bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Lesion Location on Upper Limb Motor Recovery After Stroke
Authors: Shelton Fátima de N. A. P. , Reding Michael J.
Published: June 2011

Background and Purpose
—The purpose of this study was to assess the effects of stroke involvement of primary and secondary hemispheric motor systems and corticofugal tracts on arm and hand recovery.

Methods
—Forty-one patients participating in an inpatient stroke rehabilitation database, admitted 17±2 (SEM) days after initial unilateral hemispheric ischemic stroke, with neuroimaging studies performed >48 hours after stroke and with minimal upper limb (UL) movement (admission Fugl-Meyer UL motor scores ≤9; normal score, 58) were studied. Patients were divided into 3 groups according to their UL discharge Fugl-Meyer score: 0 to 9, no/poor recovery; 10 to 18, well-defined flexion-extension synergies; and >18, synergies+isolated movements. Lesions affecting the following structures were recorded: primary motor cortex, premotor area, supplementary motor area, anterior half of the middle third of corona radiata (secondary motor efferents), posterior half of the middle third of corona radiata (primary motor efferents), genu, anterior and posterior limbs of the internal capsule (PLIC), basal ganglia, and thalamus. χ
2
Analysis and ANOVA were used to study the significance of stroke location on UL motor recovery.

Results
—The effect of involvement of primary, premotor, or supplementary motor areas on motor recovery did not reach statistical significance. Patients with purely cortical stroke were likely to recover UL isolated movement (3 of 4) compared with purely subcortical (1 of 17) or mixed cortical-subcortical stroke location (2 of 20) (
P
=0.009). Of those with cortical, subcortical, or mixed cortical plus subcortical lesions sparing the PLIC, 5 of 13 recovered isolated UL movement (
P
=0.01). Only 1 of 28 patients with involvement of the PLIC plus adjacent corona radiata, basal ganglia, or thalamus recovered isolated UL movement (
P
=0.01). Patients with small lacunar strokes affecting only the PLIC did not have sufficient motor deficits 2 weeks after stroke to meet inclusion criteria.

Conclusions
—The probability of recovery of isolated UL movement decreases progressively with lesion location as follows: cortex, corona radiata, and PLIC. This is consistent with our current understanding of redundant cortical motor representation and convergence of corticofugal motor efferents as they pass through the corona radiata to the PLIC.
Quantitative Analysis of Gene Expressions Related to Inflammation in Canine Spastic Artery After Subarachnoid Hemorrhage
Authors: Aihara Yasuo , Kasuya Hidetoshi , Onda Hideaki , Hori Tomokatsu , Takeda Jun
Published: June 2011

Background and Purpose
—The possible role of inflammatory reaction of the cerebral artery in the pathogenesis of cerebral vasospasm has been noted in recent studies. We quantitatively measured the levels of expression of genes related to inflammation in the spastic artery in a canine double-hemorrhage model.

Methods
—Twenty dogs were assigned to 4 groups: group D0, control; group D2, dogs killed 2 days after cisternal injection of blood; group D7, dogs given double cisternal injections of blood and killed 7 days after the first injection; and group D14. Angiography was performed twice: on the first day and before the animals were killed. Total RNA was extracted from the basilar artery. The expressions of interleukin (IL)-1α, IL-6, IL-8, IL-10, tumor necrosis factor-α, E-secretin, fibronectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule-1, transforming growth factor-β, basic fibroblast growth factor, and collagen types I, III, and IV were examined with TaqMan real-time quantitative reverse transcription–polymerase chain reaction.

Results
—Prolonged arterial narrowing peaking on 7 day was observed. There was a significant difference in vessel caliber between D0, D2, D7, and D14 groups (
P
<0.0001). There were significant differences in mRNA expression in the basilar artery for IL-1α, IL-6, IL-8, ICAM-1, and collagen type I between D0, D2, D7, and D14 groups (
P
=0.0079, 0.0196, 0.0040, 0.0017, and <0.0001, respectively). The average level of mRNA was highest in D7 for IL-1α, IL-6, IL-8, and ICAM-1 (17-, 16-, 131-, and 1.7-fold compared with those of D0, respectively) and in D14 for collagen type I (10.9-fold).

Conclusions
—Increased expression of genes related to inflammation in the spastic artery suggests that inflammatory reaction of the cerebral artery is associated with sustained contraction.
Involuntary Movements After Anterior Cerebral Artery Territory Infarction
Authors: Kim Jong S.
Published: June 2011

Background and Purpose
—Patients with anterior cerebral artery territory infarction presenting with involuntary movements have rarely been described in the literature.

Case Descriptions
—The author reports 9 such patients: 3 with asterixis, 5 with hemiparkinsonism (tremor, rigidity, hypokinesia), and 1 with both. Asterixis developed in the acute stage in patients with minimal arm weakness, whereas parkinsonism was usually observed after the motor dysfunction improved in patients with initially severe limb weakness. Asterixis correlated with small lesions preferentially involving the prefrontal area; parkinsonism is related to relatively large lesions involving the supplementary motor area.

Conclusions
—Anterior cerebral artery territory infarction should be included in the differential diagnosis of asterixis and hemiparkinsonism.
Does the Organization of Postacute Stroke Care Really Matter?
Authors: Langhorne Peter , Duncan Pamela
Published: June 2011

Background and Purpose
—Postacute rehabilitation stroke services represent a large component of stroke care. In the United States and elsewhere, major changes in the organization and funding of these services are limiting patient access to organized inpatient multidisciplinary care. We conducted a systematic review to evaluate the effectiveness of such services.

