bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult-Onset MELAS
Authors: Gilchrist James M. , Sikirica Michael , Stopa Edward , Shanske Sara
Published: June 2011

Background
We report a 46-year-old woman with implications regarding pathogenesis of strokelike episodes in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). She had a 10-month history of episodic seizures, strokes, cognitive decline, vomiting, and ileus. She also had sensorineural hearing loss, insulin-dependent diabetes mellitus of several years' duration, and persistent lactic acidosis. Family history was pertinent for a similar syndrome in her deceased mother (onset in her sixties), for hearing loss and diabetes mellitus in two brothers, and for hearing loss in her only child, a son.

Case Description
Serial MRIs of the brain revealed severe but evanescent cerebral cortical abnormalities. A left temporal brain biopsy was performed to exclude encephalitis. Light microscopy revealed a diffuse fibrillary gliosis with abundant reactive gemistocytes, focal evidence of ischemic neuronal injury, and edema. Electron microscopy revealed bizarre enlarged mitochondria and changes consistent with cellular edema. Succinate dehydrogenase staining was strongly reactive within cerebral blood vessels and within neurons. A point mutation was subsequently found at nt 3243 of the mitochondrial tRNA
Leu(UUR)
gene in peripheral leukocytes and in brain, confirming the clinical diagnosis of MELAS. Quantitation revealed that 82% of brain mitochondria carried the disease mutation, indicating that most, if not all, tissues were affected.

Conclusions
Our findings suggest that strokelike episodes in MELAS result from defects in neuronal metabolism, as well as in cerebral vasculature.
Role of Ca
2+
-Dependent K
+
Channels in Cerebral Vasodilatation Induced by Increases in Cyclic GMP and Cyclic AMP in the Rat
Authors: Paternò Roberto , Faraci Frank M. , Heistad Donald D.
Published: June 2011

Background and Purpose
The mechanisms by which cAMP and cGMP produce vasorelaxation are not entirely clear. In this study we examined the hypothesis that relaxation of cerebral arterioles in response to receptor-mediated activation of adenylate cyclase (increase in cAMP) is mediated through Ca
2+
-dependent K
+
channels.

Methods
We measured the diameter of cerebral arterioles (basal diameter, 47±1 μm) using an open cranial window in anesthetized rats. Agonists and antagonists were applied locally in the cranial window.

Results
Topical application of adenosine (0.1 and 1 mmol/L), a receptor-mediated activator of adenylate cyclase, and dibutyryl cAMP (60 and 200 μmol/L), a cell-permeable analogue of cAMP, dilated cerebral arterioles. Iberiotoxin (50 nmol/L), a selective inhibitor of Ca
2+
-dependent K
+
channels, reduced vasodilatation in response to 0.1 and 1 mmol/L adenosine by 66% and 28%, respectively. Tetraethylammonium (TEA) (1 mmol/L), another inhibitor of Ca
2+
-dependent K
+
channels, reduced vasodilatation to 0.1 and 1 mmol/L adenosine by 58% and 42%, respectively, and reduced vasodilatation in response to 60 and 200 μmol/L dibutyryl cAMP by 75% and 66%, respectively. Topical application of sodium nitroprusside (0.1 and 1 μmol/L), a direct activator of guanylate cyclase, and 8-bromo cGMP (200 and 600 μmol/L), a cell-permeable analogue, produced dilatation of cerebral arterioles that was inhibited by iberiotoxin (50 nmol/L) and TEA (1 and 3 mmol/L). In contrast, dilatation of cerebral arterioles in response to papaverine (which produces vasodilatation in large part by inhibition of Ca
2+
channels) and aprikalim (which produces vasodilatation by activation of ATP-sensitive K
+
channels) was not inhibited by iberiotoxin or TEA.

Conclusions
These findings suggest that dilatation of cerebral arterioles by receptor-mediated activation of adenylate cyclase and by direct activation of guanylate cyclase in the rat is mediated in large part by activation of Ca
2+
-dependent K
+
channels.
Middle Cerebral Artery Occlusion in the Rat by Intraluminal Suture
Authors: Belayev Ludmila , Alonso Ofelia F. , Busto Raul , Zhao Weizhao , Ginsberg Myron D.
Published: June 2011

Background and Purpose
The purpose of the present study was to evaluate a modified method of intraluminal suture occlusion of the middle cerebral artery (MCA) on the volume of brain infarction and on neurobehavioral function in rats subjected to a temporary focal ischemic insult.

Methods
Male Sprague-Dawley rats were anesthetized with halothane and subjected to 60 minutes or 2 hours of temporary MCA occlusion (MCAo) by an intraluminal thread. In one group of rats, the suture was coated with poly-
l
-lysine, while in a second group, a conventional uncoated suture was used. Behavioral function was evaluated at 50 to 60 minutes after occlusion and during a 3-day period after MCAo. Three days after MCAo, brains were perfusion-fixed and infarct volumes were measured.

Results
In rats with 60-minute MCAo, only 3 of 7 animals with uncoated sutures had infarcts, whereas in the group with poly-
l
-lysine–coated sutures, all rats (n=7) exhibited infarction (
P
=.009, Fisher's exact test). With 2 hours of MCAo, total infarct volume (corrected for brain edema) was significantly larger in rats with poly-
l
-lysine–coated sutures than in the group with uncoated sutures (mean±SEM, 122.1±4.8 versus 67.0±18.2 mm
3
, respectively;
P
=.03; n=4 in each group). In the 2-hour MCAo study, infarct volumes in the uncoated-suture group tended to be variable and inconsistent (coefficient of variation, 54%) compared with the group in which sutures were coated with poly-
l
-lysine, in which a highly consistent infarct was produced (coefficient of variation of infarct volume, 8%).

