Metronidazole-induced encephalopathy: Case report and literature review

A 59-year-old male patient treated with metronidazole during the last two weeks for hidradenitis suppurativa who came to our clinic for several falls to the ground in the last days. The neurological examination showed a cerebellar ataxic motion with dysmetria and slight dysarthria.

MRI brain showed bilateral and symmetrical T2W and FLAIR hyperintensities in the areas of cerebellar dentate nucleus, splenium of the corpus callosum, periaqueductal region in mid-brain, inferior colliculus and left front subcortical white matter. High signal on diffusion weighted imaging was detected in all of these locations. No enhancement could be seen after contrast administration. Furthermore, there are white matter hyper-intensities because of chronic small vessel disease and an ancient haemorrhagic stroke in the left occipitotemporal gyrus with dead brain tissue and remains of haemosiderin.
Due to the patient being on metronidazole treatment, the possibility of drug induced encephalopathy was suggested and the neurologists stop metronidazole. A few days later, the patient started to improve with the disappearance of symptoms.
Five days after the withdrawal of the drug, the MRI was repeated. A significant improvement was observed compared to the first test, except for the changes due to chronic vascular pathology.

Metronidazole is an antibiotic and antiparasitic drug that acts inhibiting the synthesis of nucleic acids. It is used to the treatment of protozoa and anaerobic bacterial infections. Neurological toxicity is rare and the typical symptoms are cerebellar dysfunction, ataxia, vestibulocochlear alteration, dysarthria, visual deficit, seizures or encephalopathy. [1] Most cases have a complete resolution of symptoms after the interruption of metronidazole (65%) or at least an important improve (29%). However, some cases may suffer a permanent deterioration (3%), even resulting in death. [1, 2, 3, 4] Therefore it is important to stop the treatment with metronidazole as soon as possible to not aggravate the patient's clinical state. The pathophysiological mechanisms are not clear yet, although several of them have been proposed, for example: the rupture of the blood-brain barrier [5], reversible demyelination [6] or selective neuronal vulnerability. [7] The typical findings on T2W and FLAIR MRI are: bilateral hyperintensity of the dentate nuclei and corpus callosum, followed by the periaqueductal substance and tegmentum, dorsal aspect of the protuberance, basal ganglia and thalamus, cerebellar peduncles, subcortical white matter and spinal cord. [1, 2] The signal in DWI is variable and it does not always correspond to a fix value of ADC, there is controversy in this regard. A hyperintensity of dentate nuclei, midbrain, protuberance or spinal cord detected in T2W, FLAIR and DWI together with a ADC value higher or equal to normal white matter is suggestive of vasogenic oedema. Against, a hyperintensity of corpus callosum detected in T2W, FLAIR and DWI that shows lower ADC values is suggestive of cytotoxic oedema probably due to a ischaemic process of the axonal fibers. [1] Some hyperintensities DWI without low values of ADC could be explained by effect T2. [8] Although the main publications do not report about any significant enhancement after gadolinium administration, it has been recently published that an enhancement in corpus callosum lesions with cystic degeneration in the follow-up images, makes it difficult to differentiate from Marchiafava-Bignami disease. [8] The time for clinical improvement changes from patient to patient and may depend on factors such as severity of symptoms, duration of clinical features, underlying diseases, comorbid factors and also abnormalities in the images. In most cases, the clinical and radiological improvement after withdrawal from drug occurs simultaneously, such as hyperintensity in corpus callosum and lower olive groves. However most takes longer to disappear. [1]

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