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[Guidelines for the management of acute stroke--2005].

Stroke is a major cause for morbidity and mortality in Israel, the third most common cause of death and the main cause for neurological disability among adults. Several significant breakthroughs occurred over recent years in the management of stroke, and acute stroke has increasingly been recognized as a medical emergency--a "brain attack" comparable to a "heart attack". Several new scientific publications, guidelines and consensus statements from Europe and North America necessitate a paradigm shift in the management of acute stroke. The guidelines focus on a number of issues: acute stroke as a medical emergency, dedicated stroke units, early reperfusion therapy for acute ischemic stroke, emergency management and general stroke treatment, use of diagnostic tests in the acute phase, and the prevention and treatment of complications.

Acute Disease↗

[Basics of acute stroke treatment].

Acute stroke presents an emergency that requires immediate referral to a specialized hospital, preferably with a stroke unit. Disability and mortality are reduced by 30% in patients treated in stroke units compared to those treated on regular wards, even if a specialized team is present on the ward. Systolic blood pressure may remain high at 200-220 mmHg in the acute phase and should not be lowered too quickly. Further guidelines for basic care include: optimal O2 delivery, blood sugar levels below 100-150 mg%, and lowering body temperature below 37.5 degrees C using physical means or drugs. Increased intracranial pressure should be treated by raising the upper body of the patient, administration of glycerol, mannitol, and/or sorbitol, artificial respiration, and special monitoring of Tris buffer. Decompressive craniectomy may be considered in cases of "malignant" media stroke and expansive cerebellar infarction. Fibrinolysis is the most effective stroke treatment and is twice as effective in the treatment of stroke than myocardial infarction. Fibrinolysis may be initiated within 3 h of a stroke in the anterior circulation. If a penumbra is detectable by "PWI-DWI mismatch MRI," specialized hospitals may perform fibrinolysis up to 6 h after symptom onset. In cases of stroke in the basilar artery, fibrinolysis may be performed even later after symptom onset. Intra-arterial fibrinolysis is performed in these cases using rt-PA or urokinase. Follow-up treatment of stroke patients should not only address post-stroke depression and neuropsychological deficits, but also include patient education about risk factors such as high blood pressure, diabetes mellitus, and cardiac arrhythmias.

Acute Disease↗

An open, multicenter trial of recombinant tissue plasminogen activator in acute stroke. A progress report. The rt-PA Acute Stroke Study Group.

Sixteen clinical centers in two countries have undertaken a prospective open angiography- and computed tomography scan-based safety and efficacy dose-rate finding study of recombinant (two-chain) tissue plasminogen activator (rt-PA) in acute thrombotic and thromboembolic stroke. Preliminary experience with 71 rt-PA treated patients in seven dose-rate groups has demonstrated both partial and complete recanalization, documented by angiography, although a dose response has not yet been achieved. Hemorrhagic infarction has been documented at all dose rates, and dose-rate independent cerebral hematomas have been observed. The study continues at higher dose rates while still remaining within the safety guidelines.

Brain Ischemia↗

Expanded modes of tissue plasminogen activator delivery in a comprehensive stroke center increases regional acute stroke interventions.

BACKGROUND AND PURPOSE: We sought to evaluate whether a comprehensive stroke center could work with regional hospitals to increase the use of tissue plasminogen activator (tPA) in acute stroke. METHODS: In 30 months, 142 patients seen at the Mid America Brain and Stroke Institute received tPA. Site of presentation, protocol selection, and outcomes were analyzed. RESULTS: We found that 18.2% (142 of 781) of all ischemic strokes received tPA. Of those, 70% (99 of 142) were transferred from hospitals within 100 miles of Kansas City (Mo). Mortality rate was 12.7% (18 of 142). Symptomatic hemorrhage rate was 9.2%. CONCLUSIONS: A comprehensive stroke center can serve as a hub for a regional network and increase the number of stroke interventions with acceptable outcomes.

