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Recovery from Gentamicin Ototoxicity

Timothy C. Hain, MD. Page last modified: October 6, 2013

This page provides more detail about prognosis and recovery of vestibular function from gentamicin ototoxicity. Please see the main page on Gentamicin also.

Prognosis

In general the message is modestly encouraging. People recover from ototoxicity, although the process is slow and usually incomplete.

Usually improvement is quantified by objective testing, such as rotatory chair (best) or caloric testing(fair). This approach does have a pitfall in that the testing just measures the overall result of damage and compensation together. In other words -- suppose that the vestibular system had dropped by 75%, but compensation provided a doubling of central gain. Then one would functionally be at (100%-75%)*2 = 50% loss. This status would provide one with fairly good vestibular reflexes, but ones vestibular reserve would be completely used up. It seems likely that having a vestibular reserve is useful in responding to future damage. We don't know of any research that addresses this question.

 

Two rotatory chair test results from patient with gentamicin ototoxicity, with treatment occuring one year before first rotatory chair test. Thus the first test is at year one, and the second at the end of year 2.

 

The majority of the improvement occurs at high-frequencies on rotatory chair testing -- high-frequency gain usually returns to normal after several years, but remains depressed for lower frequencies.

On caloric testing, there may be substantial recovery too.

ENG of patient with a good recovery from gentamicin. This panel shows poor caloric function after gentamicin toxicity experienced in 2005

This panel shows low-normal vestibular function (worse on right) roughly 1 1/2 years post gentamicin.

(Examples courtesy of Dr. Dario Yacovino)

Timing of testing

All vestibular tests (caloric or rotatory chair), are generally at their worst at 3 months (although sometimes it takes a year). Testing done prior to 6 months may underestimate the degree of damage. By the same token, testing done at 3 months may overestimate the long term damage. Decisions are best made on the test at 1 year. To establish long term prognosis, a rotatory chair test done after 2 years is important.

Occupation:

Progression of vestibulotoxicity can occur for months after the last dose, and recovery can be measured out to a year or even longer (Black et al, 2001).

Generally a person who is working at a "desk job" prior to gentamicin toxicity, is ultimately able to return to that job. Person's whose occupations require extra-good balance such as persons in the construction industry may be unable to function in their previous capacity. Ototoxicity is often accompanied by difficulty in multitasking - -attributed to having to use part of one's brain to balance and see. This aspect makes it unusual for someone with gentamicin toxicity to return to a high-level administrative job. A discussion of prognosis in 35 patients was reported by Gillespie and Minor (1999).

Gentamicin toxicity, by itself, never causes so severe imbalance as to require a wheelchair on a permanent basis -- if one is necessary, it is generally only in the first year. Gentamicin toxicity combined with other conditions -- such as peripheral neuropathy, or visual impairment, can result in being wheelchair dependent.

Activity and vestibular rehabilitation speed recovery. Additional exposure to ototoxins, a sedentary life style, and habitual use of sedative medications (such as amitriptyline or diazepam) probably slow recovery.

 

Mechanism

Progression of vestibulotoxicity can occur for months after the last dose, and recovery can be measured out to a year or even longer (Black et al, 2001). Recovery likely is related to a combination of several factors:

1) Some "sick" inner ear hair cells get better. Nobody knows exactly how many inner ear hair cells are sick rather than being dead, but it seems reasonable to assume that they are not all dead, but that some remain but are not functioning at top-efficiency. In experimental animals (rodents), hair cells may lose their motion sensitive processes (stereocilia), but still survive (Zheng et al, 1999; Oei, Segenhout et al. 2004; ). This may also happen in humans. As gentamicin persists in the ear of animals for somewhere between 80 days and a year, recovery from this process might reasonably stretch over the same time frame.

2). The brain adapts to the missing inner ear information. Certainly people adapt to missing sensory input using plasticity, substitution of other senses, anticipation and behavioral changes. It has recently been suggested that the typical recovery seen on rotatory chair testing at very high-frequencies is usually due to sensory substitution rather than vestibular recovery. There is little if any evidence that plasticity can adapt to any more than a 50% loss of vestibular function. As mentioned above, compensation probably uses up ones "reserve".

3). With a great deal of skeptisism, it is fair to say that here may be a little bit of regeneration occuring. Birds can regenerate their hair cells, and although it was felt for a long time that people can't do this, there is a small amount of evidence that some regeneration does occur. At present, it is not felt that regeneration is a significant factor in recovery in humans. However, this is a very promising area for research right now.

4). Nerve axons sprout and innervate surviving hair cells. We know of no data concerning this idea.

 

Other information:

 

 

Copyright March 24, 2014 , Timothy C. Hain, M.D. All rights reserved. Last saved on March 24, 2014