intoxication levodopa

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons from the substantia nigra pars compacta (SNpc). α-synuclein (αsyn) has been linked to the pathophysiology of PD, because of its mutations causing familial PD and its accumulation in brains of patients with familial and sporadic PD. Dopamine (DA) replacement is the most effective therapy for ameliorating the motor symptoms of PD; however, it remains controversial whether DA-replacement boosts regeneration in the dopaminergic system or accelerates disease progression and enhances neuronal loss...

The present paper reports on a 68-year-old man with a 10-year history of parkinsonism who developed hallucinations and delusions after admission to an intensive care unit for the treatment of organophosphate intoxication. His initial diagnosis was delirium. On the basis of brain computed tomography findings and clinical symptoms, we diagnosed drug-induced psychosis in parkinsonism with multiple cysts in the bilateral striata.

The therapeutic potential of BL-1023, a chemical combination of L-3,4-dihydroxyphenylalanine (L-DOPA) and gamma-aminobutyric acid (GABA), was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Such animals exhibit nigrostriatal degeneration, characteristic of human Parkinson's disease. Drug was administered during and after the development of MPTP-induced nigrostriatal lesions followed by measures of motor function and behavior, surviving nigrostriatal dopaminergic neurons and termini, and striatal dopamine levels...

Hyperinnervation of the striatum by serotoninergic (5-HT) terminals occurs after destruction of the dopaminergic nigro-striatal pathway. Recent studies have suggested that non-physiological release of dopamine (DA) formed from levodopa in these serotoninergic terminals underlies abnormal involuntary movement (AIMs) induction in 6-OHDA lesioned rats. In the present study, we used tryptophan hydroxylase (TPH) immunohistochemistry to determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment and the induction of dyskinesia by levodopa alter the morphology of 5-HT fibres in the striatum of common marmosets...

We used in vivo proton ((1)H) Magnetic Resonance Spectroscopy (MRS) to measure the levels of the main excitatory amino acid, glutamate (Glu) and also glutamine (Gln) and GABA in the striatum and cerebral cortex in the MPTP-intoxicated mouse, a model of dopaminergic denervation, before and after dopamine (DA) replacement. The study was performed at 9.4T on control mice (n = 8) and MPTP-intoxicated mice (n = 8). In vivo spectra were acquired in a voxel (8 microL) centered in the striatum, and in the cortex (4...

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate-putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter...

Intoxication induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in mice results in a significant loss of nigrostriatal dopamine (DA) neurons. This is accompanied by a change in behavioural phenotype that can be reversed by L-DOPA (3,4-dihydroxy-L-phenylalanine) treatment. Here, we examined the extracellular levels of DA, behavioural deficits and the response to L-DOPA treatment in severely intoxicated mice. The MPTP intoxication produced more than a 90% reduction in tissue DA and a 65% decline in extracellular DA levels...

Parkinson's disease (PD) is a progressive neurodegenerative disorder. An experimental model of this disease is produced in nonhuman primates by the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this work, we put forward a new quantitative evaluation method that uses video recordings to measure the displacement, gate, gross and fine motor performance of freely moving subjects. Four Vervet monkeys (Cercopithecus aethiops) were trained in a behavioral observation hallway while being recorded with digital video cameras from four different angles...

Ingestion of windshield washer liquid resulted with an acute severe methanol intoxication in a 49-year old man. He developed optic atrophy with blindness, and an extrapyramidal syndrome. Putaminal injury and hyperintensity in the subcortical white matter was seen in a brain MRI. PET scanning with 6-[18F]fluoro-L-dopa confirmed symmetrical impaired presynaptic dopaminergic activity in the striatum, indicative of functional impairment of dopaminergic nigrostriatal neurons. The striatal uptake was more markedly impaired in the putamina (40% of controls) than in the caudate nuclei (60% of controls)...

