bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Intraventricular Hemorrhage With Urokinase
Authors: Naff Neal J. , Carhuapoma Juan R. , Williams Michael A. , Bhardwaj Anish , Ulatowski John A. , Bederson Joshua , Bullock Ross , Schmutzhard Erich , Pfausler Bettina , Keyl Penelope M. , Tuhrim Stanley , Hanley Daniel F.
Published: June 2011

Background and Purpose
—Intraventricular hemorrhage (IVH) remains associated with high morbidity and mortality. Therapy with external ventricular drainage alone has not modified outcome in these patients.

Methods
—Twelve pilot IVH patients who required external ventricular drainage were prospectively treated with intraventricular urokinase followed by the randomized, double-blinded allocation of 8 patients to either treatment or placebo. Observed 30-day mortality was compared with predicted 30-day mortality obtained by use of a previously validated method.

Results
—Twenty patients were enrolled; admission Glasgow Coma Scale score in 11 patients was ≤8; 10 patients had pulse pressure <85 mm Hg. Mean±SD ICH volume in 16 patients was 6.21±7.53 cm
3
(range 0 to 23.88 cm
3
), and mean±SD intraventricular hematoma volume was 44.26±31.65 cm
3
(range 1.31 to 100.36 cm
3
). Four patients (20%) died within 30 days. Predicted mortality for these 20 patients was 68.42% (range 3% to 100%). Probability of observing ≤4 deaths among 20 patients under a 68.42% expected mortality is 0.000012.

Conclusions
—Intraventricular urokinase may significantly improve 30-day survival in IVH patients. On the basis of current evidence, a double-blinded, placebo-controlled, multicenter study that uses thrombolysis to treat IVH has received funding and began January 1, 2000.
Retrospective Assessment of Initial Stroke Severity With the NIH Stroke Scale
Authors: Williams Linda S. , Yilmaz Engin Y. , Lopez-Yunez Alfredo M.
Published: June 2011

Background and Purpose
—It is important to adjust stroke outcomes for differences in initial stroke severity. The NIH Stroke Scale (NIHSS) is a commonly used stroke severity measure but has been validated for retrospective scoring only in a subset of stroke clinical trial participants. The purpose of this research was to assess the validity and reliability of an algorithm for retrospective NIHSS scoring in a setting with usual chart documentation.

Methods
—An algorithm for retrospective NIHSS scoring was developed with written history and physical admission notes. Missing physical examination data were scored as normal. One investigator prospectively scored the admission NIHSS in 32 consecutive stroke patients. Two raters retrospectively scored the NIHSS by applying the algorithm to photocopied admission notes. Linear regression was used to assess interrater reliability and agreement between prospective and retrospective NIHSS scores. The Wilcoxon signed rank test was used to assess systematic scoring bias. Weighted kappa statistics were calculated to assess the level of agreement of individual NIHSS items.

Results
—Only 1 admission note was complete for all NIHSS elements. Interrater reliability was near perfect (
r
2
=0.98,
P
<0.001). Agreement between prospective and retrospective NIHSS score was also excellent (
r
2
=0.94,
P
<0.001) and there was no systematic bias in retrospective scores. Agreement for individual items was moderate to high for all items except level of consciousness.

Conclusions
—Retrospective NIHSS scoring with the algorithm is reliable and unbiased even when physical examination elements are missing from the written record. Stroke research using retrospective review of charts or of administrative databases should adjust for differences in stroke severity using such an algorithm.
Trends in Validated Cases of Fatal and Nonfatal Stroke, Stroke Classification, and Risk Factors in Southeastern New England, 1980 to 1991
Authors: Derby Carol A. , Lapane Kate L. , Feldman Henry A. , Carleton Richard A.
Published: June 2011

Background and Purpose
—Recent US data suggest there is a slowing of the decline in stroke mortality rates, accompanied by a constant morbidity rate. Hospital discharge rates for patients with stroke are influenced by numerous factors, and community-based surveillance data for validated cases are rare. Thus, reasons for the observed trends remain unclear. In the present study, we examined trends in validated cases of stroke for 1980 to 1991 in the combined populations of the Pawtucket Heart Health Program study communities and examined concomitant trends in classification, use of diagnostic procedures, and levels of risk factors.

Methods
—Discharges for residents aged 35 to 74 years with
International Classification of Diseases, Ninth Revision
codes 431, 432, and 434 to 437 were identified through retrospective surveillance. A physician reviewed the medical records to validate case status.

Results
—Between 1980 and 1991, 2269 discharges were confirmed as representing definite or probable strokes (59.5% of 3811 cases reviewed). The fatal stroke rate declined (
P
<0.005) and the nonfatal stroke rate remained constant in both sexes. Case-fatality rates declined significantly (
P
=0.003), and among strokes, the relative odds of death in 1990 versus 1980 was 0.50 (95% CI 0.34 to 0.72). The proportion of stroke discharges in which the patient received a CT scan or MRI increased 120%, and fewer strokes were classified as ill defined. Hypertension prevalence, treatment, and control rates remained constant in these populations.

