Non-thrombolysed Patients Research Articles

Outcome of intravenous thrombolysis in acute ischemic stroke patients with small vessel disease

IntroductionLacunar stroke (LS) subtype accounts for a quarter of ischemic strokes. Intravenous thrombolysis (IVT) is known to improve overall stroke outcomes. Very few studies have focused on the outcome of IVT in lacunar strokes. Aim: To detect the outcome of IVT in LS patients compared to non-thrombolysed LS patients. MethodsFifty patients presenting with LS received the standard protocol of IVT (Group I). They were compared to fifty matched LS patients who presented beyond the time window and were selected as the control group (Group II). Clinical outcome was measured using NIHSS within 24 h, NIHSS at discharge, and MRS after 3 months. Risk factors that could have affected clinical outcomes were compared in the thrombolysis group. ResultsThe short-term clinical outcome of Group I showed statistically significant improvement of NIHSS after 24 hrs compared to Group II (mean NIHSS = 5.52±3.89 and 7.44±1.82 respectively), as well as on discharge (mean NIHSS = 3.88±3.50 and 5.78±2.97) respectively. For long-term outcomes, 94 % of GroupⅠ reached MRS 0, 1, and 2 (n = 47/50) versus 74 % (n = 36/50) in Group II. Longer door-to-needle time, severe WMCs (Fazekas score), and pneumonia were shown to be significant predictor factors for the worst outcome. ConclusionIVT has improved short- and long-term outcomes in LS patients. Longer door-to-needle time, severe WMCs, and pneumonia were shown to be significant predictor factors for the worst outcome.

Medical complications during interhospital transfer for thrombectomy in patients with acute ischemic stroke.

Patients with acute ischemic stroke (AIS) and large-vessel occlusion are frequently transferred by emergency physicians (EPs) from primary to comprehensive stroke centers (CSC) for thrombectomy, particular when thrombolysed. Data on complications during such transfers are highly limited. Consecutive AIS patients transferred between 01/2015 and 10/2021 to our CSC were included. Associations of major (MACO) and minor (MICO) complications with clinical and imaging data were assessed. In total, 985 patients were included in the analysis (58.5% thrombolysed). MACO developed in 1.6%, MICO in 14.6%. Compared to patients without complications (NOCO), patients with MACO did not differ in terms of demographics, cerebrovascular risk factors, or site of vessel occlusion. They had more severe strokes (p = 0.026), neurological worsening was more severe (p = 0.008), and transport duration was longer (p = 0.050) but geographical distances did not differ. Thrombolysed patients had any complication more often than patients without thrombolysis (20.3% vs 10.5%; p < 0.001); however, this finding was driven by patients with MICO (p < 0.001) only (MACO: p = 0.804). No associations were observed between stroke severity and complications in either thrombolysed or nonthrombolysed patients. Neurological deterioration during transfer was observed in 21.2%, but multivariate analysis revealed no association with thrombolysis (OR 0.962; 95%CI 0.670-1.380, p = 0.832). Asymptomatic intracerebral hemorrhage was present in 1.1%, symptomatic in 0.1%. In this large cohort, no patient-specific factor increasing the risk of complications during interhospital transfer was identified. Specifically, our results do not indicate that thrombolysis increases MACO. Hence, interhospital transfer without EPs appears reasonable in most patients.

Stumbling Blocks to Stroke Thrombolysis: An Indian Perspective.

Stroke is a leading cause of morbidity and mortality worldwide. Developing countries, however, still lag behind in providing timely thrombolytic therapy (TLT) to many eligible patients owing to various reasons. This study aims to identify such factors. This was a descriptive observational study undertaken over a period of 18 months at a tertiary care teaching hospital and included 252 acute ischemic stroke patients of which 200 were not thrombolyzed. The reasons for nonthrombolysis were recorded and analyzed. The study included 252 acute ischemic stroke patients of which only 20% were thrombolyzed. Of the 200 nonthrombolyzed patients, 55% arrived out of the window period while patient-related factors were the second biggest factor preventing thrombolysis. Hospital factors at 14% and financial constraints at 4.5% contributed significantly. Delayed consent emerged as an important factor making 6% of the delays. Stroke thrombolysis still faces various pre- and intrahospital barriers in India. There is an urgent need to improve infrastructure and organizational streamlining to enable eligible patients to receive prompt treatment. Shah A, Diwan A. Stumbling Blocks to Stroke Thrombolysis: An Indian Perspective. Indian J Crit Care Med 2023;27(9):616-619.

