Advancements in understanding the mechanisms of symptomatic lacunar ischemic stroke: translation of knowledge to prevention strategies.

Symptomatic lacunar ischemic stroke (25% of all brain infarctions) results from occlusion of a single penetrating artery by microatheromas or lipohyalinosis and rarely from an intracranial atheromatous branch disease. Recurrent lacunar stroke may be associated with more severe clinical features and has been involved in producing lacunar state and vascular subcortical dementia. In the first multicenter randomized clinical trial (SPS3) focused on stroke prevention among patients with recent lacunar stroke, the addition of clopidogrel to aspirin not only did not reduced significantly the risk of recurrent stroke, but also increased significantly the likelihood of hemorrhage and fatal outcome. If lacunar stroke is primarily non-atherothromboembolic, secondary prevention aimed at preventing atheroma progression may not be very effective. The efficacy of drugs that improve endothelial function in lacunar stroke patients remains to be studied in the future.

Statin pretreatment may increase the risk of symptomatic intracranial haemorrhage in thrombolysis for ischemic stroke: results from a case-control study and a meta-analysis.

The influence of statins on the results of intravenous thrombolysis for ischemic stroke is controversial. We studied the risks and benefits of statin pretreatment (SP) in patients treated with intravenous alteplase (t-PA) at our institution, and included our data to a meta-analysis of previous related studies. We reviewed prospectively collected data from consecutive patients with acute ischemic stroke treated with IV rt-PA at our institution over the past 9 years. We compared symptomatic intracranial haemorrhage (SICH), favourable short-term outcome (decrease of ≥4 points on the NIHSS score after 24 h from baseline assessment), favourable long-term outcome (mRS score ≤2 at 3 months) and mortality rates between statin-pretreated (SPP) and nonstatin-pretreated patients (NSPP). We performed a systematic search through MEDLINE/PubMed and Embase datasets to identify similar English language studies. A total of 182 patients were included (mean age 68.3 ± 11.4 years, 54.3% men). There were no significant differences between SPP and NSPP regarding SICH (3.3 vs. 1.7%, p = 0.47), favourable short-term outcome (44.8 vs 56%, p = 0.31) and favourable long-term outcome rates (40 vs 44.1%, p = 0.84). In a meta-analysis of 1,055 patients, SP was neither related to long-term functional outcome nor mortality, but it was a risk factor for SICH (OR 1.99, 95% CI 1.03-3.84, p = 0.04). Statin pretreatment may increase the risk of SICH in patients receiving IV t-PA for ischemic stroke, though it does not influence the 3 months outcome. Prospective studies are needed to confirm this safety concern.

Hemostatic proteins and their association with hematoma growth in patients with acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: We tested the hypothesis that proteins of hemostasia could be associated with hematoma growth (HG) in patients with acute intracerebral hemorrhage. METHODS: We prospectively studied patients with spontaneous supratentorial intracerebral hemorrhage within the first 6 hours after the onset of symptoms. HG was defined as an increase > 33% in the volume of hematoma on CT obtained 24 to 72 hours after the onset of symptoms in comparison with the CT obtained at admission. We collected admission and follow-up blood samples. We measured fibrinogen, factor XIII, thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor, plasminogen, α2-antiplasmin, tissue plasminogen activator, d-dimer, thrombomodulin, thrombin-antithrombin complex, and plasmin-antiplasmin complex. RESULTS: We included 90 patients with a mean age of 71 ± 10.8 years; 61% were men. HG was observed in 35 (39%) of the patients. Mean baseline and follow-up protein measurements showed no difference between the groups with and without HG. The analysis of variance showed that factor XIII activity decreased in the non-HG group in the 24 to 72 hours sample, whereas it increased in the HG group (P = 0.001). CONCLUSIONS: Factor XIII was the only measured protein related to HG. The levels at the follow-up sample decreased in the non-HG group and increased in the HG group. Further studies are needed to confirm this association.

Remote cerebral hematomas in patients treated with intravenous rt-PA.

The frequency, clinical presentation, radiological features, and prognosis of remote cerebral hematomas (rPH) are not well known. We report our experience in patients treated with intravenous rt-PA. We reviewed our database of consecutive patients treated at our hospital from 1999 to 2008. We used the inclusion/exclusion criteria of the ECASS-2 study from 1999 to 2003, and the criteria of the SITS-MOST study since 2004. A follow-up CT scan was obtained in all of the patients within the first 36 h of treatment. Cerebral hemorrhagic complications were classified as hemorrhagic infarction (HI-1/HI-2) and parenchymal hematoma (PH-1/PH-2). The rPH was defined as any extra-ischemic hemorrhagic lesion observed in the follow-up CT. A favorable outcome was defined as a score 0-1 on the Rankin scale at 3 months. We treated 210 patients (mean age 67.6 +/- 12.4 years, 56% were men). The median initial NIHSS score was 14. Patients with rPH (n = 7) had a mean age of 72.4 +/- 7.5 years and 43% were men. The median initial NIHSS score was 15. Three patients had multifocal rPH; three patients had a single rPH and in one patient the rPH was associated with a PH-2. rPH were lobar in six patients and in brainstem in one patient, symptomatic in five patients and asymptomatic in two patients. The outcome was unfavorable in all of them; four deaths (57%) were recorded. Remote cerebral hemorrhage is an infrequent complication after rt-PA treatment (3.3%), it is usually lobar and symptomatic and has an uniformly unfavorable outcome.

Mutations in the NKX2-5 gene in patients with stroke and patent foramen ovale.

OBJECTIVE: Patent foramen ovale (PFO) has been related to stroke but its existence has not been explained to date. NKX2-5 is the most implicated gene in fetal atrial septation. We studied NKX2-5 with respect to the presence or absence of PFO in stroke patients. METHODS: A prospective analysis of NKX2-5 regarding age, gender, PFO, right-to-left shunt (RLS) size and atrial septal aneurysm (ASA) was performed in consecutive stroke patients and in 50 controls. The entire coding region and intron-exon boundaries of NKX2-5 gene were analyzed by PCR and sequencing of DNA from peripheral lymphocytes. RESULTS: One hundred patients participated in the study (mean age 56.5+/-12.4 years, 58% males) and PFO was diagnosed in 34% of them by transesophageal echocardiography. RLS was small (12%), moderate (2%) and large (20%). ASA was present in four patients. DNA revealed a novel c.2357G>A change in one PFO patient with cryptogenic stroke. Furthermore, c.182C>T, a mutation previously described in patients with cardiac defects, was detected in two non-PFO women with cryptogenic stroke. None of these changes were detected in our controls. The c.172A>G polymorphism was found in 21% of controls. It appeared more frequently in ASA patients (p=0.084), in cryptogenic PFO stroke patients (p=0.097) and in patients with known causes of stroke (p=0.037). The c.2850C>A polymorphism was also detected in our series with no differences in PFO, RLS size or ASA. CONCLUSION: Despite the fact that the NKX2-5 could account for the persistence of PFO, mutations of this gene in peripheral blood DNA were barely detected in our study.

Lacunar stroke.

Lacunar infarcts or small subcortical infarcts result from occlusion of a single penetrating artery and account for one quarter of cerebral infarctions. Patients with a lacunar infarct usually present with a classical lacunar syndrome (pure motor hemiparesis, pure sensory syndrome, sensorimotor stroke, ataxic hemiparesis or dysarthria-clumsy hand) and, less frequently, an atypical lacunar syndrome. Hypertension and diabetes mellitus are major risk factors for lacunar stroke. Lacunar infarcts show a paradoxical clinical course with a favorable prognosis in the short term, characterized by a low early mortality and reduced functional disability on hospital discharge, but with an increased risk of death, stroke recurrence and dementia in the mid- and long term. Asymptomatic progression of small-vessel disease is a typical feature of the lacunar infarcts. For this reason, lacunar infarction should be regarded as a potentially severe condition rather than a relatively benign disorder and, therefore, lacunar stroke patients require adequate and rigorous management and follow-up. Antiplatelet drugs, careful blood pressure control, the use of statins and modification of lifestyle risk factors are key elements in secondary prevention after lacunar stroke.

Influence of antiplatelet pre-treatment on the risk of symptomatic intracranial haemorrhage after intravenous thrombolysis.

