bluuebunny/crossref_metadata_2025 huggingface dataset:
Absolute Quantitation of Diffusion Constants in Human Stroke
Authors: Uluğ Aziz M. , Beauchamp Norman , Bryan R. Nick , van Zijl Peter C.M.
Published: June 2011

Background and Purpose
Animal studies have shown that MR diffusion imaging can outline acute ischemic regions before irreversible damage (infarction) occurs. To study evolution of ischemic lesions in humans, it is therefore important to quantify absolute diffusion constants (
D
values), but quantitation has not been reproducible among different clinics. These problems are explained, and a method for reproducible quantitation is suggested.

Methods
Diffusion-weighted and absolute diffusion images were acquired, and the absolute apparent diffusion constants in three orthogonal spatial directions (
D

xx

,
D

yy

, and
D

zz

) were measured. These were combined to calculate images of the orientation-independent apparent diffusion parameter
D

av

=1/3 Trace{D̄}=1/3(
D

xx

+
D

yy

+
D

zz

). Values of the individual diffusion constants and
D

av

were evaluated in 6 patients and 6 normal volunteers.

Results
Patient data show that comparison of diffusion constants between contralateral and ipsilateral hemispheres after ischemia may give results varying by more than 100% depending on orientation. Findings in normal-appearing regions containing a mixture of gray and white matter in patients (n=5) and in normal volunteers (n=6) show that
D

av

=(0.92±0.11)×10
–3
mm
2
/s, with a small intersubject variation, whereas
D

xx

,
D

yy

, and
D

zz

vary strongly. Hemispheric ratios (ipsilateral/contralateral [I/C]) in these subjects were (I/C)

D

av

=1.00±0.05, (I/C)

D

xx

=1.02±0.15, (I/C)

D

yy

=1.07±0.24, and (I/C)

D

zz

=0.96±0.28. The individual subjects in this group all had an (I/C)

D

av

within 10% of unity, while the other three ratios showed intersubject variations as large as 100%.

Conclusions
(I/C)

D

av

ratios are a reliable means to quantitate changes in absolute diffusion constants for the study of stroke evolution independent of tissue orientation, gradient orientation, and diffusion time. The use of these ratios will enable reproducible intersubject and interclinic quantitation.
Prevalence of Asymptomatic Carotid Atherosclerotic Lesions Detected by High-Resolution Ultrasonography and Its Relation to Cardiovascular Risk Factors in the General Population of a Japanese City
Authors: Mannami Toshifumi , Konishi Masamitsu , Baba Shunroku , Nishi Nobuo , Terao Atsushi
Published: June 2011

Background and Purpose
Because extracranial carotid atherosclerotic lesions have been considered rare, no reports have been published on the prevalence and distribution of these lesions in a general Japanese population. However, recent changes in lifestyle are thought to have caused an increase in these lesions. The aim of this study was to use high-resolution ultrasonography to examine the prevalence of asymptomatic extracranial carotid artery lesions and its relation to cardiovascular risk factors in an urban Japanese population.

Methods
The subjects were 814 men and 880 women aged 50 to 79 years randomly sampled from the residents of Suita, a city located in the second largest urban area of Japan. Asymptomatic carotid lesions were detected and evaluated by a single physician with high-resolution B-mode ultrasonography.

Results
We found significant sex differences in the prevalence of atherosclerotic lesions in the extracranial carotid artery; 4.4% of all the subjects, 7.9% of the men, and 1.3% of the women had atherosclerosis accompanied by stenosis of >50%. A strong association between these lesions and the results of a 75-g oral glucose tolerance test was found in both sexes. Multiple regression analysis of carotid atherosclerosis showed significant relationships with age, systolic blood pressure, fasting blood glucose, pack-years of smoking, total serum cholesterol, and HDL cholesterol in men (
P
<.05) and significant relationships with age, systolic blood pressure, pack-years of smoking, and total serum cholesterol in women (
P
<.05).

Conclusions
Our data showed that cardiovascular risk factors were strongly related to carotid atherosclerosis and that the proportion of severe carotid atherosclerosis with >50% stenosis was not low and was almost equal to that reported in developed western countries.
Nonmedical Bed-Days for Stroke Patients Admitted to Acute-Care Hospitals in Montreal, Canada
Authors: Mayo Nancy E. , Wood-Dauphinee Sharon , Gayton David , Scott Susan C.
Published: June 2011

Background and Purpose
Reducing the amount of nonoptimal time stroke patients spend in the hospital should be a priority because prolonged hospitalization is not only costly but may be detrimental for persons with stroke through deconditioning, social isolation, and the fostering of dependent relationships. The purpose of this study was to determine the amount of time spent by stroke patients in acute-care hospitals that was not justified for medical reasons and to identify mechanisms contributing to nonmedical bed-days.

Methods
A retrospective cohort study was performed with 2232 persons admitted for acute stroke to one of 13 hospitals in Montreal, Canada, during 1991. Information was collected on the patient, the stroke, functional status, course in hospital, services, and discharge. Nonmedical bed-days were calculated as the difference between the time to meet specified criteria and time of discharge. Associations with nonmedical bed-days were estimated with adjustment for patient mix.

