bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequencies of Certain Complement Protein Alleles and Serum Levels of Anti–Heat-Shock Protein Antibodies in Cerebrovascular Diseases
Authors: Kramer Judit , Harcos Péter , Prohászka Zoltán , Horváth Laura , Karádi István , Singh Mahavir , Császár Albert , Romics László , Füst George
Published: June 2011

Background and Purpose
—A strong correlation exists between the intensity of atherosclerotic alterations in different arteries. Marked differences exist, however, in the age and sex distribution and risk factors for coronary heart disease (CHD) and cerebrovascular disease (CVD). We therefore performed genetic and immunologic studies in patients with CVD.

Methods
—We studied 292 patients with CVD (stroke or transient ischemic attack) and as control either 198 healthy blood donors and 485 healthy elderly (aged >60 years) people (genetic study) or 94 blood donors aged 45 to 60 years and 49 healthy elderly (aged >60 years) people (anti–heat-shock protein [hsp] measurements). Allele frequencies of 3 genes (C4A, C4B, and C3) encoding proteins of the complement system were determined by electrophoresis and immunofixation. Serum concentration of autoantibodies against 60-kDa heat-shock protein (anti-hsp60) was measured by the enzyme-linked immunosorbent assay method.

Results
—Marked differences were observed between CVD patients and controls in the genetic studies. In the CVD patients aged >60 years, the frequency (11.3%) of the deficient allele of the C4B gene (C4B*Q0) was significantly (
P
=0.0003) higher than that of the healthy controls (5.4%). By contrast, in the group aged 45 to 60 years, the frequency of the C4B*Q0 allele was lower in patients than in controls. Serum concentration of anti-hsp60 in the CVD patients did not differ from control values.

Conclusions
—In previous studies C4B*Q0 frequency was reported to be higher in CHD patients aged 45 to 60 years than in aged-matched controls. Moreover, high anti-hsp60 levels were found in CHD patients. These findings contrast with our present report of lower frequency of C4B*Q0 in CVD patients. Therefore, genetic and immunologic factors may at least partly explain the differences between the natural history and risk factors of CHD and CVD.
Systematic Review of Diffusion and Perfusion Imaging in Acute Ischemic Stroke
Authors: Keir S. L. , Wardlaw J. M.
Published: June 2011

Background and Purpose
—Recent advances in neuroimaging have raised hopes of early and accurate identification of ischemic brain and the discrimination of dead from salvageable tissue. We sought to determine whether the data published so far are enough to establish the roles of these techniques in everyday clinical practice.

Methods
—A systematic review of studies of MR diffusion-weighted imaging (DWI), perfusion imaging (PI), or a combination of the two, in human stroke, excluding abstracts and case reports. One reviewer extracted information on the size of each study, its main purpose, methodological details, and results.

Results
—We identified 47 studies of DWI, 18 studies of MR PI alone or in combination with another advanced imaging modality, and 19 studies of DWI and PI together. Although high proportions of the studies were prospective and gave good details of the imaging sequences used, the majority gave very limited details on patient selection and clinical characteristics or blinded imaging assessment. Pathophysiological changes were inferred from DWI/PI patterns that were not supported by other data.

Conclusions
—Despite considerable enthusiasm for and promise of these techniques, there is not sufficient information available in these studies to enable us to draw firm conclusions about the sensitivity and specificity of these techniques for identification of either ischemic lesions not visible by other means or salvageable tissue. Future studies should include larger numbers of carefully described patients, assess the contribution of DWI over and above other imaging, obtain follow-up at an appropriate time interval to determine accurate clinical and neuroradiological outcomes, and assess DWI/PI abnormality with reperfusion in randomized treatment trials. Investigators should also be encouraged to combine their individual patient data in meta-analyses to obtain a more robust assessment of the value of DWI and PI from larger sample sizes.
Assessment of the Thigh Cuff Technique for Measurement of Dynamic Cerebral Autoregulation
Authors: Mahony Peter J. , Panerai Ronney B. , Deverson Stephanie T. , Hayes Paul D. , Evans David H.
Published: June 2011

Background and Purpose
—Dynamic methods of measuring cerebral autoregulation have become an accepted alternative to static evaluation. This article aims to describe a set of data collected from healthy volunteers by a dynamic method, the purpose being to qualify and quantify expected results for those who may be designing a study using this technique.

Methods
—Cerebral blood flow velocity (CBFV) (measured by transcranial Doppler) and arterial blood pressure (Finapres) were recorded in 16 normal subjects before, during, and after the induction of a blood pressure drop (release of bilateral thigh cuffs). This procedure was repeated 6 times for each subject. A mathematical model was applied to the data to generate an autoregulatory index (ARI) with values between 0 and 9.

Results
—The ARI values for this sample population follow a normal distribution, with a mean±SD of 4.98±1.06 (n=15). Analysis of the cumulative mean ARI values of all subjects showed an exponential-type convergence of ARI toward the sample mean as the number of test iterations increased. The population average blood pressure drop on thigh cuff release was 26.4±7.1 mm Hg (n=16), occurring in 4.6±1.7 seconds. The corresponding population average drop for CBFV was 15.6±5.8 cm/s, taking 2.5±1.0 seconds. No significant trend was noted in the measurements as the number of test iterations increased. The correlation between the predicted and actual CBFV, having a mean value of 0.76±0.19, showed evidence of a nonlinear relationship to ARI values. Significant correlation was also found between ARI and (1) arterial blood pressure before cuff release and (2) the magnitude of the drop in CBFV on cuff release.

