bluuebunny/crossref_metadata_2025 huggingface dataset:
Placebo Treatment in Acute Stroke Trials
Authors: Libman Richard , Bhatnagar Rajesh , Ding Lei , Kwiatkowski Thomas , Barr William
Published: June 2011

Background and Purpose
—Some stroke patients and their families express reservations about participating in trials of experimental therapies for acute stroke. Among many reasons given for this is the concern that by participating, patients may be deprived of some component of routine care. We sought to determine the effect on outcome of participating in a clinical stroke trial while being treated with placebo.

Methods
—Prospective clinical information was collected for all patients admitted with acute ischemic stroke between July 1995 and July 1996. A subgroup of these patients was enrolled in a clinical trial of acute stroke therapy and had been randomly assigned to the placebo group. The control group was selected from concurrent stroke patients who were not enrolled in any clinical trial. The National Institutes of Health Stroke Scale (NIHSS) was performed on admission and on day 7 after admission. The Glasgow Outcome Scale (GOS) was also performed at discharge. Stroke severity was classified as “severe” if NIHSS was ≥9 or GOS ≥3. Group comparisons were performed with χ
2
tests.

Results
—One hundred twenty-six patients were evaluated. Forty-seven were placebo patients, and 79 were selected as control subjects. There were no significant differences between the groups with respect to age, sex, hematocrit, blood glucose level, history of hypertension, diabetes, smoking, or initial NIHSS. In addition, there was no difference between groups in terms of the frequency of baseline stroke subtype. Among our controls, 55 patients (70%) were on antithrombotic treatment during hospitalization, whereas none of our placebo patients were on any antithrombotic treatment. For the GOS at follow-up, a good outcome was attained by 76% of the control subjects and 72% of placebo patients (not significant). A severe NIHSS (>9) at follow-up, however, was documented in 15% of controls and 59% of placebo patients (
P
<0.001). There was a trend toward a higher (“worse”) mean follow-up NIHSS among placebo patients (mean NIHSS, 11) versus controls (mean NIHSS, 6) (
P
=0.09).

Conclusions
—Patients enrolled in the placebo arms of some acute clinical stroke trials have similar functional outcomes but more severe neurological deficits at 1 week than did a control group. These findings might be partially explained by the withholding of antithrombotic medication and the exclusion criteria inherent in most trials. Vigilance is required to ensure that all patients participating in stroke studies be guaranteed optimal known medical therapy.
Significant Association of Atrial Vulnerability With Atrial Septal Abnormalities in Young Patients With Ischemic Stroke of Unknown Cause
Authors: Berthet Karine , Lavergne Thomas , Cohen Ariel , Guize Louis , Bousser Marie-Germaine , Le Heuzey Jean-Yves , Amarenco Pierre
Published: June 2011

Background and Purpose
—Atrial septal abnormalities have been associated with cryptogenic ischemic stroke in young patients, but the causal link has not yet been established. Paradoxical embolism is considered the most likely mechanism but is rarely proven. It can be hypothesized that, in those patients, paroxysmal atrial arrhythmias, potentially favored by the anatomic abnormalities, can be another cause of thrombus formation and subsequent embolism to the brain. In this study we assessed the relationship between atrial vulnerability, reflecting arrhythmogenic properties of the atria, and atrial septal abnormalities in young patients with cryptogenic ischemic stroke.

Methods
—We enrolled 62 consecutive patients aged <55 years who had ischemic stroke of unknown cause and transesophageal echocardiography to assess atrial septal aneurysm (ASA) or patent foramen ovale (PFO) (ie, atrial septal abnormalities). These patients underwent electrophysiological study to measure atrial refractoriness and conduction time defining a vulnerability index (ie, latent atrial vulnerability) and to assess the inducibility of sustained (lasting >60 seconds) atrial fibrillation with the use of programmed atrial stimulation. Actual atrial vulnerability was defined by the presence of both latent vulnerability and inducibility of sustained atrial fibrillation lasting >60 seconds.

Results
—We found atrial vulnerability in 58% of patients with atrial septal abnormalities and in 25% of patients without (odds ratio=4.1 [95% CI, 1.3 to 12.7;
P
<0.02]). The difference between patients with and without PFO or between patients with both PFO and ASA and those without were also significant. Patients with inducible sustained atrial fibrillation had more frequent past history of palpitations and syncope than patients without (
P
<0.02).

Conclusions
—Atrial vulnerability is associated with atrial septal abnormalities in patients with cryptogenic stroke. This result raises the question of the potential role of transient atrial arrhythmias in thrombus formation in the presence of PFO or ASA.
Aortic Atherosclerosis at Middle Age Predicts Cerebral White Matter Lesions in the Elderly
Authors: de Leeuw Frank-Erik , Cees de Groot Jan , Oudkerk Matthijs , Witteman Jacqueline C. M. , Hofman Albert , van Gijn Jan , Breteler Monique M. B.
Published: June 2011

Background and Purpose
—MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions.

Methods
—We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531 subjects in late life.

