bluuebunny/crossref_metadata_2025 huggingface dataset:
Gait outcome in ambulatory hemiparetic patients after a 4-week comprehensive rehabilitation program and prognostic factors.
Authors: Hesse S A , Jahnke M T , Bertelt C M , Schreiner C , Lücke D , Mauritz K H
Published: June 2011

Although gait training is prominent in the rehabilitation of hemiparetic stroke patients, little is known about its outcome and prognostic factors in mildly affected patients. We therefore intended to assess gait in ambulatory stroke patients before and after a 4-week inpatient rehabilitation program based on the neurodevelopmental technique.

We measured vertical ground reaction forces by force plates in 148 stroke patients. Variables were stance durations, peak vertical ground reaction forces at heel strike (Fz1) and toe-off (Fz2), loading and deloading rates, time to Fz1, and time to Fz2. The absolute changes for both legs and symmetry outcome were calculated. In addition, we assessed maximal walking speed, walking endurance, stair climbing ability, and the Motricity Index.

Stance duration, weight acceptance, push-off of both legs, and the stance duration symmetry improved independent of changes of gait velocity. The symmetry of the ground reaction forces did not improve. Results were even worse for Fz1 and the loading rate at the end of treatment. Sex, age, side of hemiparesis, motor strength, stroke interval, and sensory impairment had no influence on the outcome of symmetry. Functional performance did not improve considerably.

The absolute changes of the ground reaction forces indicated better weight acceptance and push-off of both legs and thus confirmed the efficacy of the neurodevelopmental technique. The symmetry outcome and the functional performance at the end of treatment, however, challenge the efficacy of intensive rehabilitation therapy for 4 weeks in its attempts to restore physiological gait in these mildly affected patients.
Ethnic differences in stroke mortality between non-Hispanic whites, Hispanic whites, and blacks. The National Longitudinal Mortality Study.
Authors: Howard G , Anderson R , Sorlie P , Andrews V , Backlund E , Burke G L
Published: June 2011

Although US blacks are known to have an excess stroke mortality compared with US whites, little is known about the stroke burden of the Hispanic white population. This report will provide estimates of the relative burden of stroke mortality in the US black and Hispanic population relative to the white population and examine the consistency of this relation across age.

Data were from participants aged > 45 years from the National Longitudinal Mortality Study. There were 1844 stroke deaths among 239,734 non-Hispanic whites, 46 deaths among 12,527 Hispanic whites, and 234 deaths among 23,468 black participants. Standard statistical methods were used to examine the ethnic differences in stroke mortality.

The hazard ratios for black men and women (relative to non-Hispanic whites) were nearly identical, at > 4.0 at age 45 but marginally < 1.0 by age 85. For both Hispanic men and women, the hazard ratios (relative to non-Hispanic whites) were approximately 1.0 at age 45 but were marginally significantly < 1.0 at older ages. The ethnic differences in stroke death rates reveal differences in age distributions of age at fatal stroke between these groups. Approximately 6% of fatal strokes for non-Hispanic whites occurred before age 60, whereas > 15% occurred in both Hispanic whites and blacks.

These results suggest that (1) for Hispanics, stroke risk is similar to that for non-Hispanic whites at young ages but is marginally lower at older ages, (2) the excess stroke mortality in blacks mainly occurs at younger ages (between 45 and 55 years), and (3) the relation between stroke risk for blacks and Hispanics relative to whites is similar by sex. The impact of age on relative stroke mortality would argue against simple age adjustment for describing ethnic differences in stroke mortality. Finally, proportionally, more strokes occur at older ages in non-Hispanic whites than in either US blacks or Hispanic whites.
Racial disparities in severity of cerebrovascular events.
Authors: Kuhlemeier K V , Stiens S A
Published: June 2011

This study was conducted to determine if blacks hospitalized for cerebrovascular events had more severe cerebrovascular events than whites similarly hospitalized.

Data from the Maryland Health Services Cost Review Commission were used to determine incidence of coma, death rates, age at death of those who died, and length of stay for acute hemorrhagic and occlusive stroke in hospitalized blacks and whites after adjusting for sex and, if appropriate, age.

With a single exception (number of patients with hemorrhagic stroke who died during short-term hospitalization), all indices indicated that blacks incurred more severe cerebrovascular events than whites (P < .05 or less).

Maryland state data from hospitalized patients indicate that blacks had more severe strokes than whites.
Middle cerebral artery velocity changes during transfusion in sickle cell anemia.
Authors: Venketasubramanian N , Prohovnik I , Hurlet A , Mohr J P , Piomelli S
Published: June 2011

Sickle cell disease is associated with cerebral hyperemia, which is therapeutically reduced by transfusion; however, the process of transfusion-induced cerebral perfusion changes has heretofore not been observed.

We document the acute changes of intracranial arterial velocity in 10 patients (7 with strokes, 3 without) undergoing transfusion therapy using transcranial Doppler ultrasonography. Middle cerebral artery velocities were bilaterally measured every 30 minutes for the duration of transfusion (4 to 5 hours). Regional cerebral blood flow was quantified in 5 of these patients before the transfusion and 24 hours later by the 133Xe technique.

