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Year : 2016  |  Volume : 21  |  Issue : 2  |  Page : 136-139

Magnetic resonance imaging in metronidazole induced reversible encephalopathy

Departments of Radiology, TNMC and BYL Nair Hospital, Mumbai, Maharashtra, India

Date of Web Publication31-Aug-2016

Correspondence Address:
Pradip Bhimrao Rathod
159, Nirmal pooja Apartment, Shivaji Nagar, Nagpur - 440 003 Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9903.189528

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Metronidazole is a nitroimidazole derivative antibiotic, commonly used against protozoa and anaerobic bacteria, considered relatively safe at usual doses. Metronidazole induced encephalopathy (MIE) is a rare adverse effect at high doses, the incidence of which is unknown. Magnetic resonance imaging (MRI) is a useful modality in detecting these lesions very well. The lesions in MIE are always symmetrical and are reversible after 4–6 weeks of discontinuation of metronidazole. In this article, we describe MRI in a patient of MIE, which was found to be reversible upon discontinuation of the drug.

Keywords: Magnetic resonance imaging, metronidazole, metronidazole induced encephalopathy

How to cite this article:
Rathod PB, Yeragi BS, Ranwaka AA, Nanwani NJ. Magnetic resonance imaging in metronidazole induced reversible encephalopathy. J Mahatma Gandhi Inst Med Sci 2016;21:136-9

How to cite this URL:
Rathod PB, Yeragi BS, Ranwaka AA, Nanwani NJ. Magnetic resonance imaging in metronidazole induced reversible encephalopathy. J Mahatma Gandhi Inst Med Sci [serial online] 2016 [cited 2023 Mar 30];21:136-9. Available from: https://www.jmgims.co.in/text.asp?2016/21/2/136/189528

  Introduction Top

Metronidazole, a nitroimidazole derivative, is an antibiotic having broad spectrum activity against protozoa and anaerobic bacteria. It is commonly used antibiotic considered relatively safe at usual doses. Common encountered adverse effects resulting from its use were gastrointestinal discomfort, metallic taste, disulfiram-like reaction to alcohol. However, its prolonged use can result in central nervous system toxicity characterized by peripheral neuropathy, cerebral dysfunction, and encephalopathy.[1],[2] Metronidazole induced encephalopathy (MIE) is a rare adverse effect, the incidence of which is unknown. Magnetic resonance imaging (MRI) is useful in detecting MIE changes. In this case report, we describe MRI in a case of MIE, which was found to be reversible upon discontinuation of the drug.

  Case Report Top

A 48-year-old male with a history of chronic alcohol intake for more than 10 years was undergoing treatment for liver abscess at our institution for the past 2 months. The patient was admitted 2 months back and had received intravenous (IV) metronidazole in the doses of 1.2 g/day (400 mg thrice a day) for 21 days after which he was discharged. He was admitted again 7 days later for incomplete relief of symptoms after which he was administered metronidazole in oral doses of 2.4 g/day for 15 days. The patient subsequently improved clinically and was discharged. Ten days after the discharge, the patient started developing slurred speech and clumsiness of movements and was admitted for neurological evaluation.

On clinical examination, he was found to have ataxic gait along with dysdiadochokinesia and Romberg's sign. MRI of the brain was performed which showed hyperintense signal in bilateral dentate nuclei and splenium of corpus callosum on T2-weighted [Figure 1] and fluid-attenuated inversion recovery images [Figure 2]. These appeared hypointense on T1-weighted images. On diffusion-weighted imaging [Figure 3]a, restricted diffusion was noted in the above-mentioned region, which appeared dark on apparent diffusion coefficient map [Figure 3]b.
Figure1: T2-weighted magnetic resonance imaging axial images of brain showing hyperintense signal in bilateral dentate nuclei(black arrow) and corpus callosum(white arrow)

