bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenovirus-Mediated Gene Transfer Is Augmented in Basilar and Carotid Arteries of Heritable Hyperlipidemic Rabbits
Authors: Lund Donald D. , Faraci Frank M. , Ooboshi Hiroaki , Davidson Beverly L. , Heistad Donald D.
Published: June 2011

Background and Purpose
—There are major differences in susceptibility of intracranial and extracranial arteries to atherosclerosis. The goal of this study was to examine adenovirus-mediated gene transfer to basilar and carotid arteries of Watanabe heritable hyperlipidemic (WHHL) rabbits, which have spontaneous hypercholesterolemia and atherosclerosis, and normal New Zealand White (NZW) rabbits. We used 2 different adenoviral vectors, driven by either cytomegalovirus (CMV) or Rous sarcoma virus (RSV) promoters.

Methods
—Basilar and carotid arteries were removed from WHHL and NZW rabbits and cut into rings. The arteries were incubated with an adenoviral vector that expresses β-galactosidase and is driven by either a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) promoter (AdCMVβgal or AdRSVβgal). Arteries were incubated with virus for 2 hours, and then incubated in medium for 24 hours to allow expression of transgene. Transgene expression was assessed by enzyme activity (Galacto-Light assay) and by a histochemical method after X-Gal staining.

Results
—After gene transfer, β-galactosidase was expressed in endothelium and adventitia but not media. There were moderately severe atherosclerotic lesions in carotid arteries and early lesions in basilar arteries. Enzyme activity after gene transfer with AdCMVβgal (3×10
11
particles/mL) was greater in the basilar artery of WHHL than NZW (137±40 versus 25±10 mU/mg protein,
P
<0.05) (mean±SE) and in the carotid artery (133±27 versus 34±11 mU/mg protein,
P
<0.05). After gene transfer with AdRSVβgal, transgene expression was similar in arteries from WHHL and normal NZW rabbits.

Conclusions
—This is the first study to examine gene transfer to intracranial and extracranial arteries from atherosclerotic animals. The findings suggest that an adenoviral vector with a CMV, but not RSV, promoter provides greater transgene expression in the basilar and carotid arteries from spontaneously atherosclerotic rabbits than from normal rabbits.
Risk Factor Modification in Stroke Prevention
Authors: Joseph Lenore N. , Babikian Viken L. , Allen Nancy C. , Winter Michael R.
Published: June 2011

Background and Purpose
—We reviewed Stroke Clinic data to determine the extent of risk factor modification achieved in patients with cerebrovascular disease over 2 years.

Methods
—Visits to the Stroke Clinic of a tertiary medical center from July 1, 1994, through June 30, 1996, were reviewed. Obesity, smoking, hypertension, hyperlipidemia, hyperglycemia, and lifestyle changes were noted in patients with ≥2 visits (n=61) and measures (number varied) of these parameters.

Results
—Fifty-six patients (92%) had primary care physicians. In the 49 patients with ≥2 weight measurements, 33 (67%) were moderately or severely overweight by weight-height correlation. Forty-four patients (90%) remained in the same weight category. Of the 60 patients with available blood pressure data, 50 (83%) were hypertensive. At their last visits, 43 of the 50 (86%) were receiving medications, and 22 of the 43 treated (51%) were controlled. Serum glucose remained elevated in 14 of 47 patients (30%) and in 11 of 16 diabetic patients (69%). Thirty-six of 47 patients (55%) had elevated lipid measurements. None of the 21 smokers quit during the study period. Few patients modified dietary and exercise practices. Of 61 patients, 29 (48%) sustained vascular events during the study, with 17 of these 29 patients (59%) having strokes or transient ischemic attacks.

Conclusions
—Although most patients were asked to quit smoking, received advice regarding diet and exercise, and were medicated for hypertension, elevated glucose, and cholesterol levels, their risk factor profiles showed little improvement during the 2-year period. More effective methods of controlling stroke risk factors are needed.
Correlation Between Functional and Electrophysiological Recovery in Acute Ischemic Stroke
Authors: Vang Chu , Dunbabin David , Kilpatrick David
Published: June 2011

Background and Purpose
—There is still controversy about the prognostic value of motor evoked potentials (MEPs) in the assessment of hemiplegia. The aims of this study are to determine the relationship between functional and electrophysiological recovery and thus the value of MEP as a prognostic indicator of clinical outcome in acute ischemic stroke.

Methods
—Seventeen healthy subjects and 38 stroke patients were included in this study. Functional recovery was assessed with the Modified Canadian Neurological Scale (MCNS), the Barthel Activities of Daily Living Index (BI), and the Rankin scale. Transcranial magnetic stimulation was used to determine the change in central motor conduction time (CMCT). Stroke outcome was assessed at the end of 2 weeks. One-way ANOVA with post hoc comparisons using the Scheffé procedure as well as
t
tests were used to assess the significance of the results in this study.

Results
—Unpaired
t
test showed significantly higher mean scores of the MCNS (2
P
=0.001), BI (2
P
=0.002), and Rankin scale (
P
<0.001) at day 14 in the group of patients with recordable MEP at day 1. A better clinical improvement with a higher mean score of the MCNS (2
P
<0.001), BI (2
P
<0.001), and the Rankin scale (2
P
<0.001) was also observed in the patients in whom the CMCT improved.