Conclusions
—Although causes for the observed trends remain unclear, results suggest that the decline in mortality rates is due to improved survival rates for patients with stroke. However, constant morbidity rates combined with constant rates of hypertension highlight the need for improved prevention to reduce the impact of stroke.
Linkage of Familial Moyamoya Disease (Spontaneous Occlusion of the Circle of Willis) to Chromosome 17q25
Authors: Yamauchi Tohru , Tada Mitsuhiro , Houkin Kiyohiro , Tanaka Toshihiro , Nakamura Yusuke , Kuroda Satoshi , Abe Hiroshi , Inoue Takuya , Ikezaki Kiyonobu , Matsushima Toshio , Fukui Masashi
Published: June 2011

Background and Purpose
—Moyamoya disease is a cerebrovascular disease of unknown cause that mainly affects Japanese children. The incidence of familial occurrence accounts for 9% of cases. The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (
NF1
) has been assigned to chromosome 17q11.2.

Methods
—To determine whether a gene related to moyamoya disease is located on chromosome 17, we conducted microsatellite linkage analyses on 24 families containing 56 patients with moyamoya disease. Leukocyte DNA extracted from the family members was subjected to polymerase chain reaction for a total of 22 microsatellite markers on chromosome 17. The amplified polymerase chain reaction fragments were analyzed with GeneScan on an automated sequencer.

Results
—Two-point linkage analysis gave a maximum log
10
odds (LOD) score of 3.11 at the recombination fraction of 0.00 for the marker at locus D17S939. The affected pedigree member method also showed a significantly low
P
value (<1.0×10
−5
) for the 5 adjacent markers at 17q25. Multipoint linkage analysis also indicated that the disease gene is contained within the 9-cM region of D17S785 to D17S836, with a maximum LOD score of 4.58.

Conclusions
—A gene for familial moyamoya disease is located on chromosome 17q25.
C242T Polymorphism of NADPH Oxidase p22
PHOX
Gene and Ischemic Cerebrovascular Disease in the Japanese Population
Authors: Ito Daisuke , Murata Mitsuru , Watanabe Kiyoaki , Yoshida Tadashi , Saito Ikuo , Tanahashi Norio , Fukuuchi Yasuo
Published: June 2011

Background and Purpose
—Superoxide has been implicated in the pathogenesis of ischemic stroke and atherosclerosis. NADPH oxidase, a major source of superoxide generation in neutrophils and the vascular system, plays a critical role in ischemic injury and atherogenesis. Recently, an association between the C242T polymorphism of p22
PHOX
, an essential component of NADPH oxidase, and coronary artery disease (CAD) has been reported in several studies. To investigate the relationship between the C242T polymorphism of p22
PHOX
and ischemic cerebrovascular disease (CVD), we conducted a case-control study.

Methods
—We recruited 226 CVD patients (atherothrombotic infarction, lacunar infarction, and transient ischemic attack) and 301 control subjects and analyzed C242T polymorphism of p22
PHOX
by detection of restriction fragment length polymorphism.

Results
—The TC+TT genotype frequencies in the CVD group and control group were 21.7% and 13.3%, respectively, and the prevalence of the TC+TT genotype was significantly higher in the CVD patients (χ
2
=6.477,
P
=0.01, OR 1.81, 95% CI 1.15 to 2.86). Analysis by CVD subtypes showed that the OR for the TC+TT genotype was higher in the CVD patients with atherothrombotic infarction than in those with lacunar infarction and transient ischemic attack.

Conclusions
—The C242T polymorphism of the NADPH oxidase p22
PHOX
gene is a novel pathogenetic risk factor for CVD.
Transient and Permanent Resolution of Ischemic Lesions on Diffusion-Weighted Imaging After Brief Periods of Focal Ischemia in Rats
Authors: Li Fuhai , Liu Kai-Feng , Silva Matthew D. , Omae Tsuyoshi , Sotak Christopher H. , Fenstermacher Joseph D. , Fisher Marc
Published: June 2011

Background and Purpose
—The early ischemic lesions demonstrated by diffusion-weighted imaging (DWI) are potentially reversible. The purposes of this study were to determine whether resolution of initial DWI lesions is transient or permanent after different brief periods of focal brain ischemia and to evaluate histological outcomes.

Methods
—Sixteen rats were subjected to 10 minutes (n=7) or 30 minutes (n=7) of temporary middle cerebral artery occlusion or sham operation (n=2). DWI, perfusion-weighted imaging (PWI), and T
2
-weighted imaging (T
2
WI) were performed during occlusion; immediately after reperfusion; and at 0.5, 1.0, 1.5, 12, 24, 48, and 72 hours after reperfusion. After the last MRI study, the brains were fixed, sectioned, stained with hematoxylin and eosin, and evaluated for neuronal necrosis.

Results
—No MRI or histological abnormalities were observed in the sham-operated rats. In both the 10-minute and 30-minute groups, the perfusion deficits and DWI hyperintensities that occurred during occlusion disappeared shortly after reperfusion. The DWI, PWI, and T
2
WI results remained normal thereafter in the 10-minute group, whereas secondary DWI hyperintensity and T
2
WI abnormalities developed at the 12-hour observation point in the 30-minute group. Histological examinations demonstrated neuronal necrosis in both groups, but the number of necrotic neurons was significantly higher in the 30-minute group (95±4%) than in the 10-minute group (17±10%,
P
<0.0001).