Summary of Review
—We defined our intervention as organized inpatient multidisciplinary rehabilitation commencing at least 1 week after stroke and sought randomized trials that compared this model of care with an alternative. The analysis was stratified by the particular service characteristics. We identified a heterogeneous group of 9 trials (6 of stroke rehabilitation units; 3 of general rehabilitation wards) recruiting 1437 patients. Organized inpatient multidisciplinary rehabilitation was associated with a reduced odds of death (odds ratio, 0.66; 95% CI, 0.49 to 0.88;
P
<0.01), death or institutionalization (odds ratio, 0.70; 95% CI, 0.56 to 0.88;
P
<0.001), and death or dependency (odds ratio, 0.65; 95% CI, 0.50 to 0.85;
P
<0.001), which was consistent across a variety of trial subgroups. For every 100 patients receiving organized inpatient multidisciplinary rehabilitation, an extra 5 returned home in an independent state.

Conclusions
—The results indicate that there can be substantial benefit from organized inpatient multidisciplinary rehabilitation in the postacute period, which is both statistically significant and clinically important.
Stroke in Young Adults in the Community-Based L’Aquila Registry
Authors: Marini Carmine , Totaro Rocco , De Santis Federica , Ciancarelli Irene , Baldassarre Massimo , Carolei Antonio
Published: June 2011

Background and Purpose
—Stroke type in the young may influence the outcome and may have a dramatic impact on the quality of life in survivors. This study aimed to evaluate the incidence and prognosis of first-ever stroke in the young and to make comparisons with older patients within a well-defined population.

Methods
—All first-ever strokes occurring in the L’Aquila district, central Italy, were traced by active monitoring of inpatient and outpatient health services. Incidence rates were standardized to the 1996 European population according to the direct method. Long-term survival was estimated by the Kaplan-Meier method; outcome in survivors was evaluated by the modified Rankin scale.

Results
—Of 4353 patients who had a first-ever stroke, 89 patients <45 years of age (55 men and 34 women) (2%) were identified in a 5-year period. Mean age±SD was 36.1±8.1 years. Twenty patients (22.5%) had a subarachnoid hemorrhage, 18 (20.2%) an intracerebral hemorrhage, and 51 (57.3%) a cerebral infarction. The corresponding proportions in patients >45 years of age were 2.4%, 13.3%, and 83.1%. Neuroimaging studies of the brain detected 14 intracranial aneurysms and 6 arteriovenous malformations in 20 of 38 patients (52.6%) with either subarachnoid (n=17) or intracerebral (n=3) hemorrhage. The crude annual incidence rate was 10.18/100 000 (95% CI, 8.14 to 12.57) and 10.23/100 000 when standardized to the 1996 European population. The 30-day case-fatality rate was 11.2% (95% CI, 6.2 to 19.4). Patients with subarachnoid hemorrhage had the highest proportion of good recovery (60%), patients with intracerebral hemorrhage had the highest mortality (44%), and patients with cerebral infarction had the highest proportion of severe disability (47%).

Conclusions
—Stroke patients <45 years of age showed a disproportionate cumulative high prevalence (42.7%) of subarachnoid and intracerebral hemorrhage with respect to older patients (15.7%), mainly (52.6%) due to aneurysms and arteriovenous malformations. Therefore, screening procedures and preventive strategies in the young should also be addressed to subjects at risk of subarachnoid and intracerebral hemorrhage.
Alcohol Intake, Type of Beverage, and the Risk of Cerebral Infarction in Young Women
Authors: Malarcher Ann M. , Giles Wayne H. , Croft Janet B. , Wozniak Marcella A. , Wityk Robert J. , Stolley Paul D. , Stern Barney J. , Sloan Michael A. , Sherwin Roger , Price Thomas R. , Macko Richard F. , Johnson Constance J. , Earley Christopher J. , Buchholz David W. , Kittner Steven J.
Published: June 2011

Background and Purpose
—The relationship between alcohol consumption and cerebral infarction remains uncertain, and few studies have investigated whether the relationship varies by alcohol type or is present in young adults. We examined the relationship between alcohol consumption, beverage type, and ischemic stroke in the Stroke Prevention in Young Women Study.

Methods
—All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. Case patients (n=224) were aged 15 to 44 years with a first cerebral infarction, and control subjects (n=392), identified by random-digit dialing, were frequency matched by age and region of residence. The interview assessed lifetime alcohol consumption and consumption and beverage type in the previous year, week, and day. ORs were obtained from logistic regression models controlling for age, race, education, and smoking status, with never drinkers as the referent.

Results
—Alcohol consumption, up to 24 g/d, in the past year was associated with fewer ischemic strokes (<12 g/d: OR 0.57, 95% CI 0.38 to 0.86; 12 to 24 g/d: OR 0.38, 95% CI 0.17 to 0.86; >24 g/d: OR 0.95, 95% CI 0.43 to 2.10) in comparison to never drinking. Analyses of beverage type (beer, wine, liquor) indicated a protective effect for wine consumption in the previous year (<12 g/wk: OR 0.58, 95% CI 0.35 to 0.97; 12 g/wk to <12 g/d: OR 0.55, 95% CI 0.28 to 1.10; ≥12 g/d: OR 0.92, 95% CI 0.23 to 3.64).