Conclusions
Reversible MCAo in which a poly-
l
-lysine–coated intraluminal suture was used proved to be a reliable and effective modification of this technique, yielding consistently larger infarcts and greatly reduced interanimal variability.
Differential Effects of Short-term Hypoxia and Hypercapnia on
N
-Methyl-
d
-Aspartate–Induced Cerebral Vasodilatation in Piglets
Authors: Bari Ferenc , Errico Robert A. , Louis Thomas M. , Busija David W.
Published: June 2011

Background and Purpose
Recent studies in piglets show that either asphyxia or global cerebral ischemia, which combines effects of hypoxia and hypercapnia, transiently attenuates
N
-methyl-
d
-aspartate (NMDA)–induced pial arteriolar dilation. The purpose of this study was to determine individually the effects of hypoxic hypoxia and normoxic hypercapnia on NMDA-dependent cerebrovascular reactivity. In addition, we examined mechanisms involved in reduced cerebral vascular dilation to NMDA.

Methods
In anesthetized piglets, we examined pial arteriolar diameters using a cranial window and intravital microscopy. Arteriolar responses to topically applied NMDA were determined under control conditions and after arterial hypoxia or arterial hypercapnia. In addition, arteriolar responses to NMDA were examined in animals given indomethacin (10 mg/kg IV) or superoxide dismutase (100 U/mL, topical application) before hypoxia.

Results
Under control conditions, application of NMDA produced a dose-related dilation of pial arterioles (eg, 9±1% to 10
−5
, 15±2% to 5×10
−5
, and 28±5% to 10
−4
mol/L NMDA above baseline, respectively, in the hypoxic group; n=6,
P
<.05). After transient exposure to 15 minutes of hypoxic hypoxia, arteriolar responses to NMDA were reduced at 30 minutes and at 60 minutes (10
−4
mol/L NMDA dilated by 12±5% and 18±5%, respectively; n=6,
P
<.05). Five minutes of hypoxic hypoxia also reduced dilatation to NMDA. Indomethacin or superoxide dismutase preserved arteriolar responses to NMDA after 15 minutes of hypoxia. Pial arteriolar responses to NMDA remained unimpaired during and after hypercapnia.

Conclusions
Short-term severe hypoxic hypoxia and reventilation impair the NMDA-induced dilatation of pial arterioles. Respiratory acidosis alone does not modify pial arteriolar reactivity to NMDA. The reduced responsiveness of the cerebral blood vessels to NMDA caused by hypoxia appears to be due to action of oxygen radicals.
Mapping of Motor Cortical Reorganization After Stroke
Authors: Traversa Raimondo , Cicinelli Paola , Bassi Andrea , Rossini Paolo Maria , Bernardi Giorgio
Published: June 2011

Background and Purpose
Focal transcranial magnetic stimulation (TCS) is used for noninvasive and painless mapping of the somatotopical organization of the motor cortex. TCS mapping of motor cortical output to the abductor digiti minimi (ADM) muscle was followed up in monohemispheric stroke patients by evaluating motor evoked potentials (MEPs). This approach allowed noninvasive investigation of the functional reorganization of hand motor areas.

Methods
Motor maps were constructed for 15 subacute stroke patients about 2 months from the ictus by recording MEPs from the ADM muscle via focal TCS in the affected hemisphere (AH) and unaffected hemisphere (UH) at the beginning of (T1) and after 8 to 10 weeks of neurorehabilitation (T2). Barthel Index and Canadian Neurological Scale scores were evaluated as well. An age-sex matched group of 15 healthy control subjects was enrolled to establish normative data.

Results
MEP excitability threshold was significantly higher in the AH of stroke patients than in normal subjects and in the UH (
P
<.001); excitability threshold was not significantly different between normal subjects and UH. In the AH, MEPs were significantly (
P
<.001) delayed in latency both in T1 and T2, with a significant decrease of the extenuation of motor output area to the ADM muscle (
P
<.05) in T1 versus control group and UH. This area was significantly enlarged (
P
<.05) in T2. Amplitude of MEPs from the AH, both at rest and during voluntary contraction, was significantly lower than normal in T1 (
P
<.001); it increased in T2 (
P
<.01) during relaxation but was still smaller than normal during contraction (
P
<.001). In combination with these findings, an improvement of Barthel Index and Canadian Neurological Scale scores (
P
<.001) was observed between T1 and T2 (
P
<.001). Central conduction time was prolonged in stroke patients both in T1 and T2. Changes in the shape of motor maps in the AH during follow-up in T2 were either isolated (therefore increasing the interhemispheric asymmetry) or also were “mirrored” on the UH.

Conclusions
Our neurophysiological data are consistent with the presence of a rearrangement of the motor cortical output area and correlate well with an improvement of motor performances. These findings confirm the existence in adults of a “plasticity” in the central nervous system that is still operating between 2 and 4 months from the acute ictal episode. The observed neurophysiological modifications are significantly correlated with clinical improvement of disability and clinical scores.
Lifestyle-Associated Risk Factors for Acute Brain Infarction Among Persons of Working Age
Authors: Haapaniemi Helena , Hillbom Matti , Juvela Seppo
Published: June 2011

Background and Purpose
This study was designed to identify whether cigarette smoking, alcohol drinking, obesity, and use of oral contraceptives are independent risk factors for brain infarction among persons of working age.

