UNIVERSITY OF CINCINNATI

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1 UNIVERSITY OF CINCINNATI Date: I,, hereby submit this work as part of the requirements for the degree of: in: It is entitled: This work and its defense approved by: Chair:

2 Pediatric Cochlear Implant Outcomes in Auditory Neuropathy/Auditory Dys-Synchrony A thesis submitted to the Division of Research and Advanced Studies of the University of Cincinnati In partial fulfillment of the Requirements for the degree of MASTER OF ARTS in the Department of Communication Sciences and Disorders of the College of Allied Health Sciences 2004 by Christine A. Eby B.A., The Ohio State University, 2001 Committee Chair: Robert Keith, Ph.D.

3 ABSTRACT: Objective: To describe the clinical outcomes in children diagnosed with Auditory Neuropathy/Auditory Dys-synchrony (AN/AD) who have received cochlear implants. Study Design: A prospective study of children diagnosed with AN/AD who have received a cochlear implant. Setting: Tertiary care pediatric referral center. Patients: Seven children with AN/AD identified from a pediatric otology/audiology clinic, whose treatment included cochlear implantation. Results: All 7 children were seen for follow-up testing. Testing included, when age-appropriate: soundfield NBN and speech awareness testing, LNT and/or MLNT, HINT sentences, IT-MAIS and/or MAIS, and otoacoustic emissions. In addition, parents completed a Perceived Benefits Questionnaire, which was developed at Cincinnati Children s Hospital Medical Center (CCHMC). All children showed some measure of improvement with the use of a cochlear implant. Performance varied and was likely affected by additional handicapping conditions, age at implantation, duration of implant use, educational setting and/or communication mode. Conclusion: Children with AN/AD receive measurable benefit from the use of a cochlear implant. Their progress is similar to that of other children with cochlear implants without AN/AD. The degree of clinical outcome variability seen in the general pediatric cochlear implant population is also evident in the subgroup of children with AN/AD. Parents may perceive benefits for their child using a cochlear implant even though objective testing may not reflect those benefits. Additional medical and/or educational disabilities may impact the results obtained on standard tests in children with AN/AD. Development of the Perceived Benefits Questionnaire may be helpful in measuring cochlear implant benefit in children who are not able to participate in standard testing.

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5 Acknowledgements: I would like to take the opportunity to thank all of the people who have contributed to the success of this thesis and have made this experience truly enjoyable for me! First, Dr. Keith, my mentor and buddy! I can not thank you enough for your constant encouragement, support, and brilliance. You have become an integral part of my academic development and I feel privileged to have worked with you. Lisa Hilbert, over the last year you have become a wonderful role-model. Thank you for giving your time and insight into this study. Your direction made this project possible and I owe you a great deal of gratitude. Dr. Boston, thank you so much for your kind patience and helpfulness. Without your logistical knowledge this thesis would not have been possible. It was such a pleasure to work with you. Dr. Martin, your honest feedback was always well appreciated. Our department has been enriched since you have joined UC s faculty. My parents, your continual support during my academic endeavors has been wonderful; I promise I m almost done with school! Over the years, your example of a strong work ethic and commitment to purpose has shaped me into the individual I am today. To my sisters, Jennifer and Patrice, you have both set a precedence that I can only strive to achieve. You are the strongest and most intelligent women in my life and your support means more to me than you ll ever know. I m so proud to be your little sister. My brother, Michael, my only sibling in Cincinnati. Thank you for being such a great friend and charming brother. I m excited to see what the future holds for you. And finally, the children and families involved in this study. Your openness and unreserved participation has made this thesis a success and a joy! I hope that this research and future studies will provide you and other families with both answers and support.

6 Table of Contents ABSTRACT Page ACKNOWLEDGEMENTS CHAPTER 1 OBJECTIVE CHAPTER 2 REVIEW OF THE LITERATURE What is AN/AD...4 Clinical Findings...5 Pathophysiology/Neuropathology...11 Diagnosis of AN/AD...16 Genetics and Risk Factors...19 Management Cochlear Implants Hearing Aids Modes of Communication CHAPTER 3 METHODS Subjects...27 Materials & Procedures...35 Instrumentation...36 CHAPTER 4 RESULTS & DISCUSSION AN/AD Results...41 AN/AD Group Results vs. Non-AN/AD Group Results...46 Limitations of this Study...47 Direction for Future Research...48 CHAPTER 5 1

7 CONCLUSIONS APPENDICES A. Perceived Benefits Questionnaire (PBQ) REFERENCES FIGURES: 3.1 Primary Auditory Pathway Inner Hair Cell, including dendrite synapse Inner Hair Cell Innervations AN/AD Auditory Nerve vs. Normal Auditory Nerve AN/AD Group Results AN/AD SRT and PTA Results AN/AD vs. Non-AN/AD PTA & SRT AN/AD vs. Non-AN/AD PBQ Scores...52 TABLES: 1 Clinical Findings of AN/AD patients Diagnosis Protocol Demographic Representation of Participants Aided Audiologic Results of the AN/AD Group Pre & Post-Implant PTA & SAT/SRT Scores of the AN/AD Group Subject Characteristics AN/AD vs. Non-AN/AD Group

8 Chapter 1: Objective/Hypothesis This is a prospective qualitative study designed to determine the benefit of cochlear implantation in children with Auditory Neuropathy/Dys-Synchrony (AN/AD). AN/AD is a type of sensorineural hearing loss (SNHL) characterized by the preservation of normal cochlear amplification function, but a disruption in the synchronous activities of the auditory nerve. Typically patients have absent or abnormal auditory brainstem response (ABR), but normal cochlear microphonics (CM) or otoacoustic emissions (OAEs), indicating normal outer hair cell function. Usually patients will also have normal cortical potentials and negative brain imaging indicating normal central auditory structure functions. Clinically patients can exhibit bilateral hearing losses that range from normal to profound and will characteristically recognize sounds but demonstrate poor speech perception. Issues surrounding the evaluation, diagnosis, and management of patients diagnosed with AN/AD are complex and unique to each patient due to the variability and pathogenesis of this disorder. Because outer hair cell function is normal, many individuals with AN/AD do not benefit from standard amplification. However, cochlear implantation allows the opportunity to provide electrical stimulation to the auditory nerve with the hope of reintroducing synchronous neural activity. Cochlear implants (CI), coupled with an appropriate post-implant plan can provide near age-equivalent spoken language skills in congenitally deaf children. However, little is known about the communication performance in AN/AD children with CI s. Studies such as this are crucial to the development of better postimplant habilitation strategies, including mapping algorithms and educational options for children with AN/AD. It is the investigators intent to determine the quantitative and qualitative benefits of cochlear implantation in children with Auditory Neuropathy/Dys-synchrony. 3

