bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Estradiol on Acute and Recurrent Insulin-Induced Hypoglycemia-Associated Patterns of Arcuate Neuropeptide Y, Proopiomelanocortin, and Cocaine- and Amphetamine-Related Transcript Gene Expression in the Ovariectomized Rat
Authors: Nedungadi T. Prashant , Briski Karen P.
Published: October 2007

The ovarian steroid hormone, estradiol, is one of several peripheral metabolic signal modulators that are integrated at the level of the arcuate nucleus of the hypothalamus (ARH), and is implicated in the control of ARH neuropeptides that maintain energy balance, including neuropeptide Y (NPY) and proopiomelanocortin (POMC). The present studies utilized quantitative real-time RT-PCR techniques to examine the hypothesis that estradiol regulates ARH NPY, POMC, and cocaine- and amphetamine-related transcript (CART) gene expression during acute insulin-induced hypoglycemia (IIH) and that adaptive modifications in transcriptional reactivity during recurring exposure are steroid dependent. ARH tissue was obtained by micropunch dissection from estradiol benzoate- and oil-implanted ovariectomized (OVX) rats that were treated by subcutaneous injection of one or four doses of the intermediate insulin formulation, Humulin NPH, over as many days, or vehicle alone. Our data show that in OVX plus estradiol benzoate and OVX plus oil groups, a single injection of insulin did not modify gene expression profiles, with the exception of acute hypoglycemic reduction of ARH NPY transcripts in the presence of estrogen. Prior exposure to daily hypoglycemia significantly diminished basal NPY and POMC mRNA levels in estradiol benzoate-, but not oil-implanted OVX rats, but elevated baseline CART transcripts in oil-treated animals. Recurring IIH enhanced ARH NPY gene expression relative to baseline, irrespective of the estradiol manipulation, but net tissue levels were greater in the absence of estrogen. In contrast, reexposure to hypoglycemia decreased POMC and CART gene transcription in estradiol benzoate- and oil-implanted OVX animals, respectively, relative to the single-dose groups. These studies show that estrogen modulates the impact of precedent exposure to IIH on basal and/or hypoglycemia-associated patterns of expression of ARH neuropeptide genes of characterized significance for energy homeostasis. The novel evidence for transcriptional acclimation of NPY, POMC, and CART to recurring IIH supports the possibility that adaptation of compensatory behavioral and physiological responses to acute versus chronic exposure to this metabolic stress may reflect neural regulatory mechanisms involving one or more neurotransmitters encoded by these genes.
Diffusion Tensor Imaging Study of Subcortical Gray Matter in CADASIL
Authors: Molko N. , Pappata S. , Mangin J.F. , Poupon C. , Vahedi K. , Jobert A. , LeBihan D. , Bousser M.G. , Chabriat H.
Published: October 2007

Background and Purpose

—

In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown.

Methods

—

We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images.

Results

—

A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score.

Conclusions

—

Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.
Chlamydia pneumoniae

in Atherosclerotic Middle Cerebral Artery
Authors: Virok Dezso , Kis Zoltan , Karai Laszlo , Intzedy Laszlo , Burian Katalin , Szabo Arpad , Ivanyi Bela , Gonczol Eva
Published: October 2007

Background and Purpose

—

Atherosclerotic middle cerebral arteries are frequent sites of thrombosis, leading to stroke. Previous studies have suggested a role for
Chlamydia pneumoniae
in the pathogenesis of atherosclerosis. However, the presence of this pathogen in atherosclerotic middle cerebral arteries has heretofore not been documented. In the present study, we analyzed atheromatous plaques from middle cerebral arteries for the presence of
C pneumoniae
.

Methods

—

Atherosclerotic middle cerebral arteries from 15 cadavers who died of natural causes and corresponding nonatherosclerotic arteries from 4 otherwise healthy trauma victims were examined. Assays for
C pneumoniae
DNA were carried out by nested polymerase chain reaction (nPCR) specific for the
C pneumoniae
ompA gene. The presence of the bacterium was assessed by transmission electron microscopy.

Results

—

Five of the 15 atherosclerotic arterial samples and none of the control tissues were positive for
C pneumoniae
by nPCR. Particles similar in morphology and size to
C pneumoniae
elementary bodies were detected by transmission electron microscopy in 4 of the 5 nPCR-positive atherosclerotic samples.

Conclusions

—

The demonstration of
C pneumoniae
in atherosclerotic middle cerebral arteries is consistent with the hypothesis that this bacterium is involved in acute and chronic cerebrovascular diseases.
Effect of Age on Cerebral Blood Flow Velocity and Incidence of Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Authors: Torbey Michel T. , Hauser Till-Karsten , Bhardwaj Anish , Williams Michael A. , Ulatowski John A. , Mirski Marek A. , Razumovsky Alexander Y.
Published: October 2007

Background and Purpose

—

Current transcranial Doppler criteria for vasospasm after aneurysmal subarachnoid hemorrhage are not age specific. We analyzed the effect of age on cerebral blood flow velocity changes after subarachnoid hemorrhage and constructed an age-adjusted predictive model of cerebral blood flow velocity in subarachnoid hemorrhage patients.

