bluuebunny/crossref_metadata_2025 huggingface dataset:
An Approach for the Use of Doppler Ultrasound as a Screening Tool for Hemodynamically Significant Stenosis (Despite Heterogeneity of Doppler Performance)
Authors: Howard George , Baker William H. , Chambless Lloyd E. , Howard Virginia J. , Jones Anne M. , Toole James F.
Published: June 2011

Background and Purpose
The Asymptomatic Carotid Atherosclerosis Study (ACAS) Doppler validation study assessed the performance of individual Doppler machines across a spectrum of laboratories. We attempted to establish a threshold specific to individual machines to predict angiographically defined hemodynamic stenosis. The reliability of these Doppler ultrasound criteria was prospectively and independently evaluated among patients screened with ultrasound in the ACAS trial.

Methods
Regression techniques were used to establish the relationship between Doppler velocity and percent stenosis by angiography for 63 specific Doppler machines. This relationship was used to establish a Doppler threshold to provide a 90% positive predictive value (PPV) of a 60% stenosis by angiography. The sensitivity of each Doppler machine to detect a 60% stenosis (at the 90% PPV threshold) was estimated. The efficacy of these Doppler thresholds was then prospectively evaluated by calculating the PPV among ACAS participants eligible by ultrasound.

Results
Of the 63 machines, 13 (21%) had an excellent sensitivity (80%+) at 90% PPV. In 32 devices (51%) only a marginal sensitivity (50% to 80%) could be achieved. In 9 devices (14%) the sensitivity was poor (0% to 50%), and in 9 (14%) no threshold could be established. Despite the heterogeneity of Doppler performance, the standardization program worked as designed in the ACAS trial. Of 825 surgical patients, 399 were eligible by Doppler and 395 subsequently underwent angiography. Of these, 32 (8.1%; 95% confidence interval, 5.4% to 10.8%) did not have hemodynamically significant stenosis by arteriography, a proportion nonsignificantly lower than the planned 10% by the PPV.

Conclusions
The performance of Doppler ultrasound was highly variable. This suggests that Doppler performance is likely overstated in the literature, but specific devices may perform satisfactorily to detect individuals with hemodynamically significant stenosis. Because performance differs substantially among devices, local investigators are strongly urged to maintain local standardization series. With such standardization, ultrasound performance is sufficient for admission to clinical trials and as the basis for carotid surgery. However, without quality control many ultrasound machines are not adequate to accurately predict the degree of carotid stenosis and should not be the only test to decide whether surgery is warranted.
Impairments of the Protein C System and Fibrinolysis in Infection-Associated Stroke
Authors: Macko Richard F. , Ameriso Sebastian F. , Gruber Andras , Griffin John H. , Fernandez Jose A. , Barndt Robert , Quismorio Francisco P. , Weiner John M. , Fisher Mark
Published: June 2011

Background and Purpose
Infection/inflammation appears to be an important predisposing risk factor for brain infarction, but little is known regarding underlying molecular mechanisms. We examined the hypothesis that patients with brain infarction preceded by infection/inflammation within 1 week could be identified by a distinctive procoagulant laboratory profile characterized by abnormalities in the protein C system and endogenous fibrinolysis.

Methods
We performed a case-control study examining the relationship between preceding systemic infectious/inflammatory syndromes and selected immunohematologic variables in 36 patients with acute brain infarction and 81 control subjects (community control subjects [n=47] and hospitalized nonstroke neurological patient controls [n=34]).

Results
The stroke group had a lower mean level of the circulating antithrombotic enzyme activated protein C (APC) (4.33±0.34% [log-transformed percentage of control value, mean±SD]) than community control subjects (4.51±0.27%,
P
<.02) or hospitalized neurological patient controls (4.57±0.31%,
P
<.005). The lowest circulating APC levels were found in the stroke group with antecedent infection/inflammation within 1 week preceding index brain infarction (4.23±0.4%, n=12). Within the stroke group, circulating APC levels were inversely related to IgG isotype anticardiolipin antibody titers (
r
=−.55,
P
<.001). Only the stroke group with infection/inflammation within 1 week had elevated plasma C4b binding protein compared with control subjects (141±61% versus 112±44%,
P
<.05). Stroke patients with antecedent infection/inflammation had a distinctively lower ratio of active tissue plasminogen activator to plasminogen activator inhibitor (0.11±0.04, n=9) than other stroke patients (0.19±0.06, n=9,
P
<.01) and control subjects (0.22±0.16, n=17,
P
<.02).

Conclusions
Impairments in the protein C pathway and endogenous fibrinolysis may contribute to the increased risk for brain infarction after recent (≤1 week) infection/inflammation. A decrease in the circulating anticoagulant APC may be related to elevated antiphospholipid antibody titers.
Response of Patients With Major Depression and Silent Cerebral Infarction to Antidepressant Drug Therapy, With Emphasis on Central Nervous System Adverse Reactions
Authors: Fujikawa Tokumi , Yokota Norio , Muraoka Mitsutaro , Yamawaki Shigeto
Published: June 2011

Background and Purpose
We previously found that silent cerebral infarction (SCI) is present in most patients older than 50 years with major depression. The present study was designed to clarify the response to antidepressant pharmacotherapy in patients with major depression associated with SCI.

