RESUMO
BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been shown to assess iron content in cerebral cavernous malformations. In this study, our aim was to correlate lesional iron deposition assessed by quantitative susceptibility mapping with clinical and disease features in patients with cerebral cavernous malformations. MATERIALS AND METHODS: Patients underwent routine clinical scans in addition to quantitative susceptibility mapping on 3T systems. Data from 105 patients met the inclusion criteria. Cerebral cavernous malformation lesions identified on susceptibility maps were cross-verified by T2-weighted images and differentiated on the basis of prior overt hemorrhage. Mean susceptibility per cerebral cavernous malformation lesion (χÌlesion) was measured to correlate with lesion volume, age at scanning, and hemorrhagic history. Temporal rates of change in χÌlesion were evaluated in 33 patients. RESULTS: Average χÌlesion per patient was positively correlated with patient age at scanning (P < .05, 4.1% change with each decade of life). Cerebral cavernous malformation lesions with prior overt hemorrhages exhibited higher χÌlesion than those without (P < .05). Changes in χÌlesion during 3- to 15-month follow-up were small in patients without new hemorrhage between the 2 scans (bias = -0.0003; 95% CI, -0.06-0.06). CONCLUSIONS: The study revealed a positive correlation between mean quantitative susceptibility mapping signal and patient age in cerebral cavernous malformation lesions, higher mean quantitative susceptibility mapping signal in hemorrhagic lesions, and minimum longitudinal quantitative susceptibility mapping signal change in clinically stable lesions. Quantitative susceptibility mapping has the potential to be a novel imaging biomarker supplementing conventional imaging in cerebral cavernous malformations. The clinical significance of such measures merits further study.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Mapeamento Encefálico , Criança , Pré-Escolar , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Processamento de Imagem Assistida por Computador , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/etiologia , Ferro/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Adulto JovemRESUMO
Constitutive activation of the NF-kappaB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IkappaB kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-alpha, -beta, -gamma, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-gamma, while K48-ubiquitylated Tax is stabilized upon proteasome inhibition. Altogether, these results support a model in which K63-ubiquitylated Tax activates IKK in a centrosome-associated signalosome, leading to the production of Tax-free active cytoplasmic IKK. These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome.