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Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Research Article

Levamisole-Induced Leukoencephalopathy in Russia: Analysis of 30 Cases

Author(s): Maria Zakharova*, Inessa Zakroyshchikova, Alexandra Kozlova, Alfiia Zabirova, Lola Askarova and Ekaterina Zhirova

Volume 17, Issue 4, 2022

Published on: 12 April, 2022

Page: [319 - 326] Pages: 8

DOI: 10.2174/1574886317666211224121517

Price: $65

Abstract

Aims: The study aims to raise medical specialists’ awareness regarding the severity of possible complications of levamisole administration, and demonstrate the role of accurate medical history collection in a differential diagnosis.

Background: Levamisole, an anthelmintic drug with immunomodulatory effects, has long been used worldwide till the early 2000s, when its association with demyelinating leukoencephalopathy was established. However, in the developing countries, it is still widely used for the prevention and treatment of helminthic invasion in humans. The actual prevalence of levamisole-induced multiple inflammatory leukoencephalopathy (LEV-induced MIL) in Russia remains unknown, and therefore, the study of its frequency and characteristics is indisputably important.

Objectives: The objective of this study is to determine the clinical features and MRI findings of levamisole- induced MIL in the Russian population, and to analyse the frequency of diagnostic errors at the initial assessment.

Methods: A single-center retrospective analysis of total 30 patients who were diagnosed with LEV- induced MIL and attended the Research Center of Neurology was conducted. Inclusion criteria were 1) clinically: acute or subacute polysymptomatic onset of neurological disturbances, 2) MRI: multifocal demyelinating lesion with no evidence of dissemination in time, 3) anamnestic data: levamisole exposure from 2 to 8 weeks before symptoms onset as well as monophasic disease course (absence of relapses according to follow up assessments up to 3 years).

Results: Clinically, presentation with constitutional symptoms including headache, fever, fatigue and myalgia, focal motor disturbances and dysarthria prevailed in our cohort. On the brain MRI, multiple foci of demyelination with simultaneous gadolinium enhancement were observed. The link between neurological symptoms and levamisole intake has often been detected only during follow- up assessments. Patients were most often misdiagnosed with acute disseminated encephalomyelitis, stroke and multiple sclerosis. In most cases, LEV-induced MIL was successfully treated with intravenous corticosteroids and/or plasma exchange (PLEX), however, residual neurologic symptoms were preserved in some patients. Additionally, two detailed clinical cases of patients being initially misdiagnosed are presented in the article.

Conclusion: The differential diagnosis remains difficult for suspected cases of LEV-induced MIL that could lead to delayed therapy initiation, and consequently incomplete recovery. Growing evidence suggests that a single administration of levamisole even in low doses might potentially lead to severe neurological deficit or death. Therefore, changes in medication management policies are required in order to prevent the uncontrolled use of levamisole.

Keywords: Leukoencephalopathy, demyelination, neuroinflammation, MIL, autoimmune disorders, levamisole.