Results
Acute-care stay averaged 27 days, yielding 60 279 bed-days. Almost 50% of the cohort remained in the hospital after meeting criteria for medical discharge, resulting in 43% of total bed-days not accounted for medically. Fifty percent of persons with delayed discharge did not go home but were discharged to another acute-care hospital or to rehabilitation or long-term care, accounting for 66% of the nonmedical bed-days. Hospital and discharge destination remained strongly associated with nonmedical days, even after adjustment for patient mix.

Conclusions
The single greatest contributor to excessive nonmedical stay appeared to be the need in Quebec for increased access to alternate levels of care, including skilled nursing facilities and rehabilitation centers.
Serum Creatinine Concentration and Risk of Cardiovascular Disease
Authors: Wannamethee S. Goya , Shaper A. Gerald , Perry Ivan J.
Published: June 2011

Background and Purpose
Elevated serum creatinine has been associated with increased mortality in hypertensive persons, the elderly, and patients with myocardial infarction or stroke in whom cardiovascular disease is the major cause of death. We have examined the relationship between serum creatinine concentration and the risk of major ischemic heart disease and stroke events and all-cause mortality in a general population of middle-aged men.

Methods
We present a prospective study of middle-aged men (aged 40 to 59 years) drawn from 24 British towns who have been followed up for an average of 14.75 years. Data on serum creatinine were available for 7690 men in whom there were 287 major stroke events, 967 major ischemic heart disease events, and 1259 deaths from all causes during follow-up.

Results
The median serum creatinine concentration was 98 μmol/L (95% range, 76 to 129 μmol/L). Stroke risk was significantly increased at levels above 116 μmol/L (90th percentile) even after adjustment for a wide range of cardiovascular risk factors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; ≥116 μmol/L versus the rest). Risk of a major ischemic heart disease event was significantly increased at or above 130 μmol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% CI, 0.8 to 1.7; ≥130 μmol/L versus the rest). There was a weak but significant positive association between diastolic blood pressure and creatinine concentration. However, elevated creatinine concentration (≥116 μmol/L) was associated with a significant increase in stroke in both normotensive and hypertensive men. All-cause mortality and overall cardiovascular mortality were significantly increased only above the 97.5 percentile, and no significant association was seen with cancer or other noncardiovascular mortality.

Conclusions
A high serum creatinine concentration within the normal range is a marker for increased risk of cerebrovascular disease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal function is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.
Microemboli in Patients With Vertebrobasilar Ischemia
Authors: Koennecke Hans-Christian , Mast Henning , Trocio Samuel S. , Sacco Ralph L. , Thompson John L. P. , Mohr Jay P.
Published: June 2011

Background and Purpose
Microembolic high-intensity transient signals (HITS) on transcranial Doppler ultrasound (TCD) are associated with carotid stenosis, artificial heart valves, and other cardiac conditions. Only one case report describes stroke-related HITS in the posterior cerebral circulation. This study was designed to assess prospectively the prevalence of asymptomatic microemboli in vertebrobasilar ischemia and to determine whether potential cardioembolic sources, vertebral or basilar occlusive disease, and infarct subtypes predict the detection of HITS.

Methods
We investigated 52 consecutive patients with acute or recent vertebrobasilar ischemia within 48 hours after admission. TCD monitoring was performed according to established criteria for 20 minutes on each posterior cerebral artery. Fetal origin of the posterior cerebral artery was an exclusion criterion and ruled out by carotid compression.

Results
Microembolic signals were detected in 10 patients (19.2%). In a multivariate logistic regression analysis that included all independent variables, potential cardiac sources were significantly associated with HITS (odds ratio [OR], 14.3; 95% confidence interval [CI], 1.6 to 128.4), in particular when more than one cardiac abnormality (OR, 32.7; CI, 4.1 to 259.3) or a high-risk source (OR, 14.0; 95% CI, 2.3 to 84.9) was found. Vertebrobasilar vessel lesions and infarct subtype were not related to the detection of microemboli.

Conclusions
Cardiac sources of embolism are a determinant of HITS in posterior cerebral circulation ischemia, suggesting that cardioembolic infarcts in that territory might be more common than suspected. Vertebrobasilar vessel abnormalities are less likely to lodge microemboli, which may indicate histopathological changes different from carotid artery disease.
Correlation Between Transcranial Doppler Ultrasonography and Regional Cerebral Blood Flow in Experimental Intracranial Hypertension
Authors: Nagai Hidemasa , Moritake Kouzo , Takaya Mikio
Published: June 2011

Background and Purpose
Transcranial Doppler ultrasonography (TCD) provides useful information on cerebral circulation even under raised intracranial pressure. This study was designed to evaluate the correlation between cerebral blood flow (CBF) and TCD parameters under conditions of boundary intracranial hypertension that can cause brain death.

Methods
Intracranial pressure was raised by inflation of a supratentorial epidural balloon in cats. Blood flow velocity of the middle cerebral artery was measured transorbitally with microvascular Doppler sonography, and intracranial pressure and CBF were evaluated.

Results
In this study, four characteristic flow patterns were observed, appearing in the following order with progressive increases in intracranial pressure: sharp wave, systolic flow, systolic spike, and no flow. These flow patterns showed a significant correlation with flow velocity, CBF, the pulsatility index, and cerebral perfusion pressure. The systolic-spike and no-flow patterns and pulsatility index over 4.0 indicated decreased CBF, under 10% of control values.

