modern otoneurosurgical techniques and methods of radiotherapy ( such as the use of -rays , the  gamma knife ) make it possible to remove small acoustic neuromas without affecting hearing thresholds , even when the patient s hearing sensitivity is normal [ 15 ] . however ,
to effectively use these techniques , one must detect acoustic neuromas or tumors of the cerebellopontine angle at a very early phase , when their size does not exceed 1 cm in diameter .
for this reason , the key issue is to use screening methods with high sensitivity and specificity , and diagnostic methods that allow for early detection .
electrophysiological methods satisfy these requirements , and are often based on recording auditory brainstem responses ( abrs ) or using magnetic resonance imaging with gadolinium ( mri - gd ) .
because of the increased accessibility of mri examinations and its high sensitivity for diagnosis of small acoustic neuromas , some researchers have in recent years developed the view that to detect small acoustic neuromas ( smaller than 1 cm ) one may give up abr testing altogether and rely only on mri . however , taking economic considerations into account , many authors still believe that a combination of abr and mri methods remains a better option [ 6,810 ] at the same time , clinical symptoms in retrocochlear pathologies are not very specific , so it is difficult to accept that one should directly refer all patients with a suspected retrocochlear pathology for an mri examination  because mris are much more costly than abr tests ( in polish conditions approximately 6 times more expensive ) .
such a process would lead to a large number of false - negatives , low predictive value , and significantly increased diagnostic cost .
additionally , one can not overlook the problem of claustrophobia in some patients , who are reluctant to subject themselves to mri examination . on this basis
, it still seems reasonable to adopt a two - stage procedure in which all patients suspected of having a retrocochlear pathology are first subjected to an abr examination and then followed up with an mri examination at a second stage if necessary [ 2,1012 ] .
obviously , the abr method used must satisfy the criteria for an efficient screening method : it must have high sensitivity and specificity , and be inexpensive and easy to apply on a large scale . in the case of acoustic neuromas and tumors exceeding 1
cm , the standard abr method ( abr std ) , which relies on click - evoked responses , has very high sensitivity ( over 95% ) and high specificity .
however , if the size of the tumor is less than 1 cm , sensitivity of the abr std method drops quickly , according to some authors to 85% , or even to 63% .
because of this limitation , researchers have for many years been seeking an abr method which , with appropriate stimulus and analysis , might give enough sensitivity to detect small tumors .
one successful approach has come from the investigations of don , who has developed the so - called stacked abr method .
its most important feature is very high sensitivity in detecting small tumors , comparable to that of the mri method [ 1518 ] the method is based on the recording and registration of so - called derived band responses that originate from narrow segments of the basilar membrane , and which can be obtained by applying a masking technique employing high - pass filtered noise .
such an approach provides an integrated response , the stacked abr , which represents activity of the whole cochlea as generated by nearly all auditory nerve fibers .
deterioration of transmission through any group of fibers ( e.g. , that resulting from pressure from an acoustic neuroma ) significantly decreases the amplitude of the integrated response . however , popularity of the stacked abr method is limited by the fact that it is more troublesome and time - consuming than a standard abr examination , and because the availability of commercial abr - measuring devices equipped with a stacked abr option is poor .
yet another disadvantage of the method is that it is based on measuring wave v amplitudes , which have high variability and low repeatability .
the result is that the stacked abr method , despite its obvious advantages , is very rarely used in clinical practice .
an attempt to replace the time - consuming registration of derived - band responses used in the stacked abr method by much more easily obtained responses evoked by tone - bursts was undertaken by philibert and co - workers .
although tone - burst stimuli are not as often used as click stimuli , their usefulness in electrophysiology is well documented [ 2225 ] .
the comparison done by philibert showed that the basic characteristics of the stacked abr waveforms are similar , regardless of whether one uses the derived - band technique or responses evoked by tone - bursts .
however , in the approaches used by both don and philibert , , the responses must be analyzed using the stacked - abr software , which is implemented in only one commercially - available device produced by bio - logic  natus .
