Manganese-induced parkinsonism in methcathinone abusers: bio-markers of exposure and follow-up.

BACKGROUND AND PURPOSE: Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users. METHODS: During 2006-2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 9-70 (20 ±â€…15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects. RESULTS: The average total UPDRS score was 43 ±â€…21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ±â€…3.8 ppm) than controls (0.82 ±â€…1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ±â€…6.2 ppb) in active than in former users (5.6 ±â€…1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum. CONCLUSION: Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.

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

OBJECTIVE: To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). METHODS: Neurophysiological examinations, magnetic resonance imaging (MRI), single-photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. RESULTS: Peripheral nervous system was not affected. No patients had reduced uptake of (123)I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. CONCLUSIONS: 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.

Irreversible motor impairment in young addicts--ephedrone, manganism or both?

BACKGROUND: Parkinsonian syndrome related to intravenous use of a "designer" psychostimulant, derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in Estonia. OBJECTIVE: To describe the symptomatology of four young patients, history of drug administration and chemical analysis of a drug batch. METHODS: Mental and motor function and quality of life were scored and ephedrone was analyzed using electrospray mass spectrometry. Manganese content of the final synthetic mixture was analyzed using Inductively Coupled Plasma-Atomic Emission Spectrometry. RESULTS: None of the four cases scored below the dementia threshold in MMSE, while other ratings (UPDRS, H&Y, PDQ-39) corresponded to disabilities seen in relatively advanced Parkinson's disease. The ephedrone yield of the reaction was approximately 44% and the mixture was found to contain 0.6 g/l of manganese. CONCLUSIONS: The cases were exposed to extreme manganese load. Their symptomatology is probably identical to manganism. The role of ephedrone is presently unknown. Physicians must be aware of early signs of manganism in patients within social risk groups.