Methods
Health habits and previous diseases of 506 patients (366 men and 140 women aged 16 to 60 years) with acute first-ever symptomatic brain infarction were compared with those of 345 hospitalized control patients (219 men and 126 women) who did not differ from case subjects in respect to day of onset of symptoms or acuteness of disease onset. With the use of stepwise logistic regression, the variables for which the simultaneous risks of acute brain infarction were tested by sex were age, amount of alcohol consumed within 24 hours and 1 week before the illness, heavy drinking, smoking status, current smoking, cardiac disease, hypertension, diabetes, hyperlipemia, migraine, body mass index, and, in women, current use of oral contraceptives.

Results
Intake of >40 g ethanol within the 24 hours preceding the onset of illness increased the risk for acute brain infarction both among men (
P
<.001) and women (
P
<.01) independently from other risk factors. Other significant independent risk factors for brain infarction among men were hypertension (
P
<.001), cardiac disease (
P
<.01), current smoking (
P
<.01), diabetes (
P
<.05), and history of migraine (
P
<.05) and among women, current use of oral contraceptives (
P
<.01) and current smoking (
P
<.05).

Conclusions
Recent heavy drinking of alcohol, hypertension, cardiac disease, current smoking, diabetes, and history of migraine among men, and recent heavy drinking of alcohol, current use of oral contraceptives, and current smoking among women, seem to be independent risk factors for acute brain infarction.
Associations Between Carotid Atherosclerosis and High Factor VIII Activity, Dyslipidemia, and Hypertension
Authors: Pan Wen-Harn , Bai Chyi-Huey , Chen Jiunn-Rong , Chiu Hou-Chang
Published: June 2011

Background and Purpose
A subsample of 147 Chinese subjects from a population-based study of cardiovascular diseases (Cardiovascular Disease Risk Factor Two-Township Study) participated in an ancillary study on extracranial carotid color duplex ultrasonography that aimed to assess the relations of coagulation factors to stroke and carotid atherosclerosis.

Methods
Logistic models were used to study the associations between cardiovascular disease risk factors and stroke/carotid atherosclerosis, controlling for the effects of age and sex.

Results
Stroke was significantly associated with hypertension and high values of plasma glucose but not with fibrinogen, factor VIIc, or factor VIIIc. Carotid plaques identified in this study were mostly mild and moderate. The presence of these mild and moderate carotid plaques was significantly associated with high values of factor VIII activity, hypercholesterolemia, hypertriglyceridemia, and hypertension. The highest tertile of factor VIIIc (>1.53) was associated with an odds ratio of 3.35 for carotid atherosclerosis when compared with the lowest tertile (<1.20). A multiple logistic regression including all significant risk factors showed that the degree of association between factor VIIIc and atherosclerosis was attenuated to an odds ratio of 2.65 (
P
=.061).

Conclusions
In the present study, the roles of hypertension, hypercholesterolemia, and hypertriglyceridemia have been implicated in the pathogenesis of carotid atherosclerosis, and roles for hypertension and hyperglycemia in stroke were indicated. A positive association between factor VIIIc and carotid atherosclerosis in this Chinese population was found. Whether this association is independent of the effect of other cardiovascular risk factors awaits further study.
Prevalence of Stroke and Stroke-Related Disability
Authors: Bonita Ruth , Solomon Neil , Broad Joanna B.
Published: June 2011

Background and Purpose
To provide estimates of the prevalence of stroke and stroke-related disability for international comparisons and for planning purposes.

Methods
Estimates of prevalence were derived from two population-based studies conducted 10 years apart in Auckland, New Zealand. The first, carried out in 1981, included information on survival and stroke-related disability to 14 years after stroke, and the second, undertaken in 1991 to 1992, included this information up to 3 years after stroke. An actuarial model was developed that took into account changes in incidence, long-term survival, and population structure.

Results
Overall, it was estimated that 7491 people (3793 men and 3698 women) living in Auckland (total population 945 000) in 1991 had experienced a stroke at some stage in the past. This represents an age-standardized rate of 833 per 100 000 (991 per 100 000 in men and 706 per 100 000 in women) in the population aged 15 years and older. When only those who have made an incomplete recovery are considered, prevalence falls to 461 per 100 000. Of this group, one third (173 per 100 000 population 15 years and older) required assistance in at least one self-care activity.

Conclusions
Usual estimates of stroke prevalence, which include all people who have ever experienced a stroke, may overestimate by almost twofold the prevalence of stroke-related disability, since many have either recovered or have no continuing dependency related to stroke. Overall prevalence does not provide information with sufficient precision for planning and purchasing ongoing services for stroke patients.
Valvular Strands and Cerebral Ischemia
Authors: Roberts J. Kirk , Omarali Iqbal , Di Tullio Marco R. , Sciacca Robert R. , Sacco Ralph L. , Homma Shunichi
Published: June 2011

Background and Purpose
Valvular strands, thin filamentous material attached to the mitral or aortic valve, are seen during transesophageal echocardiography and have been associated with stroke. Little is known about this association in different age, sex, and race-ethnic subgroups and the effect of various strand characteristics on this association.

