Skip to main content

Advertisement

SpringerLink
Log in

Metronidazole-induced encephalopathy: a systematic review

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background and aims

Metronidazole, a commonly used antibiotic drug, can cause adverse effects in the central nervous system termed metronidazole-induced encephalopathy, leading to diagnostic challenges. The condition is rare and a detailed description of its phenotype is lacking. In this systematic review we investigated the clinical features of metronidazole-induced encephalopathy to promote recognition and elaborate the description.

Methods

We performed a systematic literature search using PubMed.gov and hand searched the reference lists of included articles and other publications of interest. We included case series and single reports describing individual patients developing symptoms from the central nervous system in relation to metronidazole treatment. Data were extracted and analyzed descriptively.

Results

We identified 779 publications of which 112 papers comprising 136 patients were included. Typical findings were dysarthria, gait instability, limb dyscoordination and altered mental status. Frequently, patients concomitantly presented with metronidazole-induced polyneuropathy. Liver disease was the most common pre-existing condition. MRI showed a characteristic pattern of reversible symmetrical hyperintense lesions on T2/FLAIR of the dentate nuclei in 90% of patients. Most patients improved significantly after discontinuation of metronidazole. Poor outcome was associated with severe comorbidity.

Conclusion

Metronidazole-induced encephalopathy should be considered in patients presenting with neurological symptoms in relation to newly initiated or prolonged metronidazole treatment. MRI changes are highly characteristic and specific. Patients with liver disease are at increased risk. Prognosis is good if recognized early.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

*:

Denotes patients for whom polyneuropathy presented before CNS symptoms

+PNS:

Remaining symptoms of polyneuropathy at follow-up

CC:

Corpus callosum

CNS:

Central nervous system

COPD:

Chronic obstructive pulmonary disease

CWM:

Cerebral white matter

DIC:

Disseminated intravascular coagulation

DM:

Diabetes mellitus

DN:

Dentate nuclei

MB:

Midbrain

MBD :

Dorsal midbrain

MBRN :

Midbrain with involvement of the red nuclei

MO:

Medulla oblongata

MOION :

Medulla oblongata with involvement of the inferior olivary nuclei

N/R:

Not reported

References

  1. Klein EY et al (2018) Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci USA 115(15):E3463–E3470

    PubMed  CAS  Google Scholar 

  2. Morgan DJ et al (2011) Non-prescription antimicrobial use worldwide: a systematic review. Lancet Infect Dis 11(9):692–701

    PubMed  PubMed Central  Google Scholar 

  3. Bhattacharyya S et al (2016) Antibiotic-associated encephalopathy. Neurology 86(10):963–971

    PubMed  CAS  Google Scholar 

  4. Lofmark S, Edlund C, Nord CE (2010) Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis 50(Suppl 1):S16–S23

    PubMed  Google Scholar 

  5. Goolsby TA, Jakeman B, Gaynes RP (2018) Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature. Int J Antimicrob Agents 51(3):319–325

    PubMed  CAS  Google Scholar 

  6. Liberati A et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6(7):e1000100

    PubMed  PubMed Central  Google Scholar 

  7. Agah E et al (2017) Metronidazole-induced neurotoxicity presenting with sudden bilateral hearing loss, encephalopathy, and cerebellar dysfunction. Eur J Clin Pharmacol 73(2):249–250

    PubMed  Google Scholar 

  8. Agarwal A et al (2016) Metronidazole-Induced Cerebellar Tox. Neurol Int 8(1):6365

    PubMed  PubMed Central  Google Scholar 

  9. Ahmed A, Loes DJ, Bressler EL (1995) Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy. Neurology 45(3 Pt 1):588–589

    PubMed  CAS  Google Scholar 

  10. AlDhaleei W, AlMarzooqi A, Gaber N (2018) Reversible metronidazole-induced neurotoxicity after 10 weeks of therapy. BMJ Case Rep. https://doi.org/10.1136/bcr-2017-223463

    Article  PubMed  Google Scholar 

  11. Alvarez RS et al (1983) Central nervous system toxicity related to prolonged metronidazole therapy. Am J Obstet Gynecol 145(5):640–641

    PubMed  CAS  Google Scholar 

  12. Arik N, Cengiz N, Bilge A (2001) Metronidazole-induced encephalopathy in a uremic patient: a case report. Nephron 89(1):108–109

    PubMed  CAS  Google Scholar 

  13. Bae EH et al (2016) Metronidazole-Induced Encephalopathy: a case report. J Nippon Med Sch 83(2):44–45

    PubMed  CAS  Google Scholar 

  14. Bahn Y et al (2010) Metronidazole induced encephalopathy in a patient with brain abscess. J Korean Neurosurg Soc 48(3):301–304

    PubMed  PubMed Central  Google Scholar 

  15. Bailes J et al (1983) Encephalopathy with metronidazole in a child. Am J Dis Child 137(3):290–291

    PubMed  CAS  Google Scholar 

  16. Bates JE, Almast J, Augustine EF (2015) Neonatal dentate nucleus T2 hyperintensity after in utero metronidazole exposure. Neurology 85(11):1006

    PubMed  PubMed Central  Google Scholar 

  17. Beloosesky Y et al (2000) Convulsions induced by metronidazole treatment for Clostridium difficile-associated disease in chronic renal failure. Am J Med Sci 319(5):338–339

    PubMed  CAS  Google Scholar 

  18. Bonda C, Evans MS (2015) Metronidazole CNS toxicity. Acta Neurol Belg 115(4):709–710

    PubMed  Google Scholar 

  19. Bonkowsky JL, Sondrup C, Benedict SL (2007) Acute reversible cerebellar lesions associated with metronidazole therapy. Neurology 68(3):180

    PubMed  Google Scholar 

  20. Bottenberg MM et al (2011) Metronidazole-induced encephalopathy: a case report and review of the literature. J Clin Pharmacol 51(1):112–116

    PubMed  Google Scholar 

  21. Cacao G et al (2015) Metronidazole-induced central and peripheral nervous system toxicity. Neurol Sci 36(9):1737–1739

    PubMed  CAS  Google Scholar 

  22. Cantador AA et al (2013) Nonconvulsive status with metronidazole. Neurohospitalist 3(4):185–189

    PubMed  PubMed Central  CAS  Google Scholar 

  23. Cecil KM et al (2002) Reversible MR imaging and MR spectroscopy abnormalities in association with metronidazole therapy. J Comput Assist Tomogr 26(6):948–951

    PubMed  Google Scholar 

  24. Chacko J et al (2011) Clinical, neuroimaging and pathological features of 5-nitroimidazole-induced encephalo-neuropathy in two patients: Insights into possible pathogenesis. Neurol India 59(5):743–747

    PubMed  CAS  Google Scholar 

  25. Chakrabarti S, Pan K (2014) Metronidazole-induced encephalopathy: an uncommon scenario. N Z Med J 127(1393):120–122

    PubMed  Google Scholar 

  26. Chandak S et al (2016) A case report of metronidazole induced neurotoxicity in liver abscess patient and the usefulness of MRI for its diagnosis. J Clin Diagn Res 10(1):TD06–T7

    PubMed  PubMed Central  CAS  Google Scholar 

  27. Chatzkel JA, Vossough A (2010) Metronidazole-induced cerebellar toxicity. Pediatr Radiol 40(8):1453

    PubMed  Google Scholar 

  28. Chaudhari TS, Malhotra HS, Garg RK (2014) Face of the giant panda with bright eyes in metronidazole neurotoxicity. Neurol India 62(2):212–213

    PubMed  Google Scholar 

  29. Cheong HC et al (2011) Metronidazole-induced encephalopathy in a patient with liver cirrhosis. Korean J Hepatol 17(2):157–160

