bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcranial Doppler detection of vertebrobasilar vasospasm following subarachnoid hemorrhage.
Authors: Sloan M A , Burch C M , Wozniak M A , Rothman M I , Rigamonti D , Permutt T , Numaguchi Y
Published: June 2011

Transcranial Doppler sonography is of established value in the detection and monitoring of middle cerebral artery vasospasm. Little information exists on the utility of transcranial Doppler for detection of posterior circulation vasospasm.

Cerebral angiography and conventional hand-held transcranial Doppler sonography were compared to determine sensitivity and specificity of transcranial Doppler for detection of vertebral and basilar artery vasospasm.

Of 59 consecutive subarachnoid hemorrhage patients with transcranial Doppler angiogram correlations, 42 underwent posterior circulation angiography to evaluate 64 vertebral arteries and 42 basilar arteries during the period of risk for vasospasm and had technically adequate transcranial Doppler examinations within 24 hours of the angiogram. A mean flow velocity of 60 cm/s and above was indicative of both vertebral and basilar artery vasospasm. For the vertebral artery, there were 7 true-positive test results, 42 true-negatives, 6 false-positives (unknown cause in 3, increased collateral flow in 1, adjacent vessel vasospasm in 1, hyperperfusion in 1), and 9 false-negatives (anatomic in 7, operator error in 2). Sensitivity was 44% and specificity was 87.5%. For the basilar artery, there were 10 true-positives, 23 true-negatives, 6 false-positives (unknown cause in 4, hyperemia/hyperperfusion in 1, increased collateral flow in 1), and 3 false-negatives (operator error in 2, tortuous vessel course in 1). Sensitivity was 76.9% and specificity was 79.3%. When the diagnostic criterion was changed to > or = 80 cm/s (vertebral artery) and > or = 95 cm/s (basilar artery), all false-positive results were eliminated (specificity and positive predictive value, 100%).

Our data suggest that transcranial Doppler has good specificity for the detection of vertebral artery vasospasm and good sensitivity and specificity for the detection of basilar artery vasospasm. Transcranial Doppler is highly specific (100%) for vertebral and basilar artery vasospasm when flow velocities are > or = 80 and > or = 95 cm/s, respectively.
Prognostic value and reproducibility of measurements of carotid stenosis. A comparison of three methods on 1001 angiograms. European Carotid Surgery Trialists' Collaborative Group.
Authors: Rothwell P M , Gibson R J , Slattery J , Warlow C P
Published: June 2011

The use of three methods of measuring carotid stenosis, which produce different values on the same angiograms, has caused confusion and reduced the generalizability of the results of research. If the results of future studies are to be properly applied to clinical practice, and if noninvasive methods of imaging are to be properly validated against angiography, a single, standard method of measurement of stenosis on angiograms must be adopted. This standard method should be selected on the bases of its ability to predict risk of ipsilateral carotid distribution ischemic stroke and its reproducibility.

The method of measurement of carotid stenosis used in the European Carotid Surgery Trial (ECST), that used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and a method based on the measurement of the common carotid (CC) lumen diameter were studied. Their use in the prediction of ipsilateral carotid distribution ischemic stroke was assessed in 1001 consecutively selected patients randomly assigned to medical treatment in the ECST. Carotid stenosis was measured by two observers working independently, using all three methods, on the angiographic view that showed the most severe stenosis of the symptomatic carotid bifurcation. Interobserver agreement was determined, and 50 angiograms were remeasured to determine intraobserver agreement.

There was little difference in the ability of the three methods to predict ipsilateral carotid distribution ischemic stroke. The CC method was consistently the most reproducible of the three, particularly for stenosis in the clinically important range of 50% to 90%.

The CC method of measurement should be adopted as the standard method of measuring the degree of carotid stenosis on angiograms.
Further comments on the measurement of carotid stenosis from angiograms. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group.
Authors: Eliasziw M , Smith R F , Singh N , Holdsworth D W , Fox A J , Barnett H J
Published: June 2011

Three different methods for estimating the percentage of reduction in the diameter of the internal carotid artery (ie, stenosis) have been proposed in the literature. Further comparisons of the methods were carried out with the intent of recommending a current standard for determining the percentage of stenosis from angiograms.

Angiograms from 112 patients were obtained. For each angiogram, stenosis was estimated in the manner of the European Carotid Surgery Trial (ECST method), the North American Symptomatic Carotid Endarterectomy Trial (NASCET method), and by a method using the common carotid artery lumen diameter (CC method).

Although there is much discrepancy among the estimates of stenosis arising from the three different methods for any particular patient, it is possible to predict (on average) the percentage of stenosis from one method to another. The relationship between the NASCET and CC methods is linear, with a mean ratio of distal internal carotid artery to common carotid diameter of 0.62 (SD of 0.11). The variability in the diameter of the common carotid artery lumen stabilizes only beyond 2.5 common carotid diameter units (approximately 20 to 30 mm by conventional angiography) proximal to the bifurcation. Unexpectedly, the relationships between both the ECST and NASCET methods and ECST and CC methods were parabolic (P < .001). The reasons underlying these departures from linearity are uncertain.

