Off-Label Thrombolysis for Acute Ischemic Stroke: Rate, Clinical Outcome and Safety Are Influenced by the Definition of ‘Minor Stroke’

Background: Several contraindications for intravenous thrombolysis are not based on controlled trials. Specialized stroke centers often apply less restrictive criteria. The aim of our study was to analyze how many patients at our institution receive off-label thrombolysis. In addition, clinical outcome and safety data were compared to those from patients treated on-label, and the influence of different definitions of ‘minor stroke’ were examined. Methods: Consecutive thrombolysis patients treated between January 2006 and January 2010 were included. Patients treated off-label were compared to patients given on-label therapy according to the European license. Since no specified definition for ‘minor neurological deficit’ exists in the license, two distinct definitions were considered off-label, i.e. National Institutes of Health Stroke Scale score (NIHSSS) ! 1 (definition 1) and NIHSSS ^ 4 (definition 2). Results: Of a total of 422 patients, 232 (55%) were treated off-label. The most prevalent off-label criteria (OLCs) were the following: age 1 80 years (n = 113), minor stroke (definition 1, n = 3; definition 2, n = 84), elevated blood pressure necessitating aggressive treatment (n = 75), time window 1 3 h (n = 71) and major surgery or trauma within the preceding 3 months (n = 20). In group comparisons, off-label patients had an overall worse outcome using definition 1 for minor stroke, while there was no difference when definition 2 was applied. In multivariate analysis, off-label therapy (definition 1) in general and age 1 80 years were independent predictors of poor outcome. None of the contraindications were associated with an increased bleeding risk. Conclusions: Off-label therapy is frequently applied at our center and is not associated with higher complication rates. Overall outcome of off-label treatment largely depends on the definition used for minor stroke. Besides age 1 80 years, a known poor prognostic factor, no other specific OLC was associated with poor outcome. Our data suggest that the criteria in the European license may be too restrictive

Vasospasm in Intracerebral Hemorrhage with Ventricular Involvement: A Prospective Pilot Transcranial Doppler Sonography Study

Background: Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH), but has rarely been reported after intracerebral hemorrhage (ICH) without subarachnoidal bleeding. The underlying pathophysiological mechanism is mainly mediated by circulating heme products within the cerebrospinal fluid, and thus patients with ICH and ventricular involvement (IVH) may also be in danger of developing VSP. The incidence and role of VSP in IVH, however, have not been systematically studied. Methods: We prospectively enrolled 115 patients with ICH with or without IVH into the study between April 2009 and April 2010. All patients received serial extracranial and transcranial Doppler sonography (TCD) at baseline, on days 3–5 and 7–9 to detect and monitor VSP. In addition, CT scans taken on admission, after 24 h and before discharge were evaluated for the occurrence of delayed cerebral ischemia. Results: Three out of 53 patients (5.7%) with IVH showed a significant elevation of flow velocities over the examined timeframe. One of these patients developed severe VSP re- sulting in secondary ischemic infarction. None of the ICH patients without IVH showed significantly elevated flow velocities or secondary infarction. Conclusions: Cerebral VSP with secondary infarction may occur in patients with spontaneous IVH, though far less frequently than in SAH; thus, systematic screening of all patients with IVH may not be warranted. However, serial TCD should be considered in patients with secondary clinical worsening or extensive IVH

Predictive Factors for Percutaneous Endoscopic Gastrostomy in Patients with Spontaneous Intracranial Hemorrhage