Conclusions
—Light to moderate alcohol consumption appears to be associated with a reduced risk of ischemic stroke in young women.
Detection of
Helicobacter pylori in Human Carotid Atherosclerotic Plaques
Authors: Ameriso Sebastián F. , Fridman Esteban A. , Leiguarda Ramón C. , Sevlever Gustavo E.
Published: June 2011

Background and Purpose
—Several lines of evidence point toward a relationship between infection and atherosclerotic vascular disease. Thus, infection and inflammation often precede ischemic neurological events. Transient alterations in coagulation and direct arterial invasion by certain microorganisms have been reported.
Helicobacter pylori
infection is the major cause of peptic ulcer disease and appears to be a risk factor for ischemic cerebrovascular disease. However, in contrast to other chronic infectious agents,
H pylori
has not been consistently isolated from atherosclerotic lesions.

Methods
—We investigated the presence of
H pylori
in 38 atherosclerotic plaques obtained at carotid endarterectomy by using morphological and immunohistochemical techniques and a highly sensitive polymerase chain reaction method. We performed immunohistochemical detection of intercellular adhesion molecule-1, a marker related to inflammatory cell response. We also examined 7 carotid arteries obtained at autopsy from subjects without carotid atherosclerosis.

Results
—
H pylori
DNA was found in 20 of 38 atherosclerotic plaques. Ten of the
H pylori
DNA–positive plaques also showed morphological and immunohistochemical evidence of
H pylori
infection. None of 7 normal carotid arteries was positive for
H pylori
. Intercellular adhesion molecule-1 was expressed in 75% of
H pylori
–positive plaques and in 22% of
H pylori
–negative plaques. The presence of the microorganism was associated with male sex but was independent of age, vascular risk factor profile, and prior neurological symptoms.

Conclusions
—
H pylori
is present in a substantial number of carotid atherosclerotic lesions and is associated with features of inflammatory cell response. This study provides additional evidence of the relationship between
H pylori
infection and atherosclerotic disease.
Quantitative Assessment of the Ischemic Brain by Means of Perfusion-Related Parameters Derived From Perfusion CT
Authors: Koenig Matthias , Kraus Michael , Theek Carmen , Klotz Ernst , Gehlen Walter , Heuser Lothar
Published: June 2011

Background and Purpose
—Besides the delineation of hypoperfused brain tissue, the characterization of ischemia with respect to severity is of major clinical relevance, because the degree of hypoperfusion is the most critical factor in determining whether an ischemic lesion becomes an infarct or represents viable brain tissue. CT perfusion imaging yields a set of perfusion related parameters which might be useful to describe the hemodynamic status of the ischemic brain. Our objective was to determine whether measurements of the relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative time to peak (rTP) can be used to differentiate areas undergoing infarction from reversible ischemic tissue.

Methods
—In 34 patients with acute hemispheric ischemic stroke <6 hours after onset, perfusion CT was used to calculate rCBF, rCBV, and rTP values from areas of ischemic cortical and subcortical gray matter. Results were obtained separately from areas of infarction and noninfarction, according to the findings on follow-up imaging studies. The efficiency of each parameter to predict tissue outcome was tested.

Results
—There was a significant difference between infarct and peri-infarct tissue for both rCBF and rCBV but not for rTP. Threshold values of 0.48 and 0.60 for rCBF and rCBV, respectively, were found to discriminate best between areas of infarction and noninfarction, with the efficiency of the rCBV being slightly superior to that of rCBF. The prediction of tissue outcome could not be increased by using a combination of various perfusion parameters.

Conclusions
—The assessment of cerebral ischemia by means of perfusion parameters derived from perfusion CT provides valuable information to predict tissue outcome. Quantitative analyses of the severity of ischemic lesions should be implemented into the diagnostic management of stroke patients.
Risk Factors for Severe Hemorrhagic Transformation in Ischemic Stroke Patients Treated With Recombinant Tissue Plasminogen Activator
Authors: Larrue Vincent , von Kummer Rüdiger , Müller Achim , Bluhmki Erich
Published: June 2011

Background and Purpose
—Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) improves the outcome for ischemic stroke patients who can be treated within 3 hours of symptom onset. The efficacy of thrombolysis has been demonstrated despite an increased risk of severe hemorrhagic transformation (HT) in patients treated with rtPA. We performed an analysis of risk factors for severe HT in the second European-Australasian Acute Stroke Study (ECASS II).

Methods
—HTs were classified by using clinical and radiological criteria as follows: hemorrhagic infarction (HI), parenchymal hemorrhage (PH), and symptomatic intracranial hemorrhage (SICH). Potential risk factors for HT were tested by stepwise logistic regression analysis, including rtPA-by-variable interactions. In addition, the distribution of bad outcome (modified Rankin score 5 to 6) at day 90 was stratified according to each category of HT.

Results
—PH and SICH but not HI were associated with rtPA. Also, PH and SICH but not HI were more severe in rtPA-treated patients than in those receiving placebo. Risk factors for PH were rtPA, extent of parenchymal hypoattenuation on baseline CT, congestive heart failure, increasing age, and baseline systolic blood pressure. The risk of PH on rtPA was increased in older patients and in those who were treated with aspirin before thrombolysis. Risk factors for SICH were rtPA, congestive heart failure, extent of parenchymal hypoattenuation, and increasing age. The risk of SICH on rtPA was increased in patients who were treated with aspirin before thrombolysis.

Conclusions
—This secondary analysis of ECASS II has confirmed the importance of the extent of hypoattenuation as a risk factor for severe HT. The findings also suggest that older patients and those who have used aspirin before stroke are at higher risk of a severe HT on rtPA.
Ear Oximetry: A Noninvasive Method for Detection of Patent Foramen Ovale
Authors: Karttunen Vesa , Ventilä Markku , Ikäheimo Markku , Niemelä Matti , Hillbom Matti
Published: June 2011

Background and Purpose
—Patent foramen ovale (PFO) may play an important role as a risk factor for ischemic stroke and some other neurological conditions. There is a need for low-cost and noninvasive methods for the detection of PFO. This study evaluates the accuracy of two simple bedside tests, the dye dilution method and ear oximetry, in the detection of PFO.

