selected subgroup (n=164) of patients participating in a multiple risk factor intervention study.

Results
—Elevations of any or both of the IgA or IgG titers to
C pneumoniae
at entry or after 3.5 years were found in 84 cases (55%). Of those with high titers at entry, 97% remained high at the 3.5 year reexamination. After 6.5 years of follow-up, high titers to
C pneumoniae
at entry were associated with an increased risk for future stroke (relative risk [RR], 8.58;
P
=0.043; 95% CI, 1.07 to 68.82) and for any cardiovascular event (RR, 2.69;
P
=0.042; 95% CI, 1.04 to 6.97). A high serum titer of antibodies to CMV was found in 125 cases (85%), and this was not associated with an increased risk of future cardiovascular events.

Conclusions
—Seropositivity for
C pneumoniae,
but not for CMV, was associated with an increased risk for future cardiovascular disease and, in particular, stroke.
Incidence Trends of Ischemic Stroke and Transient Ischemic Attacks in a Well-Defined French Population From 1985 Through 1994
Authors: Lemesle M. , Milan C. , Faivre J. , Moreau T. , Giroud M. , Dumas R.
Published: June 2011

Background and Purpose
—The changing incidence of ischemic stroke is of major concern in view of its public health impact, to define the population concerned, to identify risk factors, and to set up health-care systems. The aim of this study was to evaluate the time trends associated with the incidence of all the subtypes of ischemic stroke and transient ischemic attacks in a well-defined population for 10 years.

Methods
—Since 1985, a population registry has recorded each patient living in Dijon (France) who suffered from a cerebrovascular disease (CVD) regardless of the type of management. This study involved all patients suffering from their first ischemic stroke and their first transient ischemic attacks (TIAs) during 1 calendar year between January 1, 1985 and December 31, 1994. The incidence changes according to age, sex, and type of cerebral ischemic event (cortico-subcortical infarct, lacunar infarct, and TIA) were studied on the basis of their annual variations.

Results
—During the 10-year study period, 834 cortico-subcortical infarcts (52.1%), 296 lacunar infarcts (18.5%), 369 TIAs (23.1%), and 101 undetermined ischemic strokes (6.3%) were collected. The incidence of all ischemic events was relatively stable in both sexes over the 10-year period. However, the incidence rates differed according to age and type of ischemia. An increased incidence of cerebral cortico-subcortical infarct was observed in patients older than 75 years of age (+5.45% annual change [AC] in men,
P
<0.05; +5.09% AC in women, NS). In parallel, a higher proportion of emboligenic cardiac arrhythmias was observed in these patients (
P
<0.001). The incidence of lacunar infarcts tended to decrease, regardless of age but mainly in men under younger than 75 years of age (−12.74% AC in men, NS; +0.31% AC in women, NS). The incidence of TIAs was relatively stable in both sexes. Because our population consisted of a large number of elderly subjects, the increase in cardioembolic causes could partially explain the increased incidence of cerebral cortico-subcortical infarcts in patients older than 75 years of age.

Conclusions
—These preliminary data emphasize the importance of stroke surveillance in considering the variations of the different mechanisms of ischemic cerebrovascular disease. Although the incidence of TIA is stable and the incidence of lacunes tends to decrease in men, mainly before 75 years of age, we emphasize the rise of the crude incidence of cortico-subcortical infarcts in men older than 75 years of age, induced by an increase in cardioembolic causes.
Standardization of Carotid Ultrasound
Authors: Ranke Carsten , Creutzig Andreas , Becker Hartmut , Trappe Hans-Joachim
Published: June 2011

Background and Purpose
—Accurate carotid Doppler examination is an important issue in the light of large endarterectomy trials, but recommended cutoff values for detection of >70% stenosis vary widely. Standardization of diagnostic criteria should consider patient variation and instrument variability.

Methods
—We prospectively analyzed various Doppler parameters in 44 patients undergoing carotid angiography to evaluate whether normalization through individual reference measurements from the common carotid artery or the distal internal carotid artery could improve accuracy. For assessment of interindividual and interequipment variability, we performed repeated measurements of 40 carotid arteries in 21 patients. Two color-coded duplex ultrasound systems were compared for machine variability estimation: Hewlett Packard SONOS 2500 and ATL Ultramark 9 HDI.

Results
—Intrastenotic divided by distally recorded mean blood flow velocity (mean velocity ratio) showed the closest correlation with angiography:
R
2
=0.93. Mean velocity ratio >5 was 97% sensitive and 98% specific for detection of >70% carotid stenosis. Intrastenotic blood flow velocities were significantly different between the 2 duplex systems (0.22±0.16 versus 0.17±0.11 m/s;
P
<0.001), whereas mean velocity ratio values did not differ significantly. Interobserver variation expressed as 95% CI for predicted stenosis between 2 observers was 13.6% (peak systolic velocity) and 15.4% (mean velocity ratio).

