bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.
Authors: Adams H P , Bendixen B H , Kappelle L J , Biller J , Love B B , Gordon D L , Marsh E E
Published: June 2011

The etiology of ischemic stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies. "Possible" and "probable" diagnoses can be made based on the physician's certainty of diagnosis. The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria. The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients, first based only on clinical features and then after reviewing the results of diagnostic tests.

The TOAST classification denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology. Using this rating system, interphysician agreement was very high. The two physicians disagreed in only one patient. They were both able to reach a specific etiologic diagnosis in 11 patients, whereas the cause of stroke was not determined in nine.

The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.
Lifestyle factors and risk of cerebrovascular disease in women. The Copenhagen City Heart Study.
Authors: Lindenstrøm E , Boysen G , Nyboe J
Published: June 2011

The purpose of the present analysis was to determine how lifestyle influences the risk of cerebrovascular disease in women participating in the Copenhagen City Heart Study.

A random sample of a white, lower and middle-class, urban population selected in 1976 was invited to two cardiovascular examinations at 5-year intervals. The present analysis was based on 7060 women invited to an initial examination from 1976 through 1978, aged 35 years or more, and without previous stroke or transient ischemic attack. At the initial examination, potential risk factors were recorded. The 265 first cases of stroke and transient ischemic attack were ascertained at a second examination 5 years later and through hospital records and death certificates through 1988. The Cox regression model was used to estimate the influence of the factors recorded on the risk of cerebrovascular disease.

The relative risks of cigarette smoking and lack of physical activity were 1.4 and 1.45; 95% confidence limits, 1.02 to 1.94 and 1.01 to 2.08, respectively). The relative risk of daily consumption of tranquilizers was 1.25 (95% confidence limits, 0.96 to 1.62). No significant influence was found for number of cigarettes, body mass index, or alcohol intake. In postmenopausal women, there was a statistically significant interaction (P < .041) between smoking and hormone replacement therapy. Smokers receiving this therapy had a 28% lower risk of cerebrovascular disease than smokers not receiving it.

The statistically significant and equally potent effects on the risk of cerebrovascular disease were found for cigarette smoking and lack of physical activity. The risk associated with smoking seemed to be influenced by hormonal replacement therapy.
Stroke in a Saudi Arabian National Guard community. Analysis of 500 consecutive cases from a population-based hospital.
Authors: al Rajeh S , Awada A , Niazi G , Larbi E
Published: June 2011

We sought to determine the crude incidence rate, patterns, and risk factors associated with different types of stroke in a defined Saudi population.

Records of 500 (342 male, 158 female) consecutive patients with first-ever stroke admitted from December 1982 to June 1992 in a hospital that exclusively serves the Saudi Arabian National Guard community were reviewed. Diagnosis was confirmed by brain computed tomography, and the most likely etiology was determined on the basis of relevant clinical, radiological, and laboratory data.

The mean age of the patients was 63 +/- 17 years. Males predominated in all types of stroke (P < .001). The crude annual incidence rate was 43.8 per 100,000. Ischemic strokes accounted for 76.2%, and these included 52% with large and 24.2% with lacunar infarctions. Intracerebral hemorrhage was detected in 21.4%, whereas subarachnoid hemorrhage was rare (2.4%). Hypertension (56%), diabetes mellitus (42%), and cardiopathy (33%) were common risk factors. Sixty-one patients (12%) died during the first month after their stroke.

The study suggests that stroke incidence is low in Saudi Arabia compared with industrialized countries, which could be because of the predominance of young age groups. The overall distribution of stroke types was closer to that of Western populations than to the Japanese, in whom hemorrhagic strokes are highly prevalent. However, the high combined frequencies of lacunar infarctions and intracerebral hemorrhages suggest that disease of the small cerebral arteries played a more important role in Saudis than in Western populations.
Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography.
Authors: Cabanes L , Mas J L , Cohen A , Amarenco P , Cabanes P A , Oubary P , Chedru F , Guérin F , Bousser M G , de Recondo J
Published: June 2011

An association between atrial septal aneurysm and embolic events has been suggested. Atrial septal aneurysm has been shown to be associated with patent foramen ovale and, in some reports, with mitral valve prolapse. These two latter cardiac disorders have been identified as potential risk factors for ischemic stroke. The aim of this prospective study was to assess the role of atrial septal aneurysm as an independent risk factor for stroke, especially for cryptogenic stroke.

We studied the prevalence of atrial septal aneurysm, patent foramen ovale, and mitral valve prolapse in 100 consecutive patients < 55 years of age with ischemic stroke who underwent extensive etiological investigations. We compared these results with those in a control group of 50 consecutive patients. The diagnosis of atrial septal aneurysm and patent foramen ovale relied on transesophageal echocardiography with a contrast study and that of mitral valve prolapse, on two-dimensional transthoracic echocardiography.

