bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Endovascular Services and Hospital Volume on Cerebral Aneurysm Treatment Outcomes
Authors: Johnston S. Claiborne
Published: June 2011

Background and Purpose
—Endovascular coil embolization and angioplasty for cerebral vasospasm are offered by some centers for the treatment of unruptured and ruptured cerebral aneurysms. Whether the availability of these therapies improves outcomes at these institutions has not been evaluated.

Methods
—We assessed institutional factors in the outcomes of patients treated for cerebral aneurysms in the academic medical centers of the University Health Systems Consortium. In-hospital deaths (primary outcome), length of stay, and hospital charges were evaluated in multivariable models adjusted for age, sex, race, admission source, and admission status.

Results
—There were 2623 unruptured and 9534 ruptured aneurysm cases treated at 70 centers in the University Health Systems Consortium hospital discharge database during 1994–1997. Patients treated at institutions that more frequently used coil embolization were less likely to die in the hospital (relative risks [RRs] for every 10% of endovascular-treated cases: ruptured aneurysms: RR, 0.91; 95% CI, 0.86 to 0.96;
P
=0.001; unruptured aneurysms: RR, 0.84; 95% CI, 0.78 to 0.91;
P
<0.001). Patients treated at institutions that used angioplasty for vasospasm had a 16% reduction in risk of in-hospital death compared with patients treated at other institutions (RR, 0.84; 95% CI, 0.71 to 0.98;
P
=0.03). Hospital treatment volume was not independently associated with in-hospital death.

Conclusions
—-Patients treated for cerebral aneurysms at institutions offering endovascular services have lower rates of in-hospital mortality. Whether this is due to improved outcomes with endovascular therapy or is a marker for other aspects of multidisciplinary care cannot be answered in this analysis.
Early X-Ray Hypoattenuation of Brain Parenchyma Indicates Extended Critical Hypoperfusion in Acute Stroke
Authors: Grond M. , von Kummer R. , Sobesky J. , Schmülling S. , Rudolf J. , Terstegge K. , Heiss W.-D.
Published: June 2011

Background and Purpose
—The presence of early x-ray hypoattenuation is an important selection criterion for thrombolytic therapy. However, knowledge about the pathophysiological constellation reflected by this hypoattenuation is lacking. Our objective was to study the relationship between the presence of early CT hypoattenuation and the volumes of critical cortical hypoperfusion.

Methods
—In 32 patients with acute ischemic stroke, CT was performed 20 to 170 minutes (mean, 94 minutes) after symptom onset, and [
15
O]H
2
O-PET 20 to 120 minutes (mean, 67 minutes) later. CTs were scrutinized for the presence of hypoattenuation. On the PET scans, the volumes of critical cortical hypoperfusion were assessed.

Results
—CT hypoattenuation was present in 18 patients (56%), all of whom had critical cortical hypoperfusion and developed infarction. Of the 14 patients with normal CTs, critical hypoperfusion was found in 6, and 7 developed infarction. The mean volumes of critically hypoperfused tissue differed significantly (
P
=0.0001, Wilcoxon test) between the CT normal (mean 13.9 cm
3
, range 0 to 71 cm
3
) and the CT abnormal (mean 116.3 cm
3
, range 4 to 389 cm
3
) groups.

Conclusions
—Early presence of hypoattenuation is indicative of extended volumes of critically hypoperfused cortical tissue. The extent of hypoperfusion may exceed that of hypoattenuation, and some of that tissue might still be salvageable.
Neuroprotective Effects of Female Gonadal Steroids in Reproductively Senescent Female Rats
Authors: Alkayed Nabil J. , Murphy Stephanie J. , Traystman Richard J. , Hurn Patricia D.
Published: June 2011

Background and Purpose
—Young adult female rats sustain smaller infarcts after experimental stroke than age-matched males. This sex difference in ischemic brain injury in young animals disappears after surgical ovariectomy and can be restored by estrogen replacement. We sought to determine whether ischemic brain injury continues to be smaller in middle-aged, reproductively senescent female rats compared with age-matched males and to test the effect of ovarian steroids on brain injury after experimental stroke in females.

Methods
—Four groups of 16-month old Wistar rats (males [n=9], untreated females [n=9], and females pretreated with 17β-estradiol [25-μg pellets administered subcutaneously for 7 days; n=9] or progesterone [10-mg pellets administered subcutaneously for 7 days; n=9] were subjected to 2 hours of middle cerebral artery occlusion with the intraluminal filament technique, followed by 22 hours of reperfusion. Physiological variables and laser-Doppler cerebral cortical perfusion were monitored throughout ischemia and early reperfusion. In a separate cohort of males (n=3), untreated females (n=3), females pretreated with 17β-estradiol (n=3), and females pretreated with progesterone (n=3), end-ischemic regional cerebral blood flow was measured by [
14
C]iodoantipyrine autoradiography.

Results
—As predicted, infarct size was not different between middle-aged male and female rats. Cortical infarcts were 21±5% and 31±6% of ipsilateral cerebral cortex, and striatal infarcts were 44±7% and 43±5% of ipsilateral striatum in males and females, respectively. Both estrogen and progesterone reduced cortical infarct in reproductively senescent females (5±2% and 16±4% in estrogen- and progesterone-treated groups, respectively, compared with 31±6% in untreated group). Striatal infarct was smaller in the estrogen- but not in the progesterone-treated group. Relative change in laser-Doppler cerebral cortical perfusion from preischemic baseline and absolute end-ischemic regional cerebral blood flow were not affected by hormonal treatments.