Methods
Using clinical charts, we retrospectively studied patients older than 50 years who were admitted for antidepressant drug therapy. Patients with bipolar affective disorder and those with focal neurological symptoms were excluded. All patients underwent magnetic resonance imaging and were classified as SCI-negative or SCI-positive. The SCI-positive group was subclassified into those with moderate SCI (either perforating area or cortical area) (n=15) and those with severe SCI (both perforating and cortical areas) (n=7). Duration of treatment in hospital and the incidence of central nervous system adverse reactions to the antidepressant drugs were compared between the two groups.

Results
The duration of hospital treatment in patients with severe SCI was significantly longer than in those with moderate SCI (
P
<.01). The percentage of patients with adverse central nervous system reactions to antidepressant drugs was significantly higher in the SCI-positive group than in the SCI-negative group (
P
<.05). Patients with severe SCI had significantly more adverse reactions than those with moderate SCI (
P
<.05).

Conclusions
Depressed patients with severe SCI required longer hospital treatment and had more drug-related adverse reactions of the central nervous system. These findings suggest that the depression associated with severe SCI may be resistant to treatment.
Dissociation of Vasoreactivity to Acetazolamide and Hypercapnia
Authors: Kazumata Ken , Tanaka Naruhiko , Ishikawa Tatsuya , Kuroda Satoshi , Houkin Kiyohiro , Mitsumori Kenji
Published: June 2011

Background and Purpose
The aim of this study was to compare the effect of vasodilative stimuli for the measurement of cerebrovascular reactivity obtained by acetazolamide and hypercapnia in patients with chronic occlusive major cerebral artery disease.

Methods
We examined 24 patients with unilateral occlusive lesions of a major cerebral artery using the
133
Xe inhalation technique and single-photon emission CT. Regional cerebral blood flow (CBF) was measured during a resting state, during inhalation of 5% CO
2
, and 15 minutes after the administration of acetazolamide consecutively in the same patients. Normative values of resting CBF and acetazolamide reactivity were obtained in 21 normal subjects.

Results
All patients with the exception of 1 showed an increase in CBF during hypercapnia ipsilateral to the occlusive lesion. Ipsilateral acetazolamide reactivity was preserved in 13 patients. Conversely, 11 patients showed an absent response or paradoxical CBF reduction. Ipsilateral CO
2
reactivity did not correlate with acetazolamide reactivity when all 24 patients were considered. However, there was a significant correlation between acetazolamide and CO
2
in the 13 patients who showed preserved acetazolamide reactivity (
r
=.60,
P
<.05). No significant correlation was present in the remaining 11 patients with reduced acetazolamide reactivity. Although significant blood pressure augmentation was observed in hypercapnia, we could not find a correlation between change of blood pressure and CO
2
reactivity.

Conclusions
Acetazolamide identified patients with reduced vasomotor reactivity who appeared to have preserved CO
2
reactivity. Acetazolamide testing may be useful in the assessment of cerebral hemodynamics. However, further investigations are necessary to assess the clinical utility of these tests.
Cystatin C
Authors: Wei LiHong , Walker Lary C. , Levy Efrat
Published: June 2011

Background and Purpose
Cerebral amyloid angiopathy (CAA) occurs as a sporadic disorder in aged humans, as a frequent component of Alzheimer's disease, or in hereditary cerebral hemorrhage with amyloidosis (HCHWA). The primary histological locus of cerebral amyloid deposition varies in aged humans and in different species of nonhuman primates. In aged rhesus monkeys, amyloid deposition occurs most frequently in senile plaques, whereas in aged squirrel monkeys CAA is more common. We hypothesized that the preponderance of CAA in squirrel monkeys is related to a species-specific amino acid change in cystatin C, a cysteine protease inhibitor, similar to the Leu68Gln substitution found in the amyloid protein of Icelandic patients with HCHWA-I, also termed hereditary cystatin C amyloid angiopathy.

Methods
We performed immunohistochemical analyses of brain sections of aged squirrel and rhesus monkeys with anti–amyloid-β and anti–cystatin C antibodies and sequenced the cystatin C cDNA of these monkeys.

Results
Cerebral amyloid in aged squirrel and rhesus monkeys, previously shown to be immunoreactive with anti–amyloid-β antibodies, reacts also with antibodies to cystatin C. While the predicted amino acid sequence in rhesus monkeys differs from the human sequence by four residues, that of the squirrel monkeys has seven additional amino acid substitutions, one of which is Leu68Met.

Conclusions
The presence of a mutation in squirrel monkeys similar to the one found in HCHWA-I suggests that alterations in cystatin C may influence the likelihood that amyloid will be deposited in the walls of cerebral blood vessels. These observations support the utilization of the monkeys as models to study CAA.
Role of Extracellular Matrix in Experimental Vasospasm
Authors: Onoda Keisuke , Ono Shigeki , Ogihara Kotaro , Shiota Tomomi , Asari Shoji , Ohmoto Takashi , Ninomiya Yoshifumi
Published: June 2011

Background and Purpose
Although it has been suggested that collagen plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no constructive research to prove it directly. In this study we stopped the transcription of the procollagen type I gene by introducing antisense oligonucleotides for its mRNA in a rat femoral artery model of vasospasm induced by blood and assayed the changes in the vasoconstrictive activity of the vessel and expression of the procollagen mRNA.

Methods
We applied antisense, sense, or missense oligonucleotides, located at the carboxyl propeptide region for α1(I) procollagen mRNA, onto the femoral artery in a rat femoral artery model of vasospasm. The diameter of the artery was measured by angiography. The transcription level of the procollagen gene in the arterial tissue was assayed by use of reverse transcription–polymerase chain reaction. Morphological change in the artery was observed with aldehyde-fuchsin-Masson-Goldner staining.

