bluuebunny/crossref_metadata_2025 huggingface dataset:
An Animal Model for the Molecular Genetics of CADASIL
Authors: Fryxell Karl J. , Soderlund Marcus , Jordan Theodor V.
Published: June 2011

Background
—CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an inherited condition that causes repeated small-scale strokes in adults. CADASIL is caused only by mutations in the human
NOTCH3
gene that increase or decrease the number of cysteines within the epidermal growth factor (EGF) repeats of the NOTCH3 protein.
Drosophila
lethal-Abruptex is a similar condition because it is also caused only by mutations that increase or decrease the number of cysteines within the EGF repeat portion of the Notch protein.

Summary of Comment
—
Drosophila
lethal-Abruptex and human CADASIL are precisely analogous at the molecular level, and both are genetically dominant. These precise similarities, together with the fact that the structure and function of Notch has been highly conserved throughout the animal kingdom, provide an animal model for the molecular and genetic aspects of human CADASIL. It also provides support for Spinner’s proposal that CADASIL results from dominant inhibition of the Notch pathway.

Conclusions
—Because the phenotypes of Notch mutations are cell-autonomous, the symptoms of CADASIL indicate that adult vascular smooth muscle cells require the continuing function of the
NOTCH3
pathway in the adult. For this reason, further analysis of the
NOTCH3
pathway may provide more general insights into the biology of vascular smooth muscle cells. In the case of CADASIL, the powerful genetic tools available in
Drosophila
should help to facilitate future research.
Effects of Task Goal and Personal Preference on Seated Reaching Kinematics After Stroke
Authors: Wu Ching-yi , Wong May-kuen , Lin Keh-chung , Chen Hsieh-ching
Published: June 2011

Background and Purpose
—Current theories of motor control in rehabilitation focus on how the nervous system responds to many types of external and internal constraints to execute motor behavior to accomplish a task. However, the dynamic interplay between these 2 constraints remains unclear. This study examined the impact of some aspects of internal and external constraints on motor performance in persons with stroke.

Methods
—Twenty-seven persons with stroke used the uninvolved arms to perform an upper-extremity reaching task under 4 experimental conditions, formed by the crossing of functional goals and personal preferences. For the higher level of a functional goal, subjects took a drink from a can of beverage. For the lower level of a functional goal, subjects brought the can to the mouth without drinking. The level of personal preferences was determined, by interview, by the degree of predilection for particular beverages.

Results
—Significant and large effects of functional goals and personal preference were found in the variables of movement time and reaction time. However, the data trend of the 4 testing conditions varied according to presence of visuospatial neglect and side of lesion.

Conclusions
—Offering choices for the treatment activities and incorporating functional goals to therapeutic tasks might enhance response rate or movement efficiency, depending on the side of the lesion and presence of visuospatial neglect. The findings suggest that the consideration of the neglect phenomenon is a necessity when rehabilitative treatment planning incorporates constraint factors.
Intracranial Cerebral Artery Disease as a Risk Factor for Central Nervous System Complications of Coronary Artery Bypass Graft Surgery
Authors: Yoon Byung-Woo , Bae Hee-Joon , Kang Dong-Wha , Lee Seung-Hoon , Hong Keun-Sik , Kim Ki-Bong , Park Byung Joo , Roh Jae-Kyu
Published: June 2011

Background and Purpose
—Although extracranial carotid artery disease (ECAD) is accepted as a risk factor for central nervous system (CNS) complications after coronary artery bypass graft (CABG) surgery, it remains to be clarified whether intracranial cerebral artery disease (ICAD) may also increase the risk. We conducted a prospective study to elucidate the relation between ICAD and CNS complications after CABG surgery.

Methods
—We prospectively studied 201 patients undergoing nonemergency isolated CABG surgery during a 39-month period (from March 1995 to June 1998). Each patient was evaluated before surgery with neurological examination, transcranial Doppler, and carotid duplex ultrasonography. Magnetic resonance angiography was used to determine the presence and severity of ECAD and ICAD in patients with abnormal findings on clinical examination, carotid duplex ultrasonography, or transcranial Doppler. Patients were followed after surgery and evaluated for the development of CNS complications. Association between CNS complications and their potential predictors was analyzed.

Results
—One hundred nine patients (54.2%) were found to have ECAD and/or ICAD. ECAD alone was found in 48 patients (23.9%), ICAD alone in 33 (16.4%), and both ECAD and ICAD in 28 (13.9%). Fifty-one patients (25.4%) had single or multiple CNS complications: 23 (11.4%) had delirium; 18 (9.0%) had hypoxic-metabolic encephalopathy; 7 (3.5%) had stroke; and 7 (3.5%) had seizure. In multivariate analysis, ICAD was found to have an independent association with the development of CNS complications (prevalence OR, 2.28; 95% CI, 1.04 to 5.01) after controlling for covariates including age, occurrence of intraoperative events, and reoperation. The joint effect of ECAD and ICAD was also statistically significant and stronger than ICAD alone (prevalence OR, 3.87; 95% CI, 1.80 to 6.52).

