A randomized trial of intraarterial treatment for acute ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS: We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS: We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

Centralising and optimising decentralised stroke care systems: a simulation study on short-term costs and effects.

BACKGROUND: Centralisation of thrombolysis may offer substantial benefits. The aim of this study was to assess short term costs and effects of centralisation of thrombolysis and optimised care in a decentralised system. METHODS: Using simulation modelling, three scenarios to improve decentralised settings in the North of Netherlands were compared from the perspective of the policy maker and compared to current decentralised care: (1) improving stroke care at nine separate hospitals, (2) centralising and improving thrombolysis treatment to four, and (3) two hospitals. Outcomes were annual mean and incremental costs per patient up to the treatment with thrombolysis, incremental cost-effectiveness ratio (iCER) per 1% increase in thrombolysis rate, and the proportion treated with thrombolysis. RESULTS: Compared to current decentralised care, improving stroke care at individual community hospitals led to mean annual costs per patient of $US 1,834 (95% CI, 1,823-1,843) whereas centralising to four and two hospitals led to $US 1,462 (95% CI, 1,451-1,473) and $US 1,317 (95% CI, 1,306-1,328), respectively (P < 0.001). The iCER of improving community hospitals was $US 113 (95% CI, 91-150) and $US 71 (95% CI, 59-94), $US 56 (95% CI, 44-74) when centralising to four and two hospitals, respectively. Thrombolysis rates decreased from 22.4 to 21.8% and 21.2% (P = 0.120 and P = 0.001) in case of increasing centralisation. CONCLUSIONS: Centralising thrombolysis substantially lowers mean annual costs per patient compared to raising stroke care at community hospitals simultaneously. Small, but negative effects on thrombolysis rates may be expected.

A simulation-based approach for improving utilization of thrombolysis in acute brain infarction.

BACKGROUND: Treatment with tissue plasminogen activator (tPA) is the most effective treatment in acute brain infarction. However, estimated worldwide treatment rates are <10%, with many barriers hampering broad implementation. Organization and resource-intense randomized controlled trials cannot address all potential barriers simultaneously. Simulation, however, may provide an efficient research means for testing interventions aimed at resolving barriers along the care pathway. RESEARCH DESIGN: A simulation-based approach reflecting the setup of a regional Dutch acute stroke pathway was used. First, barriers along the overall pathway were identified. Next, solutions to barriers were configured, and subsequently tested using simulation. RESULTS: Barriers along the stroke pathway and possible solutions were identified from the literature and expert consultation. The simulation model closely reproduced actually observed tPA treatment rate and overall process time (21.8% and 129 min for model outcomes vs. 22.1% and 127 min, P=0.89 and 0.64, respectively). Two barriers were overcome: (1) time spent by ambulance personnel on scene by a scoop-and-run protocol (1.4% increase in tPA rate, 7 min decrease in overall process time), and (2) time to laboratory results by introducing a point-of-care diagnostic device (3.2% increase in tPA rate, 20 min decrease in overall process time). CONCLUSIONS: A simulation-based approach is well suited to efficiently assess solutions to barriers along the overall stroke pathway. Substantial improvements in treatment rates and efficacy of thrombolysis may be achieved by implementing a scoop-and-run protocol and point-of-care device.

Proportion of patients treated with thrombolysis in a centralized versus a decentralized acute stroke care setting.

BACKGROUND AND PURPOSE: Today, treatment of acute stroke consists of tissue-type plasminogen activator (tPA), admission to a stroke unit, and aspirin. Although tPA treatment is the most effective, there is substantial undertreatment. Centralized care may affect rate, timing, and outcome of thrombolysis compared to decentralized treatment in community hospitals. The present study aimed to assess the impact of organizational models on the proportion of patients undergoing tPA treatment. METHODS: A prospective, multicenter, observational study among 13 hospitals in the North of the Netherlands was conducted. In the centralized model, tPA treatment for 4 hospitals was administered in 1 stroke center. The decentralized model comprised 9 community hospitals. Primary outcome was the proportion of patients treated with tPA. Secondary outcome measures were proportion of patients arriving within 4.5 hours, safety, 90-day functional outcome, and onset-to-door, door-to-needle, and onset-to-needle times. Potential confounders were adjusted using logistic regression analysis. RESULTS: Two hundred eighty-three and 801 ischemic stroke patients were enrolled in the centralized and decentralized settings. Numbers of patients treated with tPA were 62 (21.9%) and 113 (14.1%) (OR, 1.72; 95% CI, 1.22-2.43). Adjusting for potential confounders did not alter results (OR, 2.03; 95% CI, 1.39-2.96). In the centralized setting, significantly more patients arrived at the hospital within the 4.5-hour time window (P<0.01), and shorter door-to-needle times were reached (35 versus 47 minutes). Other secondary outcome measures did not differ across setting. CONCLUSIONS: In a centralized setting, the results demonstrate a 50% increased likelihood of treatment. Prehospital factors seem to contribute to this result.

