Vessel Wall Enhancement on Black-Blood MRI Predicts Acute and Future Stroke in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients. MATERIALS AND METHODS: This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on pre- and postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy-positive and age-matched negative participants using a prevalence- and bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P < .20. RESULTS: Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalence- and bias-corrected kappa was 0.82 (95% CI, 0.71-0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio = 1.5; 95% CI, 1.1-2.2; P = .022), age (prevalence ratio = 1.02; 95% CI, 1.0-1.05; P = .036), time between symptoms and MR imaging (prevalence ratio = 0.9; 95% CI, 0.8-0.9; P < .001), and smoking (prevalence ratio = 0.7; 95% CI, 0.5-1.0; P = .042) with c-statistic = 0.92 (95% CI, 0.84-0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%-67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement-positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%-84.0%) versus 32.2% (95% CI, 14.4%-62.3%) ischemic strokes per year, chi-square = 4.9, P = .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio = 3.4; 95% CI, 1.0-12.0; P = .053) and vessel wall enhancement (hazard ratio = 2.5; 95% CI, 0.9-7.0; P = .080). CONCLUSIONS: Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy.

Lesion stability characteristics outperform degree of stenosis in predicting outcomes following stenting for symptomatic intracranial atherosclerosis.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) causes substantial morbidity and mortality. Treatment decisions have most commonly been driven by the degree of luminal stenosis. This study compares ICAD lesion stability features with percentage stenosis for associations with adverse outcomes following treatment with stents. MATERIALS AND METHODS: Retrospective analysis was performed of prospectively maintained procedure logs. Lesions were classified by symptom type as hypoperfusion, non-hypoperfusion, or indeterminate, and pretreatment asymptomatic intervals were noted. Hypoperfusion lesions and indeterminate or non-hypoperfusion lesions with ≥14 days of asymptomatic interval were classified as stable. Percentage stenosis was calculated and compared against these other symptom features for value in predicting technical complication, ischemic stroke, disability, or death at 90 days and 2 years using univariate and multivariate analysis. RESULTS: 130 lesions were treated in 124 patients. The only statistically significant percent stenosis finding was lesions with 60-99% stenosis were less likely to have technical complications. In univariate analysis, stroke at 2 years was less common with hypoperfusion and stable lesions. In multivariate analysis, only hypoperfusion status was associated with lower stroke rates at 2 years. CONCLUSIONS: Lesion stability features, particularly non-hypoperfusion symptomatology, outperform percentage stenosis in predicting outcomes following treatment of ICAD with stents. Further examination is needed to better classify the natural history of ICAD and more precisely classify lesion stability.

Patient radiation exposure during diagnostic and therapeutic interventional neuroradiology procedures.

PURPOSE: Increasing in number and complexity, interventional neuroradiology (INR) procedures are becoming an important source of radiation exposure for patients. In accordance with the ALARA principle, radiation exposure during INR procedures should be curtailed as much as possible while reaching successful treatment outcomes. Moreover, the extent of radiation exposure should be one outcome measure used to assess new technologies and procedural efficacy, and training programs should include techniques for exposure limitation. This study provides a methodology and preliminary data to assess radiation exposure during different INR procedure types. MATERIALS AND METHODS: All patients undergoing endovascular procedures in two biplanar dedicated neuroangiography suites at a major academic medical center were monitored according to procedure type, pathological indication, fluoroscopy time and machine-generated patient dose estimates between April 2006 and July 2008. RESULTS: 1678 patients underwent cerebral arteriography during the study period. Women (62.1%) accounted for the majority of patients, but men (38.9%) were more likely to undergo an interventional procedure than women (32.8%). Diagnostic studies accounted for 64.9% of procedures. Variable exposures were found between diagnostic and interventional procedures. Exposure differed depending on indications for the procedure and procedure type. CONCLUSION: Radiation exposure is an increasingly important consideration in the development of minimally invasive neurological procedures including cerebral angiography and INR. The type of procedure and lesion type allow the practitioner to estimate radiation exposure. Such information informs the clinical decision making process. Normative data should be collected and used for comparison purposes as one measure of technical and procedural success.

