Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposure

Sikk, Katrin; Taba, Pille; Haldre, Sulev; Bergquist, Jonas; Nyholm, Dag; Askmark, Håkan; Danfors, Torsten; Sørensen, Jens Benn; Thurfjell, Lennart; Raininko, Raili; Eriksson, Rolf; Flink, Roland; Färnstrand, Catarina; Aquilonius, Sten–Magnus

doi:10.1111/j.1600-0404.2009.01189.x

Cited by 46 publications

(39 citation statements)

References 28 publications

(38 reference statements)

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“…Eye movements in EP have been reported to be slow and mildly restricted in the vertical and horizontal plane [1], [5], [9], [14], however they have never been objectively studied with videooculography. The role of the basal ganglia in the control of eye movements has been supported by extensive evidence [15]–[17].…”

Section: Introductionmentioning

confidence: 99%

Eye Movements in Ephedrone-Induced Parkinsonism

et al. 2014

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Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese-induced damage to the basal ganglia, reflecting their role in oculomotor system.

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Section: Introductionmentioning

confidence: 99%

Eye Movements in Ephedrone-Induced Parkinsonism

et al. 2014

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“…In Sikk et al 122 performed FDG PET in four former ephedrone addicts with extrapyramidal symptoms after long-term intravenous use of ephedrone (methcathinone) contaminated with high concentrations of Mn. All patients demonstrated a widespread, but heterogeneous, pattern of reduced FDG uptake within the basal ganglia and the surrounding white matter.…”

Section: Pet Studies In Human Subjectsmentioning

confidence: 98%

“…46,49,122 While SPECT has shown a progressive loss of DAT density in PD patients, 109 DAT studies in Mn exposure have been mixed. An early SPECT study demonstrated significantly reduced DAT levels in the striatum of two Mn-exposed workers by [123I]-b-CIT.…”

Section: Spect Studiesmentioning

confidence: 98%

“…33 SPECT 123I-Ioflupane (DaTscan GE) scans of ephedrone addicts with clinical symptoms of manganism report normal DAT uptake. 46,49,122 Sikk et al further performed iodine-123 iobenzamine (IBZM) SPECT to measure the density of dopamine D2 receptors in their cohort of ephedrone addicts. 45 They found normal tracer uptake in the striatum, indicating preserved postsynaptic D2 receptors, which suggests that manganism in ephedrone users may be related to dopaminergic dysfunction rather than degeneration, as suggested by Guilarte.…”

Section: Spect Studiesmentioning

confidence: 98%

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Imaging Modalities for Manganese Toxicity

Dydak¹,

Criswell²

2014

Manganese in Health and Disease

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Rapidly advancing imaging technology has been essential to the study of manganese (Mn) toxicity in vivo. Over the past few decades, imaging techniques have been effectively utilized as markers of Mn exposure and to investigate the biological effects of Mn neurotoxicity. This chapter will review several of the imaging modalities that have made an impact in Mn neurotoxicity research. The scope of this chapter will include discussions of magnetic resonance imaging (MRI), including magnetic resonance spectroscopy (MRS), diffusion weighted imaging (DWI), and functional MRI (fMRI), as well as positron emission tomography (PET), single photon emission computed tomography (SPECT), and X-ray fluorescence imaging. For each modality, the basic principle of the imaging technique will be briefly described to facilitate proper data interpretation and understanding of limitations. This will be followed by a discussion on the main research findings using that modality, and how they have shaped our understanding of Mn toxicity.

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“…Recently, Mn neurotoxicity in humans has been reported in young drug abusers who used potassium permanganate in the formulations of homemade ephedron (Methcathinone), leading to clinical features of parkinsonism. 26,27 Inhalation and gastrointestinal absorption represent the two major routes for Mn absorption into the human body. 28 The absorption of Mn is tightly regulated with approximately 1-5% of ingested Mn being absorbed by the gastrointestinal tract, and 30-40% of inhaled Mn absorbed by the lungs.…”

Section: Sources Of Human Exposure To Mn and Its Transport To The Cenmentioning

confidence: 99%

Mechanism of Manganese-Induced Impairment of Astrocytic Glutamate Transporters

Karki¹,

Smith²,

Aschner³

et al. 2014

Manganese in Health and Disease

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Manganese (Mn) is an essential trace element, playing a vital role in numerous biochemical and cellular reactions; however, chronic exposure to high Mn levels from environmental and occupational sources causes a neurological disorder with shared features of Parkinson's disease (PD), referred to as manganism. Despite well-established pathological signs, the molecular mechanism(s) by which Mn induces these neurological disorders still remain to be established. In addition to oxidative stress and impairment of mitochondria, Mn dysregulates astrocytic glutamate transporters (GLAST [glutamate aspartate transporter] and GLT-1 [glutamate transporter 1]) by decreasing their promoter activity, mRNA, and protein levels as well as astrocytic glutamate uptake. The Mn-induced impairment in glutamate transporters is directly associated with excitotoxic neuronal death because the astrocytic glutamate transporters, GLAST and GLT-1, are mainly responsible for maintaining optimal glutamate levels in the synaptic clefts, thereby preventing glutamate-induced neuronal excitotoxicity. It is widely recognized that reduced expression and function of astrocytic glutamate transporters, in particular GLT-1, are associated with various neurodegenerative diseases, including PD and amyotrophic lateral sclerosis (ALS). Therefore, Mn-induced impairment of astrocytic glutamate transporters might be a critical mechanism for Mn neurotoxicity. Our latest studies have uncovered a novel mechanism of Mn-induced repression of GLT-1 at the transcriptional level. It appears that the transcription factor yin yang 1 (YY1) plays a critical role in Mn-induced repression of GLT-1 promoter activity and expression. Herein, we will discuss the cellular and molecular mechanisms by which Mn induces neurotoxicity, such as oxidative stress, mitochondrial impairment, inflammation, and dysregulation of glutamate transporters.

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Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposure

Abstract: Presynaptic neurons in the nigrostriatal pathway are intact in Mn-induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse.

Cited by 46 publications

References 28 publications

Eye Movements in Ephedrone-Induced Parkinsonism

Eye Movements in Ephedrone-Induced Parkinsonism

Imaging Modalities for Manganese Toxicity

Mechanism of Manganese-Induced Impairment of Astrocytic Glutamate Transporters

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