Clinical Review & Education

Images in Neurology

A Case of Topical Metronidazole–Induced Encephalopathy

Rishi Philip Mathew, MBBS, Masters(Rad), DMRD, EDiR; Shabeeb P. Kunhimohammed, MBBS;
Maria Joseph, MBBS, MD

A 41-year-old man with quadriparesis who had been bedbound
for 12 years following a road traffic crash and had multiple decubi-
tus ulcers presented to our emergency department with com-
plaints of 2 days of slurring of speech and facial deviation with
1 seizure episode. He had a history of type 2 diabetes. On physical
examination, he was conscious and oriented, had slurring of
speech, was able to obey simple commands, and had no menin-
geal signs. His pulse rate was 101 beats per minute, and his blood
pressure was 120/80 mm Hg.
Magnetic resonance imaging (MRI) of the brain (Figure 1)
revealed T2 and T2–fluid-attenuated inversion recovery (FLAIR)
bilateral symmetrical hyperintense and mildly T1 hypointense
lesions within the cerebellar dentate nuclei and the splenium of the
corpus callosum. The affected regions also showed true restriction

Figure 1. Magnetic Resonance Imaging (MRI) on Presentation

A Axial T2-FLAIR MRI of hyperintense lesion B Axial T2-FLAIR MRI of symmetric hyperintense lesions

Axial T2–fluid-attenuated inversion

recovery (FLAIR) MRI showing a
hyperintense lesion in the splenium
of the corpus callosum (A, yellow
arrowhead) and symmetric
hyperintense lesions in the bilateral
cerebellar dentate nuclei (B; white
arrowheads) in a 41-year-old man
who had been receiving topical
metronidazole.

Figure 2. Magnetic Resonance Imaging (MRI) on Follow-up

A Axial T2-FLAIR MRI of lesion 1 mo later B Axial T2-FLAIR MRI of lesions 1 mo later

Follow-up axial T2–fluid-attenuated

inversion recovery (FLAIR) MRI taken
1 month later, with complete
resolution of the hyperintense lesions
in the splenium of the corpus
callosum (A; yellow arrowhead) and
the bilateral cerebellar dentate nuclei
(B; white arrowheads), following
complete cessation of topical
metronidazole.

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 Clinical Review & Education Images in Neurology

on diffusion-weighted imaging. The neuroimaging pattern was highly
characteristic for metronidazole-induced toxicity, and the findings
were given to the consulting neurophysician.
On further questioning, the patient stated he had been apply-
ing powdered metronidazole tablets (with a gel) over his decubitus
ulcers for the last 8 to 10 months. The topical antimicrobial was im-
mediately stopped, and the patient showed gradual improvement.
He was discharged after 5 days in stable condition. A follow-up brain
MRI (Figure 2) was done after 1 month and showed complete reso-
lution of the previous findings.
Metronidazole is an antimicrobial agent, and when it is used
at appropriate doses, it is reasonably safe and well tolerated,
although it can easily penetrate the cerebrospinal fluid and central
nervous system.1 Metronidazole-induced encephalopathy (MIE)
is a rare complication of this drug, and 3 symptoms have been re-
ported: cerebellar dysfunction (in 75% of patients), acute altera-
tion in mental status (33%), and seizures (13%).1 Typical sites of in-
volvement are the cerebellar dentate nuclei (85%), midbrain (55%),
and splenium of corpus callosum (50%).2 Magnetic resonance
imaging plays a crucial role in the diagnosis of MIE, with the lesions
appearing hyperintense on T2 and/or T2-FLAIR sequences and oc-
casionally showing diffusion restriction.2
The most striking aspect of this condition is that, following im-
mediate cessation of the drug, most patients demonstrate clinical
improvement along with complete or near-complete resolution of
the original MIE lesions on follow-up MRI. However, there have been
a few cases of deaths associated with irreversible MIE.2,3 Differen-
tial diagnoses for MIE include Wernicke encephalopathy, methyl bro-
mide intoxication, and enteroviral encephalomyelitis.2,3
We acknowledge that the systemic metronidazole level of this
patient was not checked. However, the likelihood that there was sys-
temic absorption of the topical treatment, likely as a result of skin
breakdown associated with the ulcers, must be taken into consid-
eration. An example for comparison would be the systemic
adverse effects from topical use of corticosteroids, which are well
established in literature.4
To our knowledge, this is the first documented case of MIE re-
sulting from topical use of metronidazole. Clinicians should be aware
of the possibility of systemic absorption of this medication and the
potential resulting toxicities.

ARTICLE INFORMATION
Author Affiliations: Department of Radiology,
Rajagiri Hospital, Aluva, Kochi, Kerala, India.
Corresponding Author: Rishi Philip Mathew,
MBBS, Masters(Rad), DMRD, EDiR, Department of
Radiology, Rajagiri Hospital, Chunangamvely,
Aluva, Kochi, 683112 Kerala, India
(dr_rishimathew@yahoo.com).
Published Online: August 10, 2020.
doi:10.1001/jamaneurol.2020.2596
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for
granting permission to publish this information.
REFERENCES
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Chang KH. MR imaging of metronidazole-induced
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Neuroradiol. 2007;28(9):1652-1658. doi:10.3174/ajnr.
A0655
3. Roy U, Panwar A, Pandit A, Das SK, Joshi B.
Clinical and neuroradiological spectrum of
metronidazole induced encephalopathy: our
experience and the review of literature. J Clin Diagn
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2016/19032.8054
4. Nieman LK. Consequences of systemic
absorption of topical glucocorticoids. J Am Acad
Dermatol. 2011;65(1):250-252. doi:10.1016/j.jaad.
2010.12.037

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