Morphological and functional imaging in neurological and non‐neurological Wilson's patients

Abstract

Wilson's disease causes disturbances of the central nervous system, affecting it both directly through copper toxicity and indirectly subject to a copper-induced hepatopathy, resulting in morphological and physiological changes in brain structures that can be captured by means of magnetic resonance imaging (MRI), (123)I-β-CIT (2β-carbomethoxy-3β (4-iodophenyl)tropane)-SPECT (single photon emission computed tomography), (123)I-IBZM (benzamide)-SPECT and [(18)F]FDG -PET (fluorodeoxyglucose-positron emission tomography). MRI can reveal even slight morphological changes in non-neurological Wilson's patients. More marked findings in neurological Wilson's patients become evident in T1- and T2-weighted MRI. T1-weighted MRI predominantly detects atrophic changes, whereas T2-weighted MRI regularly records signal changes in the putamen. With the aid of these three nuclear-medicine examinations, nigrostriatal and metabolic disturbances are identified in neurological Wilson's patients only. Sufficient decoppering therapy prevents progression and even tends to improve symptoms. A correlation between any of the imaging findings in patients with the genetic phenotype and the incidence of the most common mutation H1069Q (homozygote or compound heterozygote) or other mutations could not be substantiated.

Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

“…The data from this study demonstrated age-dependent changes of 64 Cu accumulation in the brains of Atp7b −/− knockout mice, which are encouraging and support further investigation of age-dependent changes of copper metabolism in WD patients who suffer from psychiatric and neurological symptoms, using [ 64 Cu]CuCl 2 -PET/CT imaging in conjunction with [ 18 F]FDG PET [34, 35] and MRI [35, 36]. Delineation of age-dependent changes of copper metabolism in WD patients is expected to contribute to a better understanding of molecular mechanism of neurodegeneration in WD.…”

Airborne copper exposure in school environments associated with poorer motor performance and altered basal ganglia

“…In children, the highly energetic basal ganglia appear to be the main target. This occurs in our study and in Wilson's disease, in which the lenticular nucleus (putamen and globus pallidus) was originally described with the most dramatic pathological changes (Compston ), although the caudate nucleus may show the most severe reduction in glucose consumption (Hermann ). By contrast, a more persistent subtle excess of copper throughout life could be responsible for protracted but widespread brain damage.…”

Update on the clinical management of Wilson's disease

“…Structural and to some extent functional neuroimaging may be helpful in the diagnosis of WD 45–47. Magnetic resonance imaging (MRI) detects brain abnormalities in essentially every patient exhibiting neurologic symptoms.…”

“…However, these changes are nonspecific, and WD needs to be confirmed by other laboratory methods. Hyperintensity on T2 weighted and fluid-attenuated inversion recovery images are characteristically present in putamen that is the most commonly involved basal ganglia structure, followed by striatum and globus pallidus 45,46. A thin rim of T2 hyperintensity in the claustrum is also frequently seen and it is known as the bright claustrum sign.…”

“…Structural brain changes result from copper toxicity but the underlying hepatic encephalopathy also has MRI correlates in T1-weighted hyperintensity affecting the same areas of brain as seen on T2-weighted images. Patients with liver failure may have only T1-weighted abnormalities on their brain MRI scans without typical T2 changes in basal ganglia 45,49. Advanced WD with persisting neurologic morbidity cause secondary brain atrophy but this is seen in later stages of the disease.…”