Near infrared spectroscopy for the detection of desaturations in vulnerable ischemic brain tissue: a pilot study at the stroke unit bedside.

BACKGROUND AND PURPOSE: There is uncertainty whether bilateral near infrared spectroscopy (NIRS) can be used for monitoring of patients with acute stroke. METHODS: The NIRS responsiveness to systemic and stroke-related changes was studied overnight by assessing the effects of brief peripheral arterial oxygenation and mean arterial pressure alterations in the affected versus nonaffected hemisphere in 9 patients with acute stroke. RESULTS: Significantly more NIRS drops were registered in the affected compared with the nonaffected hemisphere (477 drops versus 184, P<0.001). In the affected hemispheres, nearly all peripheral arterial oxygenation drops (n=128; 96%) were detected by NIRS; in the nonaffected hemispheres only 23% (n=30; P=0.17). Only a few mean arterial pressure drops were followed by a significant NIRS drop. This was however significantly different between both hemispheres (32% versus 13%, P=0.01). CONCLUSIONS: This pilot study found good responsiveness of NIRS signal to systemic and stroke-related changes at the bedside but requires confirmation in a larger sample.

Exaggerated postural blood pressure rise is related to a favorable outcome in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: The effects of early upright positioning in the acute phase of ischemic stroke on both blood pressure and functional outcome have not been previously examined. METHODS: Prospective investigation of mean arterial pressure, heart rate, and peripheral oxygen saturation in the supine, sitting, and (if achievable) active standing position 1, 2, and 3 days after an acute stroke was performed. Also investigated was the presence of a significant postural blood pressure rise and fall using orthostatic definitions and the relation to functional outcome after 3 months. RESULTS: One hundred sixty-seven patients were included (mean age, 68.5±15.2 years; median National Institutes of Health Stroke Scale, 7). Approximately 60% of the patients were able to stand. On average the mean arterial pressure increased when patients moved from the supine to sitting (Day 1: Δ 3.9 mm Hg; P<0.001) and from sitting to an active standing position (Day 1: Δ 4.6 mm Hg; P<0.001). Changes were most pronounced within the first 24 hours after a stroke. Blood pressure decreased significantly (fall) on standing in 13% of patients and increased significantly (rise) in 20% of the patients. The latter was independently associated with a favorable outcome (P=0.003). Moving to the standing position was accompanied by an increase of heart rate. No difference in oxygen saturation was observed in the various positions over the period of investigation. CONCLUSIONS: We found that a significant blood pressure rise during early upright positioning in patients with acute stroke was independently associated with a favorable outcome. No contraindication to early mobilization was found in this study.

Intra-arterial blood pressure reading in intensive care unit patients in the lateral position.

BACKGROUND: Routine lateral turning of patients has become an accepted standard of care to prevent complications of immobility. The haemodynamic and oxygenation effects for patients in both lateral positions (45°) are still a matter of debate. We aimed to study the effect of these positions on blood pressure, heart rate and oxygenation in a general intensive care population. DESIGN: Observational study. METHOD: Twenty stable intensive care unit patients had intra-arterial blood pressure recordings in the supine and lateral positions with the correction of hydrostatic height compared with a fixed reference point (phlebostatic level). A multilevel model was used to analyse the data. RESULTS: Mean arterial pressure readings in the lateral positions were, on average, 5 mmHg higher than in the supine position (p < 0.001). There were no significant differences between mean arterial pressure recordings in the left and right lateral position (p = 1.0). No important differences in oxygenation and heart rate were observed. After correction for covariates, the effects persisted. CONCLUSION: Our study demonstrated an increase, albeit small, in blood pressure in the lateral positions. No major differences between the left and right lateral position were found. No important differences in oxygenation and heart rate were observed. RELEVANCE TO CLINICAL PRACTICE: Turning haemodynamically stable patients in the intensive care unit has no important effects on blood pressure measurements when continuous hydrostatic height correction is applied.

Variations of blood pressure in stroke unit patients may result from alternating body positions.

