bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-Dependent Inhibition of Oxotremorine-Induced Cerebral Hyperemia by
N
ω
-Nitro-
l
-Arginine in Cats
Authors: Tietjen Charisse S. , Kirsch Jeffrey R. , Clavier Nathalie , Traystman Richard J.
Published: June 2011

Background and Purpose
Oxotremorine (OXO) is a cholinergic agonist that increases cerebral blood flow (CBF) when administered intravenously. We tested the hypothesis that OXO causes a dose-related increase in CBF in cats via a muscarinic mechanism that involves stimulation of nitric oxide synthase.

Methods
Halothane-anesthetized male cats were studied under controlled ventilation. In three groups we measured cerebral blood flow (CBF; microspheres) during 30 minutes of intravenous OXO infusion at doses of 0.5 (n=3), 5 (n=6), or 50 μg · kg
−1
· min
−1
(n=6). The role of muscarinic receptor activation in the CBF response to OXO (50 μg · kg
−1
· min
−1
) was assessed by determining the effect of atropine sulfate (2 mg · kg
−1
, n=6) pretreatment in a separate group of cats. The role of nitric oxide synthase was assessed by determining the CBF response to OXO (50 μg · kg
−1
· min
−1
) either 30 (n=6) or 60 minutes (n=5) after administration of 50 mg/kg
N
ω
-nitro-
l
-arginine (LNA).

Results
CBF to forebrain (pre-OXO, 144±12 mL · min
−1
·100 g
−1
) was unchanged with OXO 0.5 or 5 μg · kg
−1
· min
−1
but increased at 10 (209±26 mL · min
−1
· 100 g
−1
) and 30 minutes (243±35 mL · min
−1
· 100 g
−1
) of OXO infusion at 50 μg · kg
−1
· min
−1
(
P
<.05). Atropine sulfate prevented OXO-induced hyperemia at 10 minutes of infusion but not at 30 minutes of infusion (135±12% of pre-OXO). LNA decreased baseline CBF by approximately 50%. Treatment with LNA 30 minutes before OXO did not affect the extent of OXO-induced hyperemia (CBF, 142±15% of pre-OXO at 10 minutes and 153±18% of pre-OXO at 30 minutes of OXO infusion). Treatment with LNA 60 minutes before OXO ablated OXO-induced hyperemia.

Conclusions
In halothane-anesthetized cats, OXO (50 μg · kg
−1
· min
−1
) increases forebrain CBF by a muscarinic mechanism that involves stimulation of nitric oxide synthase. The ability of nitric oxide synthase inhibitors to block agonist-induced nitric oxide–mediated vasodilation (response to OXO) is time dependent and may not be predicted by ability of the inhibitor to significantly decrease basal CBF.
Cerebral Microembolism and the Risk of Ischemia in Asymptomatic High-Grade Internal Carotid Artery Stenosis
Authors: Siebler Mario , Nachtmann Andreas , Sitzer Matthias , Rose Georg , Kleinschmidt Andreas , Rademacher Jörg , Steinmetz Helmuth
Published: June 2011

Background and Purpose
Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography distal to internal carotid artery stenosis occurs more frequently in recently symptomatic compared with asymptomatic patients. It has remained unclear whether cerebral microembolism also indicates a higher risk of future cerebral or retinal ischemia.

Summary of Report
Sixty-four asymptomatic patients with unilateral 70% to 90% internal carotid artery stenosis were investigated prospectively (mean follow-up, 72 weeks). Five patients developed ischemic symptoms attributable to the stenosis (transient ischemic attack, 2 patients; stroke, 3 patients). A microembolic rate of ≥2 per hour in the ipsilateral middle cerebral artery was associated with a substantially increased risk of developing ischemia of the corresponding carotid territory (odds ratio, 31; 95% confidence interval, 3 to 302;
P
=.005).

Conclusions
This prospective pilot study suggests that cerebral microembolism detected with transcranial Doppler sonography may define a high-risk subgroup among patients with asymptomatic high-grade internal carotid artery stenosis.
Characterization of an Anterior Circulation Rat Subarachnoid Hemorrhage Model
Authors: Piepgras A. , Thomé C. , Schmiedek P.
Published: June 2011

Background and Purpose
Our aim was to demonstrate the feasibility of an angiographically controlled rat model for the study of macrocirculatory and microcirculatory changes of the anterior intracranial circulation after subarachnoid hemorrhage.

Methods
Subarachnoid hemorrhage was induced by transorbital injection of 0.3 mL of nonheparinized autologous arterial blood into the chiasmatic cistern. Changes in regional cerebral blood flow were continuously recorded with the use of laser-Doppler flowmetry over the parietal cortex. Angiographic verification of middle cerebral artery diameter was performed by carotid catheterization at baseline and 2 days after injection of blood or artificial cerebrospinal fluid. We monitored intracranial and systemic blood pressure during and after injections.

Results
Injection of artificial cerebrospinal fluid in the control group did not change the diameter of the middle cerebral artery. Injection of blood caused a significant arterial narrowing of 17.5%, from 0.37±0.04 mm to 0.31±0.04 mm after 2 days (
P
=.0001). In the control group regional cerebral blood flow decreased to 75.9±16.8% of preinjection control but quickly recovered to 99.7±19.4%. Intracranial pressure increased for 5 minutes after the injection to a maximum of 27.3±8.9 mm Hg, accompanied by a 10% decrease in mean arterial pressure. A fall in cerebral blood flow to 53.1±26.3% in blood-injected animals that recovered to only 80.7±16.9% of baseline values during the observation period of 30 minutes was noted. A peak intracranial pressure of 45.7±11.5 mm Hg occurred 2 minutes after injection with a decrease in mean arterial pressure of 13%, resulting in a markedly lower cerebral perfusion pressure than in the control group.

Conclusions
An angiographically controlled model of subarachnoid hemorrhage primarily involving the anterior circulation is feasible in the rat. The resulting narrowing of the middle cerebral artery reflects moderate vasospasm and will allow further microcirculatory studies with cranial windows.
Contraction of Human Brain Endothelial Cells Induced by Thrombogenic and Fibrinolytic Factors
Authors: Nagy Zoltán , Kolev Krasimir , Csonka Éva , Pék Márta , Machovich Raymund
Published: June 2011

Background and Purpose
Vasogenic brain edema is a frequent complication of ischemic stroke. The mechanism of the blood-brain barrier opening that underlies the edema formation is poorly understood. In the present study we examined the response of endothelial cells cultured from adult human brain to thrombogenic and fibrinolytic factors that possibly accumulate in the occluded vascular segments in ischemic stroke.

Methods
The changes in the morphology of cultured human brain microvascular endothelial cells were observed by phase-contrast light microscopy and quantified with computerized morphometry.

Results
Active proteases (eg, thrombin, plasmin, urokinase) as well as heparin and protamine, but not fibrinogen and antithrombin III, produced significant changes in endothelial cell morphology. Two shape patterns of contraction were observed: protamine treatment resulted in rounded cells with a decrease in both cell perimeter and area, whereas all other agents induced spiderlike cell morphology with increased perimeter and reduced area. The rate of contraction was dose dependent, and at comparable enzyme concentrations plasmin produced faster contraction than thrombin. The observed changes were reversed 3 hours after abrogating the treatment.

Conclusions
In an in vitro model we have demonstrated that factors involved in thrombus formation and dissolution induce endothelial cell contraction, which could affect focally the permeability of the blood-brain barrier by opening paracellular avenues between endothelial cells in vivo. Thus, the genesis of brain edema in thromboembolic stroke or occasionally during fibrinolytic therapy can be attributed in part to the contact of these factors with the microvascular endothelium.
Sneddon’s Syndrome With Granulomatous Leptomeningeal Infiltration
Authors: Boortz-Marx Richard L. , Clark H. Brent , Taylor Saul , Wesa Kathleen M. , Anderson David C.
Published: June 2011

Background
There is limited neuropathologic information available from cases of Sneddon’s syndrome in which strokes are associated with livedo reticularis. Pathogenesis of the syndrome is controversial, although current opinion favors a coagulopathy, often with antiphospholipid antibodies. We describe a case lacking antiphospholipid antibodies but having a granulomatous infiltration of the leptomeninges.

Case Description
The patient presented at age 29 with stroke, livedo reticularis, essential hypertension, and Raynaud’s phenomenon. Assessment uncovered no underlying disease, including absent antiphospholipid antibodies. A leptomeningeal biopsy showed granulomatous infiltration.

Conclusions
The findings suggest that an inflammatory process plays a role in at least some cases of Sneddon’s syndrome.
Weather and Stroke in a Subtropical Area: Ilan, Taiwan
Authors: Chen Zen-Yong , Chang Shu-Feng , Su Che-Long
Published: June 2011

Background and Purpose
The aim of this study was to clarify the association of weather and stroke occurrence in a subtropical area in Ilan, Taiwan.

Methods
We studied 517 patients with stroke (date of onset, January 1 to December 31, 1991) in Poh-Ai Hospital and St Mary’s Hospital: 316 patients (61.1%) with cerebral infarction, 170 (32.9%) with intracerebral hemorrhage, and 31 (6.0%) with other types of stroke. The daily occurrence of cerebral infarction and intracerebral hemorrhage was analyzed and correlated with three major meteorologic factors: air temperature, air pressure, and relative humidity.

Results
The occurrence of cerebral infarction was rather uniform in all kinds of weather. The occurrence of intracerebral hemorrhage was approximately twice as great on cold days (0.71 case per day) and high-pressure days (0.73) as on warm days (0.31) and low-pressure days (0.39) (
P
<.005 by χ
2
test). When a linear regression model was used to test whether air temperature or air pressure had more influence on intracerebral hemorrhage, only air temperature showed a significant effect. Regarding intracerebral hemorrhage, the relative risks of cooler and median temperature days versus warmer days were 18.5 and 5.1, respectively.

Conclusions
Intracerebral hemorrhage but not cerebral infarction occurs more frequently on cooler days, with a dose-response relationship, in Ilan, Taiwan.
Neurological Deficit and Extent of Neuronal Necrosis Attributable to Middle Cerebral Artery Occlusion in Rats
Authors: Garcia Julio H. , Wagner Simone , Liu Kai-Feng , Hu Xiao-jiang
Published: June 2011

Background and Purpose
Occluding a large intracranial artery in rats produces a brain lesion that grows in terms of an increase in both surface area and number of necrotic neurons. The present study investigated whether reperfusing the ischemic territory 30 to 60 minutes after the arterial occlusion would have a beneficial effect on either the clinical or the histological outcome of the lesion.

Methods
One hundred four adult rats (including appropriate controls) were used; 97 had a middle cerebral artery occluded by inserting a nylon monofilament via the right external carotid artery. The arterial occlusion was transient in two groups and permanent in another; survival times were comparable for all groups. Control animals were subjected to a sham operation during which the artery was occluded for less than 1 minute. The outcome was evaluated by measuring the extent of the neurological deficit and the severity of the histological injury.

Results
Mean neurological score and mean number of necrotic neurons in the cortex were more favorable after transient (30- to 60-minute) compared with permanent arterial occlusion (
P
<.005). Moreover, the correlation between mean neurological score and mean number of necrotic neurons was highly significant:
r
=.951;
P
<.001.