Conclusions
—We conclude that the protection against ischemic brain injury found in young adult female rats disappears after reproductive senescence in middle-aged females and that ovarian hormones alleviate stroke injury in reproductively senescent female rats by a blood flow–independent mechanism. These findings support a role for hormone replacement therapy in stroke injury prevention in postmenopausal women.
Caspase Inhibitors Reduce Neuronal Injury After Focal but Not Global Cerebral Ischemia in Rats
Authors: Li Hui , Colbourne Frederick , Sun Ping , Zhao Zonghang , Buchan Alastair M.
Published: June 2011

Background and Purpose
—Studies show that blocking the activation of caspases by the caspase inhibitors z-VAD.FMK and z-DEVD.FMK can reduce ischemic neuronal injury after cerebral ischemia. Because the severity of ischemia was mild in some studies, we tested the efficacy of these caspase inhibitors on moderately severe but transient forebrain and focal ischemic insults in the rat.

Methods
—Various regimens of z-VAD, z-DEVD, and control DMSO were given to rats subjected to either 4-vessel occlusion ischemia (4-VO, 10-minute occlusion, 7-day survival) or distal middle cerebral artery occlusion (MCAo, 90-minute occlusion, 22.5-hour survival). In global ischemia, treatments were given immediately after ischemia (experiment 1) or as preischemic and postischemic treatments (experiment 2). Three focal ischemia experiments were done. Injection times were 60 minutes into ischemia (experiment 1) and 60 minutes into ischemia plus 30 and 120 minutes after ischemia (experiment 2). Experiment 3 was identical to experiment 2 except that a 30-minute preischemia treatment was instituted. Core normothermia was maintained in all experiments during ischemia. However, in the last focal and global experiments, core and brain temperatures, respectively, were also measured after ischemia with telemetry probes. Because hyperthermia accompanied z-DEVD treatment, an extra z-DEVD–treated group (MCAo) was included with temperature clamped at normothermia.

Results
—Neither z-VAD nor z-DEVD significantly reduced CA1 injury after global ischemia. In focal ischemia, both drugs significantly reduced infarction, but only in the third experiment, and the prevention of hyperthermia that accompanied z-DEVD treatment did not alter this.

Conclusions
—These results suggest a detrimental role of caspases in moderately severe focal but not global cerebral ischemia.
Hyperglycemia Enhances Extracellular Glutamate Accumulation in Rats Subjected to Forebrain Ischemia
Authors: Li Ping-An , Shuaib Ashfaq , Miyashita Hiro , He Qing-Ping , Siesjö Bo K.
Published: June 2011

Background and Purpose
—An increase in serum glucose at the time of acute ischemia has been shown to adversely affect prognosis. The mechanisms for the hyperglycemia-exacerbated damage are not fully understood. The objective of this study was to determine whether hyperglycemia leads to enhanced accumulation of extracellular concentrations of excitatory amino acids and whether such increases correlate with the histopathological outcome.

Methods
—Rats fasted overnight were infused with either glucose or saline 45 minutes before the induction of 15 minutes of forebrain ischemia. Extracellular glutamate, glutamine, glycine, taurine, alanine, and serine concentrations were measured before, during, and after ischemia in both the hippocampus and the neocortex in both control and hyperglycemic animals. The histopathological outcome was evaluated by light microscopy.

Results
—There was a significant increase in extracellular glutamate levels in the hippocampus and cerebral cortex in normoglycemic ischemic animals. The increase in glutamate levels in the cerebral cortex, but not in the hippocampus, was significantly higher in hyperglycemic animals than in controls. Correspondingly, exaggerated neuronal damage was observed in neocortical regions in hyperglycemic animals.

Conclusions
—The present results demonstrate that, at least in the neocortex, preischemic hyperglycemia enhances the accumulation of extracellular glutamate during ischemia, providing a tentative explanation for why neuronal damage is exaggerated.
Geographic Variation in Stroke Risk in the United States
Authors: Obisesan Thomas O. , Vargas Clemencia M. , Gillum Richard F.
Published: June 2011

Background
—In the United States, stroke mortality is higher in the south than in other regions. Hypertension is the main risk factor for stroke among older adults; however, few studies have examined group-specific regional and urbanization differences in hypertension prevalence.

Methods
—Data from the Third National Health and Nutritional Examination Survey (NHANES III), 1988 to 1994, were analyzed to calculate the prevalence of hypertension (systolic >140 mm Hg and/or diastolic >90 mm Hg and/or taking antihypertensive medication) by region and urbanization for age (40 to 59 and 60 to 79 years), sex, and ethnic subgroups. Logistic regression models were fitted to estimate the association of hypertension with region and urbanization.

Results
—With age and urbanization kept constant, southern residence was associated with hypertension among middle-aged non-Hispanic white men (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.12 to 1.90;
P
<0.006), non-Hispanic black men (OR, 1.36; 95% CI, 1.05 to 1.66;
P
=0.019), and non-Hispanic black women (OR, 1.23; 95% CI, 1.01 to 1.45;
P
=0.034). Among older non-Hispanic white men, a significant interaction was noted between region and urbanization (
P
=0.01), with a higher prevalence in the south only for nonmetropolitan residents (OR, 1.32; 95% CI, 1.06 to 1.56;
P
<0.013). A similar but not statistically significant trend was also confirmed among non-Hispanic black men in logistic regression analysis (OR, 1.38; 95% CI, 0.97 to 1.68;
P
=0.061). No statistically significant association was observed for urbanization or region in the other subgroups.