9 I. What is Auditory Neuropathy: Chapter 2: Review of the Literature Auditory Neuropathy is characterized by varying degrees of sensorineural hearing loss, poor speech discrimination, an absent or severely abnormal auditory brainstem response (ABR), and preservation of cochlear microphonics (CM) and otoacoustic emissions (OAE s). These findings, however, cannot determine an exact site of lesion for this type of hearing loss. Auditory neuropathy can be more accurately classified as neural, but the available data only permits identification of the site of lesion as being post-outer hair cell [7]. Auditory neuropathy can occur in the absence of any apparent medical problem, or it can be associated with a variety of other conditions, such as infectious processes, immune disorders, and genetic and syndromal conditions. Although auditory neuropathy (AN) is not a new disease, it is only recently that professionals have been able to clinically differentiate this disorder from other problems. Approximately 20 years ago audiologists began to treat patients with the above mentioned symptoms; Davis and Hirsh (1979), Worthington and Peters (1980), and Lenhardt (1981) were among the first to publish case studies. The prevalence is presently unknown. However, Madden et al (2002) found a high rate of prevalence, and reported 22/428 children with hearing loss had AN, or about 1/20. Several controversies surround children with auditory neuropathy. These include: pathophysiology, etiology, proper diagnosis, and the appropriate management of this select population. Although the concept of auditory neuropathy has been hypothesized for approximately 20 years, auditory neuropathy is still a grossly misunderstood condition in terms of the 4

10 pathophysiology of this disorder. In addition, auditory neuropathy may not be the anatomically correct term. To neurologists, the term neuropathy refers to pathology of peripheral nerve fibers rather than pathology in their neuronal cell bodies of origin [21]. This may accurately describe the lesion in some cases of AN, but the overwhelming conclusion is that this is too vague. AN results in impaired auditory nerve function (abnormal ABRs) in the presence of preserved cochlear receptor function (normal OAEs or CMs); Theoretically this pathophysiologic combination can occur is several ways and it not confined to a pathology of peripheral nerve fibers. For this reason, as well as others to be discussed, the appropriate term for this condition may be Auditory Dys-syncrony. Rapin et. al. (2003) urge that the term auditory neuropathy be reserved for demonstrable involvement of the 8 th nerve as whole or for selective involvement of the spiral ganglion cells or their processes, and not be used for pathologies of mixed locations. Many clinicians support these authors arguments for the need of more comprehensive behavioral, electophysiologic, and pathologic investigation of AN. For the purposes of this paper, auditory neuropathy/dys-synchrony will be referred to as AN/AD. II. Clinical Findings Many researchers have documented audiologic trends in children with AN/AD. Although the population with AD/AD is heterogenous, they consistently exhibit a constellation of findings that ultimately suggest normal outer hair cell function, and/or impaired eighth cranial nerve operation. Generally, AN/AD is demonstrated clinically by absent or abnormal ABRs, normal OHC functioned as measured by OAEs and/ or polarity sensitive CMs, absent ipsilateral and contralateral acoustic reflexes and variable behavioral responses [30]. In addition, severely handicapping speech discrimination, both in quiet and in noise, is commonly demonstrated in 5

11 AN/AD patient s. There is little information in the literature regarding the involvement, if any, of the vestibular system in children with AN/AD. Pure tone audiometry, which is generally a reliable indicator of hearing sensitivity, is quite variable among AN/AD patients. The severity of hearing loss may range from normal to profound. It is also common for these individual to demonstrate a fluctuating hearing loss with varying configurations. Hearing sensitivity may vary throughout the day for some, and throughout a lifetime from others. In fact, Madden et. al. (2002) reported that 50% of subjects with severe or profound hearing loss showed audiological evidence of a spontaneous improvement in their hearing; occurring 1 to 15 months after an AN/AD diagnosis. In addition, this phenomenon is believed to be primarily bilaterally symmetric, although there have been reported cases of unilateral AN/AD as well as asymmetric configurations. Sinninger s study concluded that 43% of the patients showed a flat audiometric shape, and 28% had a reverse sloping loss with higher thresholds for low-frequency stimuli than for high frequencies [27]. These results can also imply a site of lesion for this group of subjects. That is, a dramatic reverse slope configuration provides further evidence that the underlying etiology of this type of hearing loss is neural rather than cochlear. The laws of the basilar membrane can not explain the loss of low frequency sensitivity with normal high frequency sensitivity. Even if all low-frequency sensory elements (hair cells) were missing, the traveling wave of the basilar membrane would cause displacement and excitation of high frequency elements during low-frequency stimulation, producing a much more uniform response threshold curve [27]. Also, Zeng (1999 ) has noted that neural timing patterns are not synchronous with auditory stimuli in subjects with AN/AD. Therefore, elevation of low frequency thresholds may be attributed to poor timing accuracy in the neural representation of low frequency stimuli. 6

12 Poor speech discrimination scores in relation to pure-tone thresholds is also a common finding in AN/AD patients. The speech perception scores of individuals with AN/AD is usually significantly lower than those of individuals with only a cochlear (sensory) hearing loss. Many patients report difficulty understanding speech in quiet or in the presence of background noise. In fact, these patients speech perception complaints often mimic those of individuals with acoustic neuromas. A report by Zeng (1999) suggested that AN/AD patients have a temporal processing deficit that accounts for their speech recognition problems. Other testing, such as tympanometry and acoustic reflex thresholds, also show conflicting measures. That is, despite normal tympanometric measures, most AN/AD patients do not exhibit an acoustic middle ear muscle reflex (MEMR), even at the maximum limit of the equipment. The neural network of the acoustic reflex is located in the lower brainstem. Acoustic middle ear reflexes normally are engaged when sounds are intense and evoke high rates of discharge in the auditory nerve and afferent pathway to activate motor neurons of the stapedius muscle. However, in AN/AD, the auditory nerve may not achieve a sufficiently high rate of discharge to activate acoustic reflex contractions of middle ear muscles or the crossed olivocochlear reflex [27]. The pathophysiology of this pathway will be discussed later. Vestibular function via electronystagmography (ENG) and other balance tests have also been assessed in these individuals, however, balance concerns are not a primary complaint in AN/AD patients. Kianoush et. al. (2002) concluded that the vestibular branch of the VIII cranial nerve and its innervated structures may be affected in AN/AD individuals. They suggest the use of the term cochlear neuropathy to characterize patients with involvement of only the auditory branch of the VIIIth cranial nerve and its innervations. 7