Methods

—

We identified patients with aneurysmal subarachnoid hemorrhage admitted between 1991 and 1999 with a prospective transcranial Doppler database. Eighty-one patients, with complete medical records and transcranial Doppler examinations of the vessels of interest, were included. Patients were subdivided into 2 groups by age: younger, <68 years of age (n=47) and older, ≥68 years of age (n=34). Maximum mean flow velocity and incidence of symptomatic vasospasm were reported. Linear and nonlinear regression analyses were performed.

Results

—

Middle cerebral artery and internal carotid artery mean flow velocity were lower in older patients (median 76 versus 114 cm/s and 76 versus 126 cm/s, respectively;
P
<0.003). Incidence of symptomatic vasospasm was lower in older patients (44% versus 66%;
P
=0.05). Older patients developed symptomatic vasospasm at lower middle cerebral artery (median 57 versus 103 cm/s;
P
=0.04) and internal carotid artery (median 54 versus 81 cm/s,
P
=0.02) mean flow velocity. Relationship between middle cerebral artery and internal carotid artery mean flow velocity and age was quadratic (ANOVA,
P
<0.0001).

Conclusions

—

Older patients have a lower incidence of symptomatic vasospasm, and such vasospasm develops at lower cerebral blood flow velocity than younger patients. A quadratic relationship was found between age and cerebral blood flow velocity. This model could be used to create an age-adjusted nomogram that might improve diagnostic capabilities of transcranial Doppler.
Depressive Disorder, Dysthymia, and Risk of Stroke
Authors: Larson Sharon L. , Owens Pamela L. , Ford Daniel , Eaton William
Published: October 2007

Background and Purpose
—

This study examined depressive disorder as a risk factor for incident stroke in a prospective, population-based design.

Methods
—

The Baltimore Epidemiologic Catchment Area Study is a prospective 13-year follow-up of a probability sample of household residents from Baltimore, Md. Depressive disorder was measured with the diagnostic interview schedule, and stroke was assessed by questions from the health interview survey or by documentation on a death certificate.

Results
—

During the 13-year follow-up of 1703 individuals, 66 strokes were reported and 29 strokes were identified by death certificate search. Individuals with a history of depressive disorder were 2.6 times more likely to report stroke than those without this disorder after controlling for heart disease, hypertension, diabetes, and current and previous use of tobacco. Medications used in the treatment of depressive disorder at baseline did not alter this finding. A history of dysthymia demonstrated a similar relationship to stroke, although the estimate was not statistically significant.

Conclusions
—

Depressive disorder is a risk factor for stroke that appears to be independent of traditional cardiovascular risk factors. Further research on mechanisms for the association and the impact of treatment for depressive disorder on subsequent stroke is needed.
Feasibility and Safety of Moderate Hypothermia After Massive Hemispheric Infarction
Authors: Schwab Stefan , Georgiadis Dimitrios , Berrouschot Jörg , Schellinger Peter D. , Graffagnino Carmelo , Mayer Stephan A.
Published: October 2007

Background and Purpose

—

Moderate hypothermia decreases ischemic damage in experimental stroke models. This multicenter study was performed to evaluate (1) the safety and feasibility of moderate hypothermia and (2) its potential to reduce intracranial hypertension in acute stroke patients.

Methods

—

Fifty prospective patients with cerebral infarction involving at least the complete middle cerebral artery territory treated with moderate hypothermia were evaluated. Hypothermia was induced with the use of cooling blankets as well as alcohol and ice bags within 22±9 hours after stroke onset and maintained for 24 to 72 hours; subsequently, patients passively rewarmed over a mean duration of 17 hours. Outcome was assessed at 4 weeks and at 3 months.

Results

—

Time required for cooling to <33°C varied from 3.5 to 11 hours. The most frequent complications of hypothermic therapy were thrombocytopenia (70%), bradycardia (62%), and pneumonia (48%). Four patients (8%) died during hypothermia as a result of severe coagulopathy, cardiac failure, or uncontrollable intracranial hypertension. An additional 15 patients (30%) died during or after rewarming because of rebound increase in intracranial pressure (ICP) and fatal herniation. A shorter (<16 hours) rewarming period was associated with a more pronounced rise of ICP. Elevated ICP values were significantly reduced under hypothermia. Neurological outcome according to the National Institutes of Health Stroke Scale score 4 weeks after stroke was 29, and Rankin Scale score 3 months after stroke was 2.9.

Conclusions

—

Moderate hypothermia is feasible in patients with acute stroke, although it is associated with several side effects. Most deaths occur during rewarming as a result of excessive ICP rise. Our preliminary observation that a longer duration of the rewarming period limits the ICP increase remains to be confirmed in future studies.
Population Group Differences in Trends in Stroke Mortality in Israel
Authors: Koton S. , Bornstein N.M. , Green M.S.
Published: October 2007

Background and Purpose

—

In Israel, stroke is the third most common cause of death. In 1997 stroke accounted for 2905 deaths (8.1% of total), 1390 of them among men (7.5% of total; crude mortality rate of 48.3/100 000) and 1515 among women (8.6% of total; crude rate of 51.7/100 000). This report presents trends on stroke mortality by population group and estimates of morbidity in Israel.

