Multidisciplinary approach to carotid stenting.

BACKGROUND: Stroke neurologists, vascular surgeons, interventional neuroradiologists and interventional cardiologists have embraced carotid angioplasty and stenting (CAS) because of potential advantages over carotid endarterectomy (CEA). At Austin Health, a multidisciplinary neuro-interventional group was formed to standardise indications and facilitate training. The aims of this study were to describe our organisational model and to determine whether 30-day complications and early outcomes were similar to those of major trials. METHODS: A clinical protocol was developed to ensure optimal management. CAS was performed on patients with high medical risk for CEA, with technically difficult anatomy for CEA, or who were randomised to CAS in a trial. RESULTS: From October 2003 to May 2008, 47 patients (34 male, mean age 71.5) underwent CAS of 50 carotid arteries. Forty-three cases had ipsilateral carotid territory symptoms within the previous 12 months. The main indications for CAS were high risk for CEA (n= 17) and randomised to CAS (n= 21). Interventionists were proctored in 27 cases. The procedural success rate was 94% with two cases abandoned because of anatomical problems and one because of on-table angina. Hypotension requiring vasopressor therapy occurred in 12 cases (24%). The duration of follow up was one to 44 months (mean 6.8 months). The 30-day rate of peri-procedural stroke or death was 6% and the one-year rate of peri-procedural stroke or death or subsequent ipsilateral stroke was 10.6%. Restenosis occurred in 13% (all asymptomatic). CONCLUSION: A multidisciplinary approach is a useful strategy for initiating and sustaining a CAS programme.

Diagnostic accuracy of acute vestibular syndrome at the bedside in a stroke unit.

Acute vestibular syndrome may be due to vestibular neuritis (VN) or posterior circulation strokes. Bedside ocular motor testing performed by experts is superior to early MRI in excluding strokes. We sought to demonstrate that differentiation of strokes from VN in our stroke unit is reliable. During a prospective study at a tertiary hospital over 1 year, patients with AVS were evaluated in the emergency department (ED) and underwent admission with targeted examination: gait, gaze-holding, horizontal head impulse test (hHIT), testing for skew deviation (SD) and vertical smooth pursuit (vSP). Neuroimaging included CT, transcranial Doppler (TCD) and MRI with MR angiogram (MRA). VN was diagnosed with normal diffusion-weighted images (DWI) and absence of neurological deficits on follow-up. Acute strokes were confirmed with DWI. A total of 24 patients with AVS were enrolled and divided in two groups. In the pure vestibular group (n = 20), all VN (n = 10/10) had positive hHIT and unidirectional nystagmus, but 1 patient had SD and abnormal vertical smooth pursuit (SP). In all the strokes (n = 10/10), one of the following signs suggestive of central lesion was present: negative hHIT, central-type nystagmus, SD or abnormal vSP. Finding one of these was 100% sensitive and 90% specific for stroke. In the cochleovestibular group (n = 4) all had normal DWI, but 3 patients had central ocular motor signs (abnormal vertical SP and SD). Whilst the study is small, classification of AVS in our stroke unit is reliable. The sensitivity and specificity of bedside ocular motor testing are comparable to those previously reported by expert neuro-otologists. Acute cochleovestibular loss and normal DWI may signify a labyrinthine infarct but differentiating between different causes of inner ear dysfunction is not possible with bedside testing.

End-of-life decision-making in individuals with locked-in syndrome in the acute period after brainstem stroke.

Locked-in syndrome (LIS) is commonly associated with a poor prognosis, particularly if the aetiology is stroke. Dealing with individuals with LIS and a poor prognosis raises the issue of introducing end-of-life discussions with the patient and/or family in the acute period of the illness. Existing literature regarding LIS provides little guidance about end-of-life decision-making in the acute management phase. We aim to provide some guidance for clinicians holding end-of-life discussions in the acute management period. We report two cases of relatively young individuals with LIS secondary to brainstem stroke. Both cases had a very poor prognosis and end-of-life discussions were commenced by the treating team in the acute phase. Despite the severity of their conditions, in neither case were end-of-life discussions well tolerated by the family in the weeks following admission. We suggest that LIS patients and their families, who have chosen to persist with full medical management after diagnosis of LIS, should be provided with sufficient time to adjust to the catastrophic changes that have occurred before further end-of-life discussions are pursued. Education and support are likely to be highly beneficial in the acute period post stroke as they allow the patient and family to develop a realistic understanding of the likely outcomes of their decisions.

