Manganese (Mn) is a trace essential element with many industrial uses. Mining as well as iron and steel production have been implicated as occupational sources of exposure. It is principally used in steel production to improve hardness, stiffness, and strength. Mn is a normal constituent of air, soil, water, and food. The primary nonoccupational source of exposure is by eating food or Mn-containing nutritional supplements. Vegetarians who consume foods rich in Mn such as grains, beans, and nuts, as well as heavy tea drinkers, may have a higher intake than the average person. People who smoke tobacco or inhale second-hand smoke are also exposed to Mn at higher levels than nonsmokers.
Inhalation is the primary source of entry for Mn but is also partially absorbed (3%-5%) through the gastrointestinal tract. Only very small amounts of Mn are absorbed dermally. Signs of toxicity may appear quickly, and neurological symptoms are rarely reversible. Mn toxicity is generally recognized to progress through 3 stages. Levy describes these stages. "The first stage is a prodrome of malaise, somnolence, apathy, emotional lability, sexual dysfunction, weakness, lethargy, anorexia, and headaches. If there is continued exposure, progression to a second stage may occur, with psychological disturbances, including impaired memory and judgement, anxiety, and sometimes psychotic manifestations such as hallucinations. The third stage consists of progressive bradykinesia, dysarthria, axial and extremity dystonia, paresis, gait disturbances, cogwheel rigidity, intention tremor, impaired coordination, and a mask-like face. Many of those affected may be permanently and completely disabled." Mn is removed from the blood by the liver where it's conjugated with bile and excreted.
The major compartment for circulating Mn is the erythrocytes, bound to hemoglobin, with whole blood concentrations of Mn (in patients with normal levels) being 10 times that of the serum. Mn passes from the blood to the tissues quickly. Concentrations in the liver are highest, with 1 to 1.5 mg Mn/kg (wet weight) in normal individuals. The half-life of Mn in the body is about 40 days, with elimination primarily through the feces. Only small amounts are excreted in the urine.
Elevated levels of whole blood Mn have been reported, with and without central nervous system (CNS) symptoms, in patients with hepatitis B virus-induced liver cirrhosis, in patients on total parenteral nutrition (TPN) with Mn supplementation, and in infants born to mothers who were on TPN. The studies in cirrhotic patients with extrapyramidal symptoms indicate a possible correlation between whole blood Mn and that measured by T1-weighted magnetic resonance in the globus pallidus and midbrain, with whole blood Mn levels being 2-fold or more, higher than normal. Increases in whole blood Mn over time may be indicative of future CNS effects. The data on TPN patients is based on anecdotes or small studies and is highly variable, as is that obtained in infants.
Behcet disease, a form of chronic systemic vasculitis, has been reported to exhibit 4-fold increase in erythrocyte Mn, and it is suggested that increased activity of superoxide dismutase may contribute to the pathogenesis of the disease.
Mn has also been reported as a contaminant in "garage" preparations of the abused drug methcathinone. Continued use of the drug gives rise to CNS toxicity typical of manganism.
For monitoring therapy, whether of environmental exposure, TPN, or cirrhosis, whole blood levels have been shown to correlate well with neuropsychological improvement, although whether the laboratory changes precede the CNS or merely track with them remains unclear. It is recommended that both CNS functional testing and laboratory evaluation be used to monitor therapy of these patients. Long-term monitoring of Behcet disease has not been reported, and it is not known if the Mn levels respond to therapy.