Conclusions
—These data show that there is a close relationship between clinical and electrophysiological improvement and that MEP is a useful prognostic indicator of clinical outcome.
How Do Scores on the EuroQol Relate to Scores on the SF-36 After Stroke?
Authors: Dorman Paul J. , Dennis Martin , Sandercock Peter
Published: June 2011

Background and Purpose
—The EuroQol and Medical Outcome Survey 36-item short-form health survey (SF-36) questionnaires have both been validated for the assessment of health-related quality of life after stroke. However, the relationship between these instruments has not been studied after stroke. We therefore sought to compare the responses of a group of stroke patients to both instruments.

Methods
—A total of 2253 patients with stroke entered by United Kingdom hospitals in the International Stroke Trial were randomized to follow-up with either the EuroQol or SF-36 instruments. We randomly selected one third of patients who had responded to the EuroQol for follow-up, again using the SF-36, and two thirds of patients who had responded to the SF-36 for follow-up, again using the EuroQol. We assessed the patients’ mean score for each domain of the SF-36 categorized by their response to the corresponding EuroQol domain and the correlation between the domains of the 2 instruments.

Results
—The domains for both instruments, which assessed physical functioning, social functioning, bodily pain, and overall health-related quality of life, correlated closely. The mental health domain of the SF-36 correlated only poorly with the psychological functioning domain of the EuroQol.

Conclusions
—Both the EuroQol and SF-36 measure broadly similar domains of health. The weak relationship between the assessments of mental health may reflect a difference in content or more fundamental problems with the validity or reliability of the items in one of the instruments with respect to this domain. This study has provided the first empirical qualitative evidence by which the data on the SF-36 after stroke may be interpreted.
MRI Features of Intracerebral Hemorrhage Within 2 Hours From Symptom Onset
Authors: Linfante Italo , Llinas Rafael H. , Caplan Louis R. , Warach Steven
Published: June 2011

Background and Purpose
—MRI has been increasingly used in the evaluation of acute stroke patients. However, MRI must be able to detect early hemorrhage to be the only imaging screen used before treatment such as thrombolysis. Susceptibility-weighted imaging, an echo-planar T2* sequence, can show intracerebral hemorrhage (ICH) in patients imaged between 2.5 and 5 hours from symptom onset. It is unknown whether MRI can detect ICH earlier than 2.5 hours. We describe 5 patients with ICH who had MRI between 23 and 120 minutes from symptom onset and propose diagnostic patterns of evolution of hyperacute ICH on MRI.

Methods
—As part of our acute imaging protocol, all patients with acute stroke within 24 hours from symptom onset were imaged with a set of sequences that included susceptibility-weighted imaging, diffusion- and perfusion-weighted imaging, T1- and T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR), and MR angiography using echo-planar techniques. Five patients with ICH had MRI between 23 and 120 minutes from the onset of symptoms.

Results
—ICH was identified in all patients. Distinctive patterns of hyperacute ICH and absence of signs of ischemic stroke were the hallmark features of this diagnosis. The hyperacute hematoma appears to be composed of 3 distinct areas: (1) center: isointense to hyperintense heterogeneous signal on susceptibility-weighted and T2-weighted imaging; (2) periphery: hypointense (susceptibility effect) on susceptibility-weighted and T2-weighted imaging; and (3) rim: hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, representing vasogenic edema encasing the hematoma.

Conclusions
—MRI is able to detect hyperacute ICH and show a pattern of evolution of the hematoma within 2 hours from the onset of symptoms.
Three-Dimensional Transcranial Color-Coded Sonography of Cerebral Aneurysms
Authors: Klötzsch Christof , Bozzato Alessandro , Lammers Gero , Mull Michael , Lennartz Bernhard , Noth Johannes
Published: June 2011

Background and Purpose
—The role of 2-dimensional transcranial color-coded sonography (2D-TCCS) as a diagnostic tool in cases of vascular alteration is unquestioned. The skill of the operator, however, may be responsible for some intertrial variability. The clinical value of a new, workstation-based, 3D reconstruction system for TCCS was evaluated in patients with intracranial aneurysms.

Methods
—Thirty patients with 30 intracranial aneurysms were investigated (8 men, 22 women; mean±SD age 54±17 years). The TCCS examinations were performed with a 2-MHz probe using the power mode. The 3D system (3D-Echotech, Germany) consisted of an electromagnet, which induced a low-intensity magnetic field near the head of the patient. A magnetic position sensor was attached to the ultrasound probe and transmitted the spatial orientation of the probe to a workstation, which also received the corresponding 2D-images from the video-port of the duplex machine. The echo contrast enhancer
d
-galactose (Levovist, Schering, Germany) was used in all patients to improve the signal-to-noise ratio. All patients underwent presurgical digital subtraction angiography (DSA) to demonstrate the aneurysm.

Results
—Twenty-nine of 30 angiographically proven intracranial aneurysms (97%) were detected by 3D-TCCS. The aneurysmal diameter estimated by DSA ranged from 3 to 16 mm (mean 7.2±3.6 mm). A comparison of the 3 main diameters of each aneurysm revealed a correlation coefficient of 0.95 between DSA and 3D-TCCS. The 3D determination of the aneurysmal size by 2 experienced sonographers correlated with 0.96.

