Manganese Encephalopathy among Ephedron Abusers‐Case Reports

Abstract

Ephedrone encephalopathy is referred to as a group of symptoms of manganese deposition within the central nervous system (CNS), resulting from the abuse of ephedrone (methcathinone), obtained in reaction using the excess amount of manganese-containing oxidants. The diagnosis is based on the contrast-enhanced head MRI findings characteristic for this syndrome, clinical manifestation and history of ephedrone use. The syndrome has been reported in recent years in young people from Eastern Europe and Russia with a history of ephedrone overuse. However, no report has ever been published on ephedrone encephalopathy in Polish patients.

SLC39A14 deficiency alters manganese homeostasis and excretion resulting in brain manganese accumulation and motor deficits in mice

“…The most common cause of exposure to excess Mn is occupational, and has been documented in miners (5), welders (6), ferroalloy workers (7), battery manufacturers (8), and glass workers (9). Brain Mn accumulation has also been reported in patients receiving total parenteral nutrition therapy (10,11), patients with hepatic encephalopathy (12), and abusers of ephedrone (methcathinone) (13).…”

Manganese-Induced Parkinsonism Is Not Idiopathic Parkinson’s Disease: Environmental and Genetic Evidence

“…Over the last decade, numerous clinical reports from eastern and western European countries, Russia, and Canada have shown that young individuals who abuse ephedron (also called methcathinone) rapidly present (approximately 6 months after use) with emotional, cognitive, and movement abnormalities similar to those in Mn-induced parkinsonism, which continue to persist even after drug abstinence (Colosimo and Guidi, 2009;de Bie et al, 2007;Fudalej et al, 2013;Iqbal et al, 2012;Janocha-Litwin et al, 2014;Meral et al, 2007;Poniatowska et al, 2014;Sanotsky et al, 2007;Selikhova et al, 2008;Sikk et al, 2010Sikk et al, , 2013Stepens et al, 2008;Yildirim et al, 2009). These recreational ephedron users are reminiscent of parkinsonian cases discovered in the early 1980s, where irreversible parkinsonism was induced by the intravenous injection of an illicit opiate analog (meperidine) that was incorrectly synthesized into the nigrostriatal dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) (Davis et al, 1979;Langston et al, 1983).…”

“…However, unlike methamphetamine synthesis, potassium permanganate is used for the homemade production of ephedron, thereby creating high levels of Mn byproduct (Sikk et al, 2007). Ephedron users consequentially have increased blood Mn levels due to their intravenous injection of this homemade mixture (Fudalej et al, 2013;Janocha-Litwin et al, 2014;Poniatowska et al, 2014;Selikhova et al, 2008;Sikk et al, 2010Sikk et al, , 2013Stepens et al, 2008). As observed with occupational exposures to Mn toxicity, these individuals are levodopa-resistant (Colosimo and Guidi, 2009;Fudalej et al, 2013;Janocha-Litwin et al, 2014;Poniatowska et al, 2014;Sanotsky et al, 2007;Selikhova et al, 2008;Sikk et al, 2013;Stepens et al, 2008) and displayed abnormally high Mn concentrations in T1-weighted MRI images of the globus pallidus, striatum, and midbrain (Fudalej et al, 2013;Janocha-Litwin et al, 2014;Poniatowska et al, 2014;Selikhova et al, 2008;Sikk et al, 2010Sikk et al, , 2013Stepens et al, 2008).…”

“…Ephedron users consequentially have increased blood Mn levels due to their intravenous injection of this homemade mixture (Fudalej et al, 2013;Janocha-Litwin et al, 2014;Poniatowska et al, 2014;Selikhova et al, 2008;Sikk et al, 2010Sikk et al, , 2013Stepens et al, 2008). As observed with occupational exposures to Mn toxicity, these individuals are levodopa-resistant (Colosimo and Guidi, 2009;Fudalej et al, 2013;Janocha-Litwin et al, 2014;Poniatowska et al, 2014;Sanotsky et al, 2007;Selikhova et al, 2008;Sikk et al, 2013;Stepens et al, 2008) and displayed abnormally high Mn concentrations in T1-weighted MRI images of the globus pallidus, striatum, and midbrain (Fudalej et al, 2013;Janocha-Litwin et al, 2014;Poniatowska et al, 2014;Selikhova et al, 2008;Sikk et al, 2010Sikk et al, , 2013Stepens et al, 2008). Furthermore, SPECT neuroimaging studies revealed normal striatal DAT uptake in ephedron users despite their expression of moderate to severe parkinsonism (Colosimo and Guidi, 2009;Sanotsky et al, 2007;Selikhova et al, 2008), in contrast to that observed after methamphetamine use (Volkow et al, 2001) and in iPD (Blesa et al, 2012;Chen et al, 2008;Criswell et al, 2011;Huang, 2007;Huang et al, 2007;Pavese and Brooks, 2009;Stoessl, 2012).…”

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

“…When the homeostatic mechanisms of the gut, which regulates gastrointestinal Mn absorption, and/or the liver, which modulates the biliary excretion of Mn, fail, get bypassed or are overwhelmed, rising Mn blood levels subsequently result in Mn deposition in the brain 6 7 . Mn overexposure can occur in welding and mining industries, in individuals using Mn contaminated Ephedrone preparations, and in patients receiving high Mn concentrations in total parenteral nutrition 8 9 10 . Impaired hepatic Mn excretion in chronic liver disease may cause ‘acquired hepatocerebral degeneration' 11 .…”