Results
In the model, when the artery was exposed to antisense oligonucleotides in pluronic gel for 5 days to prevent arterial contraction, the contraction was inhibited at a significant level (76.0%±5.6) when compared with that in control experiments using sense oligonucleotides (64.0%±2.4), missense oligonucleotides (63.5%±3.5), or gel alone (62.1%±5.8). The application of antisense oligonucleotide resulted in a marked decrease in α1(I) procollagen mRNA expression as determined by polymerase chain reaction, indicating that the collagen reduction by antisense oligonucleotides occurred at the transcription level. Histological staining suggested that collagen accumulation at the site in the artery where antisense oligonucleotide had been administered was indeed less than that in the control artery.

Conclusions
The results indicate that the induction of procollagen type I could cause pathogenesis of the arterial contraction induced by blood in a rat femoral vasospasm model.
Ultrasonographic Study and Long-term Follow-up of Takayasu's Arteritis
Authors: Sun Yu , Yip Ping-Keung , Jeng Jiann-Shing , Hwang Bao-Show , Lin Win-Hwan
Published: June 2011

Background and Purpose
Takayasu's arteritis is an inflammatory vasculopathy involving the aorta and its major branches. Little information is available on the natural history and temporal profile of changes in the carotid vessels, the major vessels involved in Takayasu's arteritis. Duplex ultrasonography may provide a reliable and efficient tool for the characterization and follow-up of the brachiocephalic vascular changes in Takayasu's arteritis.

Methods
Sixteen female patients fulfilling the clinical diagnostic criteria for Takayasu's arteritis were studied. Mean age at onset was 23.6 years (SD=6.0), and mean duration of follow-up was 17.1 years (SD=11.9). The clinical features were analyzed. Only one patient had had a stroke. They had undergone at least one duplex scanning examination to evaluate the brachiocephalic vessels, including the extracranial carotid, vertebral, and subclavian arteries. Six patients underwent sequential duplex examination and long-term clinical follow-up.

Results
All the studied patients had subclavian artery involvement, and 11 (69%) had common carotid artery involvement. The percentage of bilateral concomitant involvement was 100% in the common carotid artery and 33% in the subclavian artery. Homogeneous circumferential intima-media thickening was commonly seen in stenotic common carotid arteries (89%). Four patients had internal carotid artery involvement (all on the left side). In the serial duplex follow-up study, 2 of 6 patients had progressive vascular stenosis with concentric thickening, rather than longitudinal spreading, in the bilateral common carotid arteries. Left-side lesions were more prominent. Most were clinically stationary, despite severe stenosis or occlusion of the common carotid arteries.

Conclusions
The characteristic vascular lesions and progression changes in Takayasu's arteritis detected by duplex ultrasonography are quite different from those seen in ordinary atherosclerosis. Homogeneous circumferential intima-media thickening of the common carotid arteries is a highly specific ultrasonographic finding in patients with Takayasu's arteritis, particularly young women. Sequential duplex scanning showed vascular progression to be unpredictable and unrelated to medication in our patients. Further clinical investigations of vascular progression are warranted, and duplex scanning may provide a simple, safe, and accurate long-term means of follow-up.
Slow Rhythmic Oscillations of Blood Pressure, Intracranial Pressure, Microcirculation, and Cerebral Oxygenation
Authors: Steinmeier Ralf , Bauhuf Christian , Hübner Ulrich , Bauer Rudolf Dietrich , Fahlbusch Rudolf , Laumer Rudolf , Bondar Imre
Published: June 2011

Background and Purpose
Various biological signals show nonpulsatile, slow rhythmic oscillations. These include arterial blood pressure (aBP), blood flow velocity in cerebral arteries, intracranial pressure (ICP), cerebral microflow, and cerebral tissue P
o
2
. Generation and interrelations between these rhythmic fluctuations remained unclear. The aim of this study was to analyze whether stable dynamic interrelations in the low-frequency range exist between these different variables, and if they do, to analyze their exact time delay.

Methods
In a clinical study, 16 comatose patients with either higher-grade subarachnoid hemorrhage or severe traumatic brain injury were examined. A multimodal digital data acquisition system was used to simultaneously monitor aBP, flow velocity in the middle cerebral artery (FV
MCA
), ICP, cerebral microflow, and oxygen saturation in the jugular bulb (Sj
o
2
). Cross-correlation as a means to analyze time delay and correlation between two periodic signals was applied to a time series of 30 minutes' duration divided into four segments of 2048 data points (≈436 seconds) each. This resulted in four cross-correlations for each 30-minute time series. If the four cross-correlations were consistent and reproducible, averaging of the original cross-correlations was performed, resulting in a representative time delay and correlation for the complete 30-minute interval.

Results
Reproducible cross-correlations and stable dynamic interrelations were found between aBP, FV
MCA
, ICP, and Sj
o
2
. The mean time delay between aBP and ICP was 6.89±1.90 seconds, with a negative correlation in 81%. A mean time delay of 1.50±1.29 seconds (median, 0.85 seconds) was found between FV
MCA
and ICP, with a positive correlation in 94%. The mean delay between ICP and Sj
o
2
was 9.47±2.21 seconds, with a positive correlation in 77%. Mean values of aBP and ICP did not influence the time delay and dynamic interrelation between the different parameters.