Results
—The presence of aortic atherosclerosis during midlife was significantly associated with the presence of periventricular white matter lesions ≈20 years later (adjusted relative risk, 2.4; 95% CI, 1.2 to 5.0); the relative risks increased linearly with the severity of aortic atherosclerosis. No association was found between midlife aortic atherosclerosis and subcortical white matter lesions (adjusted relative risk, 1.1; 95% CI, 0.5 to 2.3) or between late-life aortic atherosclerosis and white matter lesions.

Conclusions
—The pathogenetic process that leads to cerebral periventricular white matter lesions starts already in or before midlife. The critical period for intervention directed at prevention of white matter lesions and its cognitive consequences may be long before these lesions become clinically detectable.
Toxicity of Dutch (E22Q) and Flemish (A21G) Mutant Amyloid β Proteins to Human Cerebral Microvessel and Aortic Smooth Muscle Cells
Authors: Wang Zhenzhen , Natté Remco , Berliner Judith A. , van Duinen Sjoerd G. , Vinters Harry V.
Published: June 2011

Background and Purpose
—Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid β protein (Aβ) in cortical and leptomeningeal vessels of patients with Alzheimer’s disease and hereditary cerebral hemorrhage with amyloidosis, Dutch type. Smooth muscle cells (SMC) from cerebral microvessels (MV) are of particular interest as a site of Aβ-related injury because CAA is much more pronounced in the tunica media of cortical arterioles than meningeal arteries. Patients carrying point mutations at residues 22 (E22Q) and 21 (A21G) of Aβ show severe CAA with various degrees of brain parenchymal Aβ deposition. The purpose of this study was to investigate the effects of 2 mutant E22Q- and A21G-Aβ peptides on MV and aortic SMC.

Methods
—SMC were isolated from human cerebral MV and aorta. Cell morphology, viability, and proliferation as parameters of Aβ toxicity were investigated after 3 days of peptide treatment by trypan blue exclusion and [
3
H]thymidine incorporation.

Results
—E22Q-Aβ induced significant decreased cellular proliferation and viability, as well as obvious degeneration of both MV and aortic SMC. A21G-Aβ and wild-type Aβ did not cause significant toxicity, as judged by cell morphology, viability, or cell proliferation, on either type of SMC.

Conclusions
—E22Q-Aβ induced greater toxicity in all parameters than A21G-Aβ and wild-type Aβ with respect to both MV and aortic SMC. A21G-Aβ did not show a significant toxic effect on MV and aortic SMC. This differential effect may be linked to cell type–specific processing and metabolism of mutant forms of Aβ. Mutations in amyloid precursor protein may lead to CAA by different pathogenetic mechanisms or share an unknown property that distinguishes them from wild-type Aβ.
Functional and Neuroanatomic Correlations in Poststroke Depression
Authors: Singh Anu , Black Sandra E. , Herrmann Nathan , Leibovitch Farrell S. , Ebert Patricia L. , Lawrence Joanne , Szalai John P.
Published: June 2011

Background and Purpose
—The purpose of our study was to determine the functional and neuroanatomic correlates of poststroke depressive symptoms.

Methods
—Patients with consecutive admissions to a regional stroke center for new-onset unilateral hemispheric stroke who met World Health Organization and National Institute of Neurological and Communicative Disorders and Stroke criteria were eligible for inclusion in a longitudinal study. Acutely, patients underwent CT scanning, and at 3 months and 1 year after stroke, depressive symptoms were assessed by using both the Montgomery-Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale. The Functional Independence Measure (FIM) served as an indication of functional outcome and was obtained at 1 month, 3 months, and 1 year after stroke, along with other demographic information. The Talairach and Tournoux stereotactic atlas was used for the primary determination of CT lesion localization. Lesion proximity to the anterior frontal pole was also measured.

Results
—Eighty-one patients participated in the longitudinal study. Stepwise linear regression analyses generated a highly significant model (F
3,76
=9.8,
R
2
=28%,
P
<0.0005), with lower 1-month total FIM scores, living at home, and damage to the inferior frontal region predicting higher depression scores at 3 months. Similarly, lower 3-month total FIM scores correlated with higher 3-month depression scores, and lower 1-year total FIM scores correlated with higher 1-year depression scores.

Conclusions
—Functional measures correlated with poststroke depression across time and, together with neuroanatomic measures, predicted depressive symptoms longitudinally. Although inferior frontal lesion location, irrespective of side, appeared to play a role as a risk factor in this study, the degree of functional dependence after stroke imparted the greatest risk.
A Pilot Study of Somatotopic Mapping After Cortical Infarct
Authors: Cramer Steven C. , Moore Christopher I. , Finklestein Seth P. , Rosen Bruce R.
Published: June 2011

Background and Purpose—
Animal studies have described remodeling of sensory and motor representational maps after cortical infarct. These changes may contribute to return of function after stroke.

Methods—
Functional MRI was used to compare sensory and motor maps obtained in 35 normal control subjects with results from 2 patients with good recovery 6 months after a cortical stroke.

Results—
During finger tapping in controls, precentral gyrus activation exceeded or matched postcentral gyrus activation in 40 of 42 cases. Patient 1 had a small infarct limited to precentral gyrus. Finger tapping activated only postcentral gyrus, a pattern not seen in any control subject. During tactile stimulation of a finger or hand in controls, postcentral gyrus activation exceeded or matched precentral gyrus activation in 11 of 14 cases. Patient 2 had a small infarct limited to postcentral gyrus and superior parietal lobule. Tactile stimulation of the finger activated only precentral gyrus, a pattern not seen in any control. In both patients, activation during pectoralis contraction was medial to the site activated during finger tapping.

