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Metronidazole-induced encephalopathy: a systematic review

  • Caspar Godthaab Sørensen
  • William Kristian Karlsson
  • Faisal Mohammad Amin
  • Mette Lindelof
Review
  • 18 Downloads

Abstract

Background and aims

Metronidazole, a commonly used antibiotic drug, can cause adverse effects in the central nervous system termed metronidazole-induced encephalopathy, leading to diagnostic challenges. The condition is rare and a detailed description of its phenotype is lacking. In this systematic review we investigated the clinical features of metronidazole-induced encephalopathy to promote recognition and elaborate the description.

Methods

We performed a systematic literature search using PubMed.gov and hand searched the reference lists of included articles and other publications of interest. We included case series and single reports describing individual patients developing symptoms from the central nervous system in relation to metronidazole treatment. Data were extracted and analyzed descriptively.

Results

We identified 779 publications of which 112 papers comprising 136 patients were included. Typical findings were dysarthria, gait instability, limb dyscoordination and altered mental status. Frequently, patients concomitantly presented with metronidazole-induced polyneuropathy. Liver disease was the most common pre-existing condition. MRI showed a characteristic pattern of reversible symmetrical hyperintense lesions on T2/FLAIR of the dentate nuclei in 90% of patients. Most patients improved significantly after discontinuation of metronidazole. Poor outcome was associated with severe comorbidity.

Conclusion

Metronidazole-induced encephalopathy should be considered in patients presenting with neurological symptoms in relation to newly initiated or prolonged metronidazole treatment. MRI changes are highly characteristic and specific. Patients with liver disease are at increased risk. Prognosis is good if recognized early.

Keywords

Metronidazole Encephalopathy Dentate nuclei Ataxia Magnetic resonance imaging Toxicology 

Abbreviations

*

Denotes patients for whom polyneuropathy presented before CNS symptoms

+PNS

Remaining symptoms of polyneuropathy at follow-up

CC

Corpus callosum

CNS

Central nervous system

COPD

Chronic obstructive pulmonary disease

CWM

Cerebral white matter

DIC

Disseminated intravascular coagulation

DM

Diabetes mellitus

DN

Dentate nuclei

MB

Midbrain

MBD

Dorsal midbrain

MBRN

Midbrain with involvement of the red nuclei

MO

Medulla oblongata

MOION

Medulla oblongata with involvement of the inferior olivary nuclei

N/R

Not reported

Notes

Compliance with ethical standards

Conflicts of interest

All authors declare that they have no conflicts of interest.

Ethical standards

Patient data in this review have previously been published with consent in accordance with the ethical standards in the Declaration of Helsinki.

Informed Consent

Patient consent was obtained for the images shown in Fig. 4.

Supplementary material

415_2018_9147_MOESM1_ESM.xlsx (30 kb)
Results of the systematic literature search including clinical data on identified cases of metronidazole-induced encephalopathy (XLSX 29 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologySjællands UniversitetshospitalRoskildeDenmark
  2. 2.Department of Clinical NeurophysiologyCopenhagen University Hospital RigshospitaletCopenhagenDenmark
  3. 3.Department of NeurologyRigshospitalet GlostrupCopenhagenDenmark
  4. 4.RoskildeDenmark

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