the results achieved by don and philibert have encouraged other authors to develop their own methods of stimulation and analysis , free of the drawbacks of the stacked - abr method , but which could still provide early detection of small retrocochlear lesions in different groups of auditory nerve fibers [ 2730 ] . as this paper will attempt to show , there are reasons to believe that one satisfactory approach is a method developed by kochanek et al .   called the abr tp technique .
the method is based on registration of responses evoked by gaussian - shaped tone - pips with frequencies of 1000 , 2000 , and 4000 hz . the rise and fall times of these pips are twice as long as those used in standard abrs for objectively evaluating hearing threshold : for tone pips of 1000 and 2000 hz , the rise / fall times are 4 ms while at 4000 hz the figure is 2 ms .
times mean that the stimulus bandwidth is approximately halved , which improves frequency specificity and the ability to detect retrocochlear lesions . results of studies by many authors [ 3138 ] have shown that the increase in rise / fall time of a tone - pip leads to the reduction of wave v amplitude and increase in its latency .
this is because the auditory nerve impulses generated by such extended stimuli are averaged over a longer time , and effectiveness of averaging is poorer than in the case of a shorter rise time .
this can be explained by a decrease in synchrony of the averaged neural impulses , which in an extreme case may lead to total disappearance of the averaged response  despite the fact that the nerve potentials are still generated in auditory neurons .
then , considering the effectiveness of the averaging process , we may say that the responses to a tone - pip of a longer rise / fall time are poorly synchronized with the stimulus , compared to those evoked by a stimulus of shorter rise / fall times . it makes these responses weaker , as far as response amplitude is concerned , and more sensitive to different factors , such as reduction of stimulus intensity or retrocochlear pathology . in summary , using tone pips with relatively long rise / fall times ensures , on the one hand , adequate frequency specificity of the response , and , on the other hand , makes it more sensitive to disturbance of synchronization in the auditory nerve caused by the presence of a neuroma or other pathology . until recently ,
direct comparison of the three methods , evaluating their sensitivity , specificity , and predictive values , has not been done . from reports published so far
, it is known that both the stacked abr and abr tp methods have greater sensitivity than the standard abr std method in detecting small acoustic neuromas .
preliminary results comparing the specificity and selectivity of the three methods have shown that the stacked abr method offered very high sensitivity , approaching 100% . at the same time , however , it yielded the greatest number of false - positives , which made its specificity much lower than that of the other two methods .
a full assessment requires a comparative study on the same group of patients . in this way , it is possible to directly compare the clinical usefulness of each method for detecting retrocochlear impairments .
the aim of the study was to compare the sensitivity and specificity of three abr - based methods for early detection of retrocochlear impairments .
ideally , the comparison should lead to the development of an optimal procedure for screening for these pathologies .
the three abr methods evaluated were : method 1 : abr std , the standard abr method which makes use of click stimuli ; method 2 : stacked abr , the method developed by don from the house ear institute and based on derived - band responses ; method 3 : abr tp , the original method developed by kochanek and co - workers based on responses evoked by tone pips with relatively long rise / fall times .
the study was carried out on material consisting of 152 persons . the starting point for
the study was an evaluation of the results of magnetic resonance imaging ( mri ) with gadolinium ( gt1w mr images ) by 3 independent expert radiologists . on this basis ,
the examined subjects were divided into 2 groups : group nr : 123 persons ( 246 ears ) without retrocochlear impairments consisting of 62 men and 61 women aged between 19 and 66 years ( mean 36 years ) .
group r : 29 patients with retrocochlear hearing loss , 14 men and 15 women aged 22 to 66 years ( mean 44 years ) . among them
there were 22 cases of unilateral acoustic neuroma of size ranging from 2 mm in diameter to 2017 mm ( 13 small and 9 medium or large size ) and 7 patients with unilateral neurovascular conflicts .