Velocities in stroke-associated vessels (64.33 +/- 18.65 cm/s; n = 6) were significantly lower than in uninfarcted territories (99.54 +/- 27.39 cm/s; n = 13), and both types of vessels showed a robust reduction of blood flow velocities during transfusion. The rates of reduction were not significantly different as a function of prior stroke but did correlate with pretransfusion velocities and with the rise in hematocrit (multiple r = .887, P < .001). These reductions occurred rapidly within the first 3 hours of transfusion. Velocities attained at the end of transfusion were maintained in the hour after transfusion and the next day.

We conclude that transfusion induces rapid changes in cerebral hemodynamics that are related to pretransfusion velocities and a rise in hematocrit. Transcranial Doppler provides a safe, simple, and noninvasive technique of monitoring these changes and may provide a means of making therapeutic decisions regarding transfusion therapy in patients with sickle cell anemia.
Sensory symptoms and signs and results of quantitative sensory thermal testing in patients with lacunar infarct syndromes.
Authors: Samuelsson M , Samuelsson L , Lindell D
Published: June 2011

Quantitative data on sensory impairment in stroke patients are limited. We measured the perception thresholds for temperature and thermal pain in patients with different lacunar syndromes, correlated the results with clinical and magnetic resonance imaging (MRI) findings, and studied the long-term prognosis of sensory dysfunction.

Quantitative thermal testing was performed by means of the Marstock method in 39 patients with lacunar syndromes (pure motor, sensorimotor, or pure sensory stroke) and MRI findings compatible with occlusion of a single perforating artery. Thresholds for cold, warmth, and heat pain were obtained bilaterally from the cheek, hand, and leg. The unaffected side was used as control. Follow-up included clinical assessments and repeated quantitative thermal testing (in 17 patients) up to 1 year after stroke onset.

Patients with pure sensory stroke and sensorimotor stroke (n = 22) had a significant thermal hypoesthesia on the affected side for all modalities and test locations. Patients with pure motor stroke (n = 17) exhibited thermal hypoesthesia for cold and heat pain in the hand and for cold perception in the leg. On MRI, infarcts causing pure motor and sensorimotor stroke were predominantly lenticulocapsular, while a thalamic site of infarction was found in pure sensory stroke. The prognosis of sensory impairment was favorable, except for poststroke pain syndromes in three patients.

Quantitative thermal testing confirmed an involvement of spinothalamic pathways in lacunar infarcts causing pure sensory and sensorimotor stroke and revealed a subclinical sensory impairment in patients with pure motor stroke. Infarction sites were similar in patients with pure motor and sensorimotor stroke.
Frequency and pathogenesis of hemodynamic stroke.
Authors: Bladin C F , Chambers B R
Published: June 2011

Hemodynamic stroke is a recognized but poorly described entity. The aim of this study was to define the frequency and pathogenic mechanisms of hemodynamic stroke.

We prospectively studied 300 consecutive patients with acute ischemic stroke for evidence of a hemodynamic mechanism. All patients with a probable or possible thromboembolic source were excluded.

Twenty-nine patients (9.6%) had documented or presumed hypotension at stroke onset, with 27 of 29 (93%) having watershed infarction on computed tomography (CT). Most (21/29) patients had a slow (hours to days) progressive onset to stroke. Myocardial infarction, cardiac arrhythmias, and orthostatic changes in blood pressure related to diabetic dysautonomia and antihypertensive therapy were the predominant causes of hypotension. Ten patients had moderate or severe carotid stenosis (frequently bilateral); 9 had carotid occlusion (19/29 [66%]). Patients with normal carotid arteries (10/29 [34%]) had hypotension with a stuttering onset to stroke and watershed infarction on CT. Many patients continued to have progressive neurological deterioration, often with ongoing hemodynamic instability. Three of 7 patients who underwent carotid endarterectomy had further perioperative ischemic events. Five patients had myocardial infarction, and overall 4 died during 18.4 months of follow-up (mortality, 9%/y).

Recognition of the clinical and CT features of hemodynamic stroke allows early identification and management of cardiac and carotid disease and correction of iatrogenic causes of hypotension, which may reduce the risk of further events.
Value of immunologic testing in stroke patients. A prospective multicenter study.
Authors: Montalbán J , Rio J , Khamastha M , Davalos A , Codina M , Swana G T , Calcagnotto M E , Sumalla J , Mederer S , Gil A
Published: June 2011

The aims of this prospective and multicenter study were to determine the frequency of anticardiolipin and antinuclear antibodies in an unselected ischemic and hemorrhagic stroke population and to evaluate the clinical significance of these autoantibodies.

