Manganese mixture inhalation is a reliable Parkinson disease model in rats.

Manganese (Mn) is an essential trace metal. Regardless of its essentiality, it has been reported that the overexposure causes neurotoxicity manifested as extrapyramidal symptoms similar to those observed in Parkinson disease (PD). Recently, our group reported that mice that inhaled for 5 months the mixture of manganese chloride (MnCl(2)) and manganese acetate Mn(OAc)(3) developed movement abnormalities, significant loss of substantia nigra compacta (SNc) dopaminergic neurons, dopamine depletion and improved behavior with l-DOPA treatment. However, this model has only been characterized in mice. In order to have a well-supported and generalizable model in rodents, we used male Wistar rats that inhaled a mixture of 0.04 M MnCl(2) and 0.02 M Mn(OAc)(3), 1h three times a week for 6 months. Before Mn exposure, animals were trained to perform motor tests (Beam-walking and Single-pellet reaching tasks) and were evaluated each week after the exposure. The mixture of MnCl(2)/Mn(OAc)(3) caused alterations in the motor tests, 75.95% loss of SNc dopaminergic neurons, and no cell alterations in Globus Pallidus or striatum. With these results we conclude that the inhalation of the mixture of Mn compounds is a useful model in rodents for the study of PD.

Liver transplantation in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure.

Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.

A preliminary study revealing a new association in patients undergoing maintenance hemodialysis: manganism symptoms and T1 hyperintense changes in the basal ganglia.

BACKGROUND AND PURPOSE: Patients undergoing parenteral nutrition and those with portosystemic encephalopathy secondary to chronic liver disease and acquired and congenital portosystemic venous shunts frequently present manganese deposition in the basal ganglia, detected by MR imaging as hyperintense areas on T1-weighted sequences. We also observed similar abnormalities in the basal ganglia of patients with chronic renal failure undergoing maintenance hemodialysis. Our aim was to evaluate the pallidal signal intensity on T1-weighted images in a series of patients undergoing hemodialysis, with further evaluation of serum manganese levels and neurologic correlation, comparing them with patients with chronic renal failure without dialytic treatment. MATERIALS AND METHODS: We performed MR imaging examinations in 9 patients with chronic renal failure, 5 of whom were undergoing hemodialysis. An experienced neuroradiologist scrutinized the presence of symmetric hyperintensities in the basal ganglia on T1-weighted sequences. We also determined the serum manganese levels and performed the neurologic evaluations in all patients. RESULTS: All patients undergoing hemodialysis presented elevated serum manganese levels and symmetric hyperintensities within the globus pallidus. In this group, 4 patients presented with parkinsonian symptoms, myoclonus, and syndromes with vestibular and vestibular-auditory symptoms. The patients without dialytic treatment presented with neither bilaterally increased T1 MR imaging signal intensity within the globus pallidus nor symptoms of manganism. CONCLUSION: Our preliminary results demonstrated the occurrence of bilateral pallidal hyperintensity on T1-weighted images in all patients undergoing hemodialysis associated with high serum manganese levels, revealing a new association.

Liver transplantion in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure

Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.

Hiperintesidades simétricas e bilaterais dos gânglios da base são observadas em imagens de ressonância magnética encefálica (RM) ponderadas em T1 na maioria dos pacientes com insuficiência hepática crônica devidas ao acúmulo de manganês. Nós relatamos o caso de um homem, com 53 anos de idade, com um complexo parkinsonismo-demência rapidamente progressivo associado com o acúmulo de manganês no cérebro, secundariamente a insuficiência hepática. Uma RM encefálica foi realizada e foram observadas imagens hiperintensas/hipersinal nas imagens ponderadas em T1 no globo pálido e, também, na substância branca dos hemisférios cerebrais ponderadas em T2. Devido à falta de resposta ao tratamento clinico optamos pelo transplante hepático. O paciente faleceu no 7° dia de PO. Nossos achados corroboram o conceito dos efeitos tóxicos do manganês nos gânglios da base/globo pálido. O tratamento desta forma de parkinsonismo é controverso e o transplante hepático não deverá ser considerada uma opção terapêutica de primeira linha, porém como um tratamento alternativo considerando-se os riscos-benefícios dessa escolha.

The diagnosis of manganese-induced parkinsonism.

Parkinsonism is a clinical syndrome consisting of tremor, bradykinesia, rigidity, gait, balance problems, in addition to various non-motor symptoms. There are many causes of parkinsonism such as neurodegenerative disease, drugs, vascular causes, structural lesions, infections, and toxicants. Parkinson's disease, or idiopathic parkinsonism, is the most common form of parkinsonism observed in the clinic. There is degeneration of the substantia nigra, pars compacta, which results in loss of striatal dopamine. Parkinson's disease is a slowly progressive condition in which there is a dramatic and sustained responsiveness to levodopa therapy. Manganese is an essential trace element that can be associated with neurotoxicity. Hypermanganism can occur in a variety of clinical settings. The clinical symptoms of manganese intoxication include non-specific complaints, neurobehavioral changes, parkinsonism, and dystonia. Although the globus pallidus is the main structure of damage, other basal ganglia areas can also be involved. MRI scans may show globus pallidus changes during (and for a short period after) exposure. Fluorodopa PET scans that assess the integrity of the substantia nigra dopaminergic system are abnormal in Parkinson's disease. However, these scans re-reported to be normal in a few cases studied with manganese-induced parkinsonism. The parkinsonism due to manganese may have some clinical features that occur less commonly in Parkinson's disease, such as kinetic tremor, dystonia, specific gait disturbances, and early mental, balance and speech changes. The clinical signs tend to be bilateral whereas Parkinson's disease begins on one side of the body. Patients with manganese-induced parkinsonism may be younger at the onset of the disease than with Parkinson's disease. Lastly, there appears to be a lack of response to levodopa therapy in manganese-induced parkinsonism. In summary it may be possible to differentiate manganese-induced parkinsonism from Parkinson's disease using clinical and imaging studies.