Potential for stem cell treatment in manganism.

Development of manganism (also known as manganese neurotoxicity) is a major complication of manganese exposure in which neurological dysfunction is linked to accumulation of the metal in brain. Due to neuronal cell death in basal ganglia structures, particularly the globus pallidus, functional recovery is limited. Bearing a resemblance to Parkinson's disease, effective treatment for manganism is currently limited. However, the rapidly developing field of stem cell research offers new hope for the treatment of illnesses in which neurodegeneration is a major feature. The first part of this review will focus on the clinical features and pathophysiology of cerebral damage resulting from exposure to manganese, including the role of astrocytes, disruption of energy metabolism, involvement of oxidative stress, excitotoxicity, and inflammation, with the second part exploring how stem cells may provide an important therapeutic strategy for patients with this major neurologic disorder.

Massive intravenous manganese overdose due to compounding error: minimal role for hemodialysis.

CONTEXT: Manganese-associated parkinsonism is well described in occupational settings, in chronic methcathinone users, and in patients receiving long-term total parenteral nutrition. We present a unique case of acute intravenous manganese poisoning with a systematic evaluation of hemodialysis efficacy. CASE DETAILS: A 52-year-old woman was inadvertently administered a single intravenous dose of 800 mg compounded manganese chloride at an outpatient chelation center. In an attempt to minimize central nervous system (CNS) manganese deposition, she underwent urgent hemodialysis followed by five days of therapy with calcium disodium EDTA (1 g/m(2) over eight hours daily). Her initial whole blood manganese concentration, obtained six hours after exposure and prior to treatment, was 120 mcg/L (2.19 micromol/L); normal <5 mcg/L (< 0.09 micromol/L). Following the first four-hour hemodialysis session her blood manganese concentration decreased to 20 mcg/L (0.36 micromol/L). Despite the fall in her blood manganese concentration, analysis of dialysate revealed a total elimination of only 604 mcg (11 micromol) manganese (∼1.4% of manganese burden). Although she remained asymptomatic, an MRI on hospital day two revealed T1 hyperintensities within the bilateral globus pallidi, consistent with manganese exposure. DISCUSSION: Manganese poisoning is associated with irreversible neurologic toxicity. Hemodialysis did not appear to significantly enhance elimination in this case of acute intravenous manganese toxicity, beyond supportive care and calcium disodium EDTA chelation.

[Encephalopathy caused by intravenous potassium permanganate used for illegal production of methcathinone (ephedrone) from medicines containing pseudoephedrine]. / Encefalopatia spowodowane dozylnym uzywaniem preparatów zawierajacych nadmanganian potasu stosowany jako reagent w produkcji metkatynonu (efedronu) z leków zawierajacych pseudoefedryne.

Encephalopathy caused by manganese compounds used for illicit production of ephedrone (methcathinone) is described. The onset of disease could be observed after some months of regular intravenous use of ephedrone contaminated with manganese. In clinical picture dominate neurological signs and symptoms, mainly extrapyramidal syndromes: parkinsonism, tremor, muscle distonia, pro- and retropulsion. Some other symptoms may be observed: hypophonia or dysarthria, gain disturbances, impairment of precise movement, and micrographia. In cranial NMR often appears bilaterally an increase of an intensity of T1 signal in globus pallidus and in some other brain structures. Elimination of manganese with the use of chelating therapy as well as symptomatic treatment, mainly with the antyparkinsonic drugs, seems to be ineffective.

A case of acute prochloraz-manganese complex intoxication treated with extracorporeal elimination.

BACKGROUND/AIM: We treated a patient with critical manganese intoxication with vigorous extracorporeal elimination. In this article, we describe the clinical characteristics and treatment modalities of the patient. PATIENT: A 65-year-old man was brought to the emergency room (ER) 5.5 h after ingesting prochloraz-manganese complex. He experienced circulatory collapse and went into a coma without self-breathing on arrival at the ER. Mechanical ventilation was initiated and hemoperfusion, hemodialysis and continuous venovenous hemodiafiltration were performed with the help of norepinephrine. MEASUREMENT AND RESULT: The manganese levels on the first, second and fourth hospital days were 34.1, 23.6 and 12.5 µg/l, respectively. He recuperated from the shock state within 7 hospital days. After 4 critical weeks, the patient regained full consciousness. CONCLUSION: Rigorous extracorporeal elimination by hemoperfusion, hemodialysis and continuous venovenous hemodiafiltration was an effective treatment modality for patients with acute manganese intoxication.

