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

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.

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.

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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 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 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

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.