摘要:

Background and Purpose—Thrombolysis with alteplase is used in acute ischemic stroke within 3 hours after symptom onset in many stroke centers, but experience remains limited in Europe.Methods—Using eligibility and management criteria similar to those published by the American Heart Association, we treated 75 consecutive patients aged 21 to 83 years (mean age, 63.6 years; median Scandinavian Stroke Scale score, 32/58) with hemispheric infarction with alteplase in 1998–2001. Their neuroradiological findings (ischemic and hemorrhagic changes) and functional outcome at 3 months were evaluated.Results—Sixty-one percent of the patients had recovered functional independence (Barthel Index 95 to 100) at the 3-month follow-up. On the modified Rankin Scale (mRS), 37% (28/75) of patients had no or minimal symptoms (mRS 0 to 1), while 17% (13/75) remained dependent (mRS 4 to 5) and 5% (4/75) died. Cerebral parenchymal hematomas occurred in 8% (6/75) and hemorrhagic transformation in 8% (6/75) of the patients. Low initial diastolic blood pressure and administration of intravenous antihypertensive medication were associated with unfavorable outcome (mRS 3 to 6).Conclusions—We conclude that our management protocol for thrombolytic therapy is safe. These rates of functional outcome, case fatality, and hemorrhagic cerebral events compare favorably with those of other published series of stroke thrombolysis with similar time windows and management guidelines. Associations between blood pressure and its treatment during thrombolysis with functional outcome deserve further analysis.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—Previous studies suggest that undernourished patients with acute stroke do badly. The data, however, are not robust. We aimed to reliably assess the importance of baseline nutritional status as an independent predictor of long-term outcome after stroke in a large prospective cohort enrolled in the Feed Or Ordinary Diet (FOOD) trial, a multicenter randomized trial evaluating various feeding policies.Methods—Patients admitted to hospital with a recent stroke were enrolled in the FOOD trial. Data on nutritional status and other clinical predictors of outcome were collected at trial entry. At 6 months, the coordinating center collected data on survival and functional status (modified Rankin Scale). Outcome assessment was done by researchers blinded to baseline assessments and treatment allocation.Results—Between November 1996 and November 2001, 3012 patients were enrolled, and 2955 (98%) were followed up. Of the 275 undernourished patients, 102 (37%) were dead by final follow-up compared with only 445 (20%) of 2194 patients of normal nutritional status (odds ratio [OR], 2.32; 95% CI, 1.78 to 3.02). After adjustment for age, prestroke functional state, and stroke severity, this relationship, although weakened, still held (OR, 1.82; 95% CI, 1.34 to 2.47). Undernourished patients were more likely to develop pneumonia, other infections, and gastrointestinal bleeding during their hospital admission than other patients.Conclusions—These data provide reliable evidence that nutritional status early after stroke is independently associated with long-term outcome. It supports the rationale for the FOOD trial, which continues to recruit and aims to estimate the effect of different feeding regimes on outcome after stroke and thus determine whether the association observed in this study is likely to be causal.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—This article examines stroke recurrence and whether the subtype of the initial stroke influences the risk and subtypes of further strokes. The proportion of recurrences attributable to conventional risk factors is quantified.Methods—From January 1995 to August 2000, all first-in-a-lifetime strokes (n=1626) were identified and prospectively followed up in a defined multiethnic inner city population of 234 533. Twelve overlapping referral sources and face-to-face follow-up at 3 months and 1 and 3 years were used to attain complete registration of stroke recurrence. Index and recurrent stroke were classified according to the Oxford Community Stroke Project classification.Results—In 2744 person-years of follow-up, 153 recurrences were observed. At 5 years, the cumulative risk of first stroke recurrence was 16.6% (95% CI, 13.5 to 20.4), and the combined risk of death or stroke recurrence was 65.3% (95% CI, 61.9 to 68.6). Ethnicity and subtype of index stroke were not associated with stroke recurrence. A