Methods
—Dye dilution curves and ear oximetry recordings with a noninvasive ear densitometer were obtained from consecutive cryptogenic stroke patients referred for contrast transesophageal echocardiography (TEE). All test results were blindly assessed for the presence of PFO. Sensitivity and specificity were calculated with TEE used as a reference method. κ statistics were used to measure interrater agreement.

Results
—Dye dilution curves were obtained from 67 patients. Dye dilution correctly diagnosed 35 of the 46 patients who had PFO in TEE and all the 21 patients without PFO. Thus, the sensitivity (95% CI) of the dye dilution method was 76% (61% to 87%) and its specificity 100% (84% to 100%). Ear oximetry was done on 83 patients. Oximetry correctly diagnosed 45 of the 53 patients who had PFO in TEE and all of the 30 patients without PFO. Thus, the sensitivity of ear oximetry was 85% (72% to 93%) and its specificity 100% (88% to 100%). The interrater agreement was excellent (κ value 0.94 for dye dilution and 0.90 for oximetry).

Conclusions
—Dye dilution and oximetry are both sensitive and specific methods for the detection of PFO. Oximetry has the following primary advantages over the currently available diagnostic methods: it is noninvasive, safe, and inexpensive and causes no discomfort for the patient. We suggest that oximetry could be used as a first-line screening method for PFO in patients with cryptogenic stroke. Ear oximetry also has potential use in epidemiological studies.
Association Between Arterial Stiffness and Atherosclerosis
Authors: van Popele Nicole M. , Grobbee Diederick E. , Bots Michiel L. , Asmar Roland , Topouchian Jirar , Reneman Robert S. , Hoeks Arnold P. G. , van der Kuip Deidre A. M. , Hofman Albert , Witteman Jacqueline C. M.
Published: June 2011

Background and Purpose
—Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis.

Methods
—This study was conducted within the Rotterdam Study in >3000 elderly subjects aged 60 to 101 years. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity, and common carotid artery stiffness was assessed by measuring common carotid distensibility. Atherosclerosis was assessed by common carotid intima-media thickness, plaques in the carotid artery and in the aorta, and the presence of peripheral arterial disease. Data were analyzed by ANCOVA with adjustment for age, sex, mean arterial pressure, and heart rate.

Results
—Both aortic and common carotid artery stiffness were found to have a strong positive association with common carotid intima-media thickness, severity of plaques in the carotid artery, and severity of plaques in the aorta (
P
for trend <0.01 for all associations). Subjects with peripheral arterial disease had significantly increased aortic stiffness (
P
=0.001) and borderline significantly increased common carotid artery stiffness (
P
=0.08) compared with subjects without peripheral arterial disease. Results were similar after additional adjustment for cardiovascular risk factors and after exclusion of subjects with prevalent cardiovascular disease.

Conclusions
—This population-based study shows that arterial stiffness is strongly associated with atherosclerosis at various sites in the vascular tree.
Tolerability of the Low-Affinity, Use-Dependent NMDA Antagonist AR-R15896AR in Stroke Patients
Authors: Lees Kennedy R. , Dyker Alexander G. , Sharma Anil , Ford Gary A. , Ardron Mark E. , Grosset Donald G.
Published: June 2011

Background and Purpose
—AR-R15896AR is a use-dependent, low-affinity blocker of the NMDA ion channel with neuroprotective effects in animal models of focal cerebral ischemia. This study aimed to establish the highest safe and tolerated loading and maintenance dosing regimen of AR-R15896AR in acute ischemic stroke patients and to determine the associated plasma concentrations of AR-R15896AR.

Methods
—This was a 4-part, multicenter, randomized, double-blind, placebo-controlled study in 175 patients (mean age, 69 years) within 24 hours of acute stroke symptom recognition. Ascending 60-minute intravenous infusion loading doses of AR-R15896AR were initially examined (100, 150, 200, 250, or 300 mg or placebo in 3:1 randomization, n=36 treated); in part 2, 250, 275, or 300 mg was compared with placebo (n=33). In part 3, a 250-mg loading dose was followed by 9 maintenance doses of 60, 75, 90, 105, or 120 mg every 8 hours versus placebo in 3:1 randomization (n=59); subsequently, in part 4, maintenance doses of 90, 105, and 120 mg after the 250-mg loading dose were directly randomized against placebo (n=42). Safety, tolerability, and pharmacokinetics were the primary end points; NIHSS at 1 week and Barthel and modified Rankin scores at 1 month were also recorded, but the study was neither designed nor powered to assess efficacy.

Results
—Rates for mortality and serious adverse events (SAE) were similar in active and placebo groups (9% mortality and 23% SAE for all active combined versus 11% mortality and 33% SAE for placebo). Adverse events associated with AR-R15896AR were dizziness, vomiting, nausea, stupor, and some agitation/hallucination. Withdrawal from treatment occurred only in response to loading doses with AR-R15896AR: placebo, 3 of 46 (7%); 250 mg, 11 of 89 (12%); 275 mg, 1 of 8 (12.5%); and 300 mg, 3 of 15 (20%). No significant difference in outcome was observed between groups. Plasma concentrations of AR-R15896AR were 1524±536 ng/mL at the end of the 250-mg loading infusion and were 1847±478 ng/mL at steady state after the 9 maintenance doses of 120 mg.

