1Department of Neurology, Keimyung University Dongsan Hospital, Daegu, Korea
2Department of Neurology, Keimyung University School of Medicine, Daegu, Korea
Corresponding author: Hyun Ah Kim Department of Neurology, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea. E-mail: kha770206@gmail.com
• Received: May 31, 2025 • Revised: June 9, 2025 • Accepted: June 11, 2025
This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
We report a case of metronidazole-associated cerebellar toxicity presenting with positional downbeat nystagmus, a relatively uncommon but clinically significant manifestation. A 61-year-old man developed ataxia, dysarthria, and positional nystagmus after nearly 2 months of metronidazole treatment for a brain abscess in the frontal lobe. Brain magnetic resonance imaging (MRI) showed symmetrical T2-weighted/fluid-attenuated inversion recovery hyperintensities in the dentate nuclei and tectal plate. These findings, along with prolonged use of intravenous metronidazole, supported the diagnosis of metronidazole-induced cerebellar toxicity. Discontinuation of the drug led to marked clinical and radiologic improvement. This case highlights the importance of recognizing positional downbeat nystagmus as a potential early indicator of metronidazole-induced neurotoxicity. Early identification of this oculomotor pattern may prompt timely imaging and cessation of the offending agent, potentially preventing irreversible neurologic damage.
Metronidazole is a widely used nitroimidazole antibiotic effective against anaerobic and protozoal infections. Although it is generally well tolerated, metronidazole has been associated with various neurologic adverse effects, including peripheral neuropathy, encephalopathy, and cerebellar dysfunction. Among these, metronidazole-induced cerebellar toxicity is typically characterized by ataxia, dysarthria, and, in some cases, characteristic magnetic resonance imaging (MRI) findings involving the dentate nuclei.
Positional downbeat nystagmus is a rare but important oculomotor sign often linked to central vestibulocerebellar dysfunction, particularly involving the nodulus and uvula. While cerebellar symptoms are well recognized in metronidazole toxicity, the occurrence of central positional nystagmus (CPN), especially with a downbeat and horizontal apogeotropic pattern, has rarely been described.
We present a unique case of metronidazole-induced cerebellar toxicity initially presenting with positional downbeat nystagmus, highlighting its value as an early diagnostic clue.
CASE REPORT
A 61-year-old man presented to the emergency department with a confused mentality. His past medical history included hypertension and alcoholic liver cirrhosis. He was disoriented and unable to obey simple commands. His recent history of alcohol intake was unclear. Brain imaging revealed a brain abscess, approximately 3 cm in diameter, with vasogenic edema in the left frontal lobe, and he was admitted to the neurosurgery department. Antibiotic treatment with ceftriaxone and metronidazole was promptly initiated. Stereotactic drainage of the abscess was performed, and intraoperative culture of the abscess identified Klebsiella pneumoniae, which was negative for extended-spectrum beta-lactamase production. K. pneumoniae was also isolated from the sputum culture, raising suspicion of concurrent aspiration pneumonia. Intravenous antimicrobial therapy consisted of ceftriaxone (4 g/day) and metronidazole (2 g/day). Following nearly 8 weeks of antibiotic treatment, the patient’s consciousness level returned to normal, and follow-up imaging demonstrated improvement in both the brain abscess and the accompanying ventriculitis in the lateral ventricles. However, he began to experience new neurological symptoms, including dysarthria, dizziness, and gait disturbance, which progressively worsened over the following week. He also described bilateral numbness and tingling in the distal upper and lower limbs. He was referred to the neurology department for further evaluation. He exhibited cerebellar dysarthria and bilateral limb ataxia. Although spontaneous, gaze-evoked, and head-shaking nystagmus were not observed, positional testing revealed downbeat nystagmus. On video-oculography (VOG), a predominantly downbeat nystagmus with a horizontal apogeotropic component was observed during head turning to both sides (Supplementary Video 1). Downbeat nystagmus was most prominent in the straight head-hanging position, with a peak slow-phase velocity of approximately 16°/sec. Similar paroxysmal positional downbeat nystagmus was also observed during bilateral Dix–Hallpike maneuvers. The head impulse test was normal bilaterally. The brain MRI revealed symmetrical T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) hyperintensities in both sides of the tectal plate and both dentate nuclei (Fig. 1A, B), consistent with a diagnosis of metronidazole-induced cerebellar toxicity due to prolonged use of the drug. Metronidazole was discontinued, and within approximately 5 days, the patient's ataxia, dysarthria, and dizziness showed marked improvement. A follow-up MRI performed 1 week after discontinuation of metronidazole showed complete resolution of the previously noted hyperintensities (Fig. 1C, D). Repeat VOG after 2 weeks revealed marked improvement of the positional downbeat nystagmus. Paresthesia and sensory deficits in the distal extremities persisted with minimal improvement.