Conclusions
—The distribution of ARI values is not significantly different from normal. At least 3 iterations of the test procedure should be performed and averaged to obtain the mean ARI for each subject. There is no significant evidence of physiological accommodation as the number of test iterations increases. The effects of mean blood pressure and the magnitude of the change in CBFV should be considered as possible covariates when ARI data are analyzed.
Decreased Perihematomal Edema in Thrombolysis-Related Intracerebral Hemorrhage Compared With Spontaneous Intracerebral Hemorrhage
Authors: Gebel James M. , Brott Thomas G. , Sila Cathy A. , Tomsick Thomas A. , Jauch Edward , Salisbury Shelia , Khoury Jane , Miller Rosemary , Pancioli Arthur , Duldner John E. , Topol Eric J. , Broderick Joseph P.
Published: June 2011

Background and Purpose
—Intracerebral hemorrhage (ICH) is a highly morbid disease process. Perihematomal edema is reported to contribute to clinical deterioration and death. Recent experimental observations indicate that clotting of the intrahematomal blood is the essential prerequisite for hyperacute perihematomal edema formation rather than blood-brain barrier disruption.

Methods
—We compared a series of patients with spontaneous ICH (SICH) to a series of patients with thrombolysis-related ICH (TICH). All patients were imaged within 3 hours of clinical onset. We reviewed relevant neuroimaging features, emphasizing and quantifying perihematomal edema. We then analyzed clinical and radiological differences between the 2 ICH types and determined whether these factors were associated with perihematomal edema.

Results
—TICHs contained visible perihematomal edema less than half as often as SICHs (31% versus 69%,
P
<0.001) and had both lower absolute edema volumes (0 cc [25th, 75th percentiles: 0, 6] versus 6 cc [0, 13],
P
<0.0001) and relative edema volumes (0.16 [0.10, 0.33] versus 0.55 [0.40, 0.83],
P
<0.0001). Compared with SICHs, TICHs were 3 times larger in volume (median [25th, 75th percentiles] volume 69 cc [30, 106] versus 21 cc [8, 45],
P
<0.0001), 4 times more frequently lobar in location (62% versus 15%,
P
<0.001), 80 times more frequently contained blood-fluid level(s) (86% versus 1%,
P
<0.001), and were more frequently multifocal (22% versus 0%,
P
<0.001).

Conclusions
—The striking qualitative and quantitative lack of perihematomal edema observed in the thrombolysis-related ICHs compared with the SICHs provides the first substantial, although indirect, human evidence that intrahematomal blood clotting is a plausible pathogenetic factor in hyperacute perihematomal edema formation.
High Rate of Complete Recanalization and Dramatic Clinical Recovery During tPA Infusion When Continuously Monitored With 2-MHz Transcranial Doppler Monitoring
Authors: Alexandrov Andrei V. , Demchuk Andrew M. , Felberg Robert A. , Christou Ioannis , Barber Philip A. , Burgin W. Scott , Malkoff Marc , Wojner Anne W. , Grotta James C.
Published: June 2011

Background and Purpose
—Clot dissolution with tissue plasminogen activator (tPA) can lead to early clinical recovery after stroke. Transcranial Doppler (TCD) with low MHz frequency can determine arterial occlusion and monitor recanalization and may potentiate thrombolysis.

Methods
—Stroke patients receiving intravenous tPA were monitored during infusion with portable TCD (Multigon 500M; DWL MultiDop-T) and headframe (Marc series; Spencer Technologies). Residual flow signals were obtained from the clot location identified by TCD. National Institutes of Health Stroke Scale (NIHSS) scores were obtained before and after tPA infusion.

Results
—Forty patients were studied (mean age 70±16 years, baseline NIHSS score 18.6±6.2, tPA bolus at 132±54 minutes from symptom onset). TCD monitoring started at 125±52 minutes and continued for the duration of tPA infusion. The middle cerebral artery was occluded in 30 patients, the internal carotid artery was occluded in 11 patients, the basilar artery was occluded in 3 patients, and occlusions were multiple in 7 patients; 4 patients had no windows; and 1 patient had a normal TCD. Recanalization on TCD was found at 45±20 minutes after tPA bolus: recanalization was complete in 12 (30%) and partial in 16 (40%) patients. Dramatic recovery during tPA infusion (total NIHSS score <3) occurred in 8 (20%) of all patients (baseline NIHSS range 6 to 22; all 8 had complete recanalization). Lack of improvement or worsening was associated with no recanalization, late recanalization, or reocclusion on TCD (C=0.811,
P
≤0.01). Improvement by ≥10 NIHSS points or complete recovery was found in 30% of all patients at the end of tPA infusion and in 40% at 24 hours. Improvement by ≥4 NIHSS points was found in 62.5% of patients at 24 hours.

Conclusions
—Dramatic recovery during tPA therapy occurred in 20% of all patients when infusion was continuously monitored with TCD. Recovery was associated with recanalization on TCD, whereas no early improvement indicated persistent occlusion or reocclusion. At 24 hours, 40% of all patients improved by ≥10 NIHSS points or recovered completely. Ultrasonic energy transmission by TCD monitoring may expose more clot surface to tPA and facilitate thrombolysis and deserves a controlled trial as a way to potentiate the effect of tPA therapy.
MRI Pontine Hyperintensity After Supratentorial Ischemic Stroke Relates to Poor Clinical Outcome
Authors: Mäntylä Riitta , Pohjasvaara Tarja , Vataja Risto , Salonen Oili , Aronen Hannu J. , Standertskjöld-Nordenstam Carl-Gustaf , Kaste Markku , Erkinjuntti Timo
Published: June 2011

Background and Purpose
—MRI studies in patients with atherosclerosis often reveal ill-defined hyperintensity in the pons on T2-weighted images. This pontine hyperintensity (PHI) does not fulfill the criteria of a brain infarct, and its clinical relevance is not established. We examined the frequency, as well as the radiological and clinical correlates, of PHI in poststroke patients.