Conclusions
The critical level of brain circulation can be detected by Doppler sonography, indicating that TCD is available as a tool for the assessment of cerebral circulatory arrest in brain death.
Early Reperfusion in the Anesthetized Baboon Reduces Brain Damage Following Middle Cerebral Artery Occlusion
Authors: Young Alan R. , Touzani Omar , Derlon Jean-Michel , Sette Giuliano , MacKenzie Eric T. , Baron Jean-Claude
Published: June 2011

Background and Purpose
Because in humans the clinical benefits of reperfusion remain controversial, it is important to determine whether reperfusion per se reduces infarct volume. In the nonhuman primate, mostly semiquantitative assessments of infarction have been performed. When ischemic volumes have been calculated, it has been for the acute or subacute stages of experimental stroke and may thus not adequately reflect the total volume of consolidated infarction.

Methods
Anesthetized baboons were subjected to 6 hours of either reversible or permanent middle cerebral artery occlusion (MCAO). Approximately 4 weeks later, the brains were processed for neuropathological examination to allow assessment of the final infarct volume determined by the difference of healthy tissue between occluded and nonoccluded hemispheres.

Results
Reversible MCAO resulted in a small essentially subcortical infarction (mean±SD, 0.58±0.31 cm
3
) in 6 of 10 baboons: the infarct (pannecrosis) was restricted to the head of the caudate nucleus, internal capsule, and putamen; 4 of 10 baboons showed no evidence of macroscopic infarction. Permanent MCAO produced a larger subcortical infarct in all 7 baboons studied (2.37±1.32 cm
3
;
P
=.0006 by Wilcoxon-Mann-Whitney test); the lesion was more extensive and encompassed the external capsule and, in 2 baboons, the adjacent insular cortex.

Conclusions
We conclude that under optimal experimental conditions, an ischemic episode of 6 hours in duration is well tolerated in the anesthetized adolescent baboon, with 4 animals showing no signs of macroscopic brain damage. Thus, early reestablishment of cerebral blood flow after a focal ischemic insult is not detrimental but indeed is beneficial in terms of the final infarct volume (both at the subcortical and cortical levels) produced by occlusion of a major cerebral artery. The data further suggest a feasible time window in which to initiate and continue therapeutic interventions.
Case-Fatality Rates and Functional Outcome After Subarachnoid Hemorrhage
Authors: Hop Jeannette W. , Rinkel Gabriël J.E. , Algra Ale , van Gijn Jan
Published: June 2011

Background
During the last three decades, new management strategies have been developed for patients with aneurysmal subarachnoid hemorrhage. To assess whether the case-fatality rate has improved after the introduction of new management strategies, we studied outcome in all population-based studies from 1960 onward.

Summary of Review
To identify population-based studies that reported on case-fatality rate in subarachnoid hemorrhage, we performed a MEDLINE search and checked all reference lists of the studies found. Two authors (J.W.H. and G.J.E.R.) independently assessed all studies for eligibility, using predefined criteria for case finding and diagnosis, and extracted data on case-fatality rates. We used weighted linear regression analysis to quantify change in case-fatality rate over time. We found 21 studies, describing 25 study periods between 1960 and 1992. Case-fatality rates varied between 32% and 67%, with the exception of one recent study. The case-fatality rate decreased by 0.5% per year (95% confidence interval, −0.1 to 1.2); the decline was steeper after adjustment for age and sex (0.9% per year; 95% confidence interval, −0.7 to 2.6; data from 12 studies).

Conclusions
The case-fatality rate after subarachnoid hemorrhage has decreased during the last three decades. A plausible explanation for this decrease is the improved management of patients with subarachnoid hemorrhage.
Transcranial Doppler Monitoring and Causes of Stroke From Carotid Endarterectomy
Authors: Spencer Merrill P.
Published: June 2011

Background and Purpose
The value of carotid endarterectomy (CEA) depends on the safety of the operation. Transcranial Doppler ultrasound (TCD) was used to evaluate the possibilities of hypoperfusion, hyperperfusion, and embolization as causes of stroke and to evaluate the significance of Doppler microembolic signals (DMES).

Methods
Five hundred CEAs were monitored with TCD of the ipsilateral middle cerebral artery during various phases of CEA to determine hemodynamic changes and incidence of DMES. Complications were graded according to their severity, and their probable cause was determined from TCD criteria and review of hospital charts.

Results
We observed 24 cerebrovascular complications (4.8%), including 9 with transient ischemic attacks and 15 (3%) with permanent deficits. Among all cerebrovascular complications, embolism was judged to be responsible in 13 (54%;
P
<.02 compared with hypoperfusion), hyperperfusion in 7 (29%;
P
<.14 compared with hypoperfusion), and hypoperfusion in 4 (17%;
P
<.08 compared with embolism plus hyperperfusion). The surgeons responded to TCD information by several strategies depending on the TCD information. The incidence of permanent deficits diminished from 7% in the first 100 operations to 2% in the last 400 (
P
≤.01). Shunting was more strongly associated with cerebrovascular complications than nonshunting, but this difference was not significant (
P
=.24). Intraoperative prevalence of DMES was strongly associated with cerebrovascular complications (
P
=.02).