Over a 1-year period, we collected plasma from 481 consecutive patients with ischemic or hemorrhagic stroke attending four different hospitals. Blood (10 mL) was drawn from each subject into a citrated glass tube. Plasma was obtained immediately by centrifugation and was stored at -70 degrees C until use. Concentrations of IgM and IgG anticardiolipin antibodies were measured at room temperature in normal (not heat-treated) plasma by standardized enzyme-linked immunosorbent assay. All sera were treated by indirect immunofluorescence on mouse liver and kidney sections for antinuclear antibodies.

A total of 481 patients (325 men, 156 women) 16 to 90 years in age (mean age, 61 years) were studied. Anticardiolipin antibodies were present in 5 of 481 (1.04%) patients. One patient was IgG positive and four patients were IgM positive. Of 481 patients, 35 (7.2%) were positive for antinuclear antibodies. Anti-DNA antibodies were not demonstrable in any patient.

The frequency of anticardiolipin antibodies in a heterogeneous stroke population is possibly lower than reported. The routine screening of anticardiolipin and antinuclear antibodies in a stroke population is of questionable value.
Nitric oxide promotes arteriolar dilation during cortical spreading depression in rabbits.
Authors: Colonna D M , Meng W , Deal D D , Busija D W
Published: June 2011

Pial arterioles transiently dilate during cortical spreading depression (CSD), although the mechanisms are unclear. We tested the hypothesis that increased production of nitric oxide (NO) promotes arteriolar dilation.

Urethane-anesthetized rabbits were equipped with cranial windows, and the diameter (reported in micrometers) of a pial arteriole was determined via intravital microscopy. In each rabbit, a baseline CSD was elicited by microapplication of KCl onto the cortex, and resultant pial arteriolar dilation was measured. Either 100 mumol/L N omega-nitro-L-arginine methyl ester (L-NAME) or 50 mumol/L NG-nitro-L-arginine (L-NA), both competitive NO synthase inhibitors, was then applied to the brain surface. A CSD was elicited as before. The L-NAME and L-NA were then removed by artificial cerebrospinal fluid washes. An additional CSD was induced with KCl as before.

Control CSD in the L-NAME group dilated pial arterioles; baseline diameter, 66 +/- 7 mm, with CSD = 106 +/- 8 mm (59% increase). After topically applied L-NAME, CSD dilated pial arterioles less: baseline diameter, 61 +/- 7 mm, with CSD = 77 +/- 6 mm (26% increase), P < .05 compared with control CSD diameter. Topical L-NA had similar effects on CSD: control CSD dilated pial arterioles 51%; after topical L-NA, only 14% (P < .05). After removal of L-NAME or L-NA, CSD-induced pial arteriolar dilation was similar to original control values.

The reversible inhibition of CSD-induced pial arteriolar dilation by either L-NAME or L-NA suggests that NO contributes to arteriolar dilation observed with CSD.
Evidence for episodic platelet activation in acute ischemic stroke.
Authors: van Kooten F , Ciabattoni G , Patrono C , Schmitz P I , van Gijn J , Koudstaal P J
Published: June 2011

Enhanced thromboxane biosynthesis has previously been reported in patients with acute ischemic stroke. In this study we examined the time course of thromboxane biosynthesis after the onset of symptoms in 13 patients with acute cerebral infarction.

We obtained five to eight consecutive 6-hour urine samples from each of these 13 patients within the first 48 hours after onset of symptoms to study the dynamics of platelet activation in this setting. The urinary excretion of the major enzymatic metabolite of thromboxane B2, 11-dehydro-thromboxane B2, was measured by a previously validated radioimmunoassay. The excretion rate was compared with that of 20 control patients with nonvascular neurological diseases.

Eleven patients (85%) had at least one value exceeding 2 SD of the control mean (251 pmol/mmol creatinine). The proportion of samples with an elevated 11-dehydro-thromboxane B2 level was markedly similar in each of the eight 6-hour collection periods (mean, 52 +/- 8%; range, 40% to 67%). In 4 patients (31%) the excretion rate was elevated in all measurements obtained. In the 11 patients with enhanced thromboxane biosynthesis, no uniform pattern of changes over time in metabolite excretion emerged, with 3 patients having peak values at 0 to 12 hours, 3 at 12 to 24 hours, 3 at 24 to 36 hours, and 2 at 36 to 48 hours. The level and dynamics of 11-dehydro-thromboxane B2 excretion were related neither to the neurological symptoms nor to the type or site of the cerebral ischemia.

We conclude that episodes of platelet activation occur repeatedly during the first 48 hours after the onset of symptoms of an acute ischemic stroke. Given its apparent dynamic nature, this ongoing process may be amenable to pharmacologic modulation.
Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.
Authors: Manolio T A , Kronmal R A , Burke G L , Poirier V , O'Leary D H , Gardin J M , Fried L P , Steinberg E P , Bryan R N
Published: June 2011

Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease.

Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors.

Measures of cerebral atrophy increased with age and were greater in men than in women (each P < .01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P < .03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P < .004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound.

Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities.
Predicting the disability of first-time stroke sufferers at 1 year. 12-month follow-up of a population-based cohort in southeast England.
Authors: Taub N A , Wolfe C D , Richardson E , Burney P G
Published: June 2011

The purpose of this study was to predict the functional outcome at 1 year of first-time stroke patients aged younger than 75 years in relation to the severity of stroke and demographic characteristics.