BACKGROUND: Blood pressure (BP) is one of the major vital parameters monitored in the stroke unit. The accuracy of indirect BP measurement is strongly influenced by the position of both patient and arm during the measurement. Acute stroke patients are often nursed in lateral decubitus positions. The effect of these alternating body positions in relation to affected body side on the outcome and reliability of BP readings in acute stroke patients is unknown. METHODS: An automatic oscillometric BP device was used. BP was measured in both arms in the (back) supine and both lateral decubitus positions. RESULTS: In total, 54 consecutive acute stroke patients were included. Thirty-five patients had right-sided deficits and 19 patients had left-sided deficits. Supine BP readings were similar in the right and left arms regardless of side of deficit. Measurements of BP in the lateral decubitus positions resulted in significantly lower BP readings in the uppermost arm (around 12 mm Hg in both arms) and significantly higher readings in the right lowermost arm (around 6 mm Hg) compared to the supine position. This effect seemed less pronounced when the left lowermost arm was measured. There was no relation between change of BP readings in various lateral positions and side of stroke. CONCLUSIONS: Alternating lateral decubitus positions according to nursing standards in acute stroke patients lead to a mean 18 mm Hg BP fluctuation. This may largely be explained by hydrostatic pressure effects, partly by anatomic factors in the left lowermost arm, but not by the side of stroke.

Cerebral autoregulation in stroke: a review of transcranial Doppler studies.

BACKGROUND AND PURPOSE: Cerebral autoregulation may become impaired after stroke. To provide a review of the nature and extent of any autoregulation impairment after stroke and its course over time, a technique allowing repeated bedside measurements with good temporal resolution is required. Transcranial Doppler (TCD) in combination with continuous blood pressure measurements allows noninvasive continuous bedside investigation with high temporal resolution of the dynamic and the steady-state components of cerebral autoregulation. Therefore, this review focuses on all TCD studies on cerebral autoregulation in the setting of documented ischemic stroke. METHODS: PubMed and EMBASE were searched for studies of stroke, autoregulation, and TCD. Studies were either acute phase (<96 hours after index stroke) or chronic phase (>96 hours after index stroke) autoregulation studies. Quality of studies was studied in a standardized fashion. RESULTS: Twenty-three studies met the inclusion criteria. General agreement existed on cerebral autoregulation being impaired, even after minor stroke. Bilateral impairment of autoregulation was documented, particularly after lacunar stroke. Studies showed progressive deterioration of cerebral autoregulation in the first 5 days after stroke and recovery over the next 3 months. Impaired cerebral autoregulation as assessed by TCD was related to neurological deterioration, the necessity for decompressive surgery, and poor outcome. Synthesis of the data of various studies was, however, limited by studies not meeting key methodological criteria for observational studies. CONCLUSIONS: TCD in combination with continuous blood pressure measurement offers a method with a high temporal resolution feasible for bedside evaluation of cerebral autoregulation in the stroke unit. TCD studies have shown impairment of cerebral autoregulation in various subtypes of ischemic stroke. To improve the synthesis of data from various research groups, there is urgent need for standardization of methodology of TCD studies in cerebral autoregulation.

Risk factors for cerebral venous thrombosis and deep venous thrombosis in patients aged between 15 and 50 years.

Cerebral venous thrombosis (CVT) and deep vein thrombosis or pulmonary embolism (DVT/PE) are associated with many risk factors. It is unclear why CVT occurs less often than DVT/PE. Age dependent risk factors may play a role. The aim of our study was to compare risk factors in a uniform age group of CVT and DVT/PE patients aged between 15 and 50 years. Thrombophilic markers and clinical risk factors of 79 CVT patients and 173 DVT/PE patients aged 15-50 years were compared. Multivariable logistic regression analysis was performed to investigate if risk factors were independently associated with CVT or DVT/PE. Cerebral venous thrombosis patients were younger (median age 30 years vs. 42 years; p<0.001) and more often female (82% vs. 52%; p<0.001). There were no differences in thrombophilic markers. Cerebral venous thrombosis was less often associated with trauma, immobilisation or surgery than DVT/PE (6% vs. 21%; adjusted OR 0.29; 95%CI 0.10-0.82). In women, CVT was more frequently associated with oral contraceptive use, pregnancy or puerperium (82% vs. 53%; adjusted OR 2.34; 95%CI 1.03-5.32). This study demonstrated no differences in thrombophilic markers between CVT patients and DVT/PE patients aged between 15 and 50 years, while the frequency of some transient risk factors was different. Cerebral venous thrombosis was relatively more common in women and hormonal factors may predispose to CVT compared to DVT/PE, while trauma, immobilisation and surgery may be less important in the pathophysiology of CVT.