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Figure2: Fluid attenuated inversion recovery axial images of brain showing hyperintense signal in bilateral dentate nuclei(black arrow) and corpus callosum(white arrow)

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Figure3:(a and b) Diffusion weighted image of brain showing areas of restricted diffusion in bilateral dentate nuclei and corpus callosum appearing dark on apparent diffusion coefficient map

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In view of history of chronic alcohol intake, the possibility of acute Wernicke's encephalopathy was initially considered, but neither were the sites of involvement typical of Wernicke's encephalopathy nor did he have features of confusion or ophthalmoplegia associated with the condition. So Wernicke's encephalopathy was ruled out from a list of possible differential diagnosis.

Based on the morphology and distribution of lesions, the possibility of MIE was considered. The patient was advised to discontinue metronidazole and put on alternative drug therapy for the further treatment of a liver abscess. Within the next 6–7 days, the patient started showing signs of clinical improvement. A follow-up scan performed after 6 weeks showed complete resolution of signal changes seen in the earlier scan [Figure 4], confirming the suspicion, thus enabling the diagnosis of MIE.
Figure4: Follow-up magnetic resonance imaging images After 6weeks-Fluid attenuated inversion recovery sequence of Brain showing complete resolution of signal changes as described in earlier sequences

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  Discussion Top

Metronidazole is a commonly used nitroimidazole derivative available for treatment of anaerobic bacterial infections, parasitic infections like amoebiasis and giardiasis, Crohn's disease, postoperative prophylaxis, etc., Though considered safe at usual doses, it may produce a number of neurological side effects such as a cerebellar syndrome, encephalopathy, seizure, autonomic neuropathy, optic neuropathy and peripheral neuropathy.[1],[3],[4] In the cases described in a literature, cerebellar sign have been described at a cumulative dose of 25 g and above over a variable duration of treatment.[2] In our case, the dose was 60 g administered over a period of 6 weeks. The time required for the symptoms of MIE to appear is variable but usually prolonged. The average duration of 79 days has been reported.[5] No literature has described the difference between oral and IV drug doses of MIE. The total dosage of metronidazole for medication resulting in MIE has been reported as 45–120 g.[6]

On MRI, the lesions in patients with MIE are bilateral and typically seen in the dentate nuclei, midbrain (tectum, red nucleus, tegmentum around periaqueductal gray matter), dorsal pons (the vestibular nucleus, focal tegmental lesion of superior olivary nucleus, and the abducens nucleus), dorsal medulla and corpus callosum (splenium).[7] In our case, the lesions were seen in bilateral cerebellar dentate nuclei and splenium of corpus callosum.

Although the distribution and characteristic of lesions seen in MIE are characteristic, it becomes necessary to differentiate it from its imaging differential diagnosis. T2 hyperintense lesions of bilateral cerebellar dentate nuclei are also seen in cases of acute encephalopathy including maple syrup urine disease,[8] enteroviral encephalomyelitis.[9] Demyelinating conditions such as Marchiafava-Bignami disease, transient splenial lesions, encephalitis and osmotic myelinolysis show T2 hyperintense focal lesions in the splenium of corpus callosum.[7] The differential diagnosis of transient T2 hyperintense focal lesions in the spenium of corpus callosum also includes patients with epilepsy treated with anti-epileptic drugs,[10] acute toxic encephalopathy (methotrexate and 5 fluorouracil)[11],[12] and acute infectious encephalitis (influenza, Escherichia coli, mumps, adenovirus, Epstein bar virus).[13]

The pathogenesis of metronidazole toxicity is currently unknown. The available literature suggests that the cause is axonal degeneration due to faulty binding of metronidazole to RNA instead of DNA.[14] Rao and Manson [7],[15] found that catecholamine neurotransmitter reduce the efficacy of 5-nitroimidazole drugs such as metronidazole and produce both semiquinone radicals and nitro anion radicals. These radicals are proposed to cause nervous tissue damage. The exact mechanism, however, is still not completely understood.