Population registers in three districts of southeast England were established in August 1989, with notification by stroke registry field-workers, general practitioners, and rehabilitation practitioners. Assessments were made using the Barthel index for activities of daily living at the time of maximum impairment and at 3 and 12 months after the stroke.

Of 639 registered stroke patients, 392 without previous disability survived and were assessed for disability at 3 months, of whom 34 (9%) were severely disabled and 60 (15%) moderately disabled. Initial incontinence was the best single predictor of disability with a sensitivity of 60% and a specificity of 78%. Two hundred twenty-five patients (35%) were eligible for 12-month follow-up; 11% had moderate or severe disability, for which initial incontinence was the best predictor.

There is no evidence from this study of an association between demographic characteristics and the disability status of stroke survivors in the medium term. Multivariable predictors of disability had little advantage over incontinence within 24 hours of the stroke. The estimates of the prevalence of disability from this large population-based study are relevant when assessing the medium-term needs of stroke patients.
Noninvasive detection of intracranial vascular lesions by recording blood flow sounds.
Authors: Kurokawa Y , Abiko S , Watanabe K
Published: June 2011

Transorbital blood flow sound recordings have the potential to be used for noninvasive detection of cerebral aneurysms and arteriovenous malformations. We describe our system and experience in detecting intracranial cerebrovascular disease.

We investigated the noninvasive detection of intracranial vascular lesions by recording and analyzing the intracranial blood flow sounds. A new small transducer was placed on the unilateral eyelid to record the intracranial blood flow sounds, which were amplified and converted to digital data at a sampling frequency of 2000 Hz to provide a spectral analysis.

No spectral peaks were recorded in 30 healthy adults. Sharp peaks were recorded in 12 of 15 patients with unclipped aneurysms, and broad peaks were recorded in two patients with vasospasm after aneurysmal clipping and in all patients with severe intracranial internal carotid artery stenosis.

This noninvasive technique has the potential to be very useful in the detection of intracranial cerebrovascular disease, including aneurysm and arterial stenosis, and could be used in mass screening examinations.
Nitric oxide synthase inhibition alters cerebral blood flow and oxygen balance in focal cerebral ischemia in rats.
Authors: Wei H M , Chi O Z , Liu X , Sinha A K , Weiss H R
Published: June 2011

This study investigated whether the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) would alter blood flow and oxygen balance in the ischemic cerebrocortex of isoflurane-anesthetized Long-Evans rats.

Fifteen minutes after middle cerebral artery occlusion, L-NAME (1.5 mg/min per kilogram) was infused intravenously to the L-NAME group (n = 14), and normal saline was given to the control group (n = 14) for 45 minutes. In each group, regional cerebral blood flow was determined with [14C]iodoantipyrine, and arterial and venous oxygen saturations were determined by microspectrophotometry.

In both groups regional cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex ([mean +/- SD] 55 +/- 13 versus 110 +/- 29 mL/min per 100 g in the control group and 35 +/- 13 versus 90 +/- 24 mL/min per 100 g in the L-NAME group). Compared with the blood flow in the ischemic cortex of the control group, L-NAME significantly reduced ischemic blood flow by 36%. Venous oxygen saturation was significantly increased in the ischemic cortex (41 +/- 1% versus 44 +/- 3%) but decreased in the contralateral cortex (65 +/- 3% versus 61 +/- 4%) by L-NAME. Calculated ischemic cortical oxygen consumption in the L-NAME group was 39% lower than that in the corresponding control group, whereas the difference was only 11% in the contralateral sides between groups. In both groups, the ratio of oxygen supply to consumption was lower in the ischemic than in the nonischemic regions. In the ischemic cortex, this ratio was significantly lower in the control group than in the L-NAME group (1.7 +/- 0.1 versus 1.9 +/- 0.1). In contrast, the ratio tended to be decreased by L-NAME in nonischemic regions.

These observations suggest that despite a decrease in cerebral blood flow, inhibition of nitric oxide synthesis mildly improves the oxygen supply and consumption balance in the ischemic cortex.
Neuron-specific enolase concentrations in blood as a prognostic parameter in cerebrovascular diseases.
Authors: Schaarschmidt H , Prange H W , Reiber H
Published: June 2011

To investigate the clinical relevance of plasma concentrations of neuron-specific enolase (NSE) in patients with severe cerebrovascular diseases, serial analyses were performed during the first 10 days after the acute event.

Plasma samples taken from 61 patients (30 with brain infarction, 13 with intracerebral hemorrhage, 11 with cardiogenic hypoxia-ischemia, and 7 with myocardial infarction [as control group]) were analyzed for NSE concentration using an enzyme immunoassay. The time course of plasma NSE was correlated with clinical findings, clinical outcome, cranial computed tomography, intracranial pressure, and other laboratory data.

