bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Induction of Vascular Endothelial Growth Factor Gene Expression After Transient Middle Cerebral Artery Occlusion in Rats
Authors: Hayashi T. , Abe K. , Suzuki H. , Itoyama Y.
Published: June 2011

Background and Purpose
Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and also has the potential to increase vascular permeability. Therefore, it may contribute to the recovery of brain cells from ischemic insult through potentiating neovascularization or may exacerbate brain damage by forming brain edema. However, the exact role of this protein in cerebral ischemia is not fully understood. We investigated temporal, spatial, and cellular profiles of the induction of VEGF gene expression after transient focal cerebral ischemia at both mRNA and protein levels.

Methods
We used a transient middle cerebral artery (MCA) occlusion model. Northern blot analysis was performed to assess the chronological pattern of induction and the impact of length of ischemia on mRNA expression. Western blot analysis was performed to ensure the selective detection of immunoreactive VEGF with an antibody. Temporal, spatial, and cellular changes of immunohistochemical VEGF expression were compared with different periods of reperfusion from 1 hour to 7 days after transient MCA occlusion.

Results
(1) Northern blot analysis revealed no detectable VEGF mRNA in the control brains. The mRNA became evident at 1 hour after reperfusion, peaked at 3 hours, and then decreased. The length of ischemia from 1 to 3 hours made no differences in the degree and temporal profile of the subsequent induction of VEGF mRNA. (2) Western blot analysis showed no band in the control brain, but two bands with molecular weights of 38 and 45 kD, corresponding to VEGF
121
and VEGF
165
, were induced at 1 hour of reperfusion, peaked at 3 hours of reperfusion, and then decayed. (3) Neurons in the cerebral cortex of the MCA territory expressed VEGF at 1 hour after reperfusion with a peak at 3 hours and then diminished by 1 day. Pial cells of the MCA territory also expressed immunoreactive VEGF from 1 hour of reperfusion that was sustained until 3 to 7 days after reperfusion.

Conclusions
Rapid induction of VEGF gene expression after transient MCA occlusion was demonstrated at both mRNA and protein levels. Cortical neurons and pial cells were the source of VEGF production in this model, but the temporal profiles of the induction between these cells were different. The early but dissociative induction of VEGF between neuronal and pial cells suggests different roles of the protein in their cells after transient MCA occlusion.
Fou Rire Prodromique
Heralding a Left Internal Carotid Artery Occlusion
Authors: Carel C. , Albucher J. F. , Manelfe C. , Guiraud-Chaumeil B. , Chollet F.
Published: June 2011

Background
Fou rire prodromique
, described as pathological laughter preceding the onset of an apoplectic attack, is a rare phenomenon.

Case Description
A 61-year-old man manifested pathological laughter before a sudden right hemiplegia. MRI showed a left lenticular and caudate nucleus infarct with involvement of the external capsule and prerolandic area. MRA revealed a left internal carotid and middle cerebral artery occlusion.

Conclusions
The clinicoanatomic correlates of this phenomenon are discussed.
How Do Stroke Units Improve Patient Outcomes?
Authors: Stroke Unit Trialists’ Collaboration
Published: June 2011

Background and Purpose
We sought to clarify the way in which organized inpatient (stroke unit) care can produce reductions in case fatality and in the need for institutional care after stroke.

Methods
We performed a secondary analysis of a collaborative systematic review of all randomized trials that compared organized inpatient (stroke unit) care with contemporary conventional care. Nineteen trials were included, of which 18 (3246 patients) could provide outcome data on death, place of residence, and final functional outcome. Data were less complete (but always available for at least 12 trials; 1611 patients) for subgroup analyses examining timing and cause of death and outcomes in patients with different levels of severity of initial stroke.

Results
The reduction in case fatality of patients managed in a stroke unit setting developed between 1 and 4 weeks after the index stroke. The reduction in the odds of death was evident across all causes of death and most marked for those deaths considered to be secondary to immobility. However, data were insufficient to permit a firm conclusion. The relative increase in the number of patients discharged home from stroke units as opposed to conventional care was largely attributable to an increase in the number of patients returning home physically independent. Across the range of stroke severity, stroke unit care was associated with nonsignificant increases in the number of patients regaining independence.

Conclusions
Within the limitations of the available data, we conclude that organized inpatient stroke unit care probably benefits a wide range of stroke patients in a variety of different ways, ie, reducing death from secondary complications of stroke and reducing the need for institutional care through a reduction in disability.
A Stroke-Adapted 30-Item Version of the Sickness Impact Profile to Assess Quality of Life (SA-SIP30)
Authors: van Straten A. , de Haan R. J. , Limburg M. , Schuling J. , Bossuyt P. M. , van den Bos G. A. M.
Published: June 2011

Background and Purpose
In view of the growing therapeutic options in stroke, measurement of quality of life has become increasingly relevant as an outcome parameter. The Sickness Impact Profile (SIP) is one of the most widely used measures to assess quality of life. To overcome the major disadvantage of the SIP, its length, we constructed a short stroke adapted 30-item SIP version (SA-SIP30).

Methods
Data on the original SIP version were collected for 319 communicative patients at 6 months after stroke. The 12 subscales and the 136 items of the original SIP were reduced to 8 subscales with 30 items in a three step procedure, on the basis of relevancy and homogeneity. Reliability of the SA-SIP30 was evaluated by means of an analysis of homogeneity (Cronbach’s α coefficient). Different types of validity were assessed: construct, clinical, and external validities.