Conclusions
—The maximum tolerated loading infusion of AR-R15896AR in this study was 250 mg over a period of 1 hour. Subsequent maintenance infusions of 120 mg every 8 hours were well tolerated. With these doses, putative neuroprotective concentrations of 1240 ng/mL are attained by the loading dose and are satisfactorily maintained thereafter. The loading dose may be improved further by adjustment on an individual patient basis, but tolerability issues remain.
Factors Affecting Formation and Growth of Intracranial Aneurysms
Authors: Juvela Seppo , Poussa Kristiina , Porras Matti
Published: June 2011

Background and Purpose
—We sought to investigate factors determining growth rate of unruptured intracranial aneurysms as well as formation of new (de novo) aneurysms in patients from a time period when unruptured aneurysms were not treated surgically.

Methods
—Eighty-seven patients (79 had ruptured aneurysms clipped at start of follow-up) with 111 unruptured aneurysms as well as an additional 7 patients (2 with and 5 without unruptured aneurysms) who developed new aneurysms were followed from the 1950s to the 1970s until death or subarachnoid hemorrhage or until the last contact. Patients’ cerebral arteries were examined later either with conventional (control) angiography (n=38) and/or, for those alive during 1996–1998, with 3-dimensional CT angiography (n=57). In addition, 10 patients were studied at neuropathological autopsy.

Results
—Mean±SD duration of follow-up was 18.9±9.4 years (range, 1.2 to 38.9 years). Unruptured aneurysms increased in size ≥1 mm in 39 of the 87 patients (45%) and ≥3 mm in 31 (36%). New aneurysms were found in 15 of the 89 patients and in 5 without an unruptured aneurysm at the beginning of follow-up. Aneurysm rupture was associated very significantly (
P
<0.001) with aneurysm growth during follow-up. Of several potential risk factors tested, only cigarette smoking (odds ratio [OR], 3.92; 95% CI, 1.29 to 11.93) and female sex (OR, 3.36; 95% CI, 1.11 to 10.22) were, after adjustment for age, significant (
P
<0.05) independent risk factors for occurrence of aneurysm growth of ≥1 mm. Only cigarette smoking (OR, 3.48; 95% CI, 1.14 to 10.64;
P
<0.05) was associated with growth of ≥3 mm. Age- and hypertension-adjusted risk factors for aneurysm formation were female sex (OR, 4.73; 95% CI, 1.16 to 19.38) and cigarette smoking (OR, 4.07; 95% CI, 1.09 to 15.15).

Conclusions
—Women and cigarette smokers are at increased risk for intracranial aneurysm formation and growth. Cigarette smoking in particular hastens aneurysm growth. Cessation of smoking is important for patients with unruptured aneurysms and possibly also for those with a prior subarachnoid hemorrhage.
Pituitary Apoplexy Caused by Ruptured Internal Carotid Artery Aneurysm
Authors: Suzuki Hidenori , Muramatsu Masatoshi , Murao Kenichi , Kawaguchi Kenji , Shimizu Takeo
Published: June 2011

Background and Purpose
—We report the first case of pituitary apoplexy caused by the rupture of an intracavernous carotid artery aneurysm embedded in a pituitary adenoma.

Case Description
—A 46-year-old man presented with clinical and CT findings typical of pituitary apoplexy. MRI showed an unusual flow-void protrusion into the intratumoral hematoma, which, however, was not diagnosed as a ruptured aneurysm until severe intraoperative bleeding occurred. Angiography after surgery revealed an intracavernous carotid artery aneurysm.

Conclusions
—The possible association of adenoma and aneurysmal rupture should be kept in mind when assessing any case of pituitary apoplexy.
Effects of Aging on Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbits
Authors: Nakajima Masaaki , Date Isao , Takahashi Kenji , Ninomiya Yoshifumi , Asari Shoji , Ohmoto Takashi
Published: June 2011

Background and Purpose
—The effects of aging on cerebral vasospasm after subarachnoid hemorrhage (SAH) remain to be elucidated. The aim of this study was to clarify age-related differences of vasospasm and of papaverine reactivity in the responses of basilar arteries after SAH in rabbits.

Methods
—Rabbits receiving a single injection of arterial blood into the cisterna magna were divided into 3 groups: young (2 to 3 months old), adult (6 to 9 months old), and old (20 to 40 months old). Vertebrobasilar angiograms were obtained before SAH and 1, 2, 4, and 7 days after SAH. Papaverine was administrated selectively via the vertebral artery on day 2, and serial angiography was performed for up to 2 hours. Vessel structures were assessed with light microscopy on days 1, 2, 4, and 7 after SAH and at 10, 30, and 60 minutes after papaverine infusion.

Results
—Mortality from SAH in old rabbits was 40%, whereas that of young and adult rabbits was 0%. Angiograms revealed that SAH induced maximal constriction of the basilar arteries on day 2 in all age groups, and the constrictions were significantly increased with age at all time points investigated. The degree of dilatation of spastic basilar arteries after intra-arterial papaverine administration significantly decreased with age. Duration of the efficacy of papaverine became significantly shorter with age. Vessel diameter returned to the preinfusion value ≈120, 60, and 30 minutes after infusion in young, adult, and old rabbits, respectively. Light microscopy in old rabbits showed luminal narrowing and corrugation of the internal elastic lamina not only in the basilar arteries but also in small arteries and intraparenchymal arterioles.