The comparability of our results with those reported in the literature regarding the CC and NASCET methods provides further evidence of the reproducibility of methods measuring anatomic features that can be visualized on an angiogram. Disease of the internal carotid artery is one of the important causes of ischemic symptoms. Measuring the narrowest portion of the internal artery relative to the normal portion of the same artery, well beyond the bulb, is a logical method. Moreover, benefits of carotid endarterectomy for patients with 70% to 99% stenosis as determined by the NASCET method have been well established in a clinical trial. Converting from the NASCET method to the CC method, given that the CC method is neither superior nor easier to calculate, is not recommended.
Hypothalamic dopamine release and local cerebral blood flow during onset of heatstroke in rats.
Authors: Kao T Y , Chio C C , Lin M T
Published: June 2011

Brain dopamine has been implicated as a mediator of brain neuronal damage resulting from ischemic injury. Augmented interleukin-1 production and cerebral ischemia occurred during onset of heatstroke. This study has attempted to ascertain whether heatstroke resulting from hyperthermia causes an increase in hypothalamic dopamine release and to assess whether the administration of an interleukin-1 receptor antagonist (IL-1ra) can attenuate heat-stroke formation.

Both local cerebral blood flow and hypothalamic dopamine release during onset of heatstroke were assessed in saline-treated rats and in rats treated with an IL-1ra. Heat-stroke was induced by exposing the animals to a high ambient temperature. Hypothalamic dopamine release was determined by carbon fiber electrodes combined with in vivo differential pulse amperometry.

During onset of heatstroke, rats with heatstroke displayed higher values of colonic temperature, higher values of hypothalamic dopamine release, and lower values of blood flow in different brain regions compared with normothermic control rats. In another separate experiment in which IL-1ra (200 micrograms/kg IV) was injected 30 minutes before onset of heatstroke, both the augmented hypothalamic dopamine release and diminished cerebral blood flow during onset of heatstroke were significantly attenuated. In addition, the survival time (interval between onset of heatstroke and death) of the rats with heatstroke was prolonged by pretreatment with IL-1ra.

These results suggest that an increase in hypothalamic dopamine release and a decrease in local cerebral blood flow occur during onset of heatstroke. Pretreatment with IL-1ra attenuates the heatstroke formation resulting from cerebral ischemia by reducing hypothalamic dopamine release.
Carotid artery dissection with renal infarcts. Two cases.
Authors: Amarenco P , Seux-Levieil M L , Cohen A , Lévy C , Touboul P J , Bousser M G
Published: June 2011

Clinical features of carotid artery dissection include ipsilateral local signs, contralateral ischemic stroke, or both. We observed two patients in whom these features were associated with renal infarcts.

A 57-year-old woman had painful Horner's syndrome caused by a right internal carotid artery dissection. On days 3 and 4 she had acute abdominal pain, first on the right side and later on the left. The computed tomographic (CT) scan showed a left renal infarct. No aortic dissection or cardiac source of embolism was found. Transesophageal echocardiography showed a mild dystrophy of the ascending aorta and of the mitral valve. Cerebral angiography showed irregularities of the V3 segment of the left vertebral artery compatible with fibromuscular dysplasia. Erythrocyte sedimentation rate was 100 mm/h, and she complained of intense fatigue. She fully recovered within 3 months. A 53-year-old man had sudden severe abdominal pain followed by headache and difficulty in swallowing. He had 9th, 10th, 11th, and 12th cranial nerve involvement on both sides due to bilateral internal carotid artery dissections and pseudoaneurysms. CT scan showed a left renal infarct. Angiography showed extensive signs of fibromuscular dysplasia involving carotid, vertebral, renal, iliac, and mesenteric arteries as well as a dissection of the left renal artery. Erythrocyte sedimentation rate was 65 mm/h, and he complained of severe fatigue. His neurological signs returned to normal in 6 months.

Renal infarct due to renal artery dissection may occur together with cerebral artery dissection. Acute abdominal pain, increased erythrocyte sedimentation rate, and intense fatigue are the warning symptoms.
Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke.
Authors: Levy D E , Brott T G , Haley E C , Marler J R , Sheppard G L , Barsan W , Broderick J P
Published: June 2011

Several studies are currently evaluating tissue-type plasminogen activator (TPA) as a potential therapy in acute ischemic stroke. The possibility of inducing intracranial hematomas, however, introduces an important concern into ultimate evaluation of risk and benefit. This retrospective analysis sought to identify factors associated with intracranial hematoma formation in a pilot phase 1 study of TPA for stroke.

Ninety-four patients received TPA within 3 hours of the onset of an acute ischemic stroke. Five of these patients developed a symptomatic intracerebral hematoma: 3 of 74 (4%) among patients treated within 90 minutes of stroke onset and 2 of 20 (10%) among those treated at 91 to 180 minutes. Three of the 5 died within 2 weeks. The analysis investigated associations between clinical factors and intracerebral hematomas.

Factors significantly related to the development of an intracerebral hematoma were TPA dose and diastolic hypertension. Intracerebral hematomas developed in 4 (18%) of 22 patients given a TPA dose of at least 0.90 mg/kg versus only 1 hematoma in the remaining 72 patients (1%; P < .02, Fisher's exact test). Four (18%) of 22 patients who had initial diastolic blood pressures of at least 100 mm Hg suffered an intracerebral hematoma versus only 1 (1%) of 72 patients (P < .02) with lower initial diastolic pressures.

