Copper deficiency (hypocupremia) or toxicosis (hypercupremia) may cause disorders of central and peripheral nervous systems. Hypocupremia causes myeloneuropathy resembling vitamin B12 deficiency. However, the clinical manifestations, particularly peripheral neuropathy (PN), of hypercupremia have not been adequately evaluated. To compare clinical, laboratory and electrodiagnositc features of PN between patients with hypocupremia and hypercupremia, we retrospectively reviewed the charts of patients with abnormal copper levels. Subjects with zinc abnormalities were excluded. Five hypocupremia (Male/Female = 4/1; age: 54.6 ± 17.1 years; copper = 55.0 ± 8.5 μg/dL [normal = 72-175]; zinc = 74.4 ± 15.5 μg/dL [normal = 60-130]) and 3 hypercupremia (M/F = 1/2; age: 57.0 ± 8.2 years; copper = 215.0 ± 10.8 μg/dL; zinc = 72.3 ± 14.6 μg/dL) were studied. The notable clinical findings included ambulatory difficulty in hypocupremia (2/5); paresthesia in both hypocupremia (3/5) and hypercupremia (2/3) but pain was only seen in (3/3) hypercupremia patients. Tendon reflexes were decreased in hypocupremia (3/5) and hypercupremia (1/3) but hyperreflexias in hypocupremia (2/5) only. Preexisting comorbidity such as diarrhea were observed in (2/3) hypercupremia but not in hypocupremia patients. Laboratory findings showed vitamin D deficiency (16.4 ± 5.6 ng/mL) in (2/2) hypercupremia but normal (40.4 ± 4.7 ng/mL) in (2/2) hypocupremia. Neurophysiologic studies showed evidence of neuropathy in (3/5) hypocupremia only. Different patterns of clinical, neurological examination and electrophysiologic findings between hypocupremia and hypercupremia suggest different underlying pathophysiologies.

Essential trace elements (Cu(2+), Zn(2+), etc) lead to toxic effects above a certain threshold, which is a major environmental problem in many areas of the world. Here, environmentally relevant sub-micromolar concentrations of Cu(2+) and simulations of natural light and temperature cycles were applied to the aquatic macrophyte Ceratophyllum demersum a s a model for plant shoots. In this low irradiance study resembling non-summer conditions, growth was optimal in the range 7.5-35nM Cu, while PSII activity (Fv/Fm) was maximal around 7.5nM Cu. Damage to the light harvesting complex of photosystem II (LHCII) was the first target of Cu toxicity (>50nM Cu) where Cu replaced Mg in the LHCII-trimers. This was associated with a subsequent decrease of Chl a as well as heat dissipation (NPQ). The growth rate was decreased from the first week of Cu deficiency. Plastocyanin malfunction due to the lack of Cu that is needed for its active centre was the likely cause of diminished electron flow through PSII (ΦPSII). The pigment decrease added to the damage in the photosynthetic light reactions. These mechanisms ultimately resulted in decrease of starch and oxygen production.