    PubMed  PubMed Central  Google Scholar 

  30. Clements A (2017) Case report of metronidazole-induced encephalopathy. WMJ 116(5):221–223

    PubMed  Google Scholar 

  31. De Bleecker JL, Leroy BP, Meire VI (2005) Reversible visual deficit and Corpus callosum lesions due to metronidazole toxicity. Eur Neurol 53(2):93–95

    PubMed  Google Scholar 

  32. Deenadayalu VP et al (2005) Abnormal enhancing lesion of dentate nuclei causing neurologic symptoms induced by metronidazole toxicity. Clin Gastroenterol Hepatol 3(3):xxix

    PubMed  Google Scholar 

  33. Demel SL, Jovin TG, Jadhav AP (2015) Metronidazole toxicity presenting with acute onset of aphasia and right sided weakness. J Clin Neurosci 22(7):1199–1200

    PubMed  Google Scholar 

  34. Desai JA et al (2011) Metronidazole-induced encephalopathy: case report and review of MRI findings. Can J Neurol Sci 38(3):512–513

    PubMed  Google Scholar 

  35. Dhar A et al (2016) Mystery case: metronidazole-induced encephalopathy. Neurology 87(9):e89–e90

    PubMed  Google Scholar 

  36. Erdener SE et al (2013) Brain MRI evolution of metronidazole intoxication. Neurology 80(19):1816–1817

    PubMed  Google Scholar 

  37. Eren F et al (2017) A case with reversible neurotoxicity induced by metronidazole. Ideggyogy Szem 70(11–12):429–432

    Google Scholar 

  38. Etxeberria A et al (2012) Metronidazole-cerebellopathy associated with peripheral neuropathy, downbeat nystagmus, and bilateral ocular abduction deficit. Rev Neurol (Paris) 168(2):193–195

    CAS  Google Scholar 

  39. Farmakiotis D, Zeluff B (2016) Images in clinical medicine. Metronidazole-associated encephalopathy. N Engl J Med 374(15):1465

    PubMed  CAS  Google Scholar 

  40. Foreid H et al. (2009) Reversible iatrogenic subacute cerebellar syndrome, myoclonus and MRI findings following metronidazole administration. BMJ Case Rep

  41. Frytak S, Moertel CH, Childs DS (1978) Neurologic toxicity associated with high-dose metronidazole therapy. Ann Intern Med 88(3):361–362

    PubMed  CAS  Google Scholar 

  42. Furukawa S et al (2015) Metronidazole-induced encephalopathy with contrast enhancing lesions on MRI. J Neurol Sci 352(1–2):129–131

    PubMed  Google Scholar 

  43. Galvez M, Brahm J, Miranda M (2009) Movement disorders as a manifestation of metronidazole-induced encephalopathy in a patient with chronic liver disease. Mov Disord 24(12):1864–1866

    PubMed  Google Scholar 

  44. Godfrey MS, Finn A, Zainah H, Dapaah-Afriyie K (2015) Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis. BMJ Case Rep. https://doi.org/10.1136/bcr-2014-206162

    Article  PubMed  PubMed Central  Google Scholar 

  45. Graves TD et al (2009) Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient. J Neurol Sci 285(1–2):238–240

    PubMed  CAS  Google Scholar 

  46. Groothoff MV et al (2010) Irreversible encephalopathy after treatment with high-dose intravenous metronidazole. Clin Ther 32(1):60–64

    PubMed  CAS  Google Scholar 

  47. Gupta AK et al (2003) Metrondazole-induced neurotoxicity. J Assoc Physicians India 51:617–618

    PubMed  CAS  Google Scholar 

  48. Halloran TJ (1982) Convulsions associated with high cumulative doses of metronidazole. Drug Intell Clin Pharm 16(5):409