INTRODUCTION: Reports of acute levodopa-carbidopa overdose are rare and no case of an acute overdose with a controlled-release formulation has been described. We describe such a case in which serial concentrations of catecholamines were measured. CASE REPORT: A 55-year-old man ingested 89 tablets of Sinemet 50/200 (17.8 g of levodopa, 4.45 g of carbidopa). Clinical effects and plasma concentrations of dopamine, noradrenaline and adrenalin were assessed over 66 hours...

OBJECTIVE: To describe a patient with lithium intoxication presenting as acute parkinsonism, adverse metabolic effects and nephrogenic diabetes insipidus (DI). CASE REPORT: We report a case of a 67-year-old woman with a bipolar affective disorder who was treated with lithium for 10 years. Under concomitant renal insufficiency and urinary tract infarction, she experienced progressive hand tremor, bradykinesia, and unsteady gait. Laboratory results revealed hypercalcemia and hypermagnesiemia...

The striatum harbors a population of dopaminergic interneurons that increases in number in animal models of Parkinson's disease (PD), presumably to compensate for dopamine (DA) depletion. The purpose of the present study was to determine the fate of striatal dopaminergic neurons in parkinsonian monkeys in which striatal DA depletion had been alleviated by systemic administration of l-dopa. The number of striatal dopaminergic neurons, visualized with tyrosine hydroxylase (TH) immunohistochemistry, was measured in three groups of cynomolgus (Macaca fascicularis) monkeys: (1) normal untreated monkeys; (2) monkeys rendered parkinsonian following systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but otherwise untreated; and (3) MPTP-intoxicated monkeys that received oral l-dopa on a chronic basis...

BACKGROUND: Manganese intoxication may lead to a levodopa-resistant, akinetic-rigid syndrome. A new form of presumed manganese poisoning has been reported in drug-addicted persons from Russia, Ukraine, and Estonia who have intravenously injected self-prepared methcathinone hydrochloride (Ephedrone). PATIENT: A 36-year-old man from Azerbaijan with hepatitis C and only modest hepatic synthetic dysfunction developed rapid-onset, levodopa-resistant parkinsonism with profound hypophonia...

INTRODUCTION: Chronic overexposure to manganese (Mn) may cause neuronal degeneration. Manganese intoxication is well known to induce parkinsonism. Manganese intoxication may be associated with abnormal magnetic resonance (MR) imaging (abnormal signal hyperintensity in the globus pallidus and substantia nigra on T1-weighted images). CASES: We report an unusual presentation of manganese intoxication due to administration of a combination of acetylsalicylic acid and ephedrine HCl, potassium permanganate, and vinegar melted in tap water and administered parenterally as a psychostimulant substance in 2 cases who developed symptoms resembling parkinsonism...

Ethylene glycol and methanol are toxic alcohols commonly found in a variety of commercial products. We report two cases, one associated with ethylene glycol and one with methanol poisoning, which both led to acute hemorrhagic necrosis of the basal ganglia and resulted in acute Parkinson's syndrome. It is unlikely that oxalate crystal deposition is the only mechanism for such basal ganglia necrosis, because similar findings were seen following methanol intoxication. We discuss other possible mechanisms that may contribute towards this unusual neurotoxicity...

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...

Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P...

It has long been appreciated that manganese exposure can cause neurotoxicity and a neurologic syndrome that resembles Parkinson's disease (PD). Current evidence indicates that manganese-induced parkinsonism can be differentiated from PD because of its predilection to accumulate in and damage the pallidum and striatum rather than the SNc. The clinical syndrome, response to levodopa, imaging studies with MRI and PET, and pathologic features all help to distinguish these two conditions and permit the correct diagnosis to be established...

We conducted a new chronic sequential 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3NP) intoxication paradigm in two female monkeys in order to reproduce the striatonigral degeneration type of levodopa-unresponsive parkinsonism. A comparison was made with MPTP-, 3NP-intoxicated and control monkeys. A levodopa-responsive parkinsonism emerged in all MPTP-treated monkeys. During subsequent 3NP intoxication, one of the two MPTP +3NP monkeys exhibited hindlimb dystonia concomitantly with a reduced levodopa response...

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