Since the study was not designed to test specific safety hypotheses, results must not be overinterpreted. Nonetheless, these data emphasize the need for caution in both patient and dose selection for further studies of thrombolytic agents in stroke.
Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project.
Authors: Burn J , Dennis M , Bamford J , Sandercock P , Wade D , Warlow C
Published: June 2011

There have been few community-based studies of long-term prognosis after acute stroke. This study aims to provide precise estimates of the absolute and relative risks of stroke recurrence in an unselected cohort of patients with a first-ever stroke.

Six hundred seventy-five patients were registered in a community-based stroke register (the Oxfordshire Community Stroke Project) and prospectively followed for up to 6.5 years. Their relative risk of recurrent stroke was calculated using age- and sex-specific incidence rates for first stroke in Oxfordshire.

One hundred eighty recurrent episodes of stroke were identified, of which 135 were first recurrences. Given survival, the actuarial risk of suffering a recurrence was 30% (95% confidence interval, 20% to 39%) by 5 years, about nine times the risk of stroke in the general population. The risk was highest early after the first stroke: 13% (95% confidence interval, 10% to 16%) by 1 year, 15 times the risk in the general population. After the first year the average annual risk was about 4%. The risk of stroke recurrence did not appear to be related to age or pathological type of stroke.

The absolute and relative risks of recurrent stroke are highest early after the first stroke but remain elevated for several years thereafter. Efforts at secondary prevention should be initiated as soon as possible and continued for several years to gain greatest benefit.
Effects of hemodialysis on cerebral circulation evaluated by transcranial Doppler ultrasonography.
Authors: Hata R , Matsumoto M , Handa N , Terakawa H , Sugitani Y , Kamada T
Published: June 2011

The effects of hemodialysis on the cerebral circulation of humans and the correlation between changes in blood flow velocity in the basal cerebral arteries and those of several physiological variables influenced by hemodialysis have been inadequately studied.

Blood flow velocities were obtained from the middle cerebral artery and the basilar artery by transcranial Doppler ultrasonography in 27 patients receiving chronic maintenance hemodialysis immediately before and after the procedure. Changes in body weight, hematocrit, blood pressure, and arterial blood gases were recorded simultaneously.

There was a significant reduction in mean flow velocity in the middle cerebral artery (P < .01) and the basilar artery (P < .01) after hemodialysis. We observed a significant negative correlation between the relative change in mean flow velocity and the loss of weight after hemodialysis, the amount of fluid removed, and the increase in hematocrit in the middle cerebral artery and the basilar artery.

Hemodialysis and the associated physiological changes can significantly affect the cerebral circulation. Blood flow velocities in the middle cerebral artery and the basilar artery decrease significantly with hemodialysis. The loss of body weight, the amount of fluid removed, and the change in hematocrit significantly correlate with the change in mean flow velocity. The transcranial Doppler method can effectively monitor rapid changes in the cerebral circulation during potentially harmful procedures.
Gamma irradiation inhibits neointimal hyperplasia in rats after arterial injury.
Authors: Shimotakahara S , Mayberg M R
Published: June 2011

Restenosis complicates a significant proportion of endovascular and open vascular procedures such as carotid endarterectomy. In contrast to the primary atheroma, restenosis is characterized by intimal hyperplasia of vascular smooth muscle cells. We hypothesized that gamma radiation would reduce restenosis by limiting intimal hyperplasia after arterial injury.

To demonstrate the effect of gamma radiation on smooth muscle hyperplasia in vivo, a standardized bilateral carotid balloon catheter arterial injury was produced in 37 rats. A single dose of 750, 1500, or 2250 cGy (1cGy = 1 rad) gamma radiation was delivered to the right carotid artery at either 1 or 2 days after injury; the shielded contralateral carotid artery served as matched control. At 21 days after injury, vessels were perfusion-fixed in situ, and cross-sectional area of neointima was determined from axial sections using image analysis.

Marked reductions in neointimal cross-sectional area were demonstrated in vessels subjected to 1500- and 2250-cGy radiation at both 1 and 2 days after injury. A less prominent effect was noted for 750 cGy, reaching statistical significance only at 2 days after injury. By two-way ANOVA, radiation dose (P = .0002), timing of radiation delivery (P = .003), and an interaction between timing and dose (P = .0278) were significantly associated with reduction in neointimal cross-sectional area. At 1500 cGy, delivery of radiation 1 day after injury inhibited neointimal hyperplasia more prominently than the same dose 2 days after injury; a dose-response relation was evident at 1 day.

Radiation may be an important adjunctive therapy for reducing the incidence of restenosis after angioplasty or endarterectomy.
Effect of carbon monoxide on rabbit cerebral arteries.
Authors: Brian J E , Heistad D D , Faraci F M
Published: June 2011

Carbon monoxide produces relaxation in some peripheral arteries. Recently it has been suggested that carbon monoxide may be generated in brain tissue. In the present study we examined the hypothesis that carbon monoxide directly relaxes cerebral blood vessels.

The aorta and basilar and middle cerebral arteries were removed from New Zealand White rabbits and mounted for tension recording in vitro. Canine basilar arteries were also studied. After precontraction, cumulative relaxation concentration-response curves to carbon monoxide, nitric oxide, sodium nitroprusside, acetylcholine (rabbit arteries), and ATP (dog basilar artery) were obtained. Maximum relaxation and the concentration of agonists that induced half-maximal relaxation (ED50) were determined.