Stepwise logistic regression analysis showed that atrial septal aneurysm (odds ratio, 4.3; 95% confidence interval, 1.3 to 14.6; P = .01) and patent foramen ovale (odds ratio, 3.9; 95% confidence interval, 1.5 to 10; P = .003) but not mitral valve prolapse were significantly associated with the diagnosis of cryptogenic stroke. The stroke odds of a patient with both atrial septal aneurysm and patent foramen ovale were 33.3 times (95% confidence interval, 4.1 to 270) the stroke odds of a patient with neither of these cardiac disorders. For a patient with atrial septal aneurysm of > 10-mm excursion, the stroke odds were approximately 8 times the stroke odds of a patient with atrial septal aneurysm of < 10 mm.

This study shows that atrial septal aneurysm and patent foramen ovale are both significantly associated with cryptogenic stroke and that their association has a marked synergistic effect. Atrial septal aneurysms of > 10-mm excursion are associated with a higher risk of stroke.
Measuring quality of life in stroke.
Authors: de Haan R , Aaronson N , Limburg M , Hewer R L , van Crevel H
Published: June 2011

Little attention has been focused on quality of life in stroke outcome research. The purpose of this review is to outline the meaning of the concept, describe important methodological issues and methods of assessment, review existing quality of life measures, and discuss criteria for selecting an appropriate instrument.

The following 10 quality of life instruments were reviewed: COOP Charts; Euroqol; Frenchay Activities Index; Karnofsky Performance Status Scale; McMaster Health Index Questionnaire; Medical Outcomes Study 20-Item Short-Form Health Survey; Nottingham Health Profile; Quality of Life Index; Quality of Well-being Scale; and the Sickness Impact Profile. They were evaluated in terms of length, time needed to complete, content, scoring, and psychometric characteristics.

Emphasis should be placed on further psychometric evaluation of existing quality of life measures rather than on generating new instruments. There is particular need for supplementary data on the responsiveness of the instruments to changes in patients' clinical status over time. The choice of a suitable quality of life instrument should be based not only on psychometric properties but also on careful consideration of the research question, the relevance to the objectives of the study, the feasibility of the instrument, and the specific characteristics of the stroke patients under investigation.
Anterior ischemic optic neuropathy is not associated with carotid artery atherosclerosis.
Authors: Fry C L , Carter J E , Kanter M C , Tegeler C H , Tuley M R
Published: June 2011

The relation between anterior ischemic optic neuropathy and carotid artery atherosclerotic disease is unclear. We studied patients with anterior ischemic optic neuropathy to determine if they had an increased occurrence of carotid artery stenosis.

Fifteen consecutive patients with anterior ischemic optic neuropathy were evaluated prospectively for cervical carotid artery stenosis and compared with 30 age- and sex-matched asymptomatic patients and also with 11 age- and sex-matched patients experiencing transient monocular blindness.

There was no difference in the mean stenosis of the internal carotid artery between patients with anterior ischemic optic neuropathy (mean carotid stenosis, 19%) and asymptomatic patients (mean carotid stenosis, 9%; p > 0.05), whereas patients with transient monocular blindness had significantly more stenosis (mean, 77%) in the cervical carotid arteries than both control subjects (p < 0.0001) and patients with anterior ischemic optic neuropathy (p < 0.0001). There was also no difference in the percentage of patients with stenosis > or = 30% in anterior ischemic optic neuropathy (two of 15) and asymptomatic patients (five of 30), whereas 10 of 11 patients with transient monocular blindness had stenoses > or = 30%, significantly more than patients with anterior ischemic optic neuropathy (p < 0.0001) and asymptomatic patients (p < 0.0001).

Anterior ischemic optic neuropathy is not a marker for atherosclerotic carotid artery stenosis. The pathogenesis of nonarteritic anterior ischemic optic neuropathy does not involve carotid artery stenosis in most patients.
Two clinically distinct lacunar infarct entities? A hypothesis.
Authors: Boiten J , Lodder J , Kessels F
Published: June 2011

We investigated the hypothesis that patients with one or more asymptomatic lacunar infarcts and those with only one symptomatic lacunar infarct represent two clinically distinct lacunar infarct entities.

In a prospective series of 100 lacunar infarct patients, univariate and multivariate logistic regression analysis was performed on clinical features, vascular risk factors, and leukoaraiosis between patients with and without asymptomatic lacunar infarcts.

Patients with asymptomatic lacunar infarcts had hypertension significantly more often (71% versus 43%; [crude] odds ratio, 3.31; 95% confidence intervals, 1.16-9.43; p < 0.05) and had leukoaraiosis significantly more often (71% versus 19%; [crude] odds ratio, 10.67; 95% confidence intervals, 3.81-32.10; p < 0.001) than those with only a symptomatic lacunar infarct. After multivariate logistic regression analysis, only leukoaraiosis was significantly associated with the presence of asymptomatic lacunar infarcts. The asymptomatic lacunar infarcts differed in location, involved vascular territory, and volume from the symptomatic infarcts.

