Intra-arterial third-generation recombinant tissue plasminogen activator (reteplase) for acute ischemic stroke.

OBJECTIVE: We prospectively evaluated the safety and recanalization efficacy of intra-arterially administered reteplase, a third-generation recombinant tissue plasminogen activator, for treating ischemic stroke in patients considered poor candidates for intravenously administered alteplase therapy. METHODS: Patients were considered poor candidates for intravenously administered therapy because of severity of neurological deficits, interval from onset of symptoms to presentation of 3 hours or more, or recent major surgery. We administered a maximum total dose of 8 U of reteplase intra-arterially in 1-U increments via superselective catheterization. Adjunctive angioplasty of the occluded artery was performed in seven patients. Angiographic evidence of perfusion and thrombus was graded by use of modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Neurological examinations were performed before and 24 hours and 7 to 10 days after treatment. RESULTS: Sixteen consecutive patients were treated (mean age, 64.1 +/- 16.4 yr; seven were men). Initial National Institutes of Health Stroke Scale scores ranged from 10 to 26. Time from onset of symptoms to treatment ranged from 2 to 9 hours. Occlusion sites were the cervical internal carotid artery (n = 4), intracranial internal carotid artery (n = 4), middle cerebral artery (n = 6), and vertebrobasilar artery (n = 2). Complete or near-complete perfusion (TIMI Grade 3 or 4) was achieved in the arteries in 14 patients (88%), with partial recanalization (TIMI Grade 2) or minimal response (TIMI Grade 1) in the arteries in one patient each. Neurological improvement (defined as decrease of four or more points in National Institutes of Health Stroke Scale score) was observed in 7 (44%) of the 16 patients at 24 hours. Symptomatic intracerebral hemorrhage occurred in one patient; three other patients experienced intracerebral hemorrhages that did not result in neurological worsening. The overall mortality during hospitalization was 56%, related to massive ischemic stroke (n = 7), withdrawal of care at the family's request after the development of aspiration pneumonia and renal failure (n = 1), and a combination of intracerebral hemorrhage and massive ischemic stroke (n = 1). CONCLUSION: In this study, intra-arterially administered reteplase in doses up to 8 U with or without angioplasty resulted in a high rate of recanalization. This strategy should be considered in treating patients considered poor candidates for intravenous thrombolysis.

Orbital involvement as the initial manifestation of sarcoidosis: magnetic resonance imaging findings.

A 74-year-old man had diplopia, painful right ophthalmoplegia, proptosis, conjunctival injection, and facial skin lesions. Magnetic resonance imaging (MRI) revealed infiltration of the right intraorbital adipose tissue. Lesions were mixed low- and high-signal on T2-weighted images and enhanced on fat-suppressed T1-weighted postcontrast images. A skin biopsy revealed numerous noncaseating granulomas consistent with sarcoidosis. Treatment with corticosteroids and chlorambucil led to a full clinical recovery. Sarcoidosis should be considered in the evaluation of orbital pseudotumor in elderly patients, even if no systemic manifestations of sarcoidosis are present.

Intraarterial recombinant tissue plasminogen activator for ischemic stroke: an accelerating dosing regimen.

OBJECTIVE: Urokinase has been conventionally used for intraarterial thrombolysis in acute ischemic stroke. Recently, due to the withdrawal of urokinase from the market, attention has been focused on recombinant tissue plasminogen activator (r-tPA) for intraarterial administration. Data is limited regarding the intraarterial dose, efficacy, and safety profile of this agent. METHODS: We prospectively studied 8 consecutive patients with acute ischemic stroke who were referred for intraarterial lysis. Each patient was considered by the treating neurologist to be a poor candidate for intravenous therapy. We administered a maximum total dose of 40 mg of r-tPA intraarterially via superselective catheterization. Angiograms were obtained after each 10 mg of r-tPA, and responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria for perfusion and degree of thrombus. RESULTS: Initial National Institutes of Health Stroke Scale (NIHSS) scores ranged from 16 to 21. Intervals from presentation to treatment initiation ranged from 1 to 8 hours. After administration of r-tPA, neurological improvement (decrease in NIHSS score > or =2) was observed in 4 patients. Mean perfusion grade improved from a pretreatment score of 0 with increasing doses of r-tPA to 1.1 +/- 1.0 with 10 mg, 1.5 +/- 1.4 with 20 mg, 2.0 +/- 0.8 with 30 mg, and 2.7 +/- 1.0 with 40 mg. Mean thrombus degree decreased from a pretreatment score of 4 with increasing doses of r-tPA to 2.8 +/- 1.2 after 10 mg, 2.6 +/- 1.4 after 20 mg, 1.9 +/- 1.5 after 30 mg, and 1.4 +/- 1.5 after 40 mg. Asymptomatic intraparenchymal hemorrhage was observed on CT scan in 2 patients at 24 hours. CONCLUSION: Our study suggests that intraarterial r-tPA in doses up to 40 mg is relatively safe. The dose appears to facilitate the recanalization process by lysis of local thrombus and improvement in distal flow.