Long Term Follow up of Cerebellar Ataxia CA) and MRI Lesions Which Responded to Copper (Cu) Supplementation (P12-055-19)

Abstract

ObjectivesCu deficiency (CuD) produces anemia and leukopenia. CuD neurologic dysfunction can also occur. We follow a patient with CuD with CA and MRI lesions that responded to Cu replacement. MethodsA 64-year-old male with progressive ataxia and neuropathy was found to have a significant CuD (copper level 38 mmol/L, normal range 70–175) 7 years ago. The etiology of CuD was unknown. There was no previous gastric surgery, malabsorption, ingestion of zinc containing products or medications associated with Cu loss.He had an ataxic gait with a steppage component. Muscle stretch reflexes were brisk at the knees and absent at the ankles. He had length dependent loss to all modalities. Other etiologies for CA were not found. The blood smear showed anisocytes and poikilocytes, but anemia and leukopenia were absent. He became wheelchair bound after several weeks.Brain MRI without contrast revealed non-enhancing symmetric T2 signal prolongation of the medial cerebellar white matter extending into left middle cerebral peduncle. Neuroconductive studies showed moderate-to-severe axonal sensorimotor polyneuropathy. ResultsCu supplementation with using 5 mg cupric oxide daily raised serum Cu to 97 mmol/L. Symptoms improved after 1 month. Brain MRI 3 months later showed no cerebellar lesions with serum Cu of 123 mmol/L. At this point he was able to walk with a cane. His gait disturbance further improved to the extent that he was able to walk without assistance or support. His follow up Cu levels remain in the normal range (last value = 128 mmol/L). ConclusionsCu is a component of the neurologic metalloenzymes cytochrome-c oxidase (CcO), Cu-zinc superoxide dismutase, tyrosinase, dopamine β-hydroxylase, peptidylglycine α-amidating monooxygenase and ceruloplasmin. Cu and iron pass electrons through CcO to oxygen, forming water. CuD impacts the electron transport chain, impairing ATP production which injures susceptible tissues.This case demonstrates the reversibility of neurologic dysfunction and MRI lesions by means of correcting CuD. Our 7-year follow up period confirms the validity of the pathogenesis and management. Further study is needed to identify the specific roles of Cu metabolism in such cases and the individual factors allowing for the dramatic response we observed. Funding Sourcesnone.