Conclusions
The histological effects of an intracranial arterial occlusion in the adult rat can be predicted on day 1 by the neurological score described in this report. Significant improvement can be obtained in these animals by reestablishing arterial flow 60 minutes or sooner after the ictus. The pattern of cortical pannecrosis observed after permanent occlusion (≥72 hours) was transformed into incomplete ischemic injury in most instances of transient occlusion.
Intracerebral Human Microdialysis
Authors: Kanthan R. , Shuaib A. , Griebel R. , Miyashita H.
Published: June 2011

Background and Purpose
In vivo microdialysis was introduced in 1982 as a technique to study cerebral neurochemistry in awake, freely moving animals. In small animals, bilateral carotid occlusion produces a 7- to 10-fold increase in extracellular glutamate concentrations. This rapidly falls with reperfusion. Increase in extracellular glutamate is currently believed to be a major factor in initiating neuronal injury. Glutamate antagonists are currently undergoing clinical trials in acute stroke. Human data on the extracellular levels of glutamate and other amino acids in the normal or ischemic brain are limited. In this communication we wish to report the extracellular concentrations of glutamate, serine, glutamine, glycine, taurine, alanine, and γ-aminobutyric acid, as monitored by in vivo microdialysis, in the simulated ischemic model of the temporal lobe of the human brain.

Methods
Intracerebral microdialysis was carried out in five patients who underwent resection of the temporal lobe for intractable epilepsy. Surgical excision leads to an acute (from partial to total, ie, from incomplete to complete) ischemic state of the resected brain. This was our model to study the changes in human extracellular fluid during acute focal ischemic conditions.

Results
Extracellular glutamate concentrations were 15 to 30 μmol/L in the preischemic samples. This increased to 380.69±42.14 μmol/L with partial (incomplete) ischemia and reached a peak of 1781.67±292.34 μmol/L (>100-fold) with total isolation of the temporal pole (complete ischemia). The levels fell to 394.52±72.93 μmol/L 20 minutes after resection. Similar trends were observed with the onset of ischemia in the dialysate levels of serine, glutamine, glycine, alanine, taurine, and γ-aminobutyric acid.

Conclusions
Our results show that there is a significant increase in extracellular glutamate and other neurotransmitters with ischemia in the temporal lobe model of the human brain. This increase is of a higher magnitude than that in small animals.
Contribution of Diaschisis to the Clinical Deficit in Human Cerebral Infarction
Authors: Bowler J. V. , Wade J. P. H. , Jones B. E. , Nijran K. , Jewkes R. F. , Cuming R. , Steiner T. J.
Published: June 2011

Background and Purpose
Regions of decreased cerebral blood flow are often seen on single-photon emission computed tomography (SPECT) after stroke and have been widely reported to add to the clinical deficit. However, such reports have not distinguished between correlation and causation. We analyzed 124 serial SPECT scans performed in 50 patients to assess the role of diaschisis in the clinical deficit after stroke.

Methods
SPECT with the use of
99m
Tc–hexamethylpropyleneamine oxime (
99m
Tc-HMPAO) was performed in a prospective, unselected series of 50 patients with cerebral infarcts studied at a median of 1.1, 6.8, and 95 days after ictus. Patients were also assessed with the use of the Canadian Neurological Scale, the Barthel Index, a neuropsychological evaluation, and infarct volume measurement.

Results
One hundred twenty-four serial SPECT scans were done in 50 patients. Diaschisis was identified at 168 sites. There was insufficient correlation between diaschisis and the clinical measurements to support the suggestion that diaschisis independently causes clinical deficits beyond those due to the infarct itself. Unlike the clinical status, diaschisis showed little tendency to resolve during the 3-month follow-up period of the study. Several of the instances of correlation were shown to be of a noncausal kind, with both the diaschisis and the clinical deficit being due to the lesion directly; there was no known mechanism for the diaschisis to cause the clinical deficit.

Conclusions
Diaschisis does not independently add to the clinical deficit after stroke. It is more likely that it simply represents part of the damage done by the stroke.
Experimental Stroke and Neuroprotection in the Aging Rat Brain
Authors: Davis Michelle , Mendelow A. David , Perry Robert H. , Chambers Iain R. , James O. F. W.
Published: June 2011

Background and Purpose
Experimental stroke research has for the most part incorporated the use of young animals despite the importance of aging in cerebrovascular disease in humans. We hypothesized that age-related reductions in the density and function of cortical
N
-methyl-
d
-aspartate (NMDA) receptors might limit neuroprotective potential in the elderly. In this study, a model of occlusive stroke in the aging rat brain has been developed and used to establish the effects of age on cerebral infarction and to evaluate the scope for protecting the aging brain during ischemia.

Methods
Focal cerebral ischemia was produced by thermocoagulation of the left middle cerebral artery in adult (11 to 17 months) and aged (28 to 36 months) male Wistar rats. Infarcts were assessed histologically with volumetric analysis of infarct size, hemodynamically by serial cerebral blood flow measurement using the hydrogen clearance technique, and by analysis of specific gravity as an index of brain edema. Neuroprotective potential was assessed using the competitive NMDA receptor antagonist 3-(2-carboxy piperazin-4-yl)propyl-1-phosphonate (
d
-CPPene).

