Gert-Jan Luijckx

Optimizing Cutoff Scores for the Barthel Index and the Modified Rankin Scale for Defining Outcome in Acute Stroke Trials

Background and Purpose— There is little agreement on how to assess outcome in acute stroke trials. Cutoff scores for the Barthel Index (BI) and modified Rankin Scale (mRS) are frequently arbitrarily chosen to dichotomize favorable and unfavorable outcome. We investigated sensitivity and specificity of BI cutoff scores in relation to the mRS to obtain the optimal corresponding BI and mRS scores. Methods— BI and mRS scores were collected from 1034 ischemic stroke patients. Sensitivity and specificity were calculated for BI cutoff scores from 45 to 100 in mRS score 1, 2, and 3 and were plotted in receiver operator characteristic (ROC) curves. Results— The cutoff scores for the BI with the highest sum of sensitivity and specificity were 95 (sensitivity 85.6%; specificity 91.7%), 90 (sensitivity 90.7%; specificity 88.1%), and 75 (sensitivity 95.7%; specificity, 88.5%) for, respectively, mRS 1, 2, and 3. The area under the ROC curve was 0.933 in mRS 1, 0.960 in mRS 2, and 0.979 in mRS 3. Conclusions— The optimal cutoff scores for the BI were 95 for mRS 1, 90 for mRS 2, and 75 for mRS 3. For future acute stroke trials that assess stroke outcome with the BI and mRS, we recommend the use of these BI cutoff score(s) with the corresponding mRS cutoff score(s), to ensure the use of consistent and uniform end points.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy at Stroke Onset

Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke. Methods— We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale ≥4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale ≥4 plus any ICH]), functional outcome at 3 months and mortality. Results— A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP naïve patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naïve, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P=0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition. Conclusion— The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.

Safety of antiplatelet therapy prior to intravenous thrombolysis in acute ischemic stroke

BACKGROUNDnThere is some uncertainty whether prior use of antiplatelet (AP) drugs increases the risk of symptomatic intracerebral hemorrhage (SICH) and influences functional outcome in patients with ischemic stroke treated with intravenous thrombolysis.nnnOBJECTIVEnTo assess whether prior use of AP drugs is related to outcome following intravenous tissue plasminogen activator therapy in patients with ischemic stroke.nnnDESIGN, SETTING, AND PATIENTSnA single-center prospective observational cohort study of the relation between prior AP therapy, occurrence of SICH, and functional outcome of consecutive patients with ischemic stroke undergoing intravenous thrombolysis with tissue plasminogen activator in a university hospital between April 1, 2002, and November 30, 2006.nnnMAIN OUTCOME MEASURESnThe occurrence of SICH and favorable outcome reflecting independence defined as a modified Rankin Scale score of 2 or lower at 3 months.nnnRESULTSnOf the 301 patients who received intravenous tissue plasminogen activator, 89 used AP drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 12 patients (13.5%; 95% confidence interval, 7.8%-22.3%) who had received AP drugs and in 6 patients (2.8%; 95% confidence interval, 1.2%-6.2%) without prior AP therapy (P = .001). Multivariate analysis revealed that prior AP therapy was an independent predictor of SICH (odds ratio, 6.0; 95% confidence interval, 2.0-17.1). Nonetheless, prior AP therapy was independently associated with a favorable outcome (odds ratio, 2.0; 95% confidence interval, 1.0-4.3).nnnCONCLUSIONnDespite a higher incidence of SICH, the net benefit of intravenous tissue plasminogen activator therapy for acute ischemic stroke was greater in patients using AP drugs.

Proportion of Patients Treated With Thrombolysis in a Centralized Versus a Decentralized Acute Stroke Care Setting

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

Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome

Background and Purpose— Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Methods— Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. Results— After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group. Conclusions— Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.