13 As mentioned, a hallmark indicator of AN/AD are present OAE s and absent or severely abnormal ABR recordings, with a robust CM [1,7,9,15,18,21,27]. However, it is important to note that these tests are not tests of hearing. That is, ABRs are a test of neural synchrony, while OAE and CM measurements primarily asses the integrity and mechanical function of outer hair cells. ABR results vary among individuals, regardless of the etiology of hearing loss. Abnormal ABR s are characterized as having two or more peaks but significantly elevated thresholds relative to pure-tone average, as well as abnormal peak amplitude and latency. In addition, many patients with AN/AD will have a complete absence of any ABR waveform regardless of the level of stimulus. Sininger, et al. (2001) reported 70 % of their AN/AD population as having an absent ABR waveform, 19% showed a wave V only, and in most cases the peak is poorly defined, the latency is abnormal, and the amplitude is small. In 6 % of their patients, the ABR was abnormal but included at least tow of the traditional peaks, usually III and V; however the waveforms were still clearly abnormal. Although many researchers use OAEs to differentiate between preneural and more central pathologies [30,31], Rance (1999) suggests using CM testing to establish outer hair cell (OHC) integrity. This is because approximately one half of their AN/AD subjects had no OAEs and consequently would have gone undiagnosed had they not shown a CM response [22]. The CM in AN/AD patients has been noted to often be large and long-lasting. In some cases it may even extend for several milliseconds and have the appearance of an ABR response [1,6]. This enhanced CM seems to be more pronounced with younger patients. Starr and colleagues (2001) found that the amplitude of the CM in AN/AD cases was greater in patients aged 10 years or younger when compared to normal hearing subjects. 8

14 OAE s may actually confound the diagnosis of AN/AD. First of all, some normal hearing subjects have been found to have absent OAE s (find citation). In addition, OAEs may be absent or greatly reduced in patients who have worn hearing aids over a period of time. Rose et. al. (2002) monitored the effects of hearing aid use on two AN/AD patients. They showed decreased emissions within 24 hours of hearing aid use and a return of emissions after 24 hours of discontinued use. There have also been case studies demonstrating an eventual loss of OAE s in AN/AD patients. Delentre et. al. (1999) documented the test results of two small children. At the time of AN/AD diagnosis, both patients presented with present OAE s bilaterally. However patient 1 showed complete loss of OAE s at age 4 and patient 2 presented with absent OAE s at age 5. Both patients also demonstrated a preserved, large CM bilaterally, which is puzzling. OAE s reflect the mechanical activity of the outer hair cells and it is generally recognized that the surface recorded CM is largely dominated by outer hair cells (OHC) as well. Therefore it would seem logical to expect that if the disappearance of OAE s reflect loss of OHCs, it would have been coupled with a measureable amplitude reduction and threshold elevation of the CM; which was not the case in Delentre s study. Delentre s finding of secondary loss of otoacoustic emissions have important implications for the current operational definition of AN/AD. AN/AD is a diagnostic label defined as an absent or severely distorted ABR in the presence of preserved otoacoustic emissions. However, clinicians are sure to discover AN/AD children with absent OAE s and must prepared to encounter these cases. 9

15 Table I. Summary of expected results in AN/AD patients Test Test Parameters Result Comments Tympanometry 226 Hz, 678 Hz or 1000 Hz for infants Normal unless P.E. tubes or fluid present in middle ear Type A most commonly seen Middle Ear Muscle Reflexes (MEMRs) 500, 1000, 2000, 4000 Hz, both ipsilateral and contralateral stimulation Reflexes absent at all frequencies both ipsi and contra at the limits of the equipment or tester comfort A few rare cases have shown elevated rather that absent reflexes Otoacoustic Emissions (OAEs) Transient "nonlinear" clicks at sufficient level (80 db peak SP) or Distortion Product (65/55 db SPL) with acceptable signal to noise ratio Emissions should be present, unless the patient has worn hearing aids or has PE tubes or a conductive component A few patients do have peripheral cochlear losses in addition to AN/AD Auditory Brainstem Response (ABR)-click Run at high intensity regardless of pure tone audiogram - 80to 90 db nhl.compare responses obtained for both condensation and rarefaction clicks. We use 27.7/s or lower, sweeps, each run replicated No neural response (wave I) present, cochlear microphonics present that may have high amplitude and last several msec (can mimic ABR waves-look for reversal of waves with polarity change to identify hair cell response) If alternating polarity is used the cochlear microphonic will cancel out and the ABR will look flat - like a severe/profound hearing loss Suppression of Emissions Recommended method: 65 db peak SP "linear" transient click to the test ear and simultaneously present 70 db SPL broadband suppressor noise through an earphone to the nontest ear, replicate and average the responses No suppression in the contralateral, ipsilateral, or binaural noise conditions Speech Audiometry Use standardized word lists Speech audiometry is generally poorer than expected given the pure tone loss AN/AD patients seen at Kresge perfomed better with live voice testing Speech in noise tests Use a standardized speech test with competing ipsilateral noise, or multi-talker babble (SIN, SPIN, HINT); or use a word list with speech noise routed through same channel Patients perform very poorly in the presence of competing noise, even under favorable signal/noise conditions AN/AD patients seen at Kresge sometimes show db SNR loss on the SIN test Pure tone audiograms Administer as usual Results vary from normal to profound responses in almost any configuration. Results may fluctuate from test to test The most common pure tone configuration observed to dates is a low frequency loss-rising to normal in the high frequencies 10