Methods
From patients referred for transesophageal echocardiography, 73 patients with recent ischemic stroke (68) or transient ischemic attack (5) were age matched to 73 stroke- and transient ischemic attack–free control subjects. The association between valvular strands and cerebral ischemia was evaluated for the overall group and demographic subgroups. The effect of strand location, length, number, and valve thickness was also determined.

Results
An association between cerebral ischemia and valvular strands was observed (odds ratio [OR]=4.4; 95% confidence interval [CI]=2.0 to 9.6). The association was found for both men and women and among all three race-ethnic groups. The OR was greater in those who were younger (12.5 [95% CI=2.4 to 64.5] for age <60, 4.8 [95% CI=1.3 to 18.2] for age 60 to 69, and 1.8 [95% CI=0.5 to 6.4] for age ≥70 years). Strands on both the mitral (OR=3.5; 95% CI=1.5 to 7.9) and aortic (OR=3.7; 95% CI=1.1 to 11.9) valve were associated with cerebral ischemia, whereas the number and length of strands were not. The effect of strands was independent of mitral or aortic valve thickness.

Conclusions
Valvular strands, whether mitral or aortic, are associated with ischemic stroke, especially among younger persons.
Reproducibility of Ultrasound Assessment of Carotid Plaque Occurrence, Thickness, and Morphology
Authors: Joakimsen Oddmund , Bønaa Kaare H. , Stensland-Bugge Eva
Published: June 2011

Background and Purpose
Ultrasonography is increasingly used in vascular research, but there is limited information about the reproducibility of the ultrasound method for screening purposes. In this study the reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology was examined within the setting of a population health survey.

Methods
In 1994/1995, 6720 participants in the Tromsø Study, Norway, underwent B-mode ultrasound scanning of the right carotid artery. The between- and within-sonographer reproducibility of ultrasound assessment of plaque occurrence and thickness was estimated by repeated scanning of a random sample of 107 participants. The between- and within-sonographer reproducibility of plaque morphology classification (echogenicity, four categories and heterogeneity, two categories) was determined by repeated reading of videotaped images of 119 randomly selected arteries with plaques.

Results
Between- and within-sonographer agreement on plaque occurrence was substantial with κ values (95% CI) of 0.72 (0.60 to 0.84) and 0.76 (0.63 to 0.89), respectively. Reproducibility of plaque thickness measurements was moderate, with mean absolute differences ranging between 0.25 and 0.55 mm (coefficients of variation between 13.8% and 22.4%). Agreement on plaque morphology classification was high, with κ values ranging between 0.54 and 0.73.

Conclusions
Population screening using B-mode ultrasound provides a valuable means for the detection and morphological evaluation of carotid plaques, whereas measurements of plaque thickness are subject to considerable measurement error.
Quantitative Cerebral Blood Flow Determinations in Acute Ischemic Stroke
Authors: Firlik Andrew D. , Kaufmann Anthony M. , Wechsler Lawrence R. , Firlik Katrina S. , Fukui Melanie B. , Yonas Howard
Published: June 2011

Background and Purpose
The advent of new modalities to treat acute ischemic stroke presents the need for accurate, early diagnosis. In acute ischemic stroke, CT scans are frequently normal or reveal only subtle hypodense changes. This study explored the utility and increased sensitivity of xenon-enhanced CT (XeCT) in the diagnosis of acute cerebral ischemia and investigated the relationship between cerebral blood flow (CBF) measurements and early CT and angiographic findings in acute stroke.

Methods
The CT scans, XeCT scans, and angiograms of 20 patients who presented within 6 hours of acute anterior circulation ischemic strokes were analyzed.

Results
CT scans were abnormal in 11 (55%) of 20 patients. XeCT scans were abnormal in all 20 (100%) patients, showing regions of interest with CBF <20 (mL/100 g per minute) in the symptomatic middle cerebral artery (MCA) territories. The mean CBF in the symptomatic MCA territories was significantly lower than that of the asymptomatic MCA territories (
P
<.0005). In patients with basal ganglia hypodensities, the mean symptomatic MCA territory CBF was significantly lower than that of patients who did not exhibit these early CT findings (
P
<.05). The mean symptomatic MCA territory CBF in patients with angiographic M1 occlusions was significantly lower than that of patients whose infarcts were caused by MCA branch occlusions (
P
<.01).

Conclusions
These results show that XeCT is more sensitive than CT in detecting acute strokes and that CBF measurements correlate with early CT and angiographic findings. XeCT may allow for the hyperacute identification of subsets of patients with acute ischemic events who are less likely to benefit and more likely to derive complications from aggressive stroke therapy.
Hypothermic Neuroprotection
Authors: Corbett D. , Nurse S. , Colbourne F.
Published: June 2011

Background and Purpose
Previous studies from this laboratory have shown that mild intraischemic or prolonged (ie, 12 to 24 hours) postischemic hypothermia conveys long-lasting (1 to 6 months) protection against CA1 injury. However, these studies have used young animals (aged ≈3 to 5 months). Stroke incidence rises sharply in late middle age at a time when changes in brain chemistry could alter the response to neuroprotective treatments. Therefore, we evaluated the efficacy of hypothermia in an older population (aged 18 to 20 months) of gerbils.