the research procedures were approved by the ethics committee of the institute of physiology and pathology of hearing , poland . among the subjects in group
nr , there were 47 persons with normal hearing , volunteers recruited from employees of the institute of physiology and pathology of hearing , and 76 patients admitted to the institute for diagnostic examinations aimed at excluding possible retrocochlear pathology . in this latter group ,
the majority reported tinnitus , episodes of vertigo , or balance disorders . in 76% of cases ,
hearing thresholds were no higher than 20 db hl ; in the others , hearing thresholds were elevated but did not exceed 50 db hl over the frequency range 0.258 khz .
average hearing thresholds in both groups are listed in table 1 and illustrated in figure 1 . according to the guidelines for the stacked abr method by biologic , and to comply with the conditions required for the abr std and abr tp methods , we excluded from both groups cases of : conductive hearing loss , sensorineural hearing loss greater than 50 db hl , steeply sloping audiograms , and interaural audiometric threshold differences greater than 10 db ( the difference between average values calculated over the frequency range 0.58 khz ) . in all abr examinations , we used the system for registration and analysis of auditory evoked potentials aep navpro v. 6.2.0 ( biologic  natus ) which was equipped with hardware and software suitable for applying the stacked abr method .
non - disposable silver electrodes were placed at cz , ml ( left mastoid ) , and mr ( right mastoid ) , as recommended .
the tests were carried out in acoustic chambers . in the stacked abr method , we used the measuring procedure described in the literature [ 1518,26 ] for implementation in the aep navpro system . in the navpro system ,
most of the measurements are performed automatically , so there is no option for the user to modify the parameters or interfere with the procedure ( such as interrupting the measurement cycle or repeating a single registration ) .
the number of sweeps is determined by the system based on signal to noise ratio , and the averaging process is continued until the residual noise level reaches approx .
control by the user is limited to maintaining a low level of noise by minimizing disturbances , and correcting waveform fitting ( when the stacked abr response is created by summing derived - band responses )
. the result of a test ( positive or negative ) is determined automatically based on the stacked abr wave v amplitude ( a ) and/or interaural amplitude difference ( iad ) after comparing them with normative values .
normative values are taken to be 800 nv ( males ) and 875 nv ( females ) , with the normative relative interaural amplitude difference equal to 10% ( both genders ) . during registration of signals in the stacked abr method ,
care was taken to comply with the requirements laid down by the system manufacturer , in particular , maintaining an adequately low level of eeg background noise and eliminating other artifacts such as sensorimotor potentials . to this end , patients were seated in a comfortable , semi - reclining position , and instructed to keep their eyes closed and not to move during the tests ( many fell asleep after a few minutes ) . in cases of excessive noise and/or myogenic artifacts , the protocol was repeated .
examinations started with the abr std test ; in cases where we observed excessive disturbance and noise ( due to patient fatigue or restlessness ) the tests were postponed to the following day , otherwise , we continued with registration of stacked abrs , and then abrs evoked by tone pips ( the abr tp method ) .
registrations of auditory evoked potentials were performed once in every subject . in measurements with the abr std method
, we used a click stimulus of alternating polarity presented through tdh 39 ( telephonics ) earphones at a level of 90 db nhl with a repetition rate of 31/s .
the amplifier bandwidth was 1001500 hz , amplification 100 000 times , and analysis time 20 ms .
the number of sweeps required for each averaged response was between 512 and 1024 ( average approximately 750 sweeps ) ; 2 traces were registered for each ear to control repeatability of the response .
we measured the latencies of waves i , iii , and v and the inter - peak time intervals i  iii and iii  v ; interaurally , we measured latency differences of wave v and other inter - peak time intervals .
if the wave v interaural latency difference and/or the interaural difference in inter - peak time intervals exceeded 0.2 ms , the result was considered abnormal . the upper normal limit for wave v latency
, we used tone pips of gaussian envelope ( no plateau ) , whose rise and fall times were equal to 4 periods at 1000 hz and 8 periods at 2000 and 4000 hz . the stimuli had alternating polarity , a repetition rate of 31/s , and were presented through tdh 39 ( telephonics ) earphones . the amplifier bandwidth , amplification , and analysis time were the same as those used in the abr std method .
however , the number of sweeps required to obtain a well - averaged response was greater , ranging from approximately 800 to 1500 ( average 1550 sweeps ) .
two traces were registered for each stimulus in order to control repeatability of the response . in the tone - pip evoked responses we analyzed morphology of the waveforms ; latency of wave v , lv ; and the interaural latency difference of wave v ( it5 ) .
waveforms of evoked potentials recorded with abr std and abr tp were analyzed by 3 independent experts . the person who evaluated the results had no information about assessments made by the other experts . in a few cases of diverging opinions
statistical analyses were performed with statistica v.7.110.2 ( statsoft inc . , tulsa , ok , usa ) and matlab ( the mathworks , natick , ma , usa ) . for statistical analysis , we used descriptive statistics ( scatter plots , t - tests ) , generalized linear regression , nonparametric statistics ( kolmogorov - smirnov 2-sample test ) , and roc analysis for assessing screening test effectiveness . generally , we used a confidence level of p=0.05
the study was carried out on material consisting of 152 persons . the starting point for
the study was an evaluation of the results of magnetic resonance imaging ( mri ) with gadolinium ( gt1w mr images ) by 3 independent expert radiologists . on this basis ,
the examined subjects were divided into 2 groups : group nr : 123 persons ( 246 ears ) without retrocochlear impairments consisting of 62 men and 61 women aged between 19 and 66 years ( mean 36 years ) .
group r : 29 patients with retrocochlear hearing loss , 14 men and 15 women aged 22 to 66 years ( mean 44 years ) . among them
there were 22 cases of unilateral acoustic neuroma of size ranging from 2 mm in diameter to 2017 mm ( 13 small and 9 medium or large size ) and 7 patients with unilateral neurovascular conflicts .
the research procedures were approved by the ethics committee of the institute of physiology and pathology of hearing , poland . among the subjects in group
nr , there were 47 persons with normal hearing , volunteers recruited from employees of the institute of physiology and pathology of hearing , and 76 patients admitted to the institute for diagnostic examinations aimed at excluding possible retrocochlear pathology . in this latter group ,
the majority reported tinnitus , episodes of vertigo , or balance disorders . in 76% of cases ,
hearing thresholds were no higher than 20 db hl ; in the others , hearing thresholds were elevated but did not exceed 50 db hl over the frequency range 0.258 khz .
average hearing thresholds in both groups are listed in table 1 and illustrated in figure 1 . according to the guidelines for the stacked abr method by biologic , and to comply with the conditions required for the abr std and abr tp methods , we excluded from both groups cases of : conductive hearing loss , sensorineural hearing loss greater than 50 db hl , steeply sloping audiograms , and interaural audiometric threshold differences greater than 10 db ( the difference between average values calculated over the frequency range 0.58 khz ) .
in all abr examinations , we used the system for registration and analysis of auditory evoked potentials aep navpro v. 6.2.0 ( biologic  natus ) which was equipped with hardware and software suitable for applying the stacked abr method .
non - disposable silver electrodes were placed at cz , ml ( left mastoid ) , and mr ( right mastoid ) , as recommended .
the tests were carried out in acoustic chambers . in the stacked abr method , we used the measuring procedure described in the literature [ 1518,26 ] for implementation in the aep navpro system . in the navpro system ,
most of the measurements are performed automatically , so there is no option for the user to modify the parameters or interfere with the procedure ( such as interrupting the measurement cycle or repeating a single registration ) .
the number of sweeps is determined by the system based on signal to noise ratio , and the averaging process is continued until the residual noise level reaches approx .