Results
Homogeneity of the SA-SIP30 was demonstrated by a high Cronbach’s α (0.85). Principal component analyses revealed the same two dimensions as in the original SIP (a physical and a psychosocial dimension). The SA-SIP30 could explain 91% of the variation in scores of the original SIP in the same cohort of patients, and 89% in a different cohort. Furthermore, the SA-SIP30 was related to other functional health measures similar to how the original SIP was. We could demonstrate that the SA-SIP30 was able to distinguish patients with lacunar infarctions from patients with cortical or subcortical lesions.

Conclusions
We conclude that the SA-SIP30 is a feasible and clinimetrically sound measure to assess quality of life after stroke.
Nonhypertensive Cerebral Small-Vessel Disease
Authors: Lammie G. Alistair , Brannan Frances , Slattery Jim , Warlow Charles
Published: June 2011

Background and Purpose
Cerebral small-vessel disease (SVD) is a common aging phenomenon that is exacerbated by hypertension and diabetes mellitus. It is regarded as an important cause of lacunar infarction and intracerebral hemorrhage. The present study was performed to highlight the existence and to some extent the frequency of pathologically verified SVD lacking in classic risk factors and to extend the scope of risk factor analysis.

Methods
The study group comprised 70 consecutively referred autopsy brains with microscopic evidence of SVD. In each case clinical records, autopsy reports, and central nervous system and systemic autopsy histology were reviewed. SVD was graded as mild, moderate, or severe in six standardized brain regions, and the results analyzed in relation to the presence or absence of classic SVD risk factors.

Results
SVD was manifest largely as concentric hyaline wall thickening; lipohyalinosis and fibrinoid necrosis were rarely observed. Thirty-one percent of cases failed to meet stringent clinicopathological criteria for significant prior hypertension. In 9% of cases, patients had been nonelderly, nondiabetic, and normotensive. Five of six cases lacking classic risk factors had systemic conditions known to enhance small-vessel permeability.

Conclusions
The nature of SVD appears to have been modified by effective treatment of hypertension. Classic risk factors are often absent. The hypothesis that a variety of conditions that enhance small-vessel permeability may contribute to the pathogenesis of SVD merits consideration.
Mildly Oxidized Low-Density Lipoprotein Impairs Responses of Carotid but Not Basilar Artery in Rabbits
Authors: Napoli Claudio , Paternò Roberto , Faraci Frank M. , Taguchi Hisao , Postiglione Alfredo , Heistad Donald D.
Published: June 2011

Abstract
Background and Purpose Intracranial blood vessels appear to be relatively resistant to development of atherosclerosis. The goal of this study was to compare effects of mildly oxidized LDL (ox-LDL) on endothelium-dependent responses of intracranial and extracranial arteries in vitro.

Methods
LDL was purified from plasma of healthy subjects and mildly oxidized by means of a xanthine/xanthine oxidase reaction. Contraction of the rabbit basilar and carotid arteries in response to histamine and phenylephrine and relaxation in precontracted vessels to acetylcholine and sodium nitroprusside were evaluated after 30 minutes of exposure to LDL or ox-LDL (100 μg/mL).

Results
Exposure to LDL had little or no effect on vascular responses. After exposure to ox-LDL, contraction to histamine and phenylephrine and relaxation to acetylcholine were impaired significantly in carotid (
P
<.05) but not in basilar artery. Relaxation to sodium nitroprusside was not significantly impaired by ox-LDL in the basilar artery. In the carotid artery, relaxation to sodium nitroprusside was significantly impaired by ox-LDL when the vessels were precontracted with phenylephrine but not histamine. Impairment of vascular responses by ox-LDL was prevented by addition of superoxide dismutase, catalase, or dimethylthiourea to the LDL solution before addition of xanthine/xanthine oxidase.

Conclusions
Mildly ox-LDL impairs contraction and endothelium-dependent relaxation in the carotid but not in basilar artery. Thus, intracranial arteries may be relatively resistant to mildly ox-LDL.
Sex Dependency of Cerebrovascular CO
2
Reactivity in Normal Subjects
Authors: Kastrup Andreas , Thomas Christine , Hartmann Claudia , Schabet Martin
Published: June 2011

Background and Purpose
Cerebrovascular CO
2
reactivity can be assessed easily and reliably by transcranial Doppler sonography. The objectives of the present study were to evaluate sex differences in cerebral CO
2
reactivity and to specify the relation between CO
2
and cerebral blood flow velocity.

Methods
CO
2
reactivity of the circulation of both middle cerebral arteries was measured by bilateral transcranial Doppler sonography in 60 healthy volunteers (30 men, 30 women) aged 21 to 58 years. End-tidal carbon dioxide tensions (P
etco
2
) were elevated with the use of carbogene gas (95% O
2
, 5% CO
2
). In each subject the mean blood flow velocity (V
mean
) was plotted as a function of P
etco
2
.

Results
The best-fit curves for the relation of V
mean
/P
etco
2
were exponential functions, with the following basic equation: V
mean
(cm/s)=
a
e
bx
, where
a
is a theoretical quantity representing V
mean
at a P
co
2
of 0 mm Hg,
b
is the relative slope of the curve (slope divided by the value of the function) corresponding to the definition of reactivity, and
x
is the P
etco
2
(mm Hg). The mean value of
b
was 0.037±0.008 in women and 0.030±0.010 in men. ANOVA demonstrated a significant difference between men and women (
P
<.001).

