A 50-year-old man presented with a sudden onset of unconsciousness and limb twitching. He had a history of schizophrenia. On the initial neurological examination, multidirectional gaze-evoked nystagmus and limb dysmetria were observed. The emergency brain CT showed no abnormalities. Subsequently, brain MRI was performed promptly and revealed symmetric hyperintensity in the bilateral cerebellar dentate nuclei and superior olivary nuclei of the dorsal pons on T2 weighted-Fluid Attenuated Inversion Recovery (T2-FLAIR) sequences (Figure 1A). We then reviewed the patient’s medical history in greater detail and discovered that the patient had pyogenic spondylitis of the lumbar spine (Figure 1B) and underwent biopsy of the L5/S1 disc three months earlier. The biopsy specimens by next-generation sequencing revealed Bacteroides fragilis (relative abundance 89.60%), which is a gram-negative anaerobic bacterial species. So he received a three-month course of oral metronidazole therapy at a dosage of 400 mg thrice daily. Based on these neuroimaging findings and prolonged exposure to metronidazole, a diagnosis of metronidazole-induced encephalopathy was confirmed. Therefore, metronidazole was discontinued immediately, and his neurological symptoms resolved within two weeks. A follow-up brain MRI two months after cessation of metronidazole showed complete resolution of the abnormalities.

Figure 1.

(A) Brain MRI shows symmetric hyperintensity in the bilateral cerebellar dentate nuclei (chestnut sign, arrows) and superior olivary nuclei of the dorsal pons (cobra sign, arrowheads) on T2-FLAIR sequences. (B) Lumbar MRI shows pyogenic spondylitis of the lumbar spine (white arrow).

Figure 1 Long description

The image consists of two parts. Part A is an axial T2-weighted Fluid Attenuated Inversion Recovery (T2-FLAIR) MRI scan of the brain. It shows symmetric hyperintensity in the bilateral cerebellar dentate nuclei, indicated by arrows, and the superior olivary nuclei of the dorsal pons, indicated by arrowheads. Part B is a sagittal T2-weighted MRI scan of the lumbar spine, showing pyogenic spondylitis at the lumbar level, marked by a white arrow.

Metronidazole, a commonly used drug in the treatment of anaerobic infections, can cause adverse effects on the central nervous system called metronidazole-induced encephalopathy, which typically presents with dysarthria, gait instability, ataxia, altered mental status, nystagmus and seizures. ^{Reference Roy, Panwar, Pandit, Das and Joshi1} The dose of metronidazole exposure required to cause metronidazole-induced encephalopathy is highly variable, with neurological symptoms occurring at total cumulative doses ranging from 0.25 to 1095 g. ^{Reference Hobbs, Stern-Nezer, Buckwalter, Fischbein and Finley Caulfield2} Metronidazole-induced encephalopathy is characterized by T2-FLAIR hyperintense lesions in the bilateral cerebellar dentate nuclei (chestnut sign); meanwhile, involvement of the bilateral superior olivary nuclei of the dorsal pons (cobra sign) is rare, but corpus callosum, midbrain, medulla and cerebellar white matter can be affected as well. ^{Reference Sørensen, Karlsson, Amin and Lindelof3} In this case, the chestnut sign and cobra sign are important neuroimaging clues to diagnose metronidazole-induced encephalopathy. The majority of patients with metronidazole-induced encephalopathy have clinical resolution within days of drug cessation. In conclusion, metronidazole-induced encephalopathy should be considered in patients presenting with acute or subacute cerebellar syndrome after the initiation of metronidazole.