bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary Report of Detecting Microembolic Signals in Transcranial Doppler Time Series With Nonlinear Forecasting
Authors: Keunen R. W. M. , Stam C. J. , Tavy D. L. J. , Mess W. H. , Titulaer B. M. , Ackerstaff R. G. A.
Published: June 2011

Background and Purpose
—Most algorithms used for automatic detection of microembolic signals (MES) are based on power spectral analysis of the Doppler shift. However, controversies exist as to whether these algorithms can replace the human expert. Therefore, a different algorithm was applied that takes advantage of the periodicity of the MES. This so-called nonlinear forecasting (NLF) is able to detect periodicity in a time series, and it is hypothesized that this technique has the potential to detect MES. Moreover, because of the lack of prominent periodicity in both the normal Doppler signals (DS) and movement artifacts (MA), the NLF has a potential to differentiate MES from normal blood flow variations and MA.

Methods
—Twenty single MES and 100 MA were selected by 2 human experts. NLF was applied to MES and MA and compared with 200 randomly chosen DS. NLF resulted in a so-called prediction value that ranges from +1 in signals with prominent periodicity to 0 in signals that lack periodicity.

Results
—NLF revealed that MES are more predictable than the normal Doppler signals (prediction [MES]=0.829±0.084 versus prediction [DS]=−0.060±0.228;
P
<0.0001). Moreover, MES are more predictable than the MA (prediction [MA]=−0.034±0.223;
P
<0.0001). No difference in prediction could be found between DS and MA.

Conclusions
—This preliminary report shows that MES can be separated from DS and MA by NLF. Research is needed as to whether this technology can be further developed for automatic detection of MES.
Osteopontin and its Integrin Receptor α
v
β
3
Are Upregulated During Formation of the Glial Scar After Focal Stroke
Authors: Ellison Julie A. , Velier James J. , Spera Patricia , Jonak Zdenka L. , Wang Xinkang , Barone Frank C. , Feuerstein Giora Z.
Published: June 2011

Background and Purpose
—Microglia and astrocytes in the peri-infarct region are activated in response to focal stroke. A critical function of activated glia is formation of a protective barrier that ultimately forms a new glial-limiting membrane. Osteopontin, a provisional matrix protein expressed during wound healing, is induced after focal stroke. The present study was performed to determine the spatial and temporal expression of osteopontin and its integrin receptor α
v
β
3
during formation of the peri-infarct gliotic barrier and subsequent formation of a new glial-limiting membrane.

Methods
—Spontaneously hypertensive rats (n=19) were subjected to permanent occlusion of the middle cerebral artery and killed 3, 6, and 24 hours and 2, 5, and 15 days after occlusion. The spatial and temporal expression of osteopontin mRNA was determined by in situ hybridization, and that of osteopontin ligand and its integrin receptor α
v
β
3
was determined by immunohistochemistry.

Results
—Osteopontin mRNA was expressed de novo in the peri-infarct region from 3 to 48 hours; by 5 days osteopontin mRNA expression was restricted to the infarct. Osteopontin protein was expressed by peri-infarct microglia beginning at 24 hours and by microglia/macrophages at 48 hours in the infarct. Integrin receptor α
v
β
3
was expressed in peri-infarct astrocytes at 5 and 15 days.

Conclusions
—Early microglial/macrophage expression of osteopontin mRNA defines the borders and final infarct area at 24 hours. At 5 days osteopontin ligand is at a distance from the peri-infarct astrocytes expressing integrin receptor α
v
β
3
. By 15 days astrocytes expressing integrin receptor α
v
β
3
are localized in an osteopontin-rich region concomitant with formation of the new glial-limiting membrane. The de novo expression and interaction of osteopontin ligand with its receptor integrin α
v
β
3
suggest a role in wound healing after focal stroke.
A New Method to Improve In-Bore Middle Cerebral Artery Occlusion in Rats
Authors: Li Fuhai , Han Sam , Tatlisumak Turgut , Carano Richard A. D. , Irie Katsumi , Sotak Christopher H. , Fisher Marc
Published: June 2011

Background and Purpose
—In-bore middle cerebral artery occlusion (MCAO) enables investigators to acquire preischemic MRI data and to image ischemic changes immediately after occlusion. We have developed a highly successful in-bore MCAO method. This study describes the methods and pertinent techniques.

Methods
—Sixty-seven Sprague-Dawley rats were subjected to temporary (n=36) or permanent (n=31) MCAO. The occluding device consisted of a supporting tubing, a driving line, and a silicone-coated 4-0 nylon suture occluder. Outside the magnet, the occluder was positioned in the carotid canal. MCAO was achieved in the magnet bore by remotely advancing the driving line until resistance was felt. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were acquired before and immediately after occlusion and were used to document the presence of MCAO.

Results
—Fifty-nine (88.1%) rats were successfully occluded, demonstrating hyperintensity on DWI, perfusion deficits on PWI, and no subarachnoid hemorrhage at postmortem examination. The average values of the apparent diffusion coefficient in both the frontoparietal cortex and the lateral caudoputamen significantly decreased as early as 3 minutes after the onset of ischemia. The failures included preocclusion damage (1/67), sliding out of the occluder during occlusion (1/67), no occlusion (2/67), and arterial perforation (4/67).

Conclusions
—Our in-bore MCAO method is easily performed and is as successful as MCAO induced outside the magnet.
Diffusion-Weighted Magnetic Resonance Imaging in Acute Stroke
Authors: van Everdingen K.J. , van der Grond J. , Kappelle L.J. , Ramos L.M.P. , Mali W.P.T.M.
Published: June 2011

Background and Purpose
—Diffusion-weighted MRI (DWI) is highly sensitive in detecting early cerebral ischemic changes in acute stroke patients. In this study we compared the sensitivity of DWI with that of conventional MRI techniques. Furthermore, we investigated the prognostic value of the volume of ischemic lesions on DWI scans and of the apparent diffusion coefficient (ADC).