6900 ) for each trace . control by the user is limited to maintaining a low level of noise by minimizing disturbances , and correcting waveform fitting ( when the stacked abr response is created by summing derived - band responses ) .
the result of a test ( positive or negative ) is determined automatically based on the stacked abr wave v amplitude ( a ) and/or interaural amplitude difference ( iad ) after comparing them with normative values .
normative values are taken to be 800 nv ( males ) and 875 nv ( females ) , with the normative relative interaural amplitude difference equal to 10% ( both genders ) . during registration of signals in the stacked abr method ,
care was taken to comply with the requirements laid down by the system manufacturer , in particular , maintaining an adequately low level of eeg background noise and eliminating other artifacts such as sensorimotor potentials . to this end , patients were seated in a comfortable , semi - reclining position , and instructed to keep their eyes closed and not to move during the tests ( many fell asleep after a few minutes ) . in cases of excessive noise and/or myogenic artifacts , the protocol was repeated .
examinations started with the abr std test ; in cases where we observed excessive disturbance and noise ( due to patient fatigue or restlessness ) the tests were postponed to the following day , otherwise , we continued with registration of stacked abrs , and then abrs evoked by tone pips ( the abr tp method ) .
registrations of auditory evoked potentials were performed once in every subject . in measurements with the abr std method
, we used a click stimulus of alternating polarity presented through tdh 39 ( telephonics ) earphones at a level of 90 db nhl with a repetition rate of 31/s .
the amplifier bandwidth was 1001500 hz , amplification 100 000 times , and analysis time 20 ms .
the number of sweeps required for each averaged response was between 512 and 1024 ( average approximately 750 sweeps ) ; 2 traces were registered for each ear to control repeatability of the response .
we measured the latencies of waves i , iii , and v and the inter - peak time intervals i  iii and iii 
v ; interaurally , we measured latency differences of wave v and other inter - peak time intervals .
if the wave v interaural latency difference and/or the interaural difference in inter - peak time intervals exceeded 0.2 ms , the result was considered abnormal . the upper normal limit for wave v latency
was assumed to be 6.2 ms . in the abr tp method , we used tone pips of gaussian envelope ( no plateau ) , whose rise and fall times were equal to 4 periods at 1000 hz and 8 periods at 2000 and 4000 hz . the stimuli had alternating polarity , a repetition rate of 31/s , and were presented through tdh 39 ( telephonics ) earphones . the amplifier bandwidth , amplification , and analysis time were the same as those used in the abr std method .
however , the number of sweeps required to obtain a well - averaged response was greater , ranging from approximately 800 to 1500 ( average 1550 sweeps ) .
two traces were registered for each stimulus in order to control repeatability of the response . in
the tone - pip evoked responses we analyzed morphology of the waveforms ; latency of wave v , lv ; and the interaural latency difference of wave v ( it5 ) .
waveforms of evoked potentials recorded with abr std and abr tp were analyzed by 3 independent experts . the person who evaluated the results had no information about assessments made by the other experts . in a few cases of diverging opinions
statistical analyses were performed with statistica v.7.110.2 ( statsoft inc . , tulsa , ok , usa ) and matlab ( the mathworks , natick , ma , usa ) . for statistical analysis , we used descriptive statistics ( scatter plots , t - tests ) , generalized linear regression , nonparametric statistics ( kolmogorov - smirnov 2-sample test ) , and roc analysis for assessing screening test effectiveness . generally , we used a confidence level of p=0.05
to illustrate the usefulness of each method for early diagnosis of retrocochlear impairment , examples of test results are presented in figures 2 and 3 .
these results were obtained from the 3 abr - based methods in otologically normal males ( figure 2 ) and in patients with confirmed retrocochlear pathologies ( figure 3 ) . in figure 2 ,
retrocochlear processes were excluded by mri - gd examination . in both cases , results of examination with abr std and abr tp were normal ( negative ) .
interestingly , however , the result of examination with the stacked abr method was abnormal ( positive ) in both subjects .
in the first case , ( a ) , the stacked abr wave v amplitude was below the limit of the norm , and in the second case , ( b ) , despite a high stacked abr wave v amplitude , the result of the test was abnormal ( positive ) because of an excessively high interaural amplitude difference ( iad > 10% ) .