In cases of hypoxia-ischemia there was close correlation between plasma NSE values during the first 72 hours and the clinical outcome. In brain infarction and intracerebral hemorrhage, high plasma NSE mostly indicated an unfavorable outcome, but low values did not permit a reliable prognostic estimation. In cases of cerebral infarction and intracerebral hemorrhage with secondary neuronal destruction (for example, due to malignant edema), increasing NSE concentrations in plasma preceded the change of clinical or other diagnostic parameters.

The course of plasma NSE levels is seen as a relevant parameter for assessing the prognosis of cerebral hypoxia-ischemia. Additionally, it may prove to be a useful tool for monitoring space-occupying brain infarctions and intracerebral hemorrhages and therefore may contribute to improved therapeutic management of severe cerebrovascular diseases.
Characteristics of patent foramen ovale associated with cryptogenic stroke. A biplane transesophageal echocardiographic study.
Authors: Homma S , Di Tullio M R , Sacco R L , Mihalatos D , Li Mandri G , Mohr J P
Published: June 2011

Patent foramen ovale is associated with ischemic stroke in patients without a clearly identifiable etiology for stroke (cryptogenic stroke). Paradoxical embolization is thought to be a potential mechanism. However, patent foramen ovale is also found in patients with known cause of stroke. Therefore, using contrast transesophageal echocardiography, we characterized the patent foramen ovale in cryptogenic stroke patients to assess morphological factors that may contribute to paradoxical embolization.

Contrast transesophageal echocardiographic studies of 74 consecutive patients referred for ischemic stroke were reviewed. Twenty-three patients with patent foramen ovale were identified. These patients were classified as having strokes of determined origin or cryptogenic strokes according to criteria developed for the Stroke Data Bank of the National Institute of Neurological Disorders and Stroke. Separation of septum primum from secundum and the number of microbubbles appearing in left atrium were then quantitated. These parameters were compared between patients with cryptogenic stroke and those with known cause of stroke.

The patent foramen ovale dimension was significantly larger in patients with cryptogenic stroke compared with patients with an identifiable cause of stroke (2.1 +/- 1.7 mm versus 0.57 +/- 0.78 mm [mean +/- SD]; P < .01). The number of microbubbles was also greater in patients with cryptogenic stroke compared with patients with an identifiable cause of stroke (13.9 +/- 10.7 versus 1.6 +/- 0.8 [mean +/- SD]; P < .0005).

Patients with cryptogenic stroke have larger patent foramen ovale with more extensive right-to-left interatrial shunting than patients with stroke of determined cause. Transesophageal echocardiographically identifiable characteristics of patent foramen ovale may be important in defining the clinical significance of individual patent foramina.
Changes in locomotor activity and passive avoidance task performance induced by cerebral ischemia in Mongolian gerbils.
Authors: Karasawa Y , Araki H , Otomo S
Published: June 2011

We investigated changes in locomotor activity, passive avoidance task performance, and hippocampal CA1 neurons induced by cerebral ischemia in Mongolian gerbils to examine the relation between these behavioral changes and CA1 neuronal damage.

Spontaneous locomotor activity was measured using the open field method before and 1, 3, 7, 14, or 28 days after 1- to 5-minute occlusion of the bilateral common carotid arteries. Locomotor activity after the second episode of 5-minute ischemia was also measured at 1-month intervals. The passive avoidance task was performed 7 or 28 days after induced ischemia. Histopathological changes in CA1 neurons after ischemia were assessed.

Locomotor activity was increased 1 and 3 days after induced ischemia but not 14 and 28 days later. When the gerbils were again subjected to 5-minute ischemia 1 month after the initial 5-minute induced ischemia, locomotor activity even 1 day later was significantly increased. In contrast, passive avoidance impairment depended on the duration of ischemia, as determined 7 and 28 days after induced ischemia. Hippocampal CA1 neuronal damage was progressive, that is, changes in CA1 neurons were apparent even 1 day after 5 minutes of induced ischemia, and the CA1 neurons disappeared 7 days after 5 minutes of ischemia.

Passive avoidance impairment after ischemia is related to damage of CA1 neurons. Changes in locomotor activity after induced ischemia do not seem to be linked to CA1 neuronal damage.
Comparison of flow and velocity during dynamic autoregulation testing in humans.
Authors: Newell D W , Aaslid R , Lam A , Mayberg T S , Winn H R
Published: June 2011

We compared relative changes in middle cerebral artery velocity and internal carotid artery flow during autoregulation testing to test the validity of using transcranial Doppler recordings of middle cerebral artery velocity to evaluate cerebral autoregulation in humans.

Seven human volunteers had dynamic autoregulation tested during surgical procedures that included exposure of the internal carotid artery. The mean arterial blood pressure and middle cerebral artery velocity spectral outline (Vmax), using transcranial Doppler, and ipsilateral internal carotid artery flow, using an electromagnetic flowmeter, were continuously and simultaneously recorded during transient sharp decreases in blood pressure that were induced by rapid deflation of thigh blood pressure cuffs. The resulting responses of velocity in the middle cerebral artery and flow in the internal carotid artery were compared.