Comparative Study On Quality of Life Between Thrombolysed and Non-Thrombolysed Ischemic Stroke Patients

Stroke is one of the leading causes of morbidity and mortality worldwide. Ischemic strokes are the most common variety of strokes caused by either thrombosis or embolism. In addition, they account for 50% – 85% of cerebrovascular accidents. Thrombolysis is used in the treatment of acute ischemic stroke. The current study examined the clinical profile and assessed risk factors, adverse events, and quality of life between thrombolytic and non-thrombotic ischemic stroke patients. A prospective observational study was conducted in a tertiary care Hospital with a sample size of 106 Ischemic stroke patients for four months. The patients were enrolled based on inclusion and exclusion criteria and were interviewed using a semi-structured questionnaire. Quality of life was assessed using Stroke specific quality of life scale (SSQOL). The results showed that the incidence of stroke is most common in the age group of 61-80 years, with a mean age of 59.9 years. Hypertension was the leading risk factor in 74.4% of cases. Speech Involvement (74.5%) was the most common presentation, followed by Hemiparesis, Altered sensorium. In our study, patients presenting to hospital &gt;4.5hrs were higher, and the quality of life between thrombolysis and non-thrombolysis patients were nearly identical. However, there was applied statistically significant distinction in energy, mobility, self-care, vision, and work items of the SSQoL scale. We conclude that the two groups had no major variations within the primary outcome of QOL. Thus, the current study tends to expect that patients with non-thrombolytic therapy will have a worse quality of life due to the greater initial stroke severity. Therefore, medical care appears to be of more importance in achieving a higher quality of life in ischemic thrombolysis stroke patients who reply to this therapy.

Systemic thrombolytics as rescue therapy for COVID-19 patients with acute respiratory distress syndrome: A retrospective observational study.

Coronavirus disease 2019 (COVID-19) pneumonia with severe acute respiratory distress syndrome (ARDS) is often associated with a progressive respiratory failure that is refractory to maximal ventilatory support and other ARDS strategies. Studies show evidence of a hypercoagulable state in COVID-19 patients, including capillary thrombosis and alveolar fibrin deposits which impede normal gas exchange. In this context, thrombolysis is considered as a salvage therapy to rescue critically hypoxemic patients. In this retrospective observational study, the efficacy of thrombolysis on outcome of COVID-19 ARDS with respiratory failure was analyzed. Patients with severe ARDS and d-dimer levels of 5 μg/ml or above were initiated on alteplase, as a 25 mg bolus followed by a 25 mg infusion over 22 h. Primary outcome was intensive care unit (ICU) mortality and secondary outcomes were change in PaO2/FiO2 24 h after thrombolysis, avoidance of intubation, ventilator free days (VFD), and ICU and hospital length-of-stay (LOS). Thirteen out of 34 patients with severe COVID ARDS underwent thrombolysis. They had lower ICU mortality than non-thrombolysed patients (23.1% vs. 71.4%, P = 0.006), greater percentage improvement in PaO2/FiO2 (116% vs. 31.5%, P = 0.002), more VFDs (13 days vs. 0 day, P = 0.004), and lesser requirement for intubation (23.1% vs. 76.2%, P = 0.004). ICU and hospital LOS were similar. Thrombolysis can be considered as a rescue therapy for nonintubated COVID-19 ARDS patients with severe hypoxemic respiratory failure, who show evidence of a procoagulant state. Larger studies are needed before inclusion into the regular treatment protocol for COVID-19 patients.

