Ulf Bodechtel

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P=0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Prediction of Outcome in Neurogenic Oropharyngeal Dysphagia within 72 Hours of Acute Stroke

BACKGROUND Stroke is the most frequent cause of neurogenic oropharyngeal dysphagia (NOD). In the acute phase of stroke, the frequency of NOD is greater than 50% and, half of this patient population return to good swallowing within 14 days while the other half develop chronic dysphagia. Because dysphagia leads to aspiration pneumonia, malnutrition, and in-hospital mortality, it is important to pay attention to swallowing problems. The question arises if a prediction of severe chronic dysphagia is possible within the first 72 hours of acute stroke. METHODS On admission to the stroke unit, all stroke patients were screened for swallowing problems by the nursing staff within 2 hours. Patients showing signs of aspiration were included in the study (n = 114) and were given a clinical swallowing examination (CSE) by the swallowing/speech therapist within 24 hours and a swallowing endoscopy within 72 hours by the physician. The primary outcome of the study was the functional communication measure (FCM) of swallowing (score 1-3, tube feeding dependency) on day 90. RESULTS The grading system with the FCM swallowing and the penetration-aspiration scale (PAS) in the first 72 hours was tested in a multivariate analysis for its predictive value for tube feeding-dependency on day 90. For the FCM level 1 to 3 (P < .0022) and PAS level 5 to 8 (P < .00001), the area under the curve (AUC) was 72.8% and showed an odds ratio of 11.8 (P < .00001; 95% confidence interval 0.036-0.096), achieving for the patient a 12 times less chance of being orally fed on day 90 and therefore still being tube feeding-dependent. CONCLUSIONS We conclude that signs of aspiration in the first 72 hours of acute stroke can predict severe swallowing problems on day 90. Consequently, patients should be tested on admission to a stroke unit and evaluated with established dysphagia scales to prevent aspiration pneumonia and malnutrition. A dysphagia program can lead to better communication within the stroke unit team to initiate the appropriate diagnostics and swallowing therapy as soon as possible.

Reliability of brain CT evaluation by stroke neurologists in telemedicine

Objective: To determine the reliability and therapeutic impact of standardized cerebral CT evaluation and quantification of early ischemic changes (EIC) with the Alberta Stroke Program Early CT Score (ASPECTS) by stroke neurologists in the Stroke Eastern Saxony Network (SOS-NET), which provides telemedical consultations for patients with acute ischemic stroke. Methods: Two neuroradiologists re-evaluated all CT scans of consecutive SOS-NET patients in 2009 blinded to clinical information providing reference standard. We defined discrepant CT findings as all false-positive or false-negative EIC and brain pathology findings and ASPECTS deviations >1 point. We subsequently discussed the clinical impact of discrepant CT findings unblinded to clinical information. Weighted kappa (κw) statistic was used to determine the interobserver agreement for ASPECTS. Results: Of 582 patients, complete imaging data were available for 536 patients (351 cerebral ischemic events, 105 primary intracranial hemorrhages, and 80 stroke mimics). The neuroradiologists detected discrepant CT findings in 43 patients (8.0%) that were rated as clinically relevant in 9 patients (1.7%). Stroke neurologists recommended IV thrombolysis in 8 patients despite extensive EIC (ASPECTS ≤5). One of these patients had symptomatic intracranial hemorrhage. In 1 nonthrombolyzed patient, the stroke neurologist missed subdural hematoma. The interobserver agreement on ASPECTS between stroke neurologists and expert readers was substantial (κw = 0.62; 95% confidence interval 0.54–0.71). Conclusions: Clinically relevant misinterpretation of the CT scans was rare in our acute telestroke service. ASPECTS is a reliable tool to assess the extent of EIC by stroke neurologists in telemedicine in real time.

