Publications (2)7.24 Total impact
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ABSTRACT: Cerebral vasospasm is the leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH) occurs. The haptoglobin 2-2 genotype likely increases the risk for developing posthemorrhagic vasospasm, but potential treatments for vasospasm have never been tested in an animal model of this genotype. We used the nitric oxide (NO) donor diethylenetriamine (DETA)/NO incorporated into ethylene/vinyl acetate (EVAc) polymers to evaluate the efficacy of controlled NO repletion in a haptoglobin 2-2 mouse basilar artery SAH model. Mice were randomized to 3 groups: autologous blood injection and empty polymer implantation into the subarachnoid space (n = 16); blood injection and 30% DETA/NO-EVAc implantation (n = 20); and sham operation (n = 19). At 24 hours after surgery, activity level was assessed on a 3-point scale, and basilar arteries were processed for morphometric measurements. Leukocyte extravasation was assessed by immunohistochemistry (n = 12). Treatment with controlled release of NO from DETA/NO-EVAc polymers after SAH resulted in a significant increase in basilar artery lumen patency (73.3% +/- 4.3% versus 96.5% +/- 4.3%, mean +/- standard error of the mean; P = 0.01), a significant improvement in activity after experimental SAH (2.14 +/- 0.14 versus 2.56 +/- 0.10 points; P = 0.025), and a significant decrease in extravasated leukocytes (21 +/- 4.55 versus 6.75 +/- 3.77 leukocytes per high-power field, untreated versus treated mice; P = 0.001). Treatment with controlled release of NO prevented posthemorrhagic vasospasm in haptoglobin 2-2 mice, and mitigated neurological deficits, suggesting that DETA/NO-EVAc would be an effective therapy in patients with a genotype that confers higher risk for vasospasm after SAH. In addition to smooth muscle relaxation, inhibition of leukocyte migration may contribute to the therapeutic mechanism of NO.
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ABSTRACT: Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are being used with increasing frequency for the diagnosis of intracranial aneurysms. Although the literature suggests that MRI and MRA are accurate, we have observed that both are associated with a high likelihood of false-positive results in the diagnosis of aneurysms. We prospectively evaluated and compared the accuracy of MRI/MRA versus digital subtraction angiography (DSA) for the diagnosis of intracranial aneurysms. Over the course of 2 years, 133 patients diagnosed with one or more unruptured intracranial aneurysms by MRI/MRA were prospectively evaluated in an outpatient setting. The patients were advised to undergo cerebral four-vessel DSA, and the results from DSA were compared with MRI/MRA findings. In 59% of cases, the DSA and MRI/MRA findings were markedly different. Specifically, in 38% of MRI/MRA-positive cases, DSA findings were completely normal, showing no aneurysms. In an additional 21% of cases, although DSA confirmed the presence of an aneurysm, it differed substantially from MRI/MRA findings in terms of aneurysm location, number of aneurysms, or aneurysm type. In general, the false-positive aneurysms by MRI/MRA were smaller than 5 mm and were most commonly identified in the anterior communicating artery region. MRI/MRA studies are often inaccurate in the diagnosis of intracranial aneurysms and should not be used as the sole diagnostic studies for intracranial aneurysms. Other radiographic modalities should be further investigated as alternatives to MRI/MRA for the diagnosis of intracranial aneurysms.