figure 3 shows examples of tests done with the 3 abr methods in patients with radiologically - confirmed small ( < 1 cm in diameter ) acoustic neuroma . in patient
a , the result of the abr std method was normal ( negative ) , but results obtained with the abr tp and stacked abr methods were both abnormal ( positive ) . in patient b , results were abnormal in all 3 methods , but in this patient ( a male ) , stacked abr wave v amplitudes in both ears were normal ( greater than 800 nv ) and only the interaural amplitude difference ( iad=42% ) exceeded the norm .
these examples indicate that the stacked abr method might not be a reliable tool for assessing retrocochlear pathologies because of apparent random variability of stacked abr amplitude observed in both normal - hearing and pathologic ears .
table 3 shows results of the three abr methods applied in the two groups of 148 subjects ( n=296 ears ) .
numbers indicate positive results ( true positive , tp , and false positive , fp ) , and negative results ( true negative , tn , and false negative , fn ) .
also shown are calculated values of sensitivity , sen , specificity , spe , and positive predictive value , ppv = tp/(tp+fp ) of each method . the same data are plotted in graphical form in figure 4 . in assessing the stacked abr method
, we applied normative values of stacked wave v amplitude as assumed in the aep navpro system ( 800 nv for males and 875 nv for females ) . the supplementary criterion based on interaural amplitude difference iad ( iad < 10% for the norm )
was not taken into account . because of limited sample size , the values of sensitivity and specificity carry uncertainty .
confidence intervals shown in the table are based on the assumption that the number of tp and tn results are independent random variables that follow a binomial distribution , with probability of success equal to sen and spe , respectively , and the number of trials is equal to the number of ears with and without pathology , respectively .
, one may estimate the interval of uncertainty for positive predictive value ( ppv ) .
one can see that the stacked abr method gives the highest sensitivity ( well over 90% ) .
unfortunately , this sensitivity is obtained at the expense of specificity , which is extremely low , and therefore the positive predictive value is also low .
this is due , among other things , to the significant variability of stacked abr amplitudes ( illustrated in the examples of figures 2 , 3 ) , which leads to a large number of false positives .
detailed analysis of the results shows that the performance of the other two abr methods depends on the kind of retrocochlear pathology and the size of the acoustic neuroma .
unfortunately , the number of acoustic neuromas in the examined population was too low to reliably determine an exact relationship between the tumor size and the test result .
all false negatives in abr std pertain to cases of small tumors ( all below 1 cm ) , but all of them were positive in the abr tp method .
indeed , we observed that in all cases of tumors , irrespective of their size , the abr tp test results were positive . both the abr std and abr tp methods exhibited worse sensitivity in cases of neuro - vascular conflict .
over 70% of these ears tested positive in the abr tp method , but the abr std method gave much poorer results  about 60% of these ears tested negative ( i.e. , false negatives ) . the stacked abr method applied with standard normative values of stacked abr amplitude ( the values assumed in the system )
had very high sensitivity ( above 90% ) , but its specificity was extremely low , much lower than either of the other 2 methods .
one might suspect that the normative values for stacked abr amplitude , as given by the system manufacturer , were too high , and an improvement in effectiveness might come from modifying the normative values .
table 4 presents test results and characteristics obtained for modified normative values  700 nv for males and 750 nv for females  derived from previous experiments by the authors .
comparison of the 2 sorts of stacked abr tests is also illustrated in figure 5 .
as one can see , in this case sensitivity drops to about 70% and specificity remains very low ( well below 50% , which is still unsatisfactory ) .
consequently , the positive predictive value of the method is almost the same as that obtained with the previous normative values .
consequently , if one applied such a screening test , the number of cases referred to mri examination would be 10 times more than the actual number of pathologies , leading to a substantial increase in the cost of diagnosis , and casting doubt on any screening test based on such a method ( instead , it might be better to do an mri examination on all patients suspected of retrocochlear pathology , as suggested by some authors . considering the practicality of each method for clinical use , it is of interest to compare the test duration of all 3 methods .
figure 6 plots the examination times of the stacked abr , abr tp , and abr std methods .
