S. T. Engelter

Predicting outcome of IV thrombolysis–treated ischemic stroke patients The DRAGON score

Objective: To develop a functional outcome prediction score, based on immediate pretreatment parameters, in ischemic stroke patients receiving IV alteplase. Methods: The derivation cohort consists of 1,319 ischemic stroke patients treated with IV alteplase at the Helsinki University Central Hospital, Helsinki, Finland. We evaluated the predictive value of parameters associated with the 3-month outcome and developed the score according to the magnitude of logistic regression coefficients. We assessed accuracy of the model with bootstrapping. External validation was performed in a cohort of 330 patients treated at the University Hospital Basel, Basel, Switzerland. We assessed the score performance with area under the receiver operating characteristic curve (AUC-ROC). Results: The DRAGON score (0–10 points) consists of (hyper)Dense cerebral artery sign/early infarct signs on admission CT scan (both = 2, either = 1, none = 0), prestroke modified Rankin Scale (mRS) score >1 (yes = 1), Age (≥80 years = 2, 65–79 years = 1, <65 years = 0), Glucose level at baseline (>8 mmol/L [>144 mg/dL] = 1), Onset-to-treatment time (>90 minutes = 1), and baseline National Institutes of Health Stroke Scale score (>15 = 3, 10–15 = 2, 5–9 = 1, 0–4 = 0). AUC-ROC was 0.84 (0.80–0.87) in the derivation cohort and 0.80 (0.74–0.86) in the validation cohort. Proportions of patients with good outcome (mRS score 0–2) were 96%, 88%, 74%, and 0% for 0–1, 2, 3, and 8–10 points, respectively. Proportions of patients with miserable outcome (mRS score 5–6) were 0%, 2%, 5%, 70%, and 100% for 0–1, 2, 3, 8, and 9–10 points, respectively. External validation showed similar results. Conclusions: The DRAGON score is valid at our site and was reliable externally. It can support clinical decision-making, especially when invasive add-on strategies are considered. The score was not studied in patients with basilar artery occlusion. Further external validation is warranted.

Thrombolysis in stroke patients aged 80 years and older: Swiss survey of IV thrombolysis

This databank-based, multicenter study compared all stroke patients with IV tissue plasminogen activator aged ≥80 years (n = 38) and those <80 years old (n = 287). Three-month mortality was higher in older patients. Favorable outcome (modified Rankin scale ≤1) and intracranial hemorrhage (asymptomatic/symptomatic/fatal) were similarly frequent in both groups. Logistic regression showed that stroke severity, time to thrombolysis, glucose level, and history of coronary heart disease independently predicted outcome, whereas age did not.

IV thrombolysis in patients with acute stroke due to spontaneous carotid dissection

The authors reviewed the histories of 33 patients (ages 44 to 50 years) treated with IV thrombolysis for acute stroke due to spontaneous cervical carotid artery dissection. Median NIH Stroke Scale (NIHSS) score on admission was 15. No new or worsened local signs, subarachnoid hemorrhage, pseudoaneurysm formation, or rupture of the cervical ICA were observed. At 3 months, median NIHSS was 7 and median modified Rankin Scale (mRS) 2.5; mRS ≤ 2 was observed in 17 patients.

Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection

Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defined by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass effect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be difficult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confirm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissections

Background Cervical artery dissection (CAD) is a frequent cause of ischemic stroke, and occasionally death, in young adults. Several lines of evidence suggest a genetic predisposition to CAD. However, previous genetic studies have been inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact. Our aim is to identify genetic variants associated with an increased risk of CAD and possibly gene-environment interactions. Methods We organized a multinational European network, Cervical Artery Dissection and Ischemic Stroke Patients (CADISP), which aims at increasing our knowledge of the pathophysiological mechanisms of this disease in a large group of patients. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, DNA from approximately 1100 patients with CAD, and 2000 healthy controls is being collected. In addition, detailed clinical, laboratory, diagnostic, therapeutic, and outcome data are being collected from all participants applying predefined criteria and definitions in a standardized way. We are expecting to reach the above numbers of subjects by early 2009. Conclusions We present the strategy of a collaborative project searching for the genetic risk factors of CAD. The CADISP network will provide detailed and novel data on environmental risk factors and genetic susceptibility to CAD.

IV thrombolysis and statins

Objective: To examine whether prior statin use affects outcome and intracranial hemorrhage (ICH) rates in stroke patients receiving IV thrombolysis (IVT). Methods: In a pooled observational study of 11 IVT databases, we compared outcomes between statin users and nonusers. Outcome measures were excellent 3-month outcome (modified Rankin scale 0–1) and ICH in 3 categories. We distinguished all ICHs (ICHall), symptomatic ICH based on the criteria of the ECASS-II trial (SICHECASS-II), and symptomatic ICH based on the criteria of the National Institute of Neurological Disorders and Stroke (NINDS) trial (SICHNINDS). Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals were calculated. Results: Among 4,012 IVT-treated patients, 918 (22.9%) were statin users. They were older, more often male, and more frequently had hypertension, hypercholesterolemia, diabetes, coronary heart disease, and concomitant antithrombotic use compared with nonusers. Fewer statin users (35.5%) than nonusers (39.7%) reached an excellent 3-month outcome (ORunadjusted 0.84 [0.72–0.98], p = 0.02). After adjustment for age, gender, blood pressure, time to thrombolysis, and stroke severity, the association was no longer significant (0.89 [0.74–1.06], p = 0.20). ICH occurred by trend more often in statin users (ICHall 20.1% vs 17.4%; SICHNINDS 9.2% vs 7.5%; SICHECASS-II 6.9% vs 5.1%). This difference was statistically significant only for SICHECASS-II (OR = 1.38 [1.02–1.87]). After adjustment for age, gender, blood pressure, use of antithrombotics, and stroke severity, the ORadjusted for each category of ICH (ICHall 1.15 [0.93–1.41]; SICHECASS-II 1.32 [0.94–1.85]; SICHNINDS 1.16 [0.87–1.56]) showed no difference between statin users and nonusers. Conclusion: In stroke patients receiving IVT, prior statin use was neither an independent predictor of functional outcome nor ICH. It may be considered as an indicator of baseline characteristics that are associated with a less favorable course.