16 III. Pathophysiology/Neuropathology Diagnostic electrophysiological test results, provide a number of theories concerning the etiology and pathophysiology of AN/AD. As stated, individuals with AN/AD display normal otoacoustic emissions, and cochlear microphonics, and an absent or severely abnormal auditory brainstem response, beginning with wave I. The etiology of AN/AD has been hypothesized for 20 years and can essentially be broken into two broad categories. First are neuropathies originating from hereditary or congenital conditions. There is reported to be a positive family history of SNHL in 40% of AN/AD children [27]. Also, hereditary, demyelinating disorders including Fiedreich s Ataxia and Charcot-Marie-Tooth Disease have been associated with AN/AD. Congenital inner hair cell loss will also be discussed as a possible root. The second form of presentation are acquired cases of AN/AD. Specifically, those resulting from hyperbilirubinemia and hypoxia, which will also be discussed further. The pathophysiology leading to the combination of impairments can theoretically occur in several ways. The Organ of Corti consists of an afferent and efferent division. The afferent division, composed of the inner hair cells and afferent nerve fibers, conduct neural energy to the auditory nerve. From the auditory nerve, the energy, in the form of an action potential, is transmitted through the auditory pathway to the auditory cortex (Figure 3.1). While the efferent division, consisting of the outer hair cells and efferent nerve fibers facilitate and tune the transduction process. Any disorder of the afferent division could result in findings similar to those shown by patients with auditory neuropathy. Because almost all afferent nerve fibers are activated via the inner hair cells, pathologic processes specifically affecting the inner hair cells, the synapse between these cells, or both and the dendrites of the auditory nerve could also lead to a severe reduction in afferent activity (Figure 3.2, 3.3). 11

17 Harrison (1998) reported animal models with auditory neuropathy in which the initial site of the functional damage is at the level of the inner hair cells and its synapse with the primary afferent neuron; suggesting AN is cochlear in origin. He suggests the nature of AN/AD is a pre-synaptic phenomenon. That is, the loss of inner hair cells results in the depletion of neurotransmitters. This considerably inhibits or distorts the auditory nerve input, and ultimately prohibits action potentials. Others believe AN/AD may be more postsynaptic in nature. Which implies that the dendrites of the auditory nerve are the altered receptors. However Starr (1996) provides evidence that AN can be caused by auditory (axonal) degeneration or demylination. Myelin plays an essential role in the rapid conduction of nerve impulses along axons. Demylination or degeneration causes a conduction block of auditory nerve fibers (eighth cranial nerve); therefore no compound nerve action potential distal to the conduction block will be produced. Demyelination results in lack of neural synchrony and poor temporal encoding. This theory accounts for the grossly abnormal or absent auditory brainstem response and degraded speech perception. Histological studies have compared the reduction of eighth nerve fibers in AN/AD patients has been documented and compared to normal eighth nerves (figure 3.4). 12

18 Figure 3.1: Primary Auditory Pathway The final neuron of the primary auditory pathway links the thalamus to the auditory cortex, where the message, already largely decoded during its passage through the previous neurons in the pathway, is recognized, memorized and perhaps integrated into a voluntary response. A final relay, before the cortex, occurs in the thalamus (medial geniculate body); it's here that an important integration occurs: preparation of a motor response Leaving this relay, a third neuron carries the message up to the level of the mesencephalus (superior colliculus). These two relays play an essential role in the localization of sound. The second major relay in the brain stem is in the superior olivary complex: the majority of the auditory fibers synapse there having already crossed the midline. The first relay of the primary auditory pathway occurs in the cochlear nuclei in the brain stem, which receive Type I spiral ganglion axons (auditory nerve); at this level an important decoding of the basic signal occurs: duration, intensity and frequency. 13

19 Figure 3.2. Inner Hair Cell, including dendrite synapse 1. Nucleus 2. Stereocilia 3. Cuticular plate 4. Radial afferent ending (dendrite of type I neuron) 5. Lateral efferent ending 6. Medial efferent ending 7. Spiral afferent ending (dendrite of type II neuron) Figure 3.3. Inner Hair Cell (IHC) Innervation The IHC is synaptically connected to all type I spiral ganglion neurons forming the radial afferent system (blue) going to the cochlear nuclei (CN). The lateral efferent system (pink) arising from small neurons in the ipsilateral lateral superior olivary complex (LSO) brings a feedback control to the IHC/type I afferent synapse. Graphics adapted from: Promenade round the Cochlea, R Pujol et al., Univ. Montpellier Drawings: S. Blatrix 14

20 Figure 3.4: AN/AD Auditory nerve vs. Normal Auditory Nerve. (Sinninger, 2000) 15

21 IV. Diagnosis Identification of AN/AD in children and infants presents a diagnostic challenge. Due to the variation of symptoms in identified AN/AD patients, it is difficult to establish a protocol for diagnosis. However, the confusion and frustration surrounding diagnosis is at the expense of the patient and his/her family. For this reason, it is imperative for clinics to establish a practice for diagnosing AN/AD. Auditory neuropathy/dys-synchrony was hypothesized as early as 20 years ago, when Davis and Hirsh (1979) reported cases in which patients had normal or near normal behavioral thresholds with absent ABRs. These results were baffling because generally an absent ABR would indicate a profound sensorineural hearing loss (SNHL). Fortunately, with the advent of OAEs, audiologists have an additional tool in assessing auditory function. However, it is also well known that many neurological diseases can desynchronize ABRs while causing little if any cochlear hair cell dysfunction [1,30]. For this reason, it is crucial to establish an AN/AD diagnostic protocol. This protocol should employ electrophysiological and behavioral tests to evaluate both the peripheral and central auditory nervous system. This perplexing disorder may not be identified immediately and it may be misdiagnosed. Misdiagnosis is most likely in children and infants, where the incidence of otitis media or other middle ear pathologies is high. If middle ear problems prevent evaluation of otoacoustic emissions, then it may be possible to evaluate outer hair cell function via the CM, since this response appears less vulnerable to middle ear problems. In addition to a compromised middle ear, it is conceivable that a patient could have a co-existing peripheral hearing loss which could affect the ability to measure OAE s. Hood (1998) encourages clinicians to complete OAE testing prior to ABR testing in patients who are sedated. The otoacoustic emission amplitude may be reduced during a deep sleep due to positive pressure in the middle ear which can alter the 16

