Manganese plays an essential role in numerous physiological processes (eg. bone growth, protection from free radicals, protein metabolism, etc.) of humans and other mammalian species [1] [2]. In the setting of excessive exposure, however, toxic effects are exerted in the body. Manganese poisoning can be seen in a wide range of occupations, as the production of steel, batteries and many other electronic devices, as well as ceramics, fertilizers, fungicides, and gasoline mandates the use of this element [3] [4] [5]. In addition to occupational exposure, many studies have confirmed that industrial emissions that contain manganese contaminate air, soil, plants and even water sources, which predisposes a number of individuals to manganese toxicity through inhalation or ingestion, particularly those living in close proximity to these industries [1] [4] [6]. Manganese has a rather short half-life in the circulation, but when it reaches the tissues, such as the bones and the central nervous system (CNS), the half-life is estimated to be around 8-9 years [6]. Signs and symptoms are primarily related to the CNS, as manganese passes through the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier, eventually depositing selectively into the globus pallidus and the basal ganglia [3] [7]. Consequently, the clinical presentation is centered around a Parkinson's-like illness developing years after exposure to high concentrations of manganese - tremor, hypertonia rigidity, micrographia, weakness, and postural instability are main symptoms [3] [4] [8]. Moreover, psychiatric complaints in the form of disorientation, memory and judgment deficits, anxiety, hallucinations, etc. are frequently reported [3] [4] [8]. Apart from nervous system toxicity, the lungs, the heart, the liver and the reproductive system are also described as potential sites where harmful effects of manganese might be seen [3].

• Metal Worker

  Workers who are most at risk of being injured by welding rod fumes include: » Welders » Steelworkers » Metal workers » Ironworkers » Pipe fitters » Electrical workers » Railroad workers » Glass manufacturers Anyone who has suffered ill health effects [ashkinlaw.com]

• Abdominal Pain

  Gastrointestinal symptoms include a flu-like illness (gastroenteritis) that is characterized by vomiting; abdominal pain; fever; and diarrhea, which, in some cases, may be bloody. [rarediseases.org]

  pain (ingestion) Copper deficiency: anemia, neurologic degeneration, osteoporosis Normal range: 0.6-1.1 mg/L (plasma) 10-14 mg/L (red cells) * *No accepted chelation regimen; contact a medical toxicologist regarding treatment plan. [emedicine.medscape.com]

• Palpitations

  The patient had palpitations, hand tremor, lower limb myalgia, hypermyotonia, and a distinct festinating gait. She received 6 g PAS per day through an intravenous drip infusion for 4 days and rested for 3 days as one therapeutic course. [flipper.diff.org]

• Hyperhidrosis

  Abstract The clinical picture of Morvan's fibrillary chorea includes a. spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin (multiplets), b. autonomic dysregulation with profuse hyperhidrosis, and [ncbi.nlm.nih.gov]

• Denial

  “They are in denial mode. There is no trust and confidence between us,” he said.—Sapa [mg.co.za]

• Compulsive Disorder

  Brain damage occurs, resulting in rigidity of the muscles with loss of facial expression, slowness of movement, speech impairment, and delusions, hallucinations and compulsive disorders. [medical-dictionary.thefreedictionary.com]

• Incontinence

  Later, he developed various neuropsychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, "cock-walk", increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of [ncbi.nlm.nih.gov]

• Tremor

  Later, he developed various neuropsychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, "cock-walk", increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of [ncbi.nlm.nih.gov]

  Parkinsonian Features - Symptoms include difficulty with movement and balance, muscle stiffness, tremors, an expressionless face, impaired writing, and postural instability. [expertlaw.com]

  Signs of the last stage include involuntary muscle movements; tremors; poor coordination; a mask–like, rigid face; and a staggering, strutting gait. This final stage is irreversible and may lead to complete disability. [welding-rod-dangers.com]

  Consequently, the clinical presentation is centered around a Parkinson's-like illness developing years after exposure to high concentrations of manganese - tremor, hypertonia rigidity, micrographia, weakness, and postural instability are main symptoms [symptoma.com]

• Headache

  The progression of manganism includes: Behavioral Changes - Symptoms include fatigue, headache, muscle cramps, loss of appetite, apathy, insomnia, and diminished libido. [expertlaw.com]