Conclusions
—This study suggests that aging increases the degree of vasospasm in rabbits. The impaired reactivity to papaverine with aging might imply the early transition of the aged vessel to the papaverine-resistant chronic stage.
Intracisternal Increase of Superoxide Anion Production in a Canine Subarachnoid Hemorrhage Model
Authors: Mori Takashi , Nagata Kazuya , Town Terrence , Tan Jun , Matsui Toru , Asano Takao
Published: June 2011

Background and Purpose
—Reactive oxygen species (ROS) are thought to be primary in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, as direct evidence of ROS has not yet been demonstrated in cerebral vasospasm, we sought to substantiate superoxide anion (·O
2
−
) generation in the subarachnoid space after SAH using a modification of Karnovsky’s manganese/diaminobenzidine (Mn
2+
/DAB) technique.

Methods
—SAH or sham operation was induced according to a 2-hemorrhage model in a total of 24 beagle dogs. On day 2 or 7 after SAH or sham operation, dogs were intrathecally infused with buffer containing Mn
2+
and DAB, and the brain stem was prepared for light and electron microscopy. Possible colocalization of ferrous (Fe
2+
) or ferric (Fe
3+
) iron ions with ·O
2
−
was also examined with the use of Turnbull blue or Berlin blue staining, respectively.

Results
—Light microscopy revealed amorphous, amber deposits within the subarachnoid hematoma, the periarterial space, and the tunica adventitia of the basilar artery on days 2 and 7 after SAH. ·O
2
−
deposits were eliminated by addition of superoxide dismutase or exclusion of either Mn
2+
or DAB from the perfusate, confirming the specificity of the reaction. These deposits were colocalized with blue reaction deposits indicating Fe
2+
and Fe
3+
. Within the subarachnoid space, ·O
2
−
indicating electron-dense fine granules were preferentially located around degenerated erythrocytes and, secondarily, infiltrating macrophages and neutrophils.

Conclusions
—We show direct evidence for enhanced production of ·O
2
−
and Fe
2+
/Fe
3+
iron ions in the subarachnoid space after SAH, lending further support to the pathogenic role of ROS in cerebral vasospasm after SAH.
Transtentorial Herniation After Unilateral Infarction of the Anterior Cerebral Artery
Authors: Leistner Stefanie , Boegner Friedrich , Marx Peter , Koennecke Hans-Christian
Published: June 2011

Background
—Fatal cerebral herniation is a common complication of large (“malignant”) middle cerebral artery infarcts but has not been reported in unilateral anterior cerebral artery (ACA) infarction.

Case Description
—We report a 47-year-old woman who developed an acute left hemiparesis during an attack of migraine. Cranial CT (CCT) was normal but demonstrated narrow external cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible with occlusion of the right ACA. Systemic thrombolytic therapy with tissue plasminogen activator was initiated 105 minutes after symptom onset. Follow-up CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic conversion. Two days later, the patient suddenly deteriorated with clinical signs of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy was immediately performed. Within 6 months, the patient regained her ability to walk but remained moderately disabled.

Conclusions
—This is the first reported case of unilateral ACA infarct leading to almost fatal cerebral herniation. Narrow external cerebrospinal fluid compartments in combination with early reperfusion, hemorrhagic transformation, and additional dysfunction of the blood-brain barrier promoted by tissue plasminogen activator and migraine may have contributed to this unusual course.
Have Randomized Controlled Trials of Neuroprotective Drugs Been Underpowered?
Authors: Samsa Gregory P. , Matchar David B.
Published: June 2011

Background and Purpose
—The results of phase III trials of neuroprotective drugs for acute ischemic stroke have been disappointing. We examine the question of whether these trials may have been underpowered.

Methods
—Computer simulations were based on the binomial distribution.

Results
—We illustrate that even small overestimates of the efficacy of an intervention can lead to a serious reduction in statistical power, that the use of data from phase II studies tends to lead to such overestimation, and that a minimum clinically important difference derived with cost-effectiveness modeling techniques is considerably smaller than might be suggested by intuition.

Conclusions
—We recommend placing more emphasis on minimum clinically important differences when planning stroke trials, with these differences being derived from an assessment of the public health impact obtained in conjunction with the use of epidemiological and cost-effectiveness models. Even small benefits, when averaged over a sufficiently large number of cases, will, in total, accrue to a large positive impact on the public health.
A Quality-of-Life Instrument for Young Hemorrhagic Stroke Patients
Authors: Hamedani Azita G. , Wells Carolyn K. , Brass Lawrence M. , Kernan Walter N. , Viscoli Catherine M. , Maraire J. Nozipo , Awad Issam A. , Horwitz Ralph I.
Published: June 2011

Background and Purpose
—Hemorrhagic stroke has a high initial mortality rate. While survivors often recover motor function, many experience significant changes in their quality of life (QOL). Available outcome measures assess neurological impairment, disability, or handicap, yet often inadequately characterize the full impact of a stroke on patients’ lives. In this study, we develop and validate a QOL instrument specific for young patients with hemorrhagic strokes.

Methods
—Methodological guidelines for instrument development were initially established. Based on the content of 40 open-ended patient interviews, a 54-item instrument (HSQuale) was developed. The reliability (test-retest and internal consistency) and validity (content and construct) of HSQuale were assessed in another 71 patients (18 to 49 years of age, 63% women, 77% white), at 1 year after their hemorrhagic stroke. Comparisons were made between HSQuale and other commonly used outcome measures.

