Metronidazole central nervous system toxicity

Last revised by Rohit Sharma on 24 Mar 2024

Metronidazole, which is used to treat a wide variety of bacterial and protozoal infections can, in exceedingly rare cases, lead to central nervous system toxicity.

Affected patients range widely in age, with the peak incidence occurring in the fifth and sixth decades. Hepatic disease is the most commonly identified risk factor; higher daily doses and longer duration of therapy are also thought to impart an increased risk. Onset is most commonly delayed by weeks to several months, although has been reported to occur within a few days.

The most common clinical manifestations include cerebellar dysfunction (75% of cases), altered mental state (33%), and seizures (13%) 1. Among patients with cerebellar dysfunction, dysarthria, abnormalities of gait, and ataxia are the most common features. Patients may report vertigo or dizziness.

Less common clinical findings may include:

  • polyneuropathy

  • oculomotor abnormalities

  • hemiparesis

Pathophysiological mechanisms of metronidazole neurotoxicity remain unclear. Metronidazole may inhibit the conversion of thiamine to its biologically active form producing a functional deficiency. Inhibition of the GABA-A receptor may also contribute. Circumstantial evidence also exists for disruption of neuronal oxidative phosphorylation.

Nearly all cases show lesions in the cerebellum (93-100%) 1,3, particularly of the cerebellar dentate nuclei. There is slightly less frequent involvement of corpus callosum, midbrain, pons, and/or medulla

A majority of cases (86%) show a characteristic pattern of bilateral symmetric involvement of the dentate nuclei, vestibular nuclei, and a focal area of the tegmentum in the superior olivary nucleus 3.

  • T2: bilateral, symmetric, hyperintense signal

  • T1 C+ (Gd): non-enhancing  

  • DWI: variable, from hyperintense to isointense to normal white matter in lesions of the dentate nucleus, midbrain, medulla, and pons

  • ADC: ADC values of lesions of the dentate nucleus, midbrain, medulla, and pons are similar or higher than those of normal white matter, whilst corpus callosum lesions can show lower values than in normal white matter 3

After discontinuation of metronidazole the majority of cases either improve (29%) or have complete resolution of symptoms (65%). A very small minority (3%) experience permanent cognitive impairment. Cases with cerebellar dysfunction seem slightly less likely to experience complete resolution than those with mental status changes or seizures 1.

Possible imaging differential considerations include

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