Methods
—We performed DWI, fluid-attenuated inversion recovery, spin-echo T2-weighted MRI, and spin-echo proton density–weighted MRI in 42 patients with acute stroke and 15 control subjects. The volume of ischemic lesions was measured on early (<60 hours after onset) and follow-up MRI scans. Clinical outcome was measured 4 months after onset of symptoms with the National Institutes of Health Stroke Scale, the Barthel Index, and the Rankin Scale.

Results
—With DWI, 98% of the ischemic lesions were detected, and with fluid-attenuated inversion recovery, 91% were detected, whereas with early T2-weighted or proton density–weighted scans, only 71% (
P
=0.002, χ
2
) and 80% (
P
=0.02, χ
2
) of lesions, respectively, were found. Lesion volume on early DWI scans correlated significantly with clinical outcome ratings (
P
<0.01). In patients with a first-ever stroke, a lesion volume of ≤22 mL on DWI predicted good outcome with a 75% sensitivity and a 100% specificity. The mean ADC of ischemic lesions was 29% lower than the ADC of normal-appearing parts of the brain (
P
<0.001). The ADC ratio correlated significantly with clinical outcome (
P
<0.05).

Conclusions
—DWI is a better imaging method than conventional MRI in detecting early ischemic lesions in stroke patients. Lesion size as measured on DWI scans and, to a lesser extent, ADC values are potential parameters for predicting clinical outcome in acute stroke patients.
Comparison of the ABC/2 Estimation Technique to Computer-Assisted Volumetric Analysis of Intraparenchymal and Subdural Hematomas Complicating the GUSTO-1 Trial
Authors: Gebel James M. , Sila Cathy A. , Sloan Michael A. , Granger Christopher B. , Weisenberger Joseph P. , Green Cindy L. , Topol Eric J. , Mahaffey Kenneth W.
Published: June 2011

Background and Purpose
—The volume of an intracerebral hemorrhage has been shown to be an important independent predictor of mortality in several reports.

1

2

3

4

5

A technique for estimating hematoma volume, known as the ABC/2 method, has been proven a reliable, simple bedside technique for the volume measurement of intraparenchymal intracerebral hemorrhage.

6

7

8

Subdural hematomas also carry a significant mortality risk but are more amenable to surgical evacuation. A reliable, simple bedside measurement of subdural hematoma volume may prove a valuable tool in prognostication and management of patients with this entity.

Methods
—Computed tomographic (CT) brain scans of 244 patients suffering from intracranial hemorrhage in the GUSTO-1 trial were systematically reviewed. The volumes of 298 intraparenchymal hematomas were measured by the ABC/2 technique, and the volumes of 44 subdural hematomas were measured by an adaptation of this technique and compared to computer-assisted volumetric analysis.

Results
—Excellent correlation between the techniques were achieved for both subdural (
r
=0.842; slope, 0.982) and intraparenchymal hematoma volume measurements (
r
=0.929; slope, 1.11).

Conclusions
—The ABC/2 method is a simple and accurate technique for the measurement of intraparenchymal hematoma volume, and a simple adaptation allows for a similarly accurate measurement of subdural hematoma volume as well.
Atrial Fibrillation Is an Independent Determinant of Low Cognitive Function
Authors: Kilander Lena , Andrén Bertil , Nyman Håkan , Lind Lars , Boberg Merike , Lithell Hans
Published: June 2011

Background and Purpose
—Cerebrovascular disease is increasingly recognized as a cause of dementia and cognitive decline. We have previously reported an association between hypertension and diabetes and low cognitive function in the elderly. Atrial fibrillation is another main risk factor for cerebrovascular disease. The aim of this study was to investigate whether atrial fibrillation is associated with low cognitive function in elderly men with and without previous manifest stroke.

Methods
—This was a cross-sectional study based on a cohort of 952 community-living men, aged 69 to 75 years, in Uppsala, Sweden. Cognitive functions were assessed by the Mini–Mental State Examination and the Trail Making Tests, and a composite
z
score was calculated. The relation between atrial fibrillation and cognitive
z
score was analyzed, with stroke and other vascular risk factors taken into account.

Results
—All analyses were adjusted for age, education, and occupational level. Men with atrial fibrillation (n=44) had lower mean adjusted cognitive
z
scores (−0.26±0.11) than men without atrial fibrillation (+0.14±0.03;
P
=0.0003). The exclusion of stroke patients did not alter this relationship; the mean cognitive
z
score was −0.24±0.12 in the 36 men with atrial fibrillation and +0.17±0.03 in those without atrial fibrillation (
P
=0.0004), corresponding to a difference of 0.4 SDs between groups. Adjustments for 24-hour diastolic blood pressure and heart rate, diabetes, and ejection fraction did not change this relationship. Men with atrial fibrillation who were treated with digoxin (n=27) performed markedly better (−0.05±0.21) than those without treatment (n=9; −1.14±0.34; adjusted
P
=0.0005). Previous myocardial infarction was not associated with impaired cognitive results.

Conclusions
—In these community-living elderly men, we found an association between atrial fibrillation and low cognitive function independent of stroke, high blood pressure, and diabetes. Interventional studies are needed to answer the question of whether optimal treatment of atrial fibrillation may prevent or postpone cognitive decline and dementia.
Prediction of Functional Outcome After Stroke
Authors: Lai Sue-Min , Duncan Pamela W. , Keighley John
Published: June 2011

Background and Purpose
—This study compared the ability of 2 stroke impairment scales, Orpington Prognostic Scale and National Institutes of Health (NIH) Stroke Scale, to predict disability as measured by the Barthel activities of daily living (ADL) Index and higher level of self-reported physical functioning as measured by the SF-36 physical functioning index (PFI) at 1, 3, and 6 months after stroke.