Conclusions
—Our results suggest that ICAD may be an independent risk factor for CNS complications after CABG surgery. These results support pre-CABG evaluation of the intracranial arteries for the risk assessment of CABG surgery, at least in black and Asian patients, in whom there may be a higher prevalence of intracranial arterial stenosis.
Evaluation of the TriSpan Neck Bridge Device for the Treatment of Wide-Necked Aneurysms
Authors: Turk Aquilla S. , Rappe Alan H. , Villar Francisco , Virmani Renu , Strother Charles M.
Published: June 2011

Background and Purpose
—Many wide-necked aneurysms are difficult or impossible to treat with the Guglielmi detachable coil (GDC). The purpose of this study was to evaluate the use of a neck bridging device, the TriSpan coil, in combination with standard GDCs for the treatment of wide-necked aneurysms in an experimental canine aneurysm model.

Methods
—Of 24 experimental aneurysms in 12 animals, 19 (7 lateral and 12 terminal) were treated with the TriSpan coil in conjunction with standard GDCs. Digital subtraction angiography (DSA) was performed on all animals immediately after treatment. In 6 animals, follow-up DSA and histological evaluation were performed 4 weeks after treatment. In the remaining 6, DSA was done at both 90 and 180 days after treatment. Histological evaluation was done immediately after the 180-day angiographic evaluation.

Results
—The TriSpan was easy to use in conjunction with the standard GDC. Because of their geometry, some lateral aneurysms were difficult or impossible to treat with this device. Greater than 90% aneurysm occlusion was obtained in all 19 aneurysms. In no instance was there evidence of coil migration, herniation, or aneurysm recanalization. Histological evaluation of the tissue surrounding the TriSpan coil showed tissue responses similar to that seen with standard GDCs.

Conclusions
—These results show that the TriSpan coil in conjunction with standard GDCs can be used safely and effectively for the treatment of wide-necked aneurysms in this canine model. Positioning and deployment of the neck bridge in aneurysms having an acute angle with the long axis of their parent artery are difficult or impossible. It is likely that this device, used in conjunction with the standard GDC, will allow treatment of some wide-necked aneurysms that are not treatable with the GDC alone.
Reduction of Inflammatory Response in the Mouse Brain With Adenoviral-Mediated Transforming Growth Factor-β1 Expression
Authors: Pang Li , Ye Wen , Che Xiao-Ming , Roessler Blake J. , Betz A. Lorris , Yang Guo-Yuan
Published: June 2011

Background and Purpose
—Chemokines have been shown to play an important role in leukocyte and monocyte/macrophage infiltration into ischemic regions. The purpose of this study is to identify whether overexpression of the active human transforming growth factor-β1 (ahTGF-β1) can downregulate expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and intercellular adhesion molecule-1 (ICAM-1) and reduce ischemic brain injury.

Methods
—Overexpression of transforming growth factor-β1 (TGF-β1) was achieved through adenoviral gene transfer. Five days after adenoviral transduction, the mouse underwent 30 minutes of middle cerebral artery occlusion followed by 1 to 7 days of reperfusion. TGF-β1, MCP-1, MIP-1α, and ICAM-1 were detected by enzyme-linked immunosorbent assay and immunohistochemistry. Infarct areas and volumes were measured by cresyl violet staining.

Results
—MCP-1 and MIP-1α expression is increased after middle cerebral artery occlusion, and double-labeled immunostaining revealed that MCP-1 is colocalized with neurons and astrocytes. Viral-mediated TGF-β1 overexpression was significantly greater at measured time points, with a peak at 7 to 9 days. The expression of MCP-1 and MIP-1α, but not ICAM-1, was reduced in the mice overexpressing ahTGF-β1 (
P
<0.05). Furthermore, infarct volume was significantly reduced in the mice overexpressing ahTGF-β1 (
P
<0.05).

Conclusions
—This study demonstrates that MCP-1 and MIP-1α expressed in the ischemic region may play an important role in attracting inflammatory cells. The reduction of MCP-1 and MIP-1α, but not ICAM-1, in the mice overexpressing ahTGF-β1 suggests that the neuroprotective effect of TGF-β1 may result from the inhibition of chemokines during cerebral ischemia and reperfusion.
Hormonal Factors and Risk of Aneurysmal Subarachnoid Hemorrhage
Authors: Mhurchu Cliona Ni , Anderson Craig , Jamrozik Konrad , Hankey Graeme , Dunbabin David
Published: June 2011

Background and Purpose
—Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women.

Methods
—This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995–1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices.

Results
—Cases and controls did not differ with regard to menstrual and reproductive history except in age at birth of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60).

Conclusions
—The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role for HRT on risk of SAH in postmenopausal women.
Retrospective Assessment of Initial Stroke Severity
Authors: Bushnell Cheryl D. , Johnston Dean C.C. , Goldstein Larry B.
Published: June 2011

Background and Purpose
—The NIH Stroke Scale (NIHSS) and the Canadian Neurological Scale (CNS) have been reported to be useful for the retrospective assessment of initial stroke severity. However, unlike the CNS, the NIHSS requires detailed neurological assessments that may not be reflected in all patient records, potentially limiting its applicability. We assessed the reliability of the retrospective algorithms and the proportions of missing items for the NIHSS and CNS in stroke patients admitted to an academic medical center (AMC) and 2 community hospitals.

Methods
—Randomly selected records of patients with ischemic stroke admitted to an AMC (n=20) and community hospitals with (CH1, n=19) and without (CH2, n=20) acute neurological consultative services were reviewed. NIHSS and CNS scores were assigned independently by 2 neurologists using published algorithms. Interrater reliability of the scores was determined with the intraclass correlation coefficient, and the numbers of missing items were tabulated.