Conclusions
These results strongly support Rosner's theory that ICP B-waves are the autoregulatory response of spontaneous fluctuations of cerebral perfusion pressure. There is casuistic evidence that failure of autoregulation significantly modifies time delay and the correlation between aBP and ICP.
Hyperinsulinism and Cerebral Microangiopathy
Authors: Zunker Peter , Schick Achim , Buschmann Hans-Christian , Georgiadis Dimitrios , Nabavi Darius G. , Edelmann Michael , Ringelstein E. Bernd
Published: June 2011

Background and Purpose
High insulin levels are a recognized risk factor for atherosclerosis. Microvascular endothelium is more susceptible to metabolic and mitogenic effects of insulin than large-vessel endothelium. Besides their atherogenic effect, high insulin levels impair fibrinolysis by enhancing plasminogen activator inhibitor–1. We undertook this study to evaluate the hypothesis that elevated serum insulin and C-peptide levels are related to cerebral small-vessel disease rather than large-vessel pathology.

Methods
One hundred ninety-four consecutive patients presenting with symptomatic cerebrovascular disease were assigned to three subgroups that were differentiated by clinical presentations, brain imaging studies, and extracranial as well as transcranial vascular ultrasound findings: (1) patients with lacunes (n=20), (2) patients with subcortical arteriosclerotic encephalopathy (n=35), and (3) patients with strokes due to large-vessel disease (n=99). Patients who had suffered a cryptogenic (n=9) or cardioembolic (n=16) stroke or who showed characteristics of the microangiopathy and macroangiopathy groups (n=15) were not further evaluated. Thirty patients without manifestations of cerebrovascular disease were also examined. Fasting blood glucose, insulin, and C-peptide levels were determined in all subjects.

Results
There were no significant differences in age or sex among the three groups and control patients. Insulin levels were significantly higher in the lacunar group compared with the subcortical arteriosclerotic encephalopathy group, the macroangiopathy group, and the control patients (median [interquartile range]: 103.8 [198.6], 72.0 [103.2], 66.0 [57.0], and 52.2 [57.0] pmol/L, respectively; all
P
<.05, Mann-Whitney test). There was a statistically significant difference in insulin concentrations between the microangiopathy group (subcortical arteriosclerotic encephalopathy and lacunes) and the macroangiopathy and control groups (81.0 [110.4], 66.0 [57.0], and 55.2 [57.0] pmol/L, respectively; all
P
<.05, Mann-Whitney). The same was true for the distribution of C-peptide levels and to a minor extent blood glucose values, but these differences failed to reach statistical significance.

Conclusions
Elevated insulin levels potentially represent a pathogenetic factor in the development of cerebral small-vessel disease, predominantly in patients presenting with lacunes. Whether this is due solely to atherosclerotic changes of the small penetrating arteries or whether changes in hemorheology are operative as well remains to be evaluated.
Interobserver Agreement in the Classification of Stroke in the Physicians’ Health Study
Authors: Berger Klaus , Kase Carlos S. , Buring Julie E.
Published: June 2011

Background and Purpose
The evaluation of cerebrovascular end points in prospective studies is often based exclusively on medical record examination and may be made by more than one observer over time. To address the issues of adequacy of medical record information and consistency in diagnosis over time, we evaluated interobserver agreement for the main items of the stroke classification system used in the Physicians’ Health Study. This trial included 22 071 physicians randomly assigned in 1982 to receive either aspirin or placebo to assess the subsequent risk of cardiovascular events, including stroke.

Methods
Stroke subtype, stroke severity, and certainty of diagnosis were first classified from medical records from the years 1982 through 1988. The 216 stroke events reported in this period were independently reclassified in 1994 and compared with the initial classification using kappa statistics.

Results
Overall agreement in major stroke types (hemorrhagic, ischemic, undetermined stroke) as well as in hemorrhagic stroke subtypes was excellent (κ=0.81 and κ=0.95, respectively). A wide range of values for the ischemic stroke subtypes (κ=0.13 to κ=0.96) was obtained. Agreement was substantial in assessment of stroke severity (κ=0.71), and it was fair (κ=0.33) for certainty of diagnosis.

Conclusions
Interobserver agreement is high for major stroke types as well as for categories of hemorrhagic stroke on the basis of review of medical records and results of imaging data. The classification of ischemic stroke subtypes, however, is subject to substantial interobserver disagreement. Periodic reclassification of random samples of end points might be considered in long-term prospective studies to assess potential misclassification of events by different observers.
Sleep-Disordered Breathing and Poor Functional Outcome After Stroke
Authors: Good David C. , Henkle Joseph Q. , Gelber David , Welsh Jennifer , Verhulst Steve
Published: June 2011

Background and Purpose
We objectively evaluated patients with recent stroke to determine the prevalence of sleep-disordered breathing (SDB) and whether SDB was associated with unfavorable clinical outcomes.

Methods
Forty-seven patients with recent ischemic stroke (median, 13 days) were studied with computerized overnight oximetry for evidence of arterial oxyhemoglobin desaturation (Sa
o
2
). Polysomnography was also performed on 19 patients. Medical history, sleep history, location of stroke, and severity of neurological deficit were recorded, and patients were observed by staff for evidence of snoring and excessive daytime sleepiness. Functional abilities were measured with the use of the Barthel Index (BI). Outcome variables included ability to return home at discharge, continued residence at home at 3 and 12 months, BI at discharge, BI at 3 and 12 months, and death from any cause at 12 months.