Timing of clinically significant microembolism after carotid endarterectomy.

PURPOSE: Post-operatively detected transcranial Doppler (TCD) embolic signals (ES) are associated with an increased risk of carotid endarterectomy (CEA) stroke/TIA. The aims here were to quantify this risk and determine the most efficient monitoring protocol. METHODS: Sequential patients undergoing CEA (enrolled in a randomised, blinded, placebo-controlled trial of peri-operative dextran therapy) had 30-min TCD monitoring in the first post-operative hour. 30-min monitoring was also performed 2-3, 4-6 and 24-36 h post-operatively. First post-operative hour ES counts were correlated with peri-operative ipsilateral carotid stroke/TIA to determine the size of a clinically significant ES load and the magnitude of the associated risk. The exact Cochran-Armitage test for trend in proportions was used to determine when a clinically significant ES load was first detected. RESULTS: 141 patients (mean age 69.3 years, 72% male) were monitored during the first post-operative hour. An ES count >10 per recording was identified as the best overall predictor of ipsilateral stroke/TIA (sensitivity 72%, specificity 89%). 3/119 (2.5%) patients with 0-10 ES had ipsilateral carotid events compared to 8/22 (36.4%) patients with 11-115 ES (OR = 22.1, 95% CI 4.5, 138.4, p < 0.0001). 13/18 (72%) of subjects with >10 ES were identified in the first post-operative hour with no significant increase in the number of new cases over the subsequent 24-36 post-operative h (p = 0.354). CONCLUSION: Patients with clinically significant post-operative microembolism had an approximately 15 times higher risk of ipsilateral stroke/TIA and most were identified during a 30-min study in the first post-operative hour.

Clinical application of transcranial Doppler monitoring for embolic signals.

A major advantage of transcranial ultrasound is its suitability for continuous monitoring. Microembolic signals (MES) are brief, high-intensity transients that occur when particulate microemboli or gaseous microbubbles pass through the ultrasound beam. These MES have been detected in several clinical scenarios, but rarely in age-matched controls. The detection of MES provides important pathophysiological information in a variety of disorders, but their clinical importance and possible therapeutic implications are still under debate. The present article summarizes the significance of MES in different clinical settings and outlines some of the problems to be resolved so that transcranial ultrasound can be applied in clinical practice.

Carotid endarterectomy for asymptomatic carotid stenosis.

BACKGROUND: Carotid endarterectomy (CEA) is of proven benefit in recently-symptomatic patients with severe carotid stenosis. Its role in asymptomatic stenosis is still debated. The Asymptomatic Carotid Surgery Trial (ACST) more than doubled the number of patients randomised to CEA trials. This revised review incorporates the recently published ACST results. OBJECTIVES: Our objective was to determine the effects of CEA for patients with asymptomatic carotid stenosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (searched May 2004), MEDLINE (1966 to May 2004), EMBASE (1980 to June 2004), Current Contents (1995 to January 1997), and reference lists of relevant articles. We contacted researchers in the field to identify additional published and unpublished studies. SELECTION CRITERIA: All completed randomised trials comparing CEA to medical treatment in patients with asymptomatic carotid stenosis. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial quality. Attempts were made to contact investigators to obtain missing information. MAIN RESULTS: Three trials with a total of 5223 patients were included. In these trials, the overall net excess of operation-related perioperative stroke or death was 2.9%. For the primary outcome of perioperative stroke or death or any subsequent stroke, patients undergoing CEA fared better than those treated medically (relative risk (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83). Similarly, for the outcome of perioperative stroke or death or subsequent ipsilateral stroke, there was benefit for the surgical group (RR 0.71, 95% CI 0.55 to 0.90). For the outcome of any stroke or death, there was a non-significant trend towards fewer events in the surgical group (RR 0.92, 95% CI 0.83 to 1.02). Subgroup analyses were performed for the outcome of perioperative stroke or death or subsequent carotid stroke. CEA appeared more beneficial in men than in women and more beneficial in younger patients than in older patients although the data for age effect were inconclusive. There was no statistically significant difference between the treatment effect estimates in patients with different grades of stenosis but the data were insufficient. AUTHORS' CONCLUSIONS: Despite about a 3% perioperative stroke or death rate, CEA for asymptomatic carotid stenosis reduces the risk of ipsilateral stroke, and any stroke, by approximately 30% over three years. However, the absolute risk reduction is small (approximately 1% per annum over the first few years of follow up in the two largest and most recent trials) but it could be higher with longer follow up.

Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke.

BACKGROUND: Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy. METHODS: Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion. RESULTS: Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group. CONCLUSIONS: These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.

Identification of patients at risk for ischaemic cerebral complications after carotid endarterectomy with TCD monitoring.

OBJECTIVES: Transcranial Doppler (TCD) monitoring for micro embolic signals (MES), directly after carotid endarterectomy (CEA) may identify patients at risk of developing ischaemic complications. In this retrospective multicentre study, this hypothesis was investigated. METHODS: Centres that monitored for MES after CEA were identified by searching Medline. Individual patient data were obtained from centres willing to collaborate. The number of emboli in 1h was computed. Uni- and multivariate logistic regression analyses were performed for the variables gender, age and number of MES. Discriminative ability of MES monitoring was investigated in a ROC curve. RESULTS: Nine hundred and ninety-one patients were monitored in the first 3h after CEA. Two percent developed ischaemic cerebral complications. Univariate analysis revealed statistically significant associations between ischaemic cerebral complications and both gender and MES, but not age. In a multivariate analysis, > or =8 MES/h showed a statistically significant relationship with cerebral complications (OR 8.1, 95% CI 1.8-36), in contrast to gender (OR 2.2, 95% CI 0.9-5.5). The ROC curve yielded an AUC of 0.83 for monitoring of MES. CONCLUSIONS: These results support the use of TCD monitoring for MES shortly after CEA in order to identify patients at risk of developing ischaemic cerebral complications.

Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke.

BACKGROUND AND PURPOSE: We sought to characterize the spatial and temporal evolution of human cerebral infarction. Using a novel method of quantitatively mapping the distribution of hypoxic viable tissue identified by 18F-fluoromisonidazole (18F-FMISO) PET relative to the final infarct, we determined its evolution and spatial topography in human stroke. METHODS: Patients with acute middle cerebral artery territory stroke were imaged with 18F-FMISO PET (n=19; <6 hours, 4; 6 to 16 hours, 4; 16 to 24 hours, 5; 24 to 48 hours, 6). The hypoxic volume (HV) comprised voxels with significant (P<0.05; >1 mL) uptake on statistical parametric mapping compared with 15 age-matched controls. Central, peripheral, and external zones of the corresponding infarct on the anatomically coregistered delayed CT were defined according to voxel distance from the infarct center and subdivided into 24 regions by coronal, sagittal, and axial planes. Maps ("penumbragrams") displaying the percentage of HV in each region were generated for each time epoch. RESULTS: Higher HV was observed in the central region of the infarct in patients studied within 6 hours of onset (analysis of covariance [ANCOVA]; P<0.05) compared with those studied later, in whom the HV was mainly in the periphery or external to the infarct. HV was maximal in the superior, mesial, and posterior regions of the infarct (ANCOVA; P<0.05). CONCLUSIONS: These observations suggest that infarct expansion occurs at the expense of hypoxic tissue from the center to the periphery of the ischemic region in humans, similar to that seen in experimental animal models. These findings have important pathophysiological and therapeutic implications.

Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is the most serious complication of thrombolytic therapy for stroke. We explored factors associated with this complication in the Australian Streptokinase Trial. METHODS: The initial CT scans (< or =4 hours after stroke) of 270 patients were reviewed retrospectively by an expert panel for early signs of ischemia and classified into the following 3 categories: no signs or < or =1/3 or >1/3 of the vascular territory. Hemorrhage on late CT scans was categorized as major or minor on the basis of location and mass effect. Stepwise, backward elimination, multivariate logistic regression analysis was used to identify risk factors for each hemorrhage category. RESULTS: Major hemorrhage occurred in 21% of streptokinase (SK) and 4% of placebo patients. Predictors of major hemorrhage were SK treatment (odds ratio [OR], 6.40; 95% CI, 2.50 to 16.36) and elevated systolic blood pressure before therapy (OR, 1.03; 95% CI, 1.01 to 1.05). Baseline systolic blood pressure >165 mm Hg in SK-treated patients resulted in a >25% risk of major secondary hemorrhage. Early ischemic CT changes, either < or =1/3 or >1/3, were not associated with major hemorrhage (OR, 1.58; 95% CI, 0.65 to 3.83; and OR, 1.11; 95% CI, 0.45 to 2.76, respectively). Minor hemorrhage occurred in 30% of the SK and 26% of the placebo group. Predictors of minor hemorrhage were male sex, severe stroke, early CT changes, and SK treatment. Ninety-one percent of patients with major hemorrhage deteriorated clinically compared with 23% with minor hemorrhage. CONCLUSIONS: SK increased the risk of both minor and major hemorrhage. Major hemorrhage was also more likely in patients with elevated baseline systolic blood pressure. However, early CT changes did not predict major hemorrhage. Results from this study highlight the importance of baseline systolic blood pressure as a potential cause of hemorrhage in patients undergoing thrombolysis.

Dextran reduces embolic signals after carotid endarterectomy.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

Carotid endarterectomy for asymptomatic carotid stenosis.

BACKGROUND: Whilst carotid endarterectomy (CEA) is of proven benefit in recently symptomatic patients with severe carotid stenosis, the role of carotid endarterectomy in preventing stroke in patients with asymptomatic carotid stenosis remains uncertain. OBJECTIVES: The objective of this review therefore was to determine the effects of CEA for patients with asymptomatic carotid stenosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (June 1998), Medline (1966-Mar 1998), Current Contents (1995-Jan 1997), and reference lists of relevant articles. We contacted researchers in the field to identify additional published and unpublished studies. SELECTION CRITERIA: All completed randomised trials comparing CEA to medical treatment in patients with asymptomatic carotid stenosis. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial quality. Attempts were made to contact investigators to obtain missing information. MAIN RESULTS: Six trials were identified, but two were excluded on methodological grounds. Four trials with 2203 patients were included. In two trials aspirin was only given to patients in the medical group, and in two all patients received aspirin. The net excess "perioperative stroke or death" rate in the surgical group was 2.7% with relative risk 6.52 (95% confidence interval 2.66-15.96). The rates of "perioperative stroke or death or subsequent ipsilateral stroke" were 6.8% in the medical group vs 4.9% in the surgical group with RR 0.73 (0.52-1.02) favouring surgery. The rates of "any stroke or perioperative death" were 10.4% (medical) vs 8.1% (surgical) with RR 0.79 (0.60-1.02). The rates of "any stroke or death" were 23.2% (medical) vs 20.2% (surgical) with RR 0.89 (0.76-1.04). There were too few patients in CEA vs aspirin trials to determine whether aspirin had any confounding effect on outcome. An additional analysis including data from a fifth small unpublished trial altered slightly the risk ratios in favour of surgery and narrowed confidence intervals sufficiently to achieve statistical significance for each outcome. However, inclusion of these data had no appreciable effect on relative or absolute risk reduction. REVIEWER'S CONCLUSIONS: There is some evidence favouring CEA for asymptomatic carotid stenosis, but the effect is at best barely significant, and extremely small in terms of absolute risk reduction.

Hippocampal sclerosis: development in adult life.

Hippocampal sclerosis (HS) is the most common pathological lesion underlying intractable temporal lobe epilepsy. It is not known whether HS exists before the onset of epilepsy or whether it is caused by seizures. Its has been proposed that childhood seizures cause HS. Optimized magnetic resonance imaging (MRI), hippocampal volumes and T(2) signal quantitation were performed 2 weeks and 8 months following at tonic-clonic seizure in a 23-year-old man. MRI 14 days after the seizure showed symmetrical hippocampal volumes (ratio R/L = 1.03) with intact internal architecture bilaterally but marked signal change in the right hippocampus (T(2) right = 121, T(2) left = 103, normal < or = 108 ms). Eight months later this hippocampus showed severe atrophy with a volume ratio of 0.65 and T(2) values of 117 (right) and 109 ms (left). High-resolution imaging showed that volume loss occurred mainly in the CA1 region which showed high signal in the initial study. Characteristic MRI features of HS can develop in adults and HS cannot always be assumed to have its origins in childhood. Hypoxia in the context of seizures may be an important component in hippocampal damage. HS may be a preventable lesion and MRI signal change seen in the neuronal layers of the hippocampus may be an indication for neuroprotection.