Conclusions
Embolism is the principal cause of cerebrovascular complications from CEA; hyperperfusion and hypoperfusion are also important causes. TCD provides information that allows prompt identification and treatment of these three major causes of stroke from this operation. The perioperative stroke rate can be reduced by appropriate measures, taken by the surgeons, based on findings of TCD monitoring.
Echocontrast-Enhanced Transcranial Color-Coded Sonography for the Diagnosis of Transverse Sinus Venous Thrombosis
Authors: Ries S. , Steinke W. , Neff K. W. , Hennerici M.
Published: June 2011

Background and Purpose
Early diagnosis of cerebral transverse sinus venous thrombosis (TSVT) is difficult because of nonspecific and variable clinical presentations. Therefore, we evaluated the diagnostic value of transcranial color-coded duplex sonography (TCCS) after administration of an echocontrast-enhancing agent (cTCCS) in clinically suspected TSVT.

Methods
We examined 14 patients (6 men, 8 women; mean age, 48 years; range, 18 to 70 years) with signs and symptoms suggestive of cerebral TSVT. Color-coded signals from the contralateral transverse sinus were displayed transtemporally before and after injections of an echocontrast agent by TCCS. Sonographic findings were correlated with MRI and MR venography (MRV).

Results
Before echocontrast enhancement, TCCS displayed color Doppler signals in 7 of 28 transverse sinus. Echocontrast TCCS obtained sufficient color signals in 27 of 28 transverse sinus. Thus, diagnostic confidence was achieved in all but 1 patient. In 13 patients, cTCCS identified 3 cases with symmetrical blood flow in the transverse sinus, which was confirmed by MRV. Accordingly, asymmetry of venous blood flow was correctly assessed by cTCCS in the other 10 patients. In 6 of these 10 patients, cTCCS demonstrated residual color flow signals, which on MRI/MRV corresponded to partial TSVT (4 cases) and to hypoplasia (1 case) of the transverse sinus. One case of complete thrombotic occlusion of the transverse sinus was missed by cTCCS because of color Doppler signals originating from an adjacent dural fistula. Echocontrast TCCS diagnosis of occlusion of a transverse sinus was confirmed by MRI/MRV in all cases (aplasia of transverse sinus, n=1; complete TSVT, n=3). Systolic peak flow velocities were significantly decreased in hypoplastic or partially occluded transverse sinus (9.4±4.0 cm/s) and significantly increased contralaterally (28.4±6.5 cm/s) with respect to patients with symmetrical appearance of the transverse sinus (17.5±1.9 cm/s) (
P
<.05).

Conclusions
TCCS examination of the cerebral venous system is difficult without contrast media application and almost useless for the study of TSVT. However, cTCCS is of practical value in the initial workup of patients with clinically suspected TSVT and may provide further insight for follow-up studies in view of monitoring the recanalization.
Health Status of Individuals With Mild Stroke
Authors: Duncan Pamela W. , Samsa Gregory P. , Weinberger Morris , Goldstein Larry B. , Bonito Arthur , Witter David M. , Enarson Cam , Matchar David
Published: June 2011

Background and Purpose
Diminished quality of life and limitations in higher levels of physical functioning are often underestimated in stroke and are not fully captured by measures such as the Barthel Index and the Rankin Outcome Scale. This study used additional measures to assess the health status of 304 persons with mild stroke and to compare these individuals with 184 persons with transient ischemic attack and 654 persons without history of stroke/transient ischemic attack but at elevated risk for stroke (asymptomatic group).

Methods
Subjects were recruited from the Academic Medical Center Consortium (inpatients), the Cardiovascular Health Study (population-based sample of community-dwelling persons 65 years and older), and United HealthCare (inpatients and outpatients typically younger than 65 years). Subjects were interviewed by telephone or in person to assess activities of daily living (Barthel Index), depression (Center for Epidemiological Studies Depression Scale), health status (MOS-36), and utility for current health state.

Results
Most respondents were independent on all Barthel items. The stroke group was more impaired on the MOS-36 than the asymptomatic group but similar to the group with transient ischemic attack. Health-related quality of life was lowest for persons with stroke. While symptom status and Barthel Index score were the strongest predictors of health status, the Barthel Index showed a consistent ceiling effect when compared with the physical function subscale of the MOS-36.

Conclusions
The consequences of even mild stroke affect all dimensions of health except pain. Standardized assessment of persons with stroke must evaluate across the entire continuum of health-related functions.
Dementia Three Months After Stroke
Authors: Pohjasvaara Tarja , Erkinjuntti Timo , Vataja Risto , Kaste Markku
Published: June 2011

Background and Purpose
Vascular dementia is a common cause of dementia, and cerebrovascular disease is related to a higher risk of dementia. The frequency of dementia associated with ischemic stroke and the effects of different definitions of dementia in the diagnosis are still incompletely known. We evaluated the frequency of cognitive decline and dementia 3 months after ischemic stroke in a large stroke cohort.

Methods
Our cohort consisted of consecutively admitted ischemic stroke patients (n=486) aged 55 to 85 years in the Helsinki (Finland) Stroke Aging Memory Study (SAM). Subjects were assessed by structured medical, neurological, and radiological examinations and interview with a close informant, as well as by the Mini-Mental State Examination and detailed clinical mental status examination of defined cognitive domains. The criteria for dementia were those of the
Diagnostic and Statistical Manual of Mental Disorders
(DSM) (DSM-III, DSM-III-R, and DSM-IV), the National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN), and the
International Classification of Diseases, 10th Revision
(ICD-10).

