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 »  Abstract
 » Introduction
 »  Materials and Me...
 » Illustrative Case
 » Discussion
 » Acknowledgment
 »  References
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BRIEF REPORT
Year : 2012  |  Volume : 60  |  Issue : 2  |  Page : 224-227

Chronic manganese toxicity due to substance abuse in Turkish patients


Department of Neurology, Bakirköy Research and Training Hospital for Neurologic and Psychiatric Diseases, Istanbul, Turkey

Date of Submission14-Sep-2011
Date of Decision07-Oct-2011
Date of Acceptance28-Nov-2011
Date of Web Publication19-May-2012

Correspondence Address:
Vedat Sozmen
Department of Neurology, Bakirkoy State Hospital for Neurologic and Psychiatric Diseases, Gelengul Sok. Ar Apt. No: 11 Caddebostan, Kadikoy, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.96407

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 » Abstract 

Background: Manganese toxicity may lead to a levodopa-resistant akinetic-rigid syndrome. Pathological changes occur mostly in the pallidium and stratium. Materials and Methods: We report seven patients with a new form of chronic manganese toxicity due to long-term intravenous use of a solution consisting of ephedrine, acetylsalicylic acid and potassium permanganate as a psycho-stimulant, popularly known as "Russian Cocktail". Results: The age of the patients ranged between 19 and 31 years, and the duration of substance abuse was between nine and 106 months. The onset of symptoms from first use ranged seven to 35 months. The initial symptom was impaired speech followed by gait disturbance and bradykinesia. In addition to these symptoms, choreic movements, ataxia presenting as backward falls and dystonia were also seen. Serum and urine samples revealed high levels of manganese. Hyperintense lesions on T1-weighted magnetic resonance imaging were seen in bilateral basal ganglia and brainstem, dentate nuclei, features consistent with manganese intoxication. Conclusion: Manganese toxicity, which may cause a distinctive irreversible neurodegenerative disorder, can be seen frequently with "Russian Cocktail" abuse, a substance which can be accessed very easily and at a low cost.


Keywords: Drug addiction, intoxication, manganese, Parkinsonism, Russian cocktail


How to cite this article:
Koksal A, Baybas S, Sozmen V, Koksal NS, Altunkaynak Y, Dirican A, Mutluay B, Kucukoglu H, Keskinkilic C. Chronic manganese toxicity due to substance abuse in Turkish patients. Neurol India 2012;60:224-7

How to cite this URL:
Koksal A, Baybas S, Sozmen V, Koksal NS, Altunkaynak Y, Dirican A, Mutluay B, Kucukoglu H, Keskinkilic C. Chronic manganese toxicity due to substance abuse in Turkish patients. Neurol India [serial online] 2012 [cited 2019 Aug 23];60:224-7. Available from: http://www.neurologyindia.com/text.asp?2012/60/2/224/96407



 » Introduction Top


Manganese (Mn) is an element commonly found in the environment and in foods such as nuts, grains, legumes and tea and Mn poisoning has been associated with damage to the nervous system. [1],[2] Neurological symptoms of Mn poisoning include hypokinetic-hypophonic dysarthria, postural instability with falling "cock-gait" (trunk extended and arm flexed, toe walking), Parkinsonian signs such as hypokinesia, hypomimia, low-amplitude rapid postural tremor typically without rest tremor, cogwheel rigidity, bradyphrenia, hypersomnia and myoclonus. [1],[2],[3] Although Mn poisoning is usually associated with occupational exposure to high levels of Mn, cases of levodopa-resistant Parkinson's disease due to Mn poisoning have been reported in Eastern Europe in recent years. [4],[5],[6] Subjects were methcathinone users who had prepared the substance by potassium permanganate oxidation of ephedrine or pseudoephedrine in the presence of acetic acid. [4],[6] In Turkey, Mn poisoning has been observed in intravenous users of "Russian Cocktail", a psycho-stimulant mixture consisting of ephedrine, acetylsalicylic acid and potassium permanganate. We report seven patients with chronic Mn toxicity due to substance abuse to discuss the neurological and pathological features of Mn poisoning-induced Parkinson's disease.