BACKGROUND: The influence of antiplatelet agents (AP) in the development of a symptomatic intracranial haemorrhage (SICH) after intravenous rt-PA is not well known. We assessed the hypothesis that pre-treatment with AP may increase that risk. METHODS: We studied data from consecutive patients with ischaemic stroke treated with intravenous rt-PA within the first 3 h after symptom onset. We recorded the antecedent of any AP therapy previous to thrombolysis. A follow-up CT was performed routinely 24-36 h after the infusion of rt-PA. Intracranial bleeding was categorized according to the criteria of the European Cooperative Acute Stroke Study II (ECASS II) into haemorrhagic infarction type 1 and 2 and parenchymal haemorrhage type 1 and 2. SICH was diagnosed if it was of the parenchymal haemorrhage type, occurred within the first 36 h and was associated with neurological deterioration. RESULTS: Of a total of 605 patients, 137 (22.6%) were pre-treated with AP, most of them (n = 106) with aspirin. Any type of intracranial haemorrhage was observed in 119 patients (19.7%), without differences between the AP (18.4%) and the non-AP (20.2%) groups. Parenchymal haemorrhage was observed in 41 patients (8.5%) and SICH in 26 (4.3%). There was a non-significant rise in the frequency of SICH in the AP group compared with the non-AP group (6.6 vs. 3.6% p = 0.10). CONCLUSIONS: Pre-treatment with AP non-significantly increases the risk of SICH and therefore this antecedent should not be a contraindication for intravenous thrombolysis.

Change in hemostatic markers after recombinant tissue-type plasminogen activator is not associated with the chance of recanalization.

BACKGROUND AND PURPOSE: We evaluated the association between recombinant tissue-type plasminogen activator recanalization and change in hemostatic markers. METHODS: We studied 40 patients. Recanalization was measured with transcranial Doppler. We evaluated the change in markers of coagulation (fibrinogen) and fibrinolysis (thrombin activatable fibrinolysis inhibitor and alpha(2)-antiplasmin) in patients with ischemic stroke treated with recombinant tissue-type plasminogen activator. Samples were obtained before and 90 minutes after recombinant tissue-type plasminogen activator infusion. RESULTS: The analyses (2-way analysis of variance) showed that the change in the value of each marker did not depend on the vascular patency status. CONCLUSIONS: From a practical point of view, the measurement of these hemostatic markers is probably not useful for predicting recanalization.

Frequency and predictors of symptomatic intracerebral hemorrhage in patients with ischemic stroke treated with recombinant tissue plasminogen activator outside clinical trials.

BACKGROUND: To determine the frequency and predictors of symptomatic intracerebral hemorrhage (SICH) in patients treated with recombinant tissue plasminogen activator (rt-PA). METHODS: We reviewed the databases of 7 tertiary hospitals that treated ischemic stroke patients with intravenous rt-PA. We recorded demographic data, vascular risk factors, time between onset and treatment, dose, the NIHSS score, body temperature, blood pressure, platelet count, blood glucose, antiplatelet treatment, and CT data. We also registered the study protocol used for treatment and deviations from the accepted protocol. A control CT was performed on all patients. SICH was diagnosed if a parenchymal hematoma was detected within the 36 h after rt-PA and was associated with an increase of > or =4 in the NIHSS score. Bivariate analyses were performed followed by a logistic regression analysis. RESULTS: A total of 347 patients were studied, whose mean age was 68 +/- 10.9 years; 56% were men. Thirty-two patients (9.2%) exhibited a parenchymal hematoma, and 8 patients (2.3%) suffered a SICH. Patients with SICH had a higher frequency of previous transient ischemic attack (p = 0.04), early signs of ischemia (p = 0.003), hyperdense arterial sign (p = 0.008), and deviations (p = 0.002). Early signs of ischemia (OR 8.5, 95% CI 1.6-45.4, p = 0.01) and deviation from the protocol (OR 11.1, 95% CI 2.4-50, p = 0.002) were independent predictors of SICH. CONCLUSIONS: SICH is infrequent in patients with ischemic stroke treated with rt-PA outside of a clinical trial. Its frequency increases in the presence of early signs of ischemia on the non-contrast CT scan and deviations from the recommended protocol.

A novel antiganglioside specificity against terminal NeuNAc(alfa 2-3)Gal in acute bulbar palsy.

