We had a typical case of a 30 year old male patient with cerebral ataxia, seizures and giddiness. The patient was under the metronidazole from 4 month and patient had this complication from past 2 months. When the Metronidazole was withdrawn the patient's condition was normalised.
I want to know what was the relationship for causality of the Cerebral Ataxia induced by Metronidazole and its mechanism of causing Adverse event.
Yes.
You can find several reports using the following search strategy in PUBMED:
("metronidazole"[MeSH Terms] OR "metronidazole"[All Fields]) AND neurological[All Fields] AND ("adverse effects"[Subheading] OR ("adverse"[All Fields] AND "effects"[All Fields]) OR "adverse effects"[All Fields])
Some interesting may be:
1. Park K-I, Chung J-M, Kim J-Y. Metronidazole neurotoxicity: sequential neuroaxis involvement. Neurol India 2011 feb;59(1):104–107.[citado 2012 abr 13 ]
2. Ferroir J-P, Corpechot C, Freudenreich A, Khalil A. [Metronidazole-related polyneuritis, convulsive seizures, and cerebellar syndrome. Contribution of MRI]. Rev. Neurol. (Paris) 2009 oct;165(10):828–830.[citado 2012 abr 13 ]
3. Takase K, Santa Y, Ohta S, Yoshimura T. [MRI and SPECT findings in a case of metronidazole-induced reversible acute cerebellar ataxia]. Rinsho Shinkeigaku 2005 may;45(5):386–389.[citado 2012 abr 13 ]
4. Moosa ANV, Perkins D. Neurological picture. MRI of metronidazole induced cerebellar ataxia. J. Neurol. Neurosurg. Psychiatr. 2010 jul;81(7):754–755.[citado 2012 abr 13 ]
5. Graves TD, Condon M, Loucaidou M, Perry RJ. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient. J. Neurol. Sci. 2009 oct;285(1-2):238–240.[citado 2012 abr 13 ]
Expect that helps.
Cheers.
Francisco Fernández
I have never heard of this adverse effect being caused by metronidazole although it is known to cause peripheral neuropathy with prolonged exposures. At this point, it seems possible but the only way to know for sure would be re-exposure to the drug and seeing if his symptoms return to show causality. Interesting though...
http://www.nejm.org/doi/full/10.1056/NEJM200201033460117
The condition is rare, but the association with prolonged metronidazole use appears to be specific, and discontinuation can result in reversal of the symptoms (both behavioral and physiological). The author of the article above suggests the toxicity is general, but that the dentate nucleus (site of lesions which accompany metronidazole-induced ataxia) is simply the most sensitive tissue, and hence suffers injury first.
Yes.
You can find several reports using the following search strategy in PUBMED:
("metronidazole"[MeSH Terms] OR "metronidazole"[All Fields]) AND neurological[All Fields] AND ("adverse effects"[Subheading] OR ("adverse"[All Fields] AND "effects"[All Fields]) OR "adverse effects"[All Fields])
Some interesting may be:
1. Park K-I, Chung J-M, Kim J-Y. Metronidazole neurotoxicity: sequential neuroaxis involvement. Neurol India 2011 feb;59(1):104–107.[citado 2012 abr 13 ]
2. Ferroir J-P, Corpechot C, Freudenreich A, Khalil A. [Metronidazole-related polyneuritis, convulsive seizures, and cerebellar syndrome. Contribution of MRI]. Rev. Neurol. (Paris) 2009 oct;165(10):828–830.[citado 2012 abr 13 ]
3. Takase K, Santa Y, Ohta S, Yoshimura T. [MRI and SPECT findings in a case of metronidazole-induced reversible acute cerebellar ataxia]. Rinsho Shinkeigaku 2005 may;45(5):386–389.[citado 2012 abr 13 ]
4. Moosa ANV, Perkins D. Neurological picture. MRI of metronidazole induced cerebellar ataxia. J. Neurol. Neurosurg. Psychiatr. 2010 jul;81(7):754–755.[citado 2012 abr 13 ]
5. Graves TD, Condon M, Loucaidou M, Perry RJ. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient. J. Neurol. Sci. 2009 oct;285(1-2):238–240.[citado 2012 abr 13 ]
Expect that helps.
Cheers.
Francisco Fernández
Another series with free access may be accessed at:
http://www.nejm.org/doi/full/10.1056/NEJM200201033460117
Regards
Dear Folks,
Thanks for your comments and We had a case of with metronidazole induced seizures & cerebellar ataxia. The patient is using Metronidazole for a period of 4 months. The patient was counseled for the cessation of alcohol. The ,metronidazole was recommended to take 500 mg 4 times a day.
But I want to find out the exact mechanism that how the Metronidazole causes cerebellar ataxia ?
In some patients cerebral ataxia and other neurotoxicities are reported as the toxic effects of metronidazole.But it is not common.
It is suggested that the main mechanism of action of these effects are inhibition of neuronal protein synthesis by binding to RNA and thiamine antagonism.Neuropathological studies in dogs revealed axonal swelling in vestibulocerebellar pathways and brain stem leukomalacia. It seems that most affected dogs recover within a week or two of drug withdrawal. treated patients with a single IV bolus of diazepam followed by TID oral treatment for three days. Dogs treated with diazepam had an average response time of 13 hours (range 20 minutes to 24 hours) and an average recovery time of 38 hours (range 24-72 hours). Dogs that were not treated with diazepam had an average response time of 4.25 days (range 2-10) and an average recovery time of 11.6 days (range 5-21).
Results of this investigation demonstrated that diazepam tended to speed-up recovery. This mesns that once the metronidazole is displaced from the binding BZD receptor by diazepam the metabolism of the displaced drug become normalised and thus benzodiazepine induced chloride conductance is improved,thereby enhancing the inhibitary effect of excitatory neurons.
Dear Krishnapriya,
Thanks for your answer and its really interesting to know the answer what i am looking for
Akshaya Srikanth
why for 4 months. it is not normal trend of therapeutics. yes it induces neurotoxicities . The enzyme inducer or inhibitor effect of the medicine should be considered before continuing for such a long period.
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