Conclusions
—Transient or permanent resolution of initial DWI lesions depends on the duration of ischemia. Transient resolution of DWI lesions is associated with widespread neuronal necrosis; moreover, permanent resolution of DWI lesions does not necessarily indicate complete salvage of brain tissue from ischemic injury.
There’s No Place Like Home
Authors: Mayo Nancy E. , Wood-Dauphinee Sharon , Côté Robert , Gayton David , Carlton Joseph , Buttery Joanne , Tamblyn Robyn
Published: June 2011

Background and Purpose
—Because stroke management is aimed at facilitating community reintegration, it would be logical that the sooner the patient can be discharged home, the sooner reintegration can commence. The purpose of this study was to determine the effectiveness of prompt discharge combined with home rehabilitation on function, community reintegration, and health-related quality of life during the first 3 months after stroke.

Methods
—A randomized trial was carried out involving patients who required rehabilitation services and who had a caregiver at home. When medically ready for discharge, persons with stroke were randomized to either the home intervention group (n=58) or the usual care group (n=56). The home group received a 4-week, tailor-made home program of rehabilitation and nursing services; persons randomized to the usual care group received services provided through a variety of mechanisms, depending on institutional, care provider, and personal preference. The main outcome measure was the Physical Health component of the Measuring Outcomes Study Short-Form-36 (SF-36). Associated outcomes measures included the Timed Up & Go (TUG), Barthel Index (BI), the Older Americans Resource Scale for instrumental activities of daily living (OARS-IADL), Reintegration to Normal Living (RNL), and the SF-36 Mental Health component.

Results
—The total length of stay for the home group was, on average, 10 days, 6 days shorter than that for the usual care group. There were no differences between the 2 groups on the BI or on the TUG at either 1 or 3 months after stroke; however, there was a significantly beneficial impact of the home intervention on IADL and reintegration (RNL). By 3 months after stroke, the home intervention group showed a significantly higher score on the SF-36 Physical Health component than the usual care group. The total number of services received by the home group was actually lower than that received by the usual care group.

Conclusions
—Prompt discharge combined with home rehabilitation appeared to translate motor and functional gains that occur through natural recovery and rehabilitation into a greater degree of higher-level function and satisfaction with community reintegration, and these in turn were translated into a better physical health.
Home or Hospital for Stroke Rehabilitation? Results of a Randomized Controlled Trial
Authors: Anderson Craig , Rubenach Sally , Mhurchu Cliona Ni , Clark Michael , Spencer Carol , Winsor Adrian
Published: June 2011

Background and Purpose
—We wished to examine the effectiveness of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke.

Methods
—This was a randomized, controlled trial comparing early hospital discharge and home-based rehabilitation with usual inpatient rehabilitation and follow-up care. The trial was carried out in 2 affiliated teaching hospitals in Adelaide, South Australia. Participants were 86 patients with acute stroke (mean age, 75 years) who were admitted to hospital and required rehabilitation. Forty-two patients received early hospital discharge and home-based rehabilitation (median duration, 5 weeks), and 44 patients continued with conventional rehabilitation care after randomization. The primary end point was self-reported general health status (SF-36) at 6 months after randomization. A variety of secondary outcome measures were also assessed.

Results
—Overall, clinical outcomes for patients did not differ significantly between the groups at 6 months after randomization, but the total duration of hospital stay in the experimental group was significantly reduced (15 versus 30 days;
P
<0.001). Caregivers among the home-based rehabilitation group had significantly lower mental health SF-36 scores (mean difference, 7 points).

Conclusions
—A policy of early hospital discharge and home-based rehabilitation for patients with stroke can reduce the use of hospital rehabilitation beds without compromising clinical patient outcomes. However, there is a potential risk of poorer mental health on the part of caregivers. The choice of this management strategy may therefore depend on convenience and costs but also on further evaluations of the impact of stroke on caregivers.
Can Readmission After Stroke Be Prevented?
Authors: Andersen Hanne Elkjær , Schultz-Larsen Kirsten , Kreiner Svend , Forchhammer Birgitte Hysse , Eriksen Karen , Brown Anne
Published: June 2011

Background and Purpose
—About 50% of stroke survivors are discharged to their homes with lasting disability. Knowledge, however, of the importance of follow-up services that targets these patients is sparse. The purpose of the present study was to evaluate 2 models of follow-up intervention after discharge. The study hypothesis was that intervention could reduce readmission rates and institutionalization and prevent functional decline. We report the results regarding readmission.

Methods
—This randomized study included 155 stroke patients with persistent impairment and disability who, after the completion of inpatient rehabilitation, were discharged to their homes. The patients were randomized to 1 of 2 follow-up interventions provided in addition to standard care or to standard aftercare. Fifty-four received follow-up home visits by a physician (INT1-HVP), 53 were provided instructions by a physiotherapist in their home (INT2-PI), and 48 received standard aftercare only (controls). Baseline characteristics for the 3 groups were comparable. Six months after discharge, data were obtained on readmission and institutionalization.

Results
—The readmission rates within 6 months after discharge were significantly lower in the intervention groups than in the control group (INT1-HVP 26%, INT2-PI 34%, controls 44%;
P
=0.028). Multivariate analysis of readmission risk showed a significant favorable effect of intervention (INT1-HVP or INT2-PI) in interaction with length of hospital stay (
P
=0.0332), indicating that the effect of intervention was strongest for patients with a prolonged inpatient rehabilitation.

