Manganese poisoning is primarily seen in the occupational setting, as numerous industries use manganese ore for the production of batteries, ceramics, steel, etc. The central nervous system is the principal site where manganese causes toxic effects, mainly in the form of a Parkinson's-like disease. Bradykinesia, gait disturbances, rigidity and other extrapyramidal signs constitute the clinical presentation of most patients. A detailed patient history and a full biochemical workup are necessary to make the diagnosis.
Presentation
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].
Entire Body System
- Movement Disorder
Clinical findings Acute—pneumonitis; chronic—psychotic or schizophrenia-like episodes, parkinsonism, movement disorders. [medical-dictionary.thefreedictionary.com]
Movement Disorders, 19 (Suppl 9), S186 (2004). Racette, B. A., Welding-related parkinsonism.: clinical features, treatment and pathophysiology. Neurology, 57, 936-937 (2001). Roels, H. A., Ortega Eslava, M. [consultox.com]
PMID: 35794251 Movement disorders and neuropathies: overlaps and mimics in clinical practice. Gentile F, Bertini A, Priori A, Bocci T. Gentile F, et al. J Neurol. 2022 Sep;269(9):4646-4662. doi: 10.1007/s00415-022-11200-0. Epub 2022 Jun 3. [pubmed.ncbi.nlm.nih.gov]
Movement Disorders. 22 (9): 1337–1343. doi : 10.1002/mds.21378. PMID 17566121. CS1 maint: Multiple names: authors list ( link ) ^ Ensing,, J. G. (1985). "Bazooka: Cocaine-Base and Manganese Carbonate". [en.wikipedia.org]
- Inflammation
[…] serve as activators of liver arginase and other enzymes. manganese poisoning a condition usually caused by inhalation of manganese dust; symptoms of chronic exposure include mental disorders accompanying a syndrome resembling Parkinson's disease, and inflammation [medical-dictionary.thefreedictionary.com]
Other symptoms include inflammation of sensory and motor nerves (polyneuritis) and the mucose membrane lining the throat. Inorganic arsenic accumulates in the liver, spleen, kidneys, lungs, and gastrointestinal tract. [rarediseases.org]
They show signs of inflammation, for example; one theory holds that PD involves an inflammatory reaction in the brain. The level of harm Either way, it is now clear that exposure to high levels of manganese is not good for the brain. [economist.com]
- Difficulty Walking
Toxicity from inhaling manganese dust (known as manganism) can be an occupational hazard, and cause a more rapid onset of neurological symptoms including tremors, irritability, aggressiveness, hallucinations difficulty walking, and facial muscle spasms [fixyourgut.com]
Symptoms including tremors, difficulty walking, and facial muscle spasms. This toxicity syndrome -- called manganism -- is sometimes preceded by psychiatric symptoms, such as irritability, aggressiveness, memory problems, and even hallucinations. [medicalassessmentonline.com]
- Chills
Manganese levels that are too high can lead to: Fever Chills Mouth and throat dryness Muscle pains/cramps Headaches Nausea Restlessness Irritability Hallucinations Hearing loss/impairment Personality change Deficient manganese levels can lead to: Impaired [healthlabs.com]
Acute symptoms of Exposure: Metal fume fever - chills, fever, muscle aches, headaches, dry throat. Chronic symptoms of Exposure: Sleepiness, weakness in legs, muscular twitchings, nocturnal leg cramps, slowness of speech, languor. [potters.org]
In cases of chronic poisoning, weakness, muscle aches, chills, and fever may develop. The onset of symptoms in chronic arsenic poisoning is about two to eight weeks after exposure. [rarediseases.org]
- Exposure to Metal Fumes
July/Aug 2003 Exposure to metal fumes from welding, cutting and brazing—especially in confined spaces—can cause brain damage. A major culprit is manganese, a component of all steel and major welding materials. [elcosh.org]
Respiratoric
- Pneumonia
Several say they have suffered bouts of pneumonia, joint pain, memory loss and other conditions. One current worker said he has seen several cases of summertime pneumonia in the last two years. [insidebayarea.com]
Symptoms associated with overexposure to manganese may include damage to the central nervous system and pneumonia. [rarediseases.org]
Toxicity to the lungs is manifested as increased susceptibility to bronchitis or, in more severe cases, manganic pneumonia. The possibilities for monitoring exposure to manganese by a biological method are still very limited. [potters.org]
He died, at the age of sixty, of pneumonia, but he had been suffering from another illness for many years. [digitalfire.com]
Gastrointestinal
- 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]
- Muscle Rigidity
Numerous 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 [ashkinlaw.com]
Parkinson-like symptoms may include tremors, slowness of movement, muscle rigidity, and poor balance. [cdc.gov]
Musculoskeletal
- Leg Cramp