Results
Mean Sa
o
2
during oximetry was 94.0±1.7%, and percentage of recording time spent at <90% Sa
o
2
was 4.3±5.7%. The number of desaturation events per hour of recording time (desaturation index [DI]) was 9.5±9.67, with 15 of 47 (32%) having DI >10 and 6 of 47 (13%) having DI >20. Oximetry measures of SDB correlated with lower BI scores at discharge and lower BI at 3- and 12-month follow-ups (
P
≤.05, Pearson coefficients). Oximetry measures correlated with return home after discharge, but the association between oximetry measures and living at home was lost at 12 months. Two oximetry variables correlated with death at 1 year. Brain stem location correlated with higher DI and time at <90% Sa
o
2
, but patients with hemispheric stroke and oximetry abnormalities also had worse functional outcome. No correlation was found between oximetry values and sex, age, preexisting medical conditions (except previous stroke), or severity of neurological deficit. Oximetry abnormalities were associated with a history of snoring. Polysomnography on 19 patients confirmed oximetry evidence of severe SDB. Eighteen of 19 patients (95%) had an apnea-hypopnea index (AHI) of >10 events per hour of recording, 13 of 19 (68%) had an AHI >20, and 10 of 19 (53%) had an AHI >30. Desaturation events were largely due to obstructive apneas.

Conclusions
SDB accompanied by arterial oxyhemoglobin desaturation is common in patients undergoing rehabilitation after stroke and is associated with higher mortality at 1 year and lower BI scores at discharge and at 3 and 12 months after stroke. SDB may be an independent predictor of worse functional outcome. Obstructive sleep apnea appeared to be the most common form of SDB, and the frequent history of snoring suggests that SDB preceded the stroke in most patients.
Contribution of Arterial Blood Pressure to the Clinical Expression of Lacunar Infarction
Authors: Chamorro A. , Saiz A. , Vila N. , Ascaso C. , Blanc R. , Alday M. , Pujol J.
Published: June 2011

Background and Purpose
The relation between symptomatic lacunar infarction, silent stroke, and arterial hypertension is controversial.

Methods
From 500 patients with ischemic or hemorrhagic stroke admitted to the Downtown Barcelona Stroke Registry between July 1992 and December 1994, we evaluated prospectively the prevalence of silent infarction in 249 patients who had a brain MRI. The association of risk factors with silent infarction was investigated with the use of logistic regression analysis. In a selected group of 43 patients with symptomatic lacunes, we performed at stroke follow-up transcranial Doppler sonography and 24-hour continuous blood pressure monitoring to evaluate whether blood pressure, cerebrovascular tone, and cerebral blood flow at rest and after the administration of 1 g acetazolamide correlated with silent infarction.

Results
A total of 147 silent infarctions were observed in 83 patients (33%). Most silent infarctions corresponded to small deep lesions in the territory of the lenticulostriate arteries. Patients with silent infarctions had higher systolic and diastolic blood pressure at stroke onset. However, on multivariate analysis, age greater than 60 years was the only risk factor associated with silent infarction. In a subgroup of 43 patients with symptomatic lacunes and patent extracranial vessels, systolic and diastolic pressure at stroke onset and diastolic pressure and vascular resistance at stroke follow-up were higher when silent infarctions coexisted. However, cerebral blood flow at rest and after acetazolamide injection were unrelated to silent infarction.

Conclusions
Silent ischemia in patients with symptomatic lacunar and nonlacunar stroke was only associated with aging. However, a history of arterial hypertension was perhaps unrecognized, since hemodynamic testing and continuous blood pressure monitoring in patients with lacunar stroke suggested that the coexistence of silent lesions indicated a more generalized cerebral arteriolosclerosis.
Persisting Perfusion Defect in Transient Ischemic Attacks
Authors: Laloux Patrice , Jamart Jacques , Meurisse Hubert , De Coster Patrick , Laterre Christian
Published: June 2011

Background and Purpose
Cerebral infarction and prolonged regional hypoperfusion have been described in patients with transient ischemic attacks (TIAs). The aim of this study was to compare the sensitivity of single-photon emission CT (SPECT) with that of brain CT and to evaluate the clinical significance of differentiation of TIA patients with or without focal hypoperfusion.

Methods
From a hospital-based population, we studied the SPECT and CT findings in 76 consecutive patients, without a stroke history, who presented with TIA in the carotid artery territory. The recorded variables were the time of SPECT imaging (<36 or ≥36 hours), clinical presentation, history of previous TIA(s), duration of the presenting attack (<2 or ≥2 hours), vascular risk factors, and etiology. We used both visual and semiquantitative analyses for the SPECT evaluation. Acetazolamide challenge was not performed.

Results
The overall SPECT sensitivity was 36% (27/76). When brain CT and SPECT were performed in the same patients, the SPECT sensitivity was significantly higher than that of CT (19/59 [32%] versus 8/59 [14%];
P
=.007). The SPECT sensitivity was not dependent on the time of investigation, duration of attacks, history of TIA(s), or the clinical presentation. The vascular risk and etiologic factors were not significantly different between the patients with or without prolonged focal hypoperfusion. Logistic regression did not identify any variable to discriminate the two groups.

