Resolution of Cranial MRI and SPECT Abnormalities in a Patient with Wilson's Disease Following Oral Zinc Monotherapy

Abstract

A 38-year-old woman with Wilson's disease developed neurological deterioration after 25 years of lowdose penicillamine administration. She showed an akinetic-rigid syndrome and cerebellar motor ataxia. Brain MRI showed increased signal intensity at the bilateral pons, midbrain, putamen, and thalamus. 123I-IMP-SPECT revealed a diffuse reduction of cerebral blood flow at the bilateral cerebral hemisphere including the basal ganglia. After the patient's regimen was changed to zinc therapy, her neurological condition gradually improved, and she showed almost complete recovery within two years. Serial MRI and SPECT studies showed a marked improvement in the lesions.

Occupancy of the Zinc-binding Site by Transition Metals Decreases the Substrate Affinity of the Human Dopamine Transporter by an Allosteric Mechanism

“…The effect relies on the Zn 2+ -dependent induction of metallothionein into the gut epithelium and the resulting reduced systemic bioavailability of dietary copper (16). Interestingly, Zn 2+ has been found to be particularly effective in improving neurological deficits (30, 35) even when prior chelation therapy failed (36, 37). Based on this circumstantial evidence and on our observations, we propose that displacement of Cu 2+ from the Zn 2+ -binding site of DAT may contribute to the therapeutic efficacy of Zn 2+ in Wilson's disease.…”

Homogeneous magnetic resonance imaging of brain abnormalities in bipolar spectrum disorders comorbid with Wilson's disease

“…The lesions occurring most frequently in patients with comorbid BDs have also been described as typical of WD in which extensive striatal, putamen, thalamic and white matter brain MRI abnormalities were identified [18,19]. However, the same lesions have been described in BD in the absence of the WD [8], even though other lesions, described as typical of BD, specifically the cortical ones [20], were not found more frequently in the sample of WD + BDs than in the other two samples of WD without BDs.…”

Wilson’s disease: A review of what we have learned

“…Since neurological worsening might be induced with the use of potent chelators, it has been proposed [98] , and it has been the experience of our groups, that the optimal therapeutic approach in patients with severe neurological impairment is to commence treatment with zinc, which acts not by rapid mobilization of copper, but by blockage of copper absorption both from food as well as from endogenously secreted copper, creating a consistent negative copper balance without inducing an intense and sudden copper redistribution [78] . Not only as initial therapy in cases of severe neurologic involvement, but also as an alternative agent after discontinuing chelators, zinc therapy has been proven to favor improvement and even resolution of neurological damage in WD [99] . Although not standardized, combined therapy, with the administration of either D-penicillamine and zinc, or trientine and zinc, at widely spaced intervals during the day, is a valid strategy that has yielded good results [100] .…”