Conclusions
—3D-TCCS is a new, noninvasive method to investigate intracranial aneurysms. The differentiation between artifacts and true changes of the vessel anatomy is much easier in 3D-TCCS than in conventional 2D-TCCS. The new method yields an excellent correlation with the gold standard, DSA. Because the same 3D-TCCS data can be postprocessed by different investigators, it may be possible to improve reproducibility and increase the objectivity of transcranial color-coded duplex sonography.
Stroke in the Very Old
Authors: Di Carlo Antonio , Lamassa Maria , Pracucci Giovanni , Basile Anna Maria , Trefoloni Gloria , Vanni Paola , Wolfe Charles D. A. , Tilling Kate , Ebrahim Shah , Inzitari Domenico
Published: June 2011

Background and Purpose
—The oldest old represent the fastest-growing segment of the elderly population in developed countries. Knowledge of age-specific aspects of stroke is essential to establish diagnostic and therapeutic pathways and to set up prevention and rehabilitation programs. We sought to evaluate stroke features and functional outcome in patients aged ≥80 years compared with the younger age groups.

Methods
—In a European Union Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month disability (Barthel Index) and handicap (Rankin Scale).

Results
—Overall, 3141 patients (69.8%) were aged <80 years, and 1358 (30.2%) were aged ≥80 years. At baseline, female sex, prestroke institutionalization, and a worse prestroke Rankin score were significantly more frequent in the older patients, as were coma, paralysis, swallowing problems, and urinary incontinence in the acute phase (all
P
values <0.001). Brain imaging and other diagnostic tools were significantly less used in the older patients. Paralysis, swallowing problems, and incontinence during hospitalization independently predicted 3-month disability or handicap in both groups. For the older patients, prestroke institutionalization proved a further strong and independent determinant of 3-month disability (odds ratio, 2.33; 95% CI, 1.22 to 4.45) and handicap (odds ratio, 7.04; 95% CI, 1.62 to 30.69).

Conclusions
—In the very old, both medical and sociodemographic factors may significantly influence stroke outcome, showing peculiar characteristics. Knowledge of these determinants may reduce the burden on health systems, improving quality of care.
Safety of Air Medical Transportation After Tissue Plasminogen Activator Administration in Acute Ischemic Stroke
Authors: Chalela Julio A. , Kasner Scott E. , Jauch Edward C. , Pancioli Arthur M.
Published: June 2011

Background and Purpose
—We sought to determine the safety of air medical transport (AMT) of patients with acute ischemic stroke (AIS) immediately after or during administration of tissue plasminogen activator (tPA). Patients with AIS treated with tPA in nonuniversity hospitals frequently need transfer to tertiary care centers that can provide specialized care. AMT is a widely available mode of transport that is crucial in providing expedient and quality health care to critically ill patients while assuring high level of care during transportation. The safety of AMT of patients with AIS after or during administration of tPA has not been examined.

Methods
—We performed retrospective chart review of 24 patients with AIS who were treated with intravenous tPA and transferred by helicopter to the Hospital of the University of Pennsylvania or the University of Cincinnati Hospital. The charts were reviewed for neurological complications, systemic complications, and adherence to the National Institutes of Neurological Disorders and Stroke (NINDS) protocol for AIS management.

Results
—No major neurological or systemic complications occurred. Four patients had hypertension warranting treatment, 3 patients experienced motion sickness, 1 patient developed a transient confusional state, and 1 patient experienced minor systemic bleeding. Four NINDS protocol violations occurred, all related to blood pressure management.

Conclusions
—In this small series, AMT of AIS patients after thrombolysis was not associated with any major neurological or systemic complications. Flight crew education on the NINDS AIS protocol is essential in limiting the number of protocol violations. AMT of patients with AIS provides fast and safe access to tertiary centers that can provide state of the art stroke therapy.
Forced Use of the Upper Extremity in Chronic Stroke Patients
Authors: van der Lee Johanna H. , Wagenaar Robert C. , Lankhorst Gustaaf J. , Vogelaar Tanneke W. , Devillé Walter L. , Bouter Lex M.
Published: June 2011

Background and Purpose
—Of all stroke survivors, 30% to 66% are unable to use their affected arm in performing activities of daily living. Although forced use therapy appears to improve arm function in chronic stroke patients, there is no conclusive evidence. This study evaluates the effectiveness of forced use therapy.

Methods
—In an observer-blinded randomized clinical trial, 66 chronic stroke patients were allocated to either forced use therapy (immobilization of the unaffected arm combined with intensive training) or a reference therapy of equally intensive bimanual training, based on Neuro-Developmental Treatment, for a period of 2 weeks. Outcomes were evaluated on the basis of the Rehabilitation Activities Profile (activities), the Action Research Arm (ARA) test (dexterity), the upper extremity section of the Fugl-Meyer Assessment scale, the Motor Activity Log (MAL), and a Problem Score. The minimal clinically important difference (MCID) was determined at the onset of the study.

Results
—One week after the last treatment session, a significant difference in effectiveness in favor of the forced use group compared with the bimanual group (corrected for baseline differences) was found for the ARA score (3.0 points; 95% CI, 1.3 to 4.8; MCID, 5.7 points) and the MAL amount of use score (0.52 points; 95% CI, 0.11 to 0.93; MCID, 0.50). The other parameters revealed no significant differential effects. One-year follow-up effects were observed only for the ARA. The differences in treatment effect for the ARA and the MAL amount of use scores were clinically relevant for patients with sensory disorders and hemineglect, respectively.

Conclusions
—The present study showed a small but lasting effect of forced use therapy on the dexterity of the affected arm (ARA) and a temporary clinically relevant effect on the amount of use of the affected arm during activities of daily living (MAL amount of use). The effect of forced use therapy was clinically relevant in the subgroups of patients with sensory disorders and hemineglect, respectively.
Incidence and Occurrence of Total (First-Ever and Recurrent) Stroke
Authors: Williams G. Rhys , Jiang John G. , Matchar David B. , Samsa Gregory P.
Published: June 2011

Background and Purpose
—It has recently been hypothesized that the figure of approximately half a million strokes substantially underestimates the actual annual stroke burden for the United States. The majority of previously reported studies on the epidemiology of stroke used relatively small and homogeneous population-based stroke registries. This study was designed to estimate the occurrence, incidence, and characteristics of total (first-ever and recurrent) stroke by using a large administrative claims database representative of all 1995 US inpatient discharges.

