Oral anticoagulants - a frequent challenge for the emergency management of acute ischemic stroke

Background: The emergency management of patients with acute ischemic stroke (IS) using oral anticoagulants (OAC) represents a great challenge. Effective anticoagulation predisposes to bleeding and represents a contraindication for systemic thrombolysis. However, patients on OAC can receive intravenous thrombolysis with recombinant tissue-type plasminogen activator if the international normalized ratio (INR) does not exceed 1.7, but data regarding the risk of hemorrhagic complications are highly controversial. Neurointerventional recanalization of intracranial artery occlusion represents an alternative option in OAC patients with acute IS. The proportion of OAC users among consecutive patients who suffer from acute IS or transient ichemic attacks (TIA) is unknown. Methods: A prospective observational study, consecutively enrolling all patients with IS or TIA admitted to our neurological emergency room (ER), was performed between August 2009 and February 2011. Basic demographic variables, present use of OAC, severity of stroke, cardiovascular risk factors, INR values and the symptom onset to presentation time were recorded. In IS patients on OAC presenting within 4.5 h after symptom onset, management was analyzed. In thrombolysed IS patients, bleeding events were documented. Outcome was assessed after 3 months

Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke

BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin

Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: individual-patient-data meta-analysis of randomized trials

Background: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims: We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods: We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results: Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions: An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality

Clinical review: Therapy for refractory intracranial hypertension in ischaemic stroke

The treatment of patients with large hemispheric ischaemic stroke accompanied by massive space-occupying oedema represents one of the major unsolved problems in neurocritical care medicine. Despite maximum intensive care, the prognosis of these patients is poor, with case fatality rates as high as 80%. Therefore, the term 'malignant brain infarction' was coined. Because conservative treatment strategies to limit brain tissue shift almost consistently fail, these massive infarctions often are regarded as an untreatable disease. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view, suggesting that mortality rates may be reduced to approximately 20%. However, critics have always argued that the reduction in mortality may be outweighed by an accompanying increase in severe disability. Due to the lack of conclusive evidence of efficacy from randomised trials, controversy over the benefit of these treatment strategies remained, leading to large regional differences in the application of this procedure. Meanwhile, data from randomised trials confirm the results of former observational studies, demonstrating that hemicraniectomy not only significantly reduces mortality but also significantly improves clinical outcome without increasing the number of completely dependent patients. Hypothermia is another promising treatment option but still needs evidence of efficacy from randomised controlled trials before it may be recommended for clinical routine use. This review gives the reader an integrated view of the current status of treatment options in massive hemispheric brain infarction, based on the available data of clinical trials, including the most recent data from randomised trials published in 2007

Repeated Intra-Arterial Thrombectomy within 72 Hours in a Patient with a Clear Contraindication for Intravenous Thrombolysis

Introduction. Treating patients with acute ischemic stroke, proximal arterial vessel occlusion, and absolute contraindication for administering intravenous recombinant tissue plasminogen activator (rtPA) poses a therapeutic challenge. Intra-arterial thrombectomy constitutes an alternative treatment option. Materials and Methods. We report a case of a 57-year-old patient with concomitant gastric adenocarcinoma, who received three intra-arterial thrombectomies in 72 hours due to repeated occlusion of the left medial cerebral artery (MCA). Findings. Intra-arterial recanalization of the left medial cerebral artery was performed three times with initially good success. However, two days later, the right medial cerebral artery became occluded. Owing to the overall poor prognosis at that time and knowing the wishes of the patient, we decided not to perform another intra-arterial recanalization procedure. Conclusion. To our knowledge, this is the first case illustrating the use of repeated intra-arterial recanalization in early reocclusion of intracranial vessels