change in subtype between index and recurrent stroke occurred in 45.5% (95% CI, 35.8 to 55.2) of cases and was most frequent among index lacunar strokes and primary intracerebral hemorrhages. In multivariable analyses, diabetes mellitus and atrial fibrillation were associated with both stroke recurrence and recurrence-free survival. In the stroke population, 9.1% (95% CI, −2.0 to 20.2) of recurrences were attributable to diabetes and 4.9% (95% CI, −7.3 to 17.2) to atrial fibrillation during the first year after the index stroke.Conclusions—The cause of stroke recurrence is multifactorial, and the subtypes of index and recurrent strokes are often not identical. Most recurrences remain unexplained by conventional risk factors.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—In the 1980s, carotid endarterectomy was controversial because proof of efficacy was lacking, complication rates were high, and one third of cases were reported to be inappropriate. Since publication of several randomized controlled trials (RCTs), rates of carotid endarterectomy have doubled nationwide. This study assesses the appropriateness and use of carotid endarterectomy since publication of the RCTs.Methods—Using the literature, we developed a list of 1557 mutually exclusive indications for carotid endarterectomy and asked a panel of national experts to rate the appropriateness of each indication using the RAND methodology. We used these ratings to assess appropriateness in a sample of 2124 patients who underwent the procedure in 1997 to 1998 in 6 hospitals. We also analyzed the reasons for the procedure and rates of death, stroke, and myocardial infarction within 30 days of surgery.Results—Overall, 84.9% of operations were done for appropriate reasons, 4.5% for uncertain reasons, and 10.6% for inappropriate reasons. Among procedures considered inappropriate, the most common reasons were high comorbidity (46.6%) and minimal stenosis (27.1%). Overall, 72.5% were asymptomatic, 17.4% had a carotid transient ischemic attack, and 10.1% had a stroke. The 30-day rate of death or stroke was 5.47% for symptomatic patients and 2.26% for asymptomatic patients. Among patients having combined carotid and coronary artery bypass graft surgery, the rate was 10.32%. The complication rate in asymptomatic patients with high comorbidity was 5.56%.Conclusions—Since the RCTs, rates of overuse appear to have fallen considerably, although they are still significant. A major shift has occurred toward operating on asymptomatic patients. Although overall complication rates were low, rates among asymptomatic patients with high comorbidity exceeded recommended thresholds.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—P2receptors are important regulators of cerebrovascular tone. However, there is functional heterogeneity of P2Yreceptors along the vascular tree, and the functionality of P2Yreceptors in small arterioles has not been studied in detail. We investigated the effects of activating P2Y1and P2Y2receptors and their underlying dilator mechanisms in rat intracerebral arterioles.Methods—We used computer-aided videomicroscopy to measure diameter responses from isolated and pressurized rat penetrating arterioles (39.9±1.2 &mgr;m) to the natural P2receptor agonist ATP in addition to ADP-&bgr;-S (P2Y1-selective) and ATP-&ggr;-S (P2Y2-selective) and inhibitors of signaling pathways.Results—Extraluminal application of ATP-&ggr;-S and ADP-&bgr;-S initiated a biphasic response (initial constriction followed by the secondary dilation) similar to ATP-induced responses. Pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid (0.1 mmol/L; a P2Y1receptor antagonist) blocked ADP-&bgr;-S- but not ATP-&ggr;-S-induced dilation and affected the ATP-mediated dilation at low concentrations.N&ohgr;-Monomethyl-l-arginine partially inhibited the dilation of ATP and ADP-&bgr;-S but not ATP-&ggr;-S. High K+saline suppressed the dilation of all agonists. Indomethacin had no effect.Conclusions—Both P2Y1and P2Y2receptors are functionally present in cerebral arterioles. ATP stimulates P2Y1receptors at low concentrations, while high concentrations of ATP activate P2Y2in addition to P2Y1receptors. Nitric oxide is involved in P2Y1but not P2Y2receptor activation. Potassium channels play an important role in the regulation of P2Yreceptor-mediated dilation.