We describe a patient with acute oropharyngeal-facial diplegia, tongue palsy and albuminocytological dissociation following upper respiratory tract infection. Electrophysiological abnormalities in blink reflex suggested a brainstem lesion. High titers of anti-GM3, GD1a and GT1b IgG class serum antibodies were initially detected. Absorption studies indicated that antibodies were directed to a common terminal epitope NeuNAc(alfa 2-3)Gal. This novel antiganglioside antibody specificity may play a role in this unusual regional form of acute bulbar palsy of possible central origin. These data are supportive for extending the panel of antiganglioside specificities with anti-GM3.

Almost perfect concordance between simultaneous transcranial Doppler and transesophageal echocardiography in the quantification of right-to-left shunts.

BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) and transcranial Doppler (TCD) are the methods of choice to study patent foramen ovale (PFO), but there are discrepancies between the 2 concerning PFO detection. No study has analyzed right-to-left shunt (RLS) quantification concordance. The 2 methods are carried out in different hemodynamic states, and the Valsalva maneuver (VM) required in each also differs. The authors compared PFO detection and concordance of RLS quantification classifications performing the 2 studies simultaneously. METHODS: The authors prospectively included consecutive stroke patients undergoing TEE and applied the TCD protocol of the Consensus Conference. Echocardiographic PFO was diagnosed when at least 3 microbubbles (MBs) were detected in the left atrium within 3 heartbeats after opacification of the right atrium. RLS quantification was (1) TCD: minimum (1-10 MBs), moderate (11-25 MBs), and massive (>25 MBs) and (2) TEE: small (3-10 MBs), moderate (11-30 MBs), and large (>30 MBs). STATISTICS: contingency tables (chi(2) and K test). Results. The authors studied 110 patients whose mean age was 56.7 +/- 12.1 years, and 60.9% were men. PFO was detected at the first VM in 30% of patients with TCD and in 31.8% with TEE. At the second VM, both methods detected the same patients (32.7%). RLS was minimum (14), moderate (5), and massive (17) in TCD and small (13), moderate (3), and large (20) in TEE. There was an almost perfect concordance in RLS quantification (K = 0.928, P = .001), with only 4 discrepancies. CONCLUSIONS: Simultaneous study with TCD and TEE showed an almost perfect concordance in PFO detection and RLS quantification.

Does thrombolysis benefit patients with lacunar syndrome?

The efficacy of thrombolysis in clinical stroke subtypes is unclear. We compared the benefit of intravenous rt-PA in 11 patients with lacunar syndrome with that in 33 patients with a non-lacunar syndrome. Patients were matched by NIHSS score and time to treatment. Although no statistically significant differences were detected in outcome, the benefit was greater in the non- lacunar syndrome group.

Pretreatment hemostatic markers of symptomatic intracerebral hemorrhage in patients treated with tissue plasminogen activator.

BACKGROUND AND PURPOSE: Symptomatic intracerebral hemorrhage (ICH) is a major complication of thrombolysis in patients with acute ischemic stroke. We analyzed whether baseline hemostatic markers could predict symptomatic ICH (SICH). METHODS: In a multicenter study of patients treated with intravenous tissue plasminogen activator (t-PA) within 3 hours of stroke onset, we analyzed the following variables: demographic data, vascular risk factors, blood glucose at admission, time from the onset of symptoms to t-PA infusion, blood pressure, neurological deficit measured by the National Institutes of Health Stroke Scale (NIHSS) score, early signs of ischemia on the baseline computed tomography (CT) scan, and protocol deviations. In blood samples, the following markers of coagulation/fibrinolysis were measured before treatment: fibrinogen, prothrombin fragments 1+2, Factor XIII, Factor VII, alpha2 antiplasmin, plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor. ICH was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. SICH was defined as a parenchymal hematoma-1 (PH1) or PH2 type, associated with an increase in > or =4 points on the NIHSS score appearing within 36 hours after infusion. RESULTS: We studied 114 patients. Mean age was 68.4+/-12.7 years, and 61% were men. The median baseline NIHSS score was 14. Mean time to treatment was 153+/-33 minutes. Eight patients had SICH (7%), and 18 patients (15.7%) had asymptomatic ICH. None of the baseline markers of coagulation/fibrinolysis were associated with SICH. In the multivariate analysis, only NIHSS on admission was an independent risk factor for SICH. CONCLUSIONS: None of the hemostatic markers analyzed in our study predicted symptomatic cerebral hemorrhage in patients with ischemic stroke treated with t-PA.

Cerebrovascular disease as a complication of cardiac transplantation.