Conclusions
This study demonstrates a highly significant sex-related difference in CO
2
-induced cerebral vasomotor reactivity. The relation between altered carbon dioxide tensions and blood flow velocities of both middle cerebral arteries in 60 healthy volunteers was found to be exponential.
Cerebral Venous Thrombosis and Anticardiolipin Antibodies
Authors: Carhuapoma Juan R. , Mitsias Panayiotis , Levine Steven R.
Published: June 2011

Background and Purpose
The association of cerebral venous thrombosis (CVT) with a variety of pathological states is well established. However, there are only rare isolated reports of CVT associated with anticardiolipin antibodies (aCL).

Methods
To clarify the clinical and neuradiological features as well as outcome of patients with CVT associated with aCL, we reviewed the records of all patients with CVT evaluated at our institution between 1989 and 1996 (retrospective and prospective) and systematically reviewed the pertinent literature.

Results
We identified 8 aCL+ and 7 aCL− patients with CVT. No patients with lupus anticoagulant (LA) were identified. The mean age was 23±11.01 (range, <1 to 36) years in the aCL+ and 38±9.30 (range, 25 to 54) years in the aCL− patients (
P
=.016). Six of 8 aCL+ and 5 of 7 aCL− patients were women. The dural sinuses were involved in all aCL+ and in 6 of 7 aCL− patients, while deep venous system thrombosis occurred in 5 of 8 (63%) aCL+ and 1 of 7 (14%) aCL− patients. In the aCL+ patients CVT was associated with puerperium or oral contraceptive use (n=6) and sickle cell trait (n=1), and in the aCL− patients CVT was associated with systemic lupus erythematosus (n=1), myelodysplastic syndrome (n=1), colonic cancer (n=1), oral contraceptive use or puerperium (n=3), and dehydration (n=1). Seven aCL+ patients received either intrasinus urokinase or intravenous heparin sulfate, and 1 received aspirin. Four aCL+ patients developed new onset or worsening of preexisting migraine, 2 developed recurrent peripheral venous thrombosis, and 1 went on to have intracranial hypertension. Twenty additional patients with CVT associated with antiphospholipid antibodies (aPL) were found reported in the literature. The overall mean age was 36±11.6 (range, 21 to 62) years, and 14 (70%) were women. LA was present in 11 of 18 tested, aCL in 7 (35%), LA and aCL in 1, and the type of aPL was not reported in 3. The mean age for the aCL+ only group was 28 years and for the LA+ (with or without aCL+) was 34 years. Only 1 patient, whose aPL type was not specified, had thrombosis of the deep venous system in addition to involvement of the dural sinuses.

Conclusions
Our series and review suggest that aCL may be an important factor contributing to development of CVT even in the presence of other potential etiologies or risk factors. Onset of aCL+ CVT occurs at a relative young age and with relatively more extensive superficial and deep cerebral venous system involvement than aCL− CVT.
Predisposing Factors to Enlargement of Spontaneous Intracerebral Hematoma
Authors: Kazui S. , Minematsu K. , Yamamoto H. , Sawada T. , Yamaguchi T.
Published: June 2011

Background and Purpose
Enlargement of intracerebral hemorrhage is a major cause of clinical deterioration. Identification of factors that predispose to hematoma enlargement is important in managing patients.

Methods
We selected 186 patients (71 women and 115 men; mean age, 64.8±12.5 years) with spontaneous intracerebral hemorrhage who had undergone an initial CT within 24 hours and a second scan within 120 hours of symptom onset. We compared patients with (n=41) and without (n=145) hematoma enlargement according to clinical characteristics and laboratory data.

Results
By multiple logistic regression analysis (n=139), interaction of long interval (>6 hours) from onset to first CT and small hematoma (<25 cm
3
) strongly reduced risk of enlargement. The analysis also demonstrated that the following factors independently predisposed to enlargement: history of brain infarction; liver disease; interaction of fasting plasma glucose ≥141 mg/dL and systolic blood pressure on admission ≥200 mm Hg; and interaction of glycosylated hemoglobin A
1c
≥5.1% and systolic blood pressure on admission ≥200 mm Hg.

Conclusions
A patient examined >6 hours after ictus who has a hematoma volume <25 cm
3
is unlikely to experience further hematoma growth. Prevention of brain infarction and premorbid management of liver disease may serve to lower the risk of hematoma enlargement. Although it remains controversial whether antihypertensive drugs should be used in the acute phase of intracerebral hemorrhage, poorly controlled diabetics with high systolic blood pressure (≥200 mm Hg) on admission also were at high risk of hematoma enlargement.
Increased Common Carotid Intima-Media Thickness
Authors: Bots Michiel L. , Hofman Albert , Grobbee Diederick E.
Published: June 2011

Background and Purpose
Carotid intima-media thickness (IMT) measurements are used widely to study atherosclerosis. Some have suggested that an increased IMT reflects a nonatherosclerotic adaptive response to changes in shear stress and tensile stress. This stems from the hypothesis that changes in shear stress and subsequently in lumen diameter are followed by changes in IMT to keep tensile stress constant. We studied the relation of common carotid IMT to common carotid end-diastolic lumen diameter and tensile stress, as approximated by mean arterial pressure · (lumen diameter/IMT)].