    PubMed  CAS  Google Scholar 

  49. Hammami N et al (2007) Reversible metronidazole-induced encephalopathy. J Neuroradiol 34(2):133–136

    PubMed  CAS  Google Scholar 

  50. Hanji Y et al (2017) Metronidazole-induced encephalopathy associated with treatment for liver abscesses. J Gen Fam Med 18(5):265–267

    PubMed  PubMed Central  Google Scholar 

  51. Hari A, Srikanth BA, Lakshmi GS (2013) Metronidazole induced cerebellar ataxia. Indian J Pharmacol 45(3):295–297

    PubMed  PubMed Central  Google Scholar 

  52. Haridas A et al (2015) Metronidazole-Induced Encephalopathy in Chronic Diarrhoea. J Assoc Physicians India 63(6):77–79

    PubMed  Google Scholar 

  53. Heaney CJ, Campeau NG, Lindell EP (2003) MR imaging and diffusion-weighted imaging changes in metronidazole (Flagyl)-induced cerebellar toxicity. AJNR Am J Neuroradiol 24(8):1615–1617

    PubMed  Google Scholar 

  54. Higashi M et al (2013) Metronidazole-induced encephalopathy. Intern Med 52(7):843–844

    PubMed  Google Scholar 

  55. Hobbs K et al (2015) Metronidazole-induced encephalopathy: not always a reversible situation. Neurocrit Care 22(3):429–436

    PubMed  Google Scholar 

  56. Horlen CK, Seifert CF, Malouf CS (2000) Toxic metronidazole-induced MRI changes. Ann Pharmacother 34(11):1273–1275

    PubMed  CAS  Google Scholar 

  57. Huang YT, Chen LA, Cheng SJ (2012) Metronidazole-induced encephalopathy: case report and review literature. Acta Neurol Taiwan 21(2):74–78

    PubMed  Google Scholar 

  58. Hwang GH et al (2012) Metronidazole induced encephalopathy with peripheral polyneuropathy in patient with spinal cord injury. Korean J Spine 9(1):44–48

    PubMed  PubMed Central  Google Scholar 

  59. Iqbal A et al (2013) Clinical and imaging perspective and unanswered questions in a case of metronidazole induced encephalopathy. Ann Indian Acad Neurol 16(4):569–571

    PubMed  PubMed Central  Google Scholar 

  60. Ito H et al (2004) Reversible cerebellar lesions induced by metronidazole therapy for helicobacter pylori. J Neuroimaging 14(4):369–371

    PubMed  Google Scholar 

  61. Iwadate D et al (2017) Thiamine deficiency in metronidazole-induced encephalopathy: a metabolic correlation? J Neurol Sci 379:324–326

    PubMed  Google Scholar 

  62. Jang HJ et al (2012) Atypical metronidazole-induced encephalopathy in anaerobic brain abscess. J Korean Neurosurg Soc 52(3):273–276

    PubMed  PubMed Central  Google Scholar 

  63. Kafadar I et al (2013) A rare adverse effect of metronidazole: nervous system symptoms. Pediatr Emerg Care 29(6):751–752

    PubMed  Google Scholar 

  64. Kalia V, Vibhuti, Saggar K (2010) Case report: MRI of the brain in metronidazole toxicity. Indian J Radiol Imaging 20(3):195–197

    PubMed  PubMed Central  Google Scholar 

  65. Khodakaram K, Barmano N (2011) Uncommon reaction to a common prescription. Lancet 378(9787):288

    PubMed  Google Scholar 

  66. Kim DW et al (2004) Metronidazole-induced encephalopathy. J Neurol Sci 224(1–2):107–111

    PubMed  Google Scholar 

  67. Kim E et al (2007) MR imaging of metronidazole-induced encephalopathy: lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 28(9):1652–1658

    PubMed  CAS  Google Scholar 

  68. Kim H et al (2011) Metronidazole-induced encephalopathy in a patient with infectious colitis: a case report. J Med Case Rep 5:63