Results
—The intraclass correlation coefficient for NIHSS and CNS, respectively, were 0.93 (95% CI, 0.82 to 1.00) and 0.97 (95% CI, 0.90 to 1.00) for the AMC, 0.89 (95% CI, 0.75 to 1.00) and 0.88 (95%, 0.73 to 1.00) for the CH1, and 0.48 (95% CI, 0.26 to 0.70) and 0.78 (95% CI, 0.60 to 0.96) for the CH2. More NIHSS items were missing at the CH2 (62%) versus the AMC (27%) and the CH1 (23%,
P
=0.0001). In comparison, 33%, 0%, and 8% of CNS items were missing from records from CH2, AMC, and CH1, respectively (
P
=0.0001).

Conclusions
—The levels of interrater agreement were almost perfect for retrospectively assigned NIHSS and CNS scores for patients initially evaluated by a neurologist at both an AMC and a CH. Levels of agreement for the CNS were substantial at a CH2, but interrater agreement for the NIHSS was only moderate in this setting. The proportions of missing items are higher for the NIHSS than the CNS in each setting, particularly limiting its application in the hospital without acute neurological consultative services.
Two Simple Questions to Assess Outcome After Stroke
Authors: McKevitt Christopher , Dundas Ruth , Wolfe Charles
Published: June 2011

Background and Purpose
—The “2 simple questions” were designed as an efficient way of measuring outcome after stroke. We assessed the sensitivity and specificity of this tool, adapted for use in 8 European centers, and used it to compare outcomes across centers.

Methods
—Data were taken from the Biomed II prospective study of stroke care and outcomes. Three-month poststroke data from 8 European centers were analyzed. Sensitivity and specificity were assessed by comparing responses to the 2 simple questions with Barthel Index and modified Rankin scale scores. Adjusting for case mix, logistic regression was used to compare patients in each center with “good” outcome (not dependent and fully recovered) at 3 months.

Results
—Data for 793 patients were analyzed. For the total sample, the dependency question had a sensitivity of 88% and a specificity of 77%; the recovery question had a sensitivity of 78% and a specificity of 90%. Dependency data from Riga had much lower sensitivity. There was variation in good outcome between centers (
P
=0.0015). Compared with the reference center (Kaunas), patients in Dijon, Florence, and Menorca were more likely to have good outcome, after adjusting for case mix.

Conclusions
—Dependency and recovery questions showed generally high sensitivity and specificity. There were significant differences across centers in outcome, but reasons for these are unclear. Such differences raise particular questions about how patients interpreted and answered the simple questions and the extent to which expectations of recovery and perceived needs for assistance vary cross-culturally.
Mortality at 12 and 24 Months After Stroke May Be Associated With Depressive Symptoms at 1 Month
Authors: House Allan , Knapp Peter , Bamford John , Vail Andy
Published: June 2011

Background and Purpose
—Previous studies have reported mood symptoms after stroke to be a risk factor for later mortality. The purpose of the study was to examine whether mood symptoms at 1 month after stroke may be a risk factor for mortality at 12 and 24 months.

Methods
—As a cohort within a randomized controlled trial, 448 hospital patients were seen at 1 month after stroke and were randomized into a trial of psychological therapy. Follow-up was at 12 and 24 months. Mood symptoms were assessed by the Present State Examination and the General Health Questionnaire (GHQ)-28. Measures of disability before and after stroke and of cognitive impairment after stroke were also taken at 1 month. Mortality was determined at 12 and 24 months after stroke.

Results
—In logistic regression analyses, mortality at 12 months was associated unifactorally with scoring on the GHQ-D subscale (odds ratio [OR] 2.4, 95% CI 1.3 to 4.5) and scoring in the highest quartile of the GHQ (OR 3.1, 95% CI 1.1 to 8.8). In multiple logistic regression analyses, only GHQ-D remained a significant predictor after controlling for other known predictors. At 24 months, scoring on GHQ-D (OR 2.4, 95% CI 1.4 to 4.1) and in the highest GHQ quartile (OR 2.2, 95% CI 1.0 to 4.8) was significantly associated with mortality in unifactoral analyses. Scoring on the GHQ-D remained a predictor of mortality after controlling for other variables. Psychiatric disorder, such as major depression (according to International Classification of Diseases, 10th Revision), was not statistically significantly associated with increased mortality at 12 or 24 months.

Conclusions
—Mood symptoms on a self-reported rating scale were associated with 12- and 24-month mortality after stroke, after adjustment for factors associated with stroke severity. The result is in keeping with other evidence that depressive symptoms are a risk factor for death from vascular disease.
Sustained Bilateral Hemodynamic Benefit of Contralateral Carotid Endarterectomy in Patients With Symptomatic Internal Carotid Artery Occlusion
Authors: Rutgers D. R. , Klijn C. J. M. , Kappelle L. J. , Eikelboom B. C. , van Huffelen A. C. , van der Grond J.
Published: June 2011

Background and Purpose
—We sought to investigate whether in patients with a symptomatic internal carotid artery (ICA) occlusion, endarterectomy of a severe stenosis of the contralateral carotid artery can establish long-term cerebral hemodynamic improvement.

