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Metronidazole-Induced Central Nervous System Toxicity

2011; Lippincott Williams & Wilkins; Volume: 34; Issue: 6 Linguagem: Inglês

10.1097/wnf.0b013e3182334b35

1537-162X

Akira Kuriyama, Jeffrey L. Jackson, Asako Doi, Toru Kamiya,

Epilepsy research and treatment

To assess patient and medication factors that contribute to metronidazole toxicity.We searched PUBMED from 1965 through April 7, 2011, and performed a hand search of bibliographies.Case reports or case series reporting metronidazole-induced central nervous toxicity.Two authors independently abstracted demographics, metronidazole indication, dose and duration, neurological manifestations, and outcomes as well as brain imaging findings.Among 64 patients, 48 (77%) had cerebellar dysfunction, 21 (33%) had altered mental status, and 8 (15%) had seizures. Patients' ages averaged 53.3 years (range, 12-87 years), and 64% were male. The median duration of metronidazole was 54 days, although 26% had taken it less than a week and 11% had taken it less than 72 hours. Among cases with outcome data, most patients either improved (n = 18 [29%]) or had complete resolution of their symptoms with discontinuation of metronidazole (n = 41 [65%]). There was no difference in resolution of symptom by age (P = 0.71) or sex (P = 0.34). The patients with cerebellar dysfunction were less likely to experience complete resolution than those with mental status changes or seizures (relative risk, 0.67; 95% confidence interval (CI), 0.49-0.92). Nearly all patients (n = 55 [86%]) underwent imaging of the brain: 44 (69%) underwent magnetic resonance imaging (MRI) and 12 (19%) underwent computed tomographic studies. All patients with cerebellar dysfunction had abnormalities on imaging: 93% (n = 39) had a cerebellar lesion, although numerous areas in the brain were affected. On follow-up MRIs, 25 patients (83%) had complete resolution of abnormalities.Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.