22 systems mechanics. An ABR is also imperative for AN/AD diagnosis. Berlin urges clinicians to compare positive versus negative polarity clicks in an ABR. Reversing click polarity may help separate ABRs from cochlear potentials and may alert clinicians of AN/AD. Therefore, findings of abnormal ABRs and normal OAEs need not always imply a single central finding, but might be consistent with dysfunction between outer hair cells and primary afferent fibers [1]. Other electrophysiologic tests, such as steady state evoked potentials (SSEP), have been used widely for research purposes. However, SSEP appears to have little or no predictive value for hearing levels in children with AN [20]. It is well documented that pure tone audiometry test results differ significantly between individuals with AN/AD. In one recent study of 33 AN/AD patients, the average pure tone loss was found to be 58.2 db HL for right ears and 56.7 dbhl for left ears [22]. Proper diagnosis of AN/AD is not dependant on pure tone thresholds and this testing is usually left out of the test battery, as it is not an accurate reflection of hearing in AN/AD patients. However, other conventional audiometric testing such tympanometry, including acoustic reflexes are required for a comprehensive evaluation of the AN/AD patient. Ipsilateral and contralateral assessment of the middle ear muscles and conduction along the auditory pathway can be achieved through acoustic reflex measures. These results further help clinicians identify a site of lesion. The activation of the Universal Newborn Hearing Screening (UNHS) program may be able to provide useful data on the incidence of AN/AD. However, the surge in awareness of AN/AD also poses a problem for UNHS. That is, because there is no mandated screening method, children who do not receive a two-tiered screening approach will be overlooked. In addition, it is difficult to document possible high risk indicators of AN/AD if neonates are not screened and documented at birth. It has been proposed that checks of ABR and/or CM should 17

23 be considered in high risk newborns who undergo OAE testing as their primary screening tool [16]. The results of this combination of tests would determine appropriate management and amplification recommendations, which differ from the recommendations for those with only a SNHL. It is likely that in the future, physicians and audiologists will include AN/AD in their differential diagnosis of SNHL in children. Table 2. Diagnosis of AN/AD Protocol for Diagnosis of AN/AD: 1.) Otoscopic Exam 2.) Tympanometry, or if not age appropriate, ENT evaluation stating no middle ear pathology 3.) No response or abnormal morphology ABR at elevated levels Low level 500 Hz Click 4.) Polarity sensitive cochear microphonic at an intensity not exceeding 90 dbnhl Cochlear microphonic should be present at 90 and 80 dbnhl 5.) Otoacoustic emissions present at passing criteria SNR of 3 db or greater Reproducibility of 70% or greater Present at 3/5 frequencies, with one of them being 3 or 4 KHz TEOAE s completed first, if not present at passing criteria, DPOAE s attempted 6.) Absent acoustic reflexes at 500, 1K, and 2 KHz (ipsi and contra) 7.) ENT consult, neurology consult, genetics consult (Adapted from Koley, This protocol is currently used at Riley Hospital for Children in Indianapolis, IN) 18

24 V. Genetics and Risk Indicators Predisposing factors and other risk indicators have been identified in the AN/AD population. However, the task of determining high risk factors specifically for AN/AD is complicated due to the variety of clinical presentations and late diagnosis. AN/AD has presented in the absence of any apparent medical problem, or it can be associated with a variety of other conditions, such as infectious processes, immune disorders, complicated perinatal periods and genetic or syndromal conditions. Perinatal factors accounted for the etiology of 68% of the subjects observed by Madden et. al. (2002). These causes included hyperbilirubinemia, prematurity, ototoxic medications, and the need for mechanical ventilation. Genetics is also a growing area of research surrounding the etiology of hearing loss. Sininger noted that 46% of AN/AD subjects in their database had a family history of hearing disorder or a genetic basis for AN/AD [27]. Hearing loss associated with peripheral neuropathies is one of the most complex types of AN/AD and can have both genetic and non-genetic causes. The association of auditory neuropathy and peripheral neuropathy is a common feature in adults but not young patients. Peripheral neuropathy is classified by selective functional involvement, anatomical distribution, time course, and other specific features, such as the findings of specific autoimmune antibodies [20]. Peripheral neuropathies documented in conjunction with auditory neuropathies include Charcot-Marie-Tooth disease, Freidreich s ataxia, Spinocerebellar degeneration, and Leukodystrophy [27]. Peripheral neuropathy affecting hearing loss may also be due to systemic disorders, such as diabetes. Also, specific infections such as Gullain-Barre Syndrome have produced AN/AD diagnostic findings. Even drugs, such as Cisplatin, can have toxic side effects resulting in a peripheral neuropathy and hearing loss. 19

25 AN/AD has been described genetically as an autosomal dominant and an autosomal recessive disorder. In a family where a parent and child are affected, an autosomal dominant pattern may be the explanation; these families may also have peripheral neuropathies. When a pattern of unaffected parents with two or more affected offspring is identified, it is consistent with autosomal recessive inheritance. Rogers (2001) found that infants with autosomal recessive AN/AD tend to have profound hearing losses. Although specific genes known to cause AN/AD have not been identified, the research is in progress. Bilirubin toxicity has emerged as an important cause of AN/AD in infants. Stein (1996) described a group of infants with elevated bilirubin levels, absent ABRs, and unaffected OAEs; these findings have been repeated in numerous case studies of AN/AD patients. Hyperbilirubinemia selectively damages the brainstem auditory nuclei, and may also damage the auditory nerve and spiral ganglion containing cell bodies of primary auditory neurons [26]. Interestingly, the inner ear, thalamic and cortical auditory pathways appear to be protected. Both the duration of exposure and the amount of bilirubin has been related to deafness. Of the 22 AN/AD patients observed by Madden et. al. (2002), 11 had hyperbilirubinemia. VI. Management Appropriate management and amplification of children with AN/AD is vital although the current specific recommendations are debatable. As with any hearing impaired child, the development of communication abilities is of utmost concern and demands early intervention. However, until the underlying etiologies of this disorder are better understood, the effectiveness of communication modes and amplification options are difficult to determine. In particular, there is an ongoing debate on the use of cochlear implants verse the use of hearing aids. Considering the nomenclature of this disorder implies that the site of lesion is proximal to the cochlea, it is 20