Conclusions—
Results during finger tapping (patient 1) and finger stimulation (patient 2) may reflect amplification of a preserved component of normal sensorimotor function, a shift in the cortical site of finger representation, or both. Cortical map reorganization along the infarct rim may be an important contributor to recovery of motor and sensory function after stroke. Functional MRI is useful for assessing motor and sensory representational maps.
Longer Duration of Cardiopulmonary Bypass Is Associated With Greater Numbers of Cerebral Microemboli
Authors: Brown William R. , Moody Dixon M. , Challa Venkata R. , Stump David A. , Hammon John W.
Published: June 2011

Background and Purpose
—Many patients who undergo cardiac surgery assisted with cardiopulmonary bypass (CPB) experience cerebral injury, and microemboli are thought to play a role. Because an increased duration of CPB is associated with an increased risk of subsequent cerebral dysfunction, we investigated whether cerebral microemboli were also more numerous with a longer duration of CPB.

Methods
—Brain specimens were obtained from 36 patients who died within 3 weeks after CPB. Specimens were embedded in celloidin, sectioned 100 μm thick, and stained for endogenous alkaline phosphatase, which outlines arterioles and capillaries. In such preparations, emboli can be seen as swellings in the vessels. Cerebral microemboli were counted in equal areas and scored as small, medium, or large to estimate the embolic load (volume of emboli).

Results
—With increasing survival time after CPB, the embolic load declined (
P
<0.0001). (Lipid emboli are known to pump slowly through the brain.) Also with increasing time after CPB, the percentage of large and medium emboli became lower (
P
=0.0034). This decline is consistent with the concept that the emboli break into smaller globules as they pass through the capillary network. A longer duration of CPB was associated with increased embolic load (
P
=0.0026). For each 1-hour increase in the duration of CPB, the embolic load increased by 90.5%.

Conclusions
—Thousands of microemboli were found in the brains of patients soon after CPB, and an increasing duration of CPB was associated with an increasing embolic load.
Adverse Outcomes and Predictors of Underuse of Antithrombotic Therapy in Medicare Beneficiaries With Chronic Atrial Fibrillation
Authors: Gage Brian F. , Boechler Michael , Doggette Amy L. , Fortune Gary , Flaker Greg C. , Rich Michael W. , Radford Martha J.
Published: June 2011

Background and Purpose
—Antithrombotic therapy can prevent strokes and transient ischemic attacks (TIAs) in carefully selected patients who have chronic nonvalvular atrial fibrillation (NVAF). Our objectives were 3-fold: to document the use of warfarin and aspirin therapy in Missouri Medicare beneficiaries with chronic NVAF; to identify factors associated with warfarin and aspirin underuse; and to determine the association between prescription of warfarin and aspirin at hospital discharge and adverse outcomes in this elderly, frail population.

Methods
—We linked chart reviews from all Missouri hospitals to Medicare claims data from 1993 to 1996. From chart reviews, we documented Medicare beneficiaries’ demographic factors, comorbid conditions, and antithrombotic therapy prescribed at the time of hospital discharge. From Medicare claims, we determined the date of outcomes—death from any cause or hospitalization for an ischemic event (a stroke, a TIA, or a myocardial infarction).

Results
—Only 328 (55%) of the 597 Medicare beneficiaries were prescribed antithrombotic therapy at hospital discharge: 34% received warfarin and 21% received aspirin. Advanced age, female gender, and rural residency predicted underuse of antithrombotic therapy. After controlling for these factors, as well as stroke risk factors and contraindications to anticoagulation, the prescription of warfarin was associated with a 24% relative risk reduction (RRR) in adverse outcomes (
P
=0.003). Prescription of aspirin was associated with a nonsignificant 5% RRR in these events (
P
=0.56).

Conclusions
—The underuse of antithrombotic therapy in Medicare beneficiaries who have NVAF is associated with measurable adverse outcomes. The benefit of warfarin therapy may extend to frail, elderly patients, a group that was excluded from randomized controlled trials. The role of antiplatelet therapy in this population deserves further study because many of these patients have relative contraindications to warfarin.
Prevalence of Stroke
Authors: Nicoletti A. , Sofia V. , Giuffrida S. , Bartoloni A. , Bartalesi F. , Bartolo M. L. Lo , Fermo S. Lo , Cocuzza V. , Gamboa H. , Salazar E. , Reggio A.
Published: June 2011

Background and Purpose
—We carried out a door-to-door survey in rural areas of the Cordillera Province, Santa Cruz Department, Bolivia. A cluster sample of 10 124 inhabitants was selected, and 9955 subjects were screened. The aim was to determine the prevalence of the most common neurological diseases (epilepsy, stroke, parkinsonism, and peripheral neuropathy) in this population.

Methods
—We used a modified version of the World Health Organization screening instrument. On screening we found that 1130 subjects tested positive, and 1027 underwent a complete neurological examination. According to the World Health Organization guidelines, we defined stroke as “rapidly developing clinical signs of focal (or global) disturbance of cerebral functions, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin.” We considered only first stroke and excluded a possible stroke.