Methods
A cross-sectional analysis was performed with data obtained from the first 1715 participants in the Rotterdam Study, a population-based cohort study among 7983 subjects aged 55 years and over who underwent ultrasonographic examination of the carotid arteries. End-diastolic lumen diameter and IMT of the common carotid arteries were evaluated and quantified.

Results
With increasing IMT, inner and outer lumen diameters increased gradually, and beyond an IMT of 1.10 mm, the inner lumen diameter decreased. Tensile stress increased with increasing lumen diameter instead of being constant. The lumen-to-IMT ratio was constant across levels of mean arterial pressure.

Conclusions
Our findings are compatible with the view that at lower degrees of IMT, the thickening appears to reflect an equilibrium state in which the effects of pressure and flow on the arteries are in balance, given a characteristic relation between shear stress and local transmural pressure. Beyond a certain level, IMT more likely may represent atherosclerosis. Regardless of whether common carotid IMT reflects local atherosclerosis, it may still serve as a graded marker for cardiovascular risk.
Role of Transcranial Doppler and Stump Pressure During Carotid Endarterectomy
Authors: Finocchi Cinzia , Gandolfo Carlo , Carissimi Tiziana , Massimo Del Sette  , Bertoglio Carlo
Published: June 2011

Background and Purpose
The aim of our study was to clarify the pathophysiology of perioperative cerebral complications during carotid endarterectomy in our series.

Methods
By means of transcranial Doppler ultrasonography and stump pressure measurement, we monitored 112 patients who underwent carotid endarterectomy under general anesthesia for symptomatic or asymptomatic severe carotid stenosis.

Results
Of 18 patients who underwent carotid endarterectomy with intra-arterial shunt, 2 (11.1%) developed an ischemic stroke. Of the other 94 patients, one suffered a nucleocapsular hemorrhage and 5 had cerebral ischemic complications. In these 5 patients, the duration of clamping was significantly longer (mean±SD, 16.4±1.1 versus 12.7±2.6 minutes;
P
=.0019), and the decrease of middle cerebral artery mean velocity on clamping was significantly greater (mean±SD, 56.4±4.9% versus 28.8±20.2%;
P
=.0031), while stump pressure was not significantly different. Microembolic signals were recorded in 70 patients (62.5%) and were not associated with cerebral ischemic complications. The 7 patients who developed cerebral ischemic complications had a significantly higher percentage of stenosis in the contralateral internal carotid artery (mean±SD, 82.0±17.8% versus 29.3±36.4%;
P
=.0018).

Conclusions
The results of our study suggest that the major complications of carotid endarterectomy may be due to hemodynamic factors. Stump pressure alone is not a reliable indicator of hemodynamic changes that predict cerebral ischemia. Particulate microembolism may cause more subtle changes in cerebral parenchyma, but further studies are needed to clarify this point.
Oxygen Inhalation Can Differentiate Gaseous From Nongaseous Microemboli Detected by Transcranial Doppler Ultrasound
Authors: Droste Dirk W. , Hansberg Tjark , Kemény Vendel , Hammel Dieter , Schulte-Altedorneburg Gernot , Nabavi Darius G. , Kaps Manfred , Scheld Hans H. , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
Clinically silent circulating microemboli can be detected by transcranial Doppler sonography. The composition of these emboli in different clinical conditions is unclear.

Methods
We performed 1-hour transcranial Doppler sonographic recordings from the middle cerebral or posterior cerebral artery in 20 patients with mechanical prosthetic heart valves, in 78 patients with an arterial embolic source, and in 20 control subjects. During 30 minutes of this recording, the patients inspired room air and 6 L of oxygen per minute via a loosely fitting facial mask; during the remaining 30 minutes, they breathed room air only.

Results
There was a significant decline of embolic signals (ES) under oxygen in the patients with mechanical prosthetic cardiac valves (144 ES without oxygen versus 63 ES with oxygen;
P
=.002) but not in the patients with arterial embolic sources (145 ES without oxygen versus 135 ES with oxygen; P=NS). In the control subjects, no ES were found.

Conclusions
ES in patients with mechanical prosthetic cardiac valves correspond mainly to gas bubbles. Oxygen inhibits the cavitation process of mechanical prosthetic heart valves or speeds up redissolution of gas bubbles generated by cavitation. In contrast, solid microemboli originating from thrombus or atheroma cannot be suppressed by oxygen inhalation. This simple method of oxygen inhalation should help to clarify the composition of microemboli in various clinical and experimental settings.
Noninvasive Prediction of Intracranial Pressure Curves Using Transcranial Doppler Ultrasonography and Blood Pressure Curves
Authors: Schmidt Bernhard , Klingelhöfer Jürgen , Schwarze Jens Jürgen , Sander Dirk , Wittich Ingo
Published: June 2011

Background and Purpose
Until now the assessment of intracranial pressure (ICP) required invasive methods. The objective of this study was to introduce an approach to a noninvasive assessment of continuous ICP curves.

