Understanding the physiology of bilateral damage to the vestibular system including gentamicin induced damage and age

Timothy C. Hain, MD

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It is well accepted that inner ear function -- including both hearing and balance declines with age. The reason for this is that the ear wears out and has no repair mechanism. It contains moving parts - -hair cells -- which gradually die off with age. It is estimated that half of inner ear function -- and in particular vestibular ganglion cells -- are lost by the age of 80. Counts of vestibular ganglion cells probably oversimplifies the entire functional deficit.



As shown above, the gain of entire system would be best represented by a cascade of [hair cells][nerve transmission][Central gain].

The timing of the system is not represented - - the central vestibular system has the ability to perseverate output from the nerve, accomplishing roughly a 3 fold increase in the "DC" response, but no effect on the high-frequency "AC" response.

Vestibular reserve

Most of our body systems can withstand considerable damage before causing a significant functional decline. For example, we have two of most things -- two eyes and 2 ears for example -- and often we can lose one of them without losing our ability to work and function in the community. Similarly, with the inner ear balance function, most people continue to work after losing half of their vestibular function to a process such as vestibular neuritis . Thus there may be a 50% vestibular reserve -- up to which people do fairly well, and after losing more function, they perform more poorly in their work and activities of daily life.

Against this idea is the well known observation that the timing of their vestubular responses changes - -persons who have lost half of their vestibular sensors perform worse with low-frequency stimuli. An example of this is here (look at rotatory chair responses).

Practically however, most persons who age continue to have nearly normal rotatory chair responses (and caloric responses). On the other hand, otolith related responses (e.g. VEMPs) deteriorate much more rapidly. Roughly half of the response is gone by the age of 60.

The resiliance of rotatory responses may have to do with redundancy in the vestibular apparatus -- all of the sensors in the canals "do the same thing". On the other hand, the otolithic sensors do something different things as they are "circularly polarized", and are also far more vulnerable. If we say (roughly) that the otoliths have to resolve 360 degrees of motion while the canals only have a single axis of rotation to deal with, the otoliths have far less neural circuitry to lose.

Following along with this line of thought, the semicircular canals should be resiliant to damage and age because each of the 3 canals has lots of hair cells that do roughly the same thing. You can lose 50% of your one of the three canals hair cells, and after some readjustment, carry on fairly well with the other 50%, because they all do the same thing (this is an oversimplification).

On the other hand, the otoliths should be vulnerable to damage and age, because the utricle and saccule have to resolve 360 degrees of rotation. Their amount of redundancy is reduced by a factor of 360. A second reason that the otoliths should degrade is that their design is much more vulnerable -- hair cells with stones on the top, are subject to a lot more force (f=ma), than vestibular hair cells that are being pushed back and forth by fluid pressure.

We made an attempt to compute the total vestibular reserve in a recent article (Hain et al, 2018). A reasonable estimate of the total vestibular reserve can be computed by multiplying the VOR gain and Time constant from rotatory chair testing. By looking at data in the literature, one can estimate the effect of age.

Gain-TC vs age

Baloh and associates reported the gains and time constants of the VOR in a study of 75 “elderly” normal people, averaging 79.6 years old, who were compared to 25 normal younger people, averaging 26.2 years old (Baloh et al., 1993). Their data results in a GainTc product of 9.5 for the younger subjects, and 6.8 for the older subjects, from which it can be calculated that the slope of the GainTc/year is -0.051/year.

Similarly, Paige (Paige, 1992) reported gain and phase data in 30 “young” (18-44) and 23 “Middle-Aged” (45-69), and older subjects whose average age was 79.5. The GainTc products for the 0.025Hz -- 50 deg/sec stimulus, similar to our methodology, were computed to be 13.23 and 10.07 for young and middle-aged, respectively, resulting in a slope of -0.12 deg/year.

Both of these analyses suggests that the GainTc product declines slowly with age, but the data of Paige suggests a greater slope.

There are numerous other studies of VOR gain and Tc vs age. While the gain tends to vary little, the time constants tend to be very variable, and depend greatly on method. This makes it difficult to draw inferences about age related deterioration. The dependence on method suggests that the assumption of linearity in vestibular responses may not be accurate in the older population.

There are presently 2 other well established measures of vestibular function - - caloric testing and VHIT. While there are many other things to consider, here are our thoughts.

Caloric total response -- a normal young person has roughly 100 deg/sec of total response. This corresponds roughly to 100% vestibular function. Here the term "function" is an important one, as this presumably reflects the combination of hair cells, nerve, and central plasticity all casaded. One might lose one ear, dropping one's total response from 100 to 50, and then have a compensatory process proceed that raises the response on the remaining ear to 75. Thus the caloric total response might reasonably underestimate peripheral vestibular damage. From a systems perspective, this is oversimplified. Caloric responses probably are mainly a measure of the low-frequency vestibular response. We don't understand entirely the mapping between total caloric responses, and vestibular loss as quantified by the product of [hair cell][vestibular nerve]. This could be worked out by simply comparing total responses in patients with well documented unilateral loss, such as due to tumors or severe vestibular neuritis.

The VHIT test is not a good way to estimate residual vestibular function, because it is confounded by compensation. You should just not even try. The VHIT only measures high frequency gain, which is ferociously defended by compensatory processes. One can lose half of one's vestibular function, and the VHIT may be unaffected.


As the normal central vestibular system has an ability to partially compensate for about 50% loss, by the age of 80, a very rough guess would be that the vestibular ganglion and vestibular nucleus processes can be completely compensated for. In other words, if the vestibular nerve drops to 0.5, the central gain goes up to 2.0, making the whole process a wash. This fits well with the general observation that vestibular rotatory chair responses are largely unaffected by age.

This would leave the "healthy" 80 year old the problem of dealing with hair cell deterioration (counts are roughly 30% down by the age of 80). In other words, an entirely healthy person should start to develop functional vestibular problems (for high frequencies) a little before the age of 80. There are some logical problems -- while the system does "compensate" for high frequency gain, the low-frequency responses are lost. Thus a "compensated" person should not expect restoration of normal function. It is always better to have the original equipment.

How rapidly does it decline ? While there are many studies of hearing function, little is understood about vestibular decline. Cell counts of both nerve cells and hair cells are generally found lessened in older persons (although not everyone agrees). As neither hair cells or vestibular neurons regenerate, and both are subject to wear and tear, it seems highly likely that there is a gradual decay in vestibular function.


Impact of vestibular damage

Here is a rough mapping between the amount of vestibular loss, and expected impairments, using anchor points which are well known. This is based on the author's clinical experience. Using the more recent

% Loss symptom
0 None, normal
50-70 Borderline, mildly unsteady
70-90 mild oscillopsia, reluctant to drive in dark
90-100 Oscillopsia, sensory ataxia, moderately unsteady

Impact of gentamicin

Ones estimate of the impact of gentamicin induced reduction of vestibular input depends on how one views the impact of vestibular input on balance in general. It is well known that balance declines with age, and very rapidly from approximately 80 onward. However, is this decline due to a rapid reduction in vestibular function (in parallel with hearing), or is it due to a combination of many factors -- reduced vision, reduced somatosensation, reduced vestibular input, poorer central integration, and poorer motor output ?

In our view, while it is reasonable to suppose that other factors than vestibular function impact balance, there is quite good evidence for reduced hearing, and because of this, we think that vestibular disturbances, especially from the otoliths, are probably very important, and may dominate the process.