Methods
—The participants in this ongoing study are 184 individuals who sustained an eligible stroke and were recruited for the Kansas City Stroke Study. All patients were prospectively evaluated using standardized assessments at enrollment (within 14 days of stroke onset) and followed at 1, 3, and 6 months after stroke. Coefficient of determination (
R
2
) was used to assess the ability of the 2 stroke scales to prognosticate outcomes.

Results
—Means and SDs of the Orpington Prognostic Scale and NIH Stroke Scale measured at baseline were 3.6±1.31 and 5.5±4.58, respectively. The Spearman’s rank correlation between the 2 baseline measures was 0.83 (
P
=0.0001). The Orpington Prognostic Scale and the NIH Stroke Scale explained well the variance in Barthel ADL Index (
P
<0.001). However, the Orpington Prognostic Scale explained more variance than did the NIH Stroke Scale. Similarly, the Orpington Prognostic Score explained more variance in higher level of physical function than did the NIH Stroke Scale. The amount of variance in Barthel ADL Index and SF-36 PFI, which were explained by both stroke severity measures, decreased over time.

Conclusions
—Our results demonstrate that in a sample of mostly mild and moderate strokes, the Orpington Prognostic Scale compared with the NIH Stroke Scale is simpler to use and is a slightly better predictor of ADL and higher levels of physical function.
Dependence and Perceived Difficulty in Daily Activities in Community-Living Stroke Survivors 2 Years After Stroke
Authors: Grimby Gunnar , Andrén Eva , Daving Yvonne , Wright Benjamin
Published: June 2011

Background and Purpose
—There is a need for better understanding of the structure of instruments for functional outcome assessment after discharge from rehabilitation. One purpose of the study was to contribute to the analysis of instrumental dimensionality. Another purpose was to compare disability in stroke patients within the younger age range 2 years after onset of stroke with that at discharge with respect to both dependence and patients’ perceived difficulty and to extend the assessments with instrumental activities.

Methods
—We studied 68 stroke survivors aged 18 to 71 years at onset (59% aged <55 years) by means of interviews in their home, using activities from the Functional Independence Measure (FIM) and Instrumental Activity Measure (IAM) for ratings of dependence and perceived difficulty. Rasch analysis was used to construct calibrated linear measures and to evaluate the level of fit.

Results
—Acceptable models for comparison of dependence between discharge and follow-up were found for the physical and the social-cognitive items in FIM. However, personal care and social-cognitive items showed an increased level of dependence at follow-up compared with at discharge. A combination of physical activities from FIM and IAM also gave acceptable models for both dependence and perceived difficulty, and the hierarchical orders of activities are presented. In general, there was agreement between the ratings of dependence and perceived difficulty, but with some discrepancies. Men found it harder to be independent in such instrumental activities as cooking and cleaning than women; the opposite was true for small-scale shopping and locomotion outdoors. Subjects aged ≥55 years had slightly higher level of dependence and perceived difficulty in IAM activities than those below that age.

Conclusions
—Changes in the hierarchical order of activities should be taken into account in follow-up studies. Differences in the environment between hospital and home, as well as differences in support and motivation, might explain the relatively larger degree of dependence at follow-up compared with at discharge and indicate the need for further rehabilitation efforts. Instrumental activities could be combined with FIM activities in a model. For individual items, ratings of both dependence and perceived difficulty may provide further insight into the disablement process.
A Quantitative Study of the Emotional Outcome of People Caring for Stroke Survivors
Authors: Dennis Martin , O’Rourke Suzanne , Lewis Stephanie , Sharpe Michael , Warlow Charles
Published: June 2011

Background and Purpose
—Although the physical and, to a lesser extent, emotional outcome of stroke survivors has been well documented, there are far fewer data relating to the outcomes of those who care for them. We aimed to describe the outcome of those caring for stroke patients and to identify both patient and caregiver factors that are associated with poor caregiver outcomes.

Methods
—As part of a randomized trial to evaluate a stroke family care worker, we identified 417 patients (67% of all referrals to our institution). We followed up 376 survivors of whom 246 identified a caregiver at a 6-month follow-up interview. The patients and caregivers were asked to complete 2 measures of emotional distress (30-item General Health Questionnaire [GHQ-30] and Hospital Anxiety and Depression [HAD] Scale). A regression analysis was used to identify factors that were independently associated with poor caregiver outcomes.

Results
—Fifty-five percent of responding caregivers scored more than 4 on the GHQ-30, indicating that emotional distress is common in this group. Caregivers were more likely to be depressed if the patients were severely dependent (
P
<0.01) or emotionally distressed themselves (
P
<0.01). Female caregivers reported more anxiety (median HAD=8) than male caregivers (median HAD=5;
P
<0.01) but caregivers’ levels of anxiety were not so clearly related to the patients’ degree of physical disability as their levels of depression. Caregivers suffered more emotional distress if the patients had been dependent before their strokes.

Conclusions
—These data may help to identify those caregivers at greatest risk of poor emotional outcomes and thus help in the planning of trials and delivery of interventions aimed at preventing or treating distress among caregivers.
The Apolipoprotein E ε4 Allele and Outcome in Cerebrovascular Disease
Authors: McCarron M. O. , Muir K. W. , Weir C. J. , Dyker A. G. , Bone I. , Nicoll J.A.R. , Lees K.R.
Published: June 2011

Background and Purpose
—Polymorphism of the apolipoprotein E gene (
APOE
) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the ε4 allele being associated with poorer prognosis. We investigated
APOE
allele distribution in acute stroke and the effect of the ε4 allele on outcome.