26 reasonable to expect limited benefits of cochlear implantation in patients with AN. However, a growing body of evidence shows the striking benefits of cochlear implantation in AN [16]. Cochlear implants have received considerable research and advocacy as an appropriate recommendation for those with AN/AD. Approximately one-third of the patients with AN/AD have audiometric thresholds in the severe-to-profound range [27]. Simply due to the severity of hearing loss, these children are considered CI candidates, after a trial period with hearing aids. A generally hypothesized cause of AN/AD is an alteration in neural synchrony and temporal encoding. Therefore, a plausible mechanism for improving auditory function by cochlear implantation is that implant stimulation may restore some degree of neural synchrony and temporal coding that are compromised in children with AN [16]. The implant is simply based on the idea of bypassing the normal hearing mechanism (outer, middle, and part of the inner ear including the hair cells) and electrically stimulating the remaining auditory neurons. This electrical stimulation has also been shown to be beneficial in promoting spiral ganglion cell survival [13]. In addition, neural response telemetry measures, which evaluates the auditory nerve compound action potential and growth function in response to electrical stimulation with an intracochlear electrode, are normal in AN/AD patients [25]. This suggests that cochlear implants do in fact reintroduce neural synchrony to the user. As discussed, patients with AN/AD display awareness of sound around them, but generally are unable to discriminate speech sounds sufficiently to understand speech. Cochlear implants work to correct the handicapping word discrimination skills of AN/AD patients. With rare exceptions, the speech perception abilities in AN/AD children receiving cochlear implants are good to excellent. However, there is great variability in the speech-recognition performance of cochlear implant patients, regardless of the etiology of the hearing loss. Peterson et. al. (2003) 21

27 reported significant improvements in post operative speech perception scores among AN/AD children. The tests included the LNT, MLNT, HINT. In addition, performance outcome measures, via the MAIS and IT-MAIS illustrated substantial postoperative improvement, as reported by the parents. Today, a growing number of researchers and clinicians support the use of cochlear implants as a viable option for children with AN/AD [4,16,19]. Another goal of amplification with AN/AD is to minimize any harmful effects amplification may have on otoacoustic emissions. Overamplification is a concern among the AN/AD population because of the possibility of fluctuating hearing sensitivity. Also, since some AN/AD patients naturally lose their emissions over time, use of hearing aids in both ears makes it difficult to tell whether loss of OAE s is naturally occurring or the result of excessive amplification [22]. A trial period with conventional amplification is always required before implantation, for various reasons. For one, it is known that some infants diagnosed with AN/AD who initially present behaviorally as deaf, may show improved auditory responses with increasing age, up to about 18 months. The possibility that extreme amplification of sound might be harmful to the residual hearing of users of high-gain hearing aid has existed for years [17]. Therefore, during the hearing trial period, most professionals recommend that 100% mild gain, wide dynamic range compression hearing aids be used [16,22,27]. This approach is intended to preserve any presence of otoacoustic emissions the patient may have. It is assumed that the site of lesion in AN/AD is central to the cochlea; therefore amplification via hearing aids is unlikely to be of benefit. Few patients have experienced any degree of benefit with hearing aids simply because the role of hearing aids is quite different than that of a cochlear implant. A conventional hearing aid is designed to simply provide more amplification and power to the user; this does not ensure that the incoming sound will be clear. 22

28 Cochlear implants, however, are designed to deliver a clearer, more natural and understandable sound. This is crucial to improving the speech detection and recognition abilities in those with AN/AD. Rose et. al. (2002) contend that hearing aids are not effective in assisting in communication or language acquisition and do not recommend their usage in AN/AD patients. However, the option of hearing aids must not be ruled out and the arguments in favor of this method are straightforward. When parental observations are consistent with behavioral thresholds that are reliable and indicate impaired hearing sensitivity, fitting hearing aid according to the behavioral thresholds seems clinically appropriate; regardless of robust OAEs. There have been some reports of limited benefit of hearing aids in the AN/AD population [20], and a trial period should still be employed before implantation. In addition, Miyamota et. al. (1999) concluded that amplification techniques for these individuals are controversial and he advises implanting these children with caution, as they have documented less than optimal results in AN/AD children with cochlear implants. In addition to amplification options; families of children with AN/AD must decide on an appropriate communication option for their child and entire family. It is imperative for professionals to inform the families of the extensive commitment, research and therapy involved in developing a communication style for their child. The options available for hearing impaired children include; manual communication, auditory-verbal communication, cued speech, auditory-oral communication, and total communication. In the current study all of the participants utilize different communication modes and are enrolled in different educational settings. Manual communication includes a variety of signing options; such as American Sign Language (ASL) and Signing Exact English (SEE). This option is viable for a child who wants 23

29 to be part of the deaf community; manual communication is used extensively. Speech and intense amplification is not encouraged. Signing is the child s primary expressive language. This option should be discussed with the family after diagnosis and prior to implantation. The goal of cochlear implants is to acclimate the hearing impaired child into the hearing world and not the deaf culture. Professionals agree that no one system designed to develop communicative competence and educational achievement can meet the individual needs of all children with cochlear implants. Auditory-Verbal communication emphasizes the child using his/her auditory skills. This program teaches the child to develop listening skills through one-on-one therapy that focuses attention on the use of the individuals hearing status when amplified. No manual communication is used and the child is discouraged from relying visual cues. The goal of Auditory-Verbal communication is for the child to develop speech, primarily through the use of hearing aids or cochlear implants alone, and to develop communication skills necessary for integration into the hearing community. Consistent and successful use amplification is critical to the auditory-verbal communication approach. Cued Speech, although it is a less employed mode due to local resources, has proven to be a successful communication style for hearing impaired children. Berlin (1998) suggests that if a visual communication system is adapted, then it should follow the grammatical structure of English such as signed English or cued speech, rather than ASL. Cued speech is a visual communication system of eight handshapes (cues) that represent different sounds of speech. These cues are used while talking to make the spoken language clear through vision. This system allows the child to distinguish sounds that look alike on the lips. This method utilizes the 24

30 use of amplification, speech reading and cues to obtain its goal of developing speech and communication skills necessary to integrate the child into the hearing community. The Auditory-Oral program teaches a child to make maximum use of his/her remaining hearing through amplification (hearing aids, cochlear implants, FM systems). This approach also stresses the use of speech reading to aid the child s communication. Use of any form of manual communication is not encouraged although natural gestures may be supported. Similar to the Auditory-Verbal approach, the goal of this mode is to develop the necessary speech and communication skills to function in a hearing world. Total Communication (TC) is a style which combines many communication techniques to provide the child with the easiest, least restrictive method both at home and school. The philosophy of total communication is to use every and all means possible to communicate with hearing impaired children. The child is exposed to a formal sign-language system (based on English), fingerspelling, natural gestures, speech reading, body language, oral speech and use of amplification. The idea is to communicate and teach language in any manner that works. 25