Background: Dysphagia is frequent after hemorrhagic stroke, and some of the affected patients require prolonged enteral nutrition, most often via percutaneous endoscopic gastrostomy (PEG) tubes. The identification of patients at risk of prolonged dysphagia permits earlier tube placement and helps guide clinicians in the decision-making process. Methods: This retrospective study included all patients with spontaneous ICH admitted to a tertiary university hospital from 2007 until 2009 (n = 208). Fifty-one patients received PEG tubes. PEG tube placement was conducted in ventilated patients within 30 days and in spontaneously breathing patients if swallowing did not improve within 14 days. Results: Twenty-five percent of patients received PEG tubes. Those patients had larger lobar hemorrhages, intraventricular hemorrhage and occlusive hydrocephalus and higher ICH scores. Furthermore, patients with PEG scored worse on Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS) and Acute Physiology And Chronic Health Evaluation (APACHE II), more frequently needed mechanical ventilation, and had more inflammatory and renal complications. A multivariate regression analysis identified GCS, occlusive hydrocephalus, mechanical ventilation, and systemic sepsis as independent risk factors for PEG tube placement. Conclusion: Disease severity and neurocritical care complications represent the major influencing parameters for PEG tube placement in spontaneous ICH patients

Waiting for Platelet Counts Causes Unsubstantiated Delay of Thrombolysis Therapy

Background: Platelet counts (PCs) <100,000/µl are considered as a contraindication for intravenous thrombolysis (IVT). While US guidelines recommend IVT initiation before the availability of clotting tests, the guidelines of the European Stroke Organization give no such practical advice. We aimed to assess the incidence of thrombocytopenia in IVT patients, outcome after thrombolysis in affected patients and the time gained by initiating treatment prior to availability of PC results. Methods: All patients with thrombocytopenia were identified in our prospectively acquired thrombolysis database. Baseline demographic data, intracerebral hemorrhage rates as well as functional outcome were assessed. The median time between initiation of thrombolysis and availability of PCs was calculated. Results: Of 625 IVT patients, 3 (0.5%) had thrombocytopenia at stroke onset. None of them developed intracerebral hemorrhage (ICH) or died during the follow-up. Waiting for PCs would have delayed treatment in 72.4% of the patients, with a median hypothetical delay of 22 min (interquartile range: 11–41 min). Conclusions: To date, there are no sufficient data to evaluate the ICH risk in thrombocytopenic patients. However, thrombocytopenia is rare in IVT patients. Thus, generally waiting for PC results prior to initiation of IVT is not warranted. Avoiding this significant delay yields shorter door-to-needle times and potentially more effective treatment

Correlation of age and haematoma volume in patients with spontaneous lobar intracerebral haemorrhage

Background Lobar intracerebral haemorrhage (LH) is gaining importance in the ageing population, but there are only limited data regarding specific clinical characteristics and risk factors of older patients with LH. Methods This retrospective analysis of patients with spontaneous supratentorial haemorrhage included 174 consecutive patients (78 LH and 96 deep ICH (DH)). Clinical data including the preadmission status, neuroradiological findings, initial presentation, treatment and outcome were evaluated using institutional databases, patients' medical charts and mailed questionnaires. Logistic regression analyses were calculated for initial parameters predisposing LH and for treatment and outcome parameters associated with LH. Results Age-stratified volume analysis revealed increasing haematoma volumes for LH (≤70 years: 26.2 ml; 70–80 years: 37 ml; >80 years: 61.3 ml), whereas DH showed no relation between volume and age (≤70 years: 10.1 ml; 70–80 years: 23.2 ml; >80 years: 12.1 ml). DH patients had significantly higher HbA1c levels. Post-ICH seizures were more frequent after LH. Logistic regression analyses identified the parameters: age, haematoma volume and post-ICH seizures to be associated with LH, whereas intraventricular haemorrhage, extraventricular drainages and elevated HbA1c were related to DH. Conclusion Haematoma volumes are substantially increasing in LH patients who are older than 70 years. Pathological HbA1c levels are significantly associated and predisposing for DH. These findings further support the ongoing debate of different disease entities for supratentorial ICH (ie, association of cerebral amyloid angiopathy and lobar ICH versus diabetes induced atherosclerosis in deep ICH). Future studies should focus on identifying specific pathological characteristics and risk factors for both bleeding sites to implement specific preventive measures, that is amyloid angiopathy modulating therapies for LH, and to avoid risk factors that are specific for each haemorrhage location