Methods
—
APOE
genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 intracerebral hemorrhage patients. The survival effect of the ε4 allele was assessed with the use of a stratified log-rank test. A Cox proportional hazards regression model was used to estimate the independent effect of ε4 dose (0, 1, or 2) on survival, and logistic regression was used to determine the effect on 3-month outcome (good if alive at home, poor if in care or dead).

Results
—Allele distribution matched the general population with no difference between the ischemic and hemorrhagic groups. Survival in the entire cohort was unaffected by ε4 dose. Improved survival with increasing ε4 dose was found in the ischemic group (relative hazard=0.76 per allele;
P
=0.04). If transient ischemic attacks were excluded, a trend for improved survival persisted (
P
=0.06). With intracerebral hemorrhage, a trend was seen toward reduced survival with ε4 (
P
=0.07, log-rank test). Three-month outcome in the ischemic group was unaffected by ε4 dose, and a trend toward poorer outcome with ε4 was seen for intracerebral hemorrhage (
P
=0.10).

Conclusions
—The
APOE
ε4 allele had divergent effects on survival and outcome in ischemic and hemorrhagic strokes in this population. The reported adverse effect on patients with intracerebral hemorrhage was supported. The favorable survival effect on ischemic stroke patients requires further study.
Expression and Function of Recombinant Endothelial Nitric Oxide Synthase Gene in Canine Basilar Artery After Experimental Subarachnoid Hemorrhage
Authors: Onoue Hisashi , Tsutsui Masato , Smith Leslie , Stelter Adele , O’Brien Timothy , Katusic Zvonimir S.
Published: June 2011

Background and Purpose
—Gene transfer with recombinant viral vectors encoding vasodilator proteins may be useful in therapy of cerebral vasospasm after subarachnoid hemorrhage (SAH). Relaxations mediated by nitric oxide are impaired in cerebral arteries affected by SAH. The present study was designed to determine the effect of SAH on the efficiency of ex vivo adenovirus-mediated gene transfer to canine basilar arteries and to examine whether expression of recombinant endothelial nitric oxide synthase (eNOS) gene may have functional effects on vasomotor reactivity of spastic arteries affected by SAH
.

Methods
—Replication-deficient recombinant adenovirus vectors encoding bovine eNOS (AdCMVeNOS) and
Escherichia coli
β-galactosidase (AdCMVβ-Gal) genes were used for ex vivo gene transfer. Rings of basilar arteries obtained from control dogs and dogs exposed to SAH were incubated with the vectors in minimum essential medium. Twenty-four hours after gene transfer, expression and function of the recombinant genes were evaluated by (1) histochemical or immunohistochemical staining, (2) β-galactosidase protein measurement, and (3) isometric tension recording.

Results
—Transduction with AdCMVβ-Gal and AdCMVeNOS resulted in the expression of recombinant β-galactosidase and eNOS proteins mostly in the vascular adventitia. The expression of β-galactosidase protein was ≈2-fold higher in SAH arteries than in normal arteries. Endothelium-dependent relaxations caused by bradykinin and substance P were suppressed in SAH arteries. The relaxations to bradykinin were significantly augmented in both normal and SAH arteries after AdCMVeNOS transduction but not after AdCMVβ-Gal transduction. The relaxations to substance P were augmented by AdCMVeNOS transduction only in normal arteries. Bradykinin and substance P caused relaxations even in endothelium-denuded arteries, when the vessels were transduced with AdCMVeNOS. These endothelium-independent (adventitia-dependent) relaxations to bradykinin observed after AdCMVeNOS transduction were similar between normal and SAH arteries, whereas those to substance P were significantly reduced in SAH arteries compared with normal arteries.

Conclusions
—These results suggest that expression of recombinant proteins after adenovirus-mediated gene transfer may be enhanced in cerebral arteries affected by SAH and that successful eNOS gene transfer to spastic arteries can at least partly restore the impaired nitric oxide–mediated relaxations through local (adventitial) production of nitric oxide.
Photothrombotic Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats: Influence of Substrain, Gender, and Distal Middle Cerebral Artery Patterns on Infarct Size
Authors: Cai Hong , Yao Hiroshi , Ibayashi Setsuro , Uchimura Hideyuki , Fujishima Masatoshi
Published: June 2011

Background and Purpose
—To analyze the effects of substrain and gender differences in spontaneously hypertensive rats (SHR) and distal middle cerebral artery (MCA) branching patterns on infarct size, we compared infarct volumes produced by photothrombotic distal MCA occlusion using SHR/Kyushu and SHR/Izumo (Izm).

Methods
—Twenty-four male and 8 female SHR/Kyushu, 15 male and 5 female SHR/Izm, and 6 male Wistar-Kyoto rats (WKY)/Izm (5 to 7 months old) were subjected to photothrombotic distal MCA occlusion, and infarct volumes were determined.

Results
—Although blood pressure levels were essentially the same between the two substrains of hypertensive rats, infarct volumes were significantly larger in the SHR/Kyushu substrain than in SHR/Izm of either sex (
P
<0.001); infarct volumes in male and female SHR/Kyushu were 83.8±11.7 and 58.5±9.2 mm
3
, and those in male and female SHR/Izm were 61.5±10.7 and 34.8±7.9 mm
3
, respectively (values are mean±SD). Male SHR/Kyushu that had simple Y-shaped MCA showed smaller infarcts (75.8±14.6 mm
3
, n=11) than those with more branching (regular) MCA (93.2±19.1, n=13), the difference being significant (
P
=0.022). Male SHR/Izm with simple distal MCA also produced smaller infarctions than those with regular MCA (51.0±3.7 versus 68.9±8.7 mm
3
,
P
=0.0004).