Methods

—

Data on stroke mortality in Israel during 1969–1997 were obtained from the Israel Central Bureau of Statistics. Age-specific and age-adjusted mortality rates were calculated for the 2 main population groups. Data on morbidity were obtained form the 1996/1997 National Health Survey. Hospitalization rates due to stroke are based on the national hospitalization data.

Results

—

A monotonic decrease in stroke mortality is evident in Jews during 1969–1997 in both sexes. Age-adjusted mortality rates declined by 62.5% for Jewish men and by 73.4% for Jewish women during 1969–1997. Among Arabs, there was a general decreasing trend in the mortality for both sexes during 1973–1997. The main difference in population group mortality trends was found in the group aged ≥75 years: a statistically significant decrease in mortality rates for Jews is evident, while no decrease is apparent for Arabs. On the basis of available data for 1990, an estimated 13 000 patients with stroke were hospitalized during 1997.

Conclusions

—

During the last 25 years, age-adjusted stroke mortality in Israel has declined substantially, but the decline has been much greater among Jews than Arabs. The group aged ≥75 years shows the greatest difference in trends between Jews and Arabs. This finding may be explained by differences in risk factor distribution and case fatality rates.
B-Mode Flow Imaging of the Carotid Artery
Authors: Umemura Atsushi , Yamada Kazuo
Published: October 2007

Background and Purpose—

B-mode ultrasonography has been used to evaluate cervical carotid artery lesions. Recently, the technology for direct visualization of blood reflectors has made B-mode flow imaging (B-flow) possible without the limitations of Doppler technology. We evaluated the efficacy of B-flow in examining the cervical carotid artery.

Methods—

Sixty patients with ischemic cerebrovascular disease were examined. Conventional B-mode imaging and blood flow images by power Doppler imaging (PDI) and B-flow were obtained.

Results—

B-flow enabled simultaneous imaging of tissue and blood flow. Compared with PDI, B-flow provided higher spatial resolution and higher frame rate hemodynamic imaging. Consequently, a clear definition of the vessel lumen was obtained even in the stenotic portion of the carotid artery. In evaluating the degree of carotid stenosis, B-flow measurement agreed with digital subtraction angiography as well as PDI measurement. In addition, bloodstream swirl at the site of wall ulceration or vascular elongation was observed.

Conclusions—

B-flow was prominent in visualizing hemodynamic flow and detection of stenotic lesion in the cervical carotid artery. Combined with conventional B-mode technique, B-flow seems to be useful in evaluating carotid stenosis.
Bone Morphogenetic Protein-6 Reduces Ischemia-Induced Brain Damage in Rats
Authors: Wang Yun , Chang Chen-Fu , Morales Marisela , Chou Jenny , Chen Hui-Ling , Chiang Yung-Hsiao , Lin Shinn-Zong , Cadet Jean Lud , Deng Xiaolin , Wang Jia-Yi , Chen Su-Yu , Kaplan Paul L. , Hoffer Barry J.
Published: October 2007

Background and Purpose

—

Bone morphogenetic protein-6 (BMP6) and its receptors are expressed in adult and fetal brain. Receptors for BMP6 are upregulated in adult brain after injury, leading to the suggestion that BMP6 is involved in the physiological response to neuronal injury. The purpose of this study was to determine whether there was a neuroprotective effect of BMP6 in vivo and in vitro.

Methods

—

Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP6 against H
2
O
2
in primary cortical cultures. The neuroprotective effects of BMP6 were also studied in chloral hydrate-anesthetized rats. BMP6 or vehicle was injected into right cerebral cortex before transient right middle cerebral artery (MCA) ligation. Animals were killed for triphenyl-tetrazolium chloride staining, caspase-3 immunoreactivity and enzymatic assays, and TUNEL assay. A subgroup of animals were used for locomotor behavioral assays.

Results

—

Application of H
2
O
2
increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment. Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats. Pretreatment with BMP6 did not alter cerebral blood flow or physiological parameters. There was decreased ischemia-induced caspase-3 immunoreactivity, caspase-3 enzymatic activity, and density of TUNEL-positive cells in ischemic cortex in BMP6-treated animals.

Conclusions

—

BMP6 reduces ischemia/reperfusion injury, perhaps by attenuating molecular events underlying apoptosis.
Behavioral/Environmental Intervention Improves Learning After Cerebral Hypoxia-Ischemia in Rats
Authors: Chou I-Ching , Trakht Tatyana , Signori Carina , Smith Julia , Felt Barbara T. , Vazquez Delia M. , Barks John D.E.
Published: October 2007

Background and Purpose

—

In premature infants, many of whom experience ischemic brain insults, the environment of rearing influences cognitive outcome. We developed a model to evaluate the effect of rearing conditions on learning after unilateral cerebral hypoxia-ischemia (HI) in 7-day-old (P7) rats. We hypothesized that neonatal handling would benefit rats recovering from an episode of HI.

Methods

—

Seventeen litters of P7 Long-Evans rats underwent either HI (right carotid ligation followed by 1.5 hours in 8% O
2
) or control procedures. From P8 to P14, randomized litters were either handled (15 minutes of separation from dam per day) or nonhandled. After P55, learning was tested in the Morris water maze. To evaluate injury severity, hippocampal, cortical, and striatal volumes were measured.

