Dolores Cocho

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 <4-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.

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 (χ2 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.

Prognostic value of Pulsatility Index in acute intracerebral hemorrhage

Objective: To investigate whether data obtained by transcranial Doppler (TCD) have prognostic value in patients with intracerebral hemorrhage (ICH). Methods: A prospective study of patients with an acute (<12 hours from onset of symptoms) spontaneous supratentorial ICH was conducted. Mortality was assessed at 30-day follow-up. TCD parameters were obtained from both middle cerebral arteries: systolic, diastolic, and mean velocities and Pulsatility Index (PI) from the affected and unaffected hemispheres. The following variables were included in a univariate analysis: age, sex, hematoma volume, hypodense volume around the hematoma, total volume, midline shift, ventricular size, Glasgow Coma Scale score, intraventricular hemorrhage, body temperature, white cell count, blood glucose, mean blood pressure, and TCD data. A multivariate analysis was performed with variables that showed significance in the univariate analysis. Receiver-operator characteristic (ROC) curves were obtained. Results: Forty-eight patients (age 66.5 ± 12.5 years; 28 men) were studied. Mortality at 30 days was 31%. The only predictor of mortality was the Glasgow Coma Scale score (odds ratio [OR] 0.67, CI 0.53 to 0.84, p = 0.001), whereas the PI from the unaffected hemisphere was correlated with mortality (OR 2.3, CI 0.92 to 5.72, p = 0.07). The area under the ROC curve was 0.92. A cutoff for PI from the unaffected hemisphere of 1.75 showed a specificity of 94% and a sensitivity of 80% as a predictor of death at 30 days. Conclusions: The PI of the unaffected hemisphere may be a predictor of death in acute ICH. These findings suggest that intracranial hypertension is the most likely cause of death in most patients with ICH.

Outcomes of a contemporary cohort of 536 consecutive patients with acute ischemic stroke treated with endovascular therapy.

Background and Purpose— We sought to assess outcomes after endovascular treatment/therapy of acute ischemic stroke, overall and by subgroups, and looked for predictors of outcome. Methods— We used data from a mandatory, population-based registry that includes external monitoring of completeness, which assesses reperfusion therapies for consecutive patients with acute ischemic stroke since 2011. We described outcomes overall and by subgroups (age ⩽ or >80 years; onset-to-groin puncture ⩽ or >6 hours; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization), and determined independent predictors of good outcome (modified Rankin Scale score ⩽2) and mortality at 3 months by multivariate modeling. Results— We analyzed 536 patients, of whom 285 received previous IV recombinant tissue-type plasminogen activator. Overall, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%, 5.6% developed symptomatic intracerebral hemorrhages, 43.3% achieved good functional outcome, and 22.2% were dead at 90 days. Adjusted comparisons by subgroups systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome). Multivariate analyses confirmed the independent protective effect of revascularization. Additionally, age >80 years, stroke severity, hypertension (deleterious), atrial fibrillation, and onset-to-groin puncture ⩽6 hours (protective) also predicted good outcome, whereas lack of previous disability and anterior circulation strokes (protective) as well as and hypertension (deleterious) independently predicted mortality. Conclusions— This study reinforces the role of revascularization and time to treatment to achieve enhanced functional outcomes and identifies other clinical features that independently predict good/fatal outcome after endovascular treatment/therapy.

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, &agr;2 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 ≥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.

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 ≧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 noncontrast CT scan and deviations from the recommended protocol.

Hemostatic markers of recanalization in patients with ischemic stroke treated with rt-PA.

Objective: To determine whether pretreatment markers of coagulation and fibrinolysis are related to recanalization and functional outcome. Methods: The authors included patients treated with IV rt-PA with occlusion on baseline transcranial Doppler (Thrombolysis in Brain Ischemia [TIBI] criteria) in whom recanalization within 6 hours was monitored. At baseline, the authors recorded data about demographics, vascular risk factors, the NIH Stroke Scale (NIHSS) score, early CT signs, etiology, blood glucose, and time to rt-PA. The authors also measured plasmatic markers of coagulation (fibrinogen, prothrombin fragments 1 + 2, Factor XIII, Factor VII) and fibrinolysis (α2-antiplasmin, Plasminogen Activator Inhibitor, Functional Thrombin Activatable Fibrinolysis Inhibitor [fTAFI]). A favorable outcome was defined as a modified Rankin score < 2 at 3 months. Results: The authors studied 63 patients with a mean age of 67.3 ± 12.5 years. The median NIHSS score was 16. Patients who recanalized had lower concentrations of α2-antiplasmin (87.5 ± 18% vs 96.5 ± 12.5%, p = 0.023) and fTAFI (91.7 ± 26.7% vs 104.4 ± 21%, p = 0.039). A multivariant logistic regression analysis showed that the level of α2-antiplasmin was the only predictive variable of recanalization (OR 0.95, 95% CI 0.91, 0.99, p = 0.038), while the NIHSS score was the only predictive variable of functional outcome (OR 0.81, 95% CI 0.72, 0.92, p = 0.001). Conclusion: Baseline levels of α2-antiplasmin were predictive of recanalization but were not related to the long-term outcome in patients treated with rt-PA within the first 3 hours.

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.

Aspirin or Anticoagulants in Stenosis of the Middle Cerebral Artery:A Randomized Trial

Background: We report the results of an open, randomized, multicenter trial that compared the efficacy of aspirin to oral anticoagulants (OA) for the prevention of vascular events in patients with symptomatic stenosis of the middle cerebral artery (MCA). Methods: Participants were randomly assigned to receive 300 mg/day of aspirin or a dose of OA (target INR 2–3). The MCA stenosis was demonstrated by conventional angiography or by at least two noninvasive examinations. Patients had either transient ischemic attack or cerebral infarct (CI) attributable to the MCA stenosis within 90 days before inclusion. The primary endpoint was: nonfatal CI, nonfatal acute myocardial infarct, vascular death and major hemorrhage. The patients were followed-up for a minimum of 1 year and a maximum of 3 years. Results: The study included 28 patients (14 in each treatment group); the average age was 67 ± 9.9 years. Men constituted 68% of the patients. After a mean follow-up of 23.1 ± 10.9 months, there were no recurrences of CI in both groups. No endpoint was reported in the aspirin group, but 2 patients in the OA group (14.3%) exhibited vascular events: 1 acute myocardial infarct and 1 intracerebral hemorrhage). However, this difference was not statistically significant (p = 0.48). Conclusions: Our study suggests that aspirin is the treatment of choice for the prevention of vascular events in patients with symptomatic MCA stenosis.