shows that the 21 cases were impaired by a variety of etiologies including congenital malformations such as Mondini and CHARGE associated cochlear malformation, and acquired diseases such as viral labyrinthitis. The subjects included 11 males and 10 females ranging in age from 0.6 to 92 years at the time of death. There was a wide range of the duration of deafness that varied between a few months in cases 13 and 3 to more than 80 years in cases 7 and 10.
While the medical history of each patient described a symmetric and profound hearing loss, audiometric test results were available in only 10 cases and are presented in . One of the case selection criteria applied to those subjects with acoustic test results was a symmetric hearing loss: a maximum 10 dB difference in hearing threshold between ears at each frequency eliciting a response. This criterion is easily applied to cases 11 and 16 where response thresholds were measured at each frequency tested. In the other eight cases with audiometric results, the subjects did not respond at the maximum acoustic intensity (indentified by the subscript to the no-response [NR] entries) at some frequencies. In these cases both the response threshold and no-response entries were symmetric across ears and the hearing loss was considered symmetric. For example, the thresholds measured for 250 and 500 Hz in case 8 were within 10 dB across ears and no response was elicited in either ear for frequencies 1,000 to 8,000 Hz for acoustic intensities up to 100 dB (NR100).
gives the segmental and total SGC counts for each subject’s right and left ears. The range of SGC counts across subjects for both segmental and total counts is large. In Case 16, not a single SGC was identified in any section of either ear, but 18,108 SGCs were counted in the left ear of case 6. Even in cases impaired by the same etiology, the number of SGCs may differ significantly across subjects. Case 2 and 21 both suffered an impairment of recent origin from neomycin ototoxicity, but the across-subject difference in the total SGC count was more than 5000 for both the left and right ears. It should be mentioned that the counts represent the number of SGCs at the time of death which was sometimes long after the last audiological measurements. For example this period for case 11 was 25 years but in case 16, in which there were no SGCs at the time of the patient’s death, the hearing threshold measured 65 dB at 500 Hz one and half years before death. Interestingly, in case 13, the number of SGCs was fewer on the side in which the cochlea had 1.5 turns where 20 SGCs were counted whereas the other side with 1 turn had 2190 SGCs.
Corrected segmental and total SGC counts of 21 subjects with profound hearing loss.
Mean right and left SGC counts (with standard deviations) are plotted by segment in . The means for the right and left ear in each segment and for the total were very similar. In general, the segment II counts tend to be higher than the other segment counts.
lists the differences between the left and right SGC counts (segmental and total) for each subject. The differences within a column tend to be evenly distributed between negative (right count > left count) and positive (left count > right count), and the column means are relatively small suggesting that right-ear counts are not consistently larger or smaller than left-ear counts. The results in show that the mean difference in SGC count associated with each column of is not significantly different than zero (all p-values>0.05). This is consistent with the left-ear and right-ear counts being similar within a subject as can be seen in the scatter plots with regression lines plotted in .
Segmental and total count differences of 21 subjects: Left -Right
Comparison of segmental and total mean counts in paired groups by t-test
Analyzing the results by whether or not the subject’s hearing status was documented audiologically did not reveal significant differences between the two subpopulations for total SGC count or for the counts made for segments II–IV. For example, the mean magnitude of the total left-right count differences for the subjects with audiological data (555 SGCs) was not significantly different from the mean for subjects without audiological measures (692 SGCs; t=−0.57, df=17, p=0.57). In the case of segment I (cochlear base), however, the mean magnitude of the left-right count difference was significantly greater (t=2.89; df=14; p=−.01) for subjects without audiological documentation (481 SGCs) than for subjects with documentation (199 SGCs).
The correlations between left-ear and right-ear SGC counts are high (R2>0.89) and very significant (all p-values < 0.0001) for the total count and all segmental counts except for segment I. The coefficient of determination (R2 =0.645) for the segment I counts is lower but significant (p<0.0001) and the range of counts across subjects is considerably smaller than the other segments (see ). When the results for subjects with and without audiological documentation were analyzed separately, the high (R2>0.89) and significant (p<0.0001) correlations found in the combined-subjects analyses were maintained for each subgroup for total count and segmental counts II–IV. In the case of segment I, the correlation between the left-ear and right-ear counts was substantially weaker for the subgroup without audiological documentation (R2=0.39; p=0.038) than the subgroup with documentation (R2 =0.90; p<0.0001). When the segmental counts are combined to produce a total count and the subject subgroups combined, the correlation between the right and left ears is especially strong with the variance in one ear accounting for 98% of the count variance found in the opposite ear.
The relatively small mean differences and high correlation between the left and right SGC counts are both consistent with a research strategy using one ear as a control for the other. However, the relatively large standard deviations listed in for the differences and the degree to which some individual points diverge from the diagonal lines in emphasize the desirability of using statistical power analysis to guide the selection of sample sizes. illustrates how to evaluate the statistical power (sensitivity) implied by the results using plots of minimum effect size (minimum mean difference between the SGC counts of the control and treatment ears required to reach significance) as a function of sample size (number of subjects for whom right and left temporal bones are available) for a set of standard parameters.
Consider, for example, the bottom panel of that represents computations based on our data for total SGC counts. In this panel: the error variance was estimated by the standard deviation of 845 listed in ; α=0.05 (a 5% chance that differences greater than the minimum effect size are due to chance); and power=0.95 (95% likelihood a real difference will be recognized as significant). Thus if we have a sample of 10 temporal bone pairs, moving vertically from the x-axis at the 10-subjects position to the filled circle and then horizontally, we intersect the y-axis just above 1000 SGCs. This means that a treatment effect (difference between the SGC counts for the control and treatment ears) greater than 1000 is very likely to be detected and found to be significant in a sample of 10 subjects drawn from a population like the one represented by this study.