Results

—

In water-maze performance, ANCOVA revealed an interaction between handling and severity of hippocampal damage. Among HI rats, handled rats learned faster when hippocampal damage was moderate (
P
<0.01, repeated-measures ANOVA), with no benefit when damage was mild or severe.

Conclusions

—

These observations suggest the beneficial cognitive effect of neonatal handling was limited to animals with moderate damage. Neonatal handling in post-HI rats may be a useful model in which to study mechanisms underlying the benefits of post-HI developmental intervention.
Early Carotid Endarterectomy for Critical Carotid Artery Stenosis After Thrombolysis Therapy in Acute Ischemic Stroke in the Middle Cerebral Artery
Authors: McPherson Christopher M. , Woo Daniel , Cohen Paul L. , Pancioli Arthur M. , Kissela Brett M. , Carrozzella Janice A. , Tomsick Thomas A. , Zuccarello Mario
Published: October 2007

Background and Purpose

—

Tissue plasminogen activator (tPA) has been shown to be effective for acute ischemic stroke. However, if a high-grade cervical carotid stenosis remains despite tPA therapy, patients are at risk for recurrent stroke. Carotid endarterectomy (CEA) has been shown to be effective in symptomatic patients with high-grade cervical carotid stenosis in reducing the risk of stroke, but it is unknown whether CEA can be performed safely after tPA thrombolysis. We describe our experience with 5 patients who underwent early (<48 hours) CEA for residual high-grade cervical carotid stenosis after thrombolytic therapy for acute ischemic stroke in the middle cerebral artery territory.

Methods

—

All patients had a critical (>99%) carotid artery stenosis on the symptomatic side after tPA therapy. All patients received intravenous tPA; 3 patients also received intra-aortic tPA. Three patients received intravenous heparin infusion immediately after administration of tPA. All patients showed marked improvement in their National Institutes for Health Stroke Scale scores after treatment with tPA. CEA was then performed within 45 hours (6 hours in 1 patient, 23 hours in 2, 26 hours in 1, and 45 hours in 1).

Results

—

All 5 patients underwent successful CEA. There were no complications related to surgery. At discharge, 2 patients had a normal examination, and the remaining patients had mild deficits. In a long-term follow-up of 5 to 22 months, no patient had a recurrent cerebrovascular event.

Conclusions

—

Early CEA can be performed safely and successfully in patients after tPA treatment for acute ischemic stroke in appropriately selected patients.
Intrathecal Baclofen for Spastic Hypertonia From Stroke
Authors: Meythaler Jay M. , Guin-Renfroe Sharon , Brunner Robert C. , Hadley Mark N.
Published: October 2007

Background and Purpose
—

We sought to determine whether continuous intrathecal delivery of baclofen can effectively decrease spastic hypertonia due to stroke.

Methods
—

Stroke patients with >6 months of intractable spasticity were screened via a randomized, double-blind, placebo-controlled crossover design of either intrathecal normal saline or 50 μg baclofen. Those who dropped an average of 2 points in either their affected lower extremity side Ashworth or Penn spasm frequency scores were then offered computer-controlled pump implantation for continuous ITB and followed prospectively for up to 12 months.

Results
—

In 21 stroke patients 6 hours after the active drug bolus, the average (±SD) lower extremity Ashworth score on the affected extremities decreased from 3.3±1.2 to 1.4±0.7 (
P
<0.0001), spasm score from 1.2±1.2 to 0.1±0.3 (
P
=0.0224), and reflex score from 2.1±1.2 to 0.1±0.5 (
P
<0.0001). The average upper extremity Ashworth score on the affected extremities decreased from 2.8±1.1 to 1.8±0.8 (
P
<0.0001), spasm score from 0.7±1.0 to 0.2±0.4 (
P
=0.1544), and reflex score from 2.1±0.9 to 1.2±0.9 (
P
=0.0004). All active drug scores were statistically different from placebo scores at 6 hours (
P
<0.05). With up to 12 months of continuous infusion of ITB in 17 implanted patients, the average lower extremity Ashworth score on the affected extremities decreased from 3.7±1.0 to 1.8±1.1 (
P
<0.0001), the spasm score dropped from 1.2±1.3 to 0.6±1.0 (
P
=0.4282), and the reflex score decreased from 2.4±1.3 to 1.0±1.3 (
P
<0.0001). The average upper extremity Ashworth score in the affected extremities decreased from 3.2±1.1 to 1.8±0.9 (
P
<0.0001), the spasm score dropped from 0.7±1.0 to 0.3±0.8 (
P
=0.8685), and the reflex score decreased from 2.4±0.8 to 1.5±1.2 (
P
=0.3337). The average continuous ITB dose required to attain these effects was 268 μg/d.

Conclusions
—

Intrathecal infusion of baclofen is capable of maintaining a reduction in the spastic hypertonia resulting from stroke.
Endothelium-Derived Endothelin-1 Reduces Cerebral Artery Sensitivity to Nitric Oxide by a Protein Kinase C–Independent Pathway
Authors: Gilbert Patricia , Tremblay Johanne , Thorin Eric
Published: October 2007

Background and Purpose

—

Nitric oxide (NO) reduces endothelin-1 (ET-1) production and blunts ET-1 dependent vasoconstriction. The direct effects of smooth muscle ET
A
receptor stimulation on NO-mediated relaxation are unknown. We hypothesized that endothelium-derived ET-1 regulates vascular tone by reducing smooth muscle sensitivity to NO, possibly through activation of protein kinase C (PKC).