Results
Aging was associated with a significant increase in infarct size, with a mean infarct volume of 40.5±2.6% of the hemisphere volume in aged rats compared with 30.9±0.7% in adult rats (
P
<.01).
d
-CPPene reduced the mean infarct volume to 33±1.8% and 20.7±3.2% in aged and adult rats, respectively (
P
<.05). Cerebral blood flow fell markedly after infarction, but thereafter
d
-CPPene–pretreated rats maintained higher cerebral blood flow than untreated animals throughout the duration of the experiment (22.8±3.2 and 30.1±5.5 mL · 100 g
−1
· min
−1
in treated aged and adult rats, respectively, compared with 11.3±2.7 and 16.5±3.2 mL · 100 g
−1
· min
−1
in untreated aged and adult groups, 90 minutes after infarction [
P
<.05]). Pretreatment also reduced cortical edema; mean cortical specific gravity 4 hours after infarction was 1.0381±0.0013 in untreated aged rats and 1.0391±0.0014 in untreated adults compared with 1.0458±0.0031 in treated aged rats and 1.0442±0.0014 in treated adult rats (
P
<.05).

Conclusions
Under similar experimental conditions, there was an age-related increase in cerebral infarct size. However, NMDA receptor antagonism was neuroprotective in the aging brain and resulted in a significant reduction in cerebral ischemic damage, less cortical edema, and preservation of cerebral blood flow.
Treadmill Training With Partial Body Weight Support Compared With Physiotherapy in Nonambulatory Hemiparetic Patients
Authors: Hesse S. , Bertelt C. , Jahnke M. T. , Schaffrin A. , Baake P. , Malezic M. , Mauritz K. H.
Published: June 2011

Background and Purpose
Treadmill training with partial body weight support is a new and promising therapy in gait rehabilitation of stroke patients. The study intended to investigate its efficiency compared with gait training within regular physiotherapy in nonambulatory patients with chronic hemiparesis.

Methods
An A-B-A single-case study design compared treadmill training plus partial body weight support (A) with physiotherapy based on the Bobath concept (B) in seven nonambulatory hemiparetic patients. The minimum poststroke interval was 3 months, and each treatment phase lasted 3 weeks. Variables were gait ability assessed by the Functional Ambulation Category, other motor functions tested by the Rivermead Motor Assessment, muscle strength assessed by the Motricity Index, muscle tone rated by the Modified Ashworth Spasticity Scale, and gait cycle parameters.

Results
Treadmill training was more effective with regard to restoration of gait ability (
P
<.05) and walking velocity (
P
<.05). Other motor functions improved steadily during the study. Muscle strength did not change, and muscle tone varied in an unsystematic way. The ratio of cadence to stride length did not alter significantly.

Conclusions
Treadmill training offers the advantages of task-oriented training with numerous repetitions of a supervised gait pattern. It proved powerful in gait restoration of nonambulatory patients with chronic hemiparesis. Treadmill training could therefore become an adjunctive tool to regain walking ability in a shorter period of time.
Medical Complications During Stroke Rehabilitation
Authors: Kalra Lalit , Yu Gloria , Wilson Koo , Roots Pauline
Published: June 2011

Background and Purpose
We sought to evaluate the effect of setting on the rate of medical complications during stroke rehabilitation.

Methods
A study of the frequency and nature of medical complications in stroke rehabilitation was undertaken in 245 patients managed either on a stroke rehabilitation unit (n=124) or on general medical wards (n=121). The stroke unit setting was characterized by established protocols for prevention, early diagnosis, and management of complications (eg, aspiration, infections, thromboembolism, pressure sores, depression, stroke progression). Similar protocols did not exist on general medical wards except for thromboembolism, pressure sores, and secondary stroke prevention.

Results
Medical complications were documented in 147 patients (60%) and were more common in patients with severe strokes (97%). The frequency of reported complications was similar in both settings. Aspiration (33% versus 20%;
P
<.01) and musculoskeletal pain (38% versus 23%;
P
<.05) were more commonly documented on the stroke unit, whereas urinary problems (18% versus 7%;
P
<.01) and infections (49% versus 25%;
P
<.01) were more commonly seen on general medical wards. The reported frequency of deep vein thrombi, pressure sores, and stroke progression was similar in both settings. Although depression was reported equally in both settings (34% on the stroke unit versus 27% on general wards), patients on the stroke unit were more likely to be treated compared with general wards (67% versus 36%;
P
<.05).

Conclusions
The study shows that inpatient stroke rehabilitation is a medically active service. Management on specialist units is associated with earlier detection and management of stroke-related problems and prevention of potentially life-threatening complications.
‘Steal’ Is an Unestablished Mechanism for the Clinical Presentation of Cerebral Arteriovenous Malformations
Authors: Mast Henning , Mohr J. P. , Osipov Andrei , Pile-Spellman John , Marshall Randolph S. , Lazar Ronald M. , Stein Bennett M. , Young William L.
Published: June 2011

Background and Purpose
Focal neurological deficits (FNDs) in patients with arteriovenous malformations (AVMs) have been widely attributed to the phenomenon of “cerebral steal.” The incidence of focal deficits was investigated in a large prospective sample.

Methods
Using data from patient history and examination, CT or MRI, and transcranial Doppler sonography, we studied 152 consecutive, prospective AVM patients for evidence of FNDs unrelated to a hemorrhagic event. Feeding mean arterial pressure was measured during superselective angiography.

Results
Two (1.3%) of 152 patients met the criteria for a progressive FND. Nonprogressive FNDs were seen in 11 (7.2%) patients (stable in 4.6%, reversible in 2.6%). The median observation time period was 17 months (range, 1 to 60 months). There were no differences in transcranial Doppler mean velocities in feeding arteries in FND versus non-FND groups (118±44 versus 112±37 cm/s,
P
>.05) or pulsatility indexes (0.53±0.20 versus 0.55±0.15,
P
>.05). Feeding artery pressure was similar in FND (n=10) and non-FND (n=96) groups (39±16 versus 39±16 mm Hg at a systemic pressure of 82±18 versus 75±14 mm Hg, NS).