Acute Disease↗

Predictors of prolonged dysphagia following acute stroke.

Dysphagia following acute stroke frequently necessitates prolonged enteral feeding. There is evidence that early enteral feeding via percutaneous endoscopic gastrostomy (PEG) is both beneficial and safe. The aim of this study was to identify predictors of prolonged dysphagia. The subjects were 149 consecutive patients admitted with acute stroke. Clinical findings and imaging results were prospectively collected, and subsequent progress recorded. Subjects were divided into 3 groups for analysis: no dysphagia; transient dysphagia (< or =14 days); or prolonged dysphagia (>14 days). Validity of the water swallow test as a predictor of aspiration pneumonia was confirmed. Significant associations for prolonged dysphagia were seen with stroke severity, dysphasia and lesions of the frontal and insular cortex on brain imaging. These results indicate that it may be possible to predict patients who will develop prolonged significant dysphagia following acute stroke thereby facilitating referral for insertion of PEG at an earlier time point.

Acute Disease↗

Common drugs may influence motor recovery after stroke. The Sygen In Acute Stroke Study Investigators.

Studies in laboratory animals indicate that certain centrally acting drugs (eg, the antihypertensives clonidine and prazosin, neuroleptics and other dopamine receptor antagonists, benzodiazepines, and the anticonvulsants phenytoin and phenobarbital) impair behavioral recovery after focal brain injury. Even single doses may have long-term harmful effects. To determine whether these medications have a similar negative impact in humans, we analyzed the recoveries of control patients who were enrolled in the Sygen in Acute Stroke Study, a multicenter study of the effects of GM1 ganglioside after ischemic stroke. Motor impairments were measured by the motor subscores of the Toronto Stroke Scale at baseline and 7, 14, 21, 28, 56, and 84 days after stroke. Using these data, we compared motor recovery between patients with initial motor deficits who received at least one of the drugs that interfere with recovery in laboratory studies ("detrimental" drug group, n = 37) and patients who did not receive these drugs ("neutral" drug group, n = 59). The groups were well balanced with regard to the frequency of comorbid conditions and other prognostic factors. For upper-extremity motor function, repeated-measures ANOVA showed a significant interaction between drug group and time after stroke [F(6,528) = 2.38; p = 0.03], with a significant (p < 0.001) difference between the groups beginning 7 days after the stroke. A similar trend was present for the lower extremity, but the overall difference between the groups was not significant [ANOVA F(6,498) = 1.22; p = 0.29]. Drug group did influence the degree of independence in activities of daily living as measured with the Barthel Index.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Using change in the National Institutes of Health Stroke Scale to measure treatment effect in acute stroke trials.

BACKGROUND AND PURPOSE: Outcome measures in acute stroke trials are being refined. Changes in neurological deficits might be useful outcome measures because they can measure the entire spectrum of deficits. METHODS: We analyzed data from the acute stroke treatment trial Trial of Org 10172 in Acute Stroke Treatment (TOAST). Using logistic regression analysis, we modeled the probability of the TOAST predefined very favorable outcome (VFO; both Glasgow Outcome Scale 1 and modified Barthel Index 19 to 20) at 3 months. Within-subject changes (baseline-3 months) on the National Institutes of Health Stroke Scale (NIHSS) was the main predictor of interest. RESULTS: The baseline median NIHSS for the entire TOAST cohort was 7, and it improved by 4 points (interquartile range 3 to 6) among 603 patient with VFO and by 2 points (interquartile range -1 to 5) among 638 patients without a VFO (P<0.001). The odds for VFO increased by 2.29 (95% CI, 2.06 to 2.54; P<0.001) for each 1-point improvement on the NIHSS. In receiver operating characteristic analysis, final NIHSS < or =2 was a good predictor of VFO, but no single NIHSS change cut point was a good predictor of VFO. CONCLUSIONS: NIHSS change appears to be a useful outcome measure for acute stroke trials and is not fully comparable to dichotomized functional outcomes.