Methods
—Three hundred nineteen patients were studied 3 months after supratentorial ischemic stroke with the use of 1.0-T MRI. Brain infarcts, atrophy, white matter hyperintensities, and PHI were registered. The clinical outcome was assessed 3 and 15 months after the stroke.

Results
—Of the patients, 152 (47.6%) had PHI. The risk factors for stroke did not differ in patients without or with PHI. PHI was related to a higher frequency (
P
=0.002) and larger volume (
P
<0.001) of supratentorial brain infarcts, to parietal (
P
=0.020) and temporal (
P
=0.002) atrophy, to central atrophy (
P
≤0.040), and to white matter hyperintensity grade (
P
<0.001). Brain infarcts that affected the corpus striatum (putamen, caudate, and pallidum) (
P
≤0.011) or pyramidal tract (
P
<0.001) were more frequent in patients with PHI. The 3- and 15-month outcomes were worse in patients with PHI (
P
≤0.004). The total volume of brain infarcts (OR 1.22), mean atrophy (OR 3.59), and PHI (OR 3.76) were independent correlates of a poor 15-month outcome.

Conclusions
—PHI after supratentorial ischemic stroke deserves attention because it relates to poor clinical outcome.
Diffusion-Weighted MRI and Proton MR Spectroscopic Imaging in the Study of Secondary Neuronal Injury After Intracerebral Hemorrhage
Authors: Carhuapoma Juan R. , Wang Paul Y. , Beauchamp Norman J. , Keyl Penelope M. , Hanley Daniel F. , Barker Peter B.
Published: June 2011

Background and Purpose
—Cerebral ischemia has been proposed as contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). Possible tools for investigating this hypothesis are diffusion-weighted (DWI) and proton magnetic resonance spectroscopic imaging (
1
H-MRSI). However, magnetic field inhomogeneity induced by paramagnetic blood products may prohibit the application of such techniques on perihematoma tissue. We report on the feasibility of DWI and
1
H-MRSI in the study of human ICH and present preliminary data on their contribution to understanding perihematoma tissue functional and metabolic profiles.

Methods
—Patients with acute supratentorial ICH were prospectively evaluated using DWI and
1
H-MRSI. Obscuration of perihematoma tissue with both sequences was assessed. Obtainable apparent diffusion coefficient (Dav) and lactate spectra in perihematoma brain tissue were recorded and analyzed.

Results
—Nine patients with mean age of 63.4 (36 to 87) years were enrolled. Mean time from symptom onset to initial MRI was 3.4 (1 to 9) days; mean hematoma volume was 35.4 (5 to 80) cm
3
. Perihematoma diffusion values were attainable in 9 of 9 patients, and
1
H-MRSI measures were obtainable in 5 of 9 cases. Dav in perihematoma regions was 172.5 (120.0 to 302.5)×10
−5
mm
2
/s and 87.6 (76.5 to 102.1)×10
−5
mm
2
/s in contralateral corresponding regions of interest (
P
=0.002). One patient showed an additional area of reduced Dav with normal T
2
intensity, which suggests ischemia.
1
H-MRSI revealed lactate surrounding the hematoma in 2 patients.

Conclusions
—DWI and
1
H-MRSI can be used in the study of ICH patients. Our preliminary data are inconsistent with ischemia as the primary mechanism for perihematoma tissue injury. Further investigation with advanced MRI techniques will give a clearer understanding of the role that ischemia plays in tissue injury after ICH.
Electromechanical Alterations in the Cerebrovasculature of Stroke-Prone Rats
Authors: Smeda John S. , King Shelley
Published: June 2011

Background and Purpose
—Cerebrovascular pressure-dependent constriction (PDC) is associated with smooth muscle (SM) depolarization and Ca
2+
influx through voltage-gated channels. We studied the alterations in electromechanical contraction in the middle cerebral arteries (MCAs) of stroke-prone Wistar-Kyoto spontaneously hypertensive rats (SHRsp) in relation to the stroke-related loss of PDC.

Methods
—Constriction to pressure, elevated [K
+
]
o
and/or [Ca
2+
]
o
, and SM membrane potentials (E
m
) were measured in isolated pressurized MCAs of SHRsp and stroke-resistant SHR.

Results
—MCAs of SHRsp exhibited an age-related decrease in PDC before hemorrhagic stroke and a loss of PDC after stroke. At 100 mm Hg, the MCAs of poststroke SHRsp maintained partial constriction that was not altered with pressure but was inhibited by nifedipine (1 μmol/L). The MCAs of poststroke SHRsp constricted to vasopressin (0.17 μmol/L) but not to elevated [K
+
]
o
. When pressure was reduced from 100 to 0 mm Hg, the MCAs from young prestroke SHRsp exhibited SM hyperpolarization (−38 to −46 mV), whereas those of poststroke SHRsp maintained a constant, depolarized E
m
(−34 mV). Alterations in E
m
with varying [K
+
]
o
suggested that there was a decrease in SM K
+
conductance in the MCAs of poststroke SHRsp.