Conclusions
—Southern residence was associated with increased hypertension prevalence among middle-aged non-Hispanic white men, non-Hispanic black men and women, and older non-Hispanic white men.
Low Plasma Antioxidant Activity Is Associated With High Lesion Volume and Neurological Impairment in Stroke
Authors: Leinonen Janne S. , Ahonen Jukka-Pekka , Lönnrot Kimmo , Jehkonen Mervi , Dastidar Prasum , Molnár Gábor , Alho Hannu
Published: June 2011

Background and Purpose
—Oxidative stress is probably involved in neuronal damage induced by ischemia-reperfusion. The purpose of this study was to assess the role of antioxidant activity in cerebral ischemic stroke.

Methods
—Antioxidant activity of blood plasma and cerebrospinal fluid was assessed in 22 patients with cerebral hemisphere infarction that was verified and quantified by MRI.

Results
—Low total peroxyl radical trapping potential of plasma, but not of cerebrospinal fluid, was associated with high lesion volume and high neurological impairment assessed by scores on NIH Stroke Scale, Barthel Index, and Hand Motor Score tests. The plasma concentrations of ascorbic acid, α-tocopherol, and protein thiols were also associated with the degree of neurological impairment.

Conclusions
—These data suggest that the antioxidant activity of plasma may be an important factor providing protection from neurological damage caused by stroke-associated oxidative stress.
Prevalence of Renal Artery Stenosis in Autopsy Patients With Stroke
Authors: Kuroda Setsuko , Nishida Naoki , Uzu Takashi , Takeji Masanobu , Nishimura Masataka , Fujii Takashi , Nakamura Satoko , Inenaga Takashi , Yutani Chikao , Kimura Genjiro
Published: June 2011

Background and Purpose
—Atherosclerotic renal artery stenosis commonly exists as one manifestation of more generalized atherosclerosis. It is a progressive but potentially curable disorder. Thus, information on renal artery involvement in atherosclerotic diseases could be important. We investigated the prevalence of renal artery stenosis in autopsied patients with stroke over 40 years of age.

Methods
—From 2167 consecutive autopsy patients who died between 1980 and 1997, we studied 346 cases of mean age of 69±11 years with clinical evidence of stroke.

Results
—Atherosclerotic renal artery stenosis (≥75% luminal area narrowing) was found in 36 patients (10.4%). Patients with renal artery stenosis were older and had worse renal function. Renal artery stenosis was found in 14.7%, 28.6%, and 23.9% of patients with hypertension, renal insufficiency, and aortic aneurysm, respectively. Extracranial carotid artery stenosis (>50% luminal area narrowing) was found in 101 patients (29.2%). Of the 346 stroke patients, 256 had a history of brain infarction. In patients with brain infarction, renal artery stenosis was found in 31 (12.1%) and carotid stenosis was found in 81 (33.6%). Patients with carotid artery stenosis were more likely to have renal artery stenosis than patients without carotid artery stenosis (24.4% versus 5.9%,
P
<0.0001). Multiple logistic regression analysis identified renal insufficiency, hypertension, female gender, and presence of carotid artery stenosis as independent predictors of renal artery stenosis in patients with brain infarction.

Conclusions
—These data reveal that atherosclerotic renal artery stenosis is common in patients with stroke, especially in those with brain infarction.
Mild Resuscitative Hypothermia to Improve Neurological Outcome After Cardiac Arrest
Authors: Zeiner Andrea , Holzer Michael , Sterz Fritz , Behringer Wilhelm , Schörkhuber Waltraud , Müllner Marcus , Frass Michael , Siostrzonek Peter , Ratheiser Klaus , Kaff Alfred , Laggner Anton N.
Published: June 2011

Background and Purpose
—Recent animal studies showed that mild resuscitative hypothermia improves neurological outcome when applied after cardiac arrest. In a 3-year randomized, prospective, multicenter clinical trial, we hypothesized that mild resuscitative cerebral hypothermia (32°C to 34°C core temperature) would improve neurological outcome after cardiac arrest.

Methods
—We lowered patients’ temperature after admission to the emergency department and continued cooling for at least 24 hours after arrest in conjunction with advanced cardiac life support. The cooling technique chosen was external head and total body cooling with a cooling device in conjunction with a blanket and a mattress. Infrared tympanic thermometry was monitored before a central pulmonary artery thermistor probe was inserted.

Results
—In 27 patients (age 58 [interquartile range [IQR] 52 to 64] years; 7 women; estimated “no-flow” duration 6 [IQR 1 to 11] minutes and “low-flow” duration 15 [IQR 9 to 23] minutes; admitted to the emergency department 36 [IQR 24 to 43] minutes after return of spontaneous circulation), we could initiate cooling within 62 (IQR 41 to 75) minutes and achieve a pulmonary artery temperature of 33±1°C 287 (IQR 42 to 401) minutes after cardiac arrest. During 24 hours of mild resuscitative hypothermia, no major complications occurred. Passive rewarming >35°C was accomplished within 7 hours.

Conclusions
—Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states.
A Population-Based Study of Transient Ischemic Attack Incidence in Novosibirsk, Russia, 1987–1988 and 1996–1997
Authors: Feigin Valery L. , Shishkin Sergey V. , Tzirkin Georgii M. , Vinogradova Tatyana E. , Tarasov Alexey V. , Vinogradov Sergey P. , Nikitin Yury P.
Published: June 2011

Background and Purpose
—Population-based data on transient ischemic attack (TIA) incidence are scarce. This study defines incidence rates of first-ever TIA in Novosibirsk, Russia, during 1987–1997 and compares the incidence of first TIA with that of first stroke.

