Methcathione (ephedrone), a psychostimulant that increases the release of catecholamines in the brain, is used recreationally in Eastern Europe and elsewhere for its amphetamine like effects. It is synthesized by oxidation of ephedrine or pseudoephedrine with potassium permanganate, injected intravenously (IV) resulting in a parkinsonian syndrome caused by manganese. 1 The parkinsonian syndrome, which is unresponsive to levodopa, 2 tends to be symmetrical with bradykinesia, dystonia, and gait impairment. 3
We report a Lithuanian 41‐year‐old right dominant man, with no familial neurological diseases, who recreationally used methcathione for 4 months in 2017. One year later he reported bradykinesia, gait impairment, and retropulsion with left foot dystonia. These symptoms did not respond to levodopa with maximal dose of levodopa/benserazide 100/25 three times daily (TID) or pentoxifylline.
He had an intact bedside cognitive assessment, monotonous speech, and slight hypomimia. Rigidity of the left limbs and neck was 2+ and right sided tone was 1+. Bradykinesia was 2+ on the left and 1+ on the right. Cerebellar tests and sensation were normal, bilateral flexor planter reflex response was elicited with a left striatal toe. He required the use of his hands to stand up, a slightly wide based gait with festination and severe retropulsion were noted.
FluroDopa positron emission tomography scan was normal, a brain magnetic resonance imaging was positive for slight atrophy of the midbrain, normal cerebellum volume, with several hyperintensities in cerebral white matter. Complete blood count, serum levels of manganese, and liver functions were within normal limits (Video 1).
Video 1.
Gait assessment during the 5 day treatment of parenteral amantadine and 6 months later.
A toxicologist did not recommend any chelate therapy because of the chronicity of the case and length of time since last exposure. He underwent a 5‐day course of IV amantadine 200 mg and continued oral amantadine 100 mg TID.
On repeated assessment slight hypomimia was noted. Speech was normal. Finger tapping was 2+ on the left and 1+ on the right, rigidity was 1+ on all four limbs. No striatal toe was noted. He was able to rise from a seated position without the use of his hands, walked independently including tandem, with a widened base. His pull test was 3+. The patient was very satisfied with the results, continued IV treatment of amantadine 200 mg every 3 weeks and oral amantadine 100 mg TID.
Six months after his last office visit, the patient reported no falls and was fully ambulant with no external gait support.
Amantadine is an anti‐glutamatergic agent with dopaminergic and anti‐cholinergic properties 4 that can also be used for the treatment of multiple sclerosis related fatigue, neuroleptic malignant syndrome, and tardive dyskinesia. IV amantadine has been used in Europe in advanced Parkinson's disease (PD). In a recent study performed by our group, subjective improvement in mobility was reported in 80% of patients with advanced PD treated with 5 days of IV amantadine. 5
As there are currently no efficacious treatments for the motor symptoms of methcathione induced parkinsonism, the use of IV amantadine should be encouraged in similar additional cases in order to assess the effectiveness of this treatment.
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
A.T.: 1C, 3A
T.G.: 1A, 1B, 3B
Disclosures
Ethical Compliance Statement: The authors confirm that approval from an institutional review board was not required. The patient gave full consent and approved the use of video material. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest: No specific funding was received for this work.
Financial Disclosures for the Previous 12 Months: A.T. received research grants from The Michael J. Fox Foundation, honoraria from AbbVie and consulting fees from Capsida. T.G. has served as an advisor to AbbVie and Truemed; received travel support for her and her team from Alphamedix, AbbVie, Medison, and Medoc; received research and educational support from Movement Disorders Society and grant of Parkinson's Foundation Center of Excellence.
References
- 1. Sikk K, Taba P, Haldre S, et al. Irreversible motor impairment in young addicts? Ephedrone, manganism or both? Acta Neurol Scand 2007;115(6):385–389. [DOI] [PubMed] [Google Scholar]
- 2. Stepens A, Logina I, Liguts V, et al. A parkinsonian syndrome in methcathinone users and the role of manganese. N Engl J Med 2008;358(10):1009–1017. [DOI] [PubMed] [Google Scholar]
- 3. Sikk K, Haldre S, Aquilonius SM, et al. Manganese‐induced parkinsonism in methcathinone abusers: bio‐markers of exposure and follow‐up. Eur J Neurol 2013;20(6):915–920. [DOI] [PubMed] [Google Scholar]
- 4. Blanpied TA, Clarke RJ, Johnson JW. Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J Neurosci 2005;25(13):3312–3322. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Kestenbaum M, Abu Snineh M, Nussbaum T, et al. Repeated intravenous amantadine infusions in advanced parkinsonism: experience of a large movement disorder center. Isr Med Assoc J 2019;21(12):812–816. [PubMed] [Google Scholar]