Intravenous Thrombolysis in Acute Ischemic Stroke

Background: Till date, no data has been published about the use of intravenous (IV) thrombolysis in acute ischemic stroke (AIS) from Kashmir valley. Objective: The objective of the study is to assess and determine the pattern of use of IV thrombolysis for AIS in Kashmir, including its efficacy and the difficulties faced in providing this modality of treatment. Materials and Methods: This was a prospective cross-sectional observational study conducted from July 2016 to July 2018. All those patients who were admitted with a diagnosis of stroke and gave informed consent were included in this study. Results: A total of 2023 patients of stroke presented to our emergency department during the study period. Out of them, 1085 (53.6%) cases were found to have hemorrhagic stroke and 938 (46.3%) patients were having ischemic stroke. 9.2% patients of ischemic stroke presented within the window period of thrombolysis, but only 34 (3.6%) patients received IV alteplase. The mean onset to door time in those who received thrombolysis was 103.5 ± 51.17 min. Door-to-needle time (DNT) of ≤60 min was achieved in only 14 (41.2%) cases, whereas mean DNT was 82.7 ± 49.17. There was a statistically significant improvement in the National Institutes of Health Stroke Scale in those who received thrombolysis as compared to those who did not receive it. Conclusion: Hemorrhagic stroke occurs in majority of stroke patients (53.6%) in our community. 3.6% of ischemic stroke patients were thrombolyzed. Thrombolytic therapy presented positive outcomes in comparison to nonthrombolyzed patients which, however, was not statistically significant.

Early decompressive hemicraniectomy in thrombolyzed acute ischemic stroke patients from the international ENCHANTED trial

Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management.

Emergency Thrombolysis During Cardiac Arrest Due to Pulmonary Thromboembolism: Our Experience Over 6 Years.

IntroductionCardiac arrest (CA) is one of the leading causes of death worldwide. Among patients with CA, pulmonary embolism (PE) accounts for approximately 10% of all cases.ObjectiveTo compare the outcomes after cardiopulmonary-cerebral resuscitation (CCPR) with and without thrombolytic therapy (TT) in patients with CA secondary to PE.MethodsWe included patients older than 17 years admitted to our hospital between 2013 and 2017 with a diagnosis of CA with confirmed or highly suspected PE who received CCPR with or without TT. Measures of central tendency were used to depict the data.ResultsThe study comprised 16 patients, 8 of whom received CCPR and thrombolysis with alteplase, whereas the remaining patients received CCPR without TT. The most frequent rhythm of CA in both groups was pulseless electrical activity. Return of spontaneous circulation (ROSC) occurred in 100% of patients who received TT and in 88% of non-thrombolysed patients. The mortality rate of patients who received TT and non-thrombolysed patients at 24 hours was 25% and 50%, respectively. However, at the time of hospital discharge, the mortality was the same in both groups (62%). In patients who received TT, mortality was related to sepsis and hemorrhage whereas in non-thrombolysed patients, mortality was due to myocardial dysfunction.ConclusionIntra-arrest thrombolysis resulted in a higher likelihood of ROSC and a higher 24-hour survival in adults with CA secondary to acute PE. Overall, the survival at hospital discharge was the same in the two groups.

Short-term outcome in ischemic stroke patients after thrombolytic therapy

BackgroundStroke represents the second leading cause of death in the world after myocardial infarction. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (alteplase, rt-PA) is the only pharmacological therapy that was approved for treatment within 4.5 h of acute ischemic stroke (AIS) onset. We aimed to predict the 3-month outcome of AIS patients who received alteplase regarding mortality, spontaneous intra-cerebral hemorrhage (sICH), and functional outcome in comparison with non-thrombolyzed patients and to evaluate the predictors of the outcome after 3 months.MethodsAll the clinical, National Institute of Health Stroke Scale (NIHSS) scores, radiological, and laboratory data of 40 AIS patients and received rt-PA during the period from 2016 to 2018 were collected and analyzed retrospectively. For comparison, 40 patients, as a control group, were selected to match the alteplase group as regards the baseline data and received regular treatment, rather than rt-PA within the first 24 h, that were obtained. The outcome of the thrombolyzed patients after 3 months was evaluated in comparison with controls by using a modified ranking scale.ResultsAfter a 90-day follow-up period, the death rate was slightly higher among the rt-PA group (7.5%) in comparison with the control group (5%). sICH occurred in 7.5% of the patients in the alteplase group and in 5% of the non-thrombolyzed patients; however, this difference was not significant. More patients had a favorable outcome (mRS = 0–2) in the rt-PA group than in the control group (65% vs 60%, OR 1.38, 95% CI 0.50–3.6, P = 0.51). NIHSS score on admission, body mass index (BMI) (≥ 30), and previous transient ischemic attacks (TIA)/previous ischemic stroke were significant predictors of outcome after IV thrombolysis. Age, sex, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, smoking, atrial fibrillation (AF), stroke subtype, size of infarction, and hyperdense middle cerebral artery had a non-significant effect.ConclusionAfter 3 months of follow-up, rt-PA had a non-significant more increase of favorable outcome with increased risk of sICH and death than controls. Baseline NIHSS, BMI, and history of TIA or previous ischemic stroke were significant predictors of outcome after thrombolysis.