31 Chapter 3: METHODS This study was designed to investigate the efficacy of cochlear implantation in pediatrics with AN/AD and to assess the child s communication abilities. Subjects who were known to have AN/AD as demonstrated by normal outer hair cell function and abnormal eighth nerve operation, and also have a cochlear implant were candidates for this study. The pre-implant audiologic data of each patient was obtained by medical chart review and through consultation with the CCHMC Cochlear Implant Team. Possible subjects were then contacted verbally by the investigator and also via a letter for their participation. Individual appointments at CCHMC, lasting approximately 90 minutes, were scheduled at the participant s convenience and free of charge. During the appointment audiologic data was gathered, including frequency specific narrow- band noise thresholds and age appropriate speech perception test results. In addition, the investigators also gained information from the subject s parent regarding their child s CI use and their perceived benefit from the prosthesis. Some testing procedures were altered or omitted to accommodate a patient s unique needs. A thorough explanation of the study was provided and written parental consent was obtained before testing began. In additions, the audiologic group results of the AN/AD group were then compared to the general SNHL population who have cochlear implants. 26

32 I. Subjects: Since 1996, 34 children have been diagnosed with AN/AD at CCHMC. This sample constitutes 4.3% of the total SNHL population at CCHMC. All 34 children displayed absent ABR s and present CM, 24/34 patients had present OAE s. Since that time, nine children with AN/AD have received CI s and are still receiving services from this facility. As is consistent with the entire AN/AD population, the current participants represent a heterogeneous sample. Seven children were included in this project, 3 girls and 4 boys, ranging in age from 2.5 years to 11.9 years old, with a mean age of 5 years 4 months (Table 3). Four children were implanted in their right ear, and three in the left ear. One child received an Advance Bionics implant, four received implants from Cochlear, and two were implanted with Med-El devices. All subjects are known to have AN/AD as demonstrated by prior diagnostic ABR and OAE results. However, age at implantation, length of deafness and current communication modalities differ between the subjects. In addition, some of the participants also have concomitant disabilities which were accounted for in both the testing procedures and data analysis. A control group of 7 children with CI s, with varying etiologies of hearing loss, was also included. A medical chart review was conducted on these children to determine the demographics of this population, although case studies will not be discussed at length. In addition, the parents of the non-an/ad group also completed the PBQ. This comparison was meant to be a descriptive analysis, and was not intended to prove the statistical benefit of either population. The non-an/ad group was not completely matched to the AN/AD group (Table 5). However, age at stimulation did correspond between the groups. The age at initial stimulation has been proven to be a factor in the success of CI use. In the current study, the mean age at 27

33 stimulation for all 14 subjects was 2.7 years old; although the non-an/ad group did encompass a larger age range. Subject 1: Born 9/17/98, subject 1 has a complicated birth history. He was born prematurely and was immediately admitted to the neonatal intensive care unit (NICU) to be treated for renal failure. Unknown doses of aminoglycosides were administered. At 2 1/2 months old, subject 1 was diagnosed with pneumonia and nephrotoxicity. At 3 months of age, subject 1 was diagnosed with a severe to profound sensorineural hearing loss bilaterally. This was confirmed by an ABR which resulted in absent waveforms. At this time he was fit with a body aid and eventually with bilateral hearing aids. Subject 1 was implanted with a MedEL Combi 40+ device in the right ear at 4 years 4 months at CCHMC. Subject 1 wears an Oticon Digifocus BTE on his left ear. Subject 1 utilized total communication in a multi handicap preschool for 2 1/2 years, but currently attends a deaf-oral elementary school. Educationally, subject 1 enjoys a low teacher to student ratio and a soundfield FM system. Subject 2: Subject 2, age 3 years 6 months was the youngest subject in this study. She was referred for audiologic testing after failing a newborn hearing screening at birth. Family history on the paternal side of subject2 is also unknown. At 3 months of age, subject 2 was diagnosed with an enlarged vestibular aqueduct and bilateral auditory neuropathy at CCHMC. AN/D was diagnosed based on ABR findings. No observable waveforms present, however cochlear microphonics were present bilaterally. DPOAE s were not significant; OAE s were not observed in her left ear, and only a very weak OAE was observed at one octave in her right ear. Subject 2 28

34 was implanted at CCHMC with a Nucleus 24 Sprint device in the left ear. She was initially stimulated at 1 year 2 months old. Subject 2 is currently enrolled in a deaf-oral toddler educational and therapy program 5 mornings a week. Subject 2 wears an Oticon Digifocus II power compact BTE on her right ear. In addition, sound field amplification is provided in her educational setting. Subject 3: Subject 3, age 5 years 6 months, is known to have a very rare skin disorder and a history of allergies. Unfortunately, this genetic skin disorder causes blistering and shearing of the skin from even the gentlest friction and sometimes spontaneously. Subject 3 was diagnosed with AN/AD at 2 yr. 11 mo., after sedated diagnostic ABR s and OAE s. There were no repeatable ABR responses at the limits of the equipment, bilaterally. A robust cochlear microphonic was observed in the left ear, however, it was absent in the right ear. Weak otoacoustic emissions were present bilaterally. Using insert phones voice awareness level (VAL) in his right ear was profound (95 db) and moderately-severe in his left ear (65 db). Soundfield VAL was 65 db. SD was fit with bilateral BTE s. Aided testing revealed a moderate-severe hearing loss in response to tonal stimuli and speech. Due to this subjects skin condition the use of hearing aids is painful, as blisters quickly form in the subjects concha. In addition, the hearing aids were very difficult for subject 3 to manipulate. Fortunately, his scalp is unaffected by this condition and his cochlear implant does not aggravate this condition. He was implanted with an Advance Bionics implant at age 3 years 6 months, at CCHMC. Before implantation, subject 3 was communicating mainly through sign language. However, he is now enrolled in an intensive deaf-oral school and is doing extremely well. In the current study, tympanometry was not performed due to SD s discomfort. 29