Methods
Three groups of gerbils were exposed to a 5-minute episode of global ischemia or sham occlusion. One group was cooled during ischemia (mean brain temperature of 32°C). A second group was maintained at normothermia (36.4°C) during occlusion and the first hour of reperfusion. Beginning 1.0 hour after occlusion, these gerbils were gradually cooled to 32°C and maintained at this level before gradual rewarming to 37°C at 25 hours after ischemia. The third ischemic group was kept at normothermia during surgery and the first hour of reperfusion. After surgery, all animals were tested for acute (ie, within 30 hours of ischemia) changes in locomotor activity as well as for chronic (ie, 5, 10, and 30 days after ischemia) habituation deficits in an open field test.

Results
Both intraischemic and postischemic hypothermia provided robust protection (
P
<.0001) of hippocampal CA1 neurons when assessed 30 days after ischemia. However, intraischemic hypothermia was more effective than postischemic hypothermia in providing behavioral protection.

Conclusions
This study demonstrates that both intraischemic and prolonged postischemic hypothermia provide robust and lasting (30-day survival) histological protection against a severe ischemic insult. The extent of behavioral protection with postischemic hypothermia was less than that previously observed in younger animals. This suggests that neuroprotective treatments in young animals may lose efficacy as a result of aging.
Brain Injury Impairs ATP-Sensitive K
+
Channel Function in Piglet Cerebral Arteries
Authors: Armstead William M.
Published: June 2011

Background and Purpose
Traumatic injury is the leading cause of death for infants and children, and mortality is increased with head injury. Previous studies have shown that pial arteries constricted and that responses to several nitric oxide (NO)–dependent dilator stimuli were blunted after fluid percussion injury (FPI) in newborn pigs. Membrane potential of vascular muscle is a major determinant of vascular tone, and activity of K
+
channels is a major regulator of membrane potential. Recent data show that the NO releasers sodium nitroprusside (SNP) and S-nitroso-
N
-acetylpenicillamine (SNAP) and 8-bromo-cGMP elicit dilation via ATP-sensitive K
+
channel (K
ATP
) activation. The present study was designed to investigate the effect of FPI on K
ATP
channel function.

Methods
Chloralose-anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device that consisted of a saline-filled cylindrical reservoir and a metal pendulum. Brain injury of moderate severity (1.9 to 2.1 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Pial artery diameter was measured with a video microscaler. Data were analyzed by repeated measures ANOVA. An α level of
P
<.05 was considered significant.

Results
FPI blunted dilation to cromakalim (10
−8
, 10
−6
mol/L), a K
ATP
agonist (10±1% and 27±2% versus 3±1% and 7±2% before and after FPI, respectively, n=8). Similarly, FPI blunted dilation to calcitonin gene–related peptide, an endogenous K
ATP
activator. FPI also blunted dilator responses to SNP, S-nitroso-
N
-acetylpenicillamine, and 8-bromo-cGMP (10
−6
to 10
−8
mol/L) (10±1% and 20±1% versus 2±1% and 8±2% for SNP before and after FPI; 9±1% and 16±1% versus 2±1% and 4±1% for 8-bromo-cGMP before and after FPI, respectively, n=8). In contrast, responses to papaverine and brain natriuretic peptide were unchanged after FPI.

Conclusions
These data show that K
ATP
channel function is impaired after FPI. Furthermore, these data suggest that impaired function of mechanisms distal to NO synthase contribute to altered cerebral hemodynamics after FPI.
Use of a Spectrophotometric Hemoglobin Assay to Objectively Quantify Intracerebral Hemorrhage in Mice
Authors: Choudhri Tanvir F. , Hoh Brian L. , Solomon Robert A. , Connolly E. Sander , Pinsky David J.
Published: June 2011

Background and Purpose
There is great interest in developing novel anticoagulant or thrombolytic strategies to treat ischemic stroke. However, at present there are limited means to accurately assess the hemorrhagic potential of these agents. The present studies were designed to develop and validate a method to accurately quantify the degree of intracerebral hemorrhage (ICH) in murine models.

Methods
In a murine model, ICH was induced by stereotaxic intraparenchymal infusion of collagenase B alone (6×10
−6
U; n=5) or collagenase B followed by intravenous recombinant tissue plasminogen activator (rt-PA) (0.1 mg/kg; n=6). Controls consisted of either sham surgery with stereotaxic infusion of saline (n=5) or untreated animals (n=5). ICH was (1) graded by a scale based on maximal hemorrhage diameter on coronal sections and (2) quantified by a spectrophotometric assay measuring cyanomethemoglobin in chemically reduced extracts of homogenized murine brain. This spectrophotometric assay was validated with the use of known quantities of hemoglobin or autologous blood added to a separate cohort of homogenized brains. With this assay, the degree of hemorrhage after focal middle cerebral artery occlusion/reperfusion was quantified in mice treated with postocclusion high-dose intravenous rt-PA (10 mg/kg; n=11) and control mice subjected to stroke but treated with physiological saline solution (n=9).

Results
Known quantities of hemoglobin or autologous blood added to fresh whole brain tissue homogenates showed a linear relationship between the amount added and optical density (OD) at the absorbance peak of cyanomethemoglobin (
r
=1.00 and .98, respectively). When in vivo studies were performed to quantify experimentally induced ICH, animals receiving intracerebral infusion of collagenase B had significantly higher ODs than saline-infused controls (2.1-fold increase;
P
=.05). In a middle cerebral artery occlusion and reperfusion model of stroke, administration of rt-PA after reperfusion increased the OD by 1.8-fold compared with animals that received physiological saline solution (
P
<.001). When the two methods of measuring ICH (visual score and OD) were compared, there was a linear correlation (
r
=.88). Additional experiments demonstrated that triphenyltetrazolium staining, which is commonly used to stain viable brain tissue, does not interfere with the spectrophotometric quantification of ICH.