Methods
—Nineteen patients were studied on average 1 month before and 6 months after contralateral carotid endarterectomy (CEA). Volume flow in the main extracranial and intracranial arteries was measured with MR angiography. Collateral flow via the circle of Willis and the ophthalmic arteries was studied with MR angiography and transcranial Doppler sonography, respectively. Cerebral metabolism and CO
2
vasoreactivity were investigated with MR spectroscopy and transcranial Doppler sonography, respectively. Twelve nonoperated patients with a symptomatic ICA occlusion and contralateral ICA stenosis, who were matched for age and sex, served as control patients.

Results
—In patients who underwent surgery, flow in the operated ICA increased significantly (
P
<0.05) and flow in the basilar artery decreased significantly (
P
<0.01) after CEA. On the occlusion side, mean flow in the middle cerebral artery increased significantly from 71 to 85 mL/min (
P
<0.05) after CEA. The prevalence of collateral flow via the anterior communicating artery to the occlusion side increased significantly (47% before and 84% after CEA;
P
<0.05), while the prevalence of reversed ophthalmic artery flow on the operation side decreased significantly (42% before and 5% after CEA;
P
<0.05). In the hemisphere on the side of the ICA occlusion, lactate was no longer detected after CEA in 80% of operated patients, whereas it was no longer detected over time in 14% of nonoperated patients (
P
<0.05). CO
2
reactivity increased significantly in operated patients in both hemispheres (
P
<0.01).

Conclusions
—Contralateral CEA in patients with a symptomatic ICA occlusion induces cerebral hemodynamic improvement not only on the side of surgery but also on the side of the ICA occlusion.
Comparison of Carotid Arterial Resistive Indices With Intima-Media Thickness as Sonographic Markers of Atherosclerosis
Authors: Frauchiger Beat , Schmid Hans Peter , Roedel Christian , Moosmann Peter , Staub Daniel
Published: June 2011

Background and Purpose
—The intima-media thickness (IMT) of the carotid artery is a (morphological) sonographic parameter that depends on the degree of atherosclerosis. In the renal arteries, the value of the (hemodynamic) resistive index (RI) is correlated with the severity of atherosclerosis. In contrast to the well-known IMT, no study has yet applied the carotid RI to estimate generalized atherosclerosis.

Methods
—The SMART atherosclerosis risk score was determined in 157 patients (94 men and 63 women; mean age 63 [range 19 to 80] years) with at least 1 vascular risk factor or a known vascular disease. Duplex sonography of the common carotid (CCA) and internal carotid artery (ICA) was then performed, with determination of IMT and RI.

Results
—The mean risk score of all patients was 8.8±3.5 (range 1 to 17), the mean IMT value in the CCA was 0.727±0.161 mm, the mean RI in CCA was 0.79±0.066, and the mean RI in ICA was 0.661±0.082. Highly significant correlations were found between the score and IMT CCA and the score and RI ICA (
r
=0.62,
P
<0.0001 and
r
=0.55,
P
<0.0001). The score–RI CCA correlation was much less marked (
r
=0.354,
P
<0.0001). The intraobserver and interobserver agreement was less for IMT than for RI CCA and ICA. The areas under the curve of the receiver operating curves to distinguish between low-risk and high-risk patients resulted in values of 0.86, 0.81, and 0.69 for IMT, RI ICA, and RI CCA, respectively.

Conclusions
—Although RI reflects the atherosclerotic process in an indirect manner, the correlation between the RI ICA and the SMART atherosclerosis score as well as the ability to distinguish between low- and high-risk patients are comparable to those of the well-known IMT.
Presence of
Chlamydia pneumoniae in Human Symptomatic and Asymptomatic Carotid Atherosclerotic Plaque
Authors: LaBiche Ronald , Koziol Deloris , Quinn Thomas C. , Gaydos Charlotte , Azhar Salman , Ketron Gary , Sood Suman , DeGraba Thomas J.
Published: June 2011

Background
—
Chlamydia pneumoniae
has been identified in atherosclerotic plaques of patients with cerebrovascular and cardiovascular disease. However, the direct causative effect of
C pneumoniae
infection in the activation of atherosclerotic plaque to a prothrombotic state remains to be established. The aim of the present study is to examine the correlation between intraplaque presence of chlamydiae and symptomatic carotid disease in humans.

Methods
—Plaques from 37 symptomatic and 57 asymptomatic consenting patients undergoing carotid endarterectomy were snap-frozen, and the tissue was prepared for polymerase chain reaction analysis for
Chlamydia pneumoniae
per Institutional Review Board–approved protocol. Blood was drawn from each patient at the time of surgery for serological analysis.

Results
—The overall rate of plaques positive for
C pneumoniae
was 14.82%, with 5 of 37 (13.5%) plaques from symptomatic patients and 9 of 57 (15.8%) from asymptomatic patients, which revealed a definitive presence of the organism. No association existed between
C pneumoniae
presence and symptomatic disease (
P
=1.0). Also, no association existed between presence of
C pneumoniae
and severity of stenosis. Finally, seropositivity for anti-chlamydial IgG, IgA, and IgM anti-chlamydial antibodies did not correlate with identification of
C pneumoniae
in the plaques. However, high-serum anti-chlamydial IgA levels (≥1:128) were associated with occurrence of symptomatic disease (
P
=0.03; odds ratio, 2.86; 95% CI, 1.12 to 7.28).

