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].

• Abdominal Pain

  Additional symptoms may include fever, headaches, fatigue, sluggishness (letheragy), vomiting, loss of appetite (anorexia), abdominal pain, constipation, joint pain, loss of recently acquired skills, incoordination, listlessness, difficulty sleeping [rarediseases.org]

  […] neuropathy, coma, autonomic instability, MODS Late: Alopecia, Mees lines, residual neurologic symptoms Alopecia, neuropathy Toxic: >3 µg/L (blood) MDAC Prussian blue Zinc MFF (oxide fumes); vomiting, diarrhea, abdominal pain (ingestion) Copper deficiency [emedicine.medscape.com]

• 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]

• Tremor

  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]

  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]

  Symptoms include tremors or shaking, shuffling walk, abnormal balance, poor memory, irregular handwriting, slurred speech, lack of facial expression, and sleep disorders. I recently met with John R. [ibew82.org]

• Headache

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

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

  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]

• Choreoathetoid Movements

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

• Vertigo

  The patient a man, aged 44, complained of severe back pain, paralysis of both upper and lower extremeties, vertigo and tremor. [webview.isho.jp]

• 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].

Thus PAS-Na appears to be an effective drug for treatment of serious chronic manganese poisoning. [ncbi.nlm.nih.gov]

Unlike Parkinson's disease, manganism is not associated with loss of smell and patients are typically unresponsive to treatment with -DOPA. [diki.pl]

An useful diagnostic criterion to distinguish between manganism and Parkinson's disease consist in the fact that L-DOPA treatment is basically ineffective as treatment for manganism. [flipper.diff.org]

Then, over 3 months, she received an experimental treatment of 15 intravenous infusions of para-aminosalicylic acid (PAS), a relative of aspirin that is used to treat tuberculosis. [sciencemag.org]

This case study suggests that PAS appears to be an effective drug for treatment of severe chronic Mn poisoning with a promising prognosis. Authors: Tommaso Pierani and Luca Rodano. [flipper.diff.org]

Management O2 administration, supportive care. manganese poisoning Acute or chronic intoxication due to manganese excess Etiology Industrial exposure to manganese-laden fumes and dusts in mining, steel foundries, welding, battery manufacture Clinical [medical-dictionary.thefreedictionary.com]

Besides an immune-mediated etiology, it is also believed to occur in gold, mercury, or manganese poisoning. The danger associated with this method is it may cause manganese poisoning if the product is not correctly purified. [diki.pl]

[…] human embryonic kidney (HEK293) cells is associated with decreased intracellular manganese concentration and attenuated cytotoxicity, characterized by the reversal of Mn-reduced glutamate uptake and diminished lactate dehydrogenase (LDH) leakage. [3] Epidemiology [en.wikipedia.org]

Fryzek worked for Maryland’s International Epidemiology Institute ( iei )—known for its industry-commissioned studies, including one that found no link between radiation and cancer in uranium millers. [motherjones.com]

Cikrt, Journal of Hygiene, Epidemiology, Microbiology & Immunology. 28(2):139-48. 1984. "Manganese exposure in steel smelters a health hazard to the nervous system," A. Wennberg et al. [digitalfire.com]

[…] methylcyclopentadienyl manganese tricarbonyl (MMT), [12] which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust, [13] [14] [15] and manganese ethylene-bis-dithiocarbamate ( Maneb ), a pesticide. [16] Pathophysiology [en.wikipedia.org]

The pathophysiology of manganese intoxication and Parkinson's disease are both associated with neurological changes in the basal ganglia; the latter correlates with loss of dopaminergic neurons within the nigrostriatal pathway, whereas the former is associated [jmedicalcasereports.biomedcentral.com]

Pathophysiology: Inadequate manganese intake has been associated with parenteral nutrition, resulting in dermatitis, changes in hair pigmentation and slowed hair growth. Low cholesterol, triglyceride and phospholipid levels were low. [tldp.com]

[…] measures to be implemented to prevent a re-occurrence of a similar nature. [labour.gov.za]

It will also engage with the employers’ Occupational Health and Safety forum to prevent further manga-nism cases. [environment.co.za]

There was evidence of cognitive impairment in both and personality change in case 1 of sufficient severity to prevent both cases from returning to work and to impact on family life. There is no antidote to methyl iodide or manganese poisoning. [ncbi.nlm.nih.gov]

As a postdoctoral fellow at the Whitehead Institute in Cambridge, Massachusetts, Gitler and colleagues started looking for genes that could prevent the cell death caused by mis-folded alpha-synuclein in yeast. [sciencedaily.com]

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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.