Conclusions
—Readmission is common among disabled stroke survivors. Follow-up intervention after discharge seems to be a way of preventing readmission, especially for patients with long inpatient rehabilitation.
A Multinational Comparison of Subarachnoid Hemorrhage Epidemiology in the WHO MONICA Stroke Study
Authors: Ingall Timothy , Asplund Kjell , Mähönen Markku , Bonita Ruth
Published: June 2011

Background and Purpose
—By official, mostly unvalidated statistics, mortality from subarachnoid hemorrhage (SAH) show large variations between countries. Using uniform criteria for case ascertainment and diagnosis, a multinational comparison of attack rates and case fatality rates of SAH has been performed within the framework of the WHO MONICA Project.

Methods
—In 25- to 64-year-old men and women, a total of 3368 SAH events were recorded during 35.9 million person-years of observation in 11 populations in Europe and China. Strict MONICA criteria were used for case ascertainment and diagnosis of stroke subtype. Case fatality was based on follow-up at 28 days after onset.

Results
—Age-adjusted average annual SAH attack rates varied 10-fold among the 11 populations studied, from 2.0 (95% CI 1.6 to 2.4) per 100 000 population per year in China-Beijing to 22.5 (95% CI 20.9 to 24.1) per 100 000 population per year in Finland. No consistent pattern was observed in the sex ratio of attack rates in the different populations. The overall 28-day case fatality rate was 42%, with 2-fold differences in age-adjusted rates between populations but little difference between men and women. Case fatality rates were consistently higher in Eastern than in Western Europe.

Conclusions
—Using a uniform methodology, the WHO MONICA Project has shown very large variations in attack rates of SAH across 11 populations in Europe and China. The generally accepted view that women have a higher risk of SAH than men does not apply to all populations. Marked differences in outcome of SAH add to the wide gap in the burden of stroke between East and West Europe.
Ischemic Stroke Subtypes
Authors: Petty George W. , Brown Robert D. , Whisnant Jack P. , Sicks JoRean D. , O’Fallon W. Michael , Wiebers David O.
Published: June 2011

Background and Purpose
—There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes.

Methods
—We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients.

Results
—Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later (
P
=0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different (
P
<0.001): ATH, 18.5% (95% CI 9.4% to 27.5%); CE, 5.3% (95% CI 1.2% to 9.6%); LAC, 1.4% (95% CI 0.0% to 4.1%); and IUC, 3.3% (95% CI 0.4% to 6.2%). After adjusting for age, sex, and stroke severity, infarct subtype was an independent determinant of recurrent stroke within 30 days (
P
=0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term (
P
=0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different (
P
<0.001): ATH, 32.2% (95% CI 21.1% to 43.2%); CE, 80.4% (95% CI 73.1% to 87.6%); LAC, 35.1% (95% CI 23.6% to 46.0%); and IUC, 48.6% (95% CI 40.5% to 56.7%). With adjustment for age, sex, cardiac comorbidity, and stroke severity, the subtype of ischemic stroke was an independent determinant of long-term (
P
=0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival (
P
=0.2).

Conclusions
—Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non–population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.
Impact on Stroke Subtype Diagnosis of Early Diffusion-Weighted Magnetic Resonance Imaging and Magnetic Resonance Angiography
Authors: Lee Lance J. , Kidwell Chelsea S. , Alger Jeffry , Starkman Sidney , Saver Jeffrey L.
Published: June 2011

Background and Purpose
—The purpose of the present study was to assess the diagnostic usefulness of early diffusion-weighted MRI (DWI) and MR angiography (MRA) in patients with ischemic stroke. Past approaches to stroke diagnosis required a series of diagnostic tests over several days of hospitalization. New magnetic resonance methodologies that include DWI and MRA may allow more rapid characterization of stroke pathophysiology. However, no previous study has assessed the impact on formal stroke subtype diagnosis of early imaging with DWI/MRA.

Methods
—We analyzed 46 consecutive patients with acute ischemic stroke who underwent DWI/MRA within 24 hours of admission. Initial diagnoses were rendered with use of the 2 most widely used formal stroke subtype classification schemes, the TOAST and the Oxfordshire methods, which were applied to patients after CT/conventional MRI but before DWI/MRA. Modified TOAST and Oxfordshire diagnoses were then rendered based on the results of day 1 DWI, MRA, and DWI plus MRA. Final TOAST/Oxfordshire diagnoses at discharge were taken as the gold standard.

Results
—Compared with final diagnoses, pre-MRI TOAST diagnoses matched final diagnoses in 48%, improving to 83% after DWI alone, 56% after MRA alone, and 94% after DWI plus MRA. For the TOAST diagnostic subtypes of large-vessel atherothromboembolism and small-vessel disease, pre-MRI diagnoses matched final diagnoses in 56% and 35% of patients, respectively, improving to 89% and 100% after DWI/MRA. Pre-MRI Oxfordshire diagnoses matched final diagnoses in 67% of patients, improving to 100% after DWI.