Two distinct lacunar infarct entities might be broadly distinguished during life: lacunar infarct patients with a single, symptomatic lacunar infarct, and patients with multiple lacunar infarcts and a high frequency of hypertension and leukoaraiosis, in which the underlying small-vessel vasculopathy might be different.
Carotid endarterectomy with transcranial Doppler and electroencephalographic monitoring. A prospective study in 130 operations.
Authors: Jansen C , Vriens E M , Eikelboom B C , Vermeulen F E , van Gijn J , Ackerstaff R G
Published: June 2011

We report the results of combined recording of hemodynamic and thromboembolic phenomena during carotid endarterectomy by means of computerized electroencephalography as well as transcranial Doppler ultrasonography. The study focuses on the additional value of transcranial Doppler to detect ischemia during surgery.

Combined monitoring was performed in 130 consecutive operations, using standard anesthesiological, surgical, and neurophysiological procedures.

A reduction of > or = 70% of blood flow velocities in the middle cerebral artery during cross-clamping was measured in 16 patients. In seven of these cases there were no severe electroencephalographic changes and a shunt was not used, but one of the patients developed a subcortical infarct with slight disability. In 55 patients, 75 episodes of embolization were detected by transcranial Doppler. In one of these, with massive embolization after release of the clamp, an intraoperative stroke occurred without changes on cranial computerized tomography or neurological disability on follow-up. In the other 54 patients, intraoperative embolization did not cause clinical or neuroradiological symptoms. Electroencephalographic changes occurred in only two of the 75 episodes. In addition to the two nondisabling strokes during surgery (1.5%), six strokes occurred within 5 days of operation, including one hemorrhage. There was no significant relation between contralateral carotid occlusion and stroke (p = 0.6).

During carotid endarterectomy, transcranial Doppler immediately provides information about thromboembolism and hemodynamic changes that are not detected by electroencephalography alone. Acoustic feedback from the transcranial Doppler monitoring unit has a direct influence on the surgical technique. Transcranial Doppler ultrasound may be a useful tool in the study and prevention of intraoperative stroke.
Increased release of tumor necrosis factor-alpha into the cerebrospinal fluid and peripheral circulation of aged rats.
Authors: Sirén A L , Liu Y , Feuerstein G , Hallenbeck J M
Published: June 2011

We earlier reported that risk factors for stroke prepare brain stem tissue for a modified Shwartzman reaction, including the development of ischemia and hemorrhage and the production of tumor necrosis factor-alpha, after a provocative dose of lipopolysaccharide. In the present study, we sought to determine whether blood and central nervous system cells of rats with the stroke risk factor of advanced age produce more proinflammatory and prothrombotic mediators than do those of young rats of the same strain.

Levels of tumor necrosis factor-alpha and platelet activating factor in the cerebrospinal fluid and tumor necrosis factor-alpha in the serum of 2-year-old and 16-week-old Sprague-Dawley rats were monitored before and after challenge with lipopolysaccharide.

No consistent tumor necrosis factor-alpha activity was found in the cerebrospinal fluid or blood of control animals. Intravenous administration of lipopolysaccharide (1.8 mg/kg) increased serum tumor necrosis factor-alpha levels but had no effect on tumor necrosis factor-alpha in the cerebrospinal fluid. Serum tumor necrosis factor-alpha increased much more in aged rats than in young rats. When lipopolysaccharide was injected intracerebroventricularly, tumor necrosis factor-alpha activity in cerebrospinal fluid increased significantly more in old rats than in young rats. Baseline levels of platelet activating factor in cerebrospinal fluid were significantly higher in old rats than in young rats, and the levels increased to a greater degree in aged rats on stimulation.

Rats with the stroke risk factor of advanced age respond to lipopolysaccharide with a more exuberant production of tumor necrosis factor-alpha and platelet activating factor than young rats of the same strain. These findings are consistent with our working hypothesis that perivascular cells are capable of exaggerated signaling of endothelium through cytokines such as tumor necrosis factor-alpha in animals with stroke risk factors. The effect of such signaling might be to prepare the endothelium of the local vascular segment for thrombosis or hemorrhage in accord with the local Shwartzman reaction paradigm.
Systemic giant cell arteritis and cerebellar infarction.
Authors: Mclean C A , Gonzales M F , Dowling J P
Published: June 2011

Systemic giant cell arteritis causing cerebellar infarction due to intracranial arteritis of the anterior inferior cerebellar artery has not been previously reported. We report this infrequent occurrence and discuss the differential diagnosis.

An 85-year-old woman was admitted with a 2-week history of episodic ataxia, unilateral headaches, and vomiting. She had a history of atrial fibrillation and breast carcinoma. Her mental state was initially normal, and there were right-sided cerebellar signs. An ejection systolic murmur was heard, and peripheral pulses were palpable. A postmortem examination revealed cerebellar infarction due to giant cell arteritis of the anterior inferior cerebellar artery and basilar arteries. Systemic giant cell arteritis was also present.