Moderate decreases in blood pressure evoked responses in cerebral autoregulation. There were no significant (P = .97) differences between the responses in middle cerebral artery velocity and internal carotid artery flow to the blood pressure decreases.

Relative changes in Vmax accurately reflect relative changes in internal carotid artery flow during dynamic autoregulation testing in humans. Therefore, alterations in middle cerebral artery diameter do not occur to the extent that they introduce a significant error in making these comparisons.
Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats.
Authors: Chopp M , Zhang R L , Chen H , Li Y , Jiang N , Rusche J R
Published: June 2011

Postischemic cerebral inflammation may contribute to ischemic cell damage. The CD11b/18 (Mac-1) integrin mediates stimulated neutrophil binding to endothelia. We therefore investigated the effect of administration of an anti-Mac-1 monoclonal antibody on cerebral ischemic cell damage in the rat.

Rats (n = 10) were subjected to 2 hours of middle cerebral artery occlusion; the anti-Mac-1 antibody was administered at a dose of 2 mg/kg i.v. at 1 hour of reperfusion and 1 mg/kg i.v. at 22 hours of reperfusion or an isotype-matched control antibody (n = 10) was administered using the same experimental protocol. Rats were killed at 46 hours of reperfusion, and brain sections were stained with hematoxylin and eosin for histological evaluation. In a separate population of rats given either vehicle (n = 8) or anti-Mac-1 antibodies (n = 9), intraparenchymal neutrophils were measured by means of a myeloperoxidase assay.

The lesion volume was significantly smaller (28%) in the anti-Mac-1 antibody group compared with the vehicle control group (P < .01). Numbers of intraparenchymal polymorphonuclear cells were significantly reduced (P < .05) in the cortex of the anti-Mac-1 antibody group compared with the vehicle control group.

Our data demonstrate that administration of anti-Mac-1 antibody 1 hour after onset of reperfusion results in significant reductions of ischemic cell damage and intraparenchymal neutrophils after transient (2-hour) focal cerebral ischemia in the rat.
Neurovascular manifestations of heritable connective tissue disorders. A review.
Authors: Schievink W I , Michels V V , Piepgras D G
Published: June 2011

Heritable disorders of connective tissue are recognized in a small minority of patients with neurovascular diseases. In this report, we review the neurovascular manifestations of four heritable connective tissue disorders: Ehlers-Danlos syndrome, Marfan's syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum, as well as two other systemic disorders with potential vascular manifestations: neurofibromatosis and polycystic kidney disease.

Typical neurovascular complications of Ehlers-Danlos syndrome are carotid-cavernous fistulae, intracranial aneurysms, and cervical artery dissections. Arterial dissections and intracranial aneurysms cause the majority of neurovascular symptoms in Marfan's syndrome. Neurovascular disease is uncommon in osteogenesis imperfecta, although carotid-cavernous fistulae and vertebral artery dissections have been reported. Neurovascular disease in pseudoxanthoma elasticum is characterized by intracranial aneurysms and cerebral ischemia caused by premature arterial occlusive disease. Intracranial occlusive arterial disease is the most common neurovascular manifestation of neurofibromatosis, followed by cervical arteriovenous fistulae and aneurysms and intracranial aneurysms. Intracranial aneurysms are the hallmark of polycystic kidney disease.

Recognition of an underlying generalized connective tissue disorder may be of considerable importance, although marked phenotypic heterogeneity often complicates the diagnosis of these disorders. Conversely, the association of certain neurovascular anomalies with generalized connective tissue disorders and recognition of their basic molecular defect may offer clues to the etiology and pathogenesis of these neurovascular diseases in general.
Similar motor recovery of upper and lower extremities after stroke.
Authors: Duncan P W , Goldstein L B , Horner R D , Landsman P B , Samsa G P , Matchar D B
Published: June 2011

This study examined the validity of the clinical tenet that poststroke recovery of the upper extremity is less rapid and complete than poststroke recovery of the lower extremity. Previous studies comparing upper and lower extremity recovery have evaluated disability rather than motor impairment. Individuals with lower extremity impairments may be more functional and appear less disabled than individuals with upper extremity impairments. Function of the upper extremity requires finer motor control, for which the patient can less readily compensate. Therefore, impairments and disability would predictably be more highly correlated in this area. We tested the hypothesis that upper and lower extremity motor recovery are similar.

The 95 patients selected for this study were enrolled in the Durham County Stroke Study and had been diagnosed with anterior circulation ischemic stroke. Each subject received Fugl-Meyer assessments within 24 hours of admission and then 5, 30, 90, and 180 days after stroke. We used these assessments to compare the time course and patterns of motor function of the upper and lower extremities.

Repeated-measures ANOVA revealed that percent maximal motor recovery was significantly (P < .001) affected by time after stroke but not by extremity (upper extremity versus lower extremity) (P = .32). When stroke severity level is controlled, the upper and lower extremities continue to show no difference in percent motor recovery (P = .19).

