621857 research-article2015

SCO0010.1177/2050313X15621857SAGE Open Medical Case ReportsGopinath et al.

SAGE Open Medical Case Reports

Case Report

Ornidazole-induced ataxia in an Indian woman: A case report

SAGE Open Medical Case Reports 3: 2050313X15621857 © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2050313X15621857 sco.sagepub.com

Kango Gopal Gopinath1, Benny Paul Wilson1, Surekha Viggeswarpu1, Prasad K Mathews1 and Sunithi Mani2

Abstract The nitroimidazole group of antibiotics like metronidazole have been reported to cause cerebellar ataxia as a rare side effect. Ornidazole, the newest derivative of this class, has a long half life and is very rarely known to cause cerebellar ataxia. Here, we report a 61-year-old patient who developed ataxia due to ornidazole to highlight an unusual adverse event that improved rapidly after discontinuation of the offending drug. Keywords Ornidazole, ataxia, Indian Date received: 23 September 2015; accepted: 19 November 2015

Introduction Ornidazole, a new nitroimidazole antibiotic, is commonly used for treating various infections including amoebiasis, giardiasis, trichomonal and anaerobic bacterial infections. Although adverse events are usually mild and transient with short-duration use, the nitroimidazole antibiotics, especially metronidazole, have been associated with serious adverse events like ataxia when prescribed for prolonged periods of time.1 Ornidazole-induced ataxia has been reported only once in literature.2 We have described the case details of a 61-year-old Indian woman who developed disabling cerebellar ataxia following long-term use of a combination tablet of ornidazole and ofloxacin that improved remarkably following drug cessation.

Case report A 61-year-old Indian woman presented to our hospital on 21 April 2014 with progressively worsening walking difficulty over the last 3 months. Initially, she noted a difficulty in negotiating narrow passageways that progressed, necessitating assistance from two family members for indoor mobility in the month preceding admission. She had multiple falls over the last 3 months. There was no difficulty in sitting up from a lying down position or getting up from a sitting position, and the unsteadiness was present only while attempting to walk with no history of sensory deficits

or cognitive decline. There was no history of alcohol or illicit drug abuse. She reported mild weight loss (2 kg in 6 months) with no loss of appetite. On review of her current medications, she reported that a year ago, she had been prescribed a 5-day course of a combination tablet consisting of ornidazole 500 mg and ofloxacin 200 mg (Tab. O2®,Nutrakare, Medley Pharmaceuticals Limited, Mumbai, Maharashtra, India) for a short-duration diarrhoeal illness. Even after resolution of her symptoms, she continued using the medication on a daily basis to avoid further episodes of diarrhoea. She was also on regular amlodipine for hypertension. On examination, she had marked gait ataxia with prominent bilateral cerebellar signs, including past pointing, dysdiadochokinesia, dysmetria, dysarthria, broad-based gait, broken pursuits and hypermetric saccades. Physical and neurological examination was otherwise unremarkable. 1Department

of Geriatric Medicine, Christian Medical College (CMC), Vellore, India 2Department of Radiology, Christian Medical College (CMC), Vellore, India Corresponding Author: Kango Gopal Gopinath, Department of Geriatric Medicine, Christian Medical College (CMC), No. 4, Arcot Road, Vellore 632004, India. Email: [email protected]

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SAGE Open Medical Case Reports walking frame until an outpatient review planned 2 weeks after discharge. During the outpatient visit, she had made substantial improvement and was walking independently.

Discussion

Figure 1.  (a, b, c) FLAIR axial sections showing near symmetric hyperintensity with swelling in the putamina (large arrowheads), Dentate nuclei (small arrowheads) and Inferior olivary nuclei (arrow). (d) Axial DWI image showing restricted diffusion in the splenium of the corpus callosum.

The differentials considered were ornidazole-induced cerebellar ataxia and paraneoplastic cerebellar syndrome. Routine blood tests including thyroid and liver function were normal. Chest X-ray, ultrasound abdomen were normal and computed tomography–positron emission tomography (CT-PET) of the whole body showed no hypermetabolic foci. Magnetic resonance imaging (MRI) of brain with contrast revealed bilateral, symmetric hyperintensities on T2 and fluid attenuated inversion recovery images (FLAIR) in the dentate nuclei of cerebellum, inferior olivary nuclei of midbrain, red nuclei of midbrain, bilateral basal ganglia, posterior midbrain around the aqueduct of Sylvius and the splenium of corpus callosum (Figure 1). A neurologist’s opinion concurred with our diagnosis of ornidazole toxicity. The combination tablet was stopped on the first day of admission to the hospital. She underwent intensive physiotherapy focussing on gait and balance training with which she made rapid improvement. At discharge from the hospital 2 weeks after admission, she was walking independently albeit with some unsteadiness. She was advised to continue using a