Conclusions
—Presence of
C pneumoniae
as a single factor does not appear to be sufficient to explain the occurrence of cerebrovascular symptoms. Low sensitivity of seropositivity for IgG, IgA, or IgM associated with PCR-identified
C pneumoniae
presence in the plaque makes it unlikely to be valuable as the single determining factor for actively infected plaque. Association of high-level anti-chlamydial IgA with symptomatic disease suggests that chronic or acute chlamydial infection anywhere in the body could play a role in atherosclerotic plaque activation and be used as a marker to target populations in future stroke prevention trials.
Should Mild or Moderate Stroke Patients Be Admitted to an Intensive Care Unit?
Authors: Briggs Deborah E. , Felberg Robert A. , Malkoff Marc D. , Bratina Patti , Grotta James C.
Published: June 2011

Background and Purpose
—Inhospital placement of patients with mild (National Institutes of Health Stroke Scale [NIHSS] score <8) or moderate (NIHSS 8 through 16) acute strokes is variable. We assessed the outcome of such patients based on intensive care unit (ICU) versus general ward placement.

Methods
—We reviewed 138 consecutive patients admitted within 24 hours of stroke onset to 2 physically adjacent hospitals with different admitting practices. Outcome measures included complication rates, discharge Rankin scale score, hospital discharge placement, costs, and length of stay (LOS).

Results
—Hospital A, a 626-bed university-affiliated hospital, admitted 43% of mild and moderate strokes (MMS) to an ICU (26% of mild, 74% of moderate), whereas hospital B, a 618-bed community facility, admitted 18% of MMS to an ICU (3% of mild, 45% of moderate;
P
<0.004). There were no significant differences in outcomes between the 2 hospitals. Analysis of only patients admitted to hospital A, and of all patients, demonstrated that mild stroke patients admitted to the general ward had fewer complications and more favorable discharge Rankin scale scores than similar patients admitted to an ICU. There was no statistically significant difference in LOS, but total room costs for a patient admitted first to the ICU averaged $15 270 versus $3638 for admission directly to the ward.

Conclusions
—While limited by the retrospective nature of our study, routinely admitting acute MMS patients to an ICU provides no cost or outcomes benefits.
Hemostatic Activation in Spontaneous Intracerebral Hemorrhage
Authors: Fujii Yukihiko , Takeuchi Shigekazu , Harada Atsuko , Abe Hiroshi , Sasaki Osamu , Tanaka Ryuichi
Published: June 2011

Background and Purpose
—There is no in-depth information available on the changes in hemostatic systems in patients in the acute phase of spontaneous intracerebral hemorrhage (ICH). This study was conducted to assess the relationships between the changes in hemostatic systems and clinical parameters in patients in acute-phase ICH.

Methods
—The records of 358 patients admitted within 6 hours of onset of ICH were reviewed to examine the relationships between changes in hemostatic systems and computed tomographic findings and clinical parameters.

Results
—The white blood cell counts and the levels of thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer in patients with intraventricular extension (IVE) or subarachnoid hemorrhage (SAH) were significantly (
P
<0.05) higher than those in patients without IVE or SAH. Most of the hemostatic system parameters in patients without IVE or SAH showed no significant differences compared with normal subjects. Multiple linear regression analysis revealed that the levels of thrombin-antithrombin complex significantly increased with an increase in the amount of SAH (
P
<0.001) and IVE (
P
<0.001). The levels of thrombin-antithrombin complex were not significantly associated with the volume of intraparenchymal hematoma. The level of the complex, however, was significantly (
P
<0.001) and independently associated with the presence of IVE or SAH (multiple logistic regression analysis).

Conclusions
—The systemic activation of hemostatic systems in ICH patients seems to take place only when blood reaches the subarachnoid space. The intraparenchymal hematoma itself seems unlikely to activate hemostatic systems in peripheral blood, although the hematoma is expected to cause local activation of hemostatic systems.
Prospective Study of Depressive Symptoms and Risk of Stroke Among Japanese
Authors: Ohira Tetsuya , Iso Hiroyasu , Satoh Shinji , Sankai Tomoko , Tanigawa Takeshi , Ogawa Yuka , Imano Hironori , Sato Shinichi , Kitamura Akihiko , Shimamoto Takashi
Published: June 2011

Background and Purpose
—We sought to examine the relationship between depressive symptoms and the incidence of stroke among Japanese men and women.

Methods
—A 10.3-year prospective study on the relationship between depressive symptoms and the incidence of stroke was conducted with 901 men and women aged 40 to 78 years in a rural Japanese community. Depressive symptoms were measured at baseline with the use of the Zung Self-Rating Depression Scale (SDS). The incidence of stroke was ascertained under systematic surveillance.

Results
—During the 10-year follow-up, 69 strokes (39 ischemic strokes, 10 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 10 unclassified strokes) occurred. Age- and sex-adjusted prevalence of mild depression (SDS scores ≥40) at baseline was 25% among subjects with incident stroke and 12% among subjects without stroke (
P
<0.01). Persons with SDS scores in the high tertile had twice the age- and sex-adjusted relative risk of total stroke as those with scores in the low tertile. The excess risk was confined to ischemic stroke. After we adjusted for body mass index, systolic blood pressure level, serum total cholesterol level, cigarette smoking, current treatment with antihypertensive medication, and history of diabetes mellitus, these relative risks remained statistically significant for total stroke (1.9; 95% CI, 1.1 to 3.5) and ischemic stroke (2.7; 95% CI, 1.2 to 6.0).