The changes seen in MIE are found to be reversible after discontinuation of the drug. This has been thought due to axonal swelling with increased water content rather than a demyelinating process.[3]

MIE is a rare but possible adverse effect of long-term consumption of metronidazole. The cumulative dose is causing encephalopathy is more than 25 g. The lesions in MRI are always symmetrical, and the changes are characteristically reversible after 4–6 weeks of discontinuation of metronidazole. The dose of metronidazole should, therefore, be monitored when required to be administered for a long period.

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Conflicts of interest

There are no conflicts of interest.

  References Top

McGrath NM, Kent-Smith B, Sharp DM. Reversible optic neuropathy due to metronidazole. Clin Experiment Ophthalmol 2007;35:585-6.  Back to cited text no. 1
Kwon KY, Lee DK, Lee KH, Cho KH, Lee E, Chung SJ. Two cases of metronidazole-induced neurotoxicity lacking of clinico-radiological correlation. J Korean Neurol Assoc 2006;24:581-4.  Back to cited text no. 2
Kim H, Kim YW, Kim SR, Park IS, Jo KW. Metronidazole-induced encephalopathy in a patient with infectious colitis: A case report. J Med Case Rep 2011;5:63.  Back to cited text no. 3
Hobson-Webb LD, Roach ES, Donofrio PD. Metronidazole: Newly recognized cause of autonomic neuropathy. J Child Neurol 2006;21:429-31.  Back to cited text no. 4
Graves TD, Condon M, Loucaidou M, Perry RJ. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient. Gen Neurol 2009;11:30-3.  Back to cited text no. 5
Lee SS, Cha SH, Lee SY, Song CJ. Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: Magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging. J Comput Assist Tomogr 2009;33:305-8.  Back to cited text no. 6
Kim E, Na DG, Kim EY, Kim JH, Son KR, Chang KH. MR imaging of metronidazole-induced encephalopathy: Lesion distribution and diffusion-weighted imaging findings. AJNR Am J Neuroradiol 2007;28:1652-8.  Back to cited text no. 7
Jan W, Zimmerman RA, Wang ZJ, Berry GT, Kaplan PB, Kaye EM. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation. Neuroradiology 2003;45:393-9.  Back to cited text no. 8
Shen WC, Chiu HH, Chow KC, Tsai CH. MR imaging findings of enteroviral encephaloymelitis: An outbreak in Taiwan. AJNR Am J Neuroradiol 1999;20:1889-95.  Back to cited text no. 9
Uchino A, Takase Y, Nomiyama K, Egashira R, Kudo S. Acquired lesions of the corpus callosum: MR imaging. Eur Radiol 2006;16:905-14.  Back to cited text no. 10
Sandoval C, Kutscher M, Jayabose S, Tenner M. Neurotoxicity of intrathecal methotrexate: MR imaging findings. AJNR Am J Neuroradiol 2003;24:1887-90.  Back to cited text no. 11
Lucato LT, McKinney AM, Short J, Teksam M, Truwit CL. Reversible findings of restricted diffusion in 5-fluorouracil neurotoxicity. Australas Radiol 2006;50:364-8.  Back to cited text no. 12
Hagemann G, Mentzel HJ, Weisser H, Kunze A, Terborg C. Multiple reversible MR signal changes caused by Epstein-Barr virus encephalitis. AJNR Am J Neuroradiol 2006;27:1447-9.  Back to cited text no. 13
Caylor KB, Cassimatis MK. Metronidazole neurotoxicosis in two cats. J Am Anim Hosp Assoc 2001;37:258-62.  Back to cited text no. 14
Rao DN, Mason RP. Generation of nitro radical anions of some 5-nitrofurans, 2-and 5-nitroimidazoles by norepinephrine, dopamine, and serotonin: A possibl emechanism for neurotoxicity caused by nitroheterocyclic drugs. J Biol Chem 1987;262:11731-6.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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