Results
—We found 16 subjects (cases) who had experienced 1 complete stroke on prevalent day (November 1, 1994). The crude prevalence of stroke was 174/100 000 (322/100 000 age-adjusted to the world standard population) and 663/100 000 in subjects aged ≥35 years. Prevalence was >2-fold higher in men than in women (247/100 000 and 99/100 000, respectively) and increased rapidly with age. Seven cases were hospitalized and received specific treatment.

Conclusions
—Our crude prevalence is lower compared with rates from developed countries, probably because of a high case fatality rate. Our findings are comparable with those reported from other surveys carried out in rural developing countries.
Deterioration Following Spontaneous Improvement
Authors: Alexandrov Andrei V. , Felberg Robert A. , Demchuk Andrew M. , Christou Ioannis , Burgin W. Scott , Malkoff Marc , Wojner Anne W. , Grotta James C.
Published: June 2011

Background and Purpose
—Some stroke patients will deteriorate following improvement (DFI), but the cause of such fluctuation is often unclear. While resolution of neurological deficits is usually related to spontaneous recanalization or restoration of collateral flow, vascular imaging in patients with DFI has not been well characterized.

Methods
—We prospectively studied patients who presented with a focal neurological deficit that resolved spontaneously within 6 hours of symptom onset. Patients were evaluated with bedside transcranial Doppler (TCD). Digital subtraction angiography (DSA), computed tomographic angiography (CTA), or magnetic resonance angiography (MRA) were performed when feasible. DFI was defined as subsequent worsening of the neurological deficit by ≥4 National Institutes of Health Stroke Scale points within 24 hours of the initial symptom onset.

Results
—We studied 50 consecutive patients presenting at 165±96 minutes from symptom onset. Mean age was 61±14 years; 50% were females. All patients had TCD at the time of presentation, and 68% had subsequent angiographic examinations (DSA 10%, CTA 4%, and MRA 44%). Overall, large-vessel occlusion on TCD was found in 16% of patients (n=8); stenosis was found in 18% (n=9); 54% (n=27) had normal studies; and 6 patients (12%) had no temporal windows. DFI occurred in 16% (n=8) of the 50 patients: in 62% of patients with TCD and angiographic evidence of occlusion, in 22% with stenosis, and in 4% with normal vascular studies (
P
<0.001, Φ=0.523, χ
2
=12.05). DFI occurred in 31% of patients with large-vessel atherosclerosis, 23% with cardioembolism, and 9% with small-vessel disease when stroke mechanisms were determined within 2 to 3 days after admission (
P
=0.2, NS).

Conclusions
—DFI is strongly associated with the presence of large-vessel occlusion or stenosis of either atherosclerotic or embolic origin. Normal vascular studies and lacunar events were associated with stable spontaneous resolution without subsequent fluctuation. Urgent vascular evaluation may help identify patients with resolving deficits and vascular lesions who may be candidates for new therapies to prevent subsequent deterioration.
Solitary Tract Nuclei in Acute Heart Failure
Authors: Raffaele De Caro  , Parenti Anna , Montisci Massimo , Guidolin Diego , Macchi Veronica
Published: June 2011

Background and Purpose
—Symmetrical necrosis of the brain stem nuclei has been described as a consequence of severe transitory cerebral hypoxia mainly in neonates or young adults who experienced an episode of acute ischemia due to transitory acute heart failure. We report selective bilateral lesions of the solitary tract nuclei in 5 adults with short survival intervals after acute heart failure.

Methods
—In 5 patients who died due to cardiovascular pathology, histological examination was performed on multiple samples of cerebral hemispheres, on transverse sections of the midbrain and pons, and on transverse serial sections of the medulla stained with hematoxylin-eosin, Klüver-Barrera, and Luxol fast blue. The 3-dimensional reconstruction of the extension and topography of the medullary lesions was obtained with computed image analysis.

Results—
In 4 subjects who died soon after an episode of acute heart failure (range of survival 10 hours to 2 days), the dorsal portion of the solitary tract nuclei showed an eosinophilic roundish aspect bilaterally. In their context, the neurons showed changes characteristic of ischemic coagulation necrosis. In a fifth patient, a 32-year-old man who died 15 days after an episode of cardiac arrest, 2 circumscribed symmetrical infarcts with macrophagic and astrocytic reactions were found at the same level. The topography of the lesions and the inflammatory reaction and gliosis of patient 5 suggest that the findings in the other 4 patients correspond to initial features of selective lesions of the solitary tract nuclei after acute heart failure: the short interval of survival prevented the evolution of the reactive process. The nucleus is localized at the watershed zone between the terminal branches of the medullary collateral vessels of the vertebral arteries, thus representing the last meadow in the case of sudden fall of the systemic blood flow due to acute heart failure. The absence of lesions of other medullary and pontine nuclei accounts for a selective vulnerability of the neurons of the solitary tract nuclei, and the selective dendritic lesions suggest an excitotoxic component to ischemic cell death.