Conclusions
These data demonstrate that the spectrophotometric assay accurately and reliably quantifies murine ICH. This new method should aid objective assessment of the hemorrhagic risks of novel anticoagulant or thrombolytic strategies to treat stroke and can facilitate quantification of other forms of ICH.
Apolipoprotein E ε2 Allele and Risk of Stroke in the Older Population
Authors: Ferrucci Luigi , Guralnik Jack M. , Pahor Marco , Harris Tamara , Corti Maria-Chiara , Hyman Brad T. , Wallace Robert B. , Havlik Richard J.
Published: June 2011

Background and Purpose
There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an ε4 allele and lower in those carrying an ε2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons.

Methods
At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged ≥71 years and free of stroke were genotyped for apo E. Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates.

Results
One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of ε3 and ε4 did not influence stroke risk. Among persons aged <80 years at the time of genotyping, ε2 carriers had lower risk of incident stroke, while no effect was detected in the older group. Compared with ε2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an ε2 had 2.6-fold higher risk of incident stroke, and those aged ≥80 years had even higher risks of stroke but without any difference according to presence/absence of ε2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages ≥80 years (94 events).

Conclusions
The conditioning influence of age on the protection conferred by the apoE ε2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range.
Cerebrovascular Reserve Capacity Many Years After Vasospasm Due to Aneurysmal Subarachnoid Hemorrhage
Authors: Szabo Sandor , Sheth Rishi N. , Novak Laszlo , Rozsa Laszlo , Ficzere Andrea
Published: June 2011

Background and Purpose
Vasospasm in aneurysmal subarachnoid hemorrhage results in proliferative vasculopathy. Systemic hypertension also causes vascular hypertrophy. Both of these histological changes can lead to rigidity of the cerebrovascular system, reducing its autoregulatory capacity.

Methods
Blood flow velocity (BFV) in the middle cerebral artery at rest and cerebrovascular reserve capacity (CVRC) (percent rise in BFV after acetazolamide stimulation) measured by means of transcranial Doppler sonography were studied many years after aneurysmal subarachnoid hemorrhage in patients with proven cerebral vasospasm (mean BFV >160 cm/s). The BFV under resting conditions and the CVRC values of the ipsilateral and the contralateral hemispheres were measured in 29 patients (mean age, 43 years; mean follow-up, 4.6 years) and compared with those of control subjects.

Results
Persistent high BFV (>120 cm/s) was found in three patients in the peripheral branch of the ipsilateral middle cerebral artery. In the main trunks of the arteries of the anterior circle of Willis, BFV was normal in all cases. CVRC was normal in all patients (ipsilateral, 52±21%; contralateral, 56±17%); values did not differ significantly from each other or from the control value (45±18%). The higher value of CVRC on the contralateral side was found to be statistically significant in selected groups (hypertensive patients and patients with residual infarct on late CT).

Conclusions
Proliferative vasculopathy developed at the time of vasospasm must have resolved and did not reduce late vasoreactivity. Comorbidity with hypertension also did not seem to influence the late vasoreactivity toward normalization.
Diameter Dependence of Myogenic Tone of Human Pial Arteries
Authors: Thorin-Trescases Nathalie , Bartolotta Tracy , Hyman Neil , Penar Paul L. , Walters Carrie L. , Bevan Rosemary D. , Bevan John A.
Published: June 2011

Background and Purpose
Responses to changes in intraluminal pressure of isolated human pial arteries (200 to 1200 μm i.d.) obtained from patients undergoing neurosurgery were measured.

Methods
The vessels were cannulated and pressurized (60 mm Hg); vascular diameter and intraluminal pressure were recorded simultaneously. After spontaneous development of steady state tone, intraluminal pressure was changed to both higher and lower levels in random sequence.

Results
Human pial arteries exhibited myogenic responses and maintained their diameter over the pressure range of 20 to 100 mm Hg. The level of myogenic tone observed at 30 mm Hg did not vary significantly with artery diameter. In contrast, at 60 and 90 mm Hg, the extent of myogenic tone increased as the diameter decreased (up to 70% to 80% of maximum in 200-μm i.d. arteries). The arteries contracted to KCl 30 mmol/L, norepinephrine 1μmol/L, and vasopressin 0.1μmol/L and relaxed to acetylcholine 3 μmol/L. The extent of these responses did not vary with the diameter of the artery. Arterial distensibility, represented by the slope of the tangent of the passive pressure-diameter curve at lower pressures (5 to 50 mm Hg), increased as arteries became smaller. This is consistent with the possibility that the level of myogenic tone is related to vessel distensibility. Human omental arteries of comparable size did not develop myogenic tone but contracted to KCl and norepinephrine and relaxed to acetylcholine to an extent similar to pial arteries.

Conclusions
There is a specific gradient of myogenic responsiveness in human pial arteries that varies inversely with their diameter. This tone does not develop in all vascular beds. These levels of tone in the pial circulation would be expected to be of profound functional significance by allowing blood flow to vary widely.
Subtypes of Ischemic Stroke
Authors: Yip Ping-Keung , Jeng Jiann-Shing , Lee Ti-Kai , Chang Yang-Chyuan , Huang Zei-Shung , Ng Sien-Kiat , Chen Rong-Chi
Published: June 2011

Background and Purpose
To better understand the clinical pattern and further elucidate the risk factors and outcome in different subtypes of cerebral infarction (CI) of the Chinese in Taiwan, we analyzed the National Taiwan University Hospital Stroke Registry in 1995 and performed an ethnic comparison with similar data banks.