Graphical Abstract

[1]
Amery WK, Bruynseels JP. Levamisole, the story and the lessons. Int J Immunopharmacol 1992; 14(3): 481-6.
[http://dx.doi.org/10.1016/0192-0561(92)90179-O] [PMID: 1618599]
[2]
Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: An emerging public health challenge. Mayo Clin Proc 2012; 87(6): 581-6.
[http://dx.doi.org/10.1016/j.mayocp.2012.03.010] [PMID: 22677078]
[3]
Vosoughi R, Schmidt BJ. Multifocal leukoencephalopathy in cocaine users: A report of two cases and review of the literature. BMC Neurol 2015; 15: 208.
[http://dx.doi.org/10.1186/s12883-015-0467-1] [PMID: 26482228]
[4]
Martin RJ, Robertson AP, Buxton SK, Beech RN, Charvet CL, Neveu C. Levamisole receptors: A second awakening. Trends Parasitol 2012; 28(7): 289-96.
[http://dx.doi.org/10.1016/j.pt.2012.04.003] [PMID: 22607692]
[5]
Wu VC, Huang JW, Lien HC, et al. Levamisole-induced multifocal inflammatory leukoencephalopathy: Clinical characteristics, outcome, and impact of treatment in 31 patients. Medicine (Baltimore) 2006; 85(4): 203-13.
[http://dx.doi.org/10.1097/01.md.0000230250.95281.60] [PMID: 16862045]
[6]
Hook CC, Kimmel DW, Kvols LK, et al. Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole. Ann Neurol 1992; 31(3): 262-7.
[http://dx.doi.org/10.1002/ana.410310306] [PMID: 1637134]
[7]
Kimmel DW, Wijdicks EF, Rodriguez M. Multifocal inflammatory leukoencephalopathy associated with levamisole therapy. Neurology 1995; 45(2): 374-6.
[http://dx.doi.org/10.1212/WNL.45.2.374] [PMID: 7854541]
[8]
Xu N, Zhou W, Li S, Zhou G, Zhang N, Liang J. Clinical and MRI characteristics of levamisole-induced leukoencephalopathy in 16 patients. J Neuroimaging 2009; 19(4): 326-31.
[http://dx.doi.org/10.1111/j.1552-6569.2008.00344.x] [PMID: 19187474]
[9]
Liu HM, Hsieh WJ, Yang CC, Wu VC, Wu KD. Leukoencephalopathy induced by levamisole alone for the treatment of recurrent aphthous ulcers. Neurology 2006; 67(6): 1065-7.
[http://dx.doi.org/10.1212/01.wnl.0000237344.06122.79] [PMID: 17000980]
[10]
Lucia P, Pocek M, Passacantando A, Sebastiani ML, De Martinis C. Multifocal leucoencephalopathy induced by levamisole. Lancet 1996; 348(9039): 1450.
[http://dx.doi.org/10.1016/S0140-6736(04)70094-X] [PMID: 8937298]
[11]
Yan R, Wu Q, Ren J, et al. Clinical features and magnetic resonance image analysis of 15 cases of demyelinating leukoencephalopathy induced by levamisole. Exp Ther Med 2013; 6(1): 71-4.
[http://dx.doi.org/10.3892/etm.2013.1077] [PMID: 23935721]
[12]
Averchenkov DM, Bejsheeva MT, Ivakina ED, et al. Clinical case of levamisole-induced multifocal inflammatory leukoencephalopathy. Zh Nevrol Psikhiatrii Im SS Korsakova 2019; 119(12): 106-14.
[13]
Belova AN, Solovieva VS, Rasteryaeva M V, Belova EM. Multifocal inflammatory levamisole-induced leukoencephalopathy. Zh Nevrol Psikhiatrii Im SS Korsakova 2020; 120: 89-96.
[14]
Voskresenskaya ON, Shmidt TE, Shavlovskaya OA, Kodjebash ND. Levamisole-induced leukoencephalopathy. Russ Neurol J 2020; 25: 45-50.
[15]
Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: current understanding and controversies. Semin Neurol 2008; 28(1): 84-94.
[http://dx.doi.org/10.1055/s-2007-1019130] [PMID: 18256989]
[16]
Franciotta D, Columba-Cabezas S, Andreoni L, et al. Oligoclonal IgG band patterns in inflammatory demyelinating human and mouse diseases. J Neuroimmunol 2008; 200(1-2): 125-8.
[http://dx.doi.org/10.1016/j.jneuroim.2008.06.004] [PMID: 18606457]
[17]
Pannewitz-Makaj K, Wurster U, Jendretzky KF, et al. Evidence of oligoclonal bands does not exclude non-inflammatory neurological diseases. Diagnostics (Basel) 2020; 11(1): 37.
[http://dx.doi.org/10.3390/diagnostics11010037] [PMID: 33379245]
[18]
Chen TC, Hinton DR, Leichman L, Atkinson RD, Apuzzo ML, Couldwell WT. Multifocal inflammatory leukoencephalopathy associated with levamisole and 5-fluorouracil: Case report. Neurosurgery 1994; 35(6): 1138-42.
[http://dx.doi.org/10.1227/00006123-199412000-00019] [PMID: 7885561]
[19]
Grasso D, Borreggine C, Castorani G, et al. Balò’s concentric sclerosis in a case of cocaine-levamisole abuse. SAGE Open Med Case Rep 2020; 8: 2050313X20940532.
[20]
Sariaslani P, Ghanbari A, Ghanbari P. Multifocal inflammatory leukoencephalopathy induced by accidental consumption of levamisole: A case report. Iran J Neurol 2012; 11(2): 65-9.
[PMID: 24250864]

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