Conclusions
—The commonly accepted resistance of the medullary centers to ischemic hypoxia in adults apparently could be due to the rapidity of death, which prevents the evolution of lesions that can be diagnosed. In addition, minor lesions in the medullary tegmentum after acute heart failure could play a role in the prevention of the resumption of autonomous cardiac and respiratory functions despite life-saving procedures.
Cervene (Nalmefene) in Acute Ischemic Stroke
Authors: Clark Wayne M. , Raps Eric C. , Tong David C. , Kelly Roger E.
Published: June 2011

Background and Purpose
—The goals of the present study were to assess the efficacy and safety of nalmefene (Cervene) in patients with acute (≤6 hours) ischemic stroke and to investigate the safety of combined recombinant tissue plasminogen activator and nalmefene in a separate subset of patients. Nalmefene, an opioid antagonist with relative κ receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. Results from an earlier phase II study in patients with acute ischemic stroke suggested that nalmefene was safe and tolerable and may be effective for patients <70 years old.

Methods
—This investigation was a phase III, placebo-controlled, double-blind, randomized study of a 24-hour infusion of nalmefene. Patients with acute ischemic stroke who had an onset of symptoms within 6 hours and a baseline score of ≥4 on the NIH Stroke Scale were randomized to receive either 60 mg nalmefene administered as a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75 hours or placebo. The primary efficacy outcome was the proportion of patients achieving a score of ≥60 on the Barthel Index and a rating of “moderate disability” or better on the Glasgow Outcome Scale at 12 weeks. Assessments were performed at baseline (predose), hours 12 and 24, days 2 and 7, and week 12.

Results
—A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old.

Conclusions
—Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours.
Anticardiolipin Antibodies Are Not an Independent Risk Factor for Stroke
Authors: Ahmed Ejaz , Stegmayr Birgitta , Trifunovic Jasmina , Weinehall Lars , Hallmans Göran , Lefvert Ann Kari
Published: June 2011

Background and Purpose
—Anticardiolipin antibodies (aCL) have been proposed to be an independent risk factor for stroke. To test this hypothesis, a nested case-control study was performed to compare aCL with the other known risk factors for stroke.

Methods
—Within the framework of the World Health Organization Multinational
Moni
toring of Trends and Determinants in
Ca
rdiovascular Disease (MONICA) project and the Västerbotten Intervention Program (VIP) health survey, 44 725 men and women were enrolled and followed up from January 1, 1985, through August 31, 1996. Individuals free from cardiovascular events were followed up, and 123 developed stroke (on average, 34.1 months after blood sampling; 21 cerebral hemorrhage and 102 cerebral infarction); they were compared with 241 age- and sex-matched control subjects from the same population. ELISA was used for the analysis of IgG, IgM, and IgA aCL.

Results
—IgM-aCL were present in 11.4% of patients (14/123) who developed stroke and in 4.1% of individuals (10/241) who remained healthy (
P
=0.013, OR 2.97, 95% CI 1.28 to 6.89). The OR for the levels of IgM-aCL was 1.34 (
P
=0.01, 95% CI 1.07 to 1.68) without adjustment for other risk factors and 1.24 when adjusted for hypertension, diabetes mellitus, cigarette smoking, and use of smokeless tobacco (
P
=0.077, 95% CI 0.98 to 1.56). There was no difference between patients and controls for the prevalence or level of IgG-aCL and IgA-aCL and also no difference between patients with cerebral hemorrhage and cerebral infarction for the prevalence of all 3 isotypes of aCL.

Conclusions
—We conclude that aCL are associated with future stroke but do not constitute an independent risk factor.
Chronic Motor Dysfunction After Stroke
Authors: Cauraugh James , Light Kathye , Kim Sangbum , Thigpen Mary , Behrman Andrea
Published: June 2011

Background and Purpose
—After stroke, many individuals have chronic unilateral motor dysfunction in the upper extremity that severely limits their functional movement control. The purpose of this study was to determine the effect of electromyography-triggered neuromuscular electrical stimulation on the wrist and finger extension muscles in individuals who had a stroke ≥1 year earlier.

Methods
—Eleven individuals volunteered to participate and were randomly assigned to either the electromyography-triggered neuromuscular stimulation experimental group (7 subjects) or the control group (4 subjects). After completing a pretest involving 5 motor capability tests, the poststroke subjects completed 12 treatment sessions (30 minutes each) according to group assignments. Once the control subjects completed 12 sessions attempting wrist and finger extension without any external assistance and were posttested, they were then given 12 sessions of the rehabilitation treatment.

Results
—The Box and Block test and the force-generation task (sustained muscular contraction) revealed significant findings (
P
<0.05). The experimental group moved significantly more blocks and displayed a higher isometric force impulse after the rehabilitation treatment.

Conclusions
—Two lines of evidence clearly support the use of the electromyography-triggered neuromuscular electrical stimulation treatment to rehabilitate wrist and finger extension movements of hemiparetic individuals ≥1 year after stroke. The treatment program decreased motor dysfunction and improved the motor capabilities in this group of poststroke individuals.
Improved Functional Outcome in Patients With Hemorrhagic Stroke in Putamen and Thalamus Compared With Those With Stroke Restricted to the Putamen or Thalamus
Authors: Miyai Ichiro , Suzuki Tsunehiko , Kang Jin , Volpe Bruce T.
Published: June 2011

Background and Purpose
—We analyzed the effect of late intensive inpatient rehabilitation on the functional outcome of patients with subcortical hemorrhagic stroke.