Predictive Factors for Rebleeding After Aneurysmal Subarachnoid Hemorrhage: Rebleeding Aneurysmal Subarachnoid Hemorrhage Study

Background and Purpose— Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating type of stroke associated with high morbidity and mortality. One of the most feared complications is an early rebleeding before aneurysm repair. Predictors for such an often fatal rebleeding are largely unknown. We therefore aimed to determine predictors for an early rebleeding after aSAH in relation with time after ictus. Methods— This observational prospective cohort study included all consecutive patients admitted with aSAH between January 1998 and December 2014 (n=1337) at our University Neurovascular Center. Clinical predictors for rebleeding ⩽24 hours were identified using multivariable Cox regression analyses. Kaplan–Meier analyses were applied to evaluate the time of rebleeding ⩽72 hours after aSAH. Results— A modified Fisher grade of 3 to 4 was a predictor for an in-hospital rebleeding ⩽24 hours after ictus (adjusted hazard ratio, 4.4; 95% confidence interval, 2.1–10.6; P<0.001). The numbers needed to treat to prevent 1 rebleeding ⩽24 hours was calculated 15 (95% confidence interval, 10–25). Also, the initiation of external cerebrospinal fluid-drainage (adjusted hazard ratio, 1.9; 95% confidence interval, 1.4–2.5; P<0.001) was independently associated with a rebleeding ⩽24 hours. Cumulative in-hospital rebleeding rates were 5.8% ⩽24 hours, and 1.2% in the time frame 24–72 hours after ictus. Conclusions— In our opinion, timing of treatment of aSAH patients, especially those with an modified Fisher grade of 3 or 4 in a good clinical condition, should be reconsidered. These aSAH patients might be regarded a medical emergency, requiring aneurysm repair as soon as possible. In this respect, our findings should provoke the debate on timing of aneurysm repair, especially in patients considered to be at high risk for rebleeding.

Repeat digital subtraction angiography after a negative baseline assessment in nonperimesencephalic subarachnoid hemorrhage: a pooled data meta-analysis

OBJECTnA repeat digital subtraction angiography (DSA) study of the cranial vasculature is routinely performed in patients with diffuse nonperimesencephalic subarachnoid hemorrhage (SAH) after negative baseline CT angiography (CTA) and DSA studies. However, DSA carries a low but substantial risk of neurological complications. Therefore, the authors evaluated the added value of repeat DSA in patients with initial angiographically negative diffuse nonperimesencephalic SAH.nnnMETHODSnA systematic review of the contemporary literature was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies from January 2000 onward were reviewed since imaging modalities have much improved over the last decade. A pooled analysis was conducted to identify the detection rate of repeat DSA. In addition, the diagnostic yield of repeat DSAs in a prospectively maintained single-center series of 1051 consecutive patients with SAH was added to the analysis.nnnRESULTSnAn initial search of the literature yielded 179 studies, 8 of which met the selection criteria. Another 45 patients from the authors institution were included in the study, providing 368 patients eligible for the pooled analysis. In 37 patients (10.0%, 95% CI 7.4%-13.6%) an aneurysm was detected on repeat DSA. The timing of the repeat DSA varied from 1 to 6 weeks after the initial DSA. The use of 3D techniques was poorly described among these studies, and no direct comparisons between CTA and DSA were made.nnnCONCLUSIONSnRepeat DSA is still warranted in patients with a diffuse nonperimesencephalic SAH and negative initial assessment. However, the exact timing of the repeat DSA is subject to debate.