  Early warning signs for welding fumes and manganese poisoning can include any or all of the following; muscle cramps, lethargy, insomnia, loss of equilibrium, weakness, headaches, and memory loss. [resource4thepeople.com]

  In the first stage, patients are exhausted, apathetic, and weak, and may get headaches. The patient’s problems may easily be confused with depression and other illnesses. Some researchers believe that this early stage is reversible. [welding-rod-dangers.com]

  Overexposure may cause headaches, drowsiness, confusion, seizures, and life-threatening complications. [rarediseases.org]

• Choreoathetoid Movements

  In sharp contrast to Parkinsonian patients, the present subjects have not shown choreoathetoid movements thus far. [nejm.org]

• Festinating Gait

  The patient had palpitations, hand tremor, lower limb myalgia, hypermyotonia, and a distinct festinating gait. She received 6 g PAS per day through an intravenous drip infusion for 4 days and rested for 3 days as one therapeutic course. [flipper.diff.org]

• Chorea

  Abstract The clinical picture of Morvan's fibrillary chorea includes a. spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin (multiplets), b. autonomic dysregulation with profuse hyperhidrosis, and [ncbi.nlm.nih.gov]

The importance of an early diagnosis lies in the fact that symptoms can completely disappear with the cessation of exposure to manganese in the initial stages of the disease, whereas an irreversible clinical course is observed when severe exposure has occurred [8]. For this reason, a detailed patient history and a complete physical examination must be performed in order to include manganese poisoning in the differential diagnosis of Parkinson's-like symptoms and psychiatric complaints. Physicians must ask about the patient's occupation (and to which hazards is he/she exposed on a daily basis) [5], while socioeconomic information (eg. living in proximity to the industrial areas) are also important. As soon as a presumptive diagnosis is made, laboratory confirmation should be attempted. Various procedures have been described in the literature, including the determination of manganese levels in blood, plasma, urine, hair, and nails [5] [6]. Ideally, assessment of manganese levels in bones would provide the most reliable results, and in fact, a non-invasive method has been developed for quantitative detection of manganese in bones [6]. Supplementary to clinical criteria and laboratory studies, magnetic resonance imaging (MRI) of the endocranium shows a specific pattern of bilateral and symmetric hyperintensity of the globus pallidus at T1-weighted studies [7], implying that this procedure is a vital constituent of manganese poisoning workup [6].

• Gliosis

  On microscopic examination gliosis can be noticed both in GP and, even if in a less degree, in SNr. The gliosis is associated with an increased number of astrocytes showing an enlarged and irregular nucleus. [flipper.diff.org]

1. Rugless F, Bhattacharya A, Succop P, et al. Childhood Exposure to Manganese and Postural Instability in Children living near a Ferromanganese Refinery in Southeastern Ohio. Neurotoxicol Teratol. 2014;41:71-79.
2. Aschner M. Manganese: brain transport and emerging research needs. Environmental Health Perspectives. 2000;108(Suppl 3):429-432.
3. Crossgrove J, Zheng W. Manganese toxicity upon overexposure. NMR Biomed. 2004;17(8):544-553.
4. Jiang Y-M, Mo X-A, Du F-Q, et al. Effective Treatment of Manganese-Induced Occupational Parkinsonism With p-Aminosalicylic Acid: A Case of 17-Year Follow-Up Study. J Occup Environ Med. 2006;48(6):644-649.
5. Bleich S, Degner D, Sprung R, Riegel A, Poser W, Ru¨ther E. Chronic manganism: fourteen years of follow-up. J Neuropsychiatry Clin Neurosci. 1999;11:117.
6. O’Neal SL, Zheng W. Manganese Toxicity Upon Overexposure: a Decade in Review. Curr Environ Health Rep. 2015;2(3):315-328.
7. Lucchini R, Albini E, Placidi D, et al. Brain magnetic resonance imaging and manganese exposure. Neurotoxicology. 2000;21(5):769-775.
8. Inoue N. Occupational neurotoxicology due to heavy metals-especially manganese poisoning. Brain Nerve [Article in Japanese]. 2007;59(6):581-589.