bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Cerebral vasodilation during hypercapnia. Role of glibenclamide-sensitive potassium channels and nitric oxide.
Authors: Faraci F M , Breese K R , Heistad D D 
Published: June 2011

The purpose of these experiments was to examine mechanisms by which hypercapnia produces vasodilatation in brain. We examined the hypothesis that dilatation of cerebral arterioles during hypercapnia is dependent on activation of ATP-sensitive potassium channels and formation of nitric oxide.
Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Changes in diameter of arterioles were measured in response to topical application of acetylcholine and sodium nitroprusside and during two levels of systemic hypercapnia.
Increasing arterial PCO2 from 32 +/- 1 mm Hg (mean +/- SE) to 54 +/- 1 and 66 +/- 1 mm Hg dilated cerebral arterioles by 25 +/- 3% and 38 +/- 5%, respectively, from a control diameter of 93 +/- 3 microns. The response to the low level of hypercapnia was attenuated (25 +/- 3% versus 16 +/- 4%, P < .05) by glibenclamide (1 mumol/L), an inhibitor of ATP-sensitive potassium channels. Vasodilatation in response to the high level of hypercapnia was not affected by glibenclamide. Increases in arteriolar diameter in response to sodium nitroprusside were not inhibited by glibenclamide. NG-nitro-L-arginine (300 mumol/L), an inhibitor of nitric oxide synthase, completely inhibited dilatation of cerebral arterioles in response to the low level of hypercapnia and inhibited vasodilatation during the high level of hypercapnia by 66%.
Thus, activation of glibenclamide-sensitive potassium channels may contribute to dilatation of cerebral arterioles during hypercapnia. Cerebral vasodilatation during hypercapnia is dependent in large part on production of nitric oxide.
Primary medullary hemorrhage. Report of four cases and review of the literature.
Authors: Barinagarrementeria F , Cantú C 
Published: June 2011

Primary medullary hemorrhage is uncommon. Its clinical profile and prognosis are not well known. We report four cases of medullary hemorrhage and a review of the English and French literature since 1964 to analyze the clinical presentation and prognosis.
Of sixteen case reports of medullary hemorrhage reviewed from the literature, sixteen contained sufficient information for review and are included in this report. The age distribution of the patients was between 13 and 72 years, and 10 of these patients were men. The most frequent symptoms at onset were vertigo, sensory symptoms, and dysphagia. Presenting signs included palatal weakness, nystagmus, hypoglossal palsy, cerebellar ataxia, and limb weakness. The diagnosis was made at autopsy in 3 patients, at surgery in 3, by computed tomography in 4, and more recently by magnetic resonance imaging in 6. In nine instances the etiology of hemorrhage was undetermined; a ruptured vascular malformation was the cause in 3 patients, 1 was attributed to the use of anticoagulants, and hypertension was the suspected cause in the other 3 patients. Mortality rate was 19%; however, survivors generally had nonincapacitating sequelaes.
These findings indicate that primary medullary hemorrhage presents with a characteristic syndrome of sudden onset of headache and vertigo with neurological signs that correspond to various combinations of medial and lateral medullary involvement. In those patients who survive, prognosis usually is good.
Effects of total hemoglobin and hemoglobin S concentration on cerebral blood flow during transfusion therapy to prevent stroke in sickle cell disease.
Authors: Hurlet-Jensen A M , Prohovnik I , Pavlakis S G , Piomelli S 
Published: June 2011

The standard treatment of stroke in sickle cell disease is chronic transfusion to maintain the fraction of abnormal hemoglobin (hemoglobin S [HbS]) below 20%. Risks associated with such transfusion can be reduced by allowing higher HbS levels, but the physiological consequences of this modification are unknown. Cerebral blood flow is elevated in sickle cell disease proportionate to the degree of anemia and is reduced by transfusion. We tested the effects of various HbS levels on cerebral blood flow during the course of transfusion therapy.
We monitored cerebral blood flow (by the 133Xe inhalation method) in three patients whose chronic transfusion program was changed from a traditional regimen (HbS < 20%) to a moderate one, allowing HbS to rise to 45% to 50% between treatments. As expected, cerebral blood flow was higher with lower hemoglobin and higher HbS concentration. However, the HbS fraction appeared to exert a separate influence on the hyperemia, independent of total hemoglobin concentration. Furthermore, cerebral blood flow was higher during the modified regimen, despite equivalent anemia.
These results suggest caution in adapting the modified transfusion regimen. Although HbS concentrations of 50% did not cause any frank neurological sequelae, the possible consequences of the associated hyperemia over time are unknown. We conclude that larger clinical and physiological studies of moderate transfusion regimens (allowing higher concentration of HbS) are necessary before it can become standard therapy.
Patient preferences for stroke outcomes.
Authors: Solomon N A , Glick H A , Russo C J , Lee J , Schulman K A 
Published: June 2011

In clinical trials stroke is reported as a major morbid outcome, but the impact of stroke on patients is not directly assessed. This study examines patient preferences for different outcomes of stroke, including death.
We presented patients with written case scenarios of stroke outcomes. The scenarios represented four categories of stroke severity (mild, moderate, severe, and fatal), and for nonfatal strokes the scenarios described motor, language, and cognitive deficits. Patients reported values for each of the 10 stroke scenarios using a rank-and-scale method over a 100-point range, with 100 representing perfect health and 0 corresponding to the worst possible health state.
One hundred seventeen of 209 consecutive patients at risk for stroke participated in this study. Severe strokes were uniformly rated as having low preference weights (mean +/- SD [median]: 3 +/- 4 [1] for disabling hemiplegia, 8 +/- 9 [5] for confusion, and 15 +/- 14 [10] for global aphasia), and severe motor impairment (a disabling hemiplegia) was rated as significantly worse than death. Even mild deficits resulted in substantial loss to patients (54 +/- 21 [55] for dysarthria and 53 +/- 21 [50] for mild anomia).
Strokes may result in a wide variety of post-stroke consequences for patients. Severe strokes may be viewed by patients as tantamount to or worse than death. Even mild strokes may cause significant declines in patient preferences for health states. These data are useful in interpreting studies that report stroke and death, in designing new studies that measure stroke in at-risk populations, and in helping patients reach treatment decisions about therapies designed to prevent strokes.
Cerebral autoregulation in orthostatic hypotension. A transcranial Doppler study.
Authors: Lagi A , Bacalli S , Cencetti S , Paggetti C , Colzi L 
Published: June 2011