Methods
—We used the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, release 4, which contains ≈20% of all 1995 US inpatient discharges. Because the accuracy of
International Classification of Diseases, 9th Revision, Clinical Modification
(ICD-9-CM) coding is suboptimal, we performed a literature review of ICD-9-CM 430 to 438 validation studies. The pooled results from the literature review were used to make appropriate adjustments in the analysis to correct for some of the inaccuracies of the diagnostic codes.

Results
—There were 682 000 occurrences of stroke with hospitalization (95% CI 660 000 to 704 000) and an estimated 68 000 occurrences of stroke without hospitalization. The overall incidence rate for occurrence of total stroke (first-ever and recurrent) was 259 per 100 000 population (age- and sex-adjusted to 1995 US population). Incidence rates increased exponentially with age and were consistently higher for males than for females.

Conclusions
—We conservatively estimate that there were 750 000 first-ever or recurrent strokes in the United States during 1995. This new figure emphasizes the importance of preventive measures for a disease that has identifiable and modifiable risk factors and for the development of new and improved treatment strategies and infrastructures that can reduce the consequences of stroke.
Association of the Platelet Glycoprotein IIb HPA-3 Polymorphism With Survival After Acute Ischemic Stroke
Authors: Carter Angela M. , Catto Andrew J. , Bamford John M. , Grant Peter J.
Published: June 2011

Background and Purpose
—The role of polymorphisms of the platelet glycoprotein (GP) IIb/IIIa receptor in the development of cardiovascular disease has been the subject of intensive research. The aim of this study was to determine the association of the HPA-3 polymorphism of platelet GPIIb with ischemic stroke and subsequent survival and to identify possible interactions of HPA-3 with classic risk factors.

Methods
—HPA-3 genotype was determined by restriction fragment length polymorphism in 515 patients with ischemic stroke and 423 healthy, age-matched control subjects.

Results
—There was no significant difference in the genotype distribution of patients and controls, nor was there any difference when patients were subclassified into small- and large-vessel disease. The genotype distribution of the 231 patients subsequently dying during 2.8 years of follow-up (
aa
=45.0%,
ab
=46.8%,
bb
=8.2%) was significantly different from that of those still alive (
aa
=37.0%,
ab
=48.2%,
bb
=14.8%) (
P
=0.03). In a Cox regression model, the relative risks for poststroke mortality in patients of
aa
and
ab
genotype compared with those of
bb
genotype were 2.42 (95% CI, 1.24 to 4.71) and 2.13 (95% CI, 1.09 to 4.17), respectively, after we accounted for confounding factors. In addition, significant interactions of HPA-3 with the Pl
A
polymorphism of GPIIIa (
P
=0.002) and with fibrinogen (
P
=0.01) were identified in relation to mortality.

Conclusions
—HPA-3 is related to poststroke mortality, and the significant interaction of HPA-3 with Pl
A
and fibrinogen suggests that it may in some way influence the interaction of GPIIb/IIIa with fibrinogen, particularly in the presence of high fibrinogen.
Cerebral Microembolism in Acute Myocardial Infarction
Authors: Nadareishvili Zurab G. , Choudary Zahid , Joyner Campbell , Brodie Dianne , Norris John W.
Published: June 2011

Background and Purpose
—This study was undertaken to determine the frequency of cerebral microemboli (high-intensity transient signals; HITS) detected by transcranial Doppler (TCD) in patients with acute myocardial infarction (AMI) and to relate them to the various putative risk factors and clinical embolic events.

Methods
—We investigated 112 consecutive patients within 72 hours of admission to an acute coronary care unit using TCD to monitor for cerebral microemboli. Twelve patients were excluded because of failure of ultrasound insonation. All patients had 2-dimensional echocardiograms within the study period.

Results
—HITS were detected in 17% of patients, with significantly higher frequency in patients with reduced (<65%) left ventricular (LV) ejection fraction (
P
=0.019), akinetic LV segments (
P
=0.002), and LV thrombus (
P
=0.015). A marginally significant (
P
=0.059) increase of HITS was found in patients with anterior AMI. Stroke was significantly more frequent in patients with cerebral microemboli (
P
=0.01).

Conclusions
—HITS were detected in 17% of patients in spite of adequate antithrombotic therapy and were increased in patients with reduced LV function, akinetic myocardial segments, and LV thrombus. They were present in all 3 patients with stroke and may represent a predictor of clinical embolic events.
Experimental Model of Small Deep Infarcts Involving the Hypothalamus in Rats
Authors: He Zhen , Yamawaki Takemori , Yang Shaohua , Day Arthur L. , Simpkins James W. , Naritomi Hiroaki
Published: June 2011

Background and Purpose
—Intraluminal middle cerebral artery (MCA) occlusion in rats has been reported to cause hyperthermia assumed to be caused by hypothalamic damage. To clarify the effects of hypothalamic ischemia on body temperature and to obtain a model simulating lacunar infarction, we attempted to produce small infarcts in deep structures (including the hypothalamus).