Methods
—This is a prospective registry population-based study of all new cases of TIA and stroke in an overall population of 455 765 residents of Novosibirsk. All new TIA and stroke incident cases (whether inpatient or outpatient) that occurred during 1987–1988 and 1996–1997 study periods were recorded and analyzed. A 95% CI was estimated for all age- and sex-specific strata.

Results
—During the 2 study periods, a total of 211 patients with first TIA were registered in the population studied. The crude annual TIA incidence rate per 100 000 residents was 16 (95% CI, 8 to 33) in 1987–1988 and 29 (95% CI, 9 to 87) in 1996–1997; these rates standardized to the European population were 17 (95% CI, 8 to 34) and 27 (95% CI, 9 to 79), respectively. Eighty-three percent of TIAs occurred in the carotid arteries (rate, 48/100 000), 10% occurred in the vertebrobasilar territory (rate, 6/100 000), and 7% of cases had a TIA of uncertain distribution (rate, 2/100 000).

Conclusions
—Unlike stroke incidence rate, the incidence rate of TIA in Novosibirsk is similar to that in other populations and constitutes approximately 10% of stroke incidence. For the last decade (1987–1997), there was a tendency, although statistically insignificant, toward increasing incidence rate of TIA in the population studied.
Serum Vitamin C Concentration Was Inversely Associated With Subsequent 20-Year Incidence of Stroke in a Japanese Rural Community
Authors: Yokoyama Tetsuji , Date Chigusa , Kokubo Yoshihiro , Yoshiike Nobuo , Matsumura Yasuhiro , Tanaka Heizo
Published: June 2011

Background and Purpose
—Epidemiological evidence suggests that vitamin C may decrease the risk of stroke. The purpose of the present study was to examine the association of serum vitamin C concentration with the subsequent incidence of stroke.

Methods
—In a Japanese rural community, a cohort of 880 men and 1241 women aged 40 years and older who were initially free of stroke was examined in 1977 and followed until 1997. The baseline examination included a measurement of serum vitamin C concentration. The incidence of stroke was determined by annual follow-up examinations and registry.

Results
—During the 20-year observation period, 196 incident cases of all stroke, including 109 cerebral infarctions and 54 hemorrhagic strokes, were documented. Strong inverse associations were observed between serum vitamin C concentration and all stroke (sex- and age-adjusted hazard ratios were 0.93, 0.72, and 0.59, respectively, for the second, third, and fourth quartiles compared with the first quartile;
P
for trend=0.002), cerebral infarction (0.71, 0.59, and 0.51;
P
for trend=0.015), and hemorrhagic stroke (0.89, 0.75, and 0.45;
P
for trend=0.013). Additional adjustments for blood pressure, serum total cholesterol, body mass index, physical activity, smoking, alcohol drinking, antihypertensive medication, atrial fibrillation, and history of ischemic heart disease did not attenuate these associations markedly.

Conclusions
—Serum vitamin C concentration was inversely related to the subsequent incidence of stroke. This relationship was significant for both cerebral infarction and hemorrhagic stroke. Additional mechanistic hypotheses may be required to explain our findings.
Orthostatic Hypotension as a Risk Factor for Stroke
Authors: Eigenbrodt Marsha L. , Rose Kathryn M. , Couper David J. , Arnett Donna K. , Smith Robert , Jones Daniel
Published: June 2011

Background and Purpose
—The association between orthostatic hypotension (OH) and stroke has rarely been investigated in longitudinal studies. The purpose of the present study was to determine whether OH predicts ischemic stroke in a middle-aged, biethnic population after adjustment for known stroke risk factors. Diastolic, systolic, and consensus OH were evaluated for baseline associations and for the ability to predict stroke.

Methods
—In 11 707 persons from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of stroke and overt heart disease at baseline, Cox proportional hazards analyses modeled the association between OH at baseline and incident ischemic stroke over 7.9 years of follow-up. OH was defined as a systolic blood pressure drop ≥20 mm Hg (systolic OH), a diastolic blood pressure drop ≥10 mm Hg (diastolic OH), or a drop in either (consensus OH) when a person changed from a supine to standing position.

Results
—OH was predictive of ischemic stroke, even after adjustment for numerous stroke risk factors (consensus OH: hazard ratio, 2.0; 95% CI, 1.2 to 3.2). While the baseline characteristics associated with OH varied depending on the type of OH, all types of OH had a similar risk of stroke.

Conclusions
—OH is an easily obtained measurement that may help to identify middle-aged persons at risk for stroke.
Cerebral Autoregulation in Subjects Adapted and Not Adapted to High Altitude
Authors: Jansen Gerard F. A. , Krins Anne , Basnyat Buddha , Bosch Andries , Odoom Joseph A.
Published: June 2011

Background and Purpose
—Impaired cerebral autoregulation (CA) from high-altitude hypoxia may cause high-altitude cerebral edema in newcomers to a higher altitude. Furthermore, it is assumed that high-altitude natives have preserved CA. However, cerebral autoregulation has not been studied at altitude.