Methods

—

Rings of rabbit middle cerebral artery were mounted on microvessel myographs to measure isometric tension. Dose-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP; an NO donor) were obtained with or without ET-1 receptor blockade. Experiments were performed in the presence of indomethacin (10 μmol/L). Results are expressed as mean±SEM.

Results

—

In depolarized conditions (40 mmol/L KCl physiological solution), ACh-induced relaxation was entirely NO-dependent, as indicated by its suppression by

N
ω

-nitro-
l
-arginine (
P
<0.05). Arterial sensitivity (pD
2
) to ACh (6.32±0.11, n=6) was increased (
P
<0.05) to 6.77±0.10 (n=6) by BQ123 (ET
A
receptor antagonist, 5 μmol/L) but not by BQ788 (ET
B
receptor antagonist, 5 μmol/L; 6.08±0.22, n=5). Consistent with this finding, blockade of ET
A
receptors increased (
P
<0.05) vascular sensitivity to SNP (6.95±0.10, n=8), whereas BQ788 had no influence on arterial sensitivity to SNP (6.17±0.07, n=7) compared with control (6.43±0.13, n=11). In denuded arteries, the sensitivity to SNP (7.10±0.08, n=8) was reduced by exogenous ET-1 (6.51±0.35, n=7,
P
<0.05). Chelerythrine, a PKC inhibitor, did not alter smooth muscle sensitivity to NO, whereas phorbol 12-myristate 13-acetate, a PKC activator, strongly increased it.

Conclusions

—

Blockade of ET
A
but not ET
B
receptors sensitizes vascular smooth muscle to exogenous and endothelium-derived NO. This suggests that ET-1 regulates smooth muscle sensitivity to NO by a PKC-independent pathway. This represents an alternative pathway by which NO and ET-1 interact to regulate vascular tone.
Nimodipine in Animal Model Experiments of Focal Cerebral Ischemia
Authors: Horn J. , de Haan R.J. , Vermeulen M. , Luiten P.G.M. , Limburg M.
Published: October 2007

Background and Purpose
—

Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials.

Methods
—

We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Embase. We assessed whether these studies showed a beneficial effect of active treatment. In-depth analyses were performed on infarct size and amount of edema, and subgroup analyses were performed on the length of the time window to the initiation of treatment and the methodological quality of the studies.

Results
—

Of 225 identified articles, 20 studies were included. The methodological quality of the studies was poor. Of the included studies, 50% were in favor of nimodipine. In-depth analyses showed statistically significant effects in favor of treatment (10 studies). No influence of the length of time to the initiation of treatment or of the methodological quality on the results was found.

Conclusions
—

We conclude that the results of this review did not show convincing evidence to substantiate the decision to perform trials with nimodipine in large numbers of patients. There were no differences between the results of the animal experiments and clinical studies. Surprisingly, we found that animal experiments and clinical studies ran simultaneously.
Reversal of Early Diffusion-Weighted Magnetic Resonance Imaging Abnormalities Does Not Necessarily Reflect Tissue Salvage in Experimental Cerebral Ischemia
Authors: Ringer Thomas M. , Neumann-Haefelin Tobias , Sobel Raymond A. , Moseley Michael E. , Yenari Midori A.
Published: October 2007

Background and Purpose

—

Diffusion-weighted MRI (DWI) can detect early ischemic changes and is sometimes used as a surrogate neurological end point in clinical trials. Recent experimental stroke studies have shown that with brief periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal.

Methods

—

Rats underwent 30 minutes of middle cerebral artery occlusion followed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours, n=5; 7 days, n=5) with the use of neuronal (microtubule-associated protein 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat-shock protein 72 (HSP72).

Results

—

DWI abnormalities reversed 3 to 5 hours after ischemia onset but recurred at 1 day. Four animals showed complete reversal of the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour DWI was completely normal, there was significant loss of MAP2 immunoreactivity, comprising approximately 30% of the initial DWI lesion. However, GFAP staining revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was extensive and corresponded to the initial DWI lesion.

Conclusions

—

After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal. Neurons already exhibit evidence of structural damage and stress. Normal GFAP staining suggests that other nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injury. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.
Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by Neurological History and Examination
Authors: Jones William J. , Williams Linda S. , Meschia James F.
Published: October 2007

Background and Purpose

—

The Questionnaire for Verifying Stroke-Free Status (QVSFS) is an 8-item structured interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review in a cohort with a low prevalence (7.1%) of stroke or transient ischemic attack (TIA). The objective of this study was to evaluate the validity of the QVSFS by comparing it with stroke status as determined by neurological history and examination in a population with a higher prevalence of stroke.

Methods

—

A research assistant administered the QVSFS to outpatients from Veterans Administration stroke and general medicine clinics. Subjects were defined as QVSFS negative if responses to all 8 questions were negative. Questions requiring rephrasing or clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and examined all subjects to determine stroke-free status, defined as no history or examination findings of previous stroke and/or TIA.