Methods
—A surgical suture was advanced to occlude the origin of the hypothalamic (HTA) and/or anterior choroidal arteries (AChA) without compromise of the anterior or middle cerebral artery origins. After treatment, rectal temperature and postural reflex were examined repeatedly for 3 days under nonanesthetic conditions. The AChA and HTA and their link with small deep infarction were then confirmed by TTC, hematoxylin and eosin, and TUNEL stains and by microsurgical dissection after colored silicone perfusion into the cerebral arteries.

Results
—Advancement of the suture near to but not occluding the MCA origin (0.5 to 1.9 mm proximal) produced small, deep, nonneocortical stokes in 25 of 36 animals without producing MCA ischemic changes. These infarctions mainly affected the hypothalamus in 13 animals (HTA area: infarct volume 6±1 mm
3
) and involved both the internal capsule and hypothalamus in 12 animals (HTA+AChA area infarct volume 48±10 mm
3
). Rats with HTA infarction alone exhibited persistent hyperthermia for 72 hours; some also had transient mild postural abnormality. The AChA+HTA infarct group showed a transient elevation of body temperature for 24 hours and definitive postural abnormality. In the remaining 11 animals, the suture was inadvertently advanced across the MCA origin, producing a large infarct that affected both the neocortex (MCA territory) and nonneocortical structures (volume 381±30 mm
3
, n=11). The MCA infarct group displayed a transient hyperthermia and severe postural abnormality.

Conclusions
—When properly positioned, the intraluminal suture method permits selective AChA and/or HTA obstruction without inducing MCA territory ischemia. This model confirms that selective hypothalamic infarction produces significant and sustained temperature regulation abnormalities. The model also may be useful in investigating the pathophysiology of small, deep, end-vessel infarction.
Should We Screen for Familial Intracranial Aneurysm?
Authors: Crawley Francesca , Clifton Andrew , Brown Martin M.
Published: June 2011

Background and Purpose
—The purpose of this study was to establish whether individuals with a family history of ≥2 first-degree relatives with intracranial aneurysm should be offered screening for aneurysm.

Methods
—We derived 3 theoretical models and calculated the outcomes of screening with magnetic resonance angiography (MRA) followed by digital subtraction angiography (DSA) if MRA was positive (model 1), screening with DSA alone (model 2), and not screening (model 3). Screening was repeated at intervals of 10 years, and aneurysms detected were treated surgically. We assumed a prevalence of aneurysm of 9.8% (95% CI, 8.9% to 10.6%) in the population screened, an annual rupture rate of asymptomatic aneurysm of 0.8% (95% CI, 0.4% to 1.5%), and a 75% chance of poor outcome from rupture. We assumed the sensitivity and specificity of MRA were each 90% and the risk of DSA was 0.1%. The risk of surgery was taken as 5.1%.

Results
—Screening 1000 individuals on 3 occasions with MRA and DSA or with DSA alone followed by surgery resulted in poor outcome in 14 and 18 individuals, respectively, over 30 years. Without screening, poor outcome occurred in 15 individuals over the same period of time.

Conclusions
—Screening is not an effective way of reducing morbidity and mortality from ruptured intracranial aneurysm in individuals with a history of ≥2 affected first-degree relatives with ruptured intracranial aneurysm unless the expected incidence of asymptomatic aneurysm is considerably >10%.
Stroke Incidence and Case Fatality in Southern Greece
Authors: Vemmos Kostas N. , Bots Michiel L. , Tsibouris Panagiotis K. , Zis Vasilios P. , Grobbee Diederick E. , Stranjalis Georgios S. , Stamatelopoulos Stamatis
Published: June 2011

Background and Purpose
—For Greece, information on incidence of stroke and distribution of type of stroke has not been reported. We determined the incidence of first-ever stroke in men and women, the incidence of stroke by type, and the associated case fatality.

Methods
—A population-based registry was established in the Arcadia province, located in eastern central Peloponessos, in the southern part of Greece. Between November 1, 1993, and October 31, 1995, all subjects with a first-ever stroke were identified. For case ascertainment, information from death certificates, hospital records, public health centers, and general practitioners was used.

Results
—During a 24-month period, 555 subjects with a first-ever stroke were registered. The incidence rates (per 100 000) by age group (18 to 34, 35 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84, ≥85 years) for men were 5, 31, 113, 240, 662, 1275, and 3218, respectively. For women, the rates were 11, 18, 48, 196, 478, 1166, and 2137, respectively. Age- and sex-standardized to the European population, the annual incidence rate for subjects aged 45 to 84 years was 319.4/100 000 (95% CI, 283 to 356). In men, cerebral infarction was diagnosed in 81% of cases, intracerebral hemorrhage in 16%, and subarachnoid hemorrhage in 2%. For women, these figures were 85%, 12%, and 3%, respectively. The 28-day case fatality rate was 26.6% (95% CI, 22.9% to 30.2%), with no differences between men and women. Case-fatality increased with age and was higher for intracerebral hemorrhage than for cerebral infarction.

Conclusions
—The incidence of stroke in our population-based study ranks low part compared with other European studies. The distribution of stroke types and case fatality rate appear to be similar to those of other industrialized countries.
Risk Factors for Silent Cerebral Infarcts in Subcortical White Matter and Basal Ganglia
Authors: Uehara Toshiyuki , Tabuchi Masayasu , Mori Etsuro
Published: June 2011

Background and Purpose
—The purpose of this study was to clarify whether the relevant risk factors for silent cerebral infarcts (SCIs) in subcortical white matter (WM) are different from those in the basal ganglia (BG).

