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.

Identification of significant protein markers by mass spectrometry after co‐treatment of cells with different drugs: An in vitro survey platform

“…With the ethosuximide and metronidazole combination, 4 candidate protein markers were identified (Table ), and CCR4‐NOT transcription complex subunit 1 associated with hepatocellular carcinoma was found. Clinical data show that metronidazole can induce encephalopathy and increase the severity of hepatocellular carcinoma; therefore, caution should be taken when prescribing this drug. All the molecules of interest in the networks simulated by the IPA Tool are shown in Figures S1–S5 (supporting information).…”

“…Tropomodulin-2 is associated with actin cytoskeleton, 35 and modification of the actin cytoskeletal organization by metformin has been reported. 36 With the ethosuximide and metronidazole combination, 4 candidate protein markers were identified ( 37 ; therefore, caution should be taken when prescribing this drug. All the molecules of interest in the networks simulated by the IPA Tool are shown in Figures S1-S5 (supporting information).…”

Metronidazole Induced Encephalopathy: Imaging of an Unusual Side Effect

“…Various proposed mechanism of encephalopathy include modulation of GABA receptors by the metabolites of metronidazole within the cerebellar and vestibular system and metronidazole's intermediate metabolites modulate inhibitory neurotransmitter GABA receptor especially within the cerebellar and vestibular systems, and generation of semiquinone and neurotoxic radicals due to reaction with catecholamine neurotransmitter [8] . Though serum and cerebrospinal fluid level of metronidazole may be obtained to substantiate the diagnosis it is almost certain if characteristic neuroimaging features are present and patient shows clinical improvement after discontinuation of the offending drug [9] . Resolution of MRI findings may be an additional proof of the diagnosis being metronidazole induced encephalopathy rather than anything else.…”

Metronidazole Encephalopathy EEG Features: A Case Report with Systematic Review of the Literature

“…It is usually well tolerated, but it has occasionally been associated with the development of serious neurological adverse events, including peripheral neuropathy, cerebellar dysfunction, visual impairment, vestibulotoxicity, cochleotoxicity, ataxic gait, dysarthria, seizures and encephalopathy (metronidazole-induced encephalopathy, MIE) [1]. The incidence is undetermined and case reports suggest a peak in the sixth and seventh decades of life [2]. MIE is commonly reversible on discontinuation of metronidazole, but long-lasting sequelae and even fatal outcomes have been reported [3].…”