Results

—

One hundred fifty-five subjects were examined; mean age was 70 years; 98.1% were male. Seventy-eight subjects were determined to be stroke free by the neurologist. The negative predictive value of the QVSFS was 0.96, with positive predictive value of 0.71. No question required rephrasing or clarification >5 times. Twenty-two subjects (14.2%) required rephrasing or clarification of at least 1 question.

Conclusions

—

The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population with a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke and/or TIA is lower, but the QVSFS may still be useful as a screening tool in that regard.
Nonrandomized Comparison of Local Urokinase Thrombolysis Versus Systemic Heparin Anticoagulation for Superior Sagittal Sinus Thrombosis
Authors: Wasay M. , Bakshi R. , Kojan S. , Bobustuc G. , Dubey N. , Unwin D.H.
Published: October 2007

Background and Purpose

—

We sought to compare the safety and efficacy of direct urokinase thrombolysis with systemic heparin anticoagulation for superior sagittal sinus thrombosis (SSST).

Methods

—

At University at Buffalo (NY) and University of Texas (Dallas, Houston), we reviewed 40 consecutive patients with SSST, treated with local urokinase (thrombolysis group) or systemic heparin anticoagulation (heparin group). The thrombolysis group (n=20) received local urokinase into the SSS followed by systemic heparin anticoagulation. The heparin group (n=20) received systemic heparin anticoagulation only. Neurological dysfunction was rated as follows: 0, normal; 1, mild (but able to ambulate and communicate); 2, moderate (unable to ambulate, normal mentation); and 3, severe (unable to ambulate, altered mentation).

Results

—

Age (
P
=0.49), sex (
P
=0.20), baseline venous infarction (
P
=0.73), and predisposing illnesses (
P
=0.52) were similar between the thrombolysis and heparin groups. Pretreatment neurological function was worse in the thrombolysis group (normal, n=5; mild, n=8; moderate, n=4; severe, n=3) than in the heparin group (normal, n=8; mild, n=8; moderate, n=3; severe, n=1) (
P
=NS). Discharge neurological function was better in the thrombolysis group (normal, n=16; mild, n=3; moderate, n=1; severe, n=0) than in the heparin group (normal, n=9; mild, n=6; moderate, n=5; severe, n=0) (
P
=0.019, Mann-Whitney
U
test). Hemorrhagic complications were 10% (n=2) in the thrombolysis group (subdural hematoma, retroperitoneal hemorrhage) and none in the heparin group (
P
=0.49). Three of the heparin group patients developed complications of the underlying disease (status epilepticus, hydrocephalus, refractory papilledema). No deaths occurred. Length of hospital stay was similar between the groups (
P
=0.79).

Conclusions

—

Local thrombolysis with urokinase is fairly well tolerated and may be more effective than systemic heparin anticoagulation alone in treating SSST. A randomized, prospective study comparing these 2 treatments for SSST is warranted.
Role of Conventional Angiography in Evaluation of Patients With Carotid Artery Stenosis Demonstrated by Doppler Ultrasound in General Practice
Authors: Qureshi Adnan I. , Suri M. Fareed K. , Ali Zulfiqar , Kim Stanley H. , Fessler Richard D. , Ringer Andrew J. , Guterman Lee R. , Budny James L. , Hopkins L. Nelson
Published: October 2007

Background and Purpose

—

Previous studies have suggested that patients with carotid stenosis who are candidates for endarterectomy can be effectively identified on the basis of carotid Doppler ultrasound alone. Before widespread acceptance of this policy, the accuracy of carotid Doppler ultrasound outside selected centers and clinical trials needs to be evaluated. We performed a 12-month prospective study to evaluate the accuracy of Doppler ultrasound in identifying patients for carotid intervention in general practice settings.

Methods

—

Each patient referred to our endovascular service for diagnostic angiography to evaluate for carotid stenosis was interviewed and examined by a neurologist. Subjects consisted of symptomatic patients with ≥50% stenosis and asymptomatic patients with ≥60% stenosis by Doppler ultrasound. Information pertaining to demographic and cerebrovascular risk factors and the results of the carotid Doppler ultrasound were recorded. The severity of stenosis on angiograms was measured with North American Symptomatic Carotid Endarterectomy Trial criteria by a blinded observer. The results of both studies were compared to determine the relative accuracy of ultrasound results.

Results

—

Of 130 patients (mean age, 69±8.8 years) who met Doppler ultrasound criteria, 22 (17%) and 8 patients (6%) were found to have 30% to 49% or <30% stenosis by angiography, respectively. The positive predictive value of carotid Doppler ultrasound for identifying appropriate symptomatic candidates for carotid intervention (angiographic stenosis ≥50%) was 80%, with a false-positive value of 20%. The positive predictive value of carotid Doppler ultrasound for identifying appropriate asymptomatic candidates for carotid intervention (angiographic stenosis ≥60%) was 59%, with a false-positive value of 41%. Carotid endarterectomy or angioplasty and stent placement were undertaken subsequently in 60 (46%) of the patients. In 94 patients who underwent cerebral angiography alone, no complications were observed.