Methods
—Subjects of this study were 219 adults without a history of stroke or transient ischemic attack and without any abnormality on a neurological examination who consecutively visited the neurology service in our hospital between January 1994 and November 1997 requesting medical evaluation for possible cerebrovascular diseases. Subjects included 141 men and 78 women ranging in age from 33 to 83 years (mean±SD, 63.2±9.5 years). We performed brain MRIs and cervical/cranial MR angiographies on all subjects. In this study, SCI was defined as a focal lesion >5 mm in diameter that was prolonged on both T2-weighted and proton density images.

Results
—SCIs in the WM and/or BG were detected in 88 (40.2%) of the 219 subjects. No SCI >15 mm was observed in this series. Fifty of the subjects had SCIs only in the WM, 32 subjects had SCIs in both the WM and BG, and 6 subjects had SCIs only in the BG. Thus, 82 (93.2%) of 88 subjects with SCIs had lesions in the WM. Most subjects with SCIs in the BG also had SCIs in the WM. Multiple logistic regression analyses revealed that age, female sex, and hypertension were significant and independent predictors of SCIs in the WM, and that age, a history of ischemic heart disease, and carotid artery stenosis were significant and independent predictors of SCIs in the BG.

Conclusions
—The present study indicated that the relevant risk factors for SCIs in the WM and those for SCI in the BG were different. Our results suggest that SCIs are prone to first appear in the WM in association with aging and hypertension, and the additional appearance of SCIs in the BG predicts a progression of generalized atherosclerosis that is manifested in the carotid and coronary arteries.
CO
2
Reactivity Testing Without Blood Pressure Monitoring?
Authors: Hetzel A. , Braune S. , Guschlbauer B. , Dohms K.
Published: June 2011

Background and Purpose
—Responsiveness to CO
2
is an established test of cerebrovascular reserve capacity. Arterial partial pressure of CO
2
(P
co
2
) and arterial blood pressure (BP) are key parameters for cerebral blood flow. To investigate the interaction between P
co
2
and BP, we performed a study with simultaneous measurement of CO
2
and BP during CO
2
reactivity testing with transcranial Doppler sonography.

Methods
—Eighty-one healthy volunteers, aged 19 to 74 years, underwent examination defined by a protocol with multimodality monitoring of BP, heart rate (HR), P
co
2
, and Doppler frequencies (DFs) of the left middle cerebral artery (MCA). Reproducibility was tested in a subgroup of 14 volunteers ≥65 years of age by CO
2
reactivity testing on different days.

Results
—Increase of P
co
2
was accompanied by a parallel increase of mean±SD time values of DF (3.6±1.6%/mm Hg CO
2
). BP levels were significantly elevated after 60-second hypercapnia (mean values, 0.5±0.55 mm Hg/mm Hg CO
2
). A significant decrease over time was seen only for pulsatility in DF but not in BP. Analysis of variance and covariance with repeated measures revealed a highly significant effect of CO
2
on MCA Doppler shift. A less-pronounced effect on DF was seen for BP. Correlation analysis showed no significance for CO
2
reactivity, but a significant correlation between test and retest was seen in BP-related CO
2
reactivity.

Conclusions
—The CO
2
response curve showed the known linear increase of DF. The parallel significant increase in BP most likely results from activation of the central sympathetic nervous system. The poor reproducibility for Doppler CO
2
reactivity is to some extent explainable by variability of BP. CO
2
-induced increases in BP can have relevant influence on MCA Doppler shift and lead to misinterpretation of Doppler CO
2
test results.
Randomized, Placebo-Controlled Trial of Anticoagulant Treatment With Low-Molecular-Weight Heparin for Cerebral Sinus Thrombosis
Authors: de Bruijn S. F. T. M. , Stam J.
Published: June 2011

Background and Purpose
—Treatment of cerebral sinus thrombosis with heparin is controversial. We conducted a double-blind, placebo-controlled multicenter trial to examine whether anticoagulant treatment improves outcome in patients with sinus thrombosis.

Methods
—Patients were randomized between body weight–adjusted subcutaneous nadroparin (180 anti–factor Xa units/kg per 24 hours) and matching placebo for 3 weeks (double-blind part of trial), followed by 3 months of oral anticoagulants for patients allocated nadroparin (open part). Patients with cerebral hemorrhage caused by sinus thrombosis were also included.

Results
—Sixty patients were enrolled, and none were lost to follow-up. In 1 patient the diagnosis proved wrong after randomization. After 3 weeks, 6 of 30 patients (20%) in the nadroparin group and 7 of 29 patients (24%) in the placebo group had a poor outcome, defined as death or Barthel Index score of <15 (risk difference, −4%; 95% CI, −25 to 17%; NS). After 12 weeks, 4 of 30 patients (13%) in the nadroparin group and 6 of 29 (21%) in the placebo group had a poor outcome, defined as death or Oxford Handicap Score of ≥3 (risk difference, −7%; 95% CI, −26% to 12%; NS). There were no new symptomatic cerebral hemorrhages. One patient in the nadroparin group had a major gastrointestinal hemorrhage, and 1 patient in the placebo group died from clinically suspected pulmonary embolism.

Conclusions
—Patients with cerebral sinus thrombosis treated with anticoagulants (low-molecular-weight heparin followed by oral anticoagulation) had a favorable outcome more often than controls, but the difference was not statistically significant. Anticoagulation proved to be safe, even in patients with cerebral hemorrhage.
Brain-Specific Protein C Activation During Carotid Artery Occlusion in Humans
Authors: Macko Richard F. , Killewich Lois A. , Fernández José A. , Cox D. Kim , Gruber Andras , Griffin John H.
Published: June 2011

Background and Purpose
—Activation of plasma protein C (PC) zymogen by thrombin-thrombomodulin at the endothelial surface is an important endogenous antithrombotic mechanism. It is unknown whether activated protein C (APC) is generated in vivo in the cerebrovasculature, because there is only limited thrombomodulin expression in human brain vascular endothelium. Therefore, we tested the hypothesis that carotid occlusion produces brain-specific PC activation.

