Leukoaraiosis Attenuates Diagnostic Accuracy of Large-Vessel Occlusion Scales.

BACKGROUND AND PURPOSE: Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales. MATERIALS AND METHODS: We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and κ. Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders. RESULTS: In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1-9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3-10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86-33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8-7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0-8.0), predicted large-vessel occlusion. CONCLUSIONS: The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.

Leukoaraiosis predicts a poor 90-day outcome after endovascular stroke therapy.

BACKGROUND AND PURPOSE: Leukoaraiosis is a common finding among patients with ischemic stroke and has been associated with poor stroke outcomes. Our aim was to ascertain whether the severity of pre-existing leukoaraiosis is associated with outcome in patients with acute ischemic stroke who are treated with endovascular stroke therapy. MATERIALS AND METHODS: We retrospectively analyzed data from 129 consecutive, prospectively enrolled patients with stroke undergoing endovascular stroke therapy at a single tertiary care center between January 2006 and August 2013. Leukoaraiosis was assessed as supratentorial white matter hypoattenuation on admission head CT and graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. We dichotomized the 90-day mRS into good (0-2 or return to baseline) versus poor (3-6) as the primary study outcome. Incremental multivariable logistic regression analyses were performed to identify independent predictors of a poor 90-day outcome. RESULTS: In all multivariable models, severe leukoaraiosis was independently (P < .05) associated with a poor outcome at 90 days (fully adjusted model: OR, 6.37; 95% CI, 1.83-12.18; P = .004). The independent association between leukoaraiosis and a poor outcome remained when the analysis was restricted to patients who were alive at discharge (n = 87, P < .05). Last, among patients who were alive at discharge, those with severe leukoaraiosis had significantly less frequent improvement on the mRS from discharge to 90 days compared with patients with absent-to-moderate leukoaraiosis (P = .034). CONCLUSIONS: The severity of pre-existing leukoaraiosis is independently associated with 90-day functional outcome in patients with stroke who underwent endovascular stroke therapy. These results highlight the need to further explore leukoaraiosis as a promising surrogate marker for poor outcome after endovascular stroke therapy to improve risk assessment, patient selection, and early prognostic accuracy.

Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies.

OBJECTIVE: To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage. METHODS: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases-9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed. RESULTS: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients < or =60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. CONCLUSION: Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.

Purification of salmon clotting factors and their use as tissue sealants.

Fibrin sealant prepared from the blood of farmed Atlantic salmon (Salmo salar) represents a potential source of well-controlled natural material with utility in a variety of clinical settings. A potential advantage of this material is a lower probability of viral or bacterial infection that has limited general approval of fibrin glues made from human or bovine proteins. This report describes the purification of fibrinogen from salmon blood, the use of fibrin glues derived from this material to promote wound healing in rats, and the antigenic response to this material. While the low ambient temperature of these cold water fish significantly lessens the probability of infectious transmission to humans, fibrinogen and factor XIII derived from S. salar are activated by human thrombin at 25 degrees C and 37 degrees C to form clots equivalent to those formed by human fibrin. We compare the reactivity of salmon and human fibrinogen with human and bovine thrombin and the structure and viscoelastic properties of the resulting fibrin gels over a range of pH and salt concentrations. The efficacy of salmon fibrin glues in a wound healing assay and the low antigenic response to salmon fibrinogen suggest that this material may substitute for proteins derived from mammalian sources with lower probability of infections.

Low molecular weight group IIA and group V phospholipase A(2) enzymes have different intracellular locations in mouse bone marrow-derived mast cells.

The subcellular location of the enzymes of eicosanoid biosynthesis is critical for their co-ordinate action in the generation of leukotrienes and prostaglandins. This activity is thought to occur predominantly at a perinuclear location. Whereas the subcellular locations of cytosolic phospholipase (PL) A(2) and each of the pathway enzymes of eicosanoid generation have been defined, the distribution of the low molecular weight species of PLA(2) has remained elusive because of the lack of antibodies that distinguish among homologous family members. We have prepared affinity-purified rabbit antipeptide IgG antibodies that distinguish mouse group IIA PLA(2) and group V PLA(2). Immunofluorescence staining and immunogold electron microscopy reveal different subcellular locations for the enzymes. Group IIA(2) PLA(2) is present in the secretory granules of mouse bone marrow-derived mast cells, consistent with its putative role in facilitating secretory granule exocytosis and its consequent extracellular action. In contrast, group V PLA(2) is associated with various membranous organelles including the Golgi apparatus, nuclear envelope, and plasma membrane. The perinuclear location of group V PLA(2) is consistent with a putative interaction with translocated cytosolic PLA(2) in supplying arachidonic acid for generation of eicosanoid products, while the location in Golgi cisternae may also reflect its action as a secreted enzyme. The spatial segregation of group IIA PLA(2) and group V PLA(2) implies that these enzymes are not functionally redundant.