Metronidazole neurotoxicity in late liver transplantation

A 67-year-old female developed subacute peripheral neuropathy, nystagmus and encephalopathy. She was on continuous metronidazole use for 65 days for a liver abscess after receiving a transplantation. Diagnostic workup revealed a sensory axonal polyneuropathy in electroneuromyography. Brain magnetic resonance imaging (MRI) showed hyperintensities at the dentate nucleus and pons ([Figure 1]). Metronidazole treatment was discontinued and within the first week the patient evolved with complete improvement of encephalopathy. However, she maintained the neuropathy symptoms. A control brain MRI was normal after 30 days ([Figure 2]). Metronidazole neurotoxicity was previously reported with these same imaging findings and clinical course[1],[2],[3],[4].

Figure 1 Brain MRI with symmetric hyperintensity on axial T2-weighted images at the dentate nucleus (A, B) and pons (B), and increased signal on axial FLAIR images (C, D).

Figure 2 Axial FLAIR image 30 days after metronidazole interruption demonstrates complete reversal of signal changes

• References

• 1 Goolsby TA, Jakeman B, Gaynes RP. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature. Int J Antimicrob Agents. 2018 Mar;51(3):319-25. https://doi.org/10.1016/j.ijantimicag.2017.08.033
• 2 Agarwal A, Kanekar S, Sabat S, Thamburaj K. Metronidazole-induced cerebellar toxicity. Neurol Int. 2016 Apr;8(1):6365. https://doi.org/10.4081/ni.2016.6365
• 3 Iemura T, Kitano T, Ishii A, Hishizawa M, Kondo T, Yamashita K. Metronidazole-induced encephalopathy during treatment for refractory diarrhea after cord blood transplantation. Clin J Gastroenterol. 2019 Oct;12(5):414-9. https://doi.org/10.1007/s12328-019-00959-x
• 4 Woodruff BK, Wijdicks EFM, Marshall WF. Reversible metronidazole-induced lesions od the cerebellar dentate nuclei. N Engl J Med. 2002 Jan;346(1):68-9. https://doi.org/10.1056/NEJM200201033460117