Methods
—We studied CA in 10 subjects at sea level and in 9 Sherpas and 10 newcomers at an altitude of 4243 m by evaluating the effect of an increase of mean arterial blood pressure (MABP) with phenylephrine infusion on the blood flow velocity in the middle cerebral artery (Vmca), using transcranial Doppler. Theoretically, no change of Vmca in response to an increase in MABP would imply perfect autoregulation. Complete loss of autoregulation is present if Vmca changes proportionally with changes of MABP.

Results
—In the sea-level group, at a relative MABP increase of 23±4% during phenylephrine infusion, relative Vmca did not change essentially from baseline Vmca (2±7%,
P
=0.36), which indicated intact autoregulation. In the Sherpa group, at a relative MABP increase of 29±7%, there was a uniform and significant increase of Vmca of 24±9% (
P
<0.0001) from baseline Vmca, which indicated loss of autoregulation. The newcomers showed large variations of Vmca in response to a relative MABP increase of 21±6%. Five subjects showed increases of Vmca of 22% to 35%, and 2 subjects showed decreases of Vmca of 21% and 23%.

Conclusions
—All Sherpas and the majority of the newcomers showed impaired CA. It indicates that an intact autoregulatory response to changes in blood pressure is probably not a hallmark of the normal human cerebral vasculature at altitude and that impaired CA does not play a major role in the occurrence of cerebral edema in newcomers to the altitude.
Finding the Most Powerful Measures of the Effectiveness of Tissue Plasminogen Activator in the NINDS tPA Stroke Trial
Authors: Broderick Joseph P. , Lu Mei , Kothari Rashmi , Levine Steven R. , Lyden Patrick D. , Haley E. Clark , Brott Thomas G. , Grotta James , Tilley Barbara C. , Marler John R. , Frankel Michael
Published: June 2011

Background and Purpose
—We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial.

Methods
—Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of “early activity” of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and “efficacy” and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results.

Results
—Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score ≤2 at 24 hours, which provided an odds ratio of 5.4 (95% CI, 2.4 to 12.1) and a projected sample size of 58 per treatment group assuming an α of 0.05 (2-sided test) and a power of 80% using part I data. The top 2 and 3 of the top 5 outcome measures for detecting the longer-term efficacy of tPA also involved the NIHSS score. A Rankin score of 0 or 1 at 3 months was the third most powerful outcome measure. Outcome measures identified by CART from part I data were not as sensitive in detecting the effectiveness of tPA when applied to part II data.

Conclusions
—Measures using the NIHSS and a Rankin score ≤1 were the most sensitive discriminators of the effectiveness of tPA in the NINDS tPA Stroke Trial compared with the other clinical and radiological measures. The outcome measures identified in this exploratory analysis (eg, NIHSS score ≤2 at 24 hours) would be best used as an outcome measure in future phase II trials of recanalization begun within the first 3 hours after stroke onset, with inclusion and exclusion criteria similar to those in the NINDS tPA Stroke Trial.
Determinants of Neurological Outcome After Surgery for Brain Arteriovenous Malformation
Authors: Hartmann A. , Stapf C. , Hofmeister C. , Mohr J. P. , Sciacca R. R. , Stein B. M. , Faulstich A. , Mast H.
Published: June 2011

Background and Purpose
—We sought to define determinants of neurological deficit after surgery for brain arteriovenous malformation (AVM).

Methods
—One hundred twenty-four prospective patients (48% women, mean age 33 years) underwent microsurgical brain AVM resection. Patients were examined by 3 study neurologists immediately before surgery, postoperatively in-hospital, by in-person long-term follow-up, and with a structured telephone follow-up. They were classified according to the 5-point Spetzler-Martin grading system, with its 3 elements: size, venous drainage pattern, and location. The functional neurological status was classified with the modified Rankin scale. Multivariate logistic regression models were applied to test the effect of patient age, gender, and the 3 Spetzler-Martin elements on early and long-term postoperative neurological complications.

Results
—Twelve patients (10%) were classified as Spetzler-Martin grade 1; 36 (29%) as grade 2; 47 (38%) as grade 3; 26 (21%) as grade 4; and 3 (2%) as grade 5. Postoperatively, in-hospital, 51 patients (41%) showed new neurological deficits (15% disabling [ie, Rankin scale score >2] and 26% nondisabling [ie, Rankin 1 or 2]). At long-term follow-up (mean follow-up time 12 months), 47 patients (38%) revealed surgery-related neurological deficits (6% disabling; 32% nondisabling). The rate of neurological complications increased by Spetzler-Martin grade. Female gender, AVM size, and deep venous drainage were significantly associated with neurological deficits at in-hospital and long-term evaluation. For patient age and AVM location, no significant association was found.

Conclusions
—The findings suggest that female gender, AVM size, and AVM drainage into the deep venous system may be determinants of neurological deficit after microsurgical AVM resection.
Relationship Between Apparent Diffusion Coefficient and Subsequent Hemorrhagic Transformation Following Acute Ischemic Stroke
Authors: Tong David C. , Adami Alessandro , Moseley Michael E. , Marks Michael P.
Published: June 2011

Background and Purpose
—A method for identifying patients at increased risk for developing secondary hemorrhagic transformation (HT) after acute ischemic stroke could be of significant value, particularly in patients being considered for thrombolytic therapy. We hypothesized that diffusion-weighted MRI might aid in the identification of such patients.

Methods
—We retrospectively analyzed 17 patients with ischemic stroke who received diffusion-weighted MRI within 8 hours of symptom onset and who also received follow-up neuroimaging within 1 week of initial scan. The apparent diffusion coefficient (ADC) for each pixel in the whole ischemic area was calculated, generating a histogram of values. Areas subsequently experiencing HT were then compared with areas not experiencing HT to determine the relationship between ADC and subsequent HT.