Conclusions
—The observation that the MCAs of poststroke SHRsp depolarize but do not constrict to elevated [K
+
]
o
suggests the presence of dysfunctional voltage-gated Ca
2+
channels. The inability to alter E
m
with pressure or to constrict to depolarization could partially contribute to the loss of PDC in the MCAs of poststroke SHRsp.
Impaired Endothelial Function in Transgenic Mice Expressing Both Human Renin and Human Angiotensinogen
Authors: Didion Sean P. , Sigmund Curt D. , Faraci Frank M.
Published: June 2011

Background and Purpose
—Chronic hypertension is a risk factor for carotid vascular disease and stroke. Mechanisms that account for alterations in carotid and cerebral vascular function during hypertension are poorly defined and based almost exclusively on studies in the spontaneously hypertensive rat, a model in which hypertension has an unknown etiology and in which the genetic background is dissimilar to the most commonly used normotensive control, the Wistar-Kyoto rat.

Methods
—In this study we examined vascular function in a defined model of hypertension, double transgenic mice that overexpress both human renin (R+) and human angiotensinogen (A+). We studied vessels in vitro from R+/A+ mice as well as nontransgenic (R−/A−) and single transgenic (R−/A+ or R+/A−) littermate controls.

Results
—After submaximal precontraction with U46619 or prostaglandin F
2α
, acetylcholine, which produces relaxation mediated by endothelial nitric oxide synthase, produced marked relaxation of carotid arteries in control mice but was impaired in R+/A+ mice. For example, 1 μmol/L acetylcholine relaxed the carotid artery by 79±4% versus 44±7% (
P
<0.01) in control and R+/A+ mice, respectively. Impaired responses to acetylcholine in R+/A+ mice could be restored toward normal with indomethacin (10 μmol/L). In contrast, relaxation of the carotid artery in response to nitroprusside and papaverine was similar in R+/A+ mice and control mice.

Conclusions
—These findings indicate that acetylcholine-induced relaxation of carotid artery is impaired selectively in mice made hypertensive by expression of human renin and human angiotensinogen. The mechanism of this impairment may involve production of a cyclooxygenase-derived contracting factor.
Clinicopathological Study of Intracranial Fusiform and Dolichoectatic Aneurysms
Authors: Nakatomi Hirofumi , Segawa Hiromu , Kurata Atsushi , Shiokawa Yoshiaki , Nagata Kazuya , Kamiyama Hiroyasu , Ueki Keisuke , Kirino Takaaki
Published: June 2011

Background and Purpose
—Intracranial fusiform aneurysms can be divided into 2 clinically different subtypes: acute dissecting aneurysms and chronic fusiform or dolichoectatic aneurysms. Of these 2, the natural history and growth mechanism of chronic fusiform aneurysms remains unknown.

Methods
—A consecutive series of 16 patients with chronic fusiform aneurysms was studied retrospectively to clarify patient clinical and neuroradiological features. Aneurysm tissues were obtained from 8 cases and were examined to identify histological features that could correspond to the radiological findings.

Results
—Four histological features were found: (1) fragmentation of internal elastic lamina (IEL), (2) neoangiogenesis within the thickened intima, (3) intramural hemorrhage (IMH) and thrombus formation, and (4) repetitive intramural hemorrhages from the newly formed vessels within thrombus. IEL fragmentation was found in all cases, which suggests that this change may be one of the earliest processes of aneurysm formation. MRI or CT detected IMH, and marked contrast enhancement of the inside of the aneurysm wall (CEI) on MRI corresponded well with intimal thickening. Eight of 9 symptomatic cases but none of 7 asymptomatic cases presented with both radiological features.

Conclusions
—Data suggest that chronic fusiform aneurysms are progressive lesions that start with IEL fragmentation. Formation of IMH seems to be a critical event necessary for lesions to become symptomatic and progress, and this can be monitored on MRI. Knowledge of this possible mechanism of progression and corresponding MRI characteristics could help determine timing of surgical intervention.
The Corticosterone Synthesis Inhibitor Metyrapone Prevents Hypoxia/Ischemia-Induced Loss of Synaptic Function in the Rat Hippocampus
Authors: Krugers Harm J. , Maslam Suharti , Korf Jakob , Joëls Marian
Published: June 2011

Background and Purpose
—Ischemia is accompanied by abundant corticosterone secretion, which could potentially exacerbate brain damage via activation of glucocorticoid receptors. We addressed whether manipulating steroid levels during ischemia affects hippocampal synaptic function along with neuronal structure. Moreover, we established whether pretreatment with the glucocorticoid receptor antagonist RU38486 is as effective in preventing deleterious effects after ischemia as is the steroid synthesis inhibitor metyrapone.

Methods
—Rats underwent 20 minutes of unilateral hypoxia/ischemia (HI). Convulsions were monitored after HI, and 24 hours later, field potentials were recorded in vitro in the hippocampal CA1 area in response to stimulation of the Schaffer collateral/commissural fibers. Morphological alterations were determined in brain slices from the same animals. Data were correlated with steroid treatment before HI.

Results
—Metyrapone suppressed plasma corticosteroid levels during HI, whereas corticosterone treatment significantly elevated plasma steroid levels. These treatments affected the incidence of visible seizures after HI: corticosterone treatment resulted in the highest incidence, whereas metyrapone attenuated the occurrence of seizures. Moreover, the HI-induced impairment in synaptic transmission in the CA1 area in vitro was exacerbated by concomitant corticosteroid treatment and alleviated by pretreatment with metyrapone. In parallel, degenerative changes in the hippocampus after HI were most pronounced after corticosterone treatment, whereas metyrapone reduced these alterations. RU38486 was effective only in reducing the incidence of seizures shortly after ischemia.