The study adhered to the ethical standards of the Declaration of Helsinki. Written informed consent was obtained from the patient for publication of the case details and associated images.
DISCUSSION
We report a case of metronidazole-induced cerebellar toxicity presenting with positional downbeat nystagmus. While cerebellar symptoms such as ataxia and dysarthria are well-known features of metronidazole toxicity, the presence of position-dependent downbeat nystagmus with a horizontal apogeotropic component is rarely described. This case suggests that positional downbeat nystagmus may serve as an early clue to metronidazole-induced cerebellar toxicity.
Metronidazole is a widely utilized 5-nitroimidazole antibiotic indicated for anaerobic and parasitic infections, with broad acceptance stemming from its clinical efficacy and tolerability [1]. Metronidazole has been associated with various neurologic adverse effects, including peripheral neuropathy, encephalopathy, cerebellar dysfunction, and seizures [2]. Although the exact mechanism of metronidazole-induced neurotoxicity remains unclear, it is hypothesized that the drug promotes the oxidation of catecholamine neurotransmitters such as norepinephrine and dopamine, leading to the formation of semiquinone and nitroanion radicals, which in turn generate reactive oxygen species, contributing to axonal swelling and neuronal damage [3].
In our case, the onset of metronidazole-induced cerebellar toxicity occurred 2 months after initiating the medication. In previous studies, the median time from drug initiation to symptom onset in patients with metronidazole-induced encephalopathy was approximately one month [4,5]. The more insidious symptom onset in our patient may be related to relatively milder symptoms due to damage being limited primarily to the cerebellum.
Oculomotor disturbances such as nystagmus, diplopia, abducens paresis, saccadic pursuit, and gaze palsy were reported in approximately 23% of cases of metronidazole-induced encephalopathy, although detailed oculomotor findings have been rarely documented [5]. Spontaneous downbeat nystagmus and bilateral gaze-evoked nystagmus with ataxia and altered mental status were reported in a single case study [6]. In our case, spontaneous and gaze-evoked nystagmus were absent; however, positional downbeat nystagmus was observed during head-turning, Dix–Hallpike, and straight head-hanging tests. This finding is consistent with CPN, which refers to nystagmus elicited by changes in head position relative to gravity and is typically attributed to lesions in the central vestibulocerebellar pathways [7]. CPN often presents as downbeat nystagmus during the straight head-hanging or Dix–Hallpike maneuvers, upbeat nystagmus upon returning to the upright position, and/or apogeotropic horizontal nystagmus during the supine head-roll test [8]. Lesion studies in humans have consistently implicated the vestibulocerebellum, particularly the nodulus and uvula, as key structures in the pathogenesis of positional downbeat nystagmus [9]. While positional downbeat nystagmus may also occur in benign paroxysmal positional vertigo (BPPV) involving the anterior canal, atypical variants of posterior canal BPPV, or ictal vestibular migraine [9], the absence of a migraine history, the presence of other neurological symptoms, marked clinical improvement after discontinuation of metronidazole, and symmetrical, reversible T2/FLAIR hyperintensities in the dentate nuclei in our case support a central etiology.
This case highlights that positional downbeat nystagmus may serve as a valuable clinical clue in identifying metronidazole-induced cerebellar toxicity, especially when spontaneous nystagmus is absent. Although MRI findings and overt cerebellar signs typically support the diagnosis, the presence of positionally induced oculomotor abnormalities may help uncover cerebellar involvement in a more subtle or early stage. Recognizing this pattern through positional testing can prompt timely neuroimaging and discontinuation of the offending agent, potentially preventing further neurological deterioration.
ARTICLE INFORMATION
Funding/Support
None.
Conflicts of Interest
Hyesoo Kwon and Hyun Ah Kim serve as members of the Editorial Board of Research in Vestibular Science and were not involved in the review process of this article.
Availability of Data and Materials
The datasets are not publicly available but are available from the corresponding author upon reasonable request.
Authors’ Contributions
Conceptualization, Methodology: Kim HA; Data curation: Kwon H, Kim HA; Formal analysis: Kwon H; Writing–original draft: Kwon H; Writing–review and editing: Kim HA.
All authors read and approved the final manuscript.
Video-oculography shows no prominent spontaneous nystagmus in the primary position, followed by downbeat nystagmus induced by the straight head-hanging position. Follow-up recording after 2 weeks shows marked improvement of the positional nystagmus after discontinuation of metronidazole. H, horizontal position of the right eye; T, torsional position of the right eye; V, vertical position of the right eye.
Fig. 1.
T2-weighted and fluid-attenuated inversion recovery axial brain magnetic resonance imaging findings. (A) Symmetrical high signal intensity (SI) in the bilateral tectal plate (yellow arrows). (B) High SI in the bilateral dentate nuclei prior to treatment (red arrows). (C) One-week follow-up image after discontinuation of metronidazole, showing improvement of the tectal plate lesions. (D) One-week follow-up image after discontinuation of metronidazole, showing resolution of the dentate lesions.
REFERENCES
1. Löfmark S, Edlund C, Nord CE. Metronidazole is still the drug of choice for treatment of anaerobic infections. Clin Infect Dis 2010;50 Suppl 1:S16–S23. ArticlePubMed
2. Ahmed A, Loes DJ, Bressler EL. Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy. Neurology 1995;45(3 Pt 1):588–589. ArticlePubMed
3. Rao DN, Mason RP. Generation of nitro radical anions of some 5-nitrofurans, 2- and 5-nitroimidazoles by norepinephrine, dopamine, and serotonin. A possible mechanism for neurotoxicity caused by nitroheterocyclic drugs. J Biol Chem 1987;262:11731–11736. ArticlePubMed
4. Choi HC, Oh SY, Shin BS, Seo MW, Kim YH. Metronidazole-induced reversible cerebellopathy. Res Vestibul Sci 2009;8:132–136.
5. Sørensen CG, Karlsson WK, Amin FM, Lindelof M. Metronidazole-induced encephalopathy: a systematic review. J Neurol 2020;267:1–13. ArticlePMCPDF
6. Ko KK, Seo JH, Kim J, Song HS. Spontaneous downbeat nystagmus in metronidazole-induced encephlaopathy. J Korean Neurol Assoc 2013;31:138–139.
7. Eggers SDZ, Bisdorff A, von Brevern M, et al. Classification of vestibular signs and examination techniques: Nystagmus and nystagmus-like movements. J Vestib Res 2019;29:57–87. ArticlePubMedPMCPDF
8. Choi JY, Kim JH, Kim HJ, Glasauer S, Kim JS. Central paroxysmal positional nystagmus: characteristics and possible mechanisms. Neurology 2015;84:2238–2246. ArticlePubMed
9. Yacovino DA, Cherchi M. Clinical spectrum of positional downbeat nystagmus: a diagnostic approach. J Neurol 2025;272:163. ArticlePubMedPDF
Positional downbeat nystagmus in metronidazole-induced cerebellar toxicity: a case report
Fig. 1. T2-weighted and fluid-attenuated inversion recovery axial brain magnetic resonance imaging findings. (A) Symmetrical high signal intensity (SI) in the bilateral tectal plate (yellow arrows). (B) High SI in the bilateral dentate nuclei prior to treatment (red arrows). (C) One-week follow-up image after discontinuation of metronidazole, showing improvement of the tectal plate lesions. (D) One-week follow-up image after discontinuation of metronidazole, showing resolution of the dentate lesions.
Fig. 1.
Positional downbeat nystagmus in metronidazole-induced cerebellar toxicity: a case report
KBS
, Hyun Ah Kim1,2
PubReader
ePub Link
Cite
XML Download