Carbon monoxide (10(-6) to 3 x 10(-4) mol/L) did not affect tension in rabbit or dog cerebral arteries. In rabbit aorta, carbon monoxide induced 29 +/- 4% (mean +/- SEM) relaxation at the highest concentration used (3 x 10(-4) mol/L). In contrast, nitric oxide produced 80% to 100% relaxation of all arteries, with ED50 values ranging from 7.1 to 7.4 -log mol/L. Nitroprusside, acetylcholine, and ATP also produced 80% to 100% relaxation of the arteries.

Carbon monoxide does not appear to have significant effect on tone in cerebral arteries. In contrast, at high concentrations carbon monoxide produces concentration-dependent relaxation in rabbit aorta. Factors that account for this regional heterogeneity are not clear. Although neurons may produce both nitric oxide and carbon monoxide, our findings suggest that only nitric oxide has direct effects on cerebral vascular tone.
Rheumatic heart disease and Sneddon's syndrome.
Authors: Antoine J C , Michel D , Garnier P , Genin C
Published: June 2011

As the pathogenesis of Sneddon's syndrome is unknown, research for associated disease can facilitate our understanding.

Of nine patients with Sneddon's syndrome, three had rheumatic heart disease (mitral valve stenosis, regurgitation, or both) due to rheumatic fever or Sydenham's chorea. Transient anticardiolipin antibodies or positive skin lupus band test were present.

Sneddon's syndrome can have multiple causes. In some patients, rheumatic heart disease is a possible causal association.
Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167.
Authors: Chimowitz M I , Weiss D G , Cohen S L , Starling M R , Hobson R W
Published: June 2011

Patients with carotid stenosis have a high frequency of asymptomatic coronary artery disease (CAD). The purpose of this study of patients with asymptomatic carotid stenosis was to test the hypothesis that patients without a history of CAD have the same cardiac prognosis as patients with a history of CAD.

Men enrolled in the Department of Veterans Affairs study on the efficacy of carotid endarterectomy for asymptomatic carotid stenosis underwent a baseline cardiac evaluation (history, physical examination, and electrocardiogram) to document previous angina or myocardial infarction. Patients were randomized to medical therapy alone or medical therapy and carotid endarterectomy. Medical therapy consisted of aspirin 650 mg twice daily and treatment of risk factors. All episodes of angina, myocardial infarction, or sudden death during follow-up (average of 47.9 months) were recorded.

Of 444 men enrolled in the study, 200 (45%) had a history of CAD. During the study 86 (43%) of 200 patients with CAD and 81 (33%) of 244 patients without a history of CAD had cardiac ischemic events (P = .03). In patients without a history of CAD, the first cardiac event was myocardial infarction or sudden death in 45 patients (56%). Factors that were independently associated with cardiac events in patients without a history of CAD were diabetes (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.15 to 3.97), intracranial occlusive disease (OR, 2.13; 95% CI, 1.13 to 4.02), and peripheral vascular disease (OR, 2.04; 95% CI, 1.14 to 3.66). Forty-two percent of patients with two of these factors and 69% of patients with all three factors had cardiac events.

Men with carotid stenosis and no history of CAD have a lower rate of cardiac events than men with carotid stenosis who have a history of CAD. However, a subgroup of patients with carotid stenosis and no history of CAD who have coexistent intracranial occlusive disease, diabetes, or peripheral vascular disease have a risk of cardiac events similar to that of patients with a history of CAD.
Paradoxical embolism as a cause of ischemic stroke of uncertain etiology. A transcranial Doppler sonographic study.
Authors: Itoh T , Matsumoto M , Handa N , Maeda H , Hougaku H , Tsukamoto Y , Kondo H , Tanouchi J , Kamada T
Published: June 2011

This study was designed to test the hypothesis that paradoxical embolization would be a cause of embolic strokes and transient ischemic attacks in patients with stroke of uncertain etiology in all age groups.

Thirty patients who had stroke of uncertain etiology were studied. They were divided into the following three groups: 13 patients with sudden onset (group A), 11 patients with subacute onset (group B), and 6 asymptomatic stroke patients (group C). Eleven patients with stroke of obvious etiology (group D) and 11 normal healthy volunteers (group E) were also studied as controls. In all patients transcranial Doppler sonography and contrast echocardiography were recorded simultaneously after intravenous injection of the contrast medium. Findings of positive patient foramen ovale in contrast echocardiography or "chirp" sounds in transcranial Doppler sonography were defined as positive for paradoxical contrast embolization. Radioisotope phlebography of the lower extremities and pulmonary scintigraphy, using technetium-99 macroaggregated albumin, were performed in all 17 patients who had positive findings of paradoxical contrast embolization and in 12 patients whose findings were negative.

Positive findings of paradoxical contrast embolization were found in 17 subjects by transcranial Doppler sonography but in only 8 on contrast echocardiography. These positive findings were detected more frequently in group A (77%) than in groups B, D, and E (9%, 18%, and 9%, respectively) (P < .05). In group C, 4 of 6 patients (67%) had positive findings. There were positive findings on both phlebography and pulmonary scintigraphy only in 6 group A patients, with positive findings of paradoxical contrast embolization.

Transcranial Doppler sonography is a sensitive detector of right-to-left shunts. Paradoxical cerebral embolization might be frequent in patients with stroke of unknown etiology, especially when the stroke is of sudden onset.
Cerebral blood flow reserve assessment in symptomatic versus asymptomatic high-grade internal carotid artery stenosis.
Authors: Nighoghossian N , Trouillas P , Philippon B , Itti R , Adeleine P
Published: June 2011

Thromboembolic stroke is likely to occur in patients with a restricted cerebral blood flow reserve. Our aims were to determine (1) whether symptomatic patients had any significant hemodynamic restriction ipsilateral to carotid occlusive disease compared with patients whose carotid stenosis is asymptomatic and (2) whether patients with carotid occlusive disease have impaired cerebral perfusion reserve compared with control subjects.