BACKGROUND AND OBJECTIVES: To characterize the frequency, risk factors, clinical presentation and etiological subtypes of cerebrovascular diseases (CVD) following cardiac transplantation (CTX). METHODS: In a retrospective review of our CTX database (period 1984-2002), we assessed demographic data, vascular risk factors, surgery and donor details. We classified ischemic stroke (IS) using the clinical criteria of the Oxfordshire Community Stroke Project and the etiological criteria of the TOAST study. Logistic regression analysis and survival curves were carried out. RESULTS: CTX was performed in a total of 314 patients (age 46 +/- 14 years, 78% male) and mean follow-up was 54 +/- 57 months. Twenty-two patients (7%) presented CVD: hemorrhagic stroke in 12%, transient ischemic attack in 28% and IS in 60%. CVD were early postoperative (less than 2 weeks) in 20% of patients and late in 80%. The clinical presentation in patients with IS was total anterior circulation (23.1%), partial anterior (38.4%), lacunar (15.4%) and posterior circulation (23.1%), and the etiological classification was large artery atherosclerosis (15.4%), cardioembolism (14.4%), small vessel disease (15.4%), unusual causes (15.4%) and undetermined cause (38.4%). The only independent predictor of CVD was a prior CVD event with an odds ratio of 8.2 (95% CI, 2.2-30.2, p < 0.02). The estimated risk of CVD at 5 years was greater (p < 0.02) in patients with prior CVD (4.1%) than in those without (1.1%). CONCLUSIONS: CVD are a relatively frequent complication after CTX (7%) and usually occur in the late postoperative phase. CVD prior to transplantation increase the risk of CVD after this procedure.

Relationship between transcranial Doppler and CT data in acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It would be useful to have a noninvasive test for correlation with CT findings in patients with intracerebral hemorrhage (ICH). We determined which transcranial Doppler (TCD) variables are related to which CT data in patients with ICH. METHODS: We prospectively included 51 patients (age +/- SD, 66.2 +/- 12.4 years; 30 men, 21 women) with first-ever supratentorial, nontraumatic ICH. CT and TCD examination were performed in the acute stage (less than 12 hours from symptom onset). TCD recordings were obtained from the middle cerebral arteries, and the following variables were analyzed: systolic (Vs), diastolic (Vd), mean (Vm) velocities, and pulsatiliy index from the affected (a) and unaffected (u) hemispheres. RESULTS: PIs obtained for both hemispheres were positively correlated with hematoma volume (aPI, r=0.43, P=.001; uPI, r=0.44, P=.001), volume of hypoattenuation (aPI r=0.64, P <.0001; uPI, r=0.39, P=.005), total volume (aPI, r=0.59, P <.0001; uPI, r=0.48, P <.0001), and midline shift (aPI, r=0.28, P=.04; uPI, r=0.29, P=.03). Both PIs were increased in patients with intraventricular hemorrhage (aPI, P=.01; uPI P=.004). No TCD parameter was correlated with ventricular size. CONCLUSION: Most TCD parameters were correlated with CT data in the acute stage of ICH. An increase in PI probably reflects intracranial hypertension and mass effect. Further studies are needed to determine the clinical application of our findings.

Benefits of a prehospital stroke code system. Feasibility and efficacy in the first year of clinical practice in Barcelona, Spain.

BACKGROUND AND OBJECTIVES: Hospital admission delay is a main limiting factor for effective thrombolytic therapy in stroke patients. We developed a stroke code system for rapid request of emergency transportation to the hospital and a priority availability of the attending neurologist on the patient's arrival at the Emergency Department (ED). METHODS: Over a 1-year period, a 24-hour telephone hotline between the attending neurologist and the Barcelona public emergency coordination service was established. Priority 1 (P1) was defined as a patient with symptoms suggestive of acute stroke with onset of less than 3 h, in which case immediate transportation service and rapid ED reception was organized. Data from patients in the P1 group (n = 39) and patients without activation of the stroke code (P0) (n = 181) were compared. RESULTS: There were significant differences between P1 and P0 groups in mean time from ED arrival to request for neurologic assessment (4.4 +/- 19.5 vs. 194.7 +/- 244.9 min, p < 0.001), from arrival to neurologic examination (12.6 +/- 21.1 vs. 225.3 +/- 258.2 min, p < 0.005), and from arrival to performance of brain CT scan (35.5 +/- 34.9 vs.120.3 +/- 143.2 min, p < 0.001), and also in the number of patients treated with thrombolytic agents (19 vs. 4.5%, p < 0.003). There were no differences between groups in the time elapsed from stroke onset to ED arrival. CONCLUSIONS: Activation of the stroke code was effective in increasing the percentage of patients treated with thrombolytic drugs and also in shortening the delay from ED arrival until neurologic assessment and from ED arrival until brain CT.