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—Previous studies have shown that contractile endothelin type B (ETB) receptors are upregulated in cerebral arteries after experimental focal cerebral ischemia. The aim of this study was to examine the upregulation of contractile ETBreceptors in cerebral arteries after organ culture and to elucidate the intracellular pathways involved.Methods—Rat middle cerebral arteries (MCAs) were incubated with or without inhibitors. The vessels were mounted in myographs, and the contractile responses to endothelin-1 (ET-1) (ETAand ETBreceptor agonist) and sarafotoxin 6c (ETBreceptor agonist) were measured. Levels of ETBreceptor mRNA were measured with real-time polymerase chain reaction.Results—In fresh MCA, sarafotoxin 6c had no contractile effect. However, after organ culture, a strong concentration-dependent contraction was induced. ET-1 produced a strong contraction, in which the Emaxwas unaffected by organ culture but the EC50was decreased with time. The sarafotoxin 6c–induced contraction after 24 hours of organ culture was attenuated by the transcriptional inhibitor actinomycin D and the translational inhibitor cycloheximide as well as the protein kinase C inhibitor Ro-31-8220. Real-time polymerase chain reaction revealed that the mRNA levels of the ETBreceptor were increased after organ culture compared with fresh vessels. Actinomycin D and Ro-31-8220 diminished the enhanced mRNA levels considerably.Conclusions—The results suggest that, in fresh MCA, the ETAreceptor is the most prominent subtype, while after organ culture ETBreceptors also contribute to the contraction. This upregulation is due to de novo transcription of receptors. Protein kinase C is involved in the upregulation as Ro-31-8220 attenuates the contraction and the mRNA increase.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—Dahl salt-sensitive rats fed an 8.7% NaCl diet exhibited hypertensive encephalopathy and developed seizures associated with areas of blood-brain barrier (BBB) disruption without brain ischemia. The incidence of hemorrhagic stroke was low (7/47). We tested the hypothesis that a defect in cerebral blood flow (CBF) autoregulation under hypertensive conditions preceded hypertensive encephalopathy.Methods—Brain ischemia and BBB disruption were assessed with the use of tetrazolium red staining and Evans blue dye extravasation, respectively. Myogenic constriction to pressure was measured in isolated middle cerebral arteries (MCAs) with a pressure myograph. CBF autoregulation was assessed with the use of laser-Doppler techniques.Results—Asymptomatic rats fed 8.7% NaCl had MCAs that developed an age-related attenuation in their ability to constrict to pressure, which was amplified in rats exhibiting hypertensive encephalopathy. The MCAs of rats with hemorrhagic stroke lost this function and developed large degrees of basal tone. The majority (4/6) of asymptomatic rats fed high salt for longer than 3 weeks exhibited a linear relationship between CBF and blood pressure. The characteristics of CBF regulation were consistent with the possible absence of autoregulation coupled with cerebrovascular vasoconstriction.Conclusions—Both MCA pressure-dependent constriction and CBF autoregulation in the MCA perfusion domain were lost before the development of hypertensive encephalopathy or hemorrhagic stroke. These defects could contribute to the development of BBB disruption during hypertension. Cerebrovascular vasoconstriction in the absence of CBF autoregulation may protect the brain from excessive overperfusion during hypertension and could account for the low incidence of cerebral hemorrhage in this model.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—The ability of middle cerebral arteries (MCAs) to utilize intracellular smooth muscle (SM) Ca2+to produce constriction in response to pressure and agonists was assessed in relation to hemorrhagic stroke development in Wistar-Kyoto stroke-prone (SHRSP) and stroke-resistant (srSHR) spontaneously hypertensive rats.Methods—MCAs were studied with the use of a pressure myograph at 100 mm Hg.Results—MCAs from srSHR and prestroke SHRSP exhibited pressure-dependent constriction and constricted in response to vasopressin or serotonin in the presence of nifedipine or the absence of [Ca2+]o. MCAs from poststroke SHRSP lost the latter functions and could only constrict in response to vasopressin/serotonin in Krebs’ solution containing Ca2+in the absence of nifedipine. This indicated that the SM could not utilize internal Ca2+for constriction and maintained constriction by Ca2+entry through L-type channels. The MCAs of poststroke SHRSP could not constrict to [K+]o-induced depolarization, suggesting that the agonist-induced opening of the L-type channels occurred by mechanisms other than SM depolarization. Depletion of the sarcoplasmic SM Ca2+stores of MCAs from srSHR with cyclopiazonic acid did not prevent pressure-dependent constriction.Conclusions—Stroke in SHRSP produced a defect in the ability of MCAs to constrict in response to vasopressin or serotonin via the use of an intracellular source of Ca2+. This could be promoted by an inability of the SM to release intracellular Ca2+, by the depletion of internal Ca2+stores, or by a decrease in the contractile sensitivity to Ca2+released from the internal stores.