Safety and efficacy of thrombolysis in telestroke: A systematic review and meta-analysis

Objective: The aim of this systematic review and meta-analysis was to evaluate the safety and efficacy of IV thrombolysis (IVT) with tissue plasminogen activator (tPA) delivered through telestroke networks in patients with acute ischemic stroke. Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines. Literature searches on MEDLINE, Embase, and CENTRAL databases covered prospective randomized controlled and nonrandomized studies comparing telemedicine-guided IVT to IVT administered at stroke centers and were published from the earliest date available until April 1, 2015. Outcomes of interest were symptomatic intracerebral hemorrhage, mortality, and functional independence (modified Rankin Scale scores 0–1) at 3 months. Random-effects meta-analysis was used to compute pooled effect estimates and the I2 statistic to assess heterogeneity. Results: Of 529 records identified, 7 studies totaling 1,863 patients fulfilled our eligibility criteria. Among these, thrombolysis was largely restricted to the 3-hour time window. Symptomatic intracerebral hemorrhage rates were similar between patients subjected to telemedicine-guided IVT and those receiving tPA at stroke centers (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.37–2.80; p = 0.978) with low evidence of heterogeneity (I2 = 37%; p = 0.189). There was no difference in mortality (RR = 1.04, 95% CI 0.74–1.48; p = 0.806) or in functional independence (RR = 1.11, 95% CI 0.78–1.57; p = 0.565) at 3 months between telemedicine-guided and stroke center thrombolysis. No heterogeneity was identified (I2 = 0%, p = 0.964 and I2 = 52%, p = 0.123, respectively). Conclusions: Our findings indicate that IV tPA delivery through telestroke networks is safe and effective in the 3-hour time window. Lack of prospective trials, however, emphasizes the need to further substantiate these findings in the 3- to 4.5-hour time window. PROSPERO registration information: URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42015017232.

Exploring the risk-factor association between depression and incident stroke: a systematic review and meta-analysis

There is growing evidence that depression increases the risk of incident stroke. However, few studies have considered possible residual confounding effects by preexistent cerebrovascular and cardiac diseases. Therefore, we synthesized data from cohort studies to explore whether depressed individuals free of cerebrovascular and cardiac diseases are at higher risk of incident stroke. We searched the electronic databases PubMed and Medline for eligible cohort studies that examined the prospective association between depression and first-ever stroke. A random-effects model was used for quantitative data synthesis. Sensitivity analyses comprised cohort studies that considered a lag period with exclusion of incident strokes in the first years of follow-up to minimize residual confounding by preexistent silent strokes and excluded cardiac disease at baseline. Overall, we identified 28 cohort studies with 681,139 participants and 13,436 (1.97%) incident stroke cases. The pooled risk estimate revealed an increased risk of incident stroke for depression (relative risk 1.40, 95% confidence interval [CI] 1.27–1.53; P<0.0001). When we excluded incident strokes that occurred in the first years of follow-up, the prospective association between depression and incident stroke remained significant (relative risk 1.64, 95% CI 1.27–2.11; P<0.0001). This positive association also remained after we considered only studies with individuals with cardiac disease at baseline excluded (relative risk 1.43, 95% CI 1.19–1.72; P<0.0001). The prospective association of depression and increased risk of first-ever stroke demonstrated in this meta-analysis appears to be driven neither by preexistence of clinically apparent cerebrovascular and cardiovascular diseases nor by silent stroke.

Systemic thrombolysis in acute ischemic stroke patients with unruptured intracranial aneurysms

Objective: We sought to determine the safety of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a multicenter study and a comprehensive meta-analysis of available case series. Methods: We analyzed prospectively collected data from consecutive AIS patients treated with IVT during a 4-year period at 4 tertiary-care stroke centers. All patients routinely underwent CT or magnetic resonance angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIH Stroke Scale score of ≥4 points. A systematic meta-analysis of case series reporting safety of IVT in AIS with concomitant UIA was conducted according to PRISMA recommendations. Results: Among 1,398 AIS patients treated with IVT, we identified 42 cases (3.0%) harboring a total of 48 UIAs. The rates of symptomatic and asymptomatic ICH were 2.4% (95% confidence interval [CI] by adjusted Wald method: 0%–12.6%) and 7.1% (95% CI: 1.8%–19.7%), respectively. A total of 5 case series met our inclusion criteria for meta-analysis, and the pooled rate of sICH among 120 IVT-treated AIS patients harboring UIA was 6.7% (95% CI: 3.1%–13.7%). In the overall analysis of 5 case-series studies, the risk ratio of sICH did not differ between AIS patients with and without UIA (risk ratio = 1.60; 95% CI: 0.54–4.77; p = 0.40) with no evidence of heterogeneity across included studies (I2 = 22% and p = 0.27 for Cochran Q test). Conclusions: Our prospectively collected multicenter data, coupled with the findings of the meta-analysis, indicate the potential safety of IVT in AIS patients with UIA.