We compared cerebral blood flow and collateral capacity using the 133Xe inhalation method and acetazolamide test in symptomatic (n = 10) and asymptomatic (n = 10) patients who had a high-grade internal carotid artery stenosis (range, 70% to 99%). Results were compared with those from 10 healthy control subjects.

Mean baseline cerebral blood flow was 40.29 +/- 1.38 mL/100 g per minute on the symptomatic side in symptomatic patients versus 45.20 +/- 2.53 mL/100 g per minute on the lesion side in asymptomatic patients (control subjects, 46.91 +/- 2.11 mL/100 g per minute in the right hemisphere versus 46.17 +/- 1.93 mL/100 g per minute in the left). There was no statistical difference between patients in symptomatic and asymptomatic groups versus control subjects (P > .10). Mean cerebral blood flow increase after acetazolamide was in the same range in symptomatic (52.89 +/- 2.54 mL/100 g per minute) and asymptomatic (56.22 +/- 3.35 mL/100 g per minute) patients (P > .10), and no difference was observed regarding control subjects (54.25 +/- 2.94 mL/100 g per minute; P > .10). Three asymptomatic and two symptomatic patients and three control subjects had no significant cerebral blood flow increase after acetazolamide.

An additional hemodynamic factor in thromboembolic ischemia related to severe unilateral carotid stenosis might be an unusual finding in patients without apparent hemodynamic induction of symptoms. The lack of significant variation in postacetazolamide cerebral blood flow in some patients and control subjects implies that this procedure may be inconsistent in assessing the cerebral perfusion reserve in the individual case.
Embolic stroke by compression maneuver during transcranial Doppler sonography.
Authors: Khaffaf N , Karnik R , Winkler W B , Valentin A , Slany J
Published: June 2011

Embolic complications during ultrasound examinations are a rare cause of neurological deficits. The present case documents the occurrence of embolism by a nonobstructive compression maneuver during transcranial Doppler examination, resulting in a minor stroke.

A 63-year-old man suffered from recurrent transient ischemic attacks. Duplex sonography showed a small echogenic plaque at the right carotid bifurcation. During transcranial Doppler studies with a reverberating compression maneuver of the right common carotid artery low in the neck, multiple emboli signals were detected, and the patient developed a left-sided hemiparesis with slurred speech. Funduscopy revealed cholesterol emboli in the inferior temporal arteriole of the right eye. These findings suggested embolization as the cause of the stroke.

Compression maneuvers should not be performed in patients with recent neurological symptoms, even in the case of only small lesions in the extracranial carotid territory.
Premature carotid atherosclerosis: does it occur in both familial hypercholesterolemia and homocystinuria? Ultrasound assessment of arterial intima-media thickness and blood flow velocity.
Authors: Rubba P , Mercuri M , Faccenda F , Iannuzzi A , Irace C , Strisciuglio P , Gnasso A , Tang R , Andria G , Bond M G
Published: June 2011

Homocystinuria due to cystathionine beta-synthase deficiency and familial hypercholesterolemia are inherited disorders of metabolism that are associated with premature development of cardiovascular disease. This study addresses the possibility that different patterns of carotid wall damage and cerebral blood flow hemodynamics are present in these two metabolic diseases.

Twelve patients with homocystinuria due to cystathionine beta-synthase deficiency (mean age, 24 years), 10 patients with homozygous familial hypercholesterolemia (mean age, 26 years), and 11 healthy control subjects (mean age, 26 years) underwent a vascular examination by noninvasive methods. B-mode ultrasound imaging was used to obtain measurements of intima-media thickness of common carotid, bifurcation, and internal carotid arteries as an index of atherosclerosis. Cerebral blood flow velocity was estimated from vascular examination of the middle cerebral artery by transcranial Doppler. Systolic, diastolic, and mean velocities were measured. Pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was also calculated.

Mean maximum intima-media thickness was 1.4 mm in patients with familial hypercholesterolemia, 0.6 mm in patients with homocystinuria, and 0.6 mm in control subjects. The difference between hypercholesterolemic and homocystinuric patients or control subjects was statistically significant (P < .001). Diastolic blood flow velocities were significantly reduced in the middle cerebral arteries of hypercholesterolemic patients compared with homocystinuric patients or control subjects (P < .05), whereas systolic or mean velocities did not differ. The pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was significantly higher in hypercholesterolemic patients compared with homocystinuric patients or healthy control subjects (P < .01). A direct relation was demonstrated between pulsatility index of the middle cerebral artery and mean maximum intima-media thickness of carotid arteries on the same side (P < .001).