Conclusions
—Photothrombotic occlusion of distal MCA in hypertensive rats provides a simple and reproducible model of focal ischemia. Most importantly, this study emphasizes the substantial variabilities in infarct sizes caused by the differences in substrains of SHR, gender, and distal MCA patterns.
A Model for Experimental Cerebral Arterial Spasm
Authors: Kuwayama Akio , Zervas Nicholas T. , Belson Roger , Shintani Akira , Pickren Kenneth
Published: June 2011

Vasospasm of the basilar artery of the dog was induced by subarachnoid injection of arterial blood through the cisterna magna. Cerebral angiography was employed to evaluate quantitative assessment of the spasm. Chronic vasospasm was successfully induced in 100% of surviving dogs.

Biphasic vasoconstriction was observed. The acute phase occurred within 30 minutes after the blood injection and tended to abate. Chronic spasm was demonstrated on the second day's angiograms and persisted to the seventh day in some cases. Etiology of the chronic spasm using this model is now under investigation.

Vasospasm was not due to alterations in blood gas concentration or blood pressure, to increased CSF pressure or to injury from contrast medium or direct trauma. The primacy of blood as the offending agent is strongly suggested.
Case Report. Spinal Cord Ischemia Associated With Repair of a Ruptured Abdominal Aortic Aneurysm
Authors: Michaels Leon
Published: June 2011

Spinal cord ischemia is a rare complication of rupture of an abdominal aortic aneurysm or its emergency surgical treatment; only seven cases have been reported previously. A patient with this complication is described. It was characterized by postoperative total loss of all forms of sensation in the legs and partial sparing of motor function. The patient had been in shock, but the only other organ to suffer ischemic changes was the bowel. The condition, therefore, was attributed to local interference with the blood supply of the lumbosacral cord which is derived principally from the abdominal aorta through varying numbers of lumbar arteries. Recovery was virtually complete.
Development and Evaluation of an Experimental Model for the Study of the Cerebral Circulation in the Unanesthetized Goat
Authors: Reimann Charles , Lluch Salvador , Glick Gerald
Published: June 2011

An animal model has been developed for the continuous measurement of total cerebral blood flow in the unanesthetized, unrestrained goat. We selected the goat because each internal maxillary artery, a branch of the external carotid artery, provides the total blood flow to each hemisphere via the rete mirabile. After the occlusion of the extracerebral vessels of the internal maxillary artery with thrombin, an electromagnetic flow transducer was chronically implanted on this artery, distal to the temporal artery, to measure hemispheric blood flow. Reproducible measurements of cerebral blood flow were obtained in ten unanesthetized goats for periods ranging between two weeks and five months. The mean cerebral blood flow for the ten goats was 133 ± 5 ml/min/100 gm tissue at an average mean aortic pressure of 91 ± 3 mm Hg, heart rate of 79 ± 3 beats/min, arterial P

CO
CO2

of 31.4 ± 1.0 mm Hg, P

0
02

of 76.6 ± 1.7 mm Hg, and pH of 7.48 ± 0.02. The present experimental preparation allows cerebrovascular hemodynamics to be evaluated under near-normal conditions and is suitable for physiological and pharmacological studies in normal and abnormal states.
Hemolobin and the Risk of Cerebral Infarction: The Framingham Study
Authors: KANNEL WILLIAM B. , GORDON TAVIA , WOLF PHILIP A. , MCNAMARA PATRICIA
Published: June 2011

Risk of cerebral infarction over 16 years was ascertained in 5,185 men and women classified according to their hemoglobin, blood pressure and cigarette habit on entry to the Framingham Study. Within the normal range of hemoglobin values, risk was found to be proportional to the blood hemoglobin concentration in both sexes.

Men with hemoglobin values of 15 gm or greater and women with 14 gm or more had twice as many cerebral infarctions as did their cohorts with lower values. The risk of initial development of 82 cerebral infarctions was also strikingly related to antecedent blood pressure status in both sexes and to the cigarette habit in men. When allowance is made for associated blood pressure and cigarette habit--factors found to correlate with both blood hemoglobin values and incidence of cerebral infarction--hemoglobin level had only a modest residual effect, no longer statistically significant.

The pathogenetic, preventive and therapeutic implications of the interrelationship of blood hemoglobin, blood pressure and the cigarette habit and their association with cerebral infarction require further exploration.
The Effect of Intracarotid Aminophylline Infusion on the Cerebral Circulation
Authors: Gottstein U. , Paulson O. B.
Published: June 2011

The influence of aminophylline infusion into the internal carotid artery on cerebral blood flow (CBF) was studied in 12 patients. Six of them were studied using the N
2
O saturation technique of Kety and Schmidt, and the other six using the Xenon-133 intra-arterial injection method of Lassen and Ingvar. Intracarotid infusion of aminophylline resulted in a significant decrease of CBF. Previous studies have shown that aminophylline also reduced CBF when injected intravenously. Furthermore, in the present study it was demonstrated that a small dose of aminophylline which was without cerebral vasoconstricting effect when infused intravenously still reduced CBF when infused into the internal carotid artery. Thus aminophylline is a cerebral vasoconstrictor due to a local action on the cerebral vessels.
Survey of Stroke Epidemiology Studies
Authors: KULLER LEWIS H. , COOK LEONARD P. , FRIEDMAN GARY D.
Published: June 2011

The Committee on Criteria and Methods of the Epidemiological Council of the American Heart Association conducted a survey of epidemiological studies of stroke. A questionnaire was sent to investigators who were involved in stroke epidemiological research. Forty studies have been reviewed.