    PubMed  PubMed Central  Google Scholar 

  69. Kim J et al (2017) Metronidazole-induced encephalopathy in a patient with Crohn’s disease. Intest Res 15(1):124–129

    PubMed  PubMed Central  Google Scholar 

  70. Kim SM et al (2011) Serially changing metronidazole-induced encephalopathy. Can J Neurol Sci 38(6):921–924

    PubMed  Google Scholar 

  71. Knorr JP et al (2012) Metronidazole-induced encephalopathy in a patient with end-stage liver disease. Case Reports Hepatol 2012:209258

    PubMed  PubMed Central  Google Scholar 

  72. Kumari P et al (2016) Metronidazole induced neurotoxicity in a case of liver abscess. Int J Hepatobiliary Pancreat Dis 6:96–99

    Google Scholar 

  73. Kuriyama A (2017) Chestnut sign: metronidazole-induced encephalopathy. J Emerg Med 52(1):101–102

    PubMed  Google Scholar 

  74. Kuriyama A et al (2011) Metronidazole-induced central nervous system toxicity: a systematic review. Clin Neuropharmacol 34(6):241–247

    PubMed  CAS  Google Scholar 

  75. Kusumi RK et al (1980) Central nervous system toxicity associated with metronidazole therapy. Ann Intern Med 93(1):59–60

    PubMed  CAS  Google Scholar 

  76. Lawford R, Sorrell TC (1994) Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report. Clin Infect Dis 19(2):346–348

    PubMed  CAS  Google Scholar 

  77. Lee HC, Kim YE, Ma HI (2017) Metronidazole-induced craniocervical myoclonus with reversible bilateral dentate nucleus lesions. J Mov Disord 10(1):67–68

    PubMed  PubMed Central  Google Scholar 

  78. Lee JH et al (2008) Metronidazole-induced toxic encephalopathy in a hemodialysis patient: a case report. Korean J Nephrol 27(6):743–746

    Google Scholar 

  79. Lee SS et al (2009) Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging. J Comput Assist Tomogr 33(2):305–308

    PubMed  Google Scholar 

  80. Lefkowitz A, Shadowitz S (2018) Reversible cerebellar neurotoxicity induced by metronidazole. CMAJ 190(32):E961

    PubMed  PubMed Central  Google Scholar 

  81. McCabe J, Neale J, Varghese A (2017) A case of metronidazole-induced neurotoxicity. Postgrad Med J 93(1105):712

    PubMed  Google Scholar 

  82. Mehndiratta MM, Pandey S, Nayak R (2013) Metronidazole encephalopathy. J Assoc Physicians India 61(7):485

    PubMed  Google Scholar 

  83. Mittal GK et al (2017) Dentate hyperintensities—the imaging signature of metronidazole induced encephalopathy. J Neurosci Rural Pract 8(2):272–273

    PubMed  PubMed Central  Google Scholar 

  84. Mizuta K et al (2018) Metronidazole-induced encephalopathy in a patient with pyogenic spondylitis: a case report. BMC Musculoskelet Disord 19(1):336

    PubMed  PubMed Central  Google Scholar 

  85. Moosa AN, Perkins D (2010) Neurological picture. MRI of metronidazole induced cerebellar ataxia. J Neurol Neurosurg Psychiatry 81(7):754–755

    PubMed  Google Scholar 

  86. Moriya M et al (2013) Reversible lesions of cerebellar dentate nuclei associated with metronidazole therapy. Neurol Clin Neurosci 1(6):227–228

    Google Scholar 

  87. Mulcahy H, Chaddha SK (2008) MRI of metronidazole-induced encephalopathy. Radiol Case Rep 3(4):239

    PubMed  Google Scholar 

  88. Naqi R, Azeemuddin M, Beg MA (2012) Magnetic resonance imaging of metronidazole induced encephalopathy. J Pak Med Assoc 62(8):843–844