Safety of the effective radiation dose received during stroke hospitalization.

BackgroundNeuroimaging is widely used for diagnosis and treatment of stroke. However, little is known about whether the radiation doses received by patients comply with international safety guidelines.ObjectivesThe aim of this study was to evaluate the effective radiation dose received while in hospital for stroke and analyze its safety according to current guidelines.MethodsThis cross-sectional study included 109 patients who were hospitalized and diagnosed with ischemic stroke. The National Institutes of Health Stroke Scale was used to evaluate stroke severity, the Bamford clinical classification was used for topography, and the TOAST classification was used for etiology. The computed tomography dose index and size-specific dose estimates were used to calculate the effective radiation dose (ERD) received while in hospital. A Mann-Whitney test was used to compare the ERD received by thrombolysed and non-thrombolysed patients. Non-parametric statistics were used to analyze the data with a 95% confidence interval.ResultsDuring the study period, the median ERD received was 10.9 mSv. Length of stay was not associated with radiation exposure. No differences were demonstrated in ERD according to stroke etiology or Bamford clinical classification. Patients who had CT perfusion (only or in addition to CT or angiotomography) received the highest ERD (46.5 mSv) and the difference compared to those who did not (10.8 mSv) was statistically significant (p<0.001). No differences were found in the ERD between thrombolysed and non-thrombolysed patients. There was no correlation between ERD while in hospital and stroke severity.ConclusionsAccording to the current national guidelines, the protocol for examining images at our stroke unit is safe in terms of the ERD received by the patient while in hospital. There was no difference in the ERD received by patients stratified by thrombolytic treatment or stroke severity.

Left Ventricular Thrombus Formation in Acute Anterior Wall Myocardial Infarction: A Comparison Between Thrombolyzed and Non-Thrombolyzed Patients

IntroductionLeft ventricular thrombus (LVT) formation is a prominent complication of acute myocardial infarction (AMI). Accurate and prompt detection of the condition is important as it poses a high risk for thromboembolic events that can be arrested by systemic anticoagulation. The purpose of our study was to evaluate the frequency of LVT formation in thrombolyzed and non-thrombolyzed patients with AMI to ascertain the current magnitude of the problem in the local population.MethodsThe study was conducted at the Chaudhry Pervaiz Elahi Institute of Cardiology in Multan, Pakistan. A total of 281 patients of either gender aged between 30-65 years with anterior wall myocardial infarction (AWMI; both thrombolyzed and non-thrombolyzed) were included in the study. Once they were enrolled in the study, all the relevant baseline investigations were performed. A detailed history was taken and examinations were done; serial ECG and echocardiography were performed till discharge from the hospital on the third day of hospitalization to record the final outcome of the study, i.e., LVT formation.ResultsThe mean age of the patients was 55.54 ± 7.26 years. Overall, LVT formation was noted in 65 cases (23.1%), of which 11 (16.9%) were thrombolyzed patients and 54 (83.1.1%) were non-thrombolyzed. A significant association of LVT was noted with age, hypertension, family history, and duration of symptoms.ConclusionWe found a high frequency of LVT formation among patients with AWMI who have not undergone thrombolytic therapy. It was observed that LVT was notably associated with advanced age, hypertension, and other comorbidities. Early presentation to the hospital and thrombolysis reduce the risk of developing LVT, which in turn can reduce morbidity and mortality in such patients.