Conclusions
—A mean velocity ratio using distal reference measurement in the internal carotid artery can normalize for interindividual and interequipment variability.
Gene Transfer of Human Prostacyclin Synthase Prevents Neointimal Formation After Carotid Balloon Injury in Rats
Authors: Todaka T. , Yokoyama C. , Yanamoto H. , Hashimoto N. , Nagata I. , Tsukahara T. , Hara S. , Hatae T. , Morishita R. , Aoki M. , Ogihara T. , Kaneda Y. , Tanabe T.
Published: June 2011

Background and Purpose
—A disordered proliferative process in the vascular wall is thought to underlie the pathogenesis of restenosis after percutaneous transluminal angioplasty and carotid endarterectomy. A growth inhibitory property of overexpressed prostacyclin (PGI
2
) synthase (PGIS) was recently implicated in the pathological proliferation of vascular smooth muscle cells (VSMC) in vitro. Here, we investigated the effects of increased PGI
2
synthesis on the pathological proliferation of VSMCs.

Methods
—The cDNA encoding human PGIS was transfected into endothelium-denuded rat carotid arteries after arterial balloon injury with the use of hemagglutinating virus Japan (HVJ). HVJ liposome vector complex without PGIS cDNA was used for vehicle control. The level of 6-keto PGF
1α
, a stable hydrolyzed metabolite of PGI
2
, the histological distribution of the immunoreactivity for human PGIS and the ratio of neointimal/medial area were analyzed.

Results
—In the analyses of 6-keto PGF
1α
, the level in the carotid arteries was significantly elevated 3 days after PGIS expression-vector transfection compared with that in the arteries after vehicle transfection. Seven days after human PGIS expression-vector transfection, the PGIS cDNA–transfected neointimal cells were strongly positive for human PGIS immunoreactivity in 81% sections examined. Fourteen days after the injury, the ratio of neointimal/medial area was 1.2±0.4 in the PGIS expression-vector transfected group, which was significantly smaller than that of the vehicle control group, 1.7±0.5;
P
<0.01.

Conclusions
—It was thus demonstrated that the gene transfer of human PGIS expression-vector into rat carotid arteries resulted in the increased production of human PGI
2
in the vascular wall, the expression of human PGIS in the developing neointima and significantly inhibited the neointimal formation generated after balloon injury.
Cross-Sectional and 4-Year Longitudinal Associations Between Brachial Pulse Pressure and Common Carotid Intima-Media Thickness in a General Population
Authors: Zureik Mahmoud , Touboul Pierre-Jean , Bonithon-Kopp Claire , Courbon Dominique , Berr Claudine , Leroux Chantal , Ducimetière Pierre
Published: June 2011

Background and Purpose
—The cross-sectional and 4-year longitudinal associations between brachial pulse pressure (PP) and ultrasound measurements of common carotid intima-media thickness (CCA-IMT) were assessed.

Methods
—A population of 957 volunteers aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France) and reexamined 4 years later. Longitudinal changes in PP and CCA-IMT were computed as the difference between 4-year follow-up and baseline values.

Results
—Baseline CCA-IMT and PP were positively associated in both age- and sex-adjusted analysis (partial correlation coefficient=0.20,
P
<0.001) and in multivariate analysis adjusted for traditional cardiovascular risk factors and mean blood pressure (partial correlation coefficient=0.18,
P
<0.001). In longitudinal analysis, baseline PP was associated with the change in 4-year CCA-IMT (partial correlation coefficient=0.11,
P
<0.001), and baseline CCA-IMT was a predictor of the 4-year change in PP (partial correlation coefficient=0.10, 0.001<
P
<0.01). No association between mean blood pressure and CCA-IMT was observed once PP was taken into account, in either cross-sectional or longitudinal analyses (partial correlation coefficients ranged from 0.00 to 0.03). Similar patterns of results were observed in hypertensive, nonhypertensive, and antihypertensive-treated and -nontreated subjects.