Conclusions
Despite its better sensitivity compared with CT, SPECT performed without the acetazolamide test provides no additional clinically useful information on the vascular risk factors and etiology in TIA patients.
Relation Between Hemostatic Variables and Increase of Common Carotid Intima-Media Thickness in Patients With Peripheral Arterial Disease
Authors: Cortellaro M. , Baldassarre D. , Cofrancesco E. , Tremoli E. , Colombo A. , Boschetti C. , Paoletti R.
Published: June 2011

Background and Purpose
Increases in common carotid intima-media thickness (CC-IMT), as measured by B-mode ultrasonography, have been widely used in both population studies and clinical trials in the search for risk factors for early atherosclerosis progression and have been found to correlate with age and with high concentrations of low-density lipoprotein cholesterol, leukocytes, and hemoglobin. We have now investigated the relation between several baseline hemostatic and conventional risk factors and CC-IMT changes over 16 months in 64 patients with peripheral arterial disease randomly selected from the prospective PLAT study series.

Methods
Samples from 24 patients (37.5%) who showed increases in CC-IMT during the follow-up period were compared with those from 40 (62.5%) in whom CC-IMT remained unchanged.

Results
Baseline conventional risk factors and coagulation variables were similar in the two groups except for higher plasma concentrations of von Willebrand factor (vWF) (178.3±53.6% versus 141.2±53.7%,
P
=.01) and factor VII (FVII) (133.9±36.4% versus 107.0±27.3%,
P
=.001) in the patients with increased CC-IMT. CC-IMT increase correlated positively with plasma levels of FVII (
r
=.31,
P
<.01) and vWF (
r
=.31,
P
<.01). Multiple stepwise regression analysis identified FVII as the only independent variable associated with an increase in CC-IMT (β=.83,
P
=.01).

Conclusions
High plasma concentration of FVII and vWF may be associated with the progression of early carotid atherosclerosis in patients with peripheral arterial disease.
Validation of Family History in Subarachnoid Hemorrhage
Authors: Bromberg J.E.C. , Rinkel G.J.E. , Algra A. , Greebe P. , Beldman T. , van Gijn J.
Published: June 2011

Background and Purpose
In 6% to 9% of patients with subarachnoid hemorrhage (SAH), familial aggregation occurs; truly familial cases carry a worse prognosis than sporadic cases and raise the question of screening. If relatives have died from SAH, the family history is often the only available clue to the diagnosis, but the sensitivity and predictive value of such a history for SAH are unknown.

Methods
We contacted a next of kin for a consecutive series of patients who had died in the hospital of subarachnoid hemorrhage (n=20), intracerebral hemorrhage (n=22), or ischemic stroke (n=23) between 3 and 5 years previously, and we compared the diagnosis based on the history from this next of kin with the medical diagnosis confirmed by a CT scan.

Results
The positive predictive value of the diagnosis of “probable SAH” from the history in our study sample was 0.7; when adjusted for incidence rates in the general population it was 0.6 (95% confidence interval, 0.3 to 0.8). The sensitivity of the diagnosis based on the history was 0.5 (95% confidence interval, 0.3 to 0.7); 10 of the 20 cases of SAH were not identified.

Conclusions
The family history of SAH, without confirmation from medical documents, is an insufficiently accurate tool to prove or disprove the diagnosis of familial SAH.
Risk Factors for Death From Stroke in Middle-aged Lithuanian Men
Authors: Rastenyte Daiva , Tuomilehto Jaakko , Domarkiene Stanislava , Cepaitis Zygimantas , Reklaitiene Regina
Published: June 2011

Background and Purpose
Although in eastern Europe, mortality from stroke at present is the highest in the world, no previous prospective study of the risk factors for stroke has been reported from this part of the world. The aim of our study, therefore, was to evaluate the relations between blood pressure, serum total cholesterol, glucose intolerance, body mass index, and cigarette smoking and the risk of death from stroke in middle-aged men in Kaunas, Lithuania.

Methods
We conducted a prospective study with an average follow-up of 17.5 years of 2295 men who had participated in risk factor surveys within the framework of the World Health Organization Kaunas-Rotterdam Intervention Study from 1972 to 1974. Risk factors included in the current analyses were smoking, blood pressure, serum total cholesterol, glucose intolerance, diabetes, and body mass index. Age- and risk factor–adjusted relative risks (RR) for death of stroke were determined by use of the Cox proportional hazards model.

Results
The strongest risk factors for death from stroke in middle-aged men were systolic blood pressure (RR=1.02;
P
=.0001), diabetes (RR=4.17;
P
=.02), and smoking (RR=2.01;
P
=.004). Serum cholesterol, impaired glucose tolerance, and body mass index were not related to the risk of death from stroke. Twenty-five percent and 19% of stroke deaths were attributed to hypertension and smoking, respectively.

Conclusions
Prevention and effective control of hypertension, smoking, and diabetes are the key elements in primary prevention of stroke in eastern Europe, where stroke mortality remains high.
Effect of Age and Sex on
N
-Methyl-
d
-Aspartate Antagonist-Induced Neuronal Necrosis in Rats
Authors: Auer Roland N.
Published: June 2011

Background and Purpose
Although
N
-methyl-
d
-aspartate (NMDA) antagonism may be a useful therapeutic approach in stroke treatment, it has been found that these pharmacological agents cause neuronal necrosis in restricted cortical regions of the rodent brain.