Results
—A significantly greater percentage of pixels possessed lower ADCs (≤550×10
−
6
mm
2
/s) in HT lesions compared with non-HT lesions (47% versus 19%;
P
<0.001). Moreover, >40% of the pixels possessed values ≤550×10
−
6
mm
2
/s in all lesions experiencing secondary HT, compared with <31% of the pixels in the non-HT-destined lesions.

Conclusions
—HT-destined stroke regions possess a significantly great percentage of low ADC values than non-HT-destined regions. Early measurement of ADC values may be a useful tool for assessing secondary HT risk.
Repetitive Bilateral Arm Training With Rhythmic Auditory Cueing Improves Motor Function in Chronic Hemiparetic Stroke
Authors: Whitall Jill , Waller Sandy McCombe , Silver Kenneth H. C. , Macko Richard F.
Published: June 2011

Background and Purpose
—Chronic upper extremity hemiparesis is a leading cause of functional disability after stroke. We investigated the hypothesis that bilateral arm training with rhythmic auditory cueing (BATRAC) will improve motor function in the hemiparetic arm of stroke patients.

Methods
—In this single group pilot study we determined the effects of 6 weeks of BATRAC on 14 patients with chronic hemiparetic stroke (median time after stroke, 30 months) immediately after training and at 2 months after training. Four 5-minute periods per session (3 times per week) of BATRAC were performed with the use of a custom-designed arm training machine.

Results
—The patients showed significant and potentially durable increases in the following: Fugl-Meyer Upper Extremity Motor Performance Test of impairment (
P
<0.0004), Wolf Motor Function Test (performance time measure,
P
<0.02), and University of Maryland Arm Questionnaire for Stroke measuring daily use of the hemiparetic arm (
P
<0.002). Isometric strength improved in elbow flexion (
P
<0.05) and wrist flexion (
P
<0.02) for the paretic arm and in elbow flexion (
P
<0.02) and wrist extension (
P
<0.02) for the nonparetic arm. Active range of motion improved for paretic-side shoulder extension (
P
<0.01), wrist flexion (
P
<0.004), and thumb opposition (
P
<0.002), and passive range of motion improved for paretic wrist flexion (
P
<0.03).

Conclusions
—Six weeks of BATRAC improves functional motor performance of the paretic upper extremity as well as a few changes in isometric strength and range of motion. These benefits are largely sustained at 8 weeks after training cessation.
Effect of Triamcinolone Acetonide Injections on Hemiplegic Shoulder Pain
Authors: Snels Ingrid A. K. , Beckerman Heleen , Twisk Jos W. R. , Dekker Jos H. M. , Peter de Koning  , Koppe Peter A. , Lankhorst Gustaaf J. , Bouter Lex M.
Published: June 2011

Background and Purpose
—Hemiplegic shoulder pain is not uncommon after stroke. Its origin is still unknown, and although many different methods of treatment are applied, none have yet been proved to be effective. We sought to study the efficacy of 3 injections of intra-articular triamcinolone acetonide on pain and arm function in stroke patients with hemiplegic shoulder pain.

Methods
—In a multicenter, randomized, placebo-controlled clinical trial, patients with hemiplegic shoulder pain received either 3 intra-articular injections of 40 mg triamcinolone acetonide or 1 mL physiological saline solution (placebo). Primary outcomes were pain measured according to 3 visual analogue scales (score range, 0 to 10), and arm function was measured by means of the Action Research Arm test and the Fugl-Meyer assessment scale; secondary outcomes were passive external rotation of the shoulder and general functioning measured according to Barthel Index and the Rehabilitation Activities Profile.

Results
—In the triamcinolone group (n=18), the median decrease in pain, 3 weeks after the last injection, was 2.3 (interquartile range, 0.3 to 4.3) versus 0.2 (interquartile range, −0.5 to 2.2) in the placebo group. This result was not statistically significant. The change in the other outcome measures did not differ significantly between the 2 treatment groups. Twenty-five patients reported side effects.

Conclusions
—In the 37 participants included in this study, triamcinolone injections seemed to decrease hemiplegic shoulder pain and to accelerate recovery, but this effect was not statistically significant. Therefore, on the basis of the results of this study, these injections cannot be recommended for the treatment of patients with hemiplegic shoulder pain.
Development of an Ischemic Stroke Survival Score
Authors: Williams G. Rhys , Jiang John G.
Published: June 2011

Background and Purpose
—There has been substantial interest in identifying predictors of survival for stroke patients. Current instruments used for measuring stroke severity are confined to either neurological, functional, or disability measures. The purpose of this study was to develop a stroke survival score that combines instruments from different domains to better predict long-term survival.

Methods
—We took advantage of a particularly broad array of clinical and physiological variables collected during the Stroke Treatment with Ancrod Trial. Four hundred fifty-three patients completed a battery of instruments at day 7 after stroke and then were followed for 1 year.

Results
—Of the 453 patients, 53% were male, 77% were aged 65 years or older, and 89% were white. One hundred nine patients (24%) died during the study period. Age was a highly significant predictor of mortality (
P
<0.001), but there were no statistically significant differences in 12-month survival with respect to sex, race, or educational level. The best model for predicting survival was the Ischemic Stroke Survival Score. This model included the Scandinavian Stroke Scale, Rapid Disability Rating Scale, age, and prior stroke. This model had substantially greater predictive power (
R
2
=0.30, c statistic=0.86) than the Scandinavian Stroke Scale alone (
R
2
=0.20, c statistic=0.78).