the times pertain only to the period of registration ; preparation time ( e.g. , electrode montage and system start - up ) is not taken into account .
the assessment of the sensitivity and specificity of the stacked abr method , based on our investigations and presented here , differs from the analyses published by the original authors of the method [ 1518 ] . in their investigations ,
the reported sensitivity and specificity were much better , and roc analysis showed much greater effectiveness ( area under the curve above 0.9 ) .
however , one must take into account that those investigations were carried out in a controlled , research environment , with the use of dedicated instrumentation and software originally created by don and co - workers . in this way
for example , as shown in , the scatter of stacked abr amplitude was reasonably low , and one could easily differentiate between normal and pathology .
our investigation generated a much greater variability of stacked abr amplitude , and more closely overlapping amplitude distributions for the normal and pathology groups .
another factor that might have contributed to higher sensitivity / specificity values in the work by don and coworkers was that the reference groups were recruited from normal - hearing , experienced , and cooperative volunteer subjects , who were compared with patients with diagnosed pathology .
the situation changes when we deal with a population of actual patients ; many have physiological or psychological deficits , for whom lengthy electrophysiological tests are difficult to withstand , and for whom high levels of stimulus and masker noise cause irritation and fatigue . even in a group without retrocochlear pathology , we can expect more disturbances and instability in abr waveforms , and this strongly affects the abr amplitude .
on the other hand , there is no evidence that the working parameters of hardware and realization of software algorithms in the commercial aep nav - pro system are identical to those originally used by the method s authors .
in particular , a key parameter is the level of residual noise that remains after the averaging process is terminated ( in theory , it should not exceed 20 nv rms ) .
this level is measured and displayed by the system , but there is no way of verifying the correctness of this value , nor can one increase the number of sweeps over the fixed maximum ( 9000 sweeps ) to improve the s / n ratio .
nonetheless , the investigations performed in this study confirmed the notion , evident from our previous works , that one can obtain high sensitivity and specificity using methods based on the morphology and latency of auditory evoked responses .
the standard method based on click - evoked responses ( abr std ) has very high specificity  in our case well over 90% ( as it generates a small number of false positives )  but its sensitivity is unsatisfactory .
unfortunately , in cases of small tumors one can barely notice abnormalities in click - evoked abrs [ 27,4244 ] .
much better results can be obtained using the method based on abrs evoked by appropriately specified tone - pips ( abr tp ) .
previous reports by the authors have shown that it can provide very high sensitivity and satisfactory specificity .
yet another advantage of the abr std and abr tp methods is the short time needed for examination .
the first method needs only 4 recordings of abrs evoked by clicks ( recordings are repeated twice in each ear ) ; the second requires 12 recordings ( at 3 frequencies , twice for each ear ) , and the number of sweeps is relatively low . in the stacked abr method , one must record 12 waveforms , and the registrations usually take much longer because of a lower stimulus level and the presence of masker noise .
consequently , the number of sweeps is much greater ( up to 9000 ) and the whole procedure is several times longer .
the proposed strategy of testing for retrocochlear pathologies would then be as follows : first , one applies the standard abr , which is simple , quick , and has high specificity . if the result of this test is abnormal ( positive ) , the patient would be referred to mri examination to confirm the diagnosis .
negative results would be followed up at a second stage using the abr tp method , which is more sensitive than the abr std .
normal ( negative ) results of both tests would justify not proceeding to an mri examination and instead referring the patient to clinical observation . running the 2 tests in series , according to the above strategy , may significantly increase sensitivity , as expressed by the following formula : at the same time , the effective specificity is slightly reduced , but it remains relatively high if both tests have sufficient specificity : where sen1 and sen2 denote sensitivities of the first and second tests , and spe1 and spe2 denote their specificities .
the above formulae are valid , however , when the tests are carried out in a large population , and true values of sensitivity / specificity are known .