Giant cell arteritis is a systemic disorder that can infrequently involve intracranial vessels, including the basilar, vertebral, and anterior cerebellar arteries. Cerebellar infarction secondary to the arteritis may occur. The distribution and size of intracranial vessel involvement is distinct from isolated cranial angiitis.
Arterial oxygen content and age are determinants of middle cerebral artery blood flow velocity.
Authors: Macko R F , Ameriso S F , Akmal M , Paganini-Hill A , Mohler J G , Massry S G , Meiselman H J , Fisher M
Published: June 2011

Transcranial Doppler blood flow velocities are inversely related to age and hematocrit, but the relative importance of age, oxygenation, and hemorheological factors has not previously been examined. We evaluated the relative contributions of these factors to middle cerebral artery blood flow velocity in adults with chronic renal failure, a population subject to significant fluctuations in hematologic profile.

Twenty-six subjects were studied, with arterial shunt blood sampled at the time of transcranial Doppler before dialysis. Twenty subjects from the original cohort were studied twice to examine the effects of intraindividual changes in blood oxygenation and rheology on Doppler velocities.

Age (r = -.61, P < .001), high-shear viscosity (r = -.46, P < .02), and arterial oxygen content (r = -.44, P < .05) were all inversely related to middle cerebral artery blood flow velocity. Age was the strongest velocity predictor, accounting for 37% of variance by simple regression analysis. Intraindividual change in arterial oxygen content explained most (54%) of the middle cerebral artery blood flow velocity variation between studies (r = -.74, P < .001). Multiple regression analysis showed that inclusion of additional variables could not account for more velocity variation than change in arterial oxygen content alone.

In this population, age and arterial oxygen content were the most important determinants of interindividual middle cerebral artery blood flow velocity variance and intraindividual middle cerebral artery blood flow velocity variation, respectively.
Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality.
Authors: Broderick J P , Brott T G , Duldner J E , Tomsick T , Huster G
Published: June 2011

The aim of this study was to determine the 30-day mortality and morbidity of intracerebral hemorrhage in a large metropolitan population and to determine the most important predictors of 30-day outcome.

We reviewed the medical records and computed tomographic films for all cases of spontaneous intracerebral hemorrhage in Greater Cincinnati during 1988. Independent predictors of 30-day mortality were determined using univariate and multivariate statistical analyses.

The 30-day mortality for the 188 cases of intracerebral hemorrhage was 44%, with half of deaths occurring within the first 2 days of onset. Volume of intracerebral hemorrhage was the strongest predictor of 30-day mortality for all locations of intracerebral hemorrhage. Using three categories of parenchymal hemorrhage volume (0 to 29 cm3, 30 to 60 cm3, and 61 cm3 or more), calculated by a quick and easy-to-use ellipsoid method, and two categories of the Glasgow Coma Scale (9 or more and 8 or less), 30-day mortality was predicted correctly with a sensitivity of 96% and a specificity of 98%. Patients with a parenchymal hemorrhage volume of 60 cm3 or more on their initial computed tomogram and a Glasgow Coma Scale score of 8 or less had a predicted 30-day mortality of 91%. Patients with a volume of less than 30 cm3 and a Glasgow Coma Scale score of 9 or more had a predicted 30-day mortality of 19%. Only one of the 71 patients with a volume of parenchymal hemorrhage of 30 cm3 or more could function independently at 30 days.

Volume of intracerebral hemorrhage, in combination with the initial Glasgow Coma Scale score, is a powerful and easy-to-use predictor of 30-day mortality and morbidity in patients with spontaneous intracerebral hemorrhage.
Does low-dose acetylsalicylic acid prevent stroke after carotid surgery? A double-blind, placebo-controlled randomized trial.
Authors: Lindblad B , Persson N H , Takolander R , Bergqvist D
Published: June 2011

The aim of this randomized double-blind, placebo-controlled trial was to evaluate whether neurological deficits could be prevented with low-dose acetylsalicylic acid (ASA) as an adjunct to carotid endarterectomy.

A total of 232 patients were randomized to two groups, 75 mg/d ASA starting preoperatively and continued for 6 months (n = 117) or placebo (identical tablets) (n = 115). The patients were followed up regularly for 1 year.

The groups were well matched regarding laboratory data and indication for operation. The number of patients with intraoperative or postoperative stroke without complete recovery within 1 week were 0 and 2 at 30 days and 6 months, respectively, in the ASA group, compared with 7 and 11 in the placebo group (P = .01). Including all neurological events within 6 months, this was found in 15 patients in the ASA group compared with 24 in the placebo group (P = .12). Mortality was 0.8% and 3.4% at 30 days and 6 months, respectively, in the ASA group. In the placebo group, the corresponding figures were 4.3% and 6.0%, respectively (P = .12). The intraoperative bleeding did not differ between the groups nor did the number of reoperations due to bleeding or other complications related to pharmacology.

