ABSTRACT
BACKGROUND: The use of self-expanding stents to treat post-hemorrhagic cerebral vasospasm was recently described. We sought to determine the clinical efficacy of the Cascade device to treat delayed cerebral vasospasm (DCV). We performed benchside tests to determine the chronic outward force exerted by the Cascade in comparison to the Solitaire. METHODS: The chronic outward force (COF) of the Cascade M agile and Cascade L Agile was tested with equivalent tests of the Solitaire 4x20mm. Further tests to determine the forces generated in pre-formed tubes of 1.5-6 mm were performed using both fully and partially unsheathed Cascades. A retrospective review to identify all patients with aSAH and DCV treated with a Cascade device between January 2020 and July 2021. We recorded the treatment arterial vessel diameters and hemorrhagic or ischemic complications. RESULTS: In vitro the Cascade generated greater radial force than the Solitaire. The force generated by the Cascade M Agile at 1.5 mm was approximately 64% higher than the Solitaire 6x40mm and approximately 350% higher than the Solitaire 4x20mm. 4 patients with DCV were identified all of whom were treated with a cascade device. In all cases there was a significant improvement in the diameter of the vasospastic vessels treated with an average diameter increase of approximately 300%. There were no complications from the Cascade. Delayed CT angiography showed persistent dilatation of the segments treated with the Cascade at 24 h. CONCLUSION: The Cascade is a safe and effective device when used to treat DCV secondary to aSAH. Larger studies are required to validate our initial results.
ABSTRACT
Although thrombin has an important role in both central and peripheral nerve diseases, characterization of the anatomical distribution of its proteolytic activity has been limited by available methods. This study presents the development, challenges, validation and implementation of a novel histochemical method for visualization of thrombin activity in the nervous system. The method is based on the cleavage of the substrate, Boc-Asp(OBzl)-Pro-Arg-4MßNA by thrombin to liberate free 4-methoxy-2-naphthylamine (4MßNA). In the presence of 5-nitrosalicylaldehyde, free 4MßNA is captured, yielding an insoluble yellow fluorescent precipitate which marks the site of thrombin activity. The sensitivity of the method was determined in vitro using known concentrations of thrombin while the specificity was verified using a highly specific thrombin inhibitor. Using this method we determined the spatial distribution of thrombin activity in mouse brain following transient middle cerebral artery occlusion (tMCAo) and in mouse sciatic nerve following crush injury. Fluorescence microscopy revealed well-defined thrombin activity localized to the right ischemic hemisphere in cortical areas and in the striatum compared to negligible thrombin activity contralaterally. The histochemical localization of thrombin activity following tMCAo was in good correlation with the infarct areas per triphenyltetrazolium chloride staining and to thrombin activity measured biochemically in tissue punches (85 ± 35 and 20 ± 3 mU/ml, in the cortical and striatum areas respectively, compared to 7 ± 2 and 13 ± 2 mU/ml, in the corresponding contralateral areas; mean ± SEM; p<0.05). In addition, 24 h following crush injury, focal areas of highly elevated thrombin activity were detected in teased sciatic fibers. This observation was supported by the biochemical assay and western blot technique. The histochemical method developed in this study can serve as an important tool for studying the role of thrombin in physiological and pathological conditions.