Methods
—Patients who were nonambulatory with hemorrhagic stroke in the internal capsule and putamen (n=55), the thalamus (n=24), or all 3 regions (n=15) underwent intensive inpatient rehabilitation. Patients with surgical intervention or an episode of ventricular hemorrhage were excluded. Lesion location was evaluated by MRI 4 months after the ictus.

Results
—Demographic data, initial disability, and impairment measures were comparable in the 3 groups. Functional outcome demonstrated significant differences in mobility subscores (
P
<0.05) of the Functional Independence Measure such that patients with injury in the 3 regions were more likely to ambulate independently than were patients in the other groups. Lesion location data demonstrated that the ventral anterior nucleus of the thalamus was always spared; the ventral posterior (lateral and medial) nucleus was always damaged, and the ventral lateral nucleus was frequently damaged. Putaminal damage always included the postcommissural area. In addition, the entire posterior half limb of the internal capsule was always damaged.

Conclusions
—Subcortical lesions to multiple structures in the basal ganglia–thalamocortical motor circuits permitted enhanced motor recovery. Lesion location predicted the level of independent ambulation and the rate of recovery in patients with stroke who were nonambulatory before neurorehabilitation therapy.
Mechanism of ATP-Induced [Ca
2+
]
i
Mobilization in Rat Basilar Smooth Muscle Cells
Authors: Aoki Kazuya , Zubkov Alexander Y. , Parent Andrew D. , Zhang John H.
Published: June 2011

Background and Purpose
—We have previously reported that extracellular ATP activates P
2u
receptors and increases intracellular free Ca
2+
([Ca
2+
]
i
) by G protein/phospholipase C/inositol 1,4,5-triphosphate pathways in cerebral artery smooth muscle cells. However, the possible contribution of other signaling pathways remains unclear. This study was undertaken to investigate the role of protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) in mediating ATP-induced Ca
2+
mobilization in rat basilar artery smooth muscle cells (RBASMCs).

Methods
—RBASMCs were freshly isolated, and [Ca
2+
]
i
was monitored by fura 2 microfluorimetry. MAPK phosphorylation was studied by the Western blot technique.

Results
—ATP produced a biphasic [Ca
2+
]
i
response, which consists of releasing Ca
2+
from internal stores and influx from extracellular space. PTK inhibitors tyrphostin 51 and genistein inhibited [Ca
2+
]
i
response to ATP. Tyrphostin A1, an inactive analogue of tyrphostins, failed to reduce the ATP-induced response. MAPK kinase inhibitor PD98059, but not U0126, reduced the ATP-induced [Ca
2+
]
i
response. Phosphatidylinositol 3-kinase (PI3-K) tyrosine kinase inhibitor wortmannin, but not janus tyrosine kinase (JAK2) inhibitor AG490, partially inhibited the [Ca
2+
]
i
response induced by ATP. In addition, ATP enhanced MAPK phosphorylation in a concentration- and time-dependent manner, and genistein, tyrphostin 51, PD98059, and U0126 inhibited MAPK phosphorylation.

Conclusions
—Extracellular ATP produced [Ca
2+
]
i
elevation and MAPK phosphorylation in RBASMCs, and the effect was regulated by PTK. The role of MAPK in ATP-induced [Ca
2+
]
i
elevation is not clear. PI3-K tyrosine kinase and JAK2 tyrosine kinase may not play an important role in the ATP-induced [Ca
2+
]
i
response in RBASMCs.
Mild and Moderate Hypothermia (α-Stat) Do Not Impair the Coupling Between Local Cerebral Blood Flow and Metabolism in Rats
Authors: Krafft Peter , Frietsch Thomas , Lenz Christian , Piepgras Axel , Kuschinsky Wolfgang , Waschke Klaus F.
Published: June 2011

Background and Purpose
—The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU).

Methods
—Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal Pa
co
2
(α-stat). Pericranial temperature was maintained normothermic (37.5°C, n=12) or was reduced to 35°C (n=12) or 32°C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals.

Results
—Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%,
P
<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (
P
<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%,
P
<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (
r
=0.93), anesthetized (
r
=0.92), and both hypothermic groups (35°C
r
=0.96, 32°C
r
=0.96,
P
<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/μmol during anesthesia (
P
<0.05), remained at 2.4 mL/μmol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/μmol,
P
<0.05).

Conclusions
—Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.
Delayed Systemic Administration of PACAP38 Is Neuroprotective in Transient Middle Cerebral Artery Occlusion in the Rat
Authors: Reglodi Dora , Somogyvari-Vigh Aniko , Vigh Sandor , Kozicz Tamas , Arimura Akira
Published: June 2011

Background and Purpose
—Many substances have been shown to reduce brain damage in models of stroke, but mainly when given either before or shortly after the onset of ischemia. Delayed systemic administration of pituitary adenylate cyclase–activating polypeptide (PACAP) has been shown to attenuate the neuronal damage in the hippocampus in a model of global ischemia in rats. The present study examined the neuroprotective action of delayed systemic administration of PACAP38 in a model of transient focal ischemia produced by middle cerebral artery occlusion (MCAO) in rats.