Results
We found that 451 (92.8%) of the patients were testable, 239 (49.2%) of the patients were women, and the mean age was 71.2 years. Any cognitive decline was present in 61.7%. In the groups aged 55 to 64, 65 to 74, and 75 to 85 years, the frequency of any cognitive decline was 45.7%, 53.8%, and 74.1% (
P
=.0008), respectively. The frequency of dementia was 25.5% by DSM-III, 20.0% by DSM-III-R, 18.4% by DSM-IV, 21.1% by NINDS-AIREN, and 6.0% by ICD-10 criteria. The frequency increased with increasing age: by the DSM-III definition, frequency in the aforementioned age groups was 19.3%, 23.7%, and 25.5%, respectively (
P
=.014). There was an overlap in the cases diagnosed as demented according to the different guidelines. Compared with standard diagnosis, the DSM-III was the most sensitive and ICD-10 the most specific. Concordance was moderate between the DSM criteria and NINDS-AIREN criteria but was poor between ICD-10 and the other criteria.

Conclusions
Cognitive decline and dementia were frequent in the cohort of ischemic stroke patients, and the frequency increased with increasing age. Different definitions gave different frequency estimates, and overlap in the cases was observed. Our findings question the validity of current criteria for dementia in the setting of cerebrovascular disease and emphasize the need for further debate and studies to refine the categories of cognitive impairment related to cerebrovascular disease.
Effects of a Novel Inhibitor of Guanylyl Cyclase on Dilator Responses of Mouse Cerebral Arterioles
Authors: Sobey Christopher G. , Faraci Frank M.
Published: June 2011

Background and Purpose
Nitric oxide–induced vasodilatation is mediated by both cGMP-dependent and -independent mechanisms. Previous studies that examined the role of soluble guanylyl cyclase in cerebral vessels have used methylene blue and LY-83583, compounds that generate superoxide anion and are not specific for inhibition of soluble guanylyl cyclase. We examined the effects of ODQ (1
H
-[1,2,4]oxadiazolo[4,3,-
a
]quinoxalin-1-one), a novel and highly selective inhibitor of soluble guanylyl cyclase, on responses of cerebral arterioles.

Methods
The effects of ODQ on responses of cerebral arterioles to acetylcholine, nitroprusside, 8-bromo-cGMP, and adenosine were examined in anesthetized mice by means of a cranial window. The effects of two concentrations of ODQ were examined in the absence and presence of superoxide dismutase. The effects of
N
G
-nitro-
l
-arginine, an inhibitor of nitric oxide synthase, were also tested.

Results
ODQ (3 and 10 μmol/L) produced concentration-dependent inhibition of dilatation of cerebral arterioles (control diameter=29±1 μm) (mean±SE) in response to acetylcholine and nitroprusside. For example, 10 μmol/L acetylcholine and 1 μmol/L nitroprusside dilated cerebral arterioles by 28±3% and 44±2% in the absence and 6±2% and 7±1%, respectively, in the presence of 10 μmol/L ODQ (
P
<.05 versus control). The inhibitory effects of ODQ were not altered by superoxide dismutase. Vasodilatation in response to 8-bromo-cGMP and adenosine was not inhibited by ODQ.
N
G
-Nitro-
l
-arginine (100 μmol/L), an inhibitor of nitric oxide synthase, inhibited responses to acetylcholine by approximately 80% but tended to enhance responses to nitroprusside.

Conclusions
Thus, nitric oxide–mediated dilatation of mouse cerebral arterioles is profoundly inhibited by ODQ, an inhibitor of activity of soluble guanylyl cyclase. Cerebral vasodilator responses to adenosine and 8-bromo-cGMP were preserved in the presence of ODQ, indicating that inhibition by ODQ was selective. In contrast to previously used inhibitors of soluble guanylyl cyclase (methylene blue and LY-83583), the effects of ODQ are not mediated by generation of superoxide anion.
Application of Interhemispheric Index for Transcranial Doppler Sonography Velocity Measurements and Evaluation of Recording Time
Authors: Bay-Hansen Jesper , Ravn Thomas , Knudsen Gitte Moos
Published: June 2011

Background and Purpose
To validate the reliability of transcranial Doppler sonography velocity measurements in clinical settings, assessment of the reproducibility of repeated bilateral simultaneous measurements and the optimal recording time is needed. Our hypothesis was that interhemispheric indices would prove more valid than the absolute velocity measurements usually applied. The potential interference between ultrasound beams in bilateral samplings also needs evaluation.

Methods
Thirty healthy volunteers were studied at rest within hours or with a 2-month interval between measurements. Absolute blood flow velocities and side-to-side indices between velocities obtained in the middle cerebral arteries were measured over a 30-second period by two independent examiners. The correlation coefficient (
r
) and the coefficients of variation of the difference between either absolute velocities (CV) or indices (CV
i
) were calculated. The beat-to-beat variation of the diastolic, systolic, and mean velocities was also recorded. For evaluation of ultrasound beam interference, measurements were performed with and without one probe unplugged.

Results
In the interobserver study in which measurements were repeated within hours,
r
=.92, CV=8.8%, and CV
i
=4.1%. In the intraobserver study in which measurements were repeated with a 2-month interval,
r
=.8, CV=13.0%, and CV
i
=7.3%. A recording time of 30 seconds reduced CV
i
to 2.6%, whereas for absolute velocities 5-second recordings produced an acceptable variation. There was no significant interference between bilaterally placed probes.

