Reversible optic neuropathy due to metronidazole

Case report

Metronidazole is a nitroimidazole antibiotic that is a potent antianaerobic agent often used to treat gastrointestinal infections. It can cause a number of neurological complications, the commonest of which is a sensory peripheral neuropathy.¹ Less well known are the possible ocular side-effects, including optic neuritis.²

A 67-year-old woman with longstanding scleroderma developed pneumatosis cystoides intestinalis, an unusual complication of scleroderma resulting in an atonic bowel with bacterial overgrowth syndrome. Treatment includes long-term antibiotics. She was trialled on short courses of doxycycline, roxithromycin, augmentin and metronidazole. Metronidazole was the most effective agent, but gastrointestinal symptoms promptly returned when the course of antibiotic was completed. She was therefore commenced on continuous metronidazole 400 mg three times daily in November 2005. In June 2006 she noted bilateral visual impairment and this became progressively worse over the next 2 months. She also became aware of loss of sensation and pain in her feet that slowly spread up the legs. Walking became difficult.

When she sought medical attention in August 2006 her visual acuity was counting fingers at 1 m with each eye. There was no improvement with pinhole. Pressures were 23 right, 19 left with Tonopen. The corneae were clear and the anterior chambers were deep and quiet. Dilated fundoscopy was entirely normal. Confrontation field testing was full, but the patient was unable to perform Humphrey automated field testing owing to inadequate visual acuity. Both pupils reacted well to light and near stimuli, there was no relative afferent pupillary defect on either side; ocular movements were normal. She had distal lower limb weakness of great toe and ankle plantar and dorsiflexion, and reduced pinprick and vibration sensation of the feet to the distal calves. Ankle reflexes were still present, 1+. A nutritional screen, which included serum zinc, vitamin B12, folate, vitamin A/beta-carotene, vitamin D, iron studies, was normal. An MRI brain scan showed some basal ganglia calcification of unlikely clinical significance, otherwise there were no abnormalities seen. Nerve conduction studies showed absent lower limb sensory responses, normal motor action potentials. Cerebrospinal fluid examination, including oligoclonal bands, was unremarkable.

She discontinued the Metronidazole and 4 days later her visual acuity improved to 6/60-1 left eye (LE), counting fingers at 2 m right eye (RE). One month later, her visual acuity was 6/7.5, N12 RE, 6/6-2, N10 LE corrected. There was reduced red-green Ishihara colour vision, RE 5/15 plates, LE 6/15. There was possible mild pallor of the temporal optic discs, otherwise the ophthalmic examination remained unremarkable. Pattern reverse visual evoked potentials at this time identified poorly defined, low amplitude morphology of the P100 waveforms with a marked increase in latency (RE 158 milliseconds [ms], LE 160 ms, Normal = 100 ms). The pattern electroretinogram had a well-defined P50 waveform, reflecting good macular function. These findings were consistent with a bilateral optic neuropathy.

Discussion

Metronidazole has previously been associated with optic and retrobulbar neuritis in a small case series.² Seven cases were reported. The length of time on the drug varied from 7 to 365 days and the dosage of metronidazole varied from 750 mg to 1 g daily. Age ranged from 26 to 53 years; there were four women and three men. Four of the patients had bilateral optic nerve involvement, most recovered normal vision although two had some residual deficit. As with our patient, peripheral neuropathy was also seen in two of the cases. The pathogenesis of metronidazole-induced neurotoxicity is unknown. However, patients with metronidazole – induced encephalopathy can have reversible MRI lesions in the supratentorial white matter and deep cerebellar nuclei that are high signal intensities on diffusion weighted imaging suggestive of cytotoxic oedema.^3,4

Although we have not rechallenged our patient with metronidazole to prove more conclusively that she developed a reversible optic neuropathy owing to this drug, this seems highly likely given the development of visual impairment after a relatively long course of metronidazole, absence of an alternative cause for her symptoms and signs, the associated sensory peripheral neuropathy that is a well-established complication of metronidazole ingestion, and resolution of her optic neuropathy with discontinuation of the drug. Because of her unusual clinical situation, she received a prolonged course of metronidazole and a large cumulative dose. This likely increased her risk of developing neurotoxicity.

Drug-induced optic neuropathy needs to be considered in patients on metronidazole who present with visual impairment.