Neurotoxicity following chronic intravenous use of "Russian cocktail".

INTRODUCTION: Recently, neurological abnormalities in methcathinone users have been attributed to manganese. We report similar toxicity in three patients following the use of a mixture similar to methcathinone: potassium permanganate, ephedrine, and aspirin. CASE REPORTS: Three teenagers (15 to 19 years old) presented with extrapyramidal abnormalities and movement disorders following chronic intravenous use of a mixture known as "Russian Cocktail". All three patients had multiple movement disorders. One patient had normal blood manganese concentration (<19 microg/L) and MRI. The other two had elevated blood manganese (2100 microg/L and 3176 microg/L) and MRIs showing bilateral symmetric hyper-intensities on T1-weighted-images in the dentate nucleus, subcortical white substance of cerebellar hemisphere, globus pallidus, and putamen. Abstinence and treatment with EDTA, levodopa, and para-aminosalicylic acid was associated with decreasing blood manganese concentrations and subjective improvement, but no change in objective findings. DISCUSSION: The "Russian Cocktail" likely contains manganese as a result of the oxidation of ephedrine by potassium permanganate in water acidified by acetylsalicylic acid. We believe that manganese with the possible contribution of methcathinone caused the neurological impairments. CONCLUSIONS: Three toxic substances have been made into a mixture administered intravenously, similar to methcathinone. Our patients learned of this mixture, called "Russian Cocktail", from their friends. The toxicity from repeated use of this mixture is one of extrapyramidal abnormalities and movement disorders. Standard therapies were unsuccessful in reversing the clinical toxicity.

The emergence of manganese-related health problems in Quebec: an integrated approach to evaluation, diagnosis, management and control.

This paper describes the strategy developed in Quebec to deal with an emerging problem: manganism in welders. Only two cases of manganism had been reported to the Commission de la santé et de la sécurité du travail (CSST, Workers Compensation Board in Quebec) before 2000. In the fall of 2001, the CSST was informed of a possible cluster of manganism and received 20 compensation claims from one plant. Action was rapidly taken to understand and tackle this emerging problem. Under the leadership of the CSST, a coordinating working group implemented medical and environmental subcommittees involving representatives of the different partners of the prevention network. After a literature review to document the health risks associated with manganese and the lack of some important information, a panel of international experts was formed to try to reach agreement on the parameters to consider in the diagnosis and management of manganism. The CSST compensation management policies would be adjusted accordingly. Simultaneously, all the available industrial hygiene data were analyzed to estimate where and at what levels workers were exposed to manganese. To complete these data, the exposure of workers in more than 50 industrial plants was evaluated and existing control measures were documented. All these data have been presented for a revision of the Quebec permissible exposure limit (PEL). In this integrated approach, the next step targets the formation of neurologists and neuropsychologists for a standardized medical evaluation, to complete workplace evaluation in the high risk sectors, inform workers and employers and recommend control measures where required, based on a revised PEL. Many strategies will be used to inform the prevention network (about 1000 people), employers and employees of the risks of overexposure to manganese and of the measures to control exposure in all the plants where workers are susceptible to be exposed to manganese.

Acute renal failure following ingestion of manganese-containing fertilizer.

Fertilizers are used to promote the survival and growth of plants and crops and have a good safety record when used properly. The basic elements in fertilizer include phosphorus, nitrite, and potassium. In addition, there are additive agents that vary for different crops and which may include some metals. Acute intoxication by ingesting fertilizer includes damage to various organ systems as well as severe cardiovascular or respiratory distress. We report the case of a 64-year-old man who ingested about 700 mL of fertilizer and suffered acute renal failure, hyperkalemia, and mild methemoglobinemia. After supportive care and emergent hemodialysis for hemodynamic instability due to hyperkalemia, the renal function of the patient recovered in four days.

Manganese intoxication.

Manganese plays an important role as a cofactor in many enzymatic reactions in humans but in excess amounts can cause irreversible nervous system damage. Although manganism is a rare condition, it can be the cause of complex nervous system symptoms, especially in the setting of environmental exposure. Specifically, manganese is a well-known cause of dystonic parkinsonism. This article highlights several historical descriptions of the clinical manifestations, pathological changes, and attempted therapeutic intervention in manganese intoxication.