Stroke epidemiological studies include a wide range of populations and geographic areas of the United States. Of the 12 prospective studies only five were primarily stroke-oriented, while the remaining initially involved the study of coronary artery disease.

Relatively few stroke studies identify cases by clinical examination at the time of the stroke; most depend on examination sometime after the stroke, review of hospital records, physician's reports and patient interviews. In relatively few of the studies are the cases being examined by a neurologist.

There is a need for better methods of stroke-case ascertainment, for standardized diagnostic techniques that can be used in field studies, and for the evaluation of specific disabilities following a stroke.
Cerebral Anoxia: Protein Metabolism During Recovery in In Vitro Model
Authors: YANAGIHARA TAKEHIKO
Published: June 2011

Amino acid incorporation into proteins of rabbit brain slices was studied during the recovery stage after various anoxic periods in an in vitro experimental model. There was a distinct difference between anoxic periods up to five minutes and those beyond ten minutes. In the former, inhibition of amino acid incorporation was of lesser degree and was reversible. On the other hand, more than 50% inhibition was observed following anoxic periods of 30 minutes and this inhibition was irreversible. Amino acid incorporation into proteins was more sensitive to anoxia than was amino acid transport into brain slices.
Acute Caudate Vascular Lesions
Authors: Kumral Emre , Evyapan Dilek , Balkir Kaan
Published: June 2011

Background and Purpose
—We sought to evaluate demographic features, risk factors, clinical profiles, and behavioral abnormalities in patients with caudate lesion, either with infarct or with hemorrhage involving the caudate nucleus.

Methods
—We studied all patients with acute caudate stroke confirmed by CT or MRI who were admitted to our stroke unit over a 5-year period. A database containing risk factors, clinical features, type and mechanism of stroke, and caudate vascular territories was analyzed.

Results
—Thirty-one patients had acute caudate stroke (24 men and 7 women; mean age, 62.3 years). Caudate infarct was present in 25 patients and caudate hemorrhage in 6. The main risk factors for caudate infarct were hypertension (64%), hypercholesterolemia (32%), diabetes mellitus (28%), and previous myocardial infarct (20%). Hypertension was present in 4 patients (67%) with caudate hemorrhage, and arteriovenous malformation was present in 1 patient (17%). Small-artery disease was diagnosed in 14 patients (59%), cardiac embolism in 5 patients (20%), and large-artery disease in 2 patients (8%), and 2 patients (8%) had mixed etiology. The most frequent neurological abnormalities were abulia and psychic akinesia (48%), frontal system abnormalities (26%), speech deficits in patients with left-sided lesions (23%), and neglect syndromes in those with right-sided lesions (10%). Fifteen patients with caudate infarct (60%) and 3 patients with hemorrhage (50%) were able to return to normal daily life. Patients with infarct in the territory of the lateral lenticulostriate arteries extending to neighboring structures showed more frequent motor and neuropsychological deficits than those with infarct in the territory of the anterior lenticulostriate arteries.

Conclusions
—The clinical presentation of patients with caudate hemorrhage mimicked subarachnoid hemorrhage with or without motor and neuropsychological signs. Caudate vascular lesions with concomitant neighboring structure involvement represent a specific stroke syndrome, usually caused by small-artery disease and in one fifth of the patients caused by cardiac embolism. The behavioral abnormalities were mostly due to medial, lateral, and ventral caudate subnuclei damage and coexisting lesion of the anterior limb of the internal capsule.
Osteogenic Protein-1 Protects Against Cerebral Infarction Induced by MCA Ligation in Adult Rats
Authors: Lin Shinn-Zong , Hoffer Barry J. , Kaplan Paul , Wang Yun
Published: June 2011

Background and Purpose
—Osteogenic protein-1 (OP1) not only possesses trophic activity on bone tissue but also influences neuronal survival and differentiation in vitro. Specific receptors for OP1 are present in brain and spinal cord and can be upregulated during cerebral contusion. OP1 is a member of the transforming growth factor-β superfamily, several of whose members possess neuroprotective activity. In this study, the neuroprotective effect of OP1 in cerebral ischemia was evaluated in adult animals.

Methods
—Adult male Sprague-Dawley rats were anesthetized with chloral hydrate. OP1 or vehicle was administered intracortically or intracerebroventricularly to the rats. Thirty minutes, 24 hours, or 72 hours after OP1 injection, the right middle cerebral artery (MCA) was ligated for 90 minutes. Twenty-four hours after reperfusion, animals were tested for motor behavior. The animals were subsequently anesthetized with urethane and perfused intracardially with saline. Brain tissue was removed, sliced, and incubated with 2% triphenyltetrazolium chloride to localize the area of infarction.

Results
—Only animals pretreated with OP1 24 hours before MCA ligation showed a reduction in motor impairment. OP1, given 30 minutes or 72 hours before MCA ligation, did not reduce cortical infarction. In contrast, pretreatment with OP1 24 hours before MCA ligation significantly attenuated the volume of infarction in the cortex, in agreement with the behavioral findings.

Conclusions
—Intracerebral administration of OP1 24 hours before MCA ligation reduces ischemia-induced injury in the cerebral cortex.
Extravasation of Radiographic Contrast Is an Independent Predictor of Death in Primary Intracerebral Hemorrhage
Authors: Becker Kyra J. , Baxter Alexander B. , Bybee Heather M. , Tirschwell David L. , Abouelsaad Tamer , Cohen Wendy A.
Published: June 2011

Background and Purpose
—Hematomas that enlarge following presentation with primary intracerebral hemorrhage (ICH) are associated with increased mortality, but the mechanisms of hematoma enlargement are poorly understood. We interpreted the presence of contrast extravasation into the hematoma after CT angiography (CTA) as evidence of ongoing hemorrhage and sought to identify the clinical significance of contrast extravasation as well as factors associated with the risk of extravasation.