Methods
The intracranial compartment was considered a “black box” system with an input signal, the arterial blood pressure (ABP), and an output signal, the ICP. A so-called weight function described the relationship between ABP and ICP curves. Certain parameters, called transcranial Doppler (TCD) characteristics, were calculated from the cerebral blood flow velocity (FV) and the ABP curves and were used to estimate this weight function. From simultaneously sampled FV, ABP, and (invasively measured) ICP curves of a defined group of patients with severe head injuries, the TCD characteristics and the weight function were computed. Multiple regression analysis revealed a mathematical formula for calculating the weight function from TCD characteristics. This formula was used to generate the ICP simulation. FV, ABP, and ICP recordings from 11 patients (mean age, 46±14 years) with severe head injury were studied. In each patient, ICP was computed by a simulation procedure, generated from the data of the remaining 10 patients. The simulation period was 100 seconds.

Results
Corresponding pressure trends with a mean absolute difference of 4.0±1.8 mm Hg between computed and measured ICP were observed. Shapes of pulse and respiratory ICP modulations were clearly predicted.

Conclusions
These results demonstrate that this method constitutes a promising step toward a noninvasive ICP prediction that may be clinically applicable under well-defined conditions.
Spinal Cord Ischemic Injury
Authors: Kanellopoulos Georgios K. , Kato Hiroyuki , Hsu Chung Y. , Kouchoukos Nicholas T.
Published: June 2011

Background and Purpose
Spinal cord ischemic injury (SCII) with resulting paralysis is a major cause of morbidity after operations on the thoracic aorta. Since the vascular supply to the spinal cord is similar in rats and humans, the rat appears important for studies of mechanisms of injury and development of therapeutic strategies to avoid this complication.

Methods
In group A rats, we induced SCII using a previously described method, by occluding the descending thoracic aorta for 15, 20, 24, or 30 minutes with the inflated balloon of a 2F Fogarty catheter inserted through the femoral artery. In group B, the catheter was inserted through the left common carotid artery, and the aorta was occluded just distal to the carotid origin for 20 minutes. In group C, in addition to the procedure described for group B, hypovolemia was induced during a 12-minute period of aortic occlusion by equilibrating the left femoral artery pressure to the atmospheric pressure. The motor function of the hind limbs and the associated spinal cord histopathology were studied.

Results
At 96 hours, 9 of 10 rats in group C were paraplegic. This rate was significantly higher than that of group A (1 of 21,
P
=.00000) or group B (4 of 10,
P
<.03). In all groups, the histopathological changes became more severe from the rostral to the caudal direction along the spinal cord and from the peripheral to the central location in transverse sections.

Conclusions
The combination of aortic arch occlusion with induced hypovolemia resulted in a reproducible model of SCII in rats.
Upper Motor Neuron Lesions in Stroke Patients Do Not Induce Anterograde Transneuronal Degeneration in Spinal Anterior Horn Cells
Authors: Terao Shin-ichi , Li Mei , Hashizume Yoshio , Osano Yutaka , Mitsuma Terunori , Sobue Gen
Published: June 2011

Background and Purpose
To determine whether upper motor neuron lesions in stroke can cause transneuronal degeneration of lower motor neurons, we assessed spinal anterior horn cells in patients dying with poststroke hemiplegia.

Methods
Subjects were four stroke patients with severe left hemiplegia and four age-matched control subjects who died of nonneurological disease. After histological processing and staining, cytoarchitectonic assessment was made of all neurons in the ventral horns of the 4th lumbar segment of the spinal cord according to cell diameter and topography.

Results
In the four stroke patients, no differences were seen in anterior horn cell populations or diameter and size distribution patterns between affected and unaffected sides or between these patients and the control subjects.

Conclusions
The present quantitative analysis provides no evidence of anterograde transneuronal degeneration of lower motor neurons after upper motor neuron damage in stroke patients.
Stroke Rates During the 1980s
Authors: Shahar Eyal , McGovern Paul G. , Pankow James S. , Doliszny Katherine M. , Smith Maureen A. , Blackburn Henry , Luepker Russell V.
Published: June 2011

Background and Purpose
The decline in stroke mortality in the United States may have resulted from declining incidence, improved survival of stroke patients, or both. We previously reported that stroke patients who were 30 to 74 years old and were treated in Minneapolis/St Paul hospitals in 1990 survived longer than did their counterparts in 1980. In the present study, we examined trends in the rate of hospitalized stroke in Minneapolis/St Paul between 1980 and 1990.

Methods
For 1980, 1985, and 1990, we obtained lists of discharge codes (
International Classification of Diseases, 9th revision
) from Minneapolis/St Paul hospitals, identified hospitalizations for acute cerebrovascular disease, and randomly selected 50% of the cases for medical record abstraction. We counted stroke events in five different ways, which were based on discharge codes as well as diagnostic criteria, and computed age-adjusted stroke rates for each year. Stroke mortality in the population was computed for 1960 through 1994.

Results
Among men, all five measures of hospitalized stroke attack rate indicated a decline between 1980 and 1985, which ranged from 5% to >20%. Among women, there was a sharp contrast between trends that relied on discharge codes and trends that relied on diagnostic criteria: the former indicated a decline (4% to 19%), whereas the latter indicated some increase. For the second half of the 1980s, most measures of stroke attack rate in men, all measures of stroke attack rate in women, and measures of stroke incidence in both sexes did not indicate a decline in stroke occurrence in the population. Mortality from stroke among 30- to 74-year-old residents of Minneapolis/St Paul, which declined rapidly during the 1970s and early 1980s, declined slowly, if at all, during the second half of the 1980s and early 1990s.