Conclusions
—The use of DWI/MRA within 24 hours of hospitalization substantially improves the accuracy of the diagnosis of early ischemic stroke subtype. When initial management and clinical trial eligibility decisions are influenced by stroke subtype, day 1 multimodal MRI is advantageous as a guide to therapy.
Leukocyte Accumulation and Hemodynamic Changes in the Cerebral Microcirculation During Early Reperfusion After Stroke
Authors: Ritter Leslie S. , Orozco Jose A. , Coull Bruce M. , McDonagh Paul F.
Published: June 2011

Background and Purpose
—Leukocytes contribute to cerebral ischemia-reperfusion injury. However, few experimental models examine both in vivo behavior of leukocytes and microvascular rheology after stroke. The purpose of the present study was to characterize patterns of leukocyte accumulation in the cerebral microcirculation and to examine the relationship between leukocyte accumulation and microcirculatory hemodynamics after middle cerebral artery occlusion and reperfusion (MCAO-R).

Methods
—Male rats (250 to 350 g) were anesthetized and ventilated. Tail catheters were inserted for measurement of arterial blood gases and administration of drugs. Body temperature was maintained at 37°C. Animals were subjected to 2 hours of MCAO by the filament method. A cranial-window preparation was performed, and the brain was superfused with warm, aerated artificial cerebrospinal fluid. Reperfusion was initiated by withdrawing the filament, and the pial microcirculation was observed by use of intravital fluorescence microscopy. Leukocyte accumulation in venules, arterioles, and capillaries; leukocyte rolling in venules; and leukocyte venular shear rate were assessed during 1 hour of reperfusion.

Results
—We found significant leukocyte adhesion in cerebral venules during 1 hour of reperfusion after 2 hours of MCAO. Leukocyte trapping in capillaries and adhesion to arterioles after MCAO-R tended to increase compared with controls, but the increase was not significant. We also found that shear rate was significantly reduced in venules during early reperfusion after MCAO.

Conclusions
—A model using the filament method of stroke and fluorescence microscopy was used to examine white-cell behavior and hemodynamics in the cerebral microcirculation after MCAO-R. We observed a significant increase in leukocyte rolling and adhesion in venules and a significant decrease in blood shear rate in the microcirculation of the brain during early reperfusion. Leukocytes may activate and damage the blood vessels and surrounding brain cells, which contributes to an exaggerated inflammatory component to reperfusion. The model described can be used to examine precisely blood cell–endothelium interactions and hemodynamic changes in the microcirculation during postischemic reperfusion. Information from these and similar experiments may contribute to our understanding of the early inflammatory response in the brain during reperfusion after stroke.
Progesterone Exacerbates Striatal Stroke Injury in Progesterone-Deficient Female Animals
Authors: Murphy Stephanie J. , Traystman Richard J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—We have previously shown that female animals experience substantial protection from brain injury after reversible middle cerebral artery occlusion (MCAO) compared with their male or ovariectomized female counterparts. The reproductive steroid estrogen has been shown to provide neuroprotection from a variety of experimental insults, but the importance of progesterone as an anti-ischemic treatment has not been well explored. We evaluated histological outcomes after MCAO in ovariectomized female rats with or without acute or chronic progesterone replacement therapy.

Methods
—Age-matched, adult female Wistar rats were ovariectomized and treated with 0, 30, or 60 mg/kg progesterone IP 30 minutes before ischemia (n=12 to 14 per group) or with 30 mg/kg progesterone IP daily for 7 to 10 days before ischemia (n=16). Each animal subsequently underwent 2 hours of MCAO with the intraluminal filament technique, followed by 22 hours of reperfusion. Ipsilateral parietal cortex perfusion was monitored with laser Doppler flowmetry throughout ischemia. Cortical, caudate-putamen, and hemispheric infarction volumes were determined with 2,3,5-triphenyltetrazolium chloride staining and digital image analysis.

Results
—Intraischemic plasma progesterone levels were 5±3, 102±20,* 181±28,* and 133±25* ng/mL in the 0, 30, and 60 mg/kg acute progesterone group and the 30 mg/kg chronic progesterone group, respectively (*
P
<0.05 compared with 0 mg/kg). Caudate-putamen infarction volume (percent contralateral structure) was significantly increased by chronic progesterone treatment: 45.6±5.1%* in the 30 mg/kg chronic progesterone group and 29.2±5.3%, 35.8±5.1%, and 42.0±5.0% in the 0, 30, and 60 mg/kg acute progesterone groups, respectively (*
P
<0.05 compared with 0 mg/kg). Cortical and total hemispheric infarction volumes (percent contralateral structure) were unchanged by progesterone treatment.

Conclusions
—Exogenous progesterone therapy does not ameliorate histological injury after MCAO in previously ovariectomized, adult female rats. Furthermore, chronic progesterone administration can exacerbate infarction in subcortical regions.
Urokinase Cisternal Irrigation Therapy for Prevention of Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Sasaki Tatsuya , Kodama Namio , Kawakami Masahisa , Sato Masahiro , Asari Jun , Sakurai Yoshiharu , Watanabe Kazuo , Onuma Takehide , Matsuda Tamotsu
Published: June 2011

Background and Purpose
—Cisternal irrigation therapy with urokinase (UK) was performed in multiple institutions to prevent symptomatic vasospasm. The efficacy and safety of this therapy were evaluated, and the optimal concentration of UK was estimated.

Methods
—This therapy was performed in 28 patients who underwent surgery within 72 hours of the onset of severe subarachnoid hemorrhage (Fisher’s group 3, CT number [Hounsfield units] >60). After the aneurysm was clipped, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally and in the prepontine or chiasmatic cistern (outlet). Lactated Ringer’s solution with UK (30, 60, or 120 IU/mL) was infused at a rate of 30 mL/h. The presence of symptomatic vasospasm was evaluated by changes in the clinical symptoms and the presence of a new low-density area on CT scan. Drained irrigation fluid and peripheral blood were examined chronologically to evaluate the fibrinolytic system.

