Metronidazole-induced cerebellar toxicity

Agarwal, Amit Kumar; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

doi:10.4081/ni.2016.6365

Cited by 62 publications

(49 citation statements)

References 12 publications

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“…A control brain MRI was normal after 30 days ( Figure 2). Metronidazole neurotoxicity was previously reported with these same imaging findings and clinical course [1][2][3][4] .…”

supporting

confidence: 68%

Metronidazole neurotoxicity in late liver transplantation

Oliveira

Marques

Lange

2020

Arq. Neuro-Psiquiatr.

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“…A control brain MRI was normal after 30 days ( Figure 2). Metronidazole neurotoxicity was previously reported with these same imaging findings and clinical course [1][2][3][4] .…”

supporting

confidence: 68%

Metronidazole neurotoxicity in late liver transplantation

Oliveira

Marques

Lange

2020

Arq. Neuro-Psiquiatr.

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“…Metronidazole, a common antibacterial and antiprotozoal agent, is known to have neurologic toxicity with a predilection for the dentate nucleus, with signal changes on MR imaging seen in the dentate and red nuclei. 25 …”

Section: Clinical Implications Of Gadolinium Accumulation In the Brainmentioning

confidence: 99%

Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents

2017

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For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.

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“…For longer therapy, there should be a strict indication or cultivation results -neither of these were available for our patient, who later suffered from neurological complications. Post-mortem histopathological examination of the CNS of intoxicated dogs revealed lesions and deaths of Purkinje cells, axonal damage as a consequence of vasogenic oedema, as well as an inhibition of RNA synthesis (Scharer 1972;Fitch et al 1991;Agarwal et al 2016). In our patient, who survived the intoxication and improved greatly upon the discontinuation of therapy, ante-or postmortem biopsies were considered unnecessary and were not taken.…”

Section: Case Descriptionmentioning

confidence: 99%

Toxic encephalopathy associated with high-dose metronidazole therapy in a dog: a case report

Hájek¹,

Šimerdová²,

Vávra³

et al. 2017

Vet. Med. - Czech

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This case report describes an episode of acute ataxia, tremor, vertical nystagmus and progressive weakness in a mixed breed dog treated with high doses of metronidazole. Complete blood cell count, serum biochemistry, coagulation profile, blood pressure measurement, urinalysis, computed tomography of the brain and cerebrospinal fluid examination were unremarkable. Metronidazole had been administered at a dose of 65 mg/ kg/day and neurotoxicity was, therefore, suspected. Drug concentrations in the patient's serum and cerebrospinal fluid were measured using high-performance liquid chromatography and compared to control dogs. Metronidazole administration was immediately discontinued; supportive care consisted of fluid therapy and diazepam treatment. The neurological status of the patient improved rapidly within 72 h. The aim of this case report is to describe the clinical presentation of metronidazole intoxication in a mixed breed dog and to interpret the chromatographic analysis which can be a beneficial diagnostic and screening tool in dogs intoxicated with metronidazole.Keywords: vestibular diseases; cerebellar dysfunction; canine diseases; gamma-aminobutyric acid; chromatography Metronidazole (MTZ) is an injectable and oral synthetic, nitroimidazole antibacterial and antiprotozoal agent. It is commonly used in veterinary practice to treat a wide variety of conditions (Watson 1980;Tams 1984;Happonen et al. 2000;Olson et al. 2005;Cattin et al. 2008;Jergens et al. 2010;Senhorinho et al. 2012). The mode of action requires strict anaerobic conditions; susceptible infectious agents include Bacteroides sp., Clostridium sp., Giardia sp. etc. (Rossignol et al. 1984;Even et al. 1998; Plumb 1999;Marks and Kather 2003;Hausen et al. 2011). MTZ is primarily metabolised in the liver and crosses the blood-brain barrier rapidly; in mice, the unaltered drug accumulates in the cerebellum and hippocampal areas (Plumb 1999;Olson et al. 2005). The recommended dosage for long-term treatment in dogs is 10 mg/kg p.o. twice or three times a day (Plumb 1999). Adverse effects include neurological disorders, lethargy, weakness, neutropenia, hepatotoxicity, haematuria, nausea, vomiting and diarrhoea (Plumb 1999;Weiss 2005). MTZ toxicity can develop suddenly and if unrecognised, can lead to rapid deterioration and death (Wright and Tyler 2003). In cases of acute toxicity from a chronic overdose in dogs, the drug should be discontinued and the patients treated supportively and symptomatically (Wright and Tyler 2003). The aim of this case report is to describe a metronidazole-induced neurotoxicity with subsequent chromatographic analysis in a dog. Case descriptionA six and a half-year-old 7.2-kg uncastrated male mixed breed dog was presented for neurological exSupported by the Ministry of Education, Youth and Sports of the Czech Republic (Institutional research development).

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Metronidazole-induced cerebellar toxicity

Cited by 62 publications

References 12 publications

Metronidazole neurotoxicity in late liver transplantation

Metronidazole neurotoxicity in late liver transplantation

Toxic encephalopathy associated with high-dose metronidazole therapy in a dog: a case report

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