Methods
From the National Taiwan University Hospital Stroke Registry in 1995, 676 patients (383 men and 293 women; mean age, 64.9 years; SD, 13.8 years; range, 1 to 98 years) with CI were recruited for this analysis. CI was classified into five subtypes based on clinical manifestations, ultrasonographic studies, and neuroimaging findings: large-artery atherosclerosis, lacunae, cardioembolism, other less common determined causes, and undetermined cause. Vascular risk factors, extracranial carotid artery atherosclerosis, and 30-day case-fatality rates were investigated in each subtype of CI.

Results
Of all CI patients, 17%, 29%, 20%, 6%, and 29% were classified as large-artery atherosclerosis, lacunae, cardioembolism, other determined causes, and undetermined cause subtypes, respectively. The present results were compared with those from eight similar Western stroke registries. The relative incidence of lacunar CI in Chinese patients was more common, but large-artery atherosclerotic CI was less common than in whites. Hypertension was frequently seen in CI patients, especially in those with lacunae (85%) and large-artery atherosclerosis (69%). Patients with cardioembolism had a higher percentage of atrial fibrillation (69%), left ventricular hypertrophy, and ischemic heart disease than the other patients. Patients with large-artery atherosclerosis had more vascular risk factors, such as hypertension, diabetes mellitus, smoking, and carotid stenosis. Cardioembolic patients had higher case-fatality rates than other CI patients. Of the cardioembolic patients, 17.3% and 21.8% died within 30 days and during hospitalization, respectively.

Conclusions
The proportion of CI subtypes varied in different stroke registries. This may be partly due to applied classification criteria and racial-ethnic differences. Awareness of the risk factors and outcome in each subtype of stroke may afford further insights into the surveillance and treatment of cerebrovascular disease.
A Putative Role for Platelet-Derived Growth Factor in Angiogenesis and Neuroprotection After Ischemic Stroke in Humans
Authors: Krupinski Jerzy , Issa Razao , Bujny Tomasz , Slevin Mark , Kumar Pat , Kumar Shant , Kaluza Jozef
Published: June 2011

Background and Purpose
Growth factors control two important processes in infarcted tissue, ie, angiogenesis and gliosis. We recently reported that transforming growth factor-β1 (TGF-β1) might be involved in angiogenesis after ischemic stroke in humans; here we present data of an extensive study on platelet-derived growth factor (PDGF) and its receptors.

Methods
We studied brain samples from patients who suffered from ischemic stroke for the expression of mRNA encoding PDGF-A, PDGF-B, and PDGF receptors (PDGF-R). Proteins were examined by Western blotting and immunohistochemistry using the antibodies to PDGF-AB, PDGF-BB, PDGF-Rα, and PDGF-Rβ.

Results
At the mRNA level, PDGF-A and PDGF-B were expressed mainly in neurons in penumbra. PDGF-R mRNA was strongly expressed in some astrocytes but mainly in type III/IV neurons in infarct and penumbra. The least expression was seen in the contralateral hemisphere (
P
<.001). In contrast, both PDGF-AB and PDGF-BB immunoreactive products were present in most cell types: PDGF-Rα and PDGF-Rβ mainly on neurons, and PDGF-Rβ on some endothelial cells, with less staining of all the isoforms in the contralateral hemisphere. On Western blots, PDGF-AB and -BB were expressed more within white matter than gray matter of infarct/penumbra, whereas both isoforms of receptor were expressed mainly in gray matter compared with contralateral hemisphere. There was no or very weak expression of the receptor in white matter.

Conclusions
PDGF proteins are highly expressed in white matter, suggesting that PDGF may exert its function in white matter participating either in regeneration of damaged axons or in glial scar formation. PDGF-BB and its receptor expressed on microvessel endothelial cells might be involved in angiogenesis after stroke. Thus, PDGF is likely to be angiogenic and neuroprotective in stroke.
Isolated Pontine Infarctions With Prominent Ipsilateral Midfacial Sensory Signs
Authors: Masjuan J. , Barón M. , Lousa M. , Gobernado J. M.
Published: June 2011

Background
Pontine infarctions may produce combined motor, sensory, cerebellar, and cranial nerve dysfunction. Midline sensory complaints and facial pain are uncommon.

Case Descriptions
Three patients are described with hypoesthesia and numbness of the midline facial area associated with dysarthria and contralateral hemiparesis due to pontine strokes. MRI demonstrated isolated ipsilateral ischemic infarctions of the ventral pons.

Conclusions
Pontine infarctions can produce diverse sensory features. Ipsilateral midfacial sensory defect has been rarely reported. The clinicoanatomic basis for the ipsilateral midfacial sensory defect described is unknown. Involvement of the dorsal trigeminothalamic tract or fiber tracts related to central regions of the face, located in the medial part of the midbrain, could help to explain these data. The symptoms could be due to direct damage or to edema resulting from the infarct. In some patients, midfacial sensory complaints, particularly of the ala nasi, could be an early sign of major pontine deficits and may be important to determine appropriate treatment.
Amelioration of Hemiplegia-Associated Osteopenia More Than 4 Years After Stroke by 1α-Hydroxyvitamin D
3
and Calcium Supplementation
Authors: Sato Yoshihiro , Maruoka Hiroshi , Oizumi Kotaro
Published: June 2011

Background and Purpose
It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients, which might increase their risk of hip fracture. We evaluated the efficacy of 1α-hydroxyvitamin D
3
[1α(OH)D
3
] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke.