Conclusions
—Depressive symptoms predict the risk of stroke, specifically ischemic stroke among Japanese.
Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials
Authors: Uchino Ken , Billheimer Dean , Cramer Steven C.
Published: June 2011

Background and Purpose
—We sought to study the range of entry criteria and baseline characteristics in acute stroke trials and to understand their effects on patient outcomes.

Methods
—Randomized, placebo-controlled therapeutic trials in patients with acute ischemic stroke were identified. Entry criteria, baseline clinical characteristics, and outcome were extracted for the placebo group of each trial. The relationship between key variables was then determined.

Results
—Across 90 placebo groups identified, there was great variation in entry criteria and outcome measures. This was associated with divergent outcomes; for example, in some studies most placebo group patients died, while in other studies nearly all had no disability. Entry criteria were significantly correlated with outcome; for example, higher age cutoff for study entry correlated with 3-month mortality. Entry criteria also predicted baseline clinical characteristics; for example, wider time window for study entry correlated directly with time to treatment and inversely with stroke severity (initial National Institutes of Health Stroke Scale score). Baseline characteristics predicted outcome. Greater stroke severity predicted higher 3-month mortality rate; despite this, successful thrombolytic trials have enrolled more severe strokes than most trials. The mean age of enrollees also predicted 3-month mortality and was inversely related to percentage of patients with 3-month Barthel Index score ≥95. The strongest predictors of 3-month mortality were obtained with multivariate models.

Conclusions
—Acute stroke studies vary widely in entry criteria and outcome measures. Across multiple studies, differences in entry criteria, and the baseline clinical characteristics they predict, influence patient outcomes along a continuum. In some studies, enrolling a specific subset of patients may have improved the chances of identifying a treatment-related effect, while in others, such chances may have been reduced. These findings may be useful in the design of future stroke therapeutic trials.
Power Transcranial Doppler Ultrasound in the Detection of Intracranial Aneurysms
Authors: White Philip M. , Wardlaw Joanna M. , Teasdale Evelyn , Sloss Stuart , Cannon Jim , Easton Valerie
Published: June 2011

Background and Purpose
—We sought to perform a large, prospective, multicenter, blinded study comparing power transcranial color duplex sonography (power TCDS) with intra-arterial digital subtraction angiography (IADSA) in the detection of intracranial aneurysms.

Methods
—Contemporaneous TCDS and IADSA examinations were performed in 171 subjects with suspected intracranial aneurysm. Via the temporal bone window, a 2-dimensional hand-held noncontrast transcranial duplex ultrasound imaging system was used operating in power and spectral modes. Sonographers were blinded to clinical history and results of brain CT and IADSA.

Results
—We found that 157 subjects (92%) had an adequate bone window. Sensitivity per patient was 0.78 (95% CI, 0.66 to 0.87) and 0.46 (95% CI, 0.36 to 0.56) for any anterior circulation aneurysms. Sensitivity was 0.35 (95% CI, 0.24 to 0.46) for aneurysms ≤5 mm and 0.81 (95% CI, 0.62 to 0.94) for aneurysms >5 mm. Accuracy was lower for aneurysms on the cavernous and terminal internal carotid arteries, including posterior communicating artery origin (0.71; 95% CI, 0.63 to 0.79), than for those on the anterior (0.82; 95% CI, 0.74 to 0.89) or the middle cerebral arteries (0.79; 95% CI, 0.71 to 0.86).

Conclusions
—Power TCDS is a promising, inexpensive, noninvasive test for anterior circulation intracranial aneurysms but is less sensitive per aneurysm than alternatives such as CT angiography or MR angiography. Sensitivity is poor for aneurysms ≤5 mm in diameter. The internal carotid artery is the most difficult segment to interpret.
Clinical Correlates and Drug Treatment of Residents With Stroke in Long-Term Care
Authors: Quilliam Brian J. , Lapane Kate L.
Published: June 2011

Background and Purpose
—Stroke incidence increases with age, and stroke survivors often require nursing home placement. Characteristics of these residents and factors associated with the secondary drug prevention of stroke in nursing homes have yet to be explored.

Methods
—We used a population-based data set of all nursing home residents in 5 states (1992 to 1995). We identified 53 829 (20.4%) with a diagnosis of stroke on the Minimum Data Set assessment. We considered aspirin, dipyridamole, ticlopidine, or warfarin alone or in combination as secondary drug prevention. We used logistic regression modeling to identify independent predictors of drug treatment.

Results
—Sixty-seven percent of stroke survivors were not receiving drug therapy for stroke prevention. Among those treated, most received aspirin alone (16%) or warfarin alone (10%). Independent predictors of drug treatment included comorbid conditions (eg, hypertension, atrial fibrillation, depression, Alzheimer’s disease, dementia, gastrointestinal bleeding, and peptic ulcer disease). Those over the age of 85 years were less likely to be treated than those 65 to 74 years of age (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.82 to 0.91); black residents were less likely to be treated than whites (OR, 0.80; 95% CI, 0.75 to 0.85); and those with severe cognitive (OR, 0.63; 95% CI, 0.60 to 0.67) or physical impairment (OR, 0.69; 95% CI, 0.64 to 0.75) were also less likely to receive drug treatment.