Conclusions
—This study demonstrates that combining day 7 poststroke information from multiple domains substantially improves the ability to predict 12-month survival of ischemic stroke patients compared with data from a single domain. The high mortality rate emphasizes the importance of preventive measures for a disease that has identifiable and modifiable risk factors.
Stroke and Apolipoprotein E ε4 Are Independent Risk Factors for Cognitive Decline
Authors: Dik M. G. , Deeg D. J. H. , Bouter L. M. , Corder E. H. , Kok A. , Jonker C.
Published: June 2011

Background and Purpose
—Stroke and apolipoprotein E ε4 (ApoE ε4) are individually important risk factors for cognitive decline, including Alzheimer disease. It has been suggested that ApoE ε4 multiplies the risk for cognitive decline following stroke. In a population-based sample, using well-defined sensitive cognitive measures, this study investigates whether cognitive decline following stroke is worse for patients who carry the ApoE ε4 allele.

Methods
—Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The sample consisted of 1224 subjects, aged 62 to 85 years, who participated in the 3-year follow-up examination and for whom ApoE and stroke data were complete. We assessed cognitive decline using the Mini-Mental State Examination, the Auditory Verbal Learning Test (memory: immediate and delayed recall), and the Coding Task (information processing speed). The effects of stroke and ApoE ε4 on cognitive decline were evaluated with ANOVA and multiple logistic regression analysis, adjusted for age, sex, education, and baseline cognition.

Results
—A synergistic effect modification for stroke and ApoE ε4 on cognitive decline was not observed. Unexpectedly, instead, stroke patients carrying the ε4 allele demonstrated a nonsignificantly lowered risk for Mini-Mental State Examination decline (OR=0.3; 95% CI 0.1 to 1.1). ApoE ε4 was associated with declines in information processing speed (OR=1.5; 95% CI 1.1 to 2.1) and small declines for immediate and delayed recall.

Conclusions
—Stroke and ApoE ε4 may impair cognition through distinct nonsynergistic mechanisms. The slowing of information processing speed for ApoE ε4 carriers was more evident than impairment in memory.
Symptomatic Ischemic Stroke in Full-Term Neonates
Authors: Günther Gudrun , Junker Ralf , Sträter Ronald , Schobess Rosemarie , Kurnik Karin , Kosch Andrea , Nowak-Göttl Ulrike , Group for the Childhood Stroke Study
Published: June 2011

Background and Purpose
—The present multicenter case-control study was prospectively designed to assess the extent to which single and combined clotting factor abnormalities influence the onset of symptomatic ischemic stroke in full-term neonates.

Methods
—Lipoprotein (Lp)(a); the factor V (FV) G1691A mutation; the prothrombin (PT) G20210A variant; the methylenetetrahydrofolate reductase (MTHFR) T677T genotype; antithrombin; protein C; protein S; and anticardiolipin antibodies (ACAs) were investigated in 91 consecutively recruited neonatal stroke patients and 182 age- and sex-matched healthy controls.

Results
—Sixty-two of 91 stroke patients (68.1%) had at least 1 prothrombotic risk factor compared with 44 control subjects (24.2%) (odds ratio [OR]/95% confidence interval [CI], 6.70/3.84 to 11.67). An increased Lp(a) level (>30 mg/dL) was found in 20 patients and 10 controls (OR/95% CI, 4.84/2.16 to 10.86); FV G1691A was present in 17 patients and 10 controls (OR/95% CI, 3.95/1.72 to 9.0); the PT G20210A variant was detected in 4 patients and 4 controls (OR/95% CI, 2.04/0.49 to 8.3); the MTHFR TT677 genotype was found in 15 patients and 20 controls (OR/95% CI, 1.59/0.77 to 3.29); and protein C type I deficiency was found in 6 neonates. Neither antithrombin deficiency nor protein S deficiency was found in the neonatal patients studied. Acquired IgG ACAs were found in 3 cases. Additional triggering factors, ie, asphyxia, septicemia, maternal diabetes, and perinatally acquired renal venous thrombosis, were reported in 54.0% of patients.

Conclusions
—Besides acquired triggering factors, the data presented here suggest that genetic prothrombotic risk factors play a role in symptomatic neonatal stroke.
Experimental Radiosurgery Simulations Using a Theoretical Model of Cerebral Arteriovenous Malformations
Authors: Massoud Tarik F. , Hademenos George J. , De Salles Antonio A.F. , Solberg Timothy D.
Published: June 2011

Background and Purpose
—A novel biomathematical arteriovenous malformation (AVM) model based on electric network analysis was used to investigate theoretically the potential role of intranidal hemodynamic perturbations in elevating the risk of rupture after simulated brain AVM radiosurgery.

Methods
—The effects of radiation on 28 interconnected plexiform and fistulous AVM nidus vessels were simulated by predefined random or stepwise occlusion. Electric circuit analysis revealed the changes in intranidal flow, pressure, and risk of rupture at intervals of 3 months during a 3-year latency period after simulated partial/complete irradiation of the nidus using doses <25 and ≥25 Gy. An expression for risk of rupture was derived on the basis of the functional distribution of the critical radii of component vessels. The theoretical effects of radiation were also tested on AVM nidus vessels with progressively increasing elastic modulus (
E
) and wall thickness during the latency period, simulating their eventual fibrosis.

