ABSTRACT
BACKGROUND AND PURPOSE: Immune therapy against amyloid-ß appears to be a promising target in Alzheimer disease. However, a dose-related risk for ARIA on FLAIR images thought to represent parenchymal vasogenic edema or sulcal effusion (termed "ARIA-E"), has been observed in clinical trials. To assess the intensity of ARIA-E presentation, an MR imaging scale that is both reproducible and easily implemented would assist in monitoring and evaluating this adverse event. MATERIALS AND METHODS: On the basis of a review of existing cases from a phase II bapineuzumab study, a scale was constructed with a 6-point score for the 6 regions on each side of the brain (range, 0-60). Scores would be obtained for both parenchymal and sulcal hyperintensities and frequently co-occurring gyral swelling. Inter-rater reliability between 2 neuroradiologists was evaluated in 20 patients, 10 with known ARIA-E and 10 without, by using the intraclass correlation coefficient. RESULTS: The 2 raters had excellent agreement in the identification of ARIA-E cases. A high inter-rater agreement was observed for scores of parenchymal hyperintensity (ICC = 0.83; 95% CI, 48-96) and sulcal hyperintensity (ICC = 0.89; 95% CI, 63-97) and for the combined scores of the 2 ARIA-E findings (ICC = 0.89; 95% CI, 62-97). Gyral swelling scores were observed to have lower inter-rater agreement (ICC = 0.54; 95% CI, -0.06-0.86). CONCLUSIONS: The proposed rating scale provides a reliable and easily implemented instrument to grade ARIA-E imaging findings. We currently do not recommend including swelling.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Brain Edema/chemically induced , Brain Edema/pathology , Cerebral Amyloid Angiopathy/pathology , Magnetic Resonance Imaging/methods , Subdural Effusion/chemically induced , Subdural Effusion/pathology , Aged , Algorithms , Cerebral Amyloid Angiopathy/complications , Cerebral Amyloid Angiopathy/drug therapy , Female , Humans , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Male , Observer Variation , Reproducibility of Results , Sensitivity and Specificity , Severity of Illness IndexSubject(s)
Antimetabolites, Antineoplastic/adverse effects , Methotrexate/adverse effects , Subdural Effusion/chemically induced , Antimetabolites, Antineoplastic/administration & dosage , Burkitt Lymphoma/drug therapy , Humans , Injections, Spinal , Magnetic Resonance Imaging , Male , Methotrexate/administration & dosage , Middle Aged , Nasopharyngeal Neoplasms/drug therapy , Radiography , Subdural Effusion/diagnostic imagingABSTRACT
STI571 is active against Bcr/Abl-, c-kit- and platelet-derived growth factor receptor (PDGFR)-driven malignancies. Mild to moderate edema is common, whereas severe edema, body cavity effusions and subdural hygromas are rarely observed. These effects have been suggested to involve inhibition of PDGFR signaling, but predisposing factors are unknown. We examined SNPs in the PDGFR alpha and beta gene regions in STI571-treated patients with and without life-threatening edema or cerebral hygromas, and in healthy volunteers. By RFLP analysis of 15 SNPs, the frequencies of genotypes did not differ between the three groups. SNPs of PDGFR genes do not appear to play a role in patient's susceptibility to clinically severe edema formation during treatment with STI571.