The Effects of Pretreatment versus De Novo Treatment with Selective Serotonin Reuptake Inhibitors on Short-term Outcome after Acute Ischemic Stroke

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) administered in patients following acute ischemic stroke have shown to improve clinical recovery independently of changes in depression. Animal studies have demonstrated that sustained SSRI treatment is superior to short-term SSRI in evoking neurogenesis but how this benefit translates into humans remains to be answered. We hypothesized that in acute ischemic stroke patients, SSRI treatment started before the event leads to improved short-term outcomes compared to de novo SSRI treatment poststroke. METHODS We performed an exploratory analysis in consecutive acute ischemic stroke patients and compared patients already receiving fluoxetine, citalopram, or escitalopram with those who started treatment de novo. RESULTS Of 2653 screened patients, 239 were included (age, 69 ± 14 years; 42% men, baseline median National Institutes of Health Stroke Scale score, 7 [IQR, 10]). Of these patients, 51 started treatment with SSRI before stroke and 188 were prescribed newly SSRIs during hospitalization. In the adjusted multivariate logistic regression models, SSRI pretreatment was associated with favorable functional outcome at discharge defined as a modified Rankin Scale score of 2 or less (odds ratio [OR], 4.00; 95% confidence interval [CI], 1.68-9.57; P < .005), improved early clinical recovery (OR, 2.35; 95% CI, 1.15-4.81; P = .02), and a trend toward prediction of superior motor recovery (OR, 1.82; 95% CI, .90-3.68; P < .01). CONCLUSIONS Our data suggest that SSRI pretreatment may improve clinical outcomes in the early stages of acute ischemic stroke supporting the hypothesis that prolonged SSRI treatment started prestroke is superior to poststroke SSRI.

Why Telestroke networks? Rationale, implementation and results of the Stroke Eastern Saxony Network

Stroke is the third leading cause of death and the leading cause of acquired long-term disability in Europe and North America. Intravenous (IV) thrombolysis with alteplase and organized inpatient (stroke unit) care have been shown to improve stroke patients’ functional outcomes. However, stroke unit care is not area-wide available and thrombolysis rates are low, partly due to limited stroke thrombolysis expertise in smaller community hospitals. Telemedical stroke networks (Telestroke network) with remote video assessment of patients and brain computed tomography (CT) scans by stroke neurologists have been shown to increase IV thrombolysis rates and functional outcomes of patients in smaller community hospitals. Our article summarizes the rationale, clinical, and currently published scientific results of Telestroke networks with special respect to the telemedical Stroke Eastern Saxony Network (SOS-NET), which has been established by the Dresden University Stroke Center (DUSC) in July 2007. From July 2007 to December 2012, 3416 teleconsultations have been performed within the SOS-NET.

Imaging-based selection for revascularization in acute ischemic stroke.

PURPOSE OF REVIEW With the positive results of recent endovascular thrombectomy (EVT) trials, intravenous thrombolysis (IVT) and EVT provide physicians with two majorly effective acute treatment options for patients with acute ischemic stroke. IVT and EVT can be used as a single treatment or as a combined IVT/EVT treatment approach. This review summarizes how imaging findings can help in selecting stroke patients who are likely to benefit from these revascularization therapies. RECENT FINDINGS IVT applied within 4.5 h from symptom onset remains the mainstay of acute stroke therapy and was also applied to most patients in the randomized EVT trials. Recent studies have failed to demonstrate the effectiveness of IVT in later time windows. Vascular imaging is crucial to identify patients with a target intracranial occlusion prior to EVT. Patients with a small ischemic core, with good leptomeningeal collaterals or with evidence of penumbral tissue may particularly benefit from EVT. These imaging findings may also identify patients who benefit from EVT if applied more than 6 h from symptom onset. SUMMARY Pretherapeutic imaging findings help in identifying stroke patients who are likely to benefit from endovascular stroke therapies, and may identify patients who benefit from revascularization therapies in later time windows.