The temporal association of ataxia with the medication, rapid resolution with drug cessation and absence of other precipitating causes strongly suggested the likelihood of ornidazole toxicity. On the Naranjo adverse drug reaction scale,3 she scored 6 points (5–8, probable), indicating that her symptoms were probably due to ornidazole. Although flouroquinolones have been associated with various neurological side effects including lowering of seizure threshold, delirium and peripheral neuropathy,4 ataxia due to flouroquinolones such as ofloxacin has been reported extremely rarely in literature,5 and the radiological findings in this patient were similar to the changes noted on brain MRI imaging in previous patients with nitroimidazole toxicity. Common adverse events with the nitroimidazoles are mild and include a metallic taste and nausea. However, prolonged use of these drugs especially metronidazole has been associated with peripheral neuropathy, seizures, reversible ataxia, optic neuropathy and encephalopathy. Cases of cerebellar ataxia have been reported with a cumulative metronidazole dose of as little as 25 g and up to a maximum of 1080 g.6 To the best of our knowledge, there has been only one case report of ornidazole-induced ataxia published by Taskapilioglu et al.2 Our patient had ingested a cumulative dose of approximately 180 g of ornidazole prior to admission. Typical MRI abnormalities reported in the literature with nitroimidazole toxicity include hyperintensities on T2 and FLAIR images in the dentate nuclei, midbrain, dorsal pons, medulla, corpus callosum, globus pallidus, putamen and caudate nuclei and frontal white matter.7,8 Similar clinical and radiological features have also been described with methyl bromide toxicity.9 The exact pathophysiology of the neuroimaging changes and the resultant clinical features due to imidazoles is not clear. Possible toxic mechanisms include direct neuronal toxicity, GABA modulation, nucleic acid binding of intermediate metabolites of metronidazole affecting neuronal protein synthesis and mitochondrial function.10,11 Awareness of this toxicity and a complete drug review will facilitate an early diagnosis as well as help limit investigations for other causes. Ataxia can occur with all the nitroimidazole antibiotics including the newer drugs. Patient education while prescribing may help to avoid this adverse drug event. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Gopinath et al. Ethics approval Our institution does not require ethical approval for reporting individual cases or case series.

Funding The author(s) received no financial support for the research, authorship and/or publication of this article.

Informed consent Verbal informed consent was obtained from the patient for their anonymized information to be published in this article.

References 1. Hari A, Srikanth BA and Lakshmi GS. Metronidazole induced cerebellar ataxia. Indian J Pharmacol 2013; 45(3): 295–297. 2. Taskapilioglu O, Seferoglu M, Kaygili E, et al. Reversible cerebellar toxicity during treatment with ornidazole: the first case report. J Neurol Neurosurg Psychiatry 2010; 81: 349–350. 3. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30(2): 239–245.

3 4. Tome AM and Filipe A. Quinolones: review of psychiatric and neurological adverse reactions. Drug Saf 2011; 34: 465–488. 5. Mohan N, Menon K and Rao PG. Oral gatifloxacin-induced ataxia. Am J Health Syst Pharm 2002; 59(19): 1894. 6. Patel K, Green-Hopkins I, Lu S, et al. Cerebellar ataxia following prolonged use of metronidazole: case report and literature review. Int J Infect Dis 2008; 12: 111–114. 7. Ito H, Maruyama M, Ogura N, et al. Reversible cerebellar lesions induced by metronidazole therapy for Helicobacter pylori. J Neuroimaging 2004; 14: 369–371. 8. Kim E, Na DG, Kim EY, et al. MR imaging of metronidazoleinduced encephalopathy: lesion distribution and diffusionweighted imaging findings. AJNR Am J Neuroradiol 2007; 28: 1652–1658. 9. Balagopal K, Muthusamy K, Alexander M, et al. Methyl bromide poisoning presenting as acute ataxia. Neurol India 2011; 59: 768–769. 10. Bichsel P. Metronidazole: uses, toxicity and management of neurologic sequelae. Vet Intern Med 2004; 17: 304–310. 11. Rao DN, Jordan S and Mason RP. Generation of nitro radical anions of some 5-nitrofurans, and 2- and 5-nitroimidazoles by rat hepatocytes. Biochem Pharmacol 1988; 37: 2907–2913.

Ornidazole-induced ataxia in an Indian woman: A case report.

The nitroimidazole group of antibiotics like metronidazole have been reported to cause cerebellar ataxia as a rare side effect. Ornidazole, the newest...
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