Methods
—We administered PACAP38 as an intravenous bolus (20 nmol/kg body wt) followed by an intravenous infusion for 48 hours using a micro-osmotic pump at a rate of 160 pmol/μL per hour, beginning 4, 8, or 12 hours after a 2-hour transient MCAO using a filament model. The size of the infarct was determined by examining 2-mm-thick brain sections stained with triphenyltetrazolium chloride, followed by image analysis. Control animals received intravenously 0.1% bovine serum albumin in 0.9% saline as a bolus and infusion at the same time intervals.

Results
—The administration of PACAP38 beginning 4 hours after MCAO significantly reduced the infarct size by 50.88%. Treatment with PACAP38 starting 8 or 12 hours after the onset of ischemia did not result in a significant reduction of the infarct size, although infarct volumes tended to be smaller than in the control groups.

Conclusions
—Systemic administration of PACAP38 should be clinically useful for reducing brain damage resulting from stroke even when administration is delayed for several hours.
A Short Screening Instrument for Poststroke Dementia
Authors: de Koning Inge , Dippel Diederik W.J. , van Kooten Fop , Koudstaal Peter J.
Published: June 2011

Background and Purpose
—The CAMCOG is a feasible cognitive screening instrument for dementia in patients with a recent stroke. A major disadvantage of the CAMCOG, however, is its lengthy and relatively complex administration for screening purposes. We therefore developed the Rotterdam CAMCOG (R-CAMCOG), based on the original version. Our aim was to reduce the estimated administration time to 15 minutes or less and to retain or perhaps even improve its diagnostic accuracy.

Methods
—We analyzed the item scores on the CAMCOG of 300 consecutive stroke patients, after exclusion of patients with a severe aphasia or lowered consciousness level, who were entered in the Rotterdam Stroke Databank. The diagnosis of dementia was made independent of the R-CAMCOG score, on the basis of clinical examination and neuropsychological test results. The R-CAMCOG was constructed in 3 steps. First, items with floor and ceiling effects were removed. Next, subscales with no additional diagnostic value were excluded. Finally, we removed items that did not contribute to the homogeneity of the subscales. The diagnostic accuracy of the R-CAMCOG and the original CAMCOG was determined by means of the area under the receiver operating characteristic (ROC) curve.

Results
—In the 3 steps, the number of items was reduced from 59 to 25, divided over the subscales orientation, memory (recent, remote, and learning), perception, and abstraction. The subscale orientation did not reach significance in a logistic regression model but was included in the R-CAMCOG because of its high face validity in dementia screening. Internal validation with ROC analysis suggests that the R-CAMCOG and the CAMCOG are equally accurate in screening for poststroke dementia (area under the curve was 0.95 for both tests).

Conclusions
—The R-CAMCOG has overcome the disadvantages of the original CAMCOG. It is a promising, short, and easy-to-administer screening instrument for poststroke dementia. It seems to be sufficiently accurate for this purpose, but the test has yet to be validated in a separate, independent study.
Vasodilatory Response of Border Zones to Acetazolamide Before and After Endarterectomy
Authors: Wiart Marlène , Berthezène Yves , Adeleine Patrice , Feugier Patrick , Trouillas Paul , Froment Jean-Claude , Nighoghossian Norbert
Published: June 2011

Background and Purpose
—The importance of hemodynamic changes related to a high-grade internal carotid artery (ICA) stenosis remains a matter of controversy. Areas between the vascular territories of major cerebral arteries, namely, the border zones, may be selectively vulnerable to hemodynamic alteration. The aim of this study was to search for any hemodynamic impact of carotid endarterectomy (CEA) on vasodilatory response, in particular, within the border zones, by means of multislice dynamic susceptibility contrast MRI.

Methods
—Thirteen patients with a high-grade unilateral ICA stenosis (>80%) were examined. Relative regional cerebral blood volume (rrCBV) was determined separately for white matter, gray matter, and anterior and posterior border zones by the acetazolamide test. A vasomotor reactivity index was evaluated from the rrCBV values. Values from the ipsilateral hemisphere were compared with contralateral ones, before and after CEA.

Results
—Before CEA, rrCBV values in the anterior border zones were significantly (
P
<0.05) higher in the ipsilateral hemisphere than in the contralateral hemisphere. A decrease in vasomotor reactivity indexes was also observed in the lesion side, but the difference from the contralateral side was not statistically significant. In posterior border zones, no differences in rrCBV or vasomotor reactivity were found between the ipsilateral and the contralateral hemispheres. After CEA, the rrCBV asymmetry in the anterior border zones cleared.

Conclusions
—High-grade ICA stenosis with efficient primary collateral pathways may have an early limited hemodynamic impact within border-zone areas. The favorable course of these abnormalities after surgery suggests an additional benefit of CEA at this stage.
Impact of Cerebral Microcirculatory Changes on Cerebral Blood Flow During Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Ohkuma Hiroki , Manabe Hiroshi , Tanaka Masahiko , Suzuki Shigeharu
Published: June 2011

Background and Purpose
—Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial and uncertain. The aim of this study was to investigate the changes of cerebral microcirculation during cerebral vasospasm and to clarify the roles of microcirculatory disturbances in cerebral ischemia by measuring cerebral circulation time (CCT) and regional cerebral blood flow (rCBF).