    PubMed  Google Scholar 

  89. Ng PS, Saini M (2014) Reversible metronidazole-induced subacute cerebellar syndrome. QJM 107(12):1051–1052

    PubMed  CAS  Google Scholar 

  90. Onuma Y et al (2017) Irreversible metronidazole encephalopathy in an elderly woman with primary biliary cholangitis. J Gen Fam Med 18(6):436–438

    PubMed  PubMed Central  Google Scholar 

  91. Papathanasiou A et al (2013) Metronidazole-induced reversible encephalopathy in a patient with facioscapulohumeral muscular dystrophy. Clin Neuroradiol 23(3):217–219

    PubMed  Google Scholar 

  92. Park KI, Chung JM, Kim JY (2011) Metronidazole neurotoxicity: sequential neuroaxis involvement. Neurol India 59(1):104–107

    PubMed  Google Scholar 

  93. Patel K et al (2008) Cerebellar ataxia following prolonged use of metronidazole: case report and literature review. Int J Infect Dis 12(6):e111–e114

    PubMed  Google Scholar 

  94. Rizvi I et al (2018) Metronidazole-associated encephalopathy: a reversible condition. Intern Emerg Med 13(8):1323–1325

    PubMed  Google Scholar 

  95. Roy U et al (2016) Clinical and neuroradiological spectrum of metronidazole induced encephalopathy: our experience and the review of literature. J Clin Diagn Res 10(6):OE01–O9

    PubMed  PubMed Central  CAS  Google Scholar 

  96. Sandip S, Afshan I, Khandelwal RK (2015) MR features of metronidazole-induced encephalopathy. BMJ Case Rep

  97. Sarna JR, Brownell AK, Furtado S (2009) Cases: reversible cerebellar syndrome caused by metronidazole. CMAJ 181(9):611–613

    PubMed  PubMed Central  Google Scholar 

  98. Senthilkumaran S et al (2015) Metronidazole encephalopathy: uncommon reaction to a common drug. Int J Crit Illn Inj Sci 5(2):123–124

    PubMed  PubMed Central  Google Scholar 

  99. Seok JI et al (2003) Metronidazole-induced encephalopathy and inferior olivary hypertrophy: lesion analysis with diffusion-weighted imaging and apparent diffusion coefficient maps. Arch Neurol 60(12):1796–1800

    PubMed  Google Scholar 

  100. Sevy A et al (2011) Central and peripheral neurotoxicity of metronidazole after treatment for brain abscess. Acta Neurochir (Wien) 153(12):2491–2492

    Google Scholar 

  101. Simonetta F, Christou F, Vandoni RE, Nierle T (2013) Walking unsteadily: a case of acute cerebellar ataxia. BMJ Case Rep. https://doi.org/10.1136/bcr-2012-007688

    Article  PubMed  PubMed Central  Google Scholar 

  102. Singh R et al (2017) Sequential MR imaging (with diffusion-weighted imaging) changes in metronidazole-induced encephalopathy. Indian J Radiol Imaging 27(2):129–132

    PubMed  PubMed Central  Google Scholar 

  103. Sonthalia N et al (2016) Metronidazole-induced encephalopathy in alcoholic liver disease: a diagnostic and therapeutic challenge. J Emerg Med 51(4):e79–e83

    PubMed  Google Scholar 

  104. Sørensen CG et al. (2018) Convulsive seizures as presenting symptom of metronidazole-induced encephalopathy: a case report. Case Rep Neurol 10(1):34–37

    PubMed  PubMed Central  Google Scholar 

  105. Sudan YS et al (2016) Headphone sign: Metronidazole-induced encephalopathy. Neurol India 64(6):1374–1376

    PubMed  Google Scholar 

  106. Takada K et al (2018) Metronidazole Induced encephalopathy mimicking an acute ischemic stroke event. Neurol Med Chir (Tokyo) 58(9):400–403

    Google Scholar 

  107. Tan CH et al (2011) Painful neuropathy due to skin denervation after metronidazole-induced neurotoxicity. J Neurol Neurosurg Psychiatry 82(4):462–465