Conclusions
Nonhemorrhagic focal neurological syndromes in AVM patients are infrequent. Progressive deficits are especially rare. There was no relation between feeding artery pressure or flow velocities and FND. There does not appear to be sufficient evidence to assign steal as an operative pathophysiological mechanism in the vast majority of AVM patients.
Angiotensin-Converting Enzyme Gene Deletion Polymorphism
Authors: Markus Hugh S. , Barley Jackie , Lunt Ros , Bland J. Martin , Jeffery Steve , Carter Nick D. , Brown Martin M.
Published: June 2011

Background and Purpose
A deletion (
D
)/insertion (
I
) polymorphism in the angiotensin-converting enzyme gene has been associated with myocardial infarction. Its relations to both stroke and atheroma remain uncertain. We examined its role as a risk factor in patients with cerebrovascular disease and its relation to carotid atheroma.

Methods
One hundred one patients with symptomatic carotid artery territory cerebral ischemia were compared with 137 age-matched control subjects. In the patient group, carotid atheroma was assessed by measurement of degree of carotid stenosis and intima-media thickness with high-resolution duplex ultrasound. The
D/I
polymorphism was examined using the polymerase chain reaction.

Results
D:I
allele frequency was 0.59:0.41 in case subjects and 0.48:0.52 in control subjects (
P
=.01). The
DD
genotype was more common in patients with cerebrovascular disease compared with control subjects (36/101 versus 30/137,
P
=.02). The
DD
genotype conferred a relative risk of any type of cerebrovascular disease of 1.98 (95% confidence interval [CI], 1.11 to 3.51;
P
=.02). However, this was largely due to a strong association in the 18 patients with lacunar stroke, in whom the
D:I
ratio was 0.75:0.25 (
P
=.0097 versus control subjects). The odds ratio for lacunar stroke associated with the
DD
genotype was 5.6 (95% CI, 2.0 to 15.7) and was still significant at 4.40 (95% CI, 1.45 to 12.6;
P
<.009) after controlling for other risk factors. There was no significant association between angiotensin-converting enzyme genotype and cerebrovascular disease due to large-vessel stenosis. There was no association between genotype and age, sex, smoking history, diabetes, or cholesterol level.

Conclusions
The deletion polymorphism in the angiotensin-converting enzyme gene is a new independent risk factor for lacunar stroke but is not a risk factor for stroke associated with carotid stenosis.
Effects of the Valsalva Maneuver on Cerebral Circulation in Healthy Adults
Authors: Tiecks Frank P. , Lam Arthur M. , Matta Basil F. , Strebel Stephan , Douville Colleen , Newell David W.
Published: June 2011

Background and Purpose
Knowledge is limited about the effects of the Valsalva maneuver on cerebral circulation because of the poor temporal resolution of traditional cerebral blood flow measurements. The purpose of this study was to investigate changes in cerebral blood flow during the Valsalva maneuver and to explore its potential use for the evaluation of cerebral autoregulation.

Methods
Using transcranial Doppler ultrasonography, we simultaneously recorded systemic arterial blood pressure in the radial artery and flow velocities in both middle cerebral arteries in 10 healthy adults during the Valsalva maneuver. Gosling’s pulsatility index was calculated for all phases of the Valsalva maneuver. Autoregulatory capacities were estimated from the change in cerebrovascular resistance (flow velocity in relationship to blood pressure) during phase II and changes in the velocity-pressure relationship in phase IV relative to phase I.

Results
The characteristic changes in blood pressure (phases I to IV) were seen in all subjects, accompanying distinct changes in cerebral blood flow velocity. The relative changes in mean velocity during phases II and IV were significantly greater than those in mean blood pressure. Compared with the baseline value, velocity decreased by 35% in phase IIa, then rose by 56.5% in phase IV (corresponding changes in blood pressure were −10.2% and +29.8%, respectively). During phase II, the pulsatility and cerebrovascular resistance decreased by 19.9%. The increase in cerebral blood flow velocity in phase IV was significantly higher than in phase I (
P
<.0004), and there was no corresponding significant difference in blood pressure.

Conclusions
These results demonstrated that in healthy humans the Valsalva maneuver causes characteristic changes in systemic blood pressure as well as in flow velocity in the middle cerebral artery, reflecting the sympathetic and cerebral autoregulatory responses, respectively. Analysis of these changes may provide an estimate of autoregulatory capacity.
Ministrokes in Rat Barrel Cortex
Authors: Wei Ling , Rovainen Carl M. , Woolsey Thomas A.
Published: June 2011

Background and Purpose
Many stroke models in rats are based on occlusion of the middle cerebral artery, which supplies a significant portion of multifunctional cortical and deep structures in the cerebral hemisphere. The purpose of this study was to develop a model for direct observation in real time of blood flow in and around focal ischemic regions of the cortex of known function.

Methods
Cranial windows were placed over the parietal cortex of adult Wistar and Sprague-Dawley rats anesthetized with ketamine and xylazine. Whisker barrel cortex responding to stimulation of the contralateral whiskers was identified by an intrinsic optical signal. Transits of vital dyes were recorded by videomicroscopy before and after ligation of three to six branches and major collaterals of the middle cerebral artery through the dura. Infarcts were demonstrated with triphenyltetrazolium chloride staining; their relation to barrel cortex was determined by Nissl and cytochrome oxidase histology.

Results
Reduced blood flow in small ischemic regions was outlined by patent blue violet in the surrounding nonischemic area; arteriovenous latencies increased more than four times in ischemic cortex. Infarcts, typically 3 mm or less, were seen at 24 hours in 8 of 16 Wistar and 9 of 9 Sprague-Dawley rats. The ministrokes were confirmed by histology to be in the somatosensory cortex.

