Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

Abstract

Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as "metronidazole induced encephalopathy"(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity.

Keywords: Cerebellum; Corpus callosum; Magnetic resonance imaging; Nitroimidazoles; Toxicity.

[Table/Fig-1]:

A 43-year-old man developed gait ataxia & incoherent talk after 6 days of metronidazole therapy for amoebic dysentery. (a) T2W MRI shows hyperintensities in bilateral dentate nuclei(white thin arrows), inferior olive (black thin arrow), bilateral caudate, lentiform nuclei & splenium of corpus callosum with corresponding FLAIR hyperintensity in dentate(black thick arrow). (b) DWI shows restricted diffusion in bilateral caudate, lentiform nuclei, splenium, dentate nuclei & subcortical white matter. (c) Complete resolution in follow-up MRI 4 weeks after stoppage of drug with complete clinical recovery.

[Table/Fig-2]:

A 50-year-old man had symptoms of sensori-motor neuropathy for past 8 months and altered sensorium for past 7 days. He had history of daily metronidazole intake for past 18 months & 1 week back, dose was increased to 2 gm/day. (a) T2W MRI shows splenium hyperintensity in axial (white thin arrow) and sagittal (black thin arrow) views. DWI and ADC maps show diffusion restriction & low ADC (black thick arrow), respectively, in the corresponding areas of corpus callosum. (b) Follow-up MRI 3 weeks after drug withdrawal shows complete resolution of lesions, and the patient also recovered of encephalopathy.

[Table/Fig-3]:

A 40-year-old man had a sensori-motor neuropathy for last 8 years and recurrent episodes of slurring of speech and ataxia lasting for 10-12 hours for last 5 years. (a) T2W MRI sagittal view shows hyperintensities in genu and body of corpus callosum (white thin arrows) & axial view shows hyperintensities in genu (black thin arrows). (b) DWI and ADC maps show diffusion restriction and a high ADC respectively, in the corresponding areas of corpus callosum. Patient improved symptomatically 8 weeks after stoppage of metronidazole, however follow up imaging didn’t show much change (only minimal resolution).

[Table/Fig-4]:

A 69-year-old man, diagnosed as a case of amoebic liver abscess developed encephalopathy 7 days after initiation of treatment with metronidazole (2gm/day). (a) T2W MRI shows splenium hyperintensity (black thin arrow) which corresponds with the spenium hyperintensity on FLAIR sequence. (b) FLAIR images show faint dentate hyperintensities (black thick arrows) and inferior colliculi hyperintensities (white thin arrows). (c) DWI shows diffusion restriction in the splenium with low ADC value. Patient’s symptoms resolved completely, one week after stoppage of metronidazole. (Follow up imaging not available)