    PubMed  Google Scholar 

  108. Taniyama D, Maruki T (2018) Metronidazole-associated encephalopathy. Am J Trop Med Hyg 98(2):351–352

    PubMed  PubMed Central  Google Scholar 

  109. Thakkar N et al (2016) Metronidazole Induced Encephalopathy. J Assoc Physicians India 64(11):72–74

    PubMed  Google Scholar 

  110. Vitturi BK et al (2018) Metronidazole-induced encephalopathy. Rev Neurol (Paris) 174(5):342–343

    CAS  Google Scholar 

  111. Vivas LL et al (2016) An 82-year-old man with ataxia and dysarthria. CMAJ 188(17–18):1251–1254

    PubMed  PubMed Central  Google Scholar 

  112. Ward F, Crowley P, Cotter PE (2015) Acute cerebellar syndrome associated with metronidazole. Pract Neurol 15(4):298–299

    PubMed  CAS  Google Scholar 

  113. Wienbren M et al (1985) Convulsions and encephalopathy in a patient with leukemia after treatment with metronidazole. J Clin Pathol 38(9):1076

    PubMed  PubMed Central  CAS  Google Scholar 

  114. Woodruff BK, Wijdicks EF, Marshall WF (2002) Reversible metronidazole-induced lesions of the cerebellar dentate nuclei. N Engl J Med 346(1):68–69

    PubMed  Google Scholar 

  115. Yagi S, Matsumoto H, Hashida H (2018) Asymmetric magnetic resonance imaging findings in metronidazole-induced encephalopathy. Intern Med 57(13):1955–1956

    PubMed  PubMed Central  Google Scholar 

  116. Yagi T et al (2015) Metronidazole-induced encephalopathy and myoclonus: case report and a review of the literature. Neurol Clin Neurosci 3(3):111–113

    Google Scholar 

  117. Yamamoto T et al (2012) Metronidazole-induced neurotoxicity developed in liver cirrhosis. J Clin Med Res 4(4):295–298

    PubMed  PubMed Central  Google Scholar 

  118. Yui JC, Bonnes SL (2017) 74-Year-old woman with dysarthria and left lower extremity weakness. Mayo Clin Proc 92(6):973–977

    PubMed  Google Scholar 

  119. de Souza A, Narvencar KP, Sindhoora KV (2013) The neurological effects of methyl bromide intoxication. J Neurol Sci 335(1–2):36–41

    PubMed  Google Scholar 

  120. Gopinath KG et al (2015) Ornidazole-induced ataxia in an Indian woman: a case report. SAGE Open Med Case Rep 3:2050313 × 15621857

    Google Scholar 

  121. Taskapilioglu O et al (2010) Reversible cerebellar toxicity during treatment with ornidazole: the first case report. J Neurol Neurosurg Psychiatry 81(3):349–350

    PubMed  CAS  Google Scholar 

  122. Bond KM et al (2017) Dentate update: imaging features of entities that affect the dentate nucleus. AJNR Am J Neuroradiol 38(8):1467–1474

    PubMed  CAS  Google Scholar 

  123. Khadilkar S et al (2016) A practical approach to diseases affecting dentate nuclei. Clin Radiol 71(1):107–119

    PubMed  CAS  Google Scholar 

  124. Dainer MJ (1979) Untoward reaction to Flagyl (metronidazole). Am J Obstet Gynecol 133(8):939–940

    PubMed  CAS  Google Scholar 

  125. Davidson K, Clare AW (1989) Psychotic illness following termination of pregnancy. Br J Psychiatry 154:559–560

    PubMed  CAS  Google Scholar 

  126. Khandheria M, Snook E, Thomas C (2014) Psychotic episode secondary to metronidazole use. Gen Hosp Psychiatry 36(2):231 e3–e4

