Module 14 · Disease pages

Ototoxicity

Aminoglycosides, platinum agents, monitoring strategies
Clinical vignette
A 64-year-old man with cystic fibrosis has had multiple intravenous tobramycin courses over the past decade for pulmonary exacerbations. He describes 18 months of slowly worsening unsteadiness and oscillopsia when walking. Bedside head impulses are abnormal in both directions. vHIT shows bilateral reduction of all six canals: lateral 0.28 and 0.30, anterior 0.45 bilaterally, posterior 0.52 bilaterally, with overt saccades throughout. Hearing is preserved.
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What it is

Vestibulotoxicity is the dose-dependent destruction of vestibular hair cells by certain systemic medications. The clinically dominant culprits are the aminoglycoside antibiotics — particularly gentamicin and tobramycin — though platinum chemotherapy (cisplatin, carboplatin), loop diuretics, and a handful of less common agents can also cause it. The classic presentation is bilateral progressive vestibular loss without (or before) hearing loss, in a patient with a documented history of exposure.

Aminoglycoside vestibulotoxicity — why and how

Aminoglycosides selectively concentrate in cochlear and vestibular hair cells, where they generate reactive oxygen species that destroy the stereociliary bundles and ultimately the hair cells themselves. Vestibular toxicity often precedes hearing loss, particularly with gentamicin and tobramycin — gentamicin is preferentially vestibulotoxic, streptomycin is severely vestibulotoxic and was historically used to deliberately ablate the vestibular system in Meniere disease, while amikacin and tobramycin are more balanced. Onset can be delayed weeks after the last dose, and damage is largely irreversible[Aw ST 2008].

The vHIT signature

The hallmark is bilaterally reduced gain in all six canals, often with the lateral canals most severely affected. Saccades are typically overt because compensation cannot fully develop when both sides are affected symmetrically. The pattern below shows a severe case.

Aminoglycoside vestibulotoxicity — six-canal panel
0100200R latg=0.280100200L latg=0.300100200R antg=0.450100200L antg=0.460100200R postg=0.520100200L postg=0.50
Severe symmetric reduction across all six canals with bilateral overt saccades. Hearing was preserved. Pattern characteristic of aminoglycoside-induced bilateral vestibulopathy.

Monitoring during aminoglycoside therapy

Patients receiving prolonged or repeated aminoglycoside courses — particularly cystic fibrosis patients, those with endocarditis, multidrug-resistant tuberculosis patients — are candidates for vestibular monitoring. The traditional monitoring was annual or biannual calorics, but vHIT is more practical: it can be performed at the bedside in minutes, costs less, and can detect Type I hair cell damage earlier than calorics (the irregular Type I afferents are the most sensitive to aminoglycoside damage[Aw ST 2008]). A practical regimen is baseline vHIT before therapy and serial testing every 3–6 months for patients on chronic courses. A 0.15 reduction in lateral canal gain compared to baseline (even if still within normal range) is a meaningful change and should prompt review of the drug.

Key teaching points

  • Bilateral symmetric reduction across all six canals + overt saccades + preserved hearing + aminoglycoside exposure = vestibulotoxicity.
  • vHIT can detect Type I hair cell damage earlier than calorics and is the practical monitoring test for patients on prolonged courses.
  • A 0.15 drop from baseline lateral canal gain is a meaningful change even if values remain "normal".
  • Mitochondrial m.1555A>G predisposes to severe ototoxicity; relevant family history matters.

References

  1. Aw ST, Todd MJ, Aw GE, Weber KP, Halmagyi GM. Gentamicin vestibulotoxicity impairs human electrically evoked vestibulo-ocular reflex. Neurology 2008;71:1776–82. doi:10.1212/01.wnl.0000335971.43443.d9
  2. Strupp M, Kim JS, Murofushi T, Straumann D, Jen JC, Rosengren SM, Della Santina CC, Kingma H. Bilateral vestibulopathy: diagnostic criteria consensus document of the Classification Committee of the Bárány Society. Journal of Vestibular Research 2017;27:177–89. doi:10.3233/VES-170619
  3. MacDougall HG, McGarvie LA, Halmagyi GM, Curthoys IS, Weber KP. The video head impulse test (vHIT) detects vertical semicircular canal dysfunction. PLoS One 2013;8:e61488. doi:10.1371/journal.pone.0061488
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