Conclusions
The incidence of stroke may have declined among 30- to 74-year-old residents of Minneapolis/St Paul in the early 1980s. However, we found little indication of such a trend between 1985 and 1990, a period of slow decline or no decline in stroke mortality in that population.
Reliability of Hemorrhagic Transformation Diagnosis in Acute Ischemic Stroke
Authors: Motto Cristina , Aritzu Elisabetta , Boccardi Edoardo , De Grandi Carlo , Piana Alessandra , Candelise Livia
Published: June 2011

Background and Purpose
Diagnosis of hemorrhagic transformation (HT) could influence the prognosis and the management of acute ischemic stroke. The interobserver reliability of CT-scan HT classification is evaluated in the present study.

Methods
Fifty 5-day CT scans of patients enrolled in the Multicenter Acute Stroke Trial–Italy (MAST-I) were reviewed independently by two neuroradiologists and one neurologist with CT training. They evaluated the presence and type of intraparenchymal HT (hemorrhagic infarction types I, II, and III and intracerebral hemorrhage) (five-item scale), as well as the presence of intraventricular and/or subarachnoid bleeding according to standardized definitions.

Results
Agreement for exclusion of HT and intraventricular/subarachnoid bleeding was good between the neuroradiologists (κ=0.70 and κ=0.72) and excellent between the neurologist and each neuroradiologist (κ=0.87 and κ=0.77, κ=0.83, and κ=0.81, respectively). The overall agreement for the five-item HT scale between the two neuroradiologists was good (κ

w

=0.65) because of discordance over the last three items. Better overall agreement was obtained with a three-item scale: no hemorrhage, petechial type I hemorrhagic infarction, and other HT (type II and type III hemorrhagic infarction and intracerebral hemorrhage) together (κ

w

=0.82).

Conclusions
Exclusion of HT is a reliable CT diagnosis when made by neuroradiologists and also by a neurologist with CT training. Five- and three-item scales of HT types showed good to excellent reliability. The validity of the scale for predicting short- and long-term outcome should be evaluated in future studies.
Reliability of the National Institutes of Health Stroke Scale
Authors: Goldstein Larry B. , Samsa Gregory P.
Published: June 2011

Background and Purpose
The reliability of the National Institutes of Health Stroke Scale (NIHSS) has been established through testing its use in live and videotaped patients. This reliability testing has primarily focused on the use of the scale by neurologists. We sought to determine the reliability of the NIHSS as used by non-neurologists in the context of a clinical trial.

Methods
In anticipation of the initiation of a randomized trial of a new therapy for patients with acute ischemic stroke, 30 physician investigators (30% of whom were not neurologists) and 29 non-physician study coordinators were trained in the use of the NIHSS at an informational and training conference using standardized videotaped patient examinations. A series of 4 patients were rated initially. After 3 months, the same 4 patients were rerated, providing a measure of intraobserver reliability. An additional series of 4 new patients were also rated after 3 months and, with the initial 4 ratings, provided data for assessment of interobserver reliability.

Results
Overall, 28% of the raters had previous experience with the NIHSS, and 22% had previously used the videotapes as used in the present trial. The coefficients of determination (
r
2
) were each greater than .95 when the means of the two ratings of the same 4 cases were compared between (1) neurologists and other types of physicians, (2) physicians and study coordinators, (3) raters who had prior experience with the NIHSS and those without prior experience, and (4) raters who had used the videotapes in the past and those who had never viewed the tapes. The calculated
r
2
s were greater than .98 for the initial rating of the first 4 cases and for the later rating of the 4 new cases. The slopes of the regression lines were all near 1, indicating that the raters were similarly calibrated. The intraclass correlation coefficients were .93 and .95, reflecting high levels of intraobserver and interobserver reliability.

Conclusions
These data extend the previously demonstrated reliability of the NIHSS to non-neurologists and show that both a variety of physician investigators and nurse study coordinators can be rapidly trained to reliably apply the scale in the context of an actual clinical trial.
Atrial Fibrillation and Dementia in a Population-Based Study
Authors: Ott Alewijn , Breteler Monique M.B. , de Bruyne Martine C. , van Harskamp Frans , Grobbee Diederick E. , Hofman Albert
Published: June 2011

Background and Purpose
Atrial fibrillation is a frequent disorder in the elderly and a known risk factor for cerebrovascular stroke. We investigated the association of atrial fibrillation with dementia and cognitive impairment in a large cross-sectional, population-based study in the elderly.

Methods
Of the 6584 participants in the Rotterdam Study aged 55 to 106 years, detailed information on dementia status and ECG abnormalities was available. Dementia was diagnosed in three phases. First, participants were screened. Screen-positive subjects were tested further. Those with possible dementia underwent an extensive diagnostic workup. Dementia and dementia subtypes were diagnosed according to prevailing criteria. Cognitive impairment was defined as a Mini-Mental State Examination test score of <26 points for a nondemented subject.

Results
Atrial fibrillation was diagnosed in 195, dementia in 276, and cognitive impairment in 635 subjects. We found significant positive associations of atrial fibrillation with both dementia and impaired cognitive function (age- and sex-adjusted odds ratios, 2.3 [95% confidence interval, 1.4 to 3.7] and 1.7 [95% confidence interval, 1.2 to 2.5]), respectively). The strongest association was found not for vascular dementia but rather for Alzheimer's disease with cerebrovascular disease. The associations were stronger in women, and the relation with dementia was more pronounced in the relatively younger elderly. A history of stroke in subjects with atrial fibrillation could not account for these associations.