Symptoms of manganese poisoning include tremors, shakes, loss of balance, slowed movement, walking problems, impotency, slurred speech, extreme drowsiness or nighttime leg cramps. [elcosh.org]
Chronic symptoms of Exposure: Sleepiness, weakness in legs, muscular twitchings, nocturnal leg cramps, slowness of speech, languor. Kong Sang Hui on tue 11 feb 97 How do you do? My name is Sang Hui Kong. Nice to meet you! [potters.org]
Skin
- Erythema
Some individuals may experience skin changes such as painful swelling and pink coloration of the fingers and toes (acrodynia); persistent redness or inflammation of the skin (erythema); extreme sensitivity (hyperesthesia) of the affected areas; and tingling [rarediseases.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]
Psychiatrical
- 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]
- Delusion
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]
Psychiatric symptomes are well described in the manganese miners and incrude sleep disturbance,disorientation,emotional lability,compulsive acts,hallucinations,illusions,and delusions. [webview.isho.jp]
Overexposure to bismuth may cause extreme drowsiness (somnolence) and neurologic disturbances such as confusion, difficulty in concentration, hallucinations, delusions, myoclonic jerks, tremors, seizures, an impaired ability to coordinate voluntary movements [rarediseases.org]
- 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]
Neurologic
- 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]
- Encephalopathy
Diabetes, hypopigmentation/ hyperkeratosis, cancer: lung, bladder, skin, encephalopathy 24-h urine: ≥50 µg/L urine, or 100 µg/g creatinine BAL (acute, symptomatic) Succimer DMPS (Europe) Bismuth Renal failure; acute tubular necrosis Diffuse myoclonic [emedicine.medscape.com]
Overexposure to aluminum may cause brain damage (encephalopathy). [rarediseases.org]
Chemoprevention of bilirubin encephalopathy with a nanoceutical agent. Adhikari A, Bhutani VK, Mondal S, Das M, Darbar S, Ghosh R, Polley N, Das AK, Bhattacharya SS, Pal D, Mallick AK, Pal SK. Adhikari A, et al. [pubmed.ncbi.nlm.nih.gov]
- Dystonia
Dystonia and Gait Disturbances - As the disease progresses, dystonia (abnormal muscle tone) becomes evident, and the patient displays a "cock-walk" gait (walking with an extended trunk and flexed arms, while strutting on one's toes). [expertlaw.com]
Clinical features include CONFUSION; HALLUCINATIONS; and an extrapyramidal syndrome (PARKINSON DISEASE, SECONDARY) that includes rigidity; DYSTONIA; retropulsion; and TREMOR. [connects.catalyst.harvard.edu]
Our cases and those in the literature indicate that, in the absence of rigidity or dystonia or both, levodopa is ineffective in chronic manganese intoxication. [jamanetwork.com]
Two patients with severe dystonia from chronic manganese poisoning were markedly improved by L-dopa. Most of the effects of L-dopa disappeared a few days after substitution of placebo for the drug. [nejm.org]
- Slurred Speech
Symptoms included somnolence, gait imbalance, slurred speech, and impaired fine movements. Signs included bradykinesia, postural instability, impaired arising ability, masked facies, and speech disorder. [jamanetwork.com]
Numerous 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 [ashkinlaw.com]
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]
Symptoms of manganese poisoning include tremors, shakes, loss of balance, slowed movement, walking problems, impotency, slurred speech, extreme drowsiness or nighttime leg cramps. [elcosh.org]
The second stage involves short–term memory loss, impaired judgment, slurred speech, and sometimes even hallucinations. [welding-rod-dangers.com]
Workup
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].
Treatment
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]
Prognosis
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]
Etiology
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]
Epidemiology
[…] 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
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]
Prevention
[…] 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]
References
- 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.
- Aschner M. Manganese: brain transport and emerging research needs. Environmental Health Perspectives. 2000;108(Suppl 3):429-432.
- Crossgrove J, Zheng W. Manganese toxicity upon overexposure. NMR Biomed. 2004;17(8):544-553.
- 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.
- 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.
- O’Neal SL, Zheng W. Manganese Toxicity Upon Overexposure: a Decade in Review. Curr Environ Health Rep. 2015;2(3):315-328.
- Lucchini R, Albini E, Placidi D, et al. Brain magnetic resonance imaging and manganese exposure. Neurotoxicology. 2000;21(5):769-775.
- Inoue N. Occupational neurotoxicology due to heavy metals-especially manganese poisoning. Brain Nerve [Article in Japanese]. 2007;59(6):581-589.