Thrombolytic therapy for ischaemic stroke in patients using warfarin: a systematic review and meta-analysis

Background It is uncertain whether thrombolytic therapy is safe in patients with acute ischaemic stroke who are treated with warfarin and have a subtherapeutic international normalised ratio (INR) at stroke onset. Methods The authors performed a systematic review of the literature and included studies that assessed the relation between prior warfarin use with subtherapeutic INR and outcome after intravenous or intra-arterial thrombolytic therapy in acute ischaemic stroke. Outcome measures were symptomatic intracranial haemorrhage (SICH), modified Rankin scale score 0–2 and mortality. Second, the authors performed a meta-analysis of the included studies. Results Seven studies with 3631 patients were included. 240 (6.6%) patients used warfarin before stroke onset. The risk of SICH was increased in the warfarin group (OR 2.6; 95% CI 1.1 to 5.9. p=0.02). There was no significant difference, however, in functional outcome (OR 0.9; 95% CI 0.6 to 1.2, p=0.32) or death from all causes (OR 1.2; 95% CI 0.9 to 1.8). Discussion The risk of SICH after thrombolytic therapy is increased in patients using warfarin with subtherapeutic INR levels. The authors found no evidence of an increase in death from all causes or worsening of functional outcome in warfarin treated patients.

Co-morbidities in heart failure

Heart failure is a clinical syndrome characterized by poor quality of life and high morbidity and mortality. Co-morbidities frequently accompany heart failure and further decrease in both quality of life and clinical outcome. We describe that the prevalence of co-morbidities in patients with heart failure is much higher compared to age-matched controls. We will specifically address the most studied organ-related co-morbidities, that is, renal dysfunction, cerebral dysfunction, anaemia, liver dysfunction, chronic obstructive pulmonary disease, diabetes mellitus and sleep apnoea. The pathophysiologic processes underlying the interaction between heart failure and co-morbid conditions are complex and remain largely unresolved. Although common risk factors are likely to contribute, it is reasonable to believe that factors associated with heart failure might cause other co-morbid conditions. Inflammation, neurohumoral pathway activation and hemodynamic changes are potential factors. We try to provide explanations for the observed association between co-morbidities and heart failure, as well as its impact on survival.

Safety and Outcome of Intra-Arterial Treatment for Basilar Artery Occlusion

ImportancenAfter the many positive results in thrombectomy trials in ischemic stroke of the anterior circulation, the question arises whether these positive results also apply to the patient with basilar artery occlusion (BAO).nnnObjectivenTo report up-to-date outcome data of intra-arterial (IA) treatment in patients with BAO and to evaluate the influence of collateral circulation on outcome.nnnDesign, Setting, and ParticipantsnSingle-center retrospective case series of 38 consecutive patients with BAO who underwent IA treatment between 2006 and 2015 at a comprehensive stroke center.nnnExposuresnIntra-arterial treatment by mechanical thrombectomy and/or IA thrombolysis.nnnMain Outcomes and MeasuresnAdequate recanalization was defined as a score of 2b or 3 on the Thrombolysis in Cerebral Infarction score. Favorable outcome was defined as a modified Rankin Scale of 0 to 3 at first follow-up. Imaging data on the patency of the vertebral arteries and posterior communicating arteries, as well as the presence of cerebellar arterial anastomosis, were recorded and posttreatment imaging results were reviewed.nnnResultsnOf the 38 patients with BAO, mean (SD) age was 58 (16) years, and 21 (55%) were male. Twenty-seven patients (71%) were treated with intravenous thrombolysis before IA therapy. Mechanical thrombectomy was applied to 30 patients, and 7 patients received local urokinase without thrombectomy. The median National Institutes of Health Stroke Scale score was 21 (interquartile range [IQR], 15-32) points, and median time to IA treatment was 288 (IQR, 216-380) minutes. Adequate recanalization was achieved in 34 of 38 cases (89%). Functional outcome was favorable in 19 (50%) patients. No association between patent collateral circulation and favorable outcome was found. Symptomatic intracranial hemorrhage occurred in 2 patients (5%).nnnConclusions and RelevancenThe proportion of patients reaching a favorable outcome in our study is comparable to the IA-treated group of the MR CLEAN trial and better than the results reported in the BASICS registry, suggesting that IA intervention in patients with BAO is an effective and safe treatment modality in daily clinical practice.