This study indicates that low-dose ASA (75 mg/d) reduces the number of postoperative strokes without complete recovery within 1 week. Overall neurological events are insignificantly reduced, as also mortality. The use of low-dose ASA (75 mg) seems safe and effective in reducing cerebrovascular events after carotid endarterectomy.
Hyperglycemia in the acute phase of stroke is not caused by stress.
Authors: van Kooten F , Hoogerbrugge N , Naarding P , Koudstaal P J
Published: June 2011

Hyperglycemia in the acute phase of stroke is associated with poor outcome. Whether hyperglycemia in nondiabetic stroke patients is caused by stress is controversial.

We studied glucose levels and glycosylated hemoglobin in 91 consecutive patients with acute stroke admitted within 24 hours after onset of symptoms. In 27 unselected patients we also measured catecholamines on days 1 and 3 after onset.

Hyperglycemia was found in 39 (43%) of the patients, 55% of whom either had diabetes mellitus or latent diabetes; the others had idiopathic hyperglycemia. Norepinephrine levels were associated with the severity of the stroke (P = .005) and with hypertension (P = .03) but not with glucose levels, irrespective of whether or not the patients had diabetes.

We conclude that hyperglycemia in the acute phase of stroke cannot be explained by increased stress.
The Frenchay Activities Index. Assessment of functional status in stroke patients.
Authors: Schuling J , de Haan R , Limburg M , Groenier K H
Published: June 2011

Assessment of functional status in stroke patients is of major importance in both clinical practice and outcome studies. The Frenchay Activities Index has been developed specifically for measuring disability and handicap in stroke patients. The purpose of the study was to evaluate the metric properties of this instrument and to obtain normal values in a group of unselected elderly subjects.

The Frenchay Activities Index was tested in a group of stroke patients and a group of unselected subjects aged 65 or older. The functional status of the stroke patients was measured 26 weeks after stroke. Their prestroke status was registered retrospectively. Reliability and validity of the instrument were assessed.

The mean scores in the prestroke, poststroke, and control group demonstrated differences in functional status. The reliability of unweighted scores (range of Cronbach's alpha-coefficients, 0.78 to 0.87) was sufficient. The construct validity was supported by meaningful correlations between the Frenchay Activities Index and scores on the Barthel Index and Sickness Impact Profile. Principal-components analysis indicated that the Frenchay Activities Index showed two traits: instrumental disability and some aspects of handicap. The reliability of the instrument could be improved by deleting two items and by creating two subscale scores: domestic and outdoors activities.

The Frenchay Activities Index is a useful stroke-specific instrument to assess functional status. Completion of the questionnaire is easy and takes only a few minutes. Currently, the instrument is suitable for use in patient care and cross-sectional, descriptive studies.
Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators.
Authors: Kistler J P , Singer D E , Millenson M M , Bauer K A , Gress D R , Barzegar S , Hughes R A , Sheehan M A , Maraventano S W , Oertel L B
Published: June 2011

The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization.

To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group).

The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1).

We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.
Estimation of arterial stiffness, compliance, and distensibility from M-mode ultrasound measurements of the common carotid artery.
Authors: Gamble G , Zorn J , Sanders G , MacMahon S , Sharpe N
Published: June 2011

Arterial stiffness may indicate early vascular changes that predispose to the development of major vascular disease. The repeatability of a variety of indices of arterial stiffness calculated from a standard carotid arterial M-mode ultrasound image was investigated.

Twenty-six asymptomatic normal subjects were imaged and had blood pressure recordings on each of two separate occasions at least 1 day apart. Using a computer-assisted method, the maximum and minimum internal diameter and average wall thickness of the right common carotid artery were measured over several cardiac cycles, and the following indices of arterial stiffness and distensibility (compliance) were derived: the pressure-strain elastic modulus (Ep), Young's modulus (E), cross-sectional compliance (CC), and the distensibility coefficient (DC).

The repeatability of these measures, expressed as coefficients of variation, was as follows: Ep, 18%; E, 24%; CC, 14%; and DC, 13%. In another group of 20 subjects, the coefficient of variation for repeat examination by different sonographers was Ep, 19%; E, 20%; CC, 14%; and DC, 17% and for the one sonographer using two ultrasound machines was Ep, 13%; E, 13%; CC, 11%; and DC, 13%. These values indicate a moderate level of repeatability. In a univariate analysis each of these indices was significantly related to increasing age (Ep = 1.0 + 12.9 x AGE, r = .80; E = 314.5 + 13.9 x AGE, r = .48; CC = 22.6-0.26 x AGE, r = -.63; DC = 64.0-0.65 x AGE, r = -.78) but not to wall thickness (all P > .47). Using multiple regression techniques to adjust for age, wall thickness is a significant predictor of distensibility (P = .017), cross-sectional compliance (P < .001), and the pressure-strain elastic modulus (P = .019). Because Young's modulus is calculated from wall thickness, it could not be included in the multivariate analysis.