Conclusions
—We tentatively conclude that synaptic function along with cellular integrity is preserved after HI by preventing the ischemia-evoked rise in corticosteroid levels rather than blocking the glucocorticoid receptor.
Risk Factors for Peripartum and Postpartum Stroke and Intracranial Venous Thrombosis
Authors: Lanska Douglas J. , Kryscio Richard J.
Published: June 2011

Background and Purpose
—The study goal was to identify potential risk factors for peripartum or postpartum stroke and intracranial venous thrombosis.

Methods
—Data from the Healthcare Cost and Utilization Project were analyzed for the years 1993 and 1994. Observed values were weighted with poststratification discharge weights to project to the universe of all discharges from community hospitals located in the United States. Nationally representative estimates of risk were calculated on the basis of age, race, mode of delivery, income, third-party payer, hospital size, hospital ownership, hospital location (rural versus urban), hospital teaching status, census region, and presence of specific complications. Multivariate models were developed with the use of logistic regression.

Results
—Among 1 408 015 sampled deliveries, there were 183 observed cases of peripartum stroke and 170 cases of peripartum intracranial venous thrombosis in 17 states in the United States in 1993 and 1994. There were an estimated 975 cases of stroke and 864 cases of intracranial venous thrombosis during pregnancy and the puerperium in the United States among 7 463 712 deliveries during 1993 and 1994, for estimated risks of 13.1 cases of peripartum stroke and 11.6 cases of peripartum intracranial venous thrombosis per 100 000 deliveries. Multivariate analysis showed that the following were strongly and significantly associated with both peripartum and postpartum stroke: cesarean delivery; fluid, electrolyte, and acid-base disorders; and hypertension. Covariates that were strongly and significantly associated with both peripartum and postpartum intracranial venous thrombosis included cesarean delivery, hypertension, and infections other than pneumonia and influenza.

Conclusions
—Pregnancy-related hypertension and cesarean delivery are important risk factors for both stroke or intracranial venous thrombosis.
Comparison of Microembolism Detected by Transcranial Doppler and Neuropsychological Sequelae of Carotid Surgery and Percutaneous Transluminal Angioplasty
Authors: Crawley Francesca , Stygall Jan , Lunn Sarah , Harrison Michael , Brown Martin M. , Newman Stanton
Published: June 2011

Background and Purpose
—Percutaneous transluminal angioplasty (PTA) is currently being assessed for the treatment of carotid stenosis. In comparison with carotid endarterectomy (CEA), there is evidence of an increased risk of cerebral microembolism during the procedure. We have sought evidence of any neuropsychological sequelae of carotid PTA and compared it with CEA to demonstrate the relative safety of the 2 treatment options.

Methods
—The neuropsychological outcomes after CEA and PTA were compared in 2 matched groups of patients with severe symptomatic carotid stenosis, 96% of whom had been randomized in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), at a single center. Transcranial Doppler insonation of the middle cerebral artery was used to measure cerebral reactivity in response to carbon dioxide inhalation before treatment and then to detect microembolization of the ipsilateral cerebral hemisphere and measure changes in blood flow velocity during the procedures. The performance on a neuropsychological test battery administered before, 6 weeks after, and 6 months after the procedure was compared in 20 patients undergoing PTA and 26 having CEA.

Results
—At 6 weeks, 5 patients in each group showed a similar decline in neuropsychological performance; global measures showed no significant difference between the 2 procedures, despite a significantly higher incidence of microemboli during PTA. Both groups showed a marked reduction in anxiety after treatment.

Conclusions
—The findings provide some reassurance that PTA is not associated with greater cerebral complications than CEA, despite the higher embolic load recorded by transcranial Doppler ultrasonography during angioplasty.
International Trends in Mortality From Stroke, 1968 to 1994
Authors: Sarti Cinzia , Rastenyte Daiva , Cepaitis Zygimantas , Tuomilehto Jaakko
Published: June 2011

Background and Purpose
—The World Health Organization data bank is an invaluable source of information for international comparison of mortality trends. We present rates and trends in mortality from stroke up to 1994, with a particular emphasis on the last 10-year period. Data are presented for men and women in 51 industrialized and developing countries from different parts of the world.

Methods
—We included all deaths from cerebrovascular disease for the population aged 35 to 84 years from all the countries in which death certificates were estimated to be available for at least 80% for the period from 1968 to 1994. Age-standardized mortality rates from stroke were calculated for each country for the last available 5 years. Time trends were calculated by using ordinary linear regression and are presented for the entire study period and for 3 separate time periods: 1968 to 1974, 1975 to 1984, and 1985 to 1994. The last 10-year period was further subdivided into 2 parts of 5 years each. We analyzed data separately for men and women and for groups aged 35 to 74 years and 75 to 84 years.

Results
—The highest rates at the end of the study period for the population aged 35 to 74 years were observed in eastern Europe and previous Soviet Union countries (309 to 156/100 000 per year among men and 222 to 101/100 000 per year among women), Mauritius (268/100 000 per year among men and 138/100 000 per year among women), and Trinidad and Tobago (185/100 000 per year among men and 134/100 000 per year among women). Relatively low to average rates (<100/100 000 per year among men and <70/100 000 per year among women) were reported for Western Europe, with an exception of Portugal (162/100 000 per year among men and 95/100 000 per year among women). The countries with lowest stroke mortality rates at the end of the study period, such as the United States, Canada, Switzerland, France, and Australia, experienced steep declining trends. However, the slope of the decline was substantially reduced during the last 5 years in these countries. Mortality from stroke increased most in the eastern European countries, especially during the last 5 years. Among other high-risk populations, no change in stroke mortality trends was observed in Mauritius, whereas somewhat declining trends were seen in Trinidad and Tobago.