Conclusions
—Stroke is highly prevalent in long-term care. Despite the increased risk of subsequent stroke in the elderly, many are not being treated. The choice to treat or not to treat may be influenced by age, comorbidity, race/ethnicity, and cognitive or physical functioning.
Stroke After Coronary Artery Bypass
Authors: Stamou Sotiris C. , Hill Peter C. , Dangas George , Pfister Albert J. , Boyce Steven W. , Dullum Mercedes K.C. , Bafi Ammar S. , Corso Paul J.
Published: June 2011

Background and Purpose
—Early postoperative stroke is a serious adverse event after coronary artery bypass grafting (CABG). This study sought to investigate risk factors, prevalence, and prognostic implications of postoperative stroke in patients undergoing CABG.

Methods
—We investigated the predictors of postoperative stroke (n=333, 2%) in 16 528 consecutive patients who underwent CABG between September 1989 and June 1999 in our institution. Predictors of postoperative stroke were identified by logistic regression analysis.

Results
—Among the preoperative and postoperative factors, significant correlates of stroke included (1) chronic renal insufficiency (
P
<0.001), (2) recent myocardial infarction (
P
=0.01), (3) previous cerebrovascular accident (
P
<0.001), (4) carotid artery disease (
P
<0.001), (5) hypertension (
P
<0.001), (6) diabetes (
P
=0.001), (7) age >75 years (
P
=0.008), (8) moderate/severe left ventricular dysfunction (
P
=0.01), (9) low cardiac output syndrome (
P
<0.001), and (10) atrial fibrillation (
P
<0.001). Postoperative stroke was associated with longer postoperative stay (11±4 versus 7±3 days for patients without stroke,
P
<0.001) and with higher in-hospital mortality (14% versus 2.7% for patients without stroke;
P
<0.001).

Conclusions
—Stroke after CABG is associated with high short-term morbidity and mortality. Increased stroke risk can be predicted by preoperative and postoperative clinical factors.
Muscle Tensing During Standing
Authors: van Lieshout Johannes J. , Pott Frank , Madsen Per Lav , van Goudoever Jeroen , Secher Niels H.
Published: June 2011

Background and Purpose
—When standing up causes dizziness, tensing of the leg muscles may alleviate the symptoms. We tested the hypothesis that leg tensing improves orthostatic tolerance via enhanced cerebral perfusion and oxygenation.

Methods
—In 10 healthy young adults, the effects of leg tensing on transcranial Doppler–determined middle cerebral artery (MCA) mean blood velocity (
V
mean
) and the near-infrared spectroscopy–determined frontal oxygenation (O
2
Hb) were assessed together with central circulatory variables and an arterial pressure low-frequency (LF) (0.07 to 0.15 Hz) domain evaluation of sympathetic activity.

Results
—Standing up reduced central venous pressure by (mean±SEM) 4.3±2.6 mm Hg, stroke volume by 49±7 mL, cardiac output by 1.9±0.4 L/min, and mean arterial pressure at MCA level by 9±4 mm Hg, whereas it increased heart rate by 30±4 beats per minute (
P
<0.05). MCA
V
mean
declined from 67±4 to 56±3 cm/s, O
2
Hb decreased by 7±2.8%, and LF spectral power increased (
P
<0.05). Leg tensing increased central venous pressure by 1.4±2.7 mm Hg and cardiac output by 1.8±0.4 L/min with no significant effect on blood pressure, whereas heart rate decreased by 11±3 beats per minute (
P
<0.05). MCA
V
mean
increased to 63±3 cm/s and O
2
Hb increased by 2.1±2.6%, whereas LF power declined (
P
<0.05). Within 2 minutes after leg tensing, these effects had disappeared.

Conclusions
—During standing, tensing of the leg muscles attenuates a reduction in cerebral perfusion and oxygenation as it stabilizes central circulatory variables and reduces sympathetic activity.
Effect of Collateral Blood Flow and Cerebral Vasomotor Reactivity on the Outcome of Carotid Artery Occlusion
Authors: Vernieri Fabrizio , Pasqualetti Patrizio , Matteis Maria , Passarelli Francesco , Troisi Elio , Rossini Paolo M. , Caltagirone Carlo , Silvestrini Mauro
Published: June 2011

Background and Purpose
—Evidence suggests that an alteration in cerebral hemodynamics plays a relevant role in the occurrence of stroke in patients with carotid occlusion. The purpose of the present study was to evaluate the relationships among baseline characteristics, type and number of collateral pathways, cerebral vasomotor reactivity (VMR), and outcome of patients with carotid occlusion.

Methods
—One hundred four patients with symptomatic or asymptomatic internal carotid artery occlusion were followed up prospectively for a median period of 24 months. Cerebral VMR to apnea was calculated with transcranial Doppler ultrasonography by means of the breath-holding index (BHI) in the middle cerebral arteries. The patency of the 3 major intracranial collateral vessels was also evaluated.

Results
—During the follow-up period, 18 patients experienced an ischemic stroke ipsilateral to internal carotid artery occlusion. Among factors considered, only older age, number of collateral pathways, and BHI values in the middle cerebral artery ipsilateral to the occluded side were significantly associated with the risk of ipsilateral stroke (
P
<0.001,
P
=0.008, and
P
<0.001, respectively; multiple Cox regression analysis). A normal VMR and favorable prognosis characterized patients with full collateral development; in this group, no patient experienced an ischemic event. On the other hand, an impaired VMR and increased probability of experiencing a stroke were found in patients without collateral pathways; the annual risk of ipsilateral stroke in this group was 32.7%. Patients with 1 or 2 collateral pathways showed a different VMR ranging from normal to strongly reduced BHI values. The ipsilateral stroke event risk was 17.5% in patients with 1 collateral vessel and 2.7% in patients with 2 collateral pathways. In this case, the risk of cerebrovascular events occurring during the follow-up period was significantly related to VMR.