In patients with anterior circulation ischemic stroke, the severity of motor impairment and the patterns of motor recovery are similar for the upper and lower extremities. The most rapid recovery for both extremities occurs within 30 days.
Mechanisms of vasodilation of cerebral vessels induced by the potassium channel opener nicorandil in canine in vivo experiments.
Authors: Ishiyama T , Dohi S , Iida H , Akamatsu S , Ohta S , Shimonaka H
Published: June 2011

Nicorandil, a potent antianginal agent characterized as a potassium channel opener, could produce cerebrovascular dilation in in vitro studies. Our aim was to investigate the pharmacologic response to the topical application of nicorandil on the vasomotor tone of pial vessels in vivo. To elucidate its mechanism, we also studied the inhibitory action of methylene blue and glibenclamide against nicorandil-induced vasodilation.

In 14 dogs prepared with a parietal cranial window, we administered five different concentrations of nicorandil solution (10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) mol/L) under the window and measured pial arterial and venular diameters. After pretreating pial vessels with either 10(-5) mol/L methylene blue or 10(-5) mol/L glibenclamide, we examined inhibitory action after the application of 10(-5) mol/L nicorandil. In additional experiments with 9 dogs, we evaluated the effects of nitroglycerin and cromakalim on pial vessels in the absence or presence of 10(-5) mol/L methylene blue and 10(-5) mol/L glibenclamide, respectively.

Nicorandil produced significant, concentration-dependent dilation of pial vessels (P < .05). Methylene blue blocked nicorandil-induced dilation, whereas glibenclamide only attenuated such action of nicorandil. Nitroglycerin and cromakalim also produced a concentration-dependent increase in pial arteriolar and venular diameters (P < .05), and those effects were blocked in the presence of methylene blue or glibenclamide, respectively.

Our in vivo study demonstrates that topical application of nicorandil dilates both pial arterioles and venules in a concentration-dependent manner and suggests that the mechanisms of such actions are most likely due to both cyclic GMP-mediated vascular smooth muscle dilation and the regulation of K+ flux.
Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets.
Authors: Schleien C L , Eberle B , Shaffner D H , Koehler R C , Traystman R J
Published: June 2011

Cardiac arrest and resuscitation in immature piglets result in a delayed increase in blood-brain barrier permeability. We tested the hypothesis that pretreatment with oxygen radical scavengers reduces postischemic permeability.

Permeability was assessed by measuring the plasma-to-brain transfer coefficient of the small amino acid, alpha-aminoisobutyric acid, in 2- to 3-week-old anesthetized piglets. Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n = 8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10,000 U/kg) and to catalase (20,000 U/kg). The ischemia protocol consisted of 8 minutes of ventricular fibrillation, 6 minutes of cardiopulmonary resuscitation, defibrillation, and 4 hours of spontaneous circulation.

The mean +/- SEM of the transfer coefficient of alpha-aminoisobutyric acid in cerebrum was (in microL/g per minute): 1.54 +/- 0.37 in the nonischemic group, 2.04 +/- 0.26 in the ischemia group treated with vehicle, and 1.29 +/- 0.25 in the ischemia group treated with oxygen radical scavengers. Postischemic values with scavenger treatment were significantly lower than those with vehicle treatment in cerebrum, cerebellum, medulla and cervical spinal cord.

Pretreatment with oxygen radical scavengers reduces postischemic blood-brain barrier permeability by a small amino acid. These data are consistent with oxygen radical-mediated dysfunction of cerebral endothelium in a pediatric model of cardiopulmonary resuscitation.
Simultaneous Cerebrovascular and Cardiovascular Responses During Presyncope
Authors: Bondar Roberta L. , Kassam Mahmood S. , Stein Flo , Dunphy Paul T. , Fortney Sue , Riedesel Marvin L.
Published: June 2011

Background and Purpose
Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve.

Methods
Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG).

Results
At presyncope, MFV dropped on average by 27.3±14% of its baseline value (
P
<.05), while MABP remained at 2.0±27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP.

Conclusions
Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation mechanism.
Phase Relationship Between Cerebral Blood Flow Velocity and Blood Pressure
Authors: Diehl Rolf R. , Linden Dieter , Lücke Dorothee , Berlit Peter
Published: June 2011

Background and Purpose
This study investigates the usefulness, as a test of dynamic autoregulation, of phase shift angle analysis between oscillations in cerebral blood flow velocity (CBFV) and in arterial blood pressure (ABP) during deep breathing.

Methods
Fifty healthy volunteers, 20 patients with occlusive cerebrovascular diseases (OCD), and 10 patients with arteriovenous malformations (AVM) took part in the study. All subjects received transcranial Doppler monitoring of both middle cerebral arteries (MCAs). In addition, continuous blood pressure monitoring was performed with the use of noninvasive servo-controlled infrared finger plethysmography during deep breathing at a rate of 6/min. With the use of a high-pass filter model of autoregulation, autoregulation was quantified as phase shift angle between oscillations in CBFV and ABP at a frequency of 6/min. A phase shift angle of 0° indicates total absence of autoregulation, while 90° can be gauged as optimal autoregulation. In addition, vasomotor reactivity of both MCAs to CO
2
stimulation was assessed among patients and calculated as percent increase in CBFV per millimeter of mercury of increase in CO
2
.