Conclusions
—We observed large differences in mortality rates from stroke around the world together with a wide variation in mortality trends. A widening gap was observed between 2 groups of nations, those with low and declining stroke mortality rates and those with high and increasing mortality, in particular, between western and eastern Europe. Eastern European countries should initiate actions aiming at the reduction of stroke risk, perhaps by looking at the examples of Japan and Finland and the other countries that have been the most successful in reducing previously very high mortality from stroke.
The
N
-Methyl-
d
-Aspartate Antagonist CNS 1102 Protects Cerebral Gray and White Matter From Ischemic Injury Following Temporary Focal Ischemia in Rats
Authors: Schäbitz Wolf-R. , Li Fuhai , Fisher Marc
Published: June 2011

Background and Purpose
—Cerebral white matter is as sensitive as gray matter to ischemic injury and is probably amenable to pharmacological intervention. In this study we investigated whether an
N
-methyl-
d
-aspartate (NMDA) antagonist, CNS 1102, protects not only cerebral gray matter but also white matter from ischemic injury.

Methods
—Ten rats underwent 15 minutes of temporary focal ischemia and were blindly assigned to CNS 1102 intravenous bolus injection (1.13 mg/kg) followed by intravenous infusion (0.33 mg/kg per hour) for 3.75 hours or to vehicle (n=5 per group) immediately after reperfusion. Seventy-two hours after ischemia, the animals were perfusion fixed for histology. The severity of neuronal necrosis in the cortex and striatum was semiquantitatively analyzed. The Luxol fast blue–periodic acid Schiff stain and Bielschowsky’s silver stain were used to measure optical densities (ODs) of myelin and axons, respectively, in the internal capsule of both hemispheres, and the OD ratio was calculated to reflect the severity of white matter damage.

Results
—Neuronal damage in both the cortex and the striatum was significantly better in the drug-treated group than in the placebo group (
P
<0.05). The OD ratio of both the axons (0.93±0.08 versus 0.61±0.18;
P
<0.01) and the myelin sheath (0.95±0.07 versus 0.67±0.19;
P
=0.01) was significantly higher in the CNS 1102 group than in the placebo group. The neurological score was significantly improved in the drug-treated group (
P
<0.05).

Conclusions
—The NMDA receptor antagonist CNS 1102 protects not only cerebral gray matter but also white matter from ischemic injury, most probably by preventing degeneration of white matter structures such as myelin and axons.
Lack of Interleukin-6 Expression Is Not Protective Against Focal Central Nervous System Ischemia
Authors: Clark Wayne M. , Rinker Lisa G. , Lessov Nikola S. , Hazel Kristin , Hill Jennifer K. , Stenzel-Poore Mary , Eckenstein Felix
Published: June 2011

Background and Purpose
—Interleukin-6 (IL-6) appears to be involved in the inflammatory response associated with central nervous system (CNS) ischemia. Although IL-6 levels increase after stroke, it is not known whether IL-6 directly influences CNS ischemic injury. In this study, we used a focal reversible stroke model to investigate whether mice lacking IL-6 were protected against acute ischemic injury.

Methods
—We bred IL-6–deficient C57 black mice (I-129 IL-6 KO back-crossed with C57), including homozygous knockouts (IL-6 −/−), heterozygous littermates (IL-6 +/−), and normal littermates (IL-6 +/+). The status of all animals was confirmed by DNA sampling and polymerase chain reaction analysis. Reversible middle cerebral artery occlusion was produced by advancing a silicone-coated 8-0 filament into the internal carotid artery for 2 hours (experiment 1) or 45 minutes (experiment 2). At 24 hours, animals were evaluated on a 28-point clinical scale, blood and cerebrospinal fluid were obtained, and the brains were evaluated for infarct volume and IL-6 mRNA levels.

Results
—In experiment 1 (severe ischemia), no differences were seen in lesion size or neurological function between the groups: lesion volume was IL-6 −/− (n=15), 57±13 mm
3
; IL-6 +/− (n=15), 58±23 mm
3
; and IL-6 +/+ (n=15), 58±18 mm
3
(
P
=NS). ELISA testing confirmed very low to absent levels of IL-6 in the serum and cerebrospinal fluid of knockout animals. Brain mRNA levels of the other proinflammatory cytokines, including tumor necrosis factor-α, IL-1β, and IL-1 receptor antagonist, were 50% lower in IL-6–deficient ischemic animals than in normal animals. In experiment 2 (mild ischemia), no differences were seen in lesion size or neurological function between the groups: lesion volume was IL-6 −/− (n=10), 16±8 mm
3
; IL-6 +/− (n=10), 14±4 mm
3
; and IL-6 +/+ (n=10), 19±12 mm
3
(
P
=NS).

Conclusions
—In this study, infarct size and neurological function at 24 hours were not different in animals deficient in IL-6 after transient CNS ischemia. This suggests that IL-6 does not have a direct influence on acute ischemic injury. Further study investigating the role of IL-6 on long-term recovery after stroke is in progress.
Serum Gamma-Glutamyl Transferase, Self-Reported Alcohol Drinking, and the Risk of Stroke
Authors: Jousilahti Pekka , Rastenyte Daiva , Tuomilehto Jaakko
Published: June 2011

Background and Purpose
—There is still conflicting evidence regarding a link between alcohol drinking and the risk of stroke. In most prospective studies, the assessment of the alcohol drinking has been based on self-reporting, which may be unreliable. The aim of the present study was to examine the relationship between stroke and both the self-reported alcohol drinking and the serum gamma-glutamyl transferase (GGT) concentration, which was regarded as a biological marker of alcohol drinking.