Transcranial Doppler measurements of blood flow velocity permit an assessment of variations in intracranial hemodynamics in response to acute arterial pressure variations. The purpose of this study was to scan healthy volunteers and patients with autonomic failure for differences in cerebral hemodynamic patterns under an acute hypotensive stimulus.
We used transcranial Doppler monitoring of blood flow velocity in the middle cerebral artery and noninvasive monitoring of arterial blood pressure and heart rate before, during, and after acute arterial hypotension induced by reactive hyperemia of the lower limbs.
After maximum hypotension, the mean blood flow velocity was higher in the healthy volunteers than in the patients. In the healthy subjects mean velocity rose significantly (P < .01) higher than arterial blood pressure after 30 seconds and 60 seconds; in the patients mean velocity and arterial pressure moved in parallel fashion. The diastolic blood flow velocity increased more in the control group than in the patients during the early stages of the test; furthermore, only in the healthy volunteers did it increase significantly more than arterial pressure after 30 seconds and 60 seconds. Regarding the pulsatility index, the differences between the two groups were similar to the diastolic velocity results.
(1) Monitoring of mean blood flow velocity showed the ability to maintain an adequate cerebral blood flow in healthy subjects; this mechanism was not efficient in the patients with autonomic failure. (2) Diastolic velocity and pulsatility index values clearly showed that only in healthy subjects were cerebral hemodynamics relatively independent of pressure values.
The layered fabric of cerebral artery fenestrations.
Authors: Finlay H M , Canham P B 
Published: June 2011

Intravascular bridges, resulting from developmental anomalies of brain arteries, are now better known as arterial fenestrations. Their tendency to develop aneurysms, similar to arterial bifurcations, makes their anatomy and microstructure important for study.
Six segments of artery, each including a fenestration (five from the vertebrobasilar junction and one from the middle cerebral artery), were pressure distended, fixed, and sectioned. We made three-dimensional orientation measurements of smooth muscle and collagen, stained to enhance their birefringence, using the polarized light microscope.
The general contour of the fenestrations is streamlined with a thickened layered subendothelium at the trailing or distal edge, structurally similar to the region of convergence of major brain arteries. Defects of the medial layer were found at both proximal and distal edges of all the fenestrations. Results included regional mean orientations of individual layers, with circular SDs. The medial layer was found to be coherently aligned perpendicular to the direction of blood flow, with a mean circular SD of 12 degrees. The adventitia was less coherent (mean circular SD, 16 degrees) with the same average orientation, and the multilayered subendothelium had layers of obliquely oriented fibers with a wide range of coherence for individual fiber groups. Layers of the side regions were analogous to those in segments of brain artery and differed significantly from the proximal and distal edges of the fenestration structure.
The plasticity of form of the fenestrations at both the proximal and distal edges is in response to hemodynamic forces and is analogous to branching regions of brain arteries. Medial defects, a common feature in both brain arteries and fenestrations, may predispose the arterial fenestration to aneurysm formation.
Fibromuscular Dysplasia of the Extracranial Internal Carotid Arteries Associated With an Ulcerative Plaque
Authors: Hooshmand H. , Boykin M. E. , Vines F. S. , Lee H. M. 
Published: June 2011

Fibromuscular dysplasia (FMD) of the extracranial internal carotid arteries is a relatively rare angiographical finding which has been reported as an incidental finding during angiography, as well as in association with a variety of different clinical conditions. A case is reported of transient attacks of amaurosis fugax and hemiparesis. Angiography in this patient revealed bilateral FMD of the internal carotids as well as a small ulcerative plaque involving the right internal carotid artery at the region of carotid bifurcation. Surgical treatment directed toward the ulcerative plaque and not the FMD of the carotid arteries has rendered the patient asymptomatic. Lack of symptoms, despite the persistence of FMD, suggests that FMD is of doubtful pathogenic significance.
A small, surgically correctable ulcerative plaque should not be overlooked in the presence of FMD of the internal carotid arteries. The significance of the rare finding of FMD of the internal carotid arteries is not clear.
The Process of Recovery: After Hemiplegia
Authors: NEWMAN MICHAEL 
Published: June 2011

A group of 39 patients with hemiplegia due to cerebral infarction was followed from the time of onset for a period of at least 20 weeks. The subjects were selected on the basis of freedom from serious concomitant disease but having neurological disability persisting at least four weeks. The process of recovery was followed with standard neurological and functional tests.
Some neurological recovery occurred in 34 patients. Recovery is usually best in the lower limb, but upper limb movement, sensation, body image, mental ability, and speech may also recover to some extent. Recovery may begin as early as the first week or as late as the seventh. Little neurological improvement took place after the fourteenth week and the average interval from onset to 80% final recovery was six weeks. Functional recovery closely follows neurological recovery.
It is suggested that much of the early recovery and that of the upper limb could be due to return of circulation to ischemic areas. Transfer of function to undamaged neurons is suggested as a mechanism of late recovery, especially of the lower limbs and of speech. The role of cerebral edema is uncertain.