Conclusions

—

The present accuracy of carotid Doppler ultrasound in general practice does not justify its use as the sole basis of selecting appropriate patients for carotid intervention. Given the relatively low rate of associated morbidity with present day techniques, additional confirmatory studies such as angiography should be performed in every patient before a decision regarding intervention is made.
Longitudinal Changes of Metabolites in Frontal Lobes After Hemorrhagic Stroke of Basal Ganglia
Authors: Kobayashi Masahito , Takayama Hideichi , Suga Sadao , Mihara Ban
Published: October 2007

Background and Purpose
—

We investigated serial metabolic changes in frontal lobes of patients with deep intracerebral hemorrhage (ICH) to examine the correlation between
N
-acetylaspartate (NAA) and degree of motor impairment or clinical outcome.

Methods
—

Twenty patients with deep ICH were examined with proton magnetic resonance spectroscopy with the application of a multivoxel method (1 voxel=10×10×20 mm; 64 voxels). NAA/creatine ratios in the white matter of the primary motor and premotor areas on both sides were measured sequentially: within 48 hours, at 2 weeks, and 1 month after onset. The National Institutes of Health Stroke Scale and Barthel Index for disability were measured for each patient.

Results
—

In the primary motor area on the affected side, where the hematoma did not extend, the NAA/creatine ratio decreased sequentially. At 48 hours and 2 weeks after onset, a negative correlation was detected between NAA/creatine and hematoma volume, but there was no correlation 1 month later. At 2 weeks, NAA/creatine correlated negatively with motor impairment (
r
=−0.750), and there was a significant correlation with clinical outcome as early as 2 weeks after onset (
r
=0.954). These sequential changes of NAA/creatine varied according to patients’ long-term clinical outcome. Patients with poor outcome demonstrated notable reduction of NAA/creatine over the bilateral frontal lobes.

Conclusions
—

The delayed gradual reduction of NAA/creatine ratio in the frontal lobes correlates with motor deficit and clinical outcome after deep ICH, suggesting that the neural networks in the frontal lobe could be important for recovery.
Deep Cerebral Infarcts Extending to the Subinsular Region
Authors: Wong Edward H. , Pullicino Patrick M. , Benedict Ralph
Published: October 2007

Background and Purpose
—

We sought to determine the clinical and radiological features and pathogenesis of deep cerebral infarcts extending to the subinsular region (DCIs).

Methods
—

We defined DCIs as subcortical infarcts extending between the lateral ventricle and the subinsular region with a paraventricular extent >1.5 cm and a subinsular extent of at least one third of the anteroposterior extent of the insula. We identified patients by review of imaging records and noted the clinical information, risk factors, and investigations. We compared risk factors and clinical features between DCIs and “internal border zone” infarcts restricted to the paraventricular region.

Results
—

Eight patients were studied. The typical clinical features of DCIs were hemiparesis, aphasia, dysarthria, and dysphagia. Aphasia was seen in 3 of 5 patients with left-sided infarcts. Six of 8 patients (75%) had hypoperfusion as a possible pathogenetic factor (carotid occlusion in 4, surgical clipping of MCA in 1, low ejection fraction in 1), and 3 patients (38%) had cardioembolism as a possible pathogenetic factor (atrial fibrillation in 2, low ejection fraction in 1). One patient (12%) had no cause for stroke. Clinical features were similar to those for paraventricular infarcts. Carotid occlusion was more frequent (
P
=0.04), and there was a trend toward a higher frequency of hypertension (
P
<0.1) and smoking with DCIs than with paraventricular infarcts. DCIs were located in a deep vascular border zone.

Conclusions
—

The clinical features and pathogenesis of DCIs overlap with those of internal border zone paraventricular infarcts. Hypoperfusion may give rise to DCIs since large-artery occlusion is their main risk factor. The larger size of DCIs compared with paraventricular infarcts may relate to a poorer collateral blood supply.
Effect of Antiplatelet and Anticoagulant Agents on Risk of Hospitalization for Bleeding Among a Population of Elderly Nursing Home Stroke Survivors
Authors: Quilliam Brian J. , Lapane Kate L. , Eaton Charles B. , Mor Vincent
Published: October 2007

Background and Purpose

—

Anticoagulants and antiplatelet agents are underutilized in the nursing home setting, perhaps because trials demonstrating treatment efficacy excluded people resembling those with long-term care needs. We sought to quantify the effect of antiplatelet and anticoagulant agents on risk of hospitalization for bleeding among an elderly nursing home population.

Methods

—

We used a case-control design and identified first hospitalizations for bleeds using Medicare claims data from 1992 to 1997 as potential cases. Cases had at least one minimum data set (MDS) assessment within the 6 months before that hospitalization and a diagnosis of stroke. We identified up to 5 controls residing in the same facility during the same year and quarter as the case with a diagnosis of stroke. Our sample consisted of 3433 cases and 13 506 controls. Using the MDS, we identified standing orders for aspirin, dipyridamole, ticlopidine, or warfarin and used conditional logistic regression modeling to estimate the effect of these agents on risk of hospitalization for a bleed.

Results

—

After adjustment, use of warfarin (odds ratio [OR], 1.26; 95% CI, 1.11 to 1.43) and combination therapy (OR, 1.34; 95% CI, 0.99 to 1.82) were associated with an increased risk of hospitalization for a bleed compared with nonusers. The odds of aspirin use was greater among cases than controls (OR, 1.07; 95% CI, 0.96 to 1.18) after adjustment.