Methods
In a randomized study, 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 μg 1α(OH)D
3
daily (treatment group, n=30) or an inactive placebo (placebo group, n=34) for 6 months and were observed for this duration. Both groups received 300 mg of elemental calcium daily. The bone mineral density (BMD) and metacarpal index (MCI) in the second metacarpals were determined by computed x-ray densitometry. The incidence of hip fractures in these patients was recorded.

Results
BMD on the hemiplegic side decreased by 2.4% in the treatment group and 8.9% in the placebo group (
P
=.0021), while BMD on the intact side increased by 3.5% and decreased by 6.3% in the treated and placebo groups, respectively (
P
=.0177). In the treatment group, the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before randomization. This difference increased in the placebo group. We observed a similar improvement in MCI in the treatment group but not in the placebo group. Four patients in the placebo group suffered a hip fracture compared with none in the treatment group (
P
=.0362).

Conclusions
Treatment with 1α(OH)D
3
and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-standing stroke. Treatment also may improve these indices on the intact side.
Primary Care Physician–Reported Secondary and Tertiary Stroke Prevention Practices
Authors: Goldstein Larry B. , Farmer Andrew , Matchar David B.
Published: June 2011

Background and Purpose
Stroke is a major healthcare problem in both the United States (US) and the United Kingdom (UK). Little comparative data are available concerning how generalist physicians in the two countries approach the management of patients at high risk of stroke.

Methods
Contemporaneous surveys of random samples of primary care physician–reported stroke prevention practices were performed in the US and UK from 1993 to 1994. The US National Survey of Physician Practices for the Secondary and Tertiary Prevention of Ischemic Stroke included 254 noninternist primary care physicians. The UK Survey of the Care of Patients With Stroke in General Practice obtained responses from 661 general practitioners. The two surveys used many of the same questions, allowing for direct comparisons of reported stroke prevention practices between American and British physicians.

Results
More than 80% of American physicians reported a variety of services (24-hour electrocardiography, echocardiography, brain CT scan, brain MR scan, carotid ultrasonography, cerebral angiography) as readily available. These same services were readily available to less than 10% of physicians in the UK (
P
<.001 for each comparison). Although physicians in the UK reported prescribing lower doses of aspirin for stroke prevention than physicians in the US, the proportions of physicians using aspirin were not different. In contrast, almost 70% of physicians in the US responded that they always or often anticoagulate patients with nonvalvular atrial fibrillation compared with 7% of British physicians (
P
<.001). Whereas 70% of American versus 14% of British physicians reported obtaining carotid ultrasound studies in patients with asymptomatic bruits (
P
<.001), physicians in the UK more commonly reported referring this type of patient to neurologists (46% versus 21%,
P
<.001). For patients with recent carotid-distribution transient ischemic attack or minor stroke, physicians in the US more commonly reported referral to neurologists (55% versus 45%,
P
=.022), referral to surgeons (39% versus 19%,
P
<.001), the performance of carotid ultrasonography (80% versus 11%,
P
<.001), echocardiography (45% versus 5%,
P
<.001), 24-hour electrocardiography (49% versus 4%,
P
<.001), brain CT scan (72% versus 3%,
P
<.001), and the prescription of anticoagulants (53% versus 4%,
P
<.001).

Conclusions
These data show significant differences in stroke prevention practices as reported by primary care physicians practicing in the US and UK. Some of these differences may be related to the relative availability of specific services in the two countries, potentially leading to overutilization in the US and underutilization in the UK in certain circumstances.
Stroke Mortality Rates in Poland Did Not Decline Between 1984 and 1992
Authors: Ryglewicz Danuta , Polakowska Maria , Lechowicz Waldemar , Broda Grazyna , Rószkiewicz Malgorzata , Jasiñski Bogdan , Hier Daniel B.
Published: June 2011

Background and Purpose
Stroke mortality has decreased in most industrialized countries in recent decades. In Poland, as in other eastern European countries, mortality rates for stroke remain high.

Methods
The Warsaw Stroke Registry (WSR) registered patients in the Mokotów district of Warsaw from 1991 through 1992. The Warsaw Pol-MONICA study registered stroke patients in the North and South Praga regions of Warsaw from 1984 through 1992. Stroke incidence rates, case-fatality rates, and stroke mortality rates were computed based on both studies and compared with published mortality rates based on death certificates. Eight-year trends of stroke incidence, case-fatality rate, and mortality were derived from the Warsaw Pol-MONICA study.

Results
The WSR and Warsaw Pol-MONICA studies showed similar incidence rates, mortality rates, and 28-day case-fatality rates for stroke. Mortality rates from the WSR and the Warsaw Pol-MONICA study were similar to rates from death certificate data. Mortality rates in the group aged 35 to 64 years were higher in men (47.5 to 50/100 000 per year) than in women (30/100 000 per year).

Conclusions
Two different population-based studies suggest that stroke mortality is high in Poland because of high 28-day case-fatality rates. Stroke mortality failed to decline in Poland in the period 1984 through 1992 because neither case fatality nor stroke incidence declined in this period.