Conclusions
—This longitudinal study of a large population of relatively aged subjects suggests that elevated levels of PP are associated with the progression of CCA-IMT, and increased CCA-IMT is associated with PP widening. The nature of these relationships and whether atherosclerosis progression over time is involved or not in these associations merit further investigations.
A Clinical Guide to Assess the Role of Lower Limb Extensor Overactivity in Hemiplegic Gait Disorders
Authors: Yelnik A. , Albert T. , Bonan I. , Laffont I.
Published: June 2011

Background and Purpose
—The aim of this study was to assess the role of knee and ankle extensor overactivity in the hemiplegic gait observed in stroke victims and to propose a clinical guide for selecting patients before treatment of a supposed disabling spasticity.

Methods
—A standardized physical examination procedure was performed in 135 consecutive stroke patients. All patients were able to walk without human assistance. The period after stroke ranged from 3 to 24 months (mean, 11.5±7.25 months). Spasticity was evaluated with the stroke victim in sitting position and during walking. Overactivity of the quadriceps was considered disabling when inducing inability to flex the knee during the swing phase despite adequate control of knee flexion in sitting and standing positions; overactivity of the triceps surae was considered to be disabling when heel strike was not possible despite good control of the ankle flexion in sitting position; triceps retraction was also considered.

Results
—Disabling overactivity was observed in 56 (41.5%) patients: 11 times for the quadriceps femoris, 21 times for the triceps surae, and 21 times for both muscles. It was considered to be the main disorder impairing gait among only 16 (12%) patients: 9 for the quadriceps alone, 3 for the triceps alone, and 4 for both. Sitting spasticity of the lower limb was not predictive of disabling overactivity during walking.

Conclusions
—Extensor muscle overactivity is one of the components of gait disorders in stroke patients. The difficulty in assessing spasticity and its real causal effect in gait disturbances are discussed. A clinical guide is proposed.
Diffusion- and Perfusion-Weighted Imaging in Vasospasm After Subarachnoid Hemorrhage
Authors: Rordorf Guy , Koroshetz Walter J. , Copen William A. , Gonzalez Gilberto , Yamada Kei , Schaefer Pamela W. , Schwamm Lee H. , Ogilvy Christopher S. , Sorensen A. Gregory
Published: June 2011

Background and Purpose
—Better measures of cerebral tissue perfusion and earlier detection of ischemic injury are needed to guide therapy in subarachnoid hemorrhage (SAH) patients with vasospasm. We sought to identify tissue ischemia and early ischemic injury with combined diffusion-weighted (DW) and hemodynamically weighted (HW) MRI in patients with vasospasm after SAH.

Methods
—Combined DW and HW imaging was used to study 6 patients with clinical and angiographic vasospasm, 1 patient without clinical signs of vasospasm but with severe angiographic vasospasm, and 1 patient without angiographic spasm. Analysis of the passage of an intravenous contrast bolus through brain was used to construct multislice maps of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and tissue mean transit time (tMTT). We hypothesize that large HW imaging (HWI) abnormalities would be present in treated patients at the time they develop neurological deficit due to vasospasm without matching DW imaging (DWI) abnormalities.

Results
—Small, sometimes multiple, ischemic lesions on DWI were seen encircled by a large area of decreased rCBF and increased tMTT in all patients with symptomatic vasospasm. Decreases in rCBV were not prominent. MRI hemodynamic abnormalities occurred in regions supplied by vessels with angiographic vasospasm or in their watershed territories. All patients with neurological deficit showed an area of abnormal tMTT much larger than the area of DWI abnormality. MRI images were normal in the asymptomatic patient with angiographic vasospasm and the patient with normal angiogram and no clinical signs of vasospasm.

Conclusions
—We conclude that DW/HW MRI in symptomatic vasospasm can detect widespread changes in tissue hemodynamics that encircle early foci of ischemic injury. With additional study, the technique could become a useful tool in the clinical management of patients with SAH.
β-Amyloid Load Is Not Influenced by the Severity of Cardiovascular Disease in Aged and Demented Patients
Authors: Irina Alafuzoff , Seppo Helisalmi , Arto Mannermaa , Paavo Riekkinen , Hilkka Soininen
Published: June 2011

Background and Purpose
—This study was conducted to analyze the association between reported risk factors for Alzheimer’s disease, apolipoprotein E ε4 allele, and cardiovascular disease and neuropathological changes essential for the diagnosis of Alzheimer’s disease.

Methods
—Our data are based on clinical and postmortem evaluations of a cohort of nondemented (n=118) and demented (n=107) individuals. A cardiovascular index was calculated at autopsy to estimate the extent of cardiovascular disease. Neuropathological lesions such as senile/neuritic plaques, neurofibrillary tangles, β-amyloid load, cerebral amyloid angiopathy, and the load of paired helical filaments were determined.