Efficacy and Safety of Thrombolytic Therapy for Stroke with Unknown Time of Onset: A Meta-Analysis of Observational Studies

BackgroundRecombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies available for patients with known-onset stroke (KOS). Whether rt-PA treatment would improve functional outcomes in patients with stroke with unknown time of onset (UTOS) is undetermined, we aimed to systematically assess the efficacy and safety of thrombolysis for UTOS patients in this meta-analysis. MethodsA systematic literature search of Medline, Embase, and Cochrane Library was conducted. We considered the relevant data comparing thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients or thrombolyzed UTOS patients versus thrombolyzed KOS patients. Treatment efficacy and safety were measured according to modified Rankin Scale scores of 0-2 (mRS 0-2), and the presence of spontaneous intracerebral hemorrhage (SICH) or mortality at 90 days respectively. ResultsA total of 11 studies with 2581 patients meeting the inclusion criteria were included in the meta-analysis. All the patients had an ischemic lesion that was assessed by imaging including computed tomography or magnetic resonance imaging. Among these studies, 6 compared the thrombolytic efficacy in thrombolyzed UTOS patients with that in nonthrombolyzed UTOS patients (mRS 0-2: odds ratio [OR] =1.76, 95% confidence interval [CI] 1.11-2.81, P = .02), and 8 studies compared thrombolyzed UTOS patients with thrombolyzed KOS patients (mRS 0-2: OR = 0.87, 95% CI 0.66-1.15, P = .33). The incidence of SICH and mortality at 90 days had no difference between thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients and thrombolyzed UTOS patients versus thrombolyzed KOS patients (all P > .05). ConclusionsData from observational studies suggest that thrombolysis for UTOS patients had significantly favorable outcomes at 90 days compared with nonthrombolyzed patients.

Missing outcome data management in acute stroke trials testing iv thrombolytics. Is there risk of bias?

Missing outcome data may undermine interpretation of randomised clinical trials by weakening power and limiting apparent effect size. We assessed bias and inefficiency of two imputation methods commonly used in stroke trials evaluating the efficacy of iv thrombolysis. We searched the virtual international stroke trials archive (VISTA)-acute for ischaemic stroke patients with 90-day modified Rankin scale as an outcome, and known thrombolysis status. We excluded any with missing 30-day modified Rankin scale. We planned two analyses; first, we calculated odds ratios for outcome in thrombolysed versus not thrombolysed from imputed-only data, (a) among patients with missing modified Rankin scale 90 and (b) among matched patients with intact data (using propensity score methods and relevant covariates). Imputation approaches were last observation carried forward (LOCF) or multiple imputation. Outcome comparisons used dichotomisation and shift analysis. Thereafter, we calculated whole-population odds ratios using LOCF and multiple imputation (also through dichotomisation and shift analysis); first with the original 1.5% missing outcome data, and then artificially increasing the burden (5%; 10%; 20%; 30%). We considered 9657 patients from eight of the studies included in VISTA, 3034 (31%) thrombolysed. Missing data replacement by LOCF with analysis by dichotomisation gave the highest estimate of thrombolysis influence. Imputing while increasing the burden of missing data progressively raised the odds ratios estimates, though thresholds for overestimation were 10% for LOCF; 20% for multiple imputation.Discussion: Replacing missing outcome data tended to overestimate differences of thrombolysed versus non-thrombolysed patients, but had minimal impact below a 10% burden of missing data.Conclusion: In the specific context of acute stroke trials testing iv thrombolytics, replacing missing data by carrying forward the last observation tended to overestimate treatment odds ratios more than multiple imputation.

A Prospective Study of Deteriorating Acute Ischemic Stroke in NonThrombolysed Patients

A Prospective Study of Deteriorating Acute Ischemic Stroke in NonThrombolysed Patients

Post-stroke patients with and without thrombolysis: analysis of deglutition in the acute phase of the disease.

To verify the frequency and severity of dysphagia after ischemic stroke with or without thrombolysis in the acute phase; and the association among dysphagia, demographic characteristics, neurological and functional impairments and thrombolysis. A retrospective study of the medical records of 94 patients who suffered from ischemic stroke during the acute phase of the disease. From these, 52 patients received thrombolytic therapy and 42 patients did not receive such therapy. We collected data on age, sex, comorbidities, therapeutic time window of thrombolytic therapy, level of consciousness, degree of neurological impairment, level of functional dependency and clinical swallowing examination. A descriptive analysis included categorical and continuous variables, and an analysis of the association using the Pearson's Chi-Square Test, in which the value of p ≤ 0.05 was considered as a statistically significant association. The frequency of dysphagia in the thrombolytic patients was 67.3%, the odds ratio was 4.6 higher than the non-thrombolysed patients. The severity of dysphagia was not associated with thrombolysis. There was an association between the presence of dysphagia and functional dependence. Demographic characteristics and neurological impairment were not associated with dysphagia. Thrombolytic patients were more likely to develop dysphagia than non-thrombolysed patients in the acute phase of stroke, with dysphagia associated to functional dependence.

