Persistent Dystonia and Basal Ganglia Involvement Following Metronidazole Induced Encephalopathy (MIE)

Introduction: Since 1978, numerous patients mainly in adults have been reported with neurological complications of metronidazole such as cerebellar dysfunction, vestibulocochlear toxicity, seizure, encephalopathy, and rarely movement disorder (myoclonus and chorea). In most reported patients, these complications have been reversible without neurologic sequels.

Case Description: A previously normal 11-year-old male presented with tinnitus and new onset hearing loss, aggressive behaviors, generalized dystonia, and generalized tonic-clonic seizures a few days after onset of a febrile bloody diarrhea, treated by metronidazole initially orally and then intravenously (total dose of 400 mg/kg over one week). Physical examination on admission revealed normal size and reactive pupils, normal fundoscopy, bilateral increased deep tendon reflexes in lower extremities, and positive Babinski sign on the left. After admission, we discontinued Metronidazole based on the clinical impression of MIE. EEG showed generalized epileptiform discharges and seizures were controlled with phenobarbital and levetiracetam. All basic biochemical and metabolic tests and 24-hour urine copper level showed normal results. Cerebrospinal fluid analysis for viral infections, autoimmune encephalitis antibodies panel by indirect immunofluorescence, and anti-TPO were negative. First, brain magnetic resonance imaging (MRI), 9 days after disease onset, showed bilateral symmetric abnormal signals, high on T2 sequences in dentate nuclei, globus pallidi, substantia nigra, splenium of corpus callosum and centrum semiovale (Fig. 1). The second EEG, 1 week after admission, revealed scattered sharp waves with a normal background. An axonal type sensorimotor peripheral polyneuropathy and severe bilateral sensorineural hearing loss were detected in electrophysiological studies. These findings were mostly compatible with MIE. The patient was discharged from hospital with severe generalized dystonia, four limbs spasticity more severe in lower limbs, anarthria, and a gastric tube. The second brain MRI, 3 weeks later showed significant improvement in dentate nucleus, upper midbrain, splenium of corpus callosum and centrum semiovale, and residual signal intensities with cystic change in basal ganglia and mild atrophic changes especially in frontoparietal lobes (Fig. 1). The third brain MRI, 7 months later revealed the same changes as the second one (Fig. 1). Therefore, irreversibility of basal ganglia signals at follow-up neuroimaging was noticeable. Partial improvement of limbs’ dystonia and spasticity with trihexyphenidyl and baclofen was seen at the last visit 1 year later. Whole exome sequencing in addition of mitochondrial genome sequencing for evaluation of nuclear and mitochondrial genes responsible for mitochondrial encephalopathies, leukodystrophies, and inborn errors of metabolism were normal

Discussion: Herein, we report the youngest patient with MIE who presented with persistent generalized dystonia, basal ganglia involvement, and leukoencephalopathy following metronidazole toxicity.Therefore, the reported patient is a unique case of MIE with persistent neurologic and imaging sequels after discontinuation of the drug.

Conclusion: In conclusion, awareness about neurologic side effects of metronidazole as a common antimicrobial agent should be considered.