Results
—The aforementioned neuropathological lesions did not show any positive significant correlation with cardiovascular index. In contrast, the extent of Alzheimer’s lesions was significantly higher in those nondemented and demented patients carrying the apolipoprotein E ε4 allele than in those without this allele.

Conclusions
—Our results demonstrate that the apolipoprotein E ε4 allele, but not cardiovascular disease, indeed influences the extent of Alzheimer’s lesions seen in the brain tissue of demented patients as well as asymptomatic controls.
Continuing Postischemic Neuronal Death in CA1
Authors: Colbourne Frederick , Li Hui , Buchan Alastair M.
Published: June 2011

Background and Purpose
—Transient forebrain ischemia results in a 24- to 72-hour delayed loss of CA1 neurons. Previous work has not assessed whether insult durations can vary the degree and maturation rate of CA1 injury and whether there are different ultrastructural features of death after brief or severe ischemia. We also tested whether known cytoprotective drugs achieve permanent or transient neuroprotection.

Methods
—In the first experiment, ischemia was induced for 5, 15, or 30 minutes with the use of the 4-vessel occlusion rat model with 1- to 28-day survival. Others subjected to 5 or 15 minutes of ischemia and allowed to survive for 14 or 7 days, respectively, were examined with electron microscopy. Finally, we determined whether NBQX (30 mg/kg ×3 at 0 or 6 hours after ischemia), an AMPA antagonist, and SNX-111 (5 mg/kg at 6 hours after ischemia), an N-type Ca
2+
channel antagonist, provided enduring CA1 protection against 10 minutes of ischemia.

Results
—CA1 damage was not detected at 24 hours. Thirty minutes of ischemia produced 47% and 84% CA1 damage at 2 and 3 days, respectively. A 15-minute occlusion yielded 11%, 74%, and 86% loss at 2, 3, and 7 days, respectively. Five minutes of ischemia produced an even slower progression with 24%, 52%, and 59% loss at 3, 7, and 14 days, respectively. Ultrastructural examination after 5 and 15 minutes of ischemia revealed necrosis with no morphological evidence of apoptosis. Both NBQX (
P
<0.021) and SNX-111 (
P
<0.001) significantly reduced CA1 death at 7 days (≤35%) but not at 28 days (≥80%) compared with saline treatment (≈79%).

Conclusions
—Brief forebrain ischemia results in a slower progression of CA1 loss than more severe insults. Nonetheless, neuronal injury had necrotic, not apoptotic, morphology. NBQX and SNX-111 only postponed CA1 injury.
Spatz-Lindenberg Disease
Authors: Larner A. J. , Kidd Desmond , Elkington Paul , Rudge Peter , Scaravilli Francesco
Published: June 2011

Background
—Isolated cerebral thromboangiitis obliterans (Spatz-Lindenberg disease) is not well recognized as a cause of vascular dementia.

Case Description
—A 58-year-old woman presented with dementia and pyramidal signs. Neuroimaging showed multiple areas of white matter change. Brain biopsy showed intimal thickening of the walls of leptomeningeal and intraparenchymal arteries, almost to complete occlusion, with an intact internal elastic lamina and media and without inflammation or infiltration. The cortex showed only moderate gliosis.

Conclusions
—Spatz-Lindenberg disease should be considered in the differential diagnosis of vascular dementia. Additional studies of its pathogenesis are required to determine appropriate treatment.
Plasticity of Language-Related Brain Function During Recovery From Stroke
Authors: Thulborn Keith R. , Carpenter Patricia A. , Just Marcel A.
Published: June 2011

Background and Purpose
—This study was undertaken to correlate functional recovery from aphasia after acute stroke with the temporal evolution of the anatomic, physiological, and functional changes as measured by MRI.

Methods
—Blood oxygenation level–dependent contrast and echo-planar MRI were used to map language comprehension in 6 normal adults and in 2 adult patients during recovery from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and conventional anatomic MRI were used to follow physiological and structural changes.

Results
—The normal activation pattern for language comprehension showed activation predominately in left-sided Wernicke’s and Broca’s areas, with laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed as having a completed stroke affecting Broca’s area occurred rapidly with a shift of activation to the homologous region in the right hemisphere within 3 days, with continued rightward lateralization over 6 months. In the second patient, in whom mapping was performed fortuitously before stroke, recovery of a Wernicke’s aphasia showed a similar increasing rightward shift in activation recruitment over 9 months after the event.

Conclusions
—Recovery of aphasia in adults can occur rapidly and is concomitant with an activation pattern that changes from left to a homologous right hemispheric pattern. Such recovery occurs even when the stroke evolves to completion. Such plasticity must be considered when evaluating stroke interventions based on behavioral and neurological measurements.