Metronidazole-induced encephalopathy (MIE) is a rare adverse effect of metronidazole, causing dysarthria, incoordination, and altered mental status. The hallmark MRI finding is symmetric T2-hyperintense lesions of the cerebellar dentate nuclei. The pathophysiology of MIE is not fully understood. One proposed mechanism is that metronidazole is converted to a thiamine analog that inhibits thiamine-dependent cellular functions.

An 87-year-old man with hypertension, diabetes, peripheral artery disease, chronic lower extremity wounds, and recent hospitalization for right foot osteomyelitis 6 weeks prior was re-admitted for 2 weeks of confusion and slurred speech. For 6 weeks, he had been maintained continuously on an antibiotic regimen that included metronidazole—in total, he received approximately 72 grams of metronidazole during this period (1.5 g/day).

Upon re-hospitalization, his neurological exam was significant for impaired attention and short-term recall, severe dysarthria, and bilateral upper limb dysmetria. MRI brain demonstrated symmetric fluid-attenuated inversion recovery (FLAIR) hyperintensities in the dentate nuclei of the cerebellum. No other significant abnormalities were observed. Metronidazole was discontinued due to concern for MIE. A few days later, his thiamine level resulted and was found to be < 6 nmol/L (normal values 70-180 nmol/L). High-dose thiamine was administered. Within 2 days of metronidazole discontinuation, modest improvement was observed in his encephalopathy and dysarthria. After thiamine was initiated, he improved even further, with near resolution of dysarthria and dysmetria within 1 week.

MIE represents an often-reversible cause of encephalopathy and cerebellar dysfunction that can be seen in cases of prolonged metronidazole administration. The hallmark MRI finding of symmetric FLAIR hyperintensity in the cerebellar dentate nuclei is generally diagnostic and should prompt drug discontinuation. In addition, patients with suspected MIE should be screened for concurrent thiamine deficiency, and high-dose thiamine administration should be considered as adjunctive therapy given the proposed mechanism of thiamine inhibition by metronidazole.