Familial hypercholesterolemia is responsible for diffuse and focal thickening of carotid arteries and possibly also for hyperlipidemic endothelial dysfunction extending to small resistance arteries and leading to a disturbed cerebral blood flow. Patients with homocystinuria due to homozygosis for cystathionine beta-synthase deficiency seldom have plaques in their carotid arteries. They are similar to healthy control subjects with regard to both intima-media thickness and blood flow velocity in the middle cerebral artery. Therefore, it is unlikely that typical atherosclerotic lesions precede thrombotic events in homocystinuria. However, it is possible that arterial dilatations caused by medial damage lead to thrombosis in homocystinuric patients.
A multifactorial analysis of risk factors for recurrence of ischemic stroke.
Authors: Lai S M , Alter M , Friday G , Sobel E
Published: June 2011

Risk factors for stroke recurrence have usually been evaluated as single variables. This study is a multivariate analysis of five risk factors (hypertension, myocardial infarction, cardiac arrhythmia, diabetes mellitus, and transient ischemic attacks) for second stroke after an initial ischemic stroke.

Six hundred twenty-one patients with an acute ischemic stroke were followed prospectively first at 4 months after onset and then at approximately 6-month intervals until death, recurrence of stroke, or the end of the study. The five risk factors were measured at each visit. A Cox multifactorial regression analysis was conducted using the risk factor status at enrollment and adjusted for age and sex.

Follow-up averaged 24 months (range, 1 to 48 months). Men comprised 52% of the cohort and were slightly older; 97% of the cohort was white, and 57% had multiple risk factors. Hypertension occurred in 59%, cardiac arrhythmia in 47% (of which 16% had atrial fibrillation), diabetes mellitus in 30%, myocardial infarction in 25%, and transient ischemic attacks in 18%. Only history of hypertension and atrial fibrillation by electrocardiogram were associated with increased risk of second stroke independently and significantly (P = .01 and P = .04, respectively).

Among the five factors analyzed, control of hypertension and atrial fibrillation appear to offer the greatest chance of reducing risk of stroke recurrence after an ischemic stroke.
Are cerebral aneurysms atherosclerotic?
Authors: Adamson J , Humphries S E , Ostergaard J R , Voldby B , Richards P , Powell J T
Published: June 2011

The aim of our study was to investigate plasma and genetic risk factors for rupture of cerebral aneurysms.

In London, a case-control study was made of 56 consecutive patients admitted to a regional neurosurgical service for treatment of ruptured cerebral aneurysm and of 93 control subjects. A further 40 consecutive patients admitted in Arhus with ruptured cerebral aneurysm also were studied.

The British case-control study showed that smoking was associated with an increased risk of ruptured cerebral aneurysm (odds ratio, 9.1; 95% confidence interval [CI], 3.4 to 23.8; P < .001 for a history of > 10 pack years). After age and sex adjustment, factors associated with ruptured cerebral aneurysm included a cholesterol concentration in the highest tertile (> or = 6.3 mmol/L; odds ratio, 10.2; 95% CI, 3.9 to 26.7; P < .001), an apolipoprotein B concentration in the highest tertile (> or = 0.84 g/L; odds ratio, 6.4; 95% CI, 2.5 to 16.3; P < .001), and concentrations of HDL cholesterol in the lowest tertile (< 1.1 mmol/L; odds ratio, 3.6; 95% CI, 1.4 to 8.2; P < .01). History of hypertension was of less importance (odds ratio, 4.0; 95% CI, 1.41 to 11.7; P < .01). Smoking history (P < .001) and increased concentrations of cholesterol (P < .0001) were the most important independent risk factors associated with ruptured cerebral aneurysm on multivariate analysis. The histories of hypertension and smoking, together with apolipoprotein B levels, in the Danish patients were similar to those in the British patients. In the entire patient group, the frequencies of two polymorphic variations in the type III collagen gene and polymorphisms at the apolipoprotein B, apolipoprotein C-III, and haptoglobin gene loci were not different from control subjects or the normal population; allele frequencies in British and Danish patients were similar.

An atherosclerotic profile including increased total cholesterol concentration and a long smoking history may contribute to the rupture of cerebral aneurysms. This study provides no support for the hypothesis that inherited abnormalities of type III collagen are a common cause of cerebral aneurysms.
Non-insulin-dependent diabetes and its metabolic control are important predictors of stroke in elderly subjects.
Authors: Kuusisto J , Mykkänen L , Pyörälä K , Laakso M
Published: June 2011

Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for stroke in the middle-aged population, but few prospective population-based studies are available in the elderly. Moreover, the importance of metabolic control and the duration of diabetes in diabetic subjects has remained controversial. There are no previous studies on association of insulin with the risk of stroke. The present study examined whether NIDDM, its metabolic control and duration, and insulin level predict stroke.

We measured cardiovascular risk factors including glucose tolerance, plasma insulin, and glycosylated hemoglobin A1c in a Finnish cohort of 1298 subjects aged 65 to 74 years and investigated the impact of these risk factors on the incidence of both fatal and nonfatal stroke during 3.5 years of follow-up.

Of 1298 subjects participating in the baseline study, 1069 did not have diabetes and 229 had NIDDM. During the 3.5-year follow-up, 3.4% (n = 36) of nondiabetic subjects and 6.1% (n = 14) of NIDDM subjects had a nonfatal or fatal stroke. The incidence of stroke was significantly higher in diabetic women compared with nondiabetic women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.65 to 3.06). In contrast, the risk of stroke was not significantly higher in diabetic men than in nondiabetic men (OR, 1.36; 95% CI, 0.44 to 4.18). In multivariate logistic regression analyses including all study subjects, fasting and 2-hour glucose (P < .01 and P < .05, respectively), glycosylated hemoglobin A1c (P < .01), atrial fibrillation (P < .05), hypertension (P < .05), and previous stroke (P < .01) predicted stroke events. In diabetic subjects, fasting and 2-hour glucose (P < .01 and P < .05, respectively), glycosylated hemoglobin A1c (P < .05), the duration of diabetes (P < .05), and atrial fibrillation (P < .05) were the baseline variables predicting stroke events. Finally, fasting insulin (P < .05), hypertension (P < .05), and previous stroke (P < .01) were associated with stroke incidence in nondiabetic subjects.

