SAN DIEGO – Metronidazole-induced encephalopathy should be considered when patients on the antibiotic are worked up for suspected multiple sclerosis, according to a case study and literature review from researchers at the Mount Sinai School of Medicine in New York.
A Crohn’s disease patient in his mid-30s who had been on metronidazole for almost 7 years presented there with a years-long diagnosis of multiple sclerosis, but MS wasn’t his problem. Doctors at the center figured out he had metronidazole-induced encephalopathy (MIE).
Dr. Corey McGraw
He had been started on 500 mg three times daily for a few months in early 2004, and then restarted on the same regimen in mid-2005. His first neurologic attack – primarily gait ataxia and dysarthria, along with nonenhancing T2 hyperintensities on MRI – came about a month later. Nonetheless, he remained on 250 mg twice daily to 500 mg three times daily until early 2011, and suffered several more attacks, notably after dosage increases. His cumulative metronidazole dose was 2,133.5 g.
Forty-one days after the patient stopped taking metronidazole, his ataxia and dysarthria were almost completely resolved; 7 months later, he was almost clear on brain MRI, with only small residua. His sole remaining complaints were poor memory, attention, and motivation.
"Neurologists should be alert to the possibility of metronidazole-induced encephalopathy in the differential diagnosis of demyelinating disease, especially in view of its potential reversibility," said lead investigator Dr. Corey McGraw, a neurologist at the school’s Corinne Goldsmith Dickinson Center for Multiple Sclerosis.
It’s widely known that metronidazole can cause peripheral neuropathy, but it is much less known that it can also cause toxic encephalopathy that mimics demyelination, he said at the Fourth Cooperative Meeting on Multiple Sclerosis.
"This is an under-recognized neurologic disease among American neurologists. Most of the [63 reported] cases have been in Korea and India, where it may be more recognized. I and my much-more-senior colleagues had never heard of metronidazole-induced encephalopathy before this case. Neurologists are probably missing it," Dr. McGraw said.
The giveaway in the Crohn’s patient’s case was that he had the same signs and symptoms with each attack, whereas MS tends to migrate around the body.
In many ways, he was a typical MIE patient.
Of the 63 cases reviewed by Dr. McGraw, 44 (70%) had MRI T2 hyperintensities of the cerebellar dentate nuclei that were the same as those found in the Crohn’s disease patient, and 19 (30%) had T2 hyperintensities of the corpus callosum splenium. Those and other MIE findings are "classic for a toxic encephalopathy," he said at the meeting, which was sponsored by the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
Dysarthria and gait ataxia are common, too, as well as problems with mentation, arm coordination, leg strength, and seizures.
The cumulative mean metronidazole dose in the 63 cases was 106.1 g (range, 3-1,095 g). The mean time from first dose to first neurologic attack was 67 days (range, 2-730 days). Symptoms resolved in anywhere from 1 to 420 days after metronidazole was stopped.
The "wide ranges in time to clinical manifestations and total cumulative doses may obscure the appropriate diagnosis," Dr. McGraw noted.
Dr. McGraw said that he had no relevant disclosures.