Methods
—Blood samples were simultaneously collected from the ipsilateral internal jugular vein and radial artery before and during carotid cross-clamping and on “de-occlusion” in 8 awake patients undergoing routine carotid endarterectomy. Plasma PC zymogen and circulating APC levels were measured using enzyme immunocapture assay and expressed as percent of pooled plasma controls.

Results
—Internal jugular vein APC levels increased 28% exclusively during carotid occlusion and then decreased 32% with de-occlusion (F=8.1,
P
<0.005). PC zymogen increased only 5.9% with occlusion (F=6.3,
P
<0.02), consistent with hemoconcentration. There were no changes in radial artery PC or APC levels.

Conclusions
—These findings demonstrate brain-specific protein C activation in humans during carotid occlusion and suggest a protective role for endogenous APC generation during cerebrovascular occlusion.
Blockade and Reversal of Endothelin-Induced Constriction in Pial Arteries From Human Brain
Authors: Pierre Lisa N. , Davenport Anthony P.
Published: June 2011

Background and Purpose
—Substantial evidence now implicates endothelin (ET) in the pathophysiology of cerebrovascular disorders such as the delayed vasospasm associated with subarachnoid hemorrhage and ischemic stroke. We investigated the ET receptor subtypes mediating vasoconstriction in human pial arteries.

Methods
—ET receptors on human pial and intracerebral arteries were visualized with the use of autoradiography, and the subtypes mediating vasoconstriction were identified by means of wire myography.

Results
—ET-1 was more potent than ET-3 as a vasoconstrictor, indicating an ET
A
-mediated effect. Similarly, the selective ET
B
agonist sarafotoxin S6c had no effect on contractile action at concentrations up to 30 nmol/L. The nonpeptide ET
A
receptor antagonist
PD156707
(3 to 30 nmol/L) caused a parallel rightward shift of the ET-1–induced response, yielding a pA
2
of 9.2. Consistent with these results,
PD156707
(30 nmol/L) fully reversed an established constriction in pial arteries induced by 1 nmol/L ET-1, while the selective ET
B
receptor antagonist BQ788 (1 μmol/L) had little effect. The calcium channel blocker nimodipine (0.3 to 3 μmol/L) significantly attenuated the maximum response to ET-1 in a concentration-dependent manner without changing potency. In agreement with the functional data, specific binding of [
125
I]
PD151242
to ET
A
receptors was localized to the smooth muscle layer of pial and intracerebral blood vessels. In contrast, little or no [
125
I]BQ3020 binding to ET
B
receptors was detected.

Conclusions
—These data indicate an important role for ET
A
receptors in ET-1–induced constriction of human pial arteries and suggest that ET
A
receptor antagonists may provide additional dilatory benefit in cerebrovascular disorders associated with raised ET levels.
Automatic Embolus Detection by a Neural Network
Authors: Kemény Vendel , Droste Dirk W. , Hermes Stefan , Nabavi Darius G. , Schulte-Altedorneburg Gernot , Siebler Mario , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
—Embolus detection using transcranial Doppler ultrasound is a useful method for the identification of active embolic sources in cerebrovascular diseases. Automated embolus detection systems have been developed to reduce the time of evaluation in long-term recordings and to provide more “objective” criteria. The purpose of this study was to evaluate the critical conditions of automated embolus detection by means of a trained neural network (EMBotec V5.1 One, STAC GmbH, Germany).

Methods
—In 11 normal volunteers and in 11 patients with arterial or cardiac embolic sources, we performed simultaneous recordings from both middle or both posterior cerebral arteries. In the normal subjects, we produced 1342 additional artifacts to use the latter as false-positives. Detection of microembolic signals (MES) was done offline from digital audiotapes (1) by an experienced blinded investigator used as a reference and (2) by a trained 3-layer–feed-forward neural network.

Results
—From the 1342 provoked artifacts the neural network labeled 216 events as microemboli, yielding an artifact rejection of 85%. In microembolus-positive patients the neural network detected 282 events as emboli, among these 122 signals originating from artifacts; 58 “real” events were not detected. This result revealed a sensitivity of 73.4% and a positive predictive value of 56.7. The spectral power of the detected artifact signals was 16.5±5 dB above background signal. MES from patients with artificial heart valves had a spectral power of 6.4±2.1 dB; however, in patients with other sources of emboli, MES had an averaged energy reflection of 2.7±0.9 dB.

Conclusions
—The neural network is a promising tool for automated embolus detection, the formal algorithm for signal identification is unknown. However, extreme signal qualities, eg, strong artifacts, lead to misdiagnosis. Similar to other automated embolus detection systems, good signal quality and verification of MES by an experienced investigator is still mandatory.
Duplex Scanning Exploration of the Ophthalmic Artery for the Detection of the Hemodynamically Significant ICA Stenosis
Authors: Nuzzaci G. , Righi D. , Borgioli F. , Nuzzaci I. , Giannico G. , Pratesi C. , Pulli R. , Chiti E. , Gori F.
Published: June 2011

Background and Purpose
—The North American and the European Carotid Endarterectomy Trials demonstrated a significant benefit of surgery in preventing stroke for patients with symptomatic hemodynamically significant internal carotid artery (ICA) stenosis. Because the 3 angiographic methods of measuring carotid stenosis provide discrepant results, the indication for surgery depends on the method used for the evaluation of the angiogram. The goal of this study was to verify whether color duplex scanning of the ophthalmic artery alone might be reliable for detection of the extracranial hemodynamically significant ICA stenosis.