Our 3.5-year follow-up study provides evidence that NIDDM, its metabolic control, and the duration of diabetes are important predictors of stroke in elderly subjects, particularly in women. Moreover, fasting insulin level appears to be a risk factor for stroke in elderly nondiabetic subjects.
Pharmacotherapy of aphasia. A critical review.
Authors: Small S L
Published: June 2011

Communication problems are a common sequela of cerebrovascular disease and other central nervous system disorders. Behavioral treatment of these disorders aims to harness uninjured parts of the brain to improve the communicative life of the individual. While pharmacotherapy has held promise for the treatment of aphasia for over 50 years, it has not fulfilled this promise. This article reviews both the promise and the disappointment of aphasia pharmacotherapy.

Diverse theories of the underlying neurological deficits in aphasia have led to different pharmacologic rationales for therapy. Animal studies have demonstrated decreased levels of brain catecholamines after cortical stroke and more rapid stroke recovery with therapy aimed at augmenting brain norepinephrine and dopamine. These studies have led to recent attempts to hasten or extend language and sensorimotor rehabilitation after human stroke by administration of catecholaminergic drugs. When used as an adjunct to behavioral therapy, such pharmacotherapy appears to have benefit.

While drug therapy is unlikely to revolutionize the treatment of aphasia, it nonetheless holds promise as an adjunct to behavioral speech and language therapy to decrease performance variability and consequently to improve mean performance in patients with mild to moderate language dysfunction. Additional studies with carefully designed methods are necessary to assess the full potential of aphasia pharmacotherapy.
Elevation of transforming growth factor-beta 1 level in cerebrospinal fluid of patients with communicating hydrocephalus after subarachnoid hemorrhage.
Authors: Kitazawa K , Tada T
Published: June 2011

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional polypeptide that controls the production of extracellular matrix protein. Platelets store a large quantity of TGF-beta 1, which is released at hemorrhage. We recently reported that human recombinant TGF-beta 1 induced communicating hydrocephalus in mice. The aim of this study was to determine whether TGF-beta 1 is related to the development of communicating hydrocephalus after subarachnoid hemorrhage (SAH).

TGF-beta 1 in the cerebrospinal fluid of 24 patients with SAH was measured with enzyme-linked immunosorbent assay. The levels were compared between hydrocephalic and nonhydrocephalic groups. Western blot analysis was performed to determine active TGF-beta 1 in the cerebrospinal fluid.

TGF-beta 1 rapidly decreased from the onset of SAH. The level of TGF-beta 1 of 13 patients showing ventricular dilatation with periventricular low density on computed tomographic scan was 1.07 +/- 0.37 ng/mL on days 12 through 14, which was significantly higher than 0.52 +/- 0.21 ng/mL in patients without ventricular dilatation (P < .02). Furthermore, the TGF-beta 1 level of patients who had undergone ventriculoperitoneal shunt (n = 11) was 1.11 +/- 0.09 ng/mL on days 12 through 14, which was also higher than the level of the nonshunt group (n = 13) (0.56 +/- 0.22 ng/mL; P < .01). A 25-kD band was demonstrated by Western blot analysis in the cerebrospinal fluid of a patient with SAH.

Our results strongly suggest that TGF-beta 1 plays an important role in generating communicating hydrocephalus after SAH.
Diabetic chronic hyperglycemia and cerebral pH recovery following global ischemia in dogs.
Authors: Sieber F E , Koehler R C , Brown P R , Eleff S M , Traystman R J
Published: June 2011

We determined the effect of chronic hyperglycemia associated with diabetes on recovery of cerebral pH after global incomplete cerebral ischemia.

31P magnetic resonance spectra and cerebral blood flow (radiolabeled microspheres) were measured in three groups of dogs: (1) chronic hyperglycemic diabetes (pancreatectomy followed by blood glucose > 10 mmol/L for 3 months; n = 8); (2) acute hyperglycemia during ischemia and reperfusion in nondiabetic dogs (n = 8); and (3) normoglycemic controls (n = 8). Incomplete ischemia was produced for 20 minutes by ventricular fluid infusion followed by 3 hours of reperfusion.

Cerebral blood flow was reduced to approximately 5 mL/min per 100 g in all groups during ischemia with individual values ranging from 1 to 11 mL/min per 100 g. Blood flow returned to preischemic values by 30 minutes of reperfusion in the normoglycemia group but remained elevated during reperfusion in the acute hyperglycemia and diabetes groups. Cerebral pH at the end of ischemia was lower in acute hyperglycemia (5.94 +/- 0.05; +/- SE) and diabetes (5.97 +/- 0.08) groups than in the normoglycemia group (6.27 +/- 0.02). However, recovery of pH through 90 minutes of reperfusion in the normoglycemia (7.08 +/- 0.05) and diabetes (7.00 +/- 0.04) groups was significantly greater than in the acute hyperglycemia group (6.74 +/- 0.11). Persistent acidosis in the acute hyperglycemia group was associated with a delayed reduction of cerebral oxygen consumption and high-energy phosphates and with greater cortical water content and impairment of somatosensory evoked potentials compared with the diabetes group.