Methods
—A prospective cohort study of 14 874 Finnish men and women aged 25 to 64 years who participated in a cardiovascular risk-factor survey in 1982 or 1987. The following risk factors, determined at baseline, were included in data analyses: self-reported alcohol drinking, GGT, smoking, blood pressure, serum cholesterol, and body mass index. The cohorts were followed until the end of 1994. Stroke events were identified through the national death registry and hospital discharge registry by computerized record linkage.

Results
—Serum GGT concentration was associated with the risk of total and ischemic stroke in both genders. There was also a significant association among men between GGT and the risk of intracerebral hemorrhage and among women between GGT and the risk of subarachnoid hemorrhage. The relationships remained statistically significant also after adjustment for other risk factors. Self-reported alcohol drinking did not associate with any type of stroke.

Conclusions
—These results support the hypothesis that excessive alcohol drinking is related to an increased risk of stroke. Biological markers of alcohol drinking, such as serum GGT level, are useful for the assessment of risks related to alcohol drinking.
Behavioral Risk Factor Prevalence and Lifestyle Change After Stroke
Authors: Redfern Judith , McKevitt Chris , Dundas Ruth , Rudd Anthony G. , Wolfe Charles D.A.
Published: June 2011

Background and Purpose
—Stroke patients have a 15-fold increased risk of recurrent stroke, and those with ≥1 risk factor have a further increased risk of recurrence. Previous work found management of physiological risk factors after stroke to be unsatisfactory, but there is little information on behavioral risks within the stroke population. This study estimates behavioral risk factor prevalence after stroke and explores lifestyle change.

Methods
—The study used data from the population-based South London Stroke Register, collected prospectively between 1995 and 1998. Main measures included smoking status, alcohol use, and obesity. Logistic regression was used to determine sociodemographic differences in these measures.

Results
—At 1 year after stroke, 22% of patients still smoked, 36% of patients were obese, and 4% drank excessively. Younger patients, whites, and men were more likely to smoke, and younger whites were more likely to drink excessively. Women and nonwhites were more likely to be obese. Those living in hospital, nursing home, or residential care and nonwhites were more likely to give up smoking, but there were no other associations between lifestyle change and the sociodemographic characteristics of patients.

Conclusions
—Different behavioral risk factors were associated with specific sociodemographic groups within the stroke population. After stroke, high-risk groups should continue to be targeted to prevent stroke recurrence. However, the relationship between sociodemographic characteristics and lifestyle change remains unclear; more research is needed into the process of change to find out how best to intervene to improve secondary prevention.
Activation of Emergency Medical Services for Acute Stroke in a Nonurban Population
Authors: Wein Theodore H. , Staub Lara , Felberg Robert , Hickenbottom Susan L. , Chan Wenyaw , Grotta James C. , Demchuk Andrew M. , Groff Janet , Bartholomew L. Kay , Morgenstern Lewis B.
Published: June 2011

Background and Purpose
—Activating emergency medical services (EMS) is the most important factor in reducing delay times to hospital arrival for stroke patients. Determining who calls 911 for stroke would allow more efficient targeting of public health initiatives.

Methods
—The T.L.L. Temple Foundation Stroke Project is an acute stroke surveillance and intervention project in nonurban East Texas. Prospective case ascertainment allowed chart abstraction and structured interviews for all hospitalized stroke patients to determine if EMS was activated, and if so, by whom.

Results
—Of 429 validated strokes, 38.0% activated EMS by calling 911. Logistic regression analysis comparing those who called 911 with those who did not activate EMS found that individuals who were employed were 81% less likely to have EMS activated (OR 0.19, 95% CI 0.04 to 0.63). Of the 163 cases in which 911 was called, the person activating EMS was: self (patient), 4.3%; family member of significant other, 60.1%; paid caregiver, 18.4%; and coworker or other, 12.9%. Significant associations between the variables age group (
P
=0.02), insurance status (
P
=0.007), and living alone (
P
=0.05) with who called 911 was found on χ
2
analysis.

Conclusions
—Educational efforts directed at patients themselves at risk for stroke may be of low yield. To increase the use of time dependent acute stroke therapy, interventions may wish to concentrate on family, caregivers, and coworkers of high-risk patients. Large employers may be good targets to increase utilization of EMS services for acute stroke.
Secondary Stroke Prevention in Atrial Fibrillation
Authors: Evans Andrew , Perez Inigo , Yu Gloria , Kalra Lalit
Published: June 2011

Background and Purpose
—Secondary prevention trials do not distinguish outcomes according to stroke cause. The purpose of the study was to determine whether trial efficacy of anticoagulation for secondary prevention could be replicated in clinical practice in strokes of different etiology.

Methods
—A 2-year observation study was undertaken in 288 stroke patients with atrial fibrillation (mean age 76 years; 55% women) who were receiving anticoagulation therapy to maintain an international normalized ratio of 2.0 to 3.0. Comparisons were made of (1) patient characteristics, anticoagulation control, and annual stroke/hemorrhage rates with those of the European Atrial Fibrillation Trial and (2) cause of recurrent stroke by initial stroke subtype.

Results
—Subjects were 5 years older (95% CI 3 to 7 years), and more patients had small-vessel stroke (26% versus 14%; 95% CI 3% to 17%) compared with corresponding trial data. The duration spent in the target anticoagulation range (55% versus 59%), recurrent stroke rate (5.1% versus 3.6% per year), and major (2.3% versus 2.2% per year) or minor (9.5% versus 11.8% per year) hemorrhage rates were comparable with those in patients receiving warfarin in the randomized study. Ten of 14 (71%) of embolic recurrences occurred in patients with a previous cardioembolic episode, and 8 of 11 (73%) lacunar recurrences occurred in patients with previous lacunar stroke as the qualifying event for anticoagulation (
P
=0.025). Only 3 of 14 cardioembolic compared with 8 of 11 lacunar recurrences occurred during adequate anticoagulation.

