Brain iron accumulation in Wilson's disease: A longitudinal imaging case study during anticopper treatment using 7.0T MRI and transcranial sonography
Abstract
Imaging studies in Wilson's disease (WD) commonly show hyperechogenicity of the lentiform nucleus (LN) on transcranial sonography (TCS)1 and hypointense lesions in the deep gray matter (DGM) on T2 -weighted magnetic resonance imaging (MRI).2,3 In a postmortem MRI-histopathology correlation study, cerebral T 2 lesions in WD were associated with increased iron content and the presence of iron-containing macrophages, but not with copper concentration.4 WD can be treated by inducing a negative copper balance. However, early worsening after treatment initiation occurs in up to 50% of patients with neurologic symptoms, and results in severe permanent disability in 20% of them.5 Possible connections between iron accumulation, neurodegeneration, and clinical worsening on anticopper treatment in WD are poorly understood.
Rapid mobilization of copper from tissues with subsequent elevation of toxic free copper may accelerate neurodegenerative changes that could be accompanied by the influx of iron and activation of macrophages. Chelation therapy can also prevent incorporation of copper into ceruloplasmin and negatively affect its ferroxidase activity, which is necessary for tissue iron efflux.
Ceruloplasmin dysfunction inherent to WD pathophysiology and aggravated by chelation therapy may thus contribute to iron accumulation in WD.6