Conclusions
Dementia and subtypes Alzheimer's disease and vascular dementia may be related to atrial fibrillation even if no clinical stokes have occurred.
Clinical Evaluation of Near-Infrared Spectroscopy for Testing Cerebrovascular Reactivity in Patients With Carotid Artery Disease
Authors: Smielewski Peter , Czosnyka Marek , Pickard John D. , Kirkpatrick Peter
Published: June 2011

Background and Purpose
Near-infrared spectroscopy (NIRS) derives information about the concentrations of oxyhemoglobin (HbO
2
) and deoxyhemoglobin (Hb) from measurements of light attenuation caused by these chromophores. The aim of this study was to assess NIRS as a tool for testing CO
2
reactivity in patients with carotid artery disease.

Methods
One hundred patients with symptomatic carotid occlusive disease were examined (age range, 44 to 83 years). The severity of stenosis ranged from 30% to 100% (median, 80%) on the ipsilateral side and 0% to 100% (median, 30%) on the contralateral side. Monitored parameters included transcranial Doppler flow velocity, changes in concentration of HbO
2
and Hb, cutaneous laser-Doppler blood flow, end-tidal CO
2
, arterial blood pressure, and arterial oxygen saturation. Hypercapnia was induced with the use of a 5% CO
2
/air mixture for inhalation. To estimate the contribution of skin flow to NIRS during reactivity testing, the superficial temporal artery was compressed, and the NIRS changes in response to the fall in laser-Doppler blood flow were recorded. Finally, reproducibility of reactivity testing was assessed in 10 patients who were subjected to repeated examinations over 3 days.

Results
Flow velocity– and HbO
2
-derived reactivity values were related to the severity of the stenosis (
P
=.0001 and
P
=.017, respectively). The correlation between the two reactivity modalities was significant (
r
=.49,
P
<.000001). The median estimated contribution of skin flow to NIRS changes was 15.8%. Another variable affecting HbO
2
signal changes during the CO
2
challenge was arterial blood pressure (
P
=.025). Reproducibility of HbO
2
reactivity was similar to flow velocity reactivity (14.3% and 18.6% variation, respectively).

Conclusions
NIRS shows potential as an alternative technique for testing CO
2
reactivity in patients with carotid disease provided that conditions are carefully controlled. Marked changes in arterial blood pressure may render the NIRS reactivity indices unreliable, and the contribution from extracranial tissue must be taken into account when significant.
Consistency of Doppler Parameters in Predicting Arteriographically Confirmed Carotid Stenosis
Authors: Schwartz Skai W. , Chambless Lloyd E. , Baker William H. , Broderick Joseph P. , Howard George
Published: June 2011

Background and Purpose
While internal carotid peak systolic velocity (IPSV) is reportedly the best Doppler parameter for predicting lower grades of carotid artery stenosis, the internal carotid end-diastolic velocity (IEDV) or the ratio of IPSV to common carotid end-diastolic velocity (CEDV) is helpful in increasing prediction of higher grade stenoses. It is important to examine the consistency of these findings across machine and technician.

Methods
Using data from 10 devices from the Asymptomatic Carotid Atherosclerosis Study, we examined the predictive ability of seven Doppler parameters: IPSV, IEDV, CEDV, common carotid peak systolic velocity (CPSV), and the ratios of IPSV/CEDV, IEDV/CEDV, and IEDV/CEDV. To assess the agreement between Doppler and arteriography in classifying percent stenosis above or below a given criterion, sensitivity, specificity, area under the receiver operating curve, and κ statistics were obtained from logistic models. The single best Doppler parameter for each of two grades of stenosis (60% and 80%) was determined, and its predictive ability was compared with that of IPSV. The usefulness of IEDV or IPSV/CEDV in addition to IPSV to determine higher grade stenosis was examined.

Results
IPSV was the best predictor in 9 of 10 devices at 60% and in 4 devices at 80% stenosis. When another parameter was better than IPSV, the improvement was minimal. Including IEDV or IPSV/CEDV in addition to IPSV did not notably improve predictive ability.

Conclusions
IPSV is the single best Doppler parameter for distinguishing severe (>80%) from less severe carotid stenosis. Information from other Doppler parameters in addition to IPSV is unlikely to be helpful.
High Signal Intensity on T2-Weighted Magnetic Resonance Imaging and Cerebral Hemodynamic Reserve in Carotid Occlusive Disease
Authors: Isaka Yoshinari , Nagano Keiko , Narita Masako , Ashida Keiichi , Imaizumi Masatoshi
Published: June 2011

Background and Purpose
The importance of MR imaging in carotid artery disease is unclear. We evaluated the sensitivity and specificity of the high signal intensity changes on MR images for diagnosis of hemodynamically compromised unilateral internal carotid artery disease.

Methods
We evaluated the association of high signal intensities on T2-weighted MR images with changes in cerebral perfusion reserve measured using
99m
Tc-hexamethylpropyleneamine oxime single-photon emission CT and acetazolamide in 23 patients.

Results
Eleven patients had a type I response (normal flow and normal perfusion reserve), 8 patients had a type II response (normal flow and decreased perfusion reserve), and 4 patients had a type III response (decreased flow and decreased perfusion reserve). High signal intensities in the centrum semiovale (11/12) and/or posterior periventricular white matter (6/12) were frequently seen in the hemodynamically compromised groups. Extensive high signal intensities were associated with severely impaired cerebral circulation. MR imaging had high sensitivity (0.92) and specificity (1.0) in predicting hemodynamically compromised patients when we used the presence of T2 high intensity in the centrum semiovale as a criterion.

Conclusions
The centrum semiovale T2 hyperintensities lateralized to the side of carotid occlusion are specific and sensitive for the presence and severity of hemodynamic compromise from carotid occlusive disease.
Human Vascular Endothelium Heterogeneity
Authors: Thorin Eric , Shatos Marie A. , Shreeve S. Martin , Walters Carrie L. , Bevan John A.
Published: June 2011

Background and Purpose
Hormones, neurotransmitters, and autacoids play a key role in the regulation of vascular tone as a result of their interaction with the endothelium. The aim of this study was to compare selected properties of three human endothelial cell lines isolated from cerebral pial arteries (PEC) and two peripheral vessels, the superficial temporal (SEC) and omental (OEC) arteries.

Methods
Intracellular free calcium concentration ([Ca
2+
]
i
) and receptor protein expression were measured in characterized primary cultures of human endothelial cells.

Results
All cell lines labeled positively for factor VIII/von Willebrand factor. Growth rate and constitutive release of endothelin-1, expressed as a function of protein, were both significantly lower in cerebral cells (PEC) than in endothelial cells derived from peripheral vessels. Basal [Ca
2+
]
i
measured with the fluorescent calcium indicator fura 2-AM (2 μmol/L) did not differ in either of the three cell lines. Although PEC responded to endothelin-1 (0.1 μmol/L) and vasoactive intestinal peptide (1 μmol/L) by a twofold to threefold increase in [Ca
2+
]
i
, OEC were unresponsive to these peptides. Moreover, the calcium response to α-thrombin (10 nmol/L) was greater in cerebral (PEC) than in peripheral (SEC, OEC) endothelial cells, while bradykinin (100 nmol/L) increased [Ca
2+
]
i
to a similar level in all three cell types.

Conclusions
This study demonstrates that endothelial cells from different sites of the vasculature exhibit different growth rates and vary in their response to agonists.
Phagocytic Response in Photochemically Induced Infarction of Rat Cerebral Cortex
Authors: Schroeter Michael , Jander Sebastian , Huitinga Inge , Witte Otto W. , Stoll Guido
Published: June 2011

Background and Purpose
In this study we assessed the relative extent to which resident microglia and blood-borne macrophages contribute to the population of phagocytes after focal infarction of the rat cortex.

Methods
Focal cerebral infarction was induced in rats by photothrombosis after hematogenous macrophages were depleted by means of liposomes containing dichloromethylene diphosphonate. The phagocytic activation of microglia and macrophages was monitored by immunocytochemistry with the antibody ED1.

Results
In both macrophage-depleted rats and controls, ED1+ phagocytes bordered the infarct to the same extent at day 3 after photothrombosis. By contrast, at day 6 after photothrombosis ED1+ phagocytes in control rats greatly outnumbered those in macrophage-depleted rats. With the use of the antibody Ox42 directed against the CR3 receptor on the surface of microglia, it was possible to selectively document the transition of resident microglia into stellate and ameboid phagocytic microglia during the first 6 days after photothrombosis in the absence of blood-borne macrophages.

Conclusions
The initial phagocytic response after focal brain ischemia is an intrinsic property of the nervous system mainly performed by resident microglia. The majority of hematogenous macrophages are recruited secondarily to participate in the removal of necrotic tissue.
Prolongation and Enhancement of Postischemic c-
fos
Expression After Fasting
Authors: Lin T.N. , Te J. , Huang H.C. , Chi S.I. , Hsu C.Y.
Published: June 2011

Background and Purpose
A rapid but transient expression of c-
fos
after cerebral ischemia has been extensively documented. However, the mechanism of this induction and whether induction of c-
fos
is neuroprotective or detrimental to the brain after ischemia is presently not clear. Fasting before transient cerebral ischemia has been shown to reduce delayed neuronal necrosis and infarct volume. The purpose of the present study was to examine the effect of preischemic fasting for 24 hours on the expression of c-
fos
after transient focal cerebral ischemia.

Methods
Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries for 60 minutes. Male Long-Evans rats weighing 250 to 300 g were randomly divided into two groups: fed (control group) and food deprived for 24 hours (fasted group) before ischemic surgery. Infarct volumes were measured on the basis of triphenyltetrazolium chloride–delineated infarct areas, and plasma glucose levels were determined by the glucose oxidase method. Temporal and spatial expression of c-
fos
was assessed by Northern blot analysis, in situ hybridization, and immunohistochemistry.

Results
Fasting for 24 hours before 60 minutes of ischemia resulted in a 26.6% decrease in preischemic plasma glucose levels and a 74.5% reduction in infarct volumes in the fasted group compared with the control group. A rapid but transient induction of c-
fos
mRNA was observed in the ischemic cortex in control animals after 60 minutes of ischemia. Fasting not only prolonged but also enhanced the intensity of c-
fos
expression in the ischemic cortex. Regional c-
fos
expression was also different between these two groups.

Conclusions
The results support the contention that c-
fos
expression may be compatible with its purported neuroprotective role in selected experimental paradigms. The signaling mechanisms underlying the effect of fasting and subsequent lowering of plasma glucose levels on postischemic c-
fos
expression remain to be explored.