taking into account the results obtained in the examined group presented in table 2 , one might expect that combined strategy of abr std and abr tp would give an effective sensitivity of 94.3% and a specificity of 87.7% . in reality , in our study , we could hardly obtain any improvement in sensitivity applying the 2-stage strategy compared to the application of the abr tp method only .
sensitivity and specificity values are loaded with uncertainly ( figure 4 ) . besides , in this particular group of patients , all positive cases detected with abr std method also tested positive in the abr tp method .
nevertheless , the 2-stage strategy is still worth using , because a number of pathologies are detected already in the first stage , so it is not necessary to use the abr tp method , which is slightly more complicated and time - consuming . in conclusion , using the combination of abr methods , one may expect a significant reduction in cost of diagnosis in comparison with a strategy that refers all patients with suspected retrocochlear lesions to mri examination .
the advantages of methods based on assessment of latencies of auditory brainstem responses  abr std and abr tp  are : high sensitivity ( in the case of the abr tp method ) ; very good specificity ( especially for the abr std method ) ; relatively high positive predictive value ( ppv ) ; availability of instrumentation ( any evoked response test system that allows appropriate tone pips to be generated ) ; uncomplicated measuring procedure , short measurement time ( less than 10 min for bilateral examination ) , and no overly loud stimulus noise . a clear disadvantage of the method is that the results must be interpreted visually , which calls for adequate qualifications and experience of the audiologist performing the tests .
the advantage of the stacked abr method consists in its very high sensitivity ( when one applies settings recommended by the manufacturer ) ; however , the disadvantage is very low specificity .
an automatic measuring process and an automatic decision about the outcome of the test are also advantages , which avoid errors made by the audiologist .
nevertheless , the stacked abr method as implemented in the aep navpro system has several serious disadvantages , including : significant variability and instability of test results ; sensitivity to disturbing phenomena ( e.g. , patient condition , noise , and spurious physiological potentials ) ; very low specificity and very low positive predictive value .
other disadvantages that one must take into account are : limited availability of instrumentation ( presently only 1 system implementing this method ) ; long measurement time ( approximately 4060 min for bilateral examination ) ; various factors that may increase discomfort for the patient ( e.g. , long time in a fixed position , appreciable acoustic level of the stimulus , and high level of masking noise ) .
the results presented above show that the stacked abr method , in its present version , is not yet an optimal clinical tool for screening for retrocochlear pathologies . at the same time , the results obtained from the other 2 abr - based methods indicate that a practical solution for screening for retrocochlear pathologies is to apply abr std and abr tp in series .
 backgroundthe purpose of this study was to compare the effectiveness of methods for screening for retrocochlear pathologies based on auditory evoked brainstem responses ( abrs ) . 
 the study compared the sensitivity , specificity , and effectiveness of these 3 techniques.material/methodsthe methods were : ( i ) standard abr utilizing click - evoked responses , ( ii ) stacked abr based on derived - band responses , and ( iii ) abrs evoked by tone - pips ( abr tp ) . 
 the methods were tested on patients with retrocochlear pathologies confirmed by mri - gd , normal - hearing subjects , and patients with cochlear hearing loss . 
 the system and software used in the tests was navpro aep v.6.2.0 ( biologic  natus ) . 
 prior to testing , all subjects were given comprehensive audiologic and otologic examinations , including mr imaging . 
 sensitivity and specificity functions and predictive values of methods were determined.resultsthe stacked abr method as realized in the navpro system exhibited high sensitivity but specificity was very low , due to the high variability of stacked abr amplitudes . 
 the standard abr method had good specificity , but low sensitivity in cases of small tumors ( below 1 cm in diameter ) . 
 best sensitivity and specificity was obtained with the abr tp method.conclusionsthe stacked abr method allows small acoustic tumors to be detected , but produces high percentage of false positive results . 
 the abr tp method offers good sensitivity and specificity , and relatively high predictive value . 
 the best option would be to use a two - stage screening , consisting of a standard abr in the first stage and an abr tp test in the second . 
Background
Material and Methods
Material
Experiment design
Analyses
Results
Discussion
Conclusions