Local intra-arterial thrombolysis in a 4-year-old male with vertebrobasilar artery thrombosis.

We report the case of a 4-year-old male with vertebrobasilar artery thrombosis for which he was treated with local intra-arterial urokinase 60 hours after onset of symptoms. Initially the patient had dysarthria and dysphagia. Brain magnetic resonance imaging (MRI) in a community hospital showed abnormalities in the pons, and vertebrobasilar artery thrombosis was suspected. The patient was transferred to the university hospital because of neurological deterioration. Just before thrombolysis, his physical examination revealed a downward ocular deviation, stretching of the arms, and spontaneous movements of the legs. Brain MRI showed recent ischaemia in the pons and caudal part of the mesencephalon, and magnetic resonance angiography showed occlusion of the basilar artery. Intra-arterial thrombolysis with urokinase (total dose 36 000U/kg) was performed 60 hours after onset of symptoms. After thrombolysis he was treated with heparin for 10 days, followed by aspirin. The patient recovered well. After 1 year he had only minor ataxia and performed all activities at school. Local vasculitis due to an infection with Borrelia burgdorferi was thought to be the cause of the local thrombosis. A review of the literature revealed 11 other case reports of successful local intra-arterial thrombolysis in children and adolescents with ischaemic stroke. This suggests that intra-arterial thrombolysis is feasible and safe in selected paediatric patients with ischaemic stroke.

Long-term sequelae after cerebral venous thrombosis in functionally independent patients.

BACKGROUND: The majority of survivors of cerebral venous thrombosis (CVT) regain functional independence, but it is unclear whether these patients experience long-term sequelae. The aim of this case-control study was to assess: (1) frequency of headache, fatigue, depression, and concentration impairment; and (2) impact of these sequelae on daily life and employment in patients with CVT who are functionally independent. METHODS: We included 44 patients with CVT older than 15 years diagnosed between January 1997 and July 2006 who were functionally independent (modified Rankin scale score

Moderate hyperglycaemia is associated with favourable outcome in acute lacunar stroke.

Hyperglycaemia in acute ischaemic stroke is traditionally associated with a worsened outcome. However, it is unclear whether the impact of hyperglycaemia on stroke outcome is similar in lacunar and non-lacunar infarctions. The relation between serum glucose measured within 6 h after stroke onset and functional outcome was investigated in 1375 ischaemic stroke patients who had been included in two placebo-controlled trials with lubeluzole. The endpoint was a favourable outcome, defined as a modified Rankin Scale score < or =2 at 3 months. Classification into lacunar (n = 168) and non-lacunar (n = 1207) strokes was based on clinical criteria according to the Oxfordshire Community Stroke Project and findings on brain CT scan. Hyperglycaemia was defined as blood glucose >8 mmol/l. A possible concentration-dependent effect of glucose on outcome was investigated in both lacunar and non-lacunar stroke. Multivariate analysis showed that hyperglycaemia was associated with decreased odds of a favourable outcome in non-lacunar stroke (OR 0.60; 95% CI 0.41-0.88, P = 0.009), but with increased odds of a favourable outcome in lacunar stroke (multivariate OR for glucose >8 mmol/l: 2.70; 95% CI 1.01-7.13, P = 0.048). In non-lacunar stroke, there appeared to be a concentration-effect relation, as the odds of favourable outcome gradually decreased with increasing glucose levels. In lacunar stroke, an association with favourable outcome was observed with glucose levels >8 mmol/l, but this beneficial effect diminished with more severe hyperglycaemia >12 mmol/l. In conclusion, hyperglycaemia has a detrimental effect in non-lacunar stroke, but moderate hyperglycaemia may be beneficial in lacunar stroke.

Trismus as manifestation of bilateral internal capsule genu infarction.

Acute trismus can have different causes. We describe the presentation, course and radiological findings of a 34-year-old man who developed acute trismus and MRI findings consistent with the combination of an old and fresh infarction in the genu of the internal capsule. We believe it is important to consider stroke as a cause of acute trismus.

The incidence of stroke mimics among stroke department admissions in relation to age group.