Impact of intravenous thrombolysis on functional outcome in patients with mild ischemic stroke without large vessel occlusion or rapidly improving symptoms.

Optimal treatment strategy in patients with mild ischemic stroke remains uncertain. While functional dependency or death has been reported in up to one-third of non-thrombolyzed mild ischemic stroke patients, intravenous thrombolysis is currently not recommended in this patient group. Emerging evidence suggests two risk factors-rapid early improvement and large vessel occlusion-as main associates of unfavorable outcome in mild ischemic stroke patients not undergoing intravenous thrombolysis. To analyze natural course as well as safety and three-month outcome of intravenous thrombolysis in mild ischemic stroke without rapid early improvement or large vessel occlusion. Mild ischemic stroke was defined by a National Institute of Health Stroke Scale score ≤6. We used the modified Rankin Scale (mRS) to compare three-month functional outcome in 370 consecutive mild ischemic stroke patients without early rapid improvement and without large vessel occlusion, who either underwent intravenous thrombolysis (n = 108) or received best medical treatment (n = 262). Favorable outcome (mRS ≤ 1) was common in both groups (intravenous thrombolysis: 91%; no intravenous thrombolysis: 90%). Although intravenous thrombolysis use was independently associated with a higher risk of asymptomatic hemorrhagic transformation (OR = 4.62, p = 0.002), intravenous thrombolysis appeared as an independent predictor of mRS = 0 at three months (OR = 3.33, p < 0.0001). Mild ischemic stroke patients without rapidly improving symptoms and without large vessel occlusion have a high chance of favorable three-month outcome, irrespective of treatment type. Patients receiving intravenous thrombolysis, however, more often achieved complete remission of symptoms, which particularly in mild ischemic stroke may constitute a meaningful endpoint.

Prominent FLAIR Vascular Hyperintensity Is a Predictor of Unfavorable Outcomes in Non-thrombolysed Ischemic Stroke Patients With Mild Symptoms and Large Artery Occlusion.

Background and objective: The aim was to evaluate the clinical significance of prominent fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) on the prognosis of mild acute ischemic stroke with middle cerebral artery (MCA) occlusion.Methods: We recruited consecutive stroke patients with initial National Institutes of Health Stroke Scale (NIHSS) scores ≤5 and MCA occlusion on magnetic resonance angiography within 24 h of stroke onset. Prominent distal FVH was defined as an extension to more than one-third of the MCA territory. We compared clinical outcomes between prominent and non-prominent FVH groups in patients who had and had not received reperfusion therapy.Results: Of 112 participants [43 women; median age, 67 years [Interquartile range, 54–79]], prominent FVH was identified in 80 (71.4%). For 75 patients who had not received reperfusion therapy, the prominent FVH group had a more unfavorable outcome (modified Rankin Scale score >1) at 3 months than the non-prominent FVH group (44.4 vs. 15.0%, P = 0.029). In multivariate analysis, a higher NIHSS score [odd ratio [OR] = 1.67; 95% confidence interval [CI], 1.16–2.41; P = 0.006], proximal MCA occlusion [OR = 7.31; 95% CI, 1.68–31.9; P = 0.008], and prominent FVH [OR = 5.49; 95% CI, 1.29–23.4; P = 0.021], were independently associated with an unfavorable outcome. There was no association between prominent FVH and the clinical outcome in the reperfusion therapy group.Conclusions: For acute stroke patients with mild symptoms and MCA occlusion who do not receive reperfusion therapy, prominent FVH and proximal MCA occlusion may be independent predictors of an unfavorable outcome.

Reduced Ischemic Lesion Growth with Heparin in Acute Ischemic Stroke

Objective: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. Methods: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. Results: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ∼5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. Conclusion: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.