    Google Scholar 

  127. Schreiber W, Spernal J (1997) Metronidazole-induced psychotic disorder. Am J Psychiatry 154(8):1170–1171

    PubMed  CAS  Google Scholar 

  128. Uhl MD, Riely CA (1996) Metronidazole in treating portosystemic encephalopathy. Ann Intern Med 124(4):455

    PubMed  CAS  Google Scholar 

  129. Zahiruddin O, Shanooha M, Mohd MY, Azhar (2014) Psychosis induced by cefuroxime and metronidazole. Med J Malaysia 69(1):33–34

    PubMed  CAS  Google Scholar 

  130. Lamp KC et al (1999) Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin Pharmacokinet 36(5):353–373

    PubMed  CAS  Google Scholar 

  131. Nau R, Sorgel F, Eiffert H (2010) Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev 23(4):858–883

    PubMed  PubMed Central  CAS  Google Scholar 

  132. Cavanagh JB (1988) Lesion localisation: implications for the study of functional effects and mechanisms of action. Toxicology 49(1):131–136

    PubMed  CAS  Google Scholar 

  133. Rogulja Pv, Kovac W, Schmid H (1973) Metronidazol-encephalopathie der ratte. Acta Neuropathol 25(1):36–45

    Google Scholar 

  134. Alston TA, Abeles RH (1987) Enzymatic conversion of the antibiotic metronidazole to an analog of thiamine. Arch Biochem Biophys 257(2):357–362

    PubMed  CAS  Google Scholar 

  135. Zuccoli G, Pipitone N (2009) Neuroimaging findings in acute Wernicke’s encephalopathy: review of the literature. AJR Am J Roentgenol 192(2):501–508

    PubMed  Google Scholar 

  136. Zuccoli G et al (2009) MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics. AJNR Am J Neuroradiol 30(1):171–176

    PubMed  CAS  Google Scholar 

  137. Evans J et al (2003) Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases. J Vet Intern Med 17(3):304–310

    PubMed  Google Scholar 

  138. Bradley WG, Karlsson IJ, Rassol CG (1977) Metronidazole neuropathy. Br Med J 2(6087):610–611

    PubMed  PubMed Central  CAS  Google Scholar 

  139. Rao DN, Mason RP (1987) Generation of nitro radical anions of some 5-nitrofurans, 2- and 5-nitroimidazoles by norepinephrine, dopamine, and serotonin. A possible mechanism for neurotoxicity caused by nitroheterocyclic drugs. J Biol Chem 262(24):11731–11736

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Sjællands Universitetshospital, Sygehusvej 10, 4000, Roskilde, Denmark

    Caspar Godthaab Sørensen & Mette Lindelof

  2. Department of Clinical Neurophysiology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    William Kristian Karlsson

  3. Department of Neurology, Rigshospitalet Glostrup, Valdemar Hansens Vej 1A, Glostrup, 2600, Copenhagen, Denmark

    Faisal Mohammad Amin

  4. Sygehusvej 10, 4000, Roskilde, Denmark

    Caspar Godthaab Sørensen

Authors
  1. Caspar Godthaab Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Kristian Karlsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faisal Mohammad Amin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mette Lindelof
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Caspar Godthaab Sørensen.

Ethics declarations

Conflicts of interest

All authors declare that they have no conflicts of interest.

Ethical standards

Patient data in this review have previously been published with consent in accordance with the ethical standards in the Declaration of Helsinki.

Informed Consent

Patient consent was obtained for the images shown in Fig. 4.

Electronic supplementary material

Below is the link to the electronic supplementary material.

415_2018_9147_MOESM1_ESM.xlsx

Results of the systematic literature search including clinical data on identified cases of metronidazole-induced encephalopathy (XLSX 29 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sørensen, C.G., Karlsson, W.K., Amin, F.M. et al. Metronidazole-induced encephalopathy: a systematic review. J Neurol 267, 1–13 (2020). https://doi.org/10.1007/s00415-018-9147-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-018-9147-6

Keywords

Search

Navigation