Methods
—We reviewed the clinical records and radiographic studies of all patients with intracranial hemorrhage undergoing CTA from 1994 to 1997. Only patients with primary ICH were included in this study. Univariate and multivariate logistic regression analyses were performed to determine the associations between clinical and radiological variables and the risk of hospital death or contrast extravasation.

Results
—Data were available for 113 patients. Contrast extravasation was seen in 46% of patients at the time of CTA, and the presence of contrast extravasation was associated with increased fatality: 63.5% versus 16.4% in patients without extravasation (
P
=0.011). There was a trend toward a shorter time (median±SD) from symptom onset to CTA in patients with extravasation (4.6±19 hours) than in patients with no evidence of extravasation (6.6±28 hours;
P
=0.065). Multivariate analysis revealed that hematoma size (
P
=0.022), Glasgow Coma Scale (GCS) score (
P
=0.016), extravasation of contrast (
P
=0.006), infratentorial ICH (
P
=0.014), and lack of surgery (
P
<0.001) were independently associated with hospital death. Variables independently associated with contrast extravasation were hematoma size (
P
=0.024), MABP >120 mm Hg (
P
=0.012), and GCS score of ≤8 (
P
<0.005).

Conclusions
—Contrast extravasation into the hematoma after ICH is associated with increased fatality. The risk of contrast extravasation is increased with extreme hypertension, depressed consciousness, and large hemorrhages. If contrast extravasation represents ongoing hemorrhage, the findings in this study may have implications for therapy of ICH, particularly with regard to blood pressure management.
Safety and Tolerability Study of Aptiganel Hydrochloride in Patients With an Acute Ischemic Stroke
Authors: Dyker A. G. , Edwards K. R. , Fayad P. B. , Hormes J. T. , Lees K. R.
Published: June 2011

Background and Purpose
—Aptiganel (CNS 1102) is a selective, noncompetitive antagonist that acts on the ion channel associated with the
N
-methyl-
d
-aspartate (NMDA) receptor and is neuroprotective in experimental focal cerebral ischemia models at a plasma concentration of 10 ng/mL. In human volunteers, dose-limiting effects of aptiganel are blood pressure increases and central nervous system (CNS) excitation or depression. This study assessed the safety and tolerability of non–weight-adjusted doses of aptiganel in patients with acute ischemic stroke.

Methods
—This was a double-blind, randomized, placebo-controlled multicenter study in patients presenting within 24 hours of acute ischemic stroke. Ascending single intravenous bolus doses of aptiganel (3, 4.5, 6, and 7.5 mg) were assessed in 21 patients with a 3:1 active drug:placebo randomization schedule. In 15 subsequent patients, selected bolus doses were followed by constant intravenous infusion for 6 to 12 hours (6 mg plus 1 mg/h, n=10; then 4.5 mg plus 0.75 mg/h, n=15) in a 4:1 randomization schedule. Prospectively collected pharmacokinetic data guided selection of infusion rates. Neurological and functional status were recorded at entry and after 1 week, although the study was not designed to test efficacy.

Results
—Forty-six patients were randomized from 4 centers (3 in the United States and 1 in the United Kingdom): 36 received aptiganel HCl, and 10 were given placebo. Hypertension and CNS events were commonly reported after a bolus dose of 7.5 mg and after a 6-mg bolus followed by an infusion of 1 mg/h. The lower regimen of 4.5-mg bolus followed by infusion of 0.75 mg/h achieved plasma aptiganel concentrations of >10 ng/mL and was well tolerated by patients but still raised systolic blood pressure by ≈30 mm Hg over baseline.

Conclusions
—A 4.5-mg intravenous bolus of aptiganel HCl followed by infusion of 0.75 mg/h for 12 hours is a tolerable dose that can produce plasma drug concentrations shown to be neuroprotective in animal models. However, increases in systolic blood pressure and an excess of CNS effects were both observed at this dose.
Magnetic Resonance Imaging White Matter Hyperintensities and Mechanism of Ischemic Stroke
Authors: Mäntylä Riitta , Aronen Hannu J. , Salonen Oili , Pohjasvaara Tarja , Korpelainen Mauno , Peltonen Teemu , Standertskjöld-Nordenstam Carl-Gustaf , Kaste Markku , Erkinjuntti Timo
Published: June 2011

Background and Purpose
—We sought to determine the relations between infarct subtype and white matter hyperintensities (WMHIs) on MRI.

Materials and Methods
—We studied 395 ischemic stroke patients with 1.0-T MRI. The number of lacunar, border-zone, and cortical infarcts was registered. WMHIs were analyzed in 6 areas. Univariate and multivariate statistical analyses were used to find the risk factors for different infarct subtypes and to study the connections between WMHIs and brain infarcts.

Results
—Lacunar infarcts were associated with hypertension (odds ratio [OR], 1.79; 95% CI, 1.17 to 2.73), alcohol consumption (OR, 1.96; 95% CI, 1.17 to 3.28), and age (OR, 1.03; 95% CI, 1.00 to 1.06). Border-zone infarcts were associated with carotid atherosclerosis (OR, 2.20; 95% CI, 1.15 to 4.19). Atrial fibrillation (OR, 3.02; 95% CI, 1.66 to 5.50) and carotid atherosclerosis (OR, 1.94; 95% CI, 1.12 to 3.36) were independent positive predictors, and history of hyperlipidemia (OR, 0.44; 95% CI, 0.26 to 0.75) and migraine (OR, 0.48; 95% CI, 0.25 to 0.93) were negative predictors for cortical infarcts. Patients with lacunar infarcts had more severe WMHIs than patients with nonlacunar infarcts in all WM areas (
P
≤0.001). Patients with border-zone infarcts showed severe periventricular lesions (
P
=0.002), especially around posterior horns (
P
=0.003). The extent of WMHIs in patients with cortical infarcts did not differ from that in those without cortical infarcts.