A novel candidate region for ALS on chromosome 14q11.2.

Sequence variations with biologic effect in ALS have been identified in the gene for vascular endothelial growth factor (VEGF). The gene for a related protein, angiogenin, lies on chromosome 14q11.2. Analysis of the angiogenin (ANG) gene in the authors' population has demonstrated a significant allelic association with the rs11701 single nucleotide polymorphism (SNP) and identified a novel mutation in two individuals with sporadic ALS that potentially inhibits angiogenin function. These observations propose a candidate region for ALS on chromosome 14q11.2 and suggest that other genes with similar function to VEGF may be important in the pathogenesis of ALS.

Modulation of guinea-pig peritoneal macrophage Fc receptor activity using D-penicillamine.

The influence of D-penicillamine and 2,2'-pyridylisatogen tosylate upon guinea-pig peritoneal IgG Fc receptor activity is examined. D-penicillamine pretreatment of guinea-pig peritoneal cells is shown to selectively reduce the specificity of the interaction between 7s-human IgG and the guinea-pig macrophage Fc receptor population. In contrast, the drug did not influence the binding of guinea-pig 7s IgG2 nor the uptake of aggregated heterologous or homologous Immunoglobulin. Both D-penicillamine and 2,2'-pyridylisatogen tosylate are shown to influence particulate immune complex binding to pretreatment peritoneal cells.

Selective action of D-penicillamine on guinea pig peritoneal macrophage Fc gamma receptors for homologous, monomeric IgG1.

Guinea pig oil-induced peritoneal exudates were pretreated with D-penicillamine. The binding of homologous, monomeric IgG2 and IgG1 to normal and pretreated exudates was examined. Whereas the 7S IgG2-IgG2 Fc gamma receptor interaction remains unaffected by the pretreatment, the binding of IgG1 to the IgG Fc gamma receptor population was affected. The significance of the selective effect of D-penicillamine is discussed.

Specificity of Fc receptors on human monocytes for IgG1 and IgG3.

Human myeloma proteins IgG1 and IgG3 have been compared for their ability to inhibit the binding of native particular immune complexes, containing either subclass, to peripheral blood monocytes. In contrast to some earlier findings, 7s IgG3 has been shown to be more effective than 7s IgG1.

The binding of human and guinea-pig IgG subclasses to homologous macrophage and monocyte Fc receptors.

Guinea-pig IgG2 and IgT1 bind to contiguous Fc receptors on homologous peritoneal macrophages. Equilibrium association constants determined for the binding of human IgG subclasses to homologous peripheral blood monocytes show that the order of binding is IgG1 greater than IgG3 greater than IgG4 greater than IgG2. Direct binding and rosette assay techniques independently established that both guinea-pig IgG2 and human IgG bind to homologous macrophage-monocyte Fc receptors through a site present in whole Fc (CH2. CH3)2, but absent in pFc' subfragments (CH3)2.

Cytophilic activity of enzymatically derived fragments of guinea pig IgG2.

The hydrolysis products from short term exposure of guinea pig IgG2 to papain and pepsin have been characterized. Papain hydrolysis liberates 4 types of Fc fragment, only one of which retains both an interchain disulfide bond and an intact CH2 domain, cFc, mol.wt. 56 000. The other three fragments noncovalently linked Fc (nFc) (mol.wt. 56 000), incomplete Fc (iFc) (mol.wt. 39 000) and Fc' (23 000) represent further degradation products of covalently linked complete Fc (cFc). The cytophilic activities of these fragments as well as F(ab')2 and pFc' from pepsin hydrolysis, were studied to determine the domain(s) responsible for binding to homologous peritoneal macrophages. Only the native immunoglobulin and the intact cFc manifested cytophilic activity; in particular pepsin-derived pFc' and Fc' were inactive. Following mild reduction and alkylation, performed to affect only the interchain disulfide bonds, the cytophilic activity of cFc was markedly reduced. The low cytophilic activity in the pFc' fragment suggests that the CH2 domains play a major part in binding to the macrophage Fc receptor through a site(s) stabilized by the interchain disulfide bonds.