Results
—HSQuale demonstrated reproducibility (test-retest κ, 0.40 to 0.96) and internal consistency (Cronbach α ≥0.80 for 5 of 7 domains). HSQuale scores had broad frequency distributions (≤33% of subjects scored in any single score decile), avoided ceiling effects found for other outcome measures (Barthel Index and Short Form-36), and discriminated among clinically distinct subject groups (eg, intracerebral versus subarachnoid hemorrhage patients).

Conclusions
—HSQuale is a reliable and valid QOL instrument. Compared with other outcome measures, it assesses a broader range of deficits and is better able to discriminate among subgroups of hemorrhagic stroke survivors.
Cardioprotection in Pigs by Exogenous Norepinephrine but not by Cerebral Ischemia–Induced Release of Endogenous Norepinephrine
Authors: de Zeeuw Sandra , Lameris Thomas W. , Duncker Dirk J. , Hasan Djo , Boomsma Frans , van den Meiracker Anton H. , Verdouw Pieter D.
Published: June 2011

Background and Purpose
—Endogenous norepinephrine release induced by cerebral ischemia may lead to small areas of necrosis in normal hearts. Conversely, norepinephrine may be one of the mediators that limit myocardial infarct size by ischemic preconditioning. Because brief ischemia in kidneys or skeletal muscle limits infarct size produced by coronary artery occlusion, we investigated whether cardiac norepinephrine release during transient cerebral ischemia also elicits remote myocardial preconditioning.

Methods
—Forty-one crossbred pigs of either sex were assigned to 1 of 7 experimental groups, of which in 6 groups myocardial infarct size was determined after a 60-minute coronary occlusion and 120 minutes of reperfusion. One group served as control (no pretreatment), while the other groups were pretreated with either cerebral ischemia or an intracoronary infusion of norepinephrine.

Results
—In 10 anesthetized control pigs, infarct size was 84±3% (mean±SEM) of the area at risk after a 60-minute coronary occlusion and 120 minutes of reperfusion. Intracoronary infusion of 0.03 nmol/kg · min
−
1
norepinephrine for 10 minutes before coronary occlusion did not affect infarct size (80±3%; n=6), whereas infusion of 0.12 nmol/kg · min
−
1
limited infarct size (65±2%; n=7;
P
<0.05). Neither 10-minute (n=5) nor 30-minute (n=6) cerebral ischemia produced by elevation of intracranial pressure before coronary occlusion affected infarct size (83±4% and 82±3%, respectively). Myocardial interstitial norepinephrine levels tripled during cerebral ischemia and during low-dose norepinephrine but increased 10-fold during high-dose norepinephrine. Norepinephrine levels increased progressively up to 500-fold in the area at risk during the 60-minute coronary occlusion, independent of the pretreatment, while norepinephrine levels remained unchanged in adjacent nonischemic myocardium and arterial plasma.

Conclusions
—Cerebral ischemia preceding a coronary occlusion did not modify infarct size, which is likely related to the modest increase in myocardial norepinephrine levels during cerebral ischemia. The infarct size limitation by high-dose exogenous norepinephrine is not associated with blunting of the ischemia-induced increase in myocardial interstitial norepinephrine levels.
Postischemic Estrogen Reduces Hypoperfusion and Secondary Ischemia After Experimental Stroke
Authors: McCullough Louise D. , Alkayed Nabil J. , Traystman Richard J. , Williams Megan J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—Estrogen is a known neuroprotective and vasoprotective agent in experimental cerebral ischemia. Preischemic steroid treatment protects animals of both sexes from focal cerebral ischemia. This study determined whether intravenous estrogen acts as a vasodilator when administered on reperfusion and whether the resulting increase in cerebral blood flow (CBF) provides tissue protection from middle cerebral artery occlusion.

Methods
—Adult male Wistar rats were treated with reversible middle cerebral artery occlusion (2 hours), then infused with intravenous estrogen (Premarin; 1 mg/kg) or vehicle during the first minutes of reperfusion (n=15 per group). Cortical laser-Doppler flowmetry was used to assess adequacy of occlusion. Ischemic lesion volume was determined at 22 hours after occlusion by 2,3,5-triphenyltetrazolium chloride staining and image analysis. Cortical and striatal CBF was measured by
14
[C]iodoantipyrine autoradiography at 10 (n=10) or 90 (n=11) minutes of reperfusion.

Results
—As expected, supraphysiological plasma estrogen levels were achieved during reperfusion (estrogen, 198±45 pg/mL; vehicle, 6±5;
P
=0.001). Physiological variables were controlled and not different between groups. Total hemispheric infarction was reduced in estrogen-treated rats (estrogen, 49±4% of ipsilateral structure; vehicle, 33±5%;
P
=0.02), which was most pronounced in striatum (estrogen, 40±6% of ipsilateral striatum; vehicle, 60±3%;
P
=0.01). CBF recovery was strikingly increased by estrogen infusion at 10 minutes in frontal (estrogen, 102±12 mL/100 g per minute; vehicle, 45±15;
P
=0.01) and parietal cortex (estrogen, 74±15 mL/100 g per minute; vehicle, 22±13;
P
=0.028) and throughout striatum (estrogen, 87±13 mL/100 g per minute; vehicle, 25±20;
P
=0.02). Hemispheric volume with low CBF recovery (eg, <20 mL/100 g per minute) was smaller in estrogen-treated animals (estrogen, 73±18 mm
3
; vehicle, 257±46;
P
=0.002). However, differences in CBF recovery could not be appreciated between groups by 90 minutes of reperfusion.