Results
—Symptomatic vasospasm was observed transiently in 3 cases (10.7%) without any low-density area on CT scan. In the 120-IU/mL group, no symptomatic vasospasm occurred. Analysis of drainage fluid suggested that UK 120 IU/mL is effective. The mean values of total drained blood volume for the respective groups were as follows: 58 mL in 30 IU/mL, 106 mL in 60 IU/mL, and 143 mL in 120 IU/mL. No abnormal changes were observed in the coagulative and fibrinolytic systems after UK irrigation.

Conclusions
—These results suggest that cisternal irrigation therapy with UK is safe and effective for the prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.
Effect of the Apolipoprotein E ε4 Allele on White Matter Hyperintensities in Dementia
Authors: Hirono Nobutsugu , Yasuda Minoru , Tanimukai Satoshi , Kitagaki Hajime , Mori Etsuro
Published: June 2011

Background and Purpose
—The clinical significance of the apoE ε4 allele in white matter changes in patients with dementia has been a subject of debate. We studied the association between the apoE ε4 allele and white matter hyperintensities (WMHs) before and after control for (1) potential vascular risk factors and (2) the presence of lacunar infarcts in patients with dementia.

Methods
—The subjects were 131 patients with dementia who had either Alzheimer’s disease or vascular dementia, or a combination of these 2 types of dementia, with or without WMHs, lacunar infarcts, or both. The association of the ε4 allele with WMHs was examined before and after control for age, sex, duration of symptoms, education level, severity of dementia, presence of lacunar infarcts, and potential vascular risk factors, including hypertension, diabetes mellitus, lipid disorders, smoking habit, drinking habit, and cardiac diseases.

Results
—WMHs were observed in 73 (55.7%) of the patients. Neither the number of apoE ε4 alleles nor their presence was significantly associated with WMHs before or after control for the potential confounding factors. Multiple logistic regression analyses revealed that age, the presence of hypertension, and the presence of lacunar infarcts were independently associated with WMHs.

Conclusions
—The apoE ε4 allele was not associated with WMHs in patients with dementia. The fact that WMHs were significantly associated with hypertension and lacunar infarcts may indicate an ischemic origin of WMHs.
Ischemic Heart Disease in Black South African Stroke Patients
Authors: Joubert J. , McLean C. A. , Reid C. M. , Davel D. , Pilloy W. , Delport R. , Steyn L. , Walker A. R. P.
Published: June 2011

Background and Purpose
—Stroke patients in western countries frequently have coronary artery disease (CAD). In black Africans, CAD has been reported as being rare in both stroke patients and the general population. In this study, an attempt has been made to determine the prevalence of CAD in a black South African stroke population.

Methods
—The prevalence of CAD was determined by indicators identified through a series of 5 observational studies in black patients diagnosed with stroke. CAD indicators included (1) bedside diagnosis in 741 patients; (2) resting ECG in 555 consecutively admitted patients; (3) a combination of clinical examination, cardiac ultrasound, radionuclide scintigraphy, and multigated blood pool studies in 102 consecutively admitted patients; (4) thallium scintigraphy in 60 patients; and (5) necropsy in 23 patients.

Results
—On bedside questioning, only 0.7% complained of previous angina. There was no history given of myocardial infarction (MI), but documentation of this was found in the clinical notes of 0.7% of the patients. In the resting ECG study, evidence of myocardial ischemia was present in 14.6% and MI in 2.1%. In the combined study, cardiac ischemia was documented on ECG in 12.7% of patients and evidence of previous MI in 5.8%. Cardiac scintigraphic studies revealed changes of myocardial ischemia in 31.7% and MI in 13.3% of the 60 patients studied. Four (17.4%) of 23 patients in the necropsy study had histological evidence of previous MI, and 50% of all patients had evidence of >50% atherosclerotic stenosis in 1, 2, or 3 coronary arteries.

Conclusions
—The prevalence of CAD in black African stroke patients is significantly higher than has been documented in the general nonstroke black population as well as in stroke patients. Black stroke patients may have a risk for CAD similar to that of their white counterparts.
Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population
Authors: Kokubo Yoshihiro , Chowdhury Anisul Haque , Date Chigusa , Yokoyama Tetsuji , Sobue Hatiki , Tanaka Heizo
Published: June 2011

Background and Purpose
—The association between apolipoprotein E (apoE) polymorphisms and stroke has been controversial. These controversies may be due to inaccurate classification of stroke and differences in age ranges. We investigated the association between apoE genotypes and stroke subtypes (confirmed by CT or MRI findings) by case-control study in a Japanese rural population.

Methods
—First-ever-stroke patients (n=322; cerebral infarction, n=201, intracerebral hemorrhage, n=84, and subarachnoid hemorrhage, n=37) aged 40 to 89 years were recruited from Hokuetsu Hospital, Japan. Healthy controls (n=1126) were selected from the general population in the same area. ApoE genotypes were determined by restriction fragment-length polymorphism analysis.