The Probability of Restenosis, Contralateral Disease Progression, and Late Neurologic Events following Carotid Endarterectomy: A Long-Term Follow-Up Study

Background: Most studies that have reported on the progression of ipsilateral and/or contralateral internal carotid artery (ICA) stenosis are restricted to a few years. Methods: Based on a single-center carotid endarterectomy (CEA) registry, we sought all patients with CEA for symptomatic high-grade ICA stenosis between 1970 and 2002. 361 CEA patients (mean age 66 years, 73% male) with annual carotid ultrasound and clinical follow-up were identified. Kaplan-Meier analysis was used to estimate the occurrence of (i) progressive ICA stenosis or restenosis of either the operated or contralateral side, and (ii) cerebrovascular events over time of either the operated or contralateral side. Results: Progressive ICA disease was more likely on the contralateral than on the ipsilateral ICA (hazard ratio 2.71; CI 1.8–4.1, p < 0.001). After 5 years, the probability for progressive ICA disease was 5.2% for the ipsilateral versus 15.8% for the contralateral ICA. After 15 years, the likelihood was 37% for both sides. In the presence of progressive restenosis of the ipsilateral ICA, the 20-year probability of further ischemic cerebrovascular events was 50% compared to 18% in patients without ICA disease progression. For the contralateral ICA, the probability of further ischemic events was 24.5% in patients with ICA disease progression compared to 9.6% without ICA disease progression (15 years). Conclusion: 15 years after CEA, one third of the patients can be expected to develop progressive ICA disease. While ICA disease progression seems to be more prominent on the contralateral ICA within the first years, this difference fades out after 15 years. One out of 2 patients with ipsilateral ICA disease progression can be expected to have a recurrent cerebral ischemic event within 15 years. It remains to be determined whether consequent application of high-dose statins, optimal blood pressure management and antithrombotic therapy can reduce this rate.

Optimizing the risk estimation after a transient ischaemic attack – the ABCDE⊕ score

Background and purpose:u2002 The risk of stroke after a transient ischaemic attack (TIA) can be predicted by scores incorporating age, blood pressure, clinical features, duration (ABCD‐score), and diabetes (ABCD2‐score). However, some patients have strokes despite a low predicted risk according to these scores. We designed the ABCDE+ score by adding the variables ‘etiology’ and ischaemic lesion visible on diffusion‐weighted imaging (DWI) –‘DWI‐positivity’– to the ABCD‐score. We hypothesized that this refinement increases the predictability of recurrent ischaemic events.

Lipid profiles and outcome in patients treated by intravenous thrombolysis for cerebral ischemia

Objective: To determine whether low low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) and triglyceride concentrations are associated with worse outcome in a large cohort of ischemic stroke patients treated with IV thrombolysis. Methods: Observational multicenter post hoc analysis of prospectively collected data in stroke thrombolysis registries. Because of collinearity between total cholesterol (TC) and LDL-C, we used 2 different models with TC (model 1) and with LDL-C (model 2). Results: Of the 2,485 consecutive patients, 1,847 (74%) had detailed lipid profiles available. Independent predictors of 3-month mortality were lower serum HDL-C (adjusted odds ratio [adjOR] 0.531, 95% confidence interval [CI] 0.321–0.877 in model 1; adjOR 0.570, 95% CI 0.348–0.933 in model 2), lower serum triglyceride levels (adjOR 0.549, 95% CI 0.341–0.883 in model 1; adjOR 0.560, 95% CI 0.353–0.888 in model 2), symptomatic ICH, and increasing NIH Stroke Scale score, age, C-reactive protein, and serum creatinine. TC, LDL-C, HDL-C, and triglycerides were not independently associated with symptomatic ICH. Increased HDL-C was associated with an excellent outcome (modified Rankin Scale score 0–1) in model 1 (adjOR 1.390, 95% CI 1.040–1.860). Conclusion: Lower HDL-C and triglycerides were independently associated with mortality. These findings were not due to an association of lipid concentrations with symptomatic ICH and may reflect differences in baseline comorbidities, nutritional state, or a protective effect of triglycerides and HDL-C on mortality following acute ischemic stroke.

Significance of microbleeds in patients with transient ischaemic attack

Background and purpose:u2002 The aim of this study was to determine the prognostic significance of microbleeds in TIA‐patients. In patients with a transient ischaemic attack (TIA), the prognostic value of microbleeds is unknown.