Neurological presentations revealing acquired copper deficiency: diagnosis features, aetiologies and evolution in seven patients.

BACKGROUND: Acquired copper deficiency (ACD) is a rare condition usually diagnosed from haematological changes. AIMS: To characterise the diagnosis features and the evolution of patients with ACD revealed by neurological symptoms. METHODS: Clinical, biological and magnetic resonance imaging (MRI) data were prospectively analysed at diagnosis and during follow up under copper supplementation. RESULTS: Seven patients were studied over a 5-year period. Time to diagnosis ranged from 2.5 to 15 months. Subacute ascending paraesthesias and gait disorder were the first symptoms. All patients had a posterior cord syndrome (PCS) with sensory ataxic gait associated with superficial hypoesthesia of the feet; 50% had also lateral cord signs. Electrodiagnostic tests diagnosed a lower limb sensory neuropathy in four patients. Spinal cord MRI was normal in three of seven patients. Anaemia and lymphopenia were diagnosed in six of seven patients. Serum copper was always low, and urinary copper was low or normal. Serum and urinary zinc were high in four patients. Decreased copper intake (stoma/parenteral nutrition, malnutrition, malabsorption with lack of vitamin supplementation after bariatric or other digestive surgeries) was found in four patients, and the chronic use of denture adhesive paste containing zinc was discovered in four patients. One patient had both the causes recorded. After copper supplementation, copper balance and then haematological disturbances were the first features to normalise gradually in 2 months. Radiological myelitis disappeared in 10 months, whereas neurological symptoms improved in six of seven patients after a mean follow up of 2 years. CONCLUSIONS: Progressive PCS with anaemia and lymphopenia must raise the possibility of an ACD. Early copper supplementation could increase the neurological prognosis.

Bioavailable Trace Metals in Neurological Diseases.

OPINION STATEMENT: Medical treatment in Wilson's disease includes chelators (D-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators' doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron.