Before Diagnosing Metronidazole Encephalopathy, Rule out Its Differential Diagnoses

To the Editor We read with interest the article by Suda on a 67-year-old woman who was admitted with impaired consciousness, dysarthria, and quadriparesis (1). She was receiving therapy with ceftriaxone and metronidazole (1,500 mg/day) for a liver abscess, and cerebral magnetic resonance imaging (MRI) showed hyperintensity on diffusion-weighted imaging (DWI) and hypointensity on the apparent diffusion coefficient (ADC) of the genu, body, and splenium of the corpus callosum, resulting in a diagnosis of metronidazole encephalopathy (1). The study is excellent but has some limitations that should be discussed.

We disagree with the diagnosis of metronidazole encephalopathy. Several differential diagnoses of MRI abnormalities were either not mentioned at all or not ruled out. The first differential diagnosis that should be ruled out is Marchiafava Bignami disease. Was there any evidence of chronic alcoholism in the index patient? Wernicke encephalopathy is the second differential diagnosis that must be ruled out. Was there evidence of ocular dysmotility, dementia, nystagmus, or vitamin-B1 deficiency? A third differential diagnosis that cannot be adequately ruled out is ischemic stroke. As the presented lesion was hyperintense on DWI and hypointense on ADC, it is imperative that all differential etiologies of cytotoxic edema, including ischemic stroke, be adequately ruled out. Hepatic encephalopathy was the fourth differential diagnosis that should have been ruled out. Because the patient had a liver abscess, the possibility that the neurological impairment was due to an increase in NH₃ cannot be ruled out. It is important to determine whether or not the serum NH₃ levels and liver transaminases were elevated.

How was the patient able to walk despite impaired consciousness (1)? Impaired consciousness does not usually allow patients to walk independently. What degree of impaired consciousness was diagnosed? Was the patient drowsy, soporose, or comatose?

One limitation associated with this study was that no cerebrospinal fluid studies were performed. Since the patient had a liver abscess, it is conceivable that the causative infectious agents were spread throughout the body and caused the encephalitis. Which infectious agent was identified as the cause of liver abscess? What infectious agents grew in the culture of abscess punctures? Another limitation is that no follow-up MRI findings were reported. Have the cerebral lesions also disappeared with clinical improvement?

In summary, this interesting study has limitations that put the results and their interpretation into doubt. Addressing these issues will strengthen the conclusions and improve the status of the study.

The author states that he has no Conflict of Interest (COI).