Methods
To test the hypothesis that age and sex influence NMDA antagonist-induced neuronal necrosis, male and female rats were studied at 2 months (young), 12 months (middle-aged), and 24 months (old) of age. A dose of 5 mg/kg MK-801 was administered, followed by quantitation of neuronal necrosis at nine coronal levels in the cingulate and retrosplenial cortex at 1 week of survival.

Results
Mortality was dependent on age but not sex and was higher in the old rats (
P
<.01). The number of necrotic neurons per hemisphere was greater in female than in male rats at all ages (
P
<.0001). Female rats also showed increasing neuronal necrosis with age (
P
<.05).

Conclusions
The results indicate a major sex difference in neuronal cytotoxicity caused by NMDA antagonists and a minor increase in susceptibility with increasing age in females. The findings may be relevant to development of drugs with NMDA antagonist properties for use in human stroke.
Recurrent Right Hemiplegia Associated With Progressive Ipsilateral Carotid Artery Stenosis
Authors: Chollet F. , Rolland Y. , Albucher J.F. , Manelfe C. , Marc-Vergnes J.P. , Guiraud-Chaumeil B.
Published: June 2011

Background
Ipsilateral sensory motor symptoms associated with carotid artery stenosis are rare, and few reports are available in the literature.

Case Description
We report the case of a 50-year-old man who presented with right hemiplegia that recurred 14 months later. A left hemisphere watershed infarction was detected. Repeated angiograms showed a left internal carotid occlusion and a right internal carotid stenosis that initially measured 50% and worsened to 80% after the second stroke.

Conclusions
Repeated quantitative measurements of cerebrovascular reserve demonstrated the hemodynamic mechanism of the strokes and the role of a right internal carotid lesion in causing the recurrence of right hemiplegia.
Clinical Relevance of Intracranial Microembolic Signals in Patients With Left Ventricular Assist Devices
Authors: Nabavi D.G. , Georgiadis D. , Mumme T. , Schmid C. , Mackay T.G. , Scheld H.H. , Ringelstein E.B.
Published: June 2011

Background and Purpose
The use of left ventricular assist devices has become an established method in bridging patients with end-stage cardiac failure to heart transplantation. Since thromboembolism is one of the major complications, we undertook this study to evaluate the clinical significance of Doppler microembolic signals (MES) in patients with left ventricular assist devices.

Methods
Six patients with left ventricular assist devices were monitored for MES with transcranial Doppler ultrasonography during the first 30 postoperative days. Additionally, repeated (10 per day and patient) and prolonged (3 hours per patient) monitorings were performed to assess the adequacy of the 30-minute recordings. Three observers evaluated 30 randomly assigned monitorings in a blinded fashion to assess the interobserver variability. The relation between MES counts and clinical, radiological, hemostaseological, and pump flow parameters and the predictive value of MES counts regarding the occurrence of embolic events was evaluated.

Results
Ten ischemic cerebrovascular accidents and 2 peripheral thromboembolic events occurred during the observation period of 177 days (total incidence, 6.8%). MES were found in 143 of 170 monitorings (84.1%). Their counts were significantly higher on days with clinically manifest embolic events as compared with event-free days (18.5 [3-74] versus 4 [0-52], respectively, median and 95% CI;
P
<.001, Mann-Whitney). The predictive value of MES counts above 7 per 30 minutes was high (75%). Significant differences in the incidence and counts of MES as well as in the incidence of clinically manifest embolic events were noted among the six patients (all
P
<.01) without equal differences in anticoagulant treatment or pump flow. Interobserver agreement was high (
P
=.78 to .89, unpaired Student’s
t
test). Considerable short- and long-term intrapatient variations of MES counts, without consistent pattern, were noted.

Conclusions
Serial monitoring for MES is prognostically superior to single monitorings in patients with left ventricular assist devices. In the future, this new application mode may individually guide anticoagulation strategies and even influence the decision regarding early cardiac transplantation versus long-term use of the assist devices.
Late Contralateral Hyperhidrosis in Lateral Medullary Infarcts
Authors: Rousseaux Marc , Hurtevent Jean François , Benaim Charles , Cassim Francois
Published: June 2011

Background and Purpose
This study describes unilateral increases of sweating reactions observed in the months after contralateral medullary infarct; evaluation of sympathetic cutaneous response may help to explain sweating disorders.

Summary of Report
After the discovery of the clinical phenomenon in one case, patients admitted between 1990 and 1993 were systematically evaluated clinically and electrophysiologically. In a group of five patients presenting with lateral or dorsal medullary lesions, two exhibited an increase of contralateral sweating reactions that appeared 6 to 8 months after stroke, were elicited by effort and exposure to heat and stress, and were more severe over the forehead, face, and upper trunk. In one case, this was clinically associated with an absence of sweating on the side of the lesion. During the late phase after stroke, in three patients presenting with lateral medullary lesions, electrophysiological evaluation revealed significant asymmetry of the sympathetic skin response, which was higher on the side contralateral to the lesion than on the ipsilateral side. In one patient, no response could be elicited by stimulations applied on the side of the lesion.

Conclusions
Contralateral hyperhidrosis can be observed in the late phase after lateral medullary infarct and is likely due to lesion of the sympathetic pathway passing through the lateral medulla, which inhibits sudomotor neurons. Evaluation of sympathetic skin response may help to explain such clinical disorders.
Familial Cerebral Aneurysms
Authors: Leblanc Richard
Published: June 2011

Background and Purpose
We evaluated the influence of gender on the formation and rupture of familial cerebral aneurysms.