Conclusions
This model of local ischemia, produced deliberately in the functionally defined barrel cortex in rats, leads to ministrokes. Changes can be followed by videomicroscopy as they develop, and processes of recovery can potentially be monitored. Infarcts are confirmed by histology for their location and extent in the somatic representation.
Oral Anticoagulants and Intracranial Hemorrhage
Authors: Hart Robert G. , Boop Bradley S. , Anderson David C.
Published: June 2011

Background
Intracranial hemorrhage is the most feared and lethal complication of oral anticoagulation. We review the frequency, predictors, and prognosis of this most common neurological complication of oral anticoagulation.

Summary of Review
Anticoagulation to conventional intensities increases the risk of intracranial hemorrhage 7- to 10-fold, to an absolute rate of nearly 1%/y for many stroke-prone patients. Most (70%) anticoagulant-related intracranial hemorrhages are intracerebral hematomas (approximately 60% are fatal); the bulk of the remainder are subdural hematomas. Predictors of anticoagulant-related intracerebral hematoma are advanced patient age, prior ischemic stroke, hypertension, and intensity of anticoagulation. In approximately half of anticoagulated patients with intracerebral hematoma the bleeding evolves slowly over 12 to 24 hours, and emergency reversal of anticoagulation is crucial.

Conclusions
Both patient factors and anticoagulation intensity importantly influence the rate of anticoagulation-related intracranial hemorrhage. Patient-related risk factors for this complication overlap with those for ischemic stroke. The risk/benefit equation of anticoagulation for elderly, stroke-prone patients is complex and differs from that for younger patients. The absolute rate reduction (not the relative risk reduction) of ischemic stroke by anticoagulation is the critical issue and must offset accentuation of often lethal brain hemorrhage.
Transient Global Amnesia and Transient Ischemic Attack
Authors: Zorzon Marino , Antonutti Lucia , Masè Giovanni , Biasutti Emanuele , Vitrani Barbara , Cazzato Giuseppe
Published: June 2011

Background and Purpose
The purpose of the present study was to make an attempt to ascertain the etiology of transient global amnesia (TGA), which is still disputed more than 30 years after the first description of this clinical entity.

Methods
In a case-control study, we compared the prevalence of vascular risk factors in 64 TGA patients with 64 first-ever transient ischemic attack (TIA) control subjects and 108 normal community-based control subjects matched for age and sex. We prospectively studied the vascular events and mortality rates of the TGA cases and of the TIA control subjects. Then we compared the outcome of the two groups using actuarial analysis based on survival curves.

Results
We did not find evidence of an increased risk of TGA associated with any vascular risk factor. In contrast to TIA control subjects, no TGA patient suffered stroke, myocardial infarction, or TIA during the follow-up period. Migraine was more common in TGA patients than in both normal and TIA control subjects. In three patients (4.5%), the TGA was eventually considered to be of epileptic origin.

Conclusions
The results of our case-control and longitudinal studies point to the conclusion that TGA and TIA do not share the same etiology. Since half of our patients had a precipitating event in their history, it is reasonable to hypothesize that spreading depression may play a role in TGA. The significant positive association between migraine and TGA may support this hypothesis. Epilepsy may mimic TGA in a minority of cases.
Asymmetrical Skin Temperature in Ischemic Stroke
Authors: Korpelainen Juha T. , Sotaniemi Kyösti A. , Myllylä Vilho V.
Published: June 2011

Background and Purpose
Sympathetic dysfunction is known to manifest commonly in stroke as cardiovascular and sudomotor dysregulation, but the knowledge so far obtained concerning skin temperature and vasomotor changes in cerebrovascular diseases is contradictory. The purpose of the present study was to evaluate cutaneous temperature in ischemic stroke in a prospective follow-up study.

Methods
Skin temperature was measured at five sites on each side of the body at rest and after a heating stimulus in 44 patients with a hemispheric infarction, and in 19 patients with a brain stem infarction, in the acute phase and at 1 month and at 6 months after the infarction.

Results
Skin temperatures on the forearm, leg, and foot on the side contralateral to the site of infarction were significantly lower than on the ipsilateral side during the whole 6-month follow-up period. Asymmetrical temperature was associated with the presence of pyramidal tract signs in hemispheric infarction and with the presence of Wallenberg’s syndrome in brain stem infarction. In hemispheric infarction, the degree of asymmetrical temperature correlated with the severity of limb paresis.

Conclusions
A temperature decline in the limbs contralateral to the site of infarction seems to be a frequent, long-lasting consequence of autonomic failure in patients with stroke. The phenomenon seems to be associated with pyramidal tract signs and the presence of Wallenberg’s syndrome.
Effect of Adenosine on Cerebral Blood Flow as Evaluated by Single-Photon Emission Computed Tomography in Normal Subjects and in Patients With Occlusive Carotid Disease
Authors: Soricelli Andrea , Postiglione Alfredo , Cuocolo Alberto , De Chiara Simona , Ruocco Antonio , Brunetti Arturo , Salvatore Marco , Ell Peter J.
Published: June 2011

Background and Purpose
Acetazolamide is commonly used with single-photon CT to assess the cerebrovascular reserve in patients with internal carotid artery stenosis or occlusion. In this study we wanted to evaluate the effects of adenosine, a well-known vasodilatatory compound with a short biological half-life, on brain circulation in humans and compare the results with those of acetazolamide.

Methods
Acetazolamide (1 g) and adenosine (140 μg/kg per minute) were injected intravenously on different days in 6 normal subjects and 6 patients: 4 with unilateral stenosis, 1 with bilateral stenosis, and 1 with complete occlusion of the internal carotid artery. Changes in regional cerebral blood flow relative to that of the cerebellum (cortico/cerebellar ratios) from resting conditions were evaluated by
99m
Tc–hexamethylpropyleneamine oxime and single-photon emission CT.