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—Thrombin is activated in the cerebrospinal fluid (CSF) after a subarachnoid hemorrhage (SAH). However, the relationship between thrombin and cerebral vasospasm has not yet been fully established. The aim of this study was to investigate the possibility of thrombin as a causative factor for cerebral vasospasm and to delineate the signal transduction mechanism that results in thrombin-inducing sustained vasoconstriction in cerebral vasospasm.Methods—In the SAH group, SAH was simulated by the 2-hemorrhage rabbit model. In the treatment group, antithrombin III (AT-III) was injected into the cisterna magna just before production of the SAH. CSF samples were obtained serially to measure d-dimer with latex photometric immunoassay. On day 4, the basilar artery was excised after perfusion-fixation. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar arterial lumen, and the expression of mitogen-activated protein kinase (MAPK) in the vascular wall was examined with an immunohistochemical technique.Results—In the treatment group, the value of d-dimer on day 4 was 0.83±0.07 &mgr;g/mL, which was statistically significantly lower than that in the nontreated SAH group (2.49±0.09 &mgr;g/mL,P<0.01). The cross-sectional area of the arterial lumen in the treatment group was 3.67×105±1.58×104square pixels, which was statistically significantly larger than that in the nontreated SAH group (2.60×105±2.29×104square pixels;P<0.01). MAPK was detected diffusely in the vascular smooth muscle cell layer in the nontreated SAH group, but it was absent in the treatment group.Conclusions—Inhibition of thrombin activity leads to amelioration of cerebral vasospasm and suppression of MAPK diphosphorylation. This suggests that thrombin and its related signal transduction, including the MAPK cascade, appear to play an important role in the pathogenesis of cerebral vasospasm after SAH.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background and Purpose—With advances in the therapy of stroke at the postacute phase, the use of animal models for chronological and region-specific evaluation of neurological function has become increasingly important. Our aim was to test long-term behavioral dysfunction in gerbils after focal ischemia and to correlate the results with the regional distribution of infarction in the coordinating cortical regions.Methods—Repetitive unilateral hemispheric ischemia (two 10-minute occlusions, 5-hour interval) was induced in Mongolian gerbils. The elevated body swing test (EBST), bilateral asymmetry test (BAT), and T-maze test were performed to assess asymmetrical motor behavior, somatosensory deficit, and spatial cognitive dysfunction during 4 weeks after ischemia. The results were correlated against the regional infarction volume of the primary motor, somatosensory, and primary visual cortices at 4 weeks after ischemia.Results—In all postischemic gerbils, persistent sensorimotor and cognitive dysfunctions were detectable throughout the postischemic period. Histological examination revealed that a cortical zone of infarction surrounded the selective neuronal death in the ipsilateral cerebral hemisphere. The regional infarction volumes of the primary motor, somatosensory, and visual cortices were significantly correlated with the scores of the EBST, BAT, and T-maze test, respectively. These combinations had the highest regression coefficient of all pairs.Conclusions—Postischemic motor and somatosensory functions were significantly correlated with regional infarction volumes in the corresponding cortical regions. In gerbils, visual abnormality could be independently detected by the T-maze test. Such regional analyses of ischemic lesions would be useful for investigating the functional outcomes of stroke therapy.

ISSN:0039-2499    

出版商:OVID    

年代:2003

数据来源: OVID