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].

• Dyspnea

  In addition, progressive loss of lung function (emphysema), abnormal buildup of fluid within the lungs (pulmonary edema), and breathlessness (dyspnea) may also be present. [rarediseases.org]

  MFF, or "brass founder’s ague," "zinc shakes," or "Monday morning fever" as it is variously known, is characterized by fever, headache, fatigue, dyspnea, cough, and a metallic taste occurring within 3-10 hours after exposure. [emedicine.medscape.com]

• 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]

• Compulsive Behavior

  Neurological symptoms of manganese poisoning consist of increased response time, irritability, mood changes, anxiety, restlessness, and compulsive behaviors. [xpertdox.com]

  In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors. The current mainstay of manganism treatment is levodopa and chelation with EDTA. [diki.pl]

  behaviors. [4] Upon protracted exposure symptoms are more prominent and resemble those of idiopathic Parkinson's disease, as which it is often misdiagnosed, although there are particular differences in both the symptoms (nature of tremors, for example [en.wikipedia.org]

  behavior and intellectual deficits. [flipper.diff.org]

• Euphoria

  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]

  But the euphoria has worn off. There’s an appeal to get through, and beyond that, an increasingly quiet life. “Jeff doesn’t laugh anymore,” Terry says. “Back when we were dating, he was the life of the party. [motherjones.com]

• Mood Swings

  Spoor says that the symptoms experienced by sufferers include fits, tremors, a burning sensation on the skin, mood swings and psychosis, in extreme cases. [environment.co.za]

• Tremor

  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]

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

  Manganese poisoning symptoms may include: tremors, muscle stiffness, rigidity, instability and lack of balance, slowness of movement, joint pain, cramps, memory loss, partial paralysis, drooling, difficulty swallowing and constipation. [yourlawyer.com]

• Headache

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

  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]

  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]

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

• Confusion

  These syndromes may initially be confused with other neurodegenerative conditions, infectious processes, and psychiatric disorders. [ncbi.nlm.nih.gov]

  Clinical features include CONFUSION; HALLUCINATIONS; and an extrapyramidal syndrome (PARKINSON DISEASE, SECONDARY) that includes rigidity; DYSTONIA; retropulsion; and TREMOR. [connects.catalyst.harvard.edu]

  […] symptoms can arise from exposure, including tremors and shaking, problems walking, balance problems, slow movement, muscle rigidity, slow or slurred speech, sleeping disorders, irregular handwriting, poor memory, sexual impotence, double vision, mental confusion [ashkinlaw.com]

  Possible confusion with other symptoms The necrotic lesions caused by manganese toxicity may be confused with those of salinity or boron toxicity. [keys.lucidcentral.org]

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

• Burning Sensation

  Spoor says that the symptoms experienced by sufferers include fits, tremors, a burning sensation on the skin, mood swings and psychosis, in extreme cases. [environment.co.za]

• 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]

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]

The patients showed a bradykinetic-rigid syndrome indistinguishable from Parkinson's disease that responded to treatment with levodopa. Full Text [jamanetwork.com]

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]

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]

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]

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.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]

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

Green tea prevents the oxidation of the LDL cholesterol, preventing it from turning into arterial plaque. Green tea has also been shown to help regulate blood glucose, keeping it at a steady level. [streetdirectory.com]

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

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.