Acute Disease↗

Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome.

BACKGROUND AND PURPOSE: The aim of this study was to characterize the response of the hypothalamic-pituitary-adrenal system in the first hours of ischemic stroke and to relate its extent to the occurrence of acute confusional state, volume of brain damage, and clinical outcome. METHODS: The secretion of corticotropin (adrenocorticotropic hormone [ACTH]) and cortisol was studied in 23 patients by determinations at hours 4, 6, 8, 10, and 14 and days 1, 3, 5, and 7 after onset of symptoms. Acute confusional state (DSM-III-R criteria), extent of lesion (volumetry of computed tomographic scans), and neurological and functional outcome (Scandinavian Stroke Scale, Barthel Index scores) were assessed. RESULTS: The massive neuroendocrine response observed consisted of an initial phase with concomitantly increased levels of ACTH and cortisol and a second phase with decreased levels of ACTH while high concentrations of cortisol persisted. Initial levels of ACTH but not cortisol were significantly increased in patients with acute confusional state and significantly correlated with volume of brain lesion and neurological and functional outcome. CONCLUSIONS: An early and persisting activation of the hypothalamic-pituitary-adrenal axis was observed in relation to severity of disease. Its characteristic biphasic pattern suggests an initial central stimulation of release of ACTH followed by feedback suppression concomitant with an increased susceptibility of the adrenal gland. Because these hormones are known to exacerbate hypoxic injury to neurons, their massive release in hyperacute stroke may increase the extent of brain damage.

Acute Disease↗

Cerebral microcirculatory disturbances of stroke prone spontaneously hypertensive rats with acute stroke and mechanism of treatment.

Cerebral microcirculatory behavior of stroke prone spontaneously hypertensive rats (SHRSP) suffering from acute stroke (WKY as control group) was studied with laser Doppler flowmetry in vivo. The pharmacological effects of Dextran 40, nimodipine and the combined use of both drugs (40:1 volume ratio) on cerebral microvessels were measured. The results of the experiment have shown that SHRSP had a serious cerebral microcirculatory disturbance when the acute stroke occurred. Both Dextran 40 and nimodipine could improve the cerebral microcirculatory disturbance, but the combined usage presented far more satisfactory effects. Hopefully it will decrease the mortality of patients with acute stroke.

Animals↗

Services for reducing duration of hospital care for acute stroke patients.

BACKGROUND: Stroke patients conventionally receive a substantial part of their rehabilitation in hospital. Services have now been developed which offer patients in hospital an early discharge with community-based rehabilitation (early supported discharge, ESD). OBJECTIVES: The objective of this review is to establish the costs and effects of ESD services compared with conventional services. SEARCH STRATEGY: The Cochrane Stroke Group Specialised Register was searched and supplemented with information from individual trialists. Searching was completed in March 1999. SELECTION CRITERIA: Randomised controlled trials recruiting stroke patients in hospital to receive either conventional care or any intervention which has provided rehabilitation and support in a community setting with an aim of reducing the duration of hospital care. DATA COLLECTION AND ANALYSIS: Two reviewers scrutinised trials and categorised them on their eligibility. Standardised information was then obtained from the primary trialists. Results were analysed for all trials and for two subgroups depending on whether the intervention was provided by a coordinated multidisciplinary team (coordinated ESD team) or not. MAIN RESULTS: Outcome data are currently available for four trials. Patients tended to be a selected elderly group with disability. Overall, the odds ratio (95% confidence interval) for death, death or institutionalisation, death or dependency at the end of scheduled follow up were 0.87 (0.39-1.93), 0.69 (0.36-1.31) and 0.88 (0.49-1. 57) respectively. Apparent benefits more evident in the three trials evaluating a coordinated ESD team. The ESD group showed significant reductions (P<0.001) in the length of hospital stay equivalent to approximately nine days. REVIEWER'S CONCLUSIONS: ESD services provided for a selected group of stroke patients can reduce the length of hospital stay. However, the relative risks and benefits and overall costs of such services remain unclear.