Results
—In an AVM with
E
=5.0×10
4
dyne/cm
2
, 4 (14.3%) of a total 28 sets of AVM radiosurgery simulations revealed theoretical nidus rupture (risk of rupture ≥100%). Three of these were associated with partial nidus coverage and 1 with complete treatment. All ruptures occurred after random occlusion of nidus vessels in AVMs receiving low-dose radiosurgery. Intranidal hemodynamic perturbations were observed in all cases of AVM rupture; the occlusion of a fistulous component resulted in intranidal rerouting of flow and escalation of the intravascular pressure in adjacent plexiform components. Risk of rupture was found to correlate with nidus vessel wall strength: a low
E
of 1.9×10
4
dyne/cm
2
resulted in a 92.8% incidence of AVM rupture, whereas a higher
E
of 7.0×10
4
dyne/cm
2
resulted in only a 3.6% incidence of AVM rupture. A dramatic reduction in rupture incidence was observed when increasing fibrosis of the nidus was modeled during the latency period.

Conclusions
—It was found that the theoretical occurrence of AVM hemorrhage after radiosurgery was low, particularly when radiation-induced fibrosis of nidus vessels was considered. When rupture does occur, it would appear from a theoretical standpoint that the occlusion of intranidal fistulas or larger-caliber plexiform vessels could be a significant culprit in the generation of critical intranidal hemodynamic surges resulting in nidus rupture. The described AVM model should serve as a useful research tool for further theoretical investigations of cerebral AVM radiosurgery and its hemodynamic sequelae.
Angiotensin II AT
1
Blockade Normalizes Cerebrovascular Autoregulation and Reduces Cerebral Ischemia in Spontaneously Hypertensive Rats
Authors: Nishimura Yasuaki , Ito Takeshi , Saavedra Juan M.
Published: June 2011

Background and Purpose
—Angiotensin II, through stimulation of AT
1
receptors, not only controls blood pressure but also modulates cerebrovascular flow. We sought to determine whether selective AT
1
antagonists could be therapeutically advantageous in brain ischemia during chronic hypertension.

Methods
—We pretreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls with the AT
1
antagonist candesartan (CV-11974), 0.5 mg/kg per day, for 3 to 14 days, via subcutaneously implanted osmotic minipumps. We analyzed cerebral blood flow by laser-Doppler flowmetry, cerebral stroke in SHR after occlusion of the middle cerebral artery with reperfusion, and brain AT
1
receptors by quantitative autoradiography.

Results
—Candesartan treatment normalized blood pressure and the shift toward higher blood pressures at both the upper and lower limits of cerebrovascular autoregulation in SHR. Candesartan pretreatment of SHR for 14 days partially prevented the decrease in blood flow in the marginal zone of ischemia and significantly reduced the volume of total and cortical infarcts after either 1 or 2 hours of middle cerebral artery occlusion with reperfusion, relative to untreated SHR, respectively. This treatment also significantly reduced brain edema after 2 hours of middle cerebral artery occlusion with reperfusion. In SHR, candesartan markedly decreased AT
1
binding in areas inside (nucleus of the solitary tract) and outside (area postrema) the blood-brain barrier and in the middle cerebral artery.

Conclusions
—Pretreatment with an AT
1
antagonist protected hypertensive rats from brain ischemia by normalizing the cerebral blood flow response, probably through AT
1
receptor blockade in cerebral vessels and in brain areas controlling cerebrovascular flow during stroke.
Inapparent Hemodynamic Insufficiency Exacerbates Ischemic Damage in a Rat Microembolic Stroke Model
Authors: Omae Tsuyoshi , Mayzel-Oreg Orna , Li Fuhai , Sotak Christopher H. , Fisher Marc
Published: June 2011

Background and Purpose
—Patients with severe carotid artery stenosis may have more severe ischemic damage after embolic stroke than patients without this abnormality. Unilateral proximal carotid occlusion (UCO) alone typically does not induce infarction in normotensive rats. The aim of this study was to investigate whether UCO increases infarct size after microembolic, experimental stroke.

Methods
—Microembolic infarction was induced in 2 groups of Sprague-Dawley rats by injecting 2000 microspheres (50-μm diameter) intracranially from the external carotid artery. The common carotid artery (CCA) was either ligated just after the injection (CCA occlusion group, n=8) or left intact (CCA open group, n=8). In the control group (n=4), vehicle without microspheres was injected and the CCA was ligated. Twenty-four hours later, the brains were removed and infarct volumes measured. Perfusion-weighted imaging was used to evaluate the cerebral circulation before and after CCA occlusion with and without microsphere injection in a separate group of animals (n=16).

Results
—All animals in the microemboli groups survived and had only a slight hemiparesis 24 hours after occlusion. No neurological deficits were observed in the control group. Infarct volumes were 145±57 mm
3
in the CCA occlusion group and 45±26 mm
3
in the CCA open group (
P
<0.01). There were no infarctions detected in the control group. Perfusion-weighted imaging showed that cerebral blood flow decreased after the CCA occlusion in both experiments with and without the microsphere injection.

Conclusions
—UCO alone does not induce ischemic damage, but it worsens ischemic lesion size after multiple microemboli. This is probably due to the slight cerebral perfusion insufficiency caused by UCO. These results suggest that patients with cerebral hemodynamic insufficiency, such as those with severe carotid stenosis, may have increased ischemic damage after microembolic events.