Methods
We studied 30 patients with ruptured cerebral aneurysms from 14 consecutive families. These patients were compared with the patients with sporadic aneurysms reported by the first Cooperative Study.

Results
Eighty percent of familial aneurysms occurred in women versus 59% of sporadic aneurysms (
P
<.05, χ
2
test). This overrepresentation of women occurred at below the age of 50 years, where 78% of patients with familial aneurysms were women compared with 45% for sporadic aneurysms (
P
<.01, χ
2
test). Above this age, there was no statistical difference in incidence of familial aneurysms in men or women compared with sporadic aneurysms. In women with familial aneurysms, rupture occurred before the age of 50 years in 59%, compared with 31% for sporadic aneurysms (
P
<.01, χ
2
test). In four of five families, aneurysms ruptured within 10 years of each other in sisters (mean, 6 years). Multiple aneurysms were equal in both groups (17%), but multiple familial aneurysms occurred mainly in women. There was no difference in the site of single cerebral aneurysms in either group, but familial aneurysms in females occurred at the same site in five of eight families (62%) and in 11 of 17 mother-daughter or sister pairs (65%), compared with 20% for two randomly selected sporadic aneurysms (
P
<.01).

Conclusions
There is an overrepresentation of women with ruptured familial aneurysms compared with those with sporadic aneurysms. Familial aneurysms rupture in females predominantly before the age of 50, in the same decade, and at the same site within families in the majority of cases. These observations support a possible genetic cause for cerebral aneurysms and a possible hormonal contribution to their rupture.
Depiction of Infarct Frequency Distribution by Computer-Assisted Image Mapping in Rat Brains With Middle Cerebral Artery Occlusion
Authors: Zhao Weizhao , Ginsberg Myron D. , Prado Ricardo , Belayev Ludmila
Published: June 2011

Background and Purpose
Histopathologic analysis of experimental brain damage has traditionally been performed by measuring areas of infarction and/or selective neuronal alterations on a section-by-section basis in individual animals. For series containing multiple replicate animals, quantitation of tissue injury is typically performed at similar coronal levels throughout an experimental group. A means of facilitating pictorial group comparisons of these histopathologic alterations between different series of replicate studies is highly desirable.

Methods
We introduce a newly designed approach to achieve this goal, based on a linear affine transformation that is used to map corresponding sections at the same anatomic level into a common template to yield a frequency distribution map depicting the aggregate data set. We have applied this approach to compare the histopathologic features of two models of middle cerebral artery (MCA) occlusion in rats: (1) photothrombotically induced permanent distal MCA occlusion in spontaneously hypertensive rats (SHR) and (2) temporary MCA occlusion by intraluminal suture in Wistar rats.

Results
The brains of SHR rats with permanent distal MCA occlusion showed a high frequency of infarction involving the dorsolateral and lateral portions of the ipsilateral neocortex, whereas Wistar rats with 90-minute MCA suture occlusion showed a zone of infarction largely concentrated in the dorsolateral portion of the ipsilateral caudoputamen. Infarct frequency distributions for the two animal groups were compared statistically at three corresponding anatomic levels by Fisher’s exact test; the resulting statistical parametric maps are shown.

Conclusions
With the use of frequency distribution maps, the pattern of trends within a group can be observed coronally or three-dimensionally. One can directly access data as to numbers of rats with infarction for any point on the map. Studies performed under different experimental conditions can also be compared with one another by means of the generated data sets.
Immune Reactions Associated With Cerebral Amyloid Angiopathy
Authors: Yamada Masahito , Itoh Yoshinori , Shintaku Masayuki , Kawamura Junichiro , Jensson Ólafur , Thorsteinsson Leifur , Suematsu Naomi , Matsushita Masaaki , Otomo Eiichi
Published: June 2011

Background and Purpose
Cerebral amyloid angiopathy (CAA) occasionally coexists with cerebral vasculitis. An immune system may influence deposition or degradation of the amyloid in cerebral blood vessels. The purpose of this study was to elucidate immune reactions associated with CAA.

Methods
In 11 elderly patients with sporadic CAA, 2 patients with Icelandic familial CAA, and 2 patients with CAA and granulomatous angiitis, the cerebrovascular amyloid proteins and infiltrating inflammatory cells were analyzed immunohistochemically.

Results
In both sporadic CAA (β-protein amyloid angiopathy) and Icelandic familial CAA (cystatin C amyloid angiopathy), leptomeningeal and cortical vessels were associated with an increase or activation of monocyte/macrophage lineage cells. In the cases of CAA with granulomatous angiitis, the vascular amyloid was of β-protein and associated with infiltration of many monocyte/macrophage lineage cells, which included multinucleated giant cells containing the amyloid in the cytoplasm as well as T cells composed of CD4
+
and CD8
+
subsets. Amyloid P component, which was reported to be a common component of amyloid deposits and to prevent phagocytic proteolysis of amyloid fibrils of β-protein, was negative for the vascular amyloid in a case of CAA with granulomatous angiitis but positive in the others.

Conclusions
In both the β-protein and cystatin C amyloid angiopathies, cerebrovascular amyloid deposition was associated with an increase or activation of monocyte/macrophage lineage cells. Prominent reactions of monocyte/macrophage lineage cells admixed with CD4
+
and CD8
+
T cells (granulomatous angiitis) were occasionally associated with β-protein angiopathy. In some of these cases, the absence of amyloid P component might be related to pathogenesis of the granulomatous reaction.