Metronidazole-induced encephalopathy

A 60-year-old male patient recently operated for cecal perforation was referred to MRI clinic in view of irrelevant talking, vomiting and altered behaviour. Patient was given intravenous antibiotic to cover anaerobic infection six hourly after laparotomy for four days in view of peritonitis.

Non-contrast Magnetic Resonance Imaging (MRI) was done with T2 and FLAIR sequences. MRI showed T2 (Figure 1) and FLAIR (Figure 2) symmetric hyperintensity in bilateral dentate nuclei of cerebellar hemispheres (arrows). No other significant abnormality was detected in entire brain in this study.

Metronidazole-induced encephalopathy (MIE) is rare form of drug-induced neuronal toxicity. Metronidazole is increasingly used in hospital setups as it has pivotal role in treating anaerobic infections. It can easily cross blood–brain barrier and thus has good cerebral penetrance [1]. Brain findings are due to spongiform changes within neurons, swelling of axonal sheaths and degeneration of purkinje cells [2].

Metronidazole-induced central nervous system toxicity may present with varied neurological symptoms. This may include confusion, dysarthria, gait imbalance, extremity weakness, headache, dizziness, visual disturbance and altered behaviour [1,3].

MRI is modality of choice for diagnosis of MIE. MRI findings of MIE are pathognomonic. The abnormal lesions are almost always bilateral and symmetrical. It presents as symmetric bilateral T2/FLAIR hyperintensity involving cerebellar dentate nuclei (most common location) and can also be seen in dorsal brainstem, including the midbrain, pons and medulla. Less common locations involve splenium of corpus callosum, inferior olivary nuclei, basal ganglia, cerebral subcortical white matter and vestibular nuclei. The lesions are typically non-enhancing [1,2]. Diffusion characteristics of lesions are variable, increased ADC value and vasogenic oedema are seen in lesions of the brainstem and cerebellar dentate nuclei, but decreased ADC value and cytotoxic oedema are seen in lesions affecting corpus callosum [2].

MIE has good prognosis, provided detected early. Treatment includes discontinuation of metronidazole and changing to another antimicrobial agent. Follow-up of patient should be done with follow-up MRI scan of brain to see for resolution of abnormal signal intensity. In most cases, encephalopathy is reversible if detected early, recovery usually takes 3-16 weeks. Irreversible neurological sequelae may remain in some patients [1,3].

Teaching points

1. MIE can be diagnosed by combination of clinical findings, proper history and imaging findings.
2. Bilateral symmetrical T2/FLAIR hyperintensity involving cerebellar dentate nuclei is most common finding on MRI.
3. Bilateral symmetrical T2/FLAIR hyperintense lesions are typically non-enhancing with variable diffusion characteristics.
4. Early diagnosis and discontinuation of metronidazole is important to prevent irreversible neurological damage.

Written informed patient consent for publication has been obtained.