 » Materials and Methods Top


Patients with a history of usage of Mn-containing psycho-stimulant "Russian Cocktail" and signs of Parkinson's disease referred to the neurology outpatient clinic were the subjects for this study. The solution is prepared by dissolving ephedrine, acetylsalicylic acid and potassium permanganate tablets in tap water. The lilac-colored solution is then filtered through a cotton pad and injected intravenously at irregular intervals many times a day. The amount of solution consumed in a day may be very high and the dose of permanganate may go up to 2000 mg/day. Permanganate is included to disinfect the solution.

Detailed neurological examinations were carried out in all the patients and patients were also rated by the Unified Parkinson's Disease Rating Scale (UPDRS). Routine biochemical tests including sedimentation, T3, T4, thyroid-stimulating hormone (TSH), serum vitamin B12, vitamin E, folic acid were obtained along with Venereal Disease Research Laboratory, human immunodeficiency virus tests (VDRL, HIV) and hepatitis markers. Serum and urine manganese levels were measured using electrothermal atomic absorption spectrometry. An electroencephalogram, detailed neuropsychiatric examination, Mini Mental State Examination (MMSE), and brain magnetic resonance imaging (MRI) scans were performed at the time of diagnosis. The clinical characteristics of the seven patients are given in [Table 1].
Table 1: The clinical characteristics and laboratory findings of the patients

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 » Illustrative Case Top


Case: 5

A 29-year-old man started injecting solution containing pseudoephedrine, potassium permanganate, and acetylsalycylic acid diluted in 2 ml of water, intravenously two to three doses per day since 10 years and used the solution at two to three-week intervals for more than nine years and stopped the use for the last six months . Five years before this admission he developed speech disturbance and one year later developed gait disturbance. In the following two years, his speech became incomprehensible and he could not walk without help. Neurological examination revealed MMSE of 28, mask-like face, dysarthric and hypophonic speech, bradykinesia, symmetric rigidity of legs and marked gait disturbances-cock gait, twisting feet, postural instability. He was unable to walk independently because of marked postural instability and falls. There was dystonic rotation of the feet during walking. Deep tendon reflexes were hyperactive in the lower extremities. UPDRS score was 44.

Serum and urine Mn levels were high and MRI showed hyperintensities in bilateral basal ganglia on T1-weighted sequences consistent with chronic manganese intoxication [Figure 1] and [Figure 2]. Neuro-psychological tests showed findings related to frontal lobe with mild verbal and non-verbal memory dysfunctions. Patient was treated with fluoxetin 20 mg per/day, amitriptyline 25 mg/day, diazepam 5 mg/day, L-Dopa 225 mg/ day. He was followed up for two years without any improvement, and L-Dopa therapy was stopped.
Figure 1: T1-weighted axial cranial magnetic resonance image of Case 5 showing hyperintensities in the substantia nigra consistent with possible chronic manganese intoxication

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Figure 2: T1-weighted coronal cranial magnetic resonance image of Case 5 showing hyperintensities in bilateral putamina and caudate nuclei consistent with possible chronic manganese intoxication

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 » Discussion Top


Neurological findings in this cohort included walking and gait disturbances, tremor and dystonia, distinct from classical Parkinsonian symptoms. Symptoms are generally symmetrical. [7] Tremor has not been a leading finding in Mn-induced  Parkinsonism More Details and tends to disappear as the disease progresses. When present, tremors are of high frequency and postural or kinetic rather than resting as is classically seen in Parkinson's disease. [1],[8] Resting tremor was not the feature in this cohort, positional tremor of the hands was seen in three patients. "Cock-walk" gait, a characteristic clinical finding in manganese toxicity, [1],[2],[3] was also a typical finding in our cohort. Cock-walk gait was prominent after walking a short distance. All our patients had typical cock-walk gait and it was more evident in Case 4 and Case 5. They had imbalance while walking, and they could not walk backwards and they had severe postural instability. Although some studies mention psychiatric symptoms like anxiety, emotional lability and compulsive behavior in manganese toxicity, [9] we did not find any studies on cognitive changes. Cook et al., reported "mental capacity abnormalities" (diminished memory and calculating abilities) [9] but these reports did not use formal cognitive tests. Our subjects had a detailed cognitive test battery, which revealed mild deficits in verbal and non-verbal memory, and executive functions accompanied by moderate deficits in attention and sustaining attention. Unfortunately, we could not repeat these tests during the follow-up period.