Conclusions
The introduction of interhemispheric indices improves interobserver and intraobserver reproducibility by approximately 50%. We recommend use of the index in clinical settings in which unilateral velocity changes are expected. For measurement of an interhemispheric index, a recording time of 30 seconds is recommended, whereas 5-second measurement periods yield a sufficient estimate of absolute velocities.
Chronic Cerebral Hypoperfusion Inhibits Calcium-Induced Long-term Potentiation in Rats
Authors: Sekhon Lali H. S. , Spence Ian , Morgan Michael K. , Weber Neville C.
Published: June 2011

Background and Purpose
Long-term potentiation (LTP) in the rat hippocampus induced by tetanic stimulation is impaired by chronic cerebral hypoperfusion. The effects of chronic cerebral hypoperfusion on other forms of LTP are unknown. Such data could help delineate the pathways of cellular alteration caused by chronic cerebral hypoperfusion. The in vitro phenomenon of calcium-induced LTP was thus examined in rat hippocampal CA1 cells that had undergone chronic hypoperfusion with a reduction in cerebral blood flow of between 25% and 50% maintained for 26 weeks.

Methods
Ten Sprague-Dawley rats had a cervical arteriovenous fistula surgically constructed, and an additional 10 animals were used as age-matched controls. Hippocampal slices were prepared after 26 weeks of hypoperfusion, and in vitro extracellular field potential recordings were taken from the Schäffer collateral CA1 region. Properties of LTP induced through transient exposure to a hypercalcemic solution were analyzed.

Results
LTP was impaired in animals with an arteriovenous fistula (
P
<.05). Control animals demonstrated potentiation lasting for the entire 2 hours of recording, whereas fistula animals showed only transient potentiation (<60 minutes) before returning to baseline values.

Conclusions
Calcium-induced LTP is impaired by chronic cerebral hypoperfusion. This form of LTP is different from that induced by tetanic stimulation. It is the most sensitive test available for in vitro detection of the changes induced in neuronal function by chronic noninfarctional reductions in cerebral blood flow of 25% to 50% and may indicate that the most basic cellular parameters involving calcium homeostasis and metabolism are being altered. The precise mechanisms remain to be elucidated, and several postulates are discussed.
Short- and Long-term Changes in Striatal Neurons and Astroglia After Transient Forebrain Ischemia in Rats
Authors: Zoli Michele , Grimaldi Roberta , Ferrari Rosaria , Zini Isabella , Agnati Luigi F.
Published: June 2011

Background and Purpose
The striatum is one of the regions most sensitive to transient forebrain ischemia. After 30-minute ischemia, areas of massive neuronal degeneration are clearly detectable a few hours after the insult and attain their maximal extension 24 hours after the insult. However, for most cellular and neurochemical parameters it is not known whether some recovery occurs at later times. We examined certain cell populations in the caudate putamen at different times after transient ischemia.

Methods
Adult male Sprague-Dawley rats were subjected to 30-minute forebrain ischemia (four-vessel occlusion model). Six experimental groups were considered: control animals and ischemic animals killed 4 hours, 1 day, 7 days, 40 days, and 8 months after reperfusion. Three striatal cell populations were examined by means of immunocytochemistry coupled to computer-assisted image analysis: vulnerable medium spiny neurons, resistant aspiny neurons, and reactive astrocytes, labeled for their content of dopamine- and cAMP-regulated phosphoprotein mr32 (DARPP-32), somatostatin and neuropeptide Y, and glial fibrillary acidic protein, respectively.

Results
(1) The area containing DARPP-32 immunoreactive neurons was markedly decreased (15% to 20% of control caudate putamen area) at 1 day after reperfusion and partially recovered at the following times (40% to 50% at 7 days and 50% to 60% at 40 days and 8 months after reperfusion). (2) The appearance of reactive astrocytes was precocious (4 hours to 1 day after ischemia) in the medial caudate putamen, the region in which DARPP-32 recovered within 40 days after ischemia, and late (7 to 40 days after ischemia) in the lateral caudate putamen, where no DARPP-32 recovery was detected. (3) Neuropeptide Y/somatostatin–containing neurons resisted the ischemic insult and could be detected in areas devoid of DARPP-32 immunoreactive neurons as long as 8 months after reperfusion.

Conclusions
The present results show a marked recovery of DARPP-32–positive neurons within 40 days after 30-minute forebrain ischemia in the medial, but not the lateral, caudate putamen. Medial caudate putamen also contains a high density of reactive astrocytes on the first day after ischemia, suggesting that astrocytic support has an important role in the spontaneous recovery of ischemic neurons.
Bilateral Increase in CO
2
Reactivity After Unilateral Carotid Endarterectomy
Authors: Visser G. H. , van Huffelen A. C. , Wieneke G. H. , Eikelboom B. C.
Published: June 2011

Background and Purpose
A low or absent CO
2
reactivity is considered indicative of a compromised hemodynamic compensatory capacity in patients with internal carotid artery (ICA) stenosis or occlusion. The aim of the present study was to investigate whether patients with preoperatively decreased or absent CO
2
reactivity show an improvement of CO
2
reactivity 3 months after carotid endarterectomy (CEA) and whether the preoperative CO
2
reactivity is correlated with clinical classification and hemodynamic factors.

Methods
A group of 65 patients with >70% ICA stenosis was studied. CO
2
reactivity was measured by bilateral transcranial Doppler sonography before and 3 months after CEA.