White matter medullary infarcts: acute subcortical infarction in the centrum ovale.

Acute infarction confined to the territory of the white matter medullary arteries is a poorly characterised acute stroke subtype. 22 patients with infarction confined to this vascular territory on CT and/or MRI were identified from a series of 1,800 consecutive admissions to our stroke unit (1.2%) between August 1993 and March 1997. 19 patients had small infarcts (< 1.5 cm maximum diameter) and 3 large infarcts (> 1.5 cm). Small infarcts were associated with a history of smoking (69%), hypertension (58%), and hyperlipidaemia (37%), and less frequently with atrial fibrillation (21%). Significant (>50%) ipsilateral carotid stenosis (16%) was a less frequent finding in this group. Patients most commonly presented with weakness and/or sensory disturbance affecting mainly the upper limbs, but dysarthria, dysphasia, and ataxia were also seen. Large infarcts were infrequent in our series, but did not differ significantly from small infarcts with respect to clinical presentation or risk factor profiles (p > 0.05 for all comparisons). The majority of symptomatic patients with white matter medullary infarcts are associated with small (< 1.5 cm diameter) lesions and a risk factor profile consistent with small vessel disease. More data are required to elucidate the mechanism of larger (> 1.5 cm) infarcts. Because of the potential overlap between white matter medullary infarcts and internal watershed infarcts, suggested criteria for each are presented.

Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group.

The Australian Streptokinase Trial was a randomized, double-blind, placebo-controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L-hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after therapy to test the hypothesis that SK may improve the hemodynamic measures of reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen patients received SK and 19 placebo. Baseline characteristics were similar in both groups, and there were no differences in clinical outcomes assessed at 3 months after stroke. Although there was no increase in the group mean perfusion defect or volume on SPECT after thrombolytic therapy, a larger number of patients demonstrating the combined end point of reperfusion or recanalization was seen in the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01). Although SK given within 4 hours of acute ischemic stroke appears to improve arterial patency/tissue reperfusion, this effect is neither early nor extensive enough to influence overall clinical outcome.

Transcranial Doppler detected cerebral microembolism following carotid endarterectomy. High microembolic signal loads predict postoperative cerebral ischaemia.

Cerebral ischaemia, the most frequent serious complication of carotid endarterectomy (CEA), usually occurs in the early postoperative period and is often the result of thromboembolism. We hypothesized that the early postoperative detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) may be of value in identifying patients at risk of postoperative cerebral ischaemia and that the MES rate may be an important determinant in risk prediction. Sixty-five patients undergoing CEA were studied at intervals up to 24 h postoperatively with TCD insonation of the middle cerebral artery ipsilateral to the operation side. Study design was open and prospective with blinded off-line analysis of MES counts. End-points were any focal ischaemic neurological deficit and/or death up to 30 days postoperatively. MES were detected in 69% of cases during the first hour postoperatively with counts ranging from 0 to 212 MES/h (means 19 MES/h; SEM +2- 4.5; median 4 MES/h). In seven cases (10.8%) counts were > 50 MES/h. Five of these seven cases developed ischaemic neurological deficits in the territory of the insonated middle cerebral artery during the monitoring period. The positive predictive value of counts > 50 MES/h for cerebral ischaemia was 0.71. Frequent signals (> 50 MES/h) occur in approximately 10% of cases in the early postoperative phase of CEA and are predictive for the development of ipsilateral focal cerebral ischaemia.

Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group.

OBJECTIVES: To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. DESIGN: Randomized, double-blind, placebo-controlled trial with 3-month follow-up. PARTICIPANTS: A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. INTERVENTION: Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. MAIN OUTCOME MEASURE: Combined death and disability score (Barthel index <60) 3 months after the stroke. RESULTS: Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2%[12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (P=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). CONCLUSION: The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.