MRI is very useful in the diagnosis of manganese toxicity. [3],[7],[10],[11],[12] Classically, MRI shows bilateral hyperintensities in the medial segment of the globus pallidus and reticular segment of substantia nigra reflecting the manganese accumulation. In our patient group, regression of basal ganglia hyperintensities tended to occur three to four months after patients stopping the use of drugs containing Mn. The exception was Patient 5, who stopped using the drug six months prior to diagnosis and still exhibited lesions on MRI. This may be due to the patient's exceptionally long period of exposure to the drug (106 months).

Clinical features caused by manganese toxicity are resistant to levodopa and Mn may lead to permanent damage. [5] Our subjects had received 750 to 1250 mg/ day of levodopa for 24-48 months . In the follow-up, while there was no progression in the symptoms after discontinuation of manganese use, no improvement was observed either, in spite of levodopa therapy.

Differentiating Parkinson's disease due to manganese toxicity from idiopathic Parkinson's disease [10] is of vital importance. Clinical features, response to L-dopa, and MRI and positron-emission tomography (PET) image characteristics are useful in the differential diagnosis of these two conditions. [7],[10],[13] Young patients exhibiting Parkinsonian symptoms and signs should be carefully examined for Mn poisoning before a diagnosis of idiopathic Parkinson's disease is made.

In conclusion, manganese toxicity causes an irreversible neurodegenerative disorder, which is resistant to levodopa therapy. It is obvious that the use of this illicit substance may become widespread among young people, causing a public health problem, since it is very easy to obtain with low cost.


 » Acknowledgment Top


The authors would like to thank Yifei Mu for proofreading this article.

 
 » References Top

1.Jankovic J. Searching for a relationship between manganese and welding and Parkinson's disease. Neurology 2005;64:2021-8.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Racette BA, McGee-Minnich L, Moerlein SM, Mink JW, Videen TO, Perlmutter JS. Welding-related parkinsonism: Clinical features, treatment, and pathophysiology. Neurology 2001;56;8-13.  Back to cited text no. 2
    
3.Josephs KA, Ahlskog JE, Klos KJ, Kumar N, Fealey RD, Trenerry MR, et al. Neurologic manifestations in welders with pallidal MRI T1 hyperintensity. Neurology 2005;64:2033-9.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Sikk K, Taba P, Haldre S, Bergquist J, Nyholm D, Ziablov G, et al. Irreversible motor impairment in young addicts-ephedrone, manganism or both? Acta Neurol Scand 2007;115:385-9.  Back to cited text no. 4
    
5.Selikhova M, Fedoryshyn L, Matviyenko Y, Komnatska I, Kyrylchuk M, Krolicki L, et al. Parkinsonism and Dystonia Caused by the Illicit Use of Ephedrone-A Longitudinal Study. Mov Disord 2008;23:2224-31.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Stepens A, Logina I, Liguts V, Aldins P, Eksteina I, Platka-jis A, et al. A Parkinsonian syndrome in methcathinone users and the role of manganese. N Engl J Med 2008;358:1009-17.  Back to cited text no. 6
    
7.Calne DB, Chu NS, Huang CC, Lu CS, Olanow W. Manganism and idiopathic parkinsonism: Similarities and differences. Neurology 1994;44:1583-6.  Back to cited text no. 7
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8.Pearl DP, Olanow CW. The neuropathology of manganese-induced Parkinsonism. J Neuropathol Exp Neurol 2007;66:675-82.  Back to cited text no. 8
    
9.Sanotsky Y, Lesyk R, Fedoryshyn LS Komnatska I, Matviyenko Y, Fahn S. Manganic Encephalopathy Due to "Ephedrone" Abuse. Mov Dis 2007;22:1337-43.  Back to cited text no. 9
    
10.Pal PK, Samii A, Calne DB. Manganese neurotoxicity: A review of clinical features, imaging and pathology. Neurotoxicology 1999;20:227-38.  Back to cited text no. 10
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11.Olanow CW. Manganese-induced parkinsonism and Parkinson's disease. Ann N Y Acad Sci 2004;1012:209-23.  Back to cited text no. 11
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12.Sato K, Ueyama H, Arakawa R, Kumamoto T, Tsuda T. A case of welder presenting with parkinsonism after chronic manganese exposure. Rinsho Shinkeigaku 2000;40:1110-5.  Back to cited text no. 12
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13.Wolters EC, Huang CC, Clark C, Peppard RF, Okada J, Chu NS, et al. Positron emission tomography in manganese intoxication. Ann Neurol 1989;26:647-51.  Back to cited text no. 13
[PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]

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