Results
The measured blood flow ratios increased significantly in the normal group 20 minutes after acetazolamide injection in several cortical and subcortical regions, as well as at the 4th minute of a 6-minute adenosine infusion. Regional cerebral blood flow ratio values were higher after adenosine than after acetazolamide in both cortical (frontal and parietal) and subcortical (thalamus and basal ganglia) regions. In 4 of the 6 patients the side-to-side asymmetry increased from the basal resting condition after the injection of acetazolamide and even more so after the injection of adenosine.

Conclusions
Adenosine infusion causes vasodilatation of cerebral arteries and can be used for the investigation of cerebrovascular perfusion capacity in patients with carotid occlusive disease. One advantage in the use of adenosine over acetazolamide is the possibility of interrupting the test with reversal of clinical symptoms or patient discomfort within a few minutes.
Sex-Related Differences in Acetazolamide-Induced Cerebral Vasomotor Reactivity
Authors: Karnik Ronald , Valentin Andreas , Winkler Walther-Benedikt , Khaffaf Nadja , Donath Peter , Slany Jörg
Published: June 2011

Background and Purpose
Cerebral vasomotor reactivity can easily be assessed reliably by measuring vasodilatory response to acetazolamide by transcranial Doppler sonography. The aim of this study was to confirm the hypothesis that female sex is associated with an increased cerebrovascular flow reserve.

Methods
Blood flow velocity of the middle cerebral artery was measured by transcranial Doppler sonography in 36 healthy sex- and age-matched subjects. After the initial blood flow velocities were recorded, the subjects received 14.3 mg/kg body wt acetazolamide, ie, 1 g/70 kg, intravenously. The measurements were repeatedly performed at 5-minute intervals starting 10 minutes after injection and lasting for 30 minutes. The highest measured flow velocities were used for further analysis.

Results
In both groups mean blood flow velocity increased significantly after acetazolamide (women, from 60.2±12.5 to 89.9±14.4 cm/s,
P
<.006; men, from 54.5±18.8 to 75.7±24.5 cm/s,
P
<.02). The difference in mean blood flow velocity after acetazolamide between groups of women and men was statistically significant (
P
<.02).

Conclusions
Female subjects show an increased vasodilatory response to the acetazolamide test compared with men.
Sonographic Assessment of Carotid Artery Stenosis
Authors: Steinke Wolfgang , Meairs Stephen , Ries Stefan , Hennerici Michael
Published: June 2011

Background and Purpose
Power Doppler imaging (PDI) is a new ultrasound technique that, in contrast to color Doppler flow imaging (CDFI), generates intravascular color signals from the reflected echo amplitude depending mainly on the density of red blood cells. We evaluated the diagnostic significance of PDI compared with CDFI for the measurement of carotid stenosis and characterization of plaque surface.

Methods
In 25 internal carotid artery stenoses, reduction of the intrastenotic lumen contrasted by blood density signals and color Doppler signals on longitudinal and transverse views was assessed for correlative evaluation. In addition, the peak systolic flow velocity of the Doppler spectrum was correlated with PDI and CDFI measurements.

Results
PDI provided good visualization of the residual lumen in all stenoses, whereas displays on CDFI were inadequate in two calcified plaques. PDI revealed two ulcerative stenoses classified as smooth on CDFI. The correlation between PDI and CDFI was high for measurement of area stenosis (
r
=.93) and moderate for diameter stenosis (
r
=.73). Similarly, cross-sectional reduction on both imaging methods correlated more significantly with peak systolic flow velocity than diameter reduction.

Conclusions
This pilot study suggests that PDI provides additional information for luminal measurement and characterization of plaque surface in complicated high-grade carotid stenosis. Because of the absent visualization of hemodynamics, PDI should be used in combination with CDFI.
Cerebrovascular Disease Assessed by Color-Flow and Power Doppler Ultrasonography
Authors: Griewing B. , Morgenstern C. , Driesner F. , Kallwellis G. , Walker M.L. , Kessler C.
Published: June 2011

Background and Purpose
An understanding of carotid atherosclerosis is important to further our knowledge regarding the etiology of cerebral ischemia, and therefore it is necessary to accurately visualize carotid stenosis. The purpose of the present study was to compare different imaging techniques to determine their advantages and disadvantages in the diagnosis and quantification of middle- and high-grade internal carotid artery stenosis. In particular, we were interested in evaluating the effectiveness of the new ultrasound technique power Doppler.

Methods
Fifty-four patients with greater than 50% extracranial internal carotid artery stenosis, as determined by continuous-wave Doppler, were recruited prospectively to serve as subjects. All subjects were examined with color-flow Doppler, power Doppler, and digital subtraction angiography to enable visualization of carotid stenosis and plaque surface morphology.

Results
Thirty-four middle-grade stenoses (50% to 69%), 32 high-grade stenoses (70% to 99%), and 7 complete occlusions of the internal carotid artery were diagnosed with the use of digital subtraction angiography. Power Doppler visualized stenosis significantly more frequently and accurately than color-flow Doppler. Color-flow Doppler tended to overestimate and underestimate in patients with both middle- and high-grade stenosis. Power Doppler was superior to both color-flow Doppler and angiography with regard to differentiation of plaque surface morphology.