Results
—Compared with apoE ε3/ε3 subjects, ε2 carriers had a 2-fold risk of cerebral infarction (OR 1.9, 95% CI 1.1 to 3.2). Among cerebral infarction patients, ε2 carriers had increased risks of cortical infarction (OR 2.4, 95% CI 1.3 to 4.6) (an anatomic subtype) and atherothrombosis (OR 3.9, 95% CI 1.7 to 9.0) and cardioembolism (OR 4.9, 95% CI 1.6 to 14.4) but not lacunar infarction (clinical subtypes). ApoE ε4 carriers had a 2.5-fold risk of subarachnoid hemorrhage (OR 2.5, 95% CI 1.1 to 5.4). ApoE ε2/ε2 subjects had an increased risk of intracerebral hemorrhage (OR 4.4, 95% CI 1.0 to 19.7). ApoE ε3/ε4 subjects showed ≈2-fold increased risk of atherothrombosis (OR 2.1, 95% CI 1.0 to 4.1) and intracerebral hemorrhage (OR 1.8, 95% CI 1.0 to 3.3). The association between ε2 and stroke was accentuated in subjects aged 70 years or older but not in those aged 40 to 69 years.

Conclusions
—Our study suggests that apoE ε2 is a risk factor for atherothrombosis, cardioembolism, and intracerebral hemorrhage, whereas ε4 is a risk factor for atherothrombosis, intracerebral hemorrhage, and subarachnoid hemorrhage. The occurrence of stroke may be affected by interaction between age and apoE gene polymorphisms.
Demographic, Morphological, and Clinical Characteristics of 1289 Patients With Brain Arteriovenous Malformation
Authors: Hofmeister C. , Stapf C. , Hartmann A. , Sciacca R. R. , Mansmann U. , terBrugge K. , Lasjaunias P. , Mohr J. P. , Mast H. , Meisel J.
Published: June 2011

Background and Purpose
—The purpose of this study was to assess demographic, clinical, and morphological characteristics of patients with brain arteriovenous malformations (AVMs).

Methods
—Prospectively collected data of 1289 consecutive AVM patients from 3 independent databases (1 multicenter [Berlin/Paris/Middle and Far East, n=662] and 2 single centers [New York, n=337, and Toronto, n=290]) were analyzed. The variables assessed were age at diagnosis, sex, AVM size, AVM drainage pattern, AVM location in functionally important brain areas (“eloquence”), and type of presentation (hemorrhage, seizure, chronic headache, or focal neurologic deficit). Comparisons were made by ANOVA, contingency tables, and log-linear models.

Results
—Overall, mean age at diagnosis was 31.2 years (95% CI 30.2 to 32.2 years), and 45% of the patients were female (95% CI 42% to 47%). AVM maximum diameter was <3 cm in 38% (95% CI 35% to 41%). Deep venous drainage was present in 55% (95% CI 52% to 59%). An eloquent AVM location was described in 71% (95% CI 69% to 74%). AVM hemorrhage occurred in 53% (95% CI 51% to 56%). Generalized or focal seizures were described in 30% (95% CI 27% to 33%) and 10% (95% CI 8% to 12%), respectively. Chronic headache was recorded in 14% (95% CI 12% to 16%). Persistent neurological deficits were found in 7% (95% CI 6% to 9%), and progressive neurological deficits in 5% (95% CI 4% to 6%). Significant differences between centers were found for age (
P
<0.001), sex (
P
=0.04), eloquence (
P
=0.04), size (
P
<0.001), hemorrhage (
P
=0.006), persistent neurological deficit (
P
<0.001), and reversible neurological deficit (
P
=0.013). The intercenter difference found for hemorrhage frequency did not remain after adjustment for AVM size.

Conclusions
—Baseline characteristics differed considerably between centers. The differences found in patient age and AVM size may be explained by center-specific referral patterns and the influence of access to treatment resources, whereas those found for other characteristics may be attributable to center-specific definitions. Analysis of natural history data from tertiary referral center databases may be improved by consistent definitions applicable to the entire population of AVM patients.
Monitoring Intravenous Recombinant Tissue Plasminogen Activator Thrombolysis for Acute Ischemic Stroke With Diffusion and Perfusion MRI
Authors: Schellinger Peter D. , Jansen Olav , Fiebach Jochen B. , Heiland Sabine , Steiner Thorsten , Schwab Stefan , Pohlers Olivia , Ryssel Henning , Sartor Klaus , Hacke Werner
Published: June 2011

Background and Purpose
—Intravenous recombinant tissue plasminogen activator (rtPA) administration is an effective therapy for ischemic stroke when initiated within 3 hours and possibly up to 6 hours after symptom onset. To improve patient selection, a fast diagnostic tool that allows reliable diagnosis of hemorrhage and ischemia, vessel status, and tissue at risk at an early stage may be useful. We studied the feasibility of stroke MRI for the initial evaluation and follow-up monitoring of patients undergoing intravenous thrombolysis.

Methods
—Stroke MRI (diffusion- and perfusion-weighted imaging [DWI and PWI, respectively], magnetic resonance angiography, and T2-weighted imaging) was performed before, during, or after thrombolysis and on days 2 and 5. We assessed clinical scores (National Institutes of Health Stroke Scale [NIHSS], Scandinavian Stroke Scale [SSS], Barthel Index, and Rankin scale) at days 1, 2, 5, 30, and 90. Furthermore, we performed volumetric analysis of infarct volumes on days 1, 2, and 5 as shown in PWI, DWI, and T2-weighted imaging.