Methods
—Three groups of patients (351 total patients) with transient ischemic attack or minor stroke referred for possible carotid endarterectomy were examined by means of color duplex scanning of the ICA, transcranial Doppler, color duplex scanning of the ophthalmic artery, and angiography of the ICA.

Results
—In the first group (n=31) the comparison of findings from each method and the direct measurement of the residual lumen of plaque removed “en bloc” showed that the findings of the ophthalmic artery color duplex scanning, subdivided into 5 categories—NP (normal positive), LP (low positive), NF (no flow), REV (reverse flow), PP (pathological positive)—were associated with the best overall agreement (96.7%). The accuracy of the various categories of the ophthalmic artery color duplex scanning signals was studied in the second group of patients (n=200). The results pointed out that all but low positive categories were associated with high diagnostic accuracy. Finally, the results obtained in the third group (n=120) showed that a significant increase in the specificity of the low positive signal could be obtained by processing this signal in terms of pulsatility index and of transmission of pulsatility index.

Conclusions
—Our results suggest that the diagnostic capacity of color duplex scanning for the detection of ICA critical stenosis can be appropriately increased if it is performed also at the level of the ophthalmic artery and if the Doppler signals are processed on the basis of criteria we applied.
Blockade of ATP-Sensitive Potassium Channels in Cerebral Arterioles Inhibits Vasoconstriction From Hypocapnic Alkalosis in Cats
Authors: Wei Enoch P. , Kontos Hermes A.
Published: June 2011

Background and Purpose
—Recent studies have shown that the cerebral arteriolar dilation from hypercapnic acidosis is blocked by agents which inhibit K
ATP
channels. These findings suggested that this response is due to opening of K
ATP
channels. Because the repose to CO
2
is a continuum, with hypercapnic acidosis causing vasodilation and hypocapnic alkalosis causing vasoconstriction, it would be expected that the response to hypocapnic alkalosis would be due to closing of K
ATP
channels. There are no studies of the effect of inhibition of K
ATP
channels on the response to hypocapnic alkalosis.

Methods
—We investigated the effect of 3 agents that in earlier studies were found to inhibit K
ATP
channels—
N
G
-nitro-
l
-arginine, hydroxylysine, and glyburide—on the cerebral arteriolar constriction caused by graded hypocapnia induced by hyperventilation in anesthetized cats equipped with cranial windows.

Results
—Hypocapnic alkalosis caused dose-dependent vasoconstriction that was inhibited completely by each of the 3 inhibitors of K
ATP
channels. The blockade induced by these agents was eliminated in the presence of topical
l
-lysine (5 μmol/L).

Conclusions
—The findings show that agents which inhibit ATP-sensitive potassium channels in cerebral arterioles inhibit the vasoconstriction from hypocapnic alkalosis. These and earlier results showing that inhibition of K
ATP
channels inhibited dilation from hypercapnic acidosis demonstrate that the response to CO
2
in cerebral arterioles is mediated by the opening and closing of K
ATP
channels.
Carotid Artery Disease as a Marker for the Presence of Severe Coronary Artery Disease in Patients Evaluated for Chest Pain
Authors: Kallikazaros Ioannis , Tsioufis Costas , Sideris Skevos , Stefanadis Christodoulos , Toutouzas Pavlos
Published: June 2011

Background and Purpose
—We sought in this study to elucidate whether carotid artery disease detected by ultrasonography can be a clinically useful marker for the presence of severe coronary artery disease (CAD) in patients evaluated for chest pain.

Methods
—Duplex ultrasonography and quantitative coronary angiography were used to assess carotid and coronary artery atherosclerosis in 225 consecutive patients (mean age, 58±9 years) with chest pain referred for cardiac catheterization.

Results
—CAD was present in 197 patients (88%). Fifty-seven patients (25%) had 1-vessel disease, 52 (23%) had 2-vessel disease, 53 (24%) had 3-vessel disease, and 35 (16%) had left main stem CAD (LMS-CAD). The incidence of severe CAD (3-vessel disease or LMS-CAD) was 24% and 63% in the normal and impaired ejection fraction (EF) subgroups, respectively (
P
<0.005). Carotid disease (lumen diameter stenosis of ≥50%) was present in 5.3%, 13.5%, 24.5%, and 40% of patients with 1-, 2-, and 3-vessel disease and LMS-CAD, respectively. Moreover, the incidence of carotid disease in patients with severe CAD was 31% in the entire study population and 46% and 5% in the subgroups with impaired and normal EF, respectively (
P
<0.005). In the entire study population, the presence of severe CAD was determined by age, male sex, and carotid disease; in the impaired EF group by age and carotid disease; and in the normal EF group only by age. Carotid disease has a high negative (92%) and a high positive (91%) predictive value for the presence of severe CAD in the subgroup with normal and impaired EF, respectively.

Conclusions
—In patients evaluated for chest pain, carotid disease is significantly correlated with severe CAD. Furthermore, in patients with impaired left ventricular systolic performance the presence of carotid disease reflects the presence of severe CAD, while in patients with normal EF the absence of carotid disease reflects the absence of severe CAD.