Conclusions

—

Although present, the risk associated with use of these agents is small. The numbers needed to treat to harm 1 resident with aspirin and warfarin were 467 and 126, respectively.
Reduction and Restoration of Mitochondrial DNA Content After Focal Cerebral Ischemia/Reperfusion
Authors: Chen Hong , Hu Chaur-Jong , He Yong Y. , Yang Ding-I , Xu Jan , Hsu Chung Y.
Published: October 2007

Background and Purpose
—

Oxidative damage of mitochondrial DNA (mtDNA) in the ischemic brain is expected after ischemia/reperfusion injury. A recent study demonstrated limited patterns of mtDNA deletion in the brain after ischemia/reperfusion. We studied the ischemia/reperfusion-induced global changes of mtDNA integrity and its restoration in a rat model of transient focal ischemia in vivo.

Methods
—

Changes in mtDNA content in the ischemic brain were assessed with the use of a rat stroke model featuring transient severe ischemia confined to the cerebral cortex of the right middle cerebral artery territory for 30 or 90 minutes. A new long polymerase chain reaction method, using mouse DNA as an internal standard, was applied to measure the relative content of intact rat mtDNA. Southern hybridization following alkaline gel electrophoresis was conducted in a parallel study to confirm long polymerase chain reaction results.

Results
—

A reduction in mtDNA content was found after ischemia for 30 and 90 minutes. The mtDNA was restored to near nonischemic levels 24 hours after 30- but not 90-minute ischemia.

Conclusions
—

These results confirm that ischemia/reperfusion causes mtDNA damages. Restoration of the mtDNA content to nonischemic levels after 30-minute ischemia raises the possibility that mtDNA repair or repletion occurs after brief ischemia.
Transcranial Doppler Versus Angiography in Patients With Vasospasm due to a Ruptured Cerebral Aneurysm
Authors: Lysakowski Christopher , Walder Bernhard , Costanza Michael C. , Tramèr Martin R.
Published: October 2007

Background and Purpose

—

Transcranial Doppler (TCD) is used for diagnosis of vasospasm in patients with subarachnoid hemorrhage due to a ruptured aneurysm. Our aim was to evaluate both the accuracy of TCD compared with angiography and its usefulness as a screening method in this setting.

Methods

—

A search (MEDLINE, EMBASE, Cochrane Library, bibliographies, hand searching, any language, through January 31, 2001) was performed for studies comparing TCD with angiography. Data were critically appraised using a modified published 10-point score and were combined using a random-effects model.

Results

—

Twenty-six reports compared TCD with angiography. Median validity score was 4.5 (range 1 to 8). Meta-analyses could be performed with data from 7 trials. For the middle cerebral artery (5 trials, 317 tests), sensitivity was 67% (95% CI 48% to 87%), specificity was 99% (98% to 100%), positive predictive value (PPV) was 97% (95% to 98%), and negative predictive value (NPV) was 78% (65% to 91%). For the anterior cerebral artery (3 trials, 171 tests), sensitivity was 42% (11% to 72%), specificity was 76% (53% to 100%), PPV was 56% (27% to 84%), and NPV was 69% (43% to 95%). Three of these 7 studies reported on the same patients, each on another artery, and for 4, data recycling could not be disproved. Other arteries were tested in only 1 trial each.

Conclusions

—

For the middle cerebral artery, TCD is not likely to indicate a spasm when angiography does not show one (high specificity), and TCD may be used to identify patients with a spasm (high PPV). For all other situations and arteries, there is either lack of evidence of accuracy or of any usefulness of TCD. Most of these data are of low methodological quality, bias cannot not be ruled out, and data reporting is often uncritical.
Critical Analysis of Cerebrovascular Autoregulation During Repeated Head-Up Tilt
Authors: Hughson Richard L. , Edwards Michael R. , O’Leary Deborah D. , Shoemaker J. Kevin
Published: October 2007

Background and Purpose

—

Cerebrovascular autoregulation has been described with a phase lead of cerebral blood flow preceding changes in cerebral perfusion pressure (CPP), but there has been less focus on the effect of CPP on cerebral vascular resistance. We investigated these relations during spontaneous fluctuations (control) and repeated head-up tilt.

Methods

—

Eight healthy adults were studied in supine rest and repeated tilt with 10-second supine, 10 seconds at 45° head-up tilt for a total of 12 cycles. Cerebral blood flow was estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP was estimated from corrected finger pressure (CPP
F
), and cerebrovascular resistance index (CVRi) was calculated in the supine position from CPP
F
/MFV. Gain and phase relations were assessed by cross-spectral analysis.

Results

—

In the supine position, MFV preceded CPP
F
, but changes in CVRi followed CPP
F
. Gain and phase relations for CPP
F
as input and MFV as output were similar in supine and repeated tilt experiments. Thus, changes in cerebrovascular resistance must have had a similar pattern in the supine and tilt experiments.

Conclusions

—

Cerebrovascular autoregulation is achieved by changes in resistance in response to modulations in perfusion pressure whether spontaneous or induced by repeated tilt. The phase lead of MFV before CPP
F
is a mathematical and physiological consequence of the relation the input variable (CPP
F
) and the manipulated variable (cerebrovascular resistance) that should not be taken as an indication of independent control of cerebral blood flow.