Conclusions
—These data suggest that cerebral hemodynamic status in patients with carotid occlusive disease is influenced by both individual anatomic and functional characteristics. The planning of strategies to define the risk profile and any attempt to influence patients’ outcome should be based on the evaluation of the intracranial hemodynamic adaptive status, with particular attention to the number of collateral vessels and the related VMR.
Gene Expressions After Thrombolytic Treatment of Middle Cerebral Artery Clot Embolism in Mice
Authors: Hara Takayuki , Mies Günter , Hata Ryuji , Hossmann Konstantin-Alexander
Published: June 2011

Background and Purpose—

Thrombolytic treatment of stroke may result in reperfusion injury. To investigate the role of selective gene expressions, C57Bl/6J mice were subjected to middle cerebral artery (MCA) clot embolism, followed after 1 hour by intracarotid infusion of 10 mg/kg recombinant tissue plasminogen activator (rtPA) or vehicle.

Methods—

Before the onset of treatment and at 1, 3, 6, and 24 hours of recirculation, animals were frozen in situ and
hsp70
, c-
fos
,
junB
, and
NSE
mRNAs were imaged on cryostat sections using in situ hybridization autoradiography. Cerebral protein synthesis (CPS) and ATP content were measured on adjacent brain sections.

Results—

hsp70
mRNA was upregulated in the penumbral cortex of untreated animals and in the MCA core region of animals receiving rtPA (ie, regions characterized by a mismatch between high ATP levels and suppressed CPS). c-
fos
and
junB
mRNAs were transiently expressed mainly in the peri-infarct intact cortex for up to 3 to 6 hours in the treated and up to 24 hours in the untreated animals. In both groups,
NSE
mRNA declined in the central parts of the MCA territory together with a loss of silver impregnation, but this decline was more pronounced in the untreated animals.

Conclusions—

The genomic expression pattern after thrombolytic recanalization of clot embolism resembles that of other types of transient ischemia such as reversible thread occlusion, although the outcome is markedly different. The investigated gene expressions, notably
hsp70
mRNA, reflect the kind and severity of the ischemic stress, but they do not predict reversibility of the ischemic injury.
The Effects of Infra-Arterial Histamine on Blood Flow in the Internal and External Carotid Artery of Man
Authors: TINDALL GEORGE T. , GREENFIELD JOSEPH C.
Published: June 2011

Both internal and external carotid artery phasic blood flow and arterial pressure were measured in five patients during a control period and after the intra-arterial injection of 13.8 µg of histamine phosphate into each vessel. In the internal carotid artery, flow for the group increased almost immediately and reached a maximum value of 59% greater than control in ten seconds. The total duration of the response in both pressure and flow lasted approximately one minute. The injection of histamine into the external carotid artery elicited a much more marked response, having a maximum increase in flow of 294% for the group with a total duration of the response lasting two and one-half to three minutes. These data define the magnitude and time course of the action of histamine phosphate on the intracranial and extracranial circulation in man.
Evidence for the Direct Effect of Adrenergic Drugs on the Cerebral Vascular Bed of the Unanesthetized Goat
Authors: LLUCH SALVADOR , REIMANN CHARLES , GLICK GERALD
Published: June 2011

Despite considerable research, the question of whether adrenergic drugs exert direct effects on the cerebral circulation has remained unresolved. With the development of a method for monitoring continuously the entire blood flow to one hemisphere in the unanesthetized goat, we have been able to study this problem directly. The effects of epinephrine, norepinephrine, and isoproterenol administered by close intra-arterial injection were investigated in 15 goats in which an electromagnetic flowmeter had been implanted previously on the internal maxillary artery, which, in this animal, provides the sole blood supply to a hemisphere. Both epinephrine and norepinephrine (0.1 to 5.0 µg) produced dose-dependent reductions in cerebral blood flow, a decrease of 55 ± 3% (SEM) occurring with the highest dose. Alpha receptor blockade of the ipsilateral hemisphere with phenoxybenzamine totally or partially abolished this cerebral vasoconstriction. Isoproterenol (0.01 to 1.0 µg) produced dose-dependent increases in cerebral blood flow, an increment of 75 ± 6% occurring with the highest dose. Beta blockade with propranolol totally or partially abolished the cerebral vasodilation induced by isoproterenol. Thus, epinephrine, norepinephrine, and isoproterenol exert powerful direct effects on the cerebral circulation of the unanesthetized goat, and these effects appear to be mediated by alpha and beta receptors.
Detecting Carotid Occlusive Disease by Thermography
Authors: CAPISTRANT T. D. , GUMNIT R. J.
Published: June 2011

The ability of facial thermography to detect disease in the internal carotid artery was evaluated. Unilateral forehead cooling of 0.7°C or greater was observed in 57% of 30 cases with angiographically proved stenosis. Two provocative tests, facial cooling and a head clamp, increased the sensitivity rate to 83% The greatest overall sensitivity and specificity was obtained by using a head clamp especially designed to bilaterally occlude superficial temporal arteries. Facial thermography is a useful screening device in detecting carotid occlusive disease. However, the necessity to use a provocative test to increase the sensitivity to acceptable levels will probably limit its use to the screening of high-risk asymptomatic patients. It does not appear to be economically feasible in the mass screening of healthy individuals.