Results
The preoperative CO
2
reactivity was not significantly different in subgroups formed according to the presenting clinical symptoms. Patients with severe ICA stenosis with contralateral ICA occlusion had mean low preoperative CO
2
reactivity on both sides. Furthermore, patients with reversed flow in the ophthalmic artery had low mean preoperative CO
2
reactivity on the same side. The CO
2
reactivity was not significantly different in the subgroups of patients with signs of collateral blood flow through the anterior or posterior communicating artery. In particular, patients with low preoperative CO
2
reactivity (approximately <30%) showed an evident increase after the operation. Such an inverse correlation was found bilaterally, although it was more pronounced on the CEA side.

Conclusions
CEA can increase CO
2
reactivity in both hemispheres. This effect is most pronounced in patients with low (<30%) preoperative CO
2
reactivity. If this group represents patients who would be at risk from low-flow stroke, then testing of CO
2
reactivity might help select a subset of patients with an especially high probability of benefit from CEA.
Socioeconomic Level, Sedentary Lifestyle, and Wine Consumption as Possible Explanations for Geographic Distribution of Cerebrovascular Disease Mortality in Spain
Authors: Artalejo Fernando Rodríguez , Guallar-Castillón Pilar , Gutiérrez-Fisac Juan Luis , Banegas José Ramón , Calero Juan del Rey
Published: June 2011

Background and Purpose
The geographic distribution of cerebrovascular disease (CVD) mortality in Spain spans a wide range, from provinces where mortality is low (70/100 000) and close to that of the United States and other Anglo-Saxon countries, to others where mortality is high (180/100 000) and more akin to that of Portugal and the Mediterranean and central European countries. This report seeks to identify the socioeconomic and lifestyle factors that most contribute to the geographic pattern of CVD mortality in Spain.

Methods
We performed a study using data collected at a provincial level. Mortality data were taken from official vital statistics, and data on risk factors were obtained from surveys of representative large Spanish population samples. Correlation and multiple linear regression analyses were performed on standardized CVD mortality ratios and potential determinants of mortality for the period 1989 to 1993.

Results
CVD mortality, unemployment and illiteracy rates, blond cigarette smoking, and sedentary lifestyle proved substantially higher in the south and east (Mediterranean coast) of Spain. Saturated fatty acid intake and wine consumption were both lower in these regions, however. Illiteracy, wine consumption, sedentary lifestyle, high blood pressure, blond cigarette smoking, prevalence of diabetes, and body mass index ≥30 explained 59% of the variation in CVD mortality. Only illiteracy, sedentary lifestyle, and wine consumption registered a statistically significant relationship (
P
<.05) with CVD mortality. Whereas lower consumption of wine showed a negative association with CVD mortality, higher consumption revealed a positive association.

Conclusions
Socioeconomic level, as measured by illiteracy, sedentary lifestyle, and wine consumption, may partly explain the higher CVD mortality registered for regions situated in the south and east of Spain.
Frequency and Severity of Asymptomatic Coronary Disease in Patients With Different Causes of Stroke
Authors: Chimowitz M. I. , Poole R. M. , Starling M. R. , Schwaiger M. , Gross M. D.
Published: June 2011

Background and Purpose
We sought (1) to compare the frequency and severity of asymptomatic coronary artery disease (CAD) in patients with different causes of brain ischemia and (2) to determine profiles of patients with brain ischemia who are at highest risk of asymptomatic CAD.

Methods
Sixty-nine patients with transient ischemic attack or stroke and without overt CAD underwent a cardiac stress test and a diagnostic evaluation to determine the cause of brain ischemia. The frequency of abnormal cardiac stress tests was compared in patients with large-artery cerebrovascular disease versus other causes of brain ischemia (90% of whom had penetrating artery disease or cryptogenic stroke). Additionally, the frequencies of vascular risk factors, resting electrocardiographic abnormalities, and cause of stroke (large-artery disease versus other causes) were compared in patients with abnormal stress tests versus patients with normal stress tests.

Results
The frequency of abnormal stress tests was 50% (15 of 30) in patients with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with other causes of brain ischemia (
P
=.04). Moreover, 60% of abnormal stress tests (9 of 15) in patients with large-artery cerebrovascular disease suggested severe underlying CAD that was confirmed in 7 of 7 patients who underwent coronary angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9) in patients with other causes of brain ischemia suggested severe underlying CAD. Features that were more common in patients with abnormal stress tests were smoking (
P
=.006), large-artery cerebrovascular disease (
P
=.02), veteran status (
P
=.02), and left ventricular hypertrophy (
P
=.07).

Conclusions
Patients with penetrating artery disease or cryptogenic stroke have a significantly lower frequency of asymptomatic CAD than patients with large-artery cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran status, and possibly left ventricular hypertrophy may be useful features for identifying patients with transient ischemic attack or stroke who are at highest risk of harboring asymptomatic CAD.
Intracerebral Hemorrhage in Blacks
Authors: Qureshi Adnan I. , Suri Muhammed A. K. , Safdar Kamran , Ottenlips Jefferey R. , Janssen Robert S. , Frankel Michael R.
Published: June 2011

Background and Purpose
Blacks are at a higher risk for intracerebral hemorrhage (ICH) than whites; however, few data are available regarding the demographic and clinical characteristics of ICH among blacks.