Conclusions
—Various infarct subtypes have different risk profiles. The association between lacunar infarcts and WMHIs supports the concept of small-vessel disease underlying these 2 phenomena. The connection between border-zone infarcts and periventricular WMHIs again raises the question of the disputed periventricular vascular border zone.
Changes in Coagulation and Fibrinolysis Markers in Acute Ischemic Stroke Treated With Recombinant Tissue Plasminogen Activator
Authors: Fassbender Klaus , Dempfle Carl-Erik , Mielke Orell , Schwartz Andreas , Daffertshofer Michael , Eschenfelder Christoph , Dollman Martina , Hennerici Michael
Published: June 2011

Background and Purpose
—Shifts of the balance between coagulation and fibrinolysis play a crucial role in pathogenesis and treatment of cerebral ischemia. In this study, we characterized the kinetics of hemostatic abnormalities induced by acute ischemic stroke and its thrombolytic (recombinant tissue plasminogen activator [rtPA]) or anticoagulant (heparin) treatment.

Methods
—Systemic generation of molecular markers of hemostasis (fibrin monomer,
d
-dimer, thrombin-antithrombin complex, and fibrinopeptide 1.2) was monitored in acute ischemic stroke, and the effects of thrombolytic and anticoagulant treatments were analyzed.

Results
—Thrombolysis with rtPA induced a massive response of markers of coagulation activation and fibrin formation that peaked after 1 to 3 hours and persisted for up to 72 hours. In contrast, only minor hemostatic changes were induced by acute ischemic stroke itself. Administration of heparin did not significantly affect these hemostatic abnormalities.

Conclusions
—This first characterization of the coagulation activation induced by rtPA treatment for acute ischemic stroke and the failure to abolish such hemostatic abnormalities by heparin may be of value for further refinement of the currently discussed thrombolytic therapy and the controversial adjunctive anticoagulant prophylaxis in stroke patients.
“Task-Oriented” Exercise Improves Hamstring Strength and Spastic Reflexes in Chronic Stroke Patients
Authors: Smith Gerald V. , Silver Kenneth H. C. , Goldberg Andrew P. , Macko Richard F.
Published: June 2011

Background and Purpose
—Despite the belief that after cerebral infarction only limited functional gains are possible beyond the subacute period, we tested the hypothesis that a 12-week program of “task-oriented” treadmill exercise would increase muscle strength and decrease spastic reflexes in chronic hemiparetic patients.

Methods
—Fourteen subjects, aged 66±3 (mean±SEM) years, with residual gait deviations due to remote stroke (>6 months), underwent repeated measures of reflexive and volitional (concentric and eccentric) torque with use of isokinetic dynamometry on the hamstring musculature bilaterally. Torque output was measured at 4 angular velocities (30
o
, 60
o
, 90
o
, and 120
o
/s).

Results
—After 3 months of 3 times/wk low-intensity aerobic exercise, there were significant main effects (2 legs [
P
<0.01]×2 times [
P
<0.01]×4 angular velocities [
P
<0.05]) for concentric torque production. Torque/time production in the concentric mode also improved significantly in the paretic (50%,
P
<0.01) and nonparetic hamstrings (31%,
P
<0.01). Eccentric torque/time production increased by 21% (
P
<0.01) and 22% (
P
<0.01) in the paretic and nonparetic hamstrings, respectively. Passive (reflexive) torque/time generation in the paretic hamstrings decreased by 11% (
P
<0.027). Reflexive torque/time was unchanged in the nonparetic hamstrings (
P
=0.45).

Conclusions
—These findings provide evidence that progressive treadmill aerobic exercise training improves volitional torque and torque/time generation and reduces reflexive torque/time production in the hemiparetic limb. Strength changes associated with improved functional mobility in chronic hemiparetic stroke survivors after treadmill training will be reported in future articles.
Lateralization of Cerebral Blood Flow Velocity Changes During Cognitive Tasks
Authors: Vingerhoets Guy , Stroobant Nathalie
Published: June 2011

Background and Purpose
—Transcranial Doppler ultrasonography (TCD) permits the assessment of cognitively induced cerebral blood flow velocity (BFV) changes. We sought to investigate the lateralization of BFV acceleration induced by a variety of cognitive tasks and to determine the influence of age, gender, IQ, and quality of the performance on the relative BFV changes.

Methods
—Simultaneous bilateral TCD monitoring of BFV in the middle cerebral arteries (MCAs) was performed in 90 normal right-handed volunteers during 13 verbal and visuospatial tasks and their preceding rest periods.

Results
—All tasks induced a significant bilateral BFV increase in the MCAs compared with the preceding rest periods. Five verbal tasks showed a significant left-hemispheric BFV acceleration. Linguistic tasks that required active or creative processing of the verbal stimuli, such as sentence construction or word fluency, elicited the most asymmetric response. Five visuospatial tasks revealed a significant right-hemispheric BFV shift. Paradigms that combined visuospatial attention and visuomotor manipulation showed the most lateralized acceleration. Older volunteers (aged >50 years) showed higher relative BFV changes, but lateralization was not influenced by age. Gender, IQ, and performance quality did not reveal significant effects on BFV change.

Conclusions
—Bilateral TCD is a noninvasive technique that has the potential to connect the particular change in flow pattern of the MCA distribution with selective cognitive activity and thus offers specific functional information of scientific and clinical value.