Timothy C. Hain, MD
Return to Index. Gentamicin ototoxicity page. Dizziness in the Elderly Please read our disclaimer. Last revision: September 18, 2010
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.
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 are reasonably well matched to cancel each other out, leaving 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.
|Simulation of exponentially decaying vestibular function with age (c) Timothy C. Hain, M.D. Also on this plot is a simulation of the effect of a course of gentamicin. See the text for a commentary about decay functions.|
Processes that depend on random events often decay exponentially, and as a first default assumption, it seems reasonable to hypothesize that this is also the case with vestibular function. To put this into mathematical terms, the t-1/2 for vestibular decay is 80 years. The rate of exponential decay is highest at onset -- thus decline would be slower for this conjecture as people age.
Other reasonable possibilities might be a linear decline, or a decline that accelerates with age. The exponential decay hypthesis assumes that there is no "history", but that cells just die at random. As there are less cells to die, the rate of decline slows down. The "linear decay" idea might suppose that cells just die off in proportion to their age -- some are tougher and last longer. Or it might be due to a combination of random (exponential) decay and another process (like wearing out) that accelerates cell death over time.
Another way to think about it is that hair cells and neurons are getting "old", more fragile, and are more prone to die off. In other words, instead of a slower decline in vestibular function with age, it might speed up. This would fit with clinical observations that balance declines very rapidly from the age of 80 onward, and also fit to some extent with theories of aging having to do with accumulating damage to mitochondria. This assumption might convert the exponential decay process to a linear one, or perhaps a reverse exponential decay. If one made this assumption, then the shape of the curve above would be "flipped" -- function would be nearly normal until roughly 60, and then start to fall off rapidly. One might simulate this by assuming a combination of a random process (exponential decay), combined with a gradually increasing fragility of hair cells (a dynamically changing likelihood of cell death). This conjecture is in the family of "nonlinear" hypotheses, which are common in biological systems, but uncommon in engineering processes such as circuit design.
In essence, the difference between these two ideas is to ask - - which process dominates -- is there a random "hit" die off of vestibular cells and neurons, or does the vestibular system get more fragile with age, and therefore decline accelerates ?
At the moment, there is simply insufficient data to say which of these general conjectures are correct.
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 vestibualr perform worse with low-frequency stimuli.
An example of this is here (look at rotatory chair responses).
There are presently 2 well established measures of vestibular function - - caloric testing and rotatory chair testing. While there are many other things to consider, roughly one can estimate remaining vestibular response in this way:
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 unilalteral loss, such as due to tumors or severe vestibular neuritis.
Rotatory chair -- gain and time constant. The peak gain and the slope of the gain vs frequency curve is another way to estimate remaining vestibular function. Peak gain is useful only for severe loss -- someone with a 100% loss has no gain at any frequencies, including high frequencies (gain of 0). Gain slope is the most useful method of estimating function when high-frequency gain is normal (which is often the case). It seems to us (without any data), that the rotatory chair data should be a more accurate way of estimating vestibular "function", as the time constant can decline even when the gain remains normal. In other words, the rotatory chair test output, covering more frequencies than the caloric test (which is DC), could encode more information concerning function.
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:
|50-70||Borderline, mildly unsteady|
|70-90||mild oscillopsia, reluctant to drive in dark|
|90-100||Oscillopsia, sensory ataxia, moderately unsteady|
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 are probably very important, and may dominate the process.