We conclude that estimates of carotid artery distensibility and cross-sectional compliance derived from M-mode ultrasound recordings are moderately repeatable and may provide useful additional end points for trials of atherosclerotic progression.
The perfluorocarbon fluoromethyloadamantane offers cerebral protection in a model of isovolemic hemodilution in rabbits.
Authors: Sakas D E , Crowell R M , Kim K , Korosue K , Zervas N T
Published: June 2011

Perfluorocarbons (PFCs) are considered promising cerebral protection agents because they could combine the beneficial effects of decreased blood viscosity with enhanced oxygen-carrying capacity and oxygen tissue delivery, but trials of PFCs as hemodilutants have been very limited. We evaluated fluoromethyloadamantane (FMA), a new perfluorocarbon compound, as an isovolemic hemodilutant and compared it with low-molecular-weight dextran 40 (D40) and a control group.

Through a transorbital craniectomy, the internal carotid, anterior, and middle cerebral arteries were coagulated to create a cerebral infarction in anesthetized, mechanically ventilated rabbits. No other experimental procedure was performed in control animals. In the two other groups, hemodilution was commenced 30 minutes after the arterial occlusion with either D40 or FMA. Hemodynamic parameters and brain and systemic temperature were monitored throughout the experiments. All animals were killed 6 hours after the arterial occlusion.

Hemodynamic and metabolic parameters and blood oxygen content were not affected by the infusion of either FMA or D40. Brain and systemic temperature remained constant. The ratio of infarct volume to the hemispheric volume was 19.6 +/- 3.7% in the FMA group (n = 17), 19.9 +/- 4.6% in the D40 group (n = 16), and 40.3 +/- 5.7% in the control group (n = 17). The difference in infarct volume of both FMA and D40 animals compared with controls was statistically significant (P < .01) when tested with Student's t test. There was no significant difference between FMA and D40 groups.

These results suggest that FMA has cerebral protective properties and should be purified, optimized, and further tested experimentally to develop a stable, efficient, and safe oxygen carrier, potentially suitable for clinical trials.
Stroke prevention. An opportunity for efficient utilization of health care resources during the coming decade.
Authors: Gorelick P B
Published: June 2011

Stroke is unique among neurological diseases, since it has a high prevalence and burden of illness, high economic cost, and is preventable. Epidemiological approaches to stroke prevention include the "high-risk" and "mass" approaches. In this review we discuss these preventive strategies, target host and discretionary risk factors that are amenable to these measures, and discuss potential cost savings.

Projected numbers of strokes prevented for specific stroke risk factors were estimated by using the population-attributable risk estimation for hypertension, cigarette smoking, atrial fibrillation, and heavy alcohol consumption. The projected numbers of strokes that could be prevented were substantial and highest for hypertension and cigarette smoking. Projected yearly cost of stroke associated with these two treatable factors was also substantial.

The prevention of stroke can be accomplished by the high-risk or mass approach or a combination of these approaches. The high-risk approach prevents strokes but is also expensive. The mass approach may be more cost-effective, which could lead to substantial savings, but this needs to be investigated.
Blinded-reader comparison of magnetic resonance angiography and duplex ultrasonography for carotid artery bifurcation stenosis.
Authors: Mittl R L , Broderick M , Carpenter J P , Goldberg H I , Listerud J , Mishkin M M , Berkowitz H D , Atlas S W
Published: June 2011

We compared two-dimensional time-of-flight magnetic resonance angiography (MRA) and duplex ultrasonography with arteriography for the detection of 70% to 99% stenoses at the carotid artery bifurcation (ie, surgical disease according to findings of the North American Carotid Endarterectomy Trial).

Three blinded readers independently measured stenoses on MRA in 73 vessels from 38 patients. Duplex ultrasonography was available in 66 vessels from 35 of these patients, and blinded reading was performed by one reader. Comparison was made to arteriography.

Magnetic resonance angiography demonstrated a sensitivity of 92.4%, specificity of 74.5%, and negative predictive value of 95.8% for 70% to 99% stenoses. Interobserver agreement was high (kappa = 0.91). Absence of signal at stenoses with evidence of distal flow usually, but not always, corresponded to surgical disease. Duplex ultrasonography demonstrated a sensitivity of 81.0%, specificity of 82.2%, and negative predictive value of 90.2% for surgical disease. There was no significant difference between MRA and duplex ultrasonography for the sensitivity or specificity in detecting 70% to 99% stenoses (P > .1, exact form of the McNemar test). MRA had no false positives or false negatives for complete occlusions of the carotid artery, whereas duplex ultrasonography missed one occlusion and falsely called two patent vessels occluded. In seven cases, both MRA and duplex ultrasonography overestimated stenoses to miscategorize them as surgical disease.

Although the sensitivity and specificity of MRA and duplex ultrasonography are not significantly different for distinguishing surgical and nonsurgical degrees of stenosis at the carotid bifurcation, MRA has some advantages that may make it the screening test of choice. Concordant MRA and duplex ultrasonography for surgical disease does not necessarily obviate the need for catheter arteriography.
Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study.
Authors: D'Agostino R B , Wolf P A , Belanger A J , Kannel W B
Published: June 2011

We sought to modify existing sex-specific health risk appraisal functions (profile functions) for the prediction of first stroke that better assess the effects of the use of antihypertensive medication.