Conclusions
—Anticoagulation for secondary stroke prevention in clinical practice achieves outcomes comparable with those of randomized trials. Nearly 26% of qualifying strokes and 40% of recurrences were nonembolic; stroke subtype should be considered when making treatment decisions.
Effects of Age on Brain Activation During Auditory-Cued Thumb-to-Index Opposition
Authors: Calautti C. , Serrati C. , Baron J-C.
Published: June 2011

Background and Purpose
—Available data indicate a decline in fine finger movements with aging, suggesting changes in central motor processes. Thus far no functional neuroimaging study has assessed the effect of age on activation patterns during finger movement.

Methods
—We used high-resolution perfusion positron emission tomography to study 2 groups of 7 healthy right-handed subjects each: a young group (mean age, 24 years) and an old group (mean age, 60 years). The task was a thumb-to-index tapping, auditory-cued at 1.26 Hz with a metronome, with either the right or the left hand. The control condition was a resting state with the metronome on.

Results
—Significant differences between old and young subjects were found, suggesting significant overactivation in older subjects affecting the superior frontal cortex (premotor-prefrontal junction) ipsilateral to the moving fingers, as if the execution of this apparently simple motor task was judged more complex by the aged brain. Similar findings in previous perceptual and cognitive paradigms have been interpreted as a compensation process for the neurobiological changes of aging. Analysis of the control condition data in our sample showed, however, that this prefrontal overactivation in the old group was due at least in part to higher resting perfusion in anterior brain areas in the young subjects.

Conclusions
—The changes in brain function observed in this study may underlie the subtle decline in fine motor functions known to occur with normal aging. Our findings emphasize the importance of using an age-matched control group in functional imaging studies of motor recovery after stroke.
Gene Transfer of Extracellular Superoxide Dismutase Increases Superoxide Dismutase Activity in Cerebrospinal Fluid
Authors: Nakane Hiroshi , Chu Yi , Faraci Frank M. , Oberley Larry W. , Heistad Donald D.
Published: June 2011

Background and Purpose
—Copper-zinc superoxide dismutase (CuZnSOD) is expressed intracellularly, while extracellular SOD (EC-SOD) is released from cells. The purpose of this study was to determine whether gene transfer of CuZnSOD increases SOD activity predominantly in tissues, and gene transfer of EC-SOD increases SOD activity in cerebrospinal fluid (CSF). We also determined whether heparin or dextran sulfate releases EC-SOD into CSF.

Methods
—We injected recombinant adenoviruses expressing EC-SOD (AdEC-SOD), CuZnSOD (AdCuZnSOD), or β-galactosidase (Adβ-gal) into the cisterna magna of rabbits.

Results
—Total SOD activity in CSF was 39±11 U/mL (mean±SE) before virus injection. Three days later, total SOD activity in CSF increased to 148±22 U/mL after AdEC-SOD and 92±10 U/mL after AdCuZnSOD (
P
<0.05 versus AdEC-SOD), with no change after Adβ-gal (49±5 U/mL). EC-SOD protein was detected in CSF after AdEC-SOD but not AdCuZnSOD or Adβ-gal. Injection of heparin or dextran sulfate into the cisterna magna increased total SOD activity 27-fold and 32-fold over basal values, respectively, in CSF of rabbits that received AdEC-SOD. In contrast to effects in CSF, total SOD activity in basilar artery and meninges was significantly higher after AdCuZnSOD and tended to be higher after AdEC-SOD than after Adβ-gal.

Conclusions
—We have developed a method for intracranial gene transfer of CuZnSOD and EC-SOD. After gene transfer, CuZnSOD was expressed mainly in tissues, and EC-SOD was released into the CSF, especially after injection of heparin or dextran sulfate. Gene transfer of different isoforms of SOD may be useful in studies of cerebral vascular physiology and pathophysiology.
NXY-059, a Free Radical–Trapping Agent, Substantially Lessens the Functional Disability Resulting From Cerebral Ischemia in a Primate Species
Authors: Marshall Jonathan W. B. , Duffin Katharine J. , Green A. Richard , Ridley Rosalind M.
Published: June 2011

Background and Purpose
—NXY-059 is a novel nitrone with free radical–trapping properties that has a considerable neuroprotective effect in rats. We have now examined the efficacy of this drug at reducing long-term functional disability in a primate model of stroke.

Methods
—Twelve monkeys were trained and tested on a variety of behavioral tasks used to dissociate and quantify motor and spatial deficits. Five minutes after permanent occlusion of the right middle cerebral artery, monkeys received a 1-mL intravenous infusion of either saline or NXY-059 (28 mg · kg
−
1
), and osmotic minipumps, model 2001D, were implanted subcutaneously to provide continuous drug or saline infusion for 48 hours. Drug-filled pumps released NXY-059 at 16 mg · kg
−
1
· h
−
1
. The monkeys were retested 3 and 10 weeks after surgery to assess functional disability. Surgery, behavioral testing, and histology were all done blinded to treatment condition.

Results
—NXY-059–treated monkeys were significantly better at reaching with their hemiparetic arm than were saline-treated monkeys when retested 3 weeks (
P
<0.01) and 10 weeks (
P
<0.01) after surgery. Drug treatment also significantly lessened the degree of spatial perceptual neglect (
P
<0.01), a debilitating though ameliorating consequence of this infarct. NXY-059 treatment reduced the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter.

Conclusions
—This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. These findings provide considerable encouragement for the clinical development of NXY-059.