Methods
—In 24 cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital subtraction angiography (DSA) were performed on the same day between 5 and 7 days after SAH and/or within 4 hours after the onset of delayed ischemic neurological deficits. CCT was obtained by analyzing the time-density curve of the contrast media on DSA images and was divided into proximal CCT, which was the circulation time through the extraparenchymal large arteries, and peripheral CCT, which was the circulation time through the intraparenchymal small vessels. They were analyzed in association with rCBF and angiographic vasospasm.

Results
—Severe angiographic vasospasm statistically decreased rCBF, and correlation between the degree of angiographic vasospasm and rCBF was seen (
r
=0.429,
P
=0.0006). Peripheral CCT showed strong inverse correlation with rCBF (
r
=−0.767,
P
<0.0001). Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT was clearly associated with decreased rCBF.

Conclusions
—In addition to the marked luminal narrowing of large arteries detected as severe angiographic vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected cerebral ischemia during cerebral vasospasm. These results suggested that impaired autoregulatory vasodilation or decreased luminal caliber in intraparenchymal vessels may take part in cerebral ischemia during cerebral vasospasm.
Detection of Early CT Signs of >1/3 Middle Cerebral Artery Infarctions
Authors: Kalafut Mary A. , Schriger David L. , Saver Jeffrey L. , Starkman Sidney
Published: June 2011

Background and Purpose
—This study had 2 goals: (1) to assess interrater reliability of academic neuroradiologists when classifying acute infarction by CT scan as >1/3 middle cerebral artery (MCA) involvement, <1/3 MCA involvement, or no infarction and (2) to determine the sensitivity of physicians potentially involved in acute stroke treatment in detecting >1/3 MCA acute infarctions. Studies of tissue plasminogen activator show an association between early signs of major infarction and poor outcome. The American Academy of Neurology and the American Heart Association recommend avoiding thrombolysis if early signs of major infarction are present.

Methods
—We presented 25 scans (normals, acute infarctions, and old infarctions) to 3 academic neuroradiologists. A scoring sheet based on Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS)/CT Summit criteria was used to determine >1/3 MCA territory involvement. Nine of the 25 scans were presented again to assess intrarater reliability. We recalculated results of our previous study in which physicians interpreted infarction scans, now designating the scans as >1/3 MCA, <1/3 MCA, or normal, as determined by the neuroradiologists.

Results
—All 3 neuroradiologists agreed on no infarction, <1/3 MCA, and >1/3 MCA on 64% of the scans. Neuroradiologist test-retest agreement was 96% for >1/3 MCA territory. Overall sensitivity for emergency physicians, neurologists, and general radiologists for detecting the presence of infarction in scans rated as >1/3 MCA was 78%.

Conclusions
—Neuroradiologists can achieve moderate agreement in detecting >1/3 MCA infarction. The emergency physicians, neurologists, and general radiologists tested were reasonably skilled at detecting >1/3 MCA acute infarction. However, their performance did not reliably identify all patients who have early CT infarct signs that place them at increased risk for cerebral hemorrhage after thrombolytic therapy.
Contribution of Microglia/Macrophages to Expansion of Infarction and Response of Oligodendrocytes After Focal Cerebral Ischemia in Rats
Authors: Mabuchi Takuma , Kitagawa Kazuo , Ohtsuki Toshiho , Kuwabara Keisuke , Yagita Yoshiki , Yanagihara Takehiko , Hori Masatsugu , Matsumoto Masayasu
Published: June 2011

Background and Purpose
—The purpose of this study was (1) to examine the contribution of microglia and macrophages with their interleukin-1β production and (2) to assess the vulnerability and response of oligodendrocytes in cerebral infarction.

Methods
—Male Wistar rats were subjected to permanent occlusion of the left middle cerebral artery. Expansion of ischemic infarction and response of oligodendrocytes were investigated together with accumulation of inflammatory cells, production of interleukin-1β, and disruption of the blood-brain barrier. Apoptotic cell death was inferred from fragmented DNA and the expression of proapoptotic Bax protein.

Results
—During expansion of infarction, amoeboid microglia and extravasation of serum albumin were observed not only in the infarcted area but also in the adjacent surviving area, whereas macrophages accumulated along the boundary and granulocytes migrated into the center of the infarction. Both amoeboid microglia and macrophages produced interleukin-1β, an inflammatory cytokine, during an early ischemic period. Furthermore, macrophages within the infarcted tissue expressed Bax protein and subsequently showed fragmented nuclear DNA. Oligodendrocytes were detected in the infarcted area even after 24 hours following middle cerebral artery occlusion, but they subsequently developed fragmented DNA. A week after onset of ischemia, oligodendrocytes were found to be accumulated in the intact area bordered with the infarct together with reactive astrocytes.

Conclusions
—-Our results suggest the importance of amoeboid microglia, macrophages, and their interleukin-1β production in gradual expansion of cerebral infarction. Resident oligodendrocytes may be resistant to ischemic insults, and oligodendrocytes accumulated at the border of the infarction may participate in tissue repair after cerebral infarction.