Health risk appraisal functions were previously developed from the Framingham Study cohort. These functions were Cox proportional hazards regression models relating age, systolic blood pressure, diabetes mellitus, cigarette smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy by electrocardiogram, and the use of antihypertensive medication to the occurrence of stroke. Closer examination of the data indicated that antihypertensive therapy effect is present only for systolic blood pressures between 110 and 200 mm Hg. Adjustments to the regressions to better fit the observed data were developed and tested for statistical significance and goodness-of-fit of the model residuals.

Modified functions more consistent with the data were developed, and, from these, tables to evaluate 10-year risk of first stroke were computed.

The stroke profile can be used for evaluation of the risk of stroke and suggestion of risk factor modification to reduce risk. The effect of antihypertensive therapy in the evaluation of stroke risk can now be better evaluated.
Lipoprotein(a) and ischemic cerebrovascular disease in young adults.
Authors: Nagayama M , Shinohara Y , Nagayama T
Published: June 2011

Serum lipoprotein(a) level is genetically determined and remains almost constant throughout life. Based on this property, we investigated the serum lipoprotein(a) levels of ischemic stroke patients in the chronic stage (mean period after stroke, 27 months) and its relation to the types of ischemic stroke.

We measured serum lipoprotein(a) levels in 101 patients with chronic ischemic stroke and 37 normal control subjects, taking the clinical profiles into consideration.

Lipoprotein(a) levels in patients with atherothrombotic stroke were 28.0 +/- 19.6 mg/dL (mean +/- SD), which were significantly (P < .01) higher than those in patients with lacunar stroke and in normal control subjects (16.4 +/- 13.5 and 11.7 +/- 10.5 mg/dL, respectively). The lipoprotein(a) levels in patients with atherothrombotic stroke were significantly higher in the subgroup who were a younger age at onset: onset before age 50 years, 35.3 +/- 20.5; onset at age 50 to 59, 35.4 +/- 21.7; onset at age 60 to 69, 17.0 +/- 12.8; and onset at age 70 or older, 16.3 +/- 6.8 mg/dL (P < .01 for onset before age 50 versus 60 to 69 years or 70 years or older; P < .01 for onset at 50 to 59 years versus 60 to 69 years or 70 years or older). Serum lipoprotein(a) was significantly increased (40.2 +/- 20.1 mg/dL) in young adults with atherothrombotic stroke (onset at younger than age 45 years) compared with that in patients older than 45 years (P < .01).

We conclude that lipoprotein(a) is a genetic, independent, and critical risk factor for ischemic stroke, especially in young adults.
A prospective study of plasma homocyst(e)ine and risk of ischemic stroke.
Authors: Verhoef P , Hennekens C H , Malinow M R , Kok F J , Willett W C , Stampfer M J
Published: June 2011

Several studies have reported elevated circulating homocyst(e)ine levels in subjects with cerebral atherosclerosis. We assessed prospectively whether high plasma levels of homocyst(e)ine affect risk of ischemic stroke and evaluated whether high blood pressure modifies any such effect.

The study sample was drawn from the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 US male physicians. A total of 14,916 subjects 40 to 84 years old with no prior history of stroke, transient ischemic attack, or myocardial infarction provided blood samples at baseline and were followed for 5 years, with 99.7% morbidity and 100% mortality follow-up. Using a nested case-control design, we assayed homocyst(e)ine in samples from 109 subjects who subsequently developed ischemic stroke and 427 control subjects.

The mean plasma concentration of homocyst(e)ine was slightly higher in subjects with stroke (11.1 +/- 4.0 [+/- SD] nmol/mL) than in control subjects (10.6 +/- 3.4 nmol/mL), but the difference was not statistically significant (P = .12). The crude odds ratio of ischemic stroke for subjects in the upper 20% (> 12.7 nmol/mL) compared with those in the bottom 80% of homocyst(e)ine levels was 1.4 (95% confidence interval, 0.8 to 2.2). The odds ratio was 1.2 (95% confidence interval, 0.7 to 2.0) after controlling for several risk factors and other potential confounders. In subgroup analyses, elevated homocyst(e)ine levels appeared to be more strongly predictive of ischemic stroke in normotensive subjects and in men 60 years or younger. Although not statistically significant, in these subgroups increases in risks of 100% and 70%, respectively, were observed for men in the upper 20% of homocyst(e)ine values.

In this study, the data were compatible with a small but nonsignificant association between elevated plasma homocyst(e)ine and risk of ischemic stroke. However, since the sample size is small and the confidence intervals are wide, either no association or a moderate increase in risk cannot be excluded, particularly in subgroups otherwise at low risk, eg, younger men and those with normal blood pressure.
Crossed cerebellar hypoperfusion indicates the degree of uncoupling between blood flow and metabolism in major cerebral arterial occlusion.
Authors: Yamauchi H , Fukuyama H , Kimura J , Ishikawa M , Kikuchi H
Published: June 2011

In patients who have major cerebral arterial occlusive disease with low perfusion, a decrease in cerebral metabolism may be reflected by a reduction in contralateral cerebellar blood flow (crossed cerebellar hypoperfusion). This study was done to investigate whether comparison of the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion could be used to estimate the degree of uncoupling of cerebral blood flow and metabolism on the basis of a single blood flow study.