Conclusions
This study demonstrates that power Doppler is an important, noninvasive imaging technique that has several advantages over color-flow Doppler in diagnosing carotid artery stenosis and visualizing plaque surface. Power Doppler, used in concert with other ultrasound techniques, should enable a more accurate detection and treatment of cerebrovascular disease.
Acute Stroke With Atrial Fibrillation
Authors: Jørgensen Henrik Stig , Nakayama Hirofumi , Reith Jakob , Raaschou Hans Otto , Olsen Tom Skyhøj
Published: June 2011

Background
Atrial fibrillation (AF) is a common arrhythmia and a major risk factor for stroke. Many physicians remain reluctant to provide stroke prevention by anticoagulant therapy especially for elderly individuals with AF. Using multivariate regression analyses, we studied the characteristics and the prognosis of stroke in patients with AF.

Methods
The study is part of the Copenhagen Stroke Study, a prospective, community-based study of 1197 patients with acute stroke treated on a stroke unit from the time of acute admission to the end of rehabilitation. Initial stroke severity was measured by the Scandinavian Neurological Stroke Scale (SSS). Neurological and functional outcomes were evaluated by the SSS and the Barthel Index.

Results
AF was diagnosed in 18% of the patients. AF increased steeply with age in the stroke population, from 2% in patients <50 years old, 15% in patients in their 70s, and 28% in patients in their 80s, to 40% in patients ≥90 years of age. In a multivariate analysis AF was associated with age (odds ratio [OR], 2.0 per 10-year increase; 95% confidence ratio [CI], 1.6 to 2.6), ischemic heart disease (OR, 3.4; 95% CI, 2.4 to 4.8), previous stroke (OR, 1.8; 95% CI, 1.2 to 2.6), and systolic blood pressure (OR, 0.93 per 10-mm Hg increase; 95% CI, 0.88 to 0.99), but not with sex, diabetes, hypertension, previous transient ischemic attack, or silent infarction on computed tomography. Patients with AF had a higher mortality rate (OR, 1.7; 95% CI, 1.2 to 2.5), longer hospital stays (50 days versus 40 days,
P
<.001), and a lower discharge rate to their own homes (OR, 0.60; 95% CI, 0.44 to 0.85). Neurological and functional outcomes were markedly poorer in patients with AF. Poorer outcome was exclusively explained by initially more-severe strokes.

Conclusions
Stroke in patients with AF is generally more severe and outcome markedly poorer than in patients with sinus rhythm. This accentuates the importance of anticoagulant treatment of individuals with AF. A lower blood pressure in the acute stage of stroke may contribute to the increased stroke severity in patients with AF.
Circadian and Circannual Rhythmicity in the Occurrence of Subarachnoid Hemorrhage
Authors: Gallerani Massimo , Portaluppi Francesco , Maida Giuseppe , Chieregato Arturo , Calzolari Ferdinando , Trapella Giorgio , Manfredini Roberto
Published: June 2011

Background and Purpose
Inconsistent data are available on the temporal pattern of onset of subarachnoid hemorrhage (SAH). We investigated the possible influence of vascular risk factors.

Methods
Of a consecutive series of 217 cases of SAH, precise determination (within 30 minutes) of the time of symptom onset was possible in 199 (91.7%). Partial Fourier series with up to six harmonics were applied to hourly and monthly data, and the best-fitting curves for circadian and annual rhythmicity were calculated. The amplitude-MESOR (rhythm-adjusted mean over the time period analyzed) ratio was used as a measure of temporal variability.

Results
In the total population, a significant circadian pattern of occurrence was demonstrated with major peaks in the morning (≈9
am
) and evening (≈9
pm
) hours and a nocturnal trough (≈3
am)
. Younger, male, and hypertensive subjects had lower amplitude-MESOR ratios; smokers had no significant rhythmicity. The annual pattern showed a 6-month periodicity with two major peaks in March and September and minor differences in the subgroups studied.

Conclusions
Our study indicates that the temporal distribution in onset of SAH may be influenced by variable combinations of environmental and vascular risk factors.
Serum Neuron-Specific Enolase, Carnosinase, and Their Ratio in Acute Stroke
Authors: Butterworth R.J. , Wassif W.S. , Sherwood R.A. , Gerges A. , Poyser K.H. , Garthwaite J. , Peters T.J. , Bath P.M.W.
Published: June 2011

Background and Purpose
Few admission variables adequately predict neuronal damage and prognosis in individual patients after stroke. Therefore, there is a need for a reliable noninvasive surrogate measure of clinical outcome.

Methods
We have developed a surrogate measure of stroke outcome using the ratio of serum neuron-specific enolase (NSE) to human serum carnosinase (HSC) in 124 patients with acute ischemic or hemorrhagic stroke and 61 matched control subjects. Serum NSE is known to rise and HSC to fall after neuronal injury such as cerebral ischemia.

Results
Serum NSE levels were significantly higher and HSC levels lower in the patient group. The NSE/HSC ratio was elevated in patients with stroke: median (semiquartile) hemorrhages, 0.072 (0.033); infarcts, 0.039 (0.026); and control subjects, 0.019 (0.014),
P
=.0001. Patients with a primary intracerebral hemorrhage had nonsignificantly higher ratios than those with an infarct (
P
=.082). The NSE/HSC ratio was significantly associated with 90-day outcome measured in two out of three disability and handicap scales: modified Barthel Index (
r
s
=−.34,
P
=.001), modified Rankin Scale (
r
s
=.30,
P
=.002), and Lindley Score (
r
s
=.19,
P
=.057). Patients who died or were institutionalized had higher ratios than those who were discharged home: 0.069 (0.043) versus 0.038 (0.024),
P
=.011. Correlations between the NSE/HSC ratio and outcome were comparable to those between patient age or consciousness level on admission and clinical outcome.

Conclusions
We believe that measurement of NSE, HSC, or their ratio may be useful in the assessment of patients with acute stroke with respect to diagnosis and prediction of clinical outcome.