Results
All normal subjects showed positive phase shift angles between CBFV and ABP (mean±SD, 70.5±29.8°). OCD patients presented with significantly decreased phase shift angles for the MCA only on the pathological side (51.7±35.1°;
P
<.05). Patients with AVM showed significantly reduced phase shift angles on both the affected side (26.8±13.5°;
P
<.001) and the unaffected side (40.6±26.6°;
P
<.01). In patients’ groups, phase shift angle and vasomotor reactivity correlated significantly (
r
=.66;
P
<.001) after results from all MCAs were pooled.

Conclusions
Results confirm the high-pass filter model of cerebral autoregulation: Normal subjects showed predicted positive phase shift angles between CBFV and ABP oscillations. Patients with expected autoregulatory disturbances showed significant decreases in phase shift angles. Close correlations existed between autoregulation and CO
2
-induced vasomotor reactivity.
Microvascular Basal Lamina Antigens Disappear During Cerebral Ischemia and Reperfusion
Authors: Hamann Gerhard F. , Okada Yasushi , Fitridge Robert , del Zoppo Gregory J.
Published: June 2011

Background and Purpose
Changes in vascular permeability are well-known and important consequences of cerebral ischemia. The development of edema and of petechial hemorrhage is connected to altered vascular integrity. A major part in microvascular integrity is played by the basal lamina.

Methods
The fates of the basal lamina components laminin, fibronectin, and type IV collagen during middle cerebral artery occlusion (2 hours, n=3) and occlusion (3 hours) with reperfusion (1 hour, n=3; 4 hours, n=3; and 24 hours, n=4) were evaluated in the nonhuman primate. Specific monoclonal antibodies against these components were used. The number and size distribution of the microvessels in each specimen were determined by video-imaging microscopy, and the relative fluorescence intensity of laminin was semiquantified by laser confocal microscopy. Basal lamina antigen presentations were compared by double-stain immunofluorescence histochemistry.

Results
The number of microvascular structures defined by the presence of each basal lamina antigen decreased significantly up to 24 hours of reperfusion (
P
<.0001). The ratio of laminin-containing vessels between the ischemic and nonischemic territories decreased significantly from control (0.98±0.04) to 2 hours of ischemia (0.83±0.09) and 1 hour (0.79±0.08), 4 hours (0.77±0.06), and 24 hours of reperfusion (0.55±0.07). The ratio of fibronectin (cellular) and of collagen (IV)-containing vessels decreased from 0.98±0.04 to 0.75±0.1 and from 1.02±0.03 to 0.57±0.1, respectively. Mean laminin fluorescence intensity decreased from 76.1±6.0 U (controls) to 52.0±14.6 U (24 hours of reperfusion;
P
<.001).

Conclusions
The significant parallel losses of three basal lamina components, both in number and intensity, contribute to loss of microvascular integrity. These phenomena may be important for understanding cell extravasation and the hemorrhagic consequences of acute stroke.
Regional Prevalence and Distribution of Ischemic Neurons in Dog Brains 96 Hours After Cardiac Arrest of 0 to 20 Minutes
Authors: Radovsky Ann , Safar Peter , Sterz Fritz , Leonov Yuval , Reich Harvey , Kuboyama Kazutoshi
Published: June 2011

Background and Purpose
In this established outcome model of cardiac arrest in dogs, we have used total (summed regional) brain histopathologic damage scores. The present study describes the regional progression of necrotic (ischemic) neuron prevalence with increasing duration of cardiac arrest. It tests the hypothesis that increases in the total prevalence of necrotic neurons better correspond to increasing arrest duration and better correlate with neurological deficit than do any individual regional scores.

Methods
Blinded evaluation with light microscopy was used to score the prevalence (five categories) and note the distribution of necrotic neurons in dog brains 96 hours after normothermic ventricular fibrillation cardiac arrest followed by standard reperfusion and control of extracerebral variables. Six coronal brain sections including 19 regions were examined from dogs subjected to 0 (n=2), 5 (n=5), 10 (n=6), 12.5 (n=12), 15 (n=8), 17 (n=5), or 20 (n=1) minutes of cardiac arrest. Dogs were neurologically evaluated before death.

Results
Necrotic neurons were widespread and scattered among normal neurons. Individual regions varied in their sensitivity to different durations of cardiac arrest. There were consistent increases in the mean prevalence of necrotic neurons with increased arrest duration in the hippocampal dentate gyrus and for cerebellar granule neurons. Regionally, the caudate nucleus had the best correlation with clinical neurological deficit (ρ=+.85,
P
<.01).

Conclusions
Compared with total (summed regional) necrotic neuron prevalence scores, increased regional prevalence scores for cerebellar granule neurons with increasing arrest duration were equally significant, and scores for the caudate nucleus had nearly the same correlation with individual clinical neurological deficit.