We used positron emission tomography before and after reconstructive vascular surgery to evaluate regional blood flow and oxygen metabolism in the cerebral and cerebellar cortexes of 11 patients with major cerebral arterial occlusive disease.

Preoperatively these patients had cortical blood flow asymmetry in the middle cerebral artery territory. The degree of crossed cerebellar hypoperfusion had no relation to the extent of cerebral blood flow asymmetry but was significantly correlated with the extent of asymmetry in cerebral oxygen metabolism. The preoperative extent of asymmetry in the cerebral oxygen extraction fraction and the postoperative improvement of asymmetry in cerebral blood flow were correlated with the preoperative difference between the severity of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion.

The difference between the extent of cerebral blood flow asymmetry and crossed cerebellar hypoperfusion can be used to estimate the degree of uncoupling between blood flow and metabolism, which can in turn predict the postoperative improvement of cerebral blood flow asymmetry. We suggest that this approach may be a simple means of estimating the relative uncoupling between blood flow and metabolism from a single blood flow study in patients who have major cerebral arterial occlusive disease with low perfusion.
Stroke in patients with diabetes. The Copenhagen Stroke Study.
Authors: Jørgensen H , Nakayama H , Raaschou H O , Olsen T S
Published: June 2011

Although diabetes is a strong risk factor for stroke, it is still unsettled whether stroke is different in patients with and without diabetes. This is true for stroke type, stroke severity, the prognosis, and the relation between admission glucose levels and stroke severity/mortality.

This community-based study included 1135 acute stroke patients (233 [20%] had diabetes). All patients were evaluated until the end of rehabilitation by weekly assessment of neurological deficits (Scandinavian Stroke Scale) and functional disabilities (Barthel Index). A computed tomographic scan was performed in 83%.

The diabetic stroke patient was 3.2 years younger than the nondiabetic stroke patient (P < .001) and had hypertension more frequently (48% versus 30%, P < .0001). Intracerebral hemorrhages were six times less frequent in diabetic patients (P = .002). Initial stroke severity, lesion size, and site were comparable between the two groups. However, mortality was higher in diabetic patients (24% versus 17%, P = .03), and diabetes independently increased the relative death risk by 1.8 (95% confidence interval [CI], 1.04 to 3.19). Outcome was comparable in surviving patients with and without diabetes, but patients with diabetes recovered more slowly. Mortality increased with increasing glucose levels on admission in nondiabetic patients independent of stroke severity (odds ratio, 1.2 per 1 mmol/L; CI, 1.01 to 1.42; P = .04). This was not the case in diabetic patients.

Diabetes influences stroke in several aspects: in age, in subtype, in speed of recovery, and in mortality. Increased glucose levels on admission independently increase mortality from stroke in nondiabetic but not in diabetic patients. The effect of reducing high admission glucose levels in nondiabetic stroke patients should be examined in future trials.
Transcranial Doppler is valid for determination of the lower limit of cerebral blood flow autoregulation.
Authors: Larsen F S , Olsen K S , Hansen B A , Paulson O B , Knudsen G M
Published: June 2011

This study validates transcranial Doppler sonography (TCD) for determination of the lower limit of cerebral blood flow (CBF) autoregulation and establishes a relation between global CBF and mean flow velocity (Vmean) in the middle cerebral artery.

Relative changes in CBF and in Vmean were compared in 12 normal volunteers (2 women and 10 men; median age, 30 years [range, 21 to 61 years]). Catheters was placed in the left radial artery and in the bulb of the right internal jugular vein, respectively. Baseline CBF was measured by single-photon emission computed tomography scanning; concomitantly, blood samples were drawn for calculation of the cerebral arteriovenous oxygen difference. Then changes in mean arterial pressure (MAP) were induced, and relative changes in global CBF were calculated according to Fick's principle assuming a constant cerebral oxygen metabolism. MAP was increased 30 mm Hg by norepinephrine infusion and was decreased by lower body negative pressure. Vmean was measured in the right middle cerebral artery by a 2-MHz probe, and blood samples were drawn at intervals of 5 mm Hg.

MAP values between 122 (range, 110 to 140) and 48 (range, 34 to 75) mm Hg were measured. The lower limit of autoregulation (the blood pressure under which autoregulation is off) as determined by Vmean did not differ significantly from that determined by relative changes in global CBF: 91 (range, 41 to 108) and 79 (range, 53 to 113) mm Hg, respectively. A significant correlation between Vmean and relative changes in global CBF was demonstrated below the lower limit of autoregulation (R2 = .73, P < .001; CBF = -6.3 + 1.0.Vmean). Above the lower limit both values were stable.

TCD is valid for determination of the lower limit of CBF autoregulation, and changes in CBF may be reliably evaluated by TCD during changes in cerebral perfusion pressure in normal subjects.