BACKGROUND: Acute stroke therapies are effective but may have serious adverse effects. This makes an accurate diagnosis mandatory. Acute stroke is diagnosed on the basis of neurologic findings, laboratory testing, and a computed tomography scan of the brain. This is the first study to investigate the incidence of stroke mimics beyond the triaging stage and just before therapy decisions across age groups. METHODS: In all, 669 consecutive patients assessed at the emergency department by a neurologist were admitted to the stroke department with a provisional diagnosis of stroke. Patient registries of possible mimics were cross-referenced. RESULTS: In all, 637 patients (95.2%) had a correct diagnosis of stroke. A total of 15 patients turned out to have migraine with prolonged aura, 13 had a conversion disorder, 4 had partial epilepsy, and one was hypoglycemic. Under the age of 50 years, stroke mimics occurred in 21% of 87 patients. Above the age of 50 years, stroke mimics were very rare (3% of 583 patients). CONCLUSIONS: In patients being considered for acute stroke interventions, stroke mimics need to be considered particularly when the patient is younger than 50 years. In older patients, features typical of stroke mimics do not rule out a stroke.

Intravenous alteplase for stroke: beyond the guidelines and in particular clinical situations.

BACKGROUND AND PURPOSE: Because of the risk of hemorrhage, especially in the brain, thrombolytic therapy with intravenous alteplase is restricted by guidelines, and only a small number of selected patients are being treated. Findings from metaanalyses, post hoc analyses of the randomized trials, and postlicensing experience suggest that more subjects, who otherwise have a poor predicted outcome without treatment, might benefit from intravenous alteplase. Summary of Review- There is a strong indication that treatment may still be beneficial beyond 3 hours up until 4.5 hours. The risk of symptomatic intracerebral hemorrhage is not increased in patients aged 80 years or older. Excluding patients with severe stroke or with early ischemic changes in more than one third of the middle cerebral artery territory on baseline CT scan is probably not necessary when treatment is started <3 hours of symptom onset. Patients with minor or improving symptoms can also benefit. Intravenous thrombolysis appears appropriate as first line therapy for posterior circulation stroke. Alteplase can be given to patients with cervical artery dissection, seizure at onset and evidence of acute ischemia on brain imaging, and after carefully weighing risk and benefit in pregnancy and during menstruation. There are anecdotal reports on its use in children, patients with recent myocardial infarction, cardiac embolus, intracranial aneurysm or arteriovenous malformation, prior stroke and recent surgery. There appears to be a substantially increased risk of symptomatic cerebral hemorrhage in hyperglycemic stroke patients. The combined intravenous and intraarterial approach to recanalization appears safe and is currently under investigation in a randomized trial. CONCLUSIONS: This document does not intend to change the guidelines but reviews the literature on the use of intravenous alteplase for stroke beyond guidelines and in particular conditions.

Can Patients With Low Back Pain Be Satisfied With Less Than Expected?

STUDY DESIGN: A prospective cohort study within care as usual. OBJECTIVE: (1) To explore the psychometric properties of a baseline disability questionnaire designed to collect patients' expectation. (2) To analyze relations between satisfaction with care and treatment success in patients with chronic low back pain (CLBP). (3) To determine the chances of being satisfied with the received care in absence of treatment success. SUMMARY OF BACKGROUND DATA: There is a lack of evidence on determinants of treatment satisfaction in patients with CLBP, specifically the role of patient's expectation of disability reduction after treatment. METHODS: Treatment expectation was measured with questions inspired by the Pain Disability Index (PDI) at baseline. Treatment success was considered if disability at the end of therapy was lower than, or equal to pretreatment expectation. An exploratory factor analysis was performed on the new questionnaire. Binary logistic regression models were used to analyze how much variance of satisfaction with care was explained by treatment success, pain disability at baseline, sex, age, duration of complaints, and pain intensity. The odds ratio of being satisfied when treatment was successful was calculated. RESULTS: Six hundred nine patients were included. The factor structure of the PDI-expectancy had optimal fit with a one factor structure. There were low correlations between the expected and baseline disability, pain intensity, and duration of pain. Correlation between treatment success and satisfaction with care was low (χ = 0.13; P < 0.01). Treatment success had a low contribution to satisfaction with care. Of all participating patients, 51.4% were satisfied with care even when treatment was not successful. The odds ratio for being satisfied was 2.42 when treatment was successful compared to when treatment was not successful. CONCLUSION: The PDI-expectancy is internally consistent. Pretreatment expectation contributes uniquely but slightly to satisfaction with care; patients whose treatment was considered successful have 1.38 to 4.24 times higher chance of being satisfied at the end of treatment. Even when treatment was not successful, 51.4% of the patients with CLBP are satisfied with care. LEVEL OF EVIDENCE: 2.