Methods
We determined the frequency of risk factors, etiologic subtypes, and outcome among consecutive black patients admitted with nontraumatic ICH to a university-affiliated public hospital.

Results
The most common risk factors in the 403 black patients with ICH were preexisting hypertension (77%), alcohol use (40%), and smoking (30%). Among the 91 nonhypertensive patients, 21 (23%) were diagnosed with hypertension after onset. Compared with women, men had a younger age of onset (54 versus 60 years;
P
<.001) and higher frequency of alcohol use (54% versus 22%;
P
<.001) and smoking (39% versus 17%;
P
<.001). ICH secondary to hypertension (n=311) and of undetermined etiology (n=73) were the most common subtypes in blacks. Patients aged 65 years and older (compared with those aged 15 to 44 years;
P
=.001) and women (compared with men;
P
=.02) were more likely to be dependent at discharge.

Conclusions
Primary preventive strategies are required to reduce the high frequency of modifiable risk factors predisposing to ICH in blacks.
Long-term Cognitive Impairment Associated With Caudate Stroke
Authors: Bokura Hirokazu , Robinson Robert G.
Published: June 2011

Background and Purpose
Neuropsychiatric findings were examined in 91 patients with acute focal subcortical lesions to determine whether cognitive outcome would differ depending on whether the head of the caudate or other subcortical structures were injured.

Methods
Patients were evaluated using the Mini-Mental State Examination (MMSE), Hamilton Rating Scale for Depression, and modified Present State Examination. Patients were reexamined at short-term (3 to 6 months) or long-term (1 to 2 years) follow-up.

Results
There were no significant intergroup differences in the MMSE scores at the initial evaluation or at short-term follow-up. At long-term follow-up, however, patients with either right or left caudate lesions had significantly lower MMSE scores than patients with other subcortical lesions.

Conclusions
A significant number of patients with caudate infarction deteriorate in their intellectual function between 1 and 2 years after stroke. This phenomenon could be mediated through disruption of cortical projections to the caudate.
Relationship Between Insulin and Carotid Atherosclerosis in the General Population
Authors: Bonora E. , Willeit J. , Kiechl S. , Oberhollenzer F. , Egger G. , Bonadonna R. , Muggeo M.
Published: June 2011

Background and Purpose
Although several studies have investigated the association between insulin and coronary heart disease, the relationship between this hormone and carotid atherosclerosis is not well established.

Methods
As a part of a population-based survey on atherosclerosis and its risk factors, serum insulin was measured at fasting (n=888) and at 2 hours after an oral glucose load (n=811; known diabetic subjects were excluded). The study population comprised an age- and sex-stratified random sample of men and women aged 40 to 79 years. Atherosclerosis in the common and internal carotid arteries was assessed twice (in 1990 and 1995) by duplex sonography. Progression during the 5-year follow-up was defined by an increase in the atherosclerosis score of more than the doubled measurement error (>27%) or by the occurrence of new plaques. Subjects were stratified in quintiles according to baseline serum insulin at fasting or 2 hours after glucose loading.

Results
Logistic regression analysis revealed a significant association of carotid atherosclerosis with both low and high insulin (U-shaped relation). This finding was found before and after adjustment for several covariates (sex, age, body mass index, glucose tolerance, triglycerides, apolipoproteins A1 and B, fibrinogen, blood pressure status, behavioral variables, and socioeconomic status). This relation applied equally to fasting and postglucose insulin and was more pronounced in the prospective analysis than in the cross-sectional analysis.

Conclusions
We conclude that both “hypoinsulinemia” and hyperinsulinemia are independent risk indicators of carotid atherosclerosis.
Silent Brain Infarction on Magnetic Resonance Imaging and Neurological Abnormalities in Community-Dwelling Older Adults
Authors: Price Thomas R. , Manolio Teri A. , Kronmal Richard A. , Kittner Steven J. , Yue Nancy C. , Robbins John , Anton-Culver Hoda , O’Leary Daniel H.
Published: June 2011

Background and Purpose
Infarctlike lesions are frequently detected in symptomatic and asymptomatic older persons undergoing cerebral MRI, but their significance in older adults has not been examined. We determined the prevalence of MRI infarcts in a population-based sample of men and women aged ≥65 years and related these findings to demographic, cognitive, and neurological status.

Methods
MRI scanning was performed in 3660 Cardiovascular Health Study (CHS) participants after brief neurological examinations and tests of cognitive function. MRIs were read centrally for the presence of an infarct ≥3 mm in diameter or smaller infarctlike lesions.

Results
MRI infarcts were detected in 1131 of 3647 participants with readable infarct information (31%) and in 961 of the subgroup of 3397 participants (28%) without known prior stroke (“silent” MRI infarcts). Smaller infarctlike lesions were found in 196 of 2516 participants who had no MRI infarcts ≥3 mm. MRI infarcts were more common in participants who were older, had prior stroke, impaired cognition, visual field deficits, slowed repetitive finger tapping (all
P
<.0001), weakness on toe and heel walking, and history of memory loss, coma, or migraine headaches. Multivariate analysis in those without prior stroke showed strong associations of silent MRI infarcts with older age, history of migraines, lower digit symbol scores, and more abnormalities on neurological examination.

Conclusions
MRI evidence of brain infarction is common in older men and women without a clinical history of stroke. Their strong associations with impaired cognition and neurological deficits suggest that they are neither silent nor innocuous.