Results
—Twenty-four patients received rtPA within a mean time interval after symptom onset of 3.27 hours and stroke MRI of 3.43 hours. Vessel occlusion was present in 20 of 24 patients; 11 vessels recanalized (group 1), and 9 did not (group 2). The baseline PWI lesion volume was significantly larger (
P
=0.008) than outcome lesion size in group 1, whereas baseline DWI lesion volume was significantly smaller (
P
=0.008) than final infarct size in group 2. Intergroup outcome differed significantly for all scores at days 30 and 90 (all
P
<0.01). Intragroup differences were significant in group 1 for change in SSS and NIHSS between day 1 and day 30 (
P
=0.003) and for SSS only between day 1 and day 90 (
P
=0.004).

Conclusions
—Stroke MRI provides comprehensive prognostically relevant information regarding the brain in hyperacute stroke. Stroke MRI may be used as a single imaging tool in acute stroke to identify and monitor candidates for thrombolysis. It is proposed that stroke MRI is safe, reliable, and cost effective; however, our data do not prove this assumption. Early recanalization achieved by thrombolysis can save tissue at risk if present and may result in significantly smaller infarcts and a significantly better outcome.
Mechanisms of Dysphagia in Suprabulbar Palsy With Lacunar Infarct
Authors: Ertekin Cumhur , Aydogdu Ibrahim , Tarlaci Sultan , Turman A. Bulent , Kiylioglu Nefati
Published: June 2011

Background and Purpose
—The objective of the present study was to investigate the neural mechanisms of dysphagia in suprabulbar palsy (SBP) with multiple lacunar infarct.

Methods
—We evaluated the swallowing disorders of patients with SBP (n=34) and age-matched healthy control subjects (n=35) by means of an electrophysiological method that recorded the oropharyngeal swallowing patterns. With this method, dysphagia limit, the triggering of voluntarily initiated swallows, duration of laryngeal relocation time, and total duration of oropharyngeal swallowing were recorded and measured. In addition, the EMG behavior of the cricopharyngeal (CP) muscle of the upper esophageal sphincter was also assessed.

Results
—In patients with SBP, the dysphagia limit in all except 1 patient was pathological with limits of <20-mL bolus volume, which is contrary to normal subjects, in whom the dysphagia limit exceeds the 20-mL bolus volume. Either triggering of swallowing reflex was delayed (
P
<0.04), or the swallow could hardly be triggered in 7 patients on the voluntary attempts for 3 mL water. Whenever the reflex swallowing could be triggered, it was slow and prolonged (
P
<0.01). The CP muscle of the upper esophageal sphincter appeared to have become hyperreflexic and incoordinated with laryngeal movements during swallowing.

Conclusions
—It was proposed that the progressive involvement of the excitatory and inhibitory corticobulbar fiber systems linked with the bulbar swallowing center is mainly responsible for the triggering difficulties of the swallowing reflex and for the hyperreflexic/incoordinated nature of the CP sphincter. In addition, the dysfunction of the extrapyramidal system has a specific role in the slowing of oropharyngeal swallowing and the accumulation of saliva in the mouth.
Amnesia due to Fornix Infarction
Authors: Moudgil Shyam S. , Azzouz Mouhannad , Al-Azzaz Abdulkader , Haut Marc , Gutmann Ludwig
Published: June 2011

Background and Purpose
—The fornix connects various structures involved in memory. We report a patient with anterograde amnesia after an acute ischemic infarct in the anterior fornix.

Case Description
—A 71-year-old female with acute-onset amnesia had neuroimaging studies showing ischemic infarction of both columns and the body of the fornix and the genu of the corpus callosum. Neuropsychological evaluation revealed anterograde amnesia without evidence of callosal disconnection. The patient showed marked improvement in her memory function on the follow-up visit.

Conclusions
—Amnesia in this case is likely due to infarction of the anterior fornix structures.
Outcome Measures in Acute Stroke Trials
Authors: Duncan Pamela W. , Jorgensen Henrik Stig , Wade Derick T.
Published: June 2011

Background
—There is little consistency in the measurement of outcome in acute stroke trials, and this may complicate interpretation of the results and reduce the likelihood of detecting worthwhile drug effects. This study aims to investigate empirically the measures used to date and to give recommendations for future studies.

Summary of Comment
—A systematic review of all published randomized studies of acute stroke drug intervention was undertaken, and the measures used were recorded. Fifty-one studies involving 57 214 subjects were identified. These studies used 14 different measures of impairment, 11 different measures of activity, 1 measure of “quality of life,” and 8 miscellaneous other measures. Timing of outcome assessments varied from 1 week to 1 year, with the modal time being 3 months. Many studies used ordinal measures but dichotomized results for analysis. Of the 51 studies included in the review, only 21 demonstrated benefit with the defined primary outcome measure. In several studies, however, post hoc analysis using varied outcome measures or varied cut points for dichotomizing outcomes resulted in positive results, whereas the primary study analysis failed to do so.

Conclusions
—There is no consensus on the level of outcome to be used, the method of measurement to be used, or the most appropriate timing of the assessment. It is recommended that future studies should include extended/instrumental activities and advanced mobility as components of the primary outcome measure, with outcome assessment being undertaken at 6 months. New initiatives in developing stroke-specific outcomes may address some of the current problems in the assessment of stroke outcomes