This study shows that cerebral pH recovery after global incomplete ischemia is improved in chronic hyperglycemia compared with acute hyperglycemia, despite similar decreases in blood flow and pH during ischemia and similar levels of blood flow and glucose levels during ischemia and reperfusion. In addition, cerebral pH recovery in chronic hyperglycemic dogs was not different from that in normoglycemic controls. These results suggest that an adaptation occurs with chronic hyperglycemia that improves recovery of cerebral pH during reperfusion and that is associated with better maintenance of energy metabolism and evoked potentials and with less edema over 3 hours of reperfusion compared with acute hyperglycemia.
Increased expression of ICAM-1 during reoxygenation in brain endothelial cells.
Authors: Hess D C , Zhao W , Carroll J , McEachin M , Buchanan K
Published: June 2011

Thrombolysis is a promising therapy for acute ischemic stroke. However, there is evidence that neutrophils may physically plug cerebral microvessels on reperfusion, preventing the full benefit of thrombolysis. We undertook this study to determine whether there was increased endothelial expression of the intercellular adhesion molecule-1 (ICAM-1) gene during hypoxia-reoxygenation.

We isolated and cultured human brain microvascular endothelial cells and subjected them to hypoxia (PO2 < 10 mm Hg) in an anaerobic chamber followed by variable periods of reoxygenation.

Twenty-hour periods of hypoxia did not lead to endothelial cytotoxicity as measured by a chromium-release assay. By Northern blot analysis, ICAM-1 mRNA transcripts were dramatically increased at 4 hours of reoxygenation but fell toward baseline (normoxia) by 12 and 24 hours. Hypoxia alone did not lead to an increase in mRNA levels. Western blot analysis showed an increased expression of ICAM-1 at 4, 12, and 24 hours of reoxygenation. The 4-hour increase in mRNA levels was not attenuated by pretreatment with 100 mumol/L allopurinol but was reduced by 30% with the addition of 20 mmol/L N-acetyl-L-cysteine at the time of reoxygenation and completely prevented by pretreatment with N-acetyl-L-cysteine.

Hypoxia-reoxygenation leads to an increase in ICAM mRNA levels that peaks at 4 hours in human brain microvascular endothelial cells. Pretreatment with N-acetyl-L-cysteine can completely block the increase in ICAM-1 mRNA levels.
Common carotid intima-media thickness measurement. A method to improve accuracy and precision.
Authors: Baldassarre D , Werba J P , Tremoli E , Poli A , Pazzucconi F , Sirtori C R
Published: June 2011

High-resolution ultrasonographic imaging is a noninvasive method that allows estimation of the thickness of the intima-media complex in human carotid arteries. The determination of intima-media thickness involves several steps, each of which may introduce an error that influences the reproducibility of the method. In the present study, apart from the general reproducibility of the determination of intima-media thickness, the error introduced by each step was evaluated.

B-mode scans were performed on 14 randomly selected patients. The common carotid arteries were examined in anterior, lateral, and posterior planes, with a standard methodology and by a new method, making use of external reference points.

The error in general reproducibility in determination of the subject's mean intima-media thickness was 5.9%. This parameter was also evaluated in a paired manner after dividing the whole artery into sectors; with this protocol, the percent error in general reproducibility was 15%. The main source of variability in the evaluation of common carotid intima-media thickness was found to lie in the operator's subjectivity in the choice of the carotid sector to be processed (percent error, 10.27%). A method was therefore designed that used external reference points, resulting in reduction of this error by 38.2%.

While the mean intima-media thickness might be considered a reproducible parameter to evaluate differences between populations exposed to diverse risk factors, evolutional or therapy-induced changes in the individual may be better monitored on defined carotid sectors. This may be achieved with a high reproducibility by use of the proposed method based on external reference points.
Alcohol consumption and carotid atherosclerosis: evidence of dose-dependent atherogenic and antiatherogenic effects. Results from the Bruneck Study.
Authors: Kiechl S , Willeit J , Egger G , Oberhollenzer M , Aichner F
Published: June 2011

Although a variety of epidemiological studies have suggested a U-shaped association between alcohol and cardiovascular disease, controversy still surrounds the role of atherogenesis in the mediation of alcohol effects.

Carotid atherosclerosis was measured with a sensitive and reproducible B-mode score in a random sample of 460 men drawn from the Bruneck Study (baseline examination in 1990).

The age-adjusted relation between alcohol and carotid artery disease was U shaped, with light drinkers facing a lower atherosclerosis risk (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.85; P = .01) than either abstainers (odds ratio, 1.00) or heavy drinkers (odds ratio, 2.78; 95% confidence interval, 1.32 to 5.84; P < .01). The association was not explained by the lifestyle of alcohol consumers (smoking) or inclusion of former (heavy) drinkers in the reference group. The effect of alcohol was modified by drinking behavior (type of beverage). Approximately a quarter of the atherosclerosis risk caused by severe alcohol consumption was mediated by the risk profile associated with drinking, whereas the apparent beneficial effect of low alcohol intake emerged independent of conventional risk attributes.

Our results support the hypothesis that adverse and beneficial effects of alcohol on cerebrovascular disease are mediated in part by analogous atherogenic and antiatherogenic properties.