Conclusions
—Acute estrogen therapy during reperfusion improves tissue outcome from experimental stroke. The steroid rapidly promotes CBF recovery and reduces hemispheric no-reflow zones. This beneficial effect appears only during early reperfusion and likely complements other known mechanisms by which estrogen salvages brain from focal necrosis.
Use of Suppression Subtractive Hybridization for Differential Gene Expression in Stroke
Authors: Wang Hugh , Zhan Yutian , Xu Lin , Feuerstein Giora Z. , Wang Xinkang
Published: June 2011

Background and Purpose
—CD44 is a transmembrane glycoprotein involved in endothelial cell recognition, lymphocyte trafficking, and regulation of cytokine gene expression in inflammatory diseases. The present report describes the discovery of upregulated CD44 gene expression and its spatial and temporal distribution in the brain after focal stroke.

Methods
—Rats were subjected to permanent occlusion of the middle cerebral artery (MCAO). Suppression subtractive hybridization (SSH) strategy was used to identify differentially expressed genes. Northern blotting and real-time polymerase chain reaction were used to evaluate the expression of CD44 and hyaluronan synthase 2 (HAS-2) mRNA. Western blotting and immunohistochemistry were used to examine CD44 expression and cellular distribution.

Results
—CD44 upregulation after focal stroke was discovered by the SSH approach and confirmed by DNA sequencing. Northern blot using a pooled poly(A)+ RNA revealed 3 splice variants of CD44 mRNA, and their inducible expression started at 6 hours (5.3-fold increase over sham operation), peaked at 24 hours (28.6-fold increase), and persisted up to 72 hours (17.8-fold increase) after MCAO. A parallel induction profile of HAS-2 mRNA was observed in the ischemic brain tissue. The levels of CD44 were markedly elevated at 6 hours (1.8-fold increase over sham; n=3), 24 hours (2.9-fold, peak induction;
P
<0.01), and 72 hours (2.4-fold increase;
P
<0.05) after MCAO by means of Western analysis. Immunohistochemical and confocal microscopy confirmed that constitutive expression of CD44 is limited to microvessels in normal brain but is strongly induced after ischemia, where the immunoreactive signal mainly resided in endothelial cells and monocytes. Double-labeling immunohistochemistry demonstrated that a marked induction of CD44 in the ischemic lesion is dominantly located in microglia and a subset of macrophages.

Conclusions
—The discovery of concomitant induction of CD44 and HAS-2 mRNA expression and the localization of CD44 in the microglia, macrophages, and microvessels of the ischemic brain tissue suggest that an active interaction between CD44 and hyaluronan may occur and play a role in the known inflammatory response and tissue remodeling after stroke.
Adenovirus-Mediated Gene Transfer to Ischemic Brain
Authors: Ooboshi Hiroaki , Ibayashi Setsuro , Takada Junichi , Yao Hiroshi , Kitazono Takanari , Fujishima Masatoshi
Published: June 2011

Background and Purpose
—Gene therapy may be a promising approach for treatment of brain ischemia, although protein synthesis is generally inhibited in ischemic conditions. Our goal in this study was to examine effects of brain ischemia on transgene expression of adenovirus-mediated gene transfer to ischemic brain.

Methods
—Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of spontaneously hypertensive rats (n=15). Ninety minutes after ischemia, adenoviral vectors encoding bacterial β-galactosidase were injected into ipsilateral (nonischemic [I-n], peri-ischemic [I-p], and ischemic core [I-c] areas) and contralateral parietal (C) cortices. Cerebral blood flow before and during ischemia at each injected area was measured by laser-Doppler flowmetry. Expression of transgene was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis.

Results
—Blood flow to the cortex decreased to 72±10% (mean±SEM) at I-n, 41±6% at I-p, and 23±3% at I-c after 10 minutes of ischemia. Expression of the reporter gene was consistently detected at C and I-n at each survival period. The semiquantitative score for transgene expression decreased according to severity of ischemia (C, 2.3; I-n, 2.6; I-p, 1.1; I-c, 0.3; mean values). β-Galactosidase activity detected by chemiluminescent assay revealed that the values (mean±SEM) in the ischemic area (I-p, 15.9±9.2 mU/mg protein; I-c, 1.3±0.5) were significantly smaller than that of the nonischemic area (C, 45.4±6.9). Analysis of cerebral blood flow at I-p revealed that cerebral blood flow threshold for transgene expression was approximately 40% of the resting value.

Conclusions
—Adenovirus-mediated gene transfer into the ischemic brain provided effective expression of transgene at the nonischemic and peri-ischemic areas. Gene transfer to the ischemic brain may be a promising approach for treatment of ischemic penumbra.
Community Use of Intravenous Tissue Plasminogen Activator for Acute Stroke
Authors: Katzan Irene L. , Sila Cathy A. , Furlan Anthony J.
Published: June 2011

Background and Purpose
—Little is known of neurologists’ viewpoints regarding intravenous tPA use or institutional readiness to evaluate potential thrombolytic candidates.

Methods
—Surveys were distributed at the Brain Matters Stroke Management Workshops held in 16 cities in the United States.

Results
—Intravenous tPA was administered by 46.9% of responding neurologists. Almost 30% (29.9%) of surveyed neurologists were “very convinced” of its efficacy, whereas 61.6% were “very concerned” about the risk of intracranial hemorrhage. Only half of the respondents believed their institutions could meet all NINDS-recommended stroke-evaluation time targets.

Conclusions
—Neurologists’ enthusiasm for the efficacy of intravenous tPA is tempered by their concern about intracranial hemorrhage. Institutional readiness for evaluating acute stroke patients is not optimized.