Depressive symptoms in stroke patients treated and non-treated with intravenous thrombolytic therapy: a 1-year follow-up study

IntroductionThis is a prospective study, first to compare the frequency of depressive symptoms in stroke survivors treated, and non-treated, with intravenous thrombolysis and second, to explore relationships between post-stroke depression (PSD) and stroke treatment modalities, taking into account other possible determinants of PSD, including post-traumatic stress symptoms.MethodsGroups of 73 thrombolysed and 73 non-thrombolysed patients matched for age and gender were examined at 3 and 12 months after discharge. PSD was assessed using the Beck Depression Inventory. Post-traumatic stress symptoms (PTSS), disability and social support were assessed with the Impact of Event Scale-Revised, the Barthel Index and the Berlin Social Support Scale.ResultsAt 3 months, PSD was present in 23.3% of the thrombolysed and 31.5% in the non-thrombolysed groups (p = 0.265). At 12 months, the frequencies were 29.2 and 20.6% (p = 0.229). Logistic regression of the combined group of thrombolysed and non-thrombolysed patients indicated that at 3 months, the adjusted predictors of PSD were disability (OR 24.35), presence of PTSS (OR 9.32), low social support (OR 3.68) and non-thrombolytic treatment (OR 3.19). At 12 months, the predictors were disability (OR 15.78) and low education (OR 3.61).LimitationsThe use of a questionnaire for the detection of depression, the relatively small sample size and a significant drop-out rate could limit the interpretation of these results.Conclusions(1) Thrombolysed and non-thrombolysed stroke survivors had similar frequency of depressive symptoms although the thrombolysed patients had more severe neurological deficits in the acute phase. It can be assumed that if thrombolysis had not been used, depressive symptoms would have been more frequent. (2) Lack of the rt-PA treatment was associated with three-time greater odds of screening for PSD at 3 months post-stroke, after adjustment for other PSD correlates. (3) Therefore, thrombolytic therapy seems to have a positive, but indirect, effect on patients’ mood, especially in the first months after stroke. (4) All stroke patients, irrespective of the method of treatment, should be monitored for the presence of depression.

Procarboxypeptidase U (proCPU, TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression, outcome and blood–brain barrier dysfunction

Background Procarboxypeptidase U (proCPU, TAFI, proCPB2), the zymogen of CPU, which is a potent antifibrinolytic enzyme and a modulator of inflammation, has previously been investigated in plasma of stroke patients, but so far, no information on the proCPU levels in cerebrospinal fluid (CSF) during acute ischemic stroke (AIS) is available. Objectives This case-control observational study investigates proCPU in CSF of AIS patients compared with controls with an intact blood-brain barrier (BBB) and evaluates the relationship of CSF/plasma proCPU ratios with stroke parameters. Methods A sensitive HPLC-based enzymatic assay was used to determine proCPU levels in CSF of non-thrombolyzed patients in the hyperacute phase (< 24 h after onset) of AIS (n = 72). Individuals (n = 32) without stroke, an intact BBB and no apparent abnormalities in biochemical and microbiological tests, served as controls. Relations between the CSF/plasma proCPU ratio and (i) stroke severity, (ii) stroke progression/recurrence, (iii) stroke outcome and (iv) BBB dysfunction (CSF/serum albumin ratio) were assessed. Results Mean (SEM) proCPU levels were elevated in the CSF of stroke patients compared with controls (4.36 (0.23) U L-1 vs. 3.50 (0.23) U L-1 ). Higher median [IQR] CSF/plasma proCPU ratios were found in patients with stroke progression ((6.0 [4.2-6.9]) × 10-3 ) and poor outcome ((6.4 [3.9-7.0]) × 10-3 ) after 3 months (modified Rankin Scale; mRS > 3) compared with patients without progression ((3.9 [2.7-5.4]) × 10-3 ) or better outcome ((4.0 [2.8-5.0]) × 10-3 ). In stroke patients with a disrupted BBB, proCPU ratios were higher compared with stroke patients with an intact BBB ((6.4 [5.8-9.0]) × 10-3 vs. (3.7 [2.8-5.0]) × 10-3 ). Conclusions ProCPU is increased in CSF during hyperacute ischemic stroke and is associated with stroke progression and outcome after 3 months, most likely due to BBB dysfunction in the hyperacute phase of ischemic stroke.