Related Experiment Videos
Neurotoxicity of intrathecal gentamicin: a case report and experimental study
Abstract:
Distinctive lesions occurred in the brainstem of a 59-year-old patient who had had recent Pseudomonas aeruginosa meningitis treated with parenteral and intrathecal gentamicin sulfate. The lesions were multiple, minute, and discrete, and were characterized by loss of axons, spongiosis, axonal swelling with frequent calcification, loss of astroglia and oligodendroglia, and slight inflammatory response. These lesions were restricted to the myelinated fiber bundles of the pons and mesencephalon. Because similar lesions can occur with other intrathecally administered medications and emboli to the brain, an experimental study in rabbits was done. Similar lesions were produced in normal adult rabbits after a single intracisternal injection of gentamicin sulfate with or without preservative at doses equivalent to 50 and 100 times the human therapeutic dose. Lesions were not seen after injection of normal saline, preservative, or gentamicin sulfate with preservative at doses equivalent to 1 and 10 times the human therapeutic dose. A direct relationship was observed between the cerebrospinal fluid concentrations of gentamicin, brain tissue concentrations of gentamicin, and occurrence of the lesions.
Insights
High-dose intrathecal gentamicin sulfate can cause brainstem lesions, including axonal damage and calcification. This risk is dose-dependent, as shown in a rabbit study following meningitis treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Intrathecal gentamicin sulfate is used to treat bacterial meningitis.
- Previous reports suggest potential neurotoxicity with intrathecal medications.
Observation:
- A patient developed distinctive brainstem lesions after treatment for Pseudomonas aeruginosa meningitis with intrathecal gentamicin sulfate.
- Lesions included axonal loss, spongiosis, swelling, calcification, and glial cell loss in the pons and mesencephalon.
Findings:
- Experimental administration of high-dose gentamicin sulfate (50-100x human therapeutic dose) to rabbits induced similar brainstem lesions.
- Lower doses (1-10x) and control substances (saline, preservative) did not cause lesions.
- A direct correlation was found between gentamicin concentrations in cerebrospinal fluid and brain tissue, and lesion development.
Implications:
- High-dose intrathecal gentamicin may pose a risk of neurotoxicity, specifically brainstem lesions.
- Careful dose monitoring and consideration of alternative treatments may be warranted.
- Further research into the mechanisms of gentamicin-induced neurotoxicity is needed.