Favorable outcome of ischemic stroke in patients pretreated with statins.

BACKGROUND AND PURPOSE: Statins may be beneficial for patients with acute ischemic stroke. We tested the hypothesis that patients pretreated with statins at the onset of stroke have less severe neurological effects and a better outcome. METHODS: We prospectively included consecutive patients with ischemic stroke of <24-hour duration. We recorded demographic data, vascular risk factors, Oxfordshire Classification, National Institutes of Health Stroke Scale (NIHSS) score, admission blood glucose and body temperature, cause (Trial of Org 10172 in Acute Treatment [TOAST] criteria), neurological progression at day 3, previous statin treatment, and outcome at 3 months. We analyzed the data using univariate methods and a logistic regression with the dependent variable of good outcome (modified Rankin Scale [mRS] 0 to 1, Barthel Index [BI] 95 to 100). RESULTS: We included 167 patients (mean age 70.7+/-12 years, 94 men). Thirty patients (18%) were using statins when admitted. In the statin group, the median NIHSS score was not significantly lower and the risk of progression was not significantly reduced. Favorable outcomes at 3 months were more frequent in the statin group (80% versus 61.3%, P=0.059 with the mRS; 76.7% versus 51.8%, P=0.015 with the BI). Predictors of favorable outcome with the BI were: NIHSS score at admission (OR: 0.72; CI: 0.65 to 0.80; P<0.0001), age (OR: 0.96; CI: 0.92 to 0.99; P=0.017), and statin group (OR: 5.55; CI: 1.42 to 17.8; P=0.012). CONCLUSIONS: Statins may provide benefits for the long-term functional outcome when administered before the onset of cerebral ischemia. However, randomized controlled trials will be required to evaluate the validity of our results.

[Intravenous tissue-type plasminogen activator for the treatment of acute cerebral ischemia]. / Tratamiento intravenoso con activador del plasminógeno tisular en la isquemia cerebral aguda.

BACKGROUND AND OBJECTIVE: Whether the risk of symptomatic hemorrhagic transformation (SHT) of cerebral infarction associated with the use of tissue plasminogen activator (t-PA) is higher in clinical practice than in clinical trials is unknown. The aim of this study was to analyze the safety profile and clinical outcome of patients with acute cerebral ischemia who received open treatment with t-PA in Spanish hospitals. PATIENTS AND METHOD: This prospective and observational study included 155 consecutive patients with an ischemic stroke treated within 3 hours from the onset of symptoms, or within 6 hours in the absence of early signs of large cerebral infarction on CT. Intravenous t-PA was administered at 0.9 mg/kg (10% as bolus) during a 60 minutes infusion. Neurological worsening within 24-36 hours was evaluated by the NIH stroke scale (NIHSS). Primary safety and outcome variables were SHT on CT performed at 24-36 hours, mortality and independence at 90 days. Patients were treated by neurologists with expertise in acute stroke, and stroke monitoring was performed in acute stroke units. RESULTS: Baseline median NIHSS was 16, and mean time from stroke onset to treatment was 163 minutes. SHT was found in 12 patients (7.7%; 95% CI, 4.0-13.1), and it was fatal in 7 (4.5%, 95% CI, 1.8-9.1). Overall mortality at 90 days was 16.8% (95% CI, 11.2-23.6). At 24 hours, 48% (95% CI, 39.7-55.9) of patients had improved >= 4 points in the NIHSS, and 29% (95 % CI, 22.0-36.8) showed a >= 10 points improvement or total recovery. At 3 months, 56% (95% CI, 47.9-64.1) of patients were independent. CONCLUSIONS: In Spanish hospitals with stroke units or stroke teams, the use in the clinical practice of intravenous t-PA by experienced neurologists is safe, and it is associated with a favourable outcome similar to that observed in clinical trials.