Home Care Services↗

GM1 ganglioside therapy in acute ischemic stroke. Italian Acute Stroke Study--Hemodilution + Drug.

Eleven of 31 clinical centers participating in the Italian Acute Stroke Study--Hemodilution carried out a preliminary study on the effectiveness of ganglioside GM1 in acute stroke; 502 patients were randomized to GM1 (GM1, n = 121), GM1 plus hemodilution (GM1 + H, n = 128), placebo (P, n = 130), or placebo plus hemodilution (P + H, n = 123) groups less than or equal to 12 hours after onset of a hemispheric cerebral infarct. The patients were treated for 15 days and were evaluated on Days 21 and 120 after the onset of stroke. Intention-to-treat analysis failed to show any differences in neurologic deficit, mortality, or neurologic disability among the groups. Efficacy analysis showed a significantly higher degree of neurologic improvement in GM1 group patients compared with patients in the P group during the first 15 days. GM1-treated patients (GM1 and GM1 + H groups) showed a significantly higher degree of neurologic improvement during the first 10 days compared with the placebo-treated patients (P and P + H groups). These differences were no longer statistically significant at Day 120. Our results provide a rationale for the planning of a larger, multicenter trial of GM1 ganglioside in acute stroke.

Aged↗

Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection.

BACKGROUND: Effective therapy was not available for treatment of acute stroke until 1995, when tissue plasminogen activator (tPA) was shown to improve neurological and functional outcome in stroke patients who were treated within 3 hours of symptom onset. SUMMARY OF REVIEW: Currently, many patients do not qualify for tPA therapy because they present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using CT to select patients, have failed. Use of early MR imaging may provide significant advantages over CT for identification of patients who are likely to benefit from thrombolytic therapy because (1) the early perfusion-weighted imaging (PWI) lesion estimates the region of acute dysfunctional brain tissue, whereas the acute diffusion-weighted imaging (DWI) lesion appears to correspond to the core of the early infarction; (2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (an estimate of the ischemic penumbra); and (3) in patients with a PWI/DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion growth. CONCLUSIONS: Clinical trials that use new MRI techniques to screen patients may be able to identify a subset of acute stroke patients who are ideal candidates for thrombolytic therapy even beyond 3 hours after stroke onset.

Diffusion↗

Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients.

BACKGROUND AND PURPOSE: The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke. METHODS: Patients with symptom onset of </=12 hours before the start of treatment were included in the study. Clomethiazole (75 mg/kg) or placebo was given as an intravenous infusion over a 24-hour period. Patients were followed up for 90 days. The primary efficacy variable was the proportion of patients reaching relative functional independence (>/=60 points on the Barthel Index) at 90 days. RESULTS: A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a "large" stroke. CONCLUSIONS: Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.

Acute Disease↗

SPASE-I: a multicenter observational study on pharmacological treatment of acute stroke in the elderly. The Italian Study of Pharmacological Treatment of Acute Stroke in the Elderly Group.

We investigated the clinical outcome and current therapeutic management of ischemic stroke in elderly patients in different neurological wards throughout Italy. Twelve centers in 10 Italian regions were involved. The clinical and instrumental data were prospectively collected for 335 patients 65 years or older, presenting in a 12-months period. At the multivariate analysis, death was associated with the presence of total anterior circulation infarct and the use of antiedema agents. Stroke-related disability was related to female sex, unified stroke scale (USS) scores at entry and mini-mental state examination (MMSE) scores at the 1-months follow-up. The majority of patients (70%) received antiplatelets to prevent stroke recurrence. Very elderly (> or =80 years) patients had worse presentation and prognosis than less elderly stroke victims (<80 years). Age played an important role in the therapeutic approach to stroke: while antiplatelets were widely used, oral anticoagulants were underused even when specifically indicated.

Age Factors↗