35 Subject 4: Subject 4 is the brother of another participant, subject 5. Although these siblings hearing loss is fairly similar, their developmental, educational, and social progress sharply contrasts each other. Subject 4 had no significant perinatal history or medical complications. Subject 4 right ear was implanted with a Nucleus 22 device and Esprit 22 speech processor at age 1 year 9 months. Subject 4, who was diagnosed with autism, is chronologically 7 years 6 months old. However, developmentally and socially he was quite delayed. It was difficult to record audiologic information on subject 4 because of his tendency to become fixated on words or objects as well as lights during the testing procedure. In this case testing was terminated because of his noncompliance. In addition, he was violently afraid of objects in his ears, which made tympanometry and OAE recordings impossible. Speech perception testing was also unable to be completed. However, the investigator did gather reliable and encouraging frequency specific narrow band noise thresholds and a voice awareness level (VAL). As well as obtain a positive interview with this subject s parents regarding their child s benefit from the use of a cochlear implant. Subject 5: Subject 5, the oldest subject in this study, was 11 years 9 months old. Subject 5 had an unremarkable perinatal period and no history of family hearing loss. She was identified at age 1 year 2 months with a bilateral severe to profound SNHL. At age 3 years 3 months, her left ear was implanted with a Nucleus 22 device and Esprit 22 speech processor. She was a successful cochlear implant user for 8 years 6 months. She and her family utilize total communication, however it became fairly easy for subject 5 to interact and socialize in the hearing world and deaf 30

36 world. In her educational setting, subject 5 used a personal FM system and had a full-time interpreter. Subject 6: Subject 6 is known to have a severe to profound sensorineural hearing loss. Her birth history and prenatal care was unremarkable. Subject 6 was fit with a personal FM system at 1 year of age. Motor milestones were within normal limits, however. Subject 6 experienced chronic middle ear problems that were treated with pressure equalization tubes. Subject 6 was diagnosed with AN/AD at 1 year 8 months when she presented with an absent ABR and present cochlear microphonic bilaterally at a presentation level of 80 db and 110 db. DPOAEs were absent in the left ear and minimal emissions were observed in the right ear. However, Subject six had pressure equalization tubes that may have obscured the DPOAE results. MH s left ear was implanted with a Cochlear implant and Sprint processor. Her initial stimulation occurred at CCHMC when she was 3 years 6 months old. Subject 6 utilizes total communication in a mainstreamed classroom without a personal soundfield FM system. However, parents of subject six verbalized an interest in changing MH s communication mode to sign language and forgoing the use of her CI. Subject 7: The participation of subject 7 in this current study was questionable because of severe medical contraindications. However, his individual case is very interesting. Subject 7 was born on 7/6/1999 and was chronologically 4 years, 6 months old at the time of this testing. Subject 7 had bilateral AN/AD and severe kernicterus. Subject 7 was the youngest of three children in his family. His mother reported normal pregnancies with all of her children. However, subject 7 required neonatal intubation and ventilatory support subsequent to a traumatic delivery. After a 31

37 normal hospital stay, he returned a week later at the urging of his mother, who had been relentlessly requesting jaundice tests. At this time he was admitted with hyperbilirubinemia (bilirubin level of 45 mg). Shortly after, 9/22/1999, he was referred for sedated audiologic testing due to hyperbilirubinemia and a double exchange transfusion. The ABR revealed an absence of any waveforms bilaterally, at the limits of the equipment; but present CM s. Due to the poor wave morphology and his kernicterus, the audiologist could not rule out neurological involvement. DPOAE testing displayed present emissions bilaterally. Acoustic reflexes were also absent bilaterally. This testing was repeated over the next month, and subject 7 was diagnosed with a profound SNHL and AN/AD bilaterally. Subsequently, he was also diagnosed with mild cerebral palsy and he is not expected to ever be ambulatory. His speech/language and motor abilities were severely delayed, he was suffered from seizures, and his overall tone was low, secondary to the cerebral palsy. Subject 7 had numerous other physical handicaps and was being evaluated for cystic fibrosis. Subject 7 had daily intensive physical therapy, occupational therapy, speech/language therapy, and aural rehabilitation. The right ear of subject 7 was implanted with an Advanced Bionics device when he was 12 months old. His post-implant plan was especially tailored to meet his needs. In regards to speech therapy and aural rehabilitation; his speech is unrecognizable and he was only able to respond and communicate through eye gaze and pointing with one hand. For this reason, some signing was integrated into his rehabilitation. In addition, at school, he uses augmentative communication devices. Subject 7 attended the CCHMC Pearlman Center 4 days a week and Fayette Progressive Preschool 1 day a week. Overall, he communicated through total communication. Interestingly, six months prior to this testing, subject 7 regained hearing in his non-implanted ear. In fact, pure tone audiometry revealed he was responding in the 32

38 moderate-severe hearing loss range. This is the only case of regained hearing abilities in an AN/AD patient at CCHMC. Subject 7 was not a consistent CI user since this was revealed; as his therapists were trying to devise an appropriate management plan for him. However, the investigator decided to keep subject 7 in this study. Aided narrow band noise frequency specific thresholds were obtained, as well as an SAT. These results were based on behavioral observations, via localizations and grunting. Speech perception testing was not appropriate and OAE s could not be obtained due to fatigue. 33

39 Table 3: Demographic Representation of Participants Name DOB/ Age Duration of Deafness Initial stimulation Length of use Type of implant Communication mode Pre-implant hearing loss Subject /5.2 4yrs 4 mo 1/22/ yr Med El / Combi 40 + Oral; deaf-oral school AU- severeprofound HL Subject /2.5 1 yr. 1 mo. 11/26/ yr. 1 mo. Subject / yrs 6 mo 12/20/ yr Cochlear / Sprint Advanced Bioncs; Clarion processor Oral; deaf-oral school Oral; deaf-oral school AD - moderate - severe HL, AS - severe - profound HL AU- severe HL Subject /7.6 1 yr. 9mo. 4/9/ yr. 8 mo Cochlear/ Spectra TC, interpreter & school AU - profound HL Subject / yrs 3 mo unknown 8 yr. 6 mo. Cochlear/ Spectra TC, interpreter & school AU - profound HL Subject /5.5 2 yr. 6 mo. 4/3/ yr. 10 mo. Cochlear / Sprint Total communication AU - severeprofound Subject /4.6 1 year 8/14/ yr. 4 mo. Advanced Bionics/ S-Series Total communication AU - profound HL Mean age at evaluation (range) = 5 year 4 months (range yrs) Mean age at initial stimulation (range) = 2.7 years (1-4.4 yrs) Mean length of use (range)= 3.4 years (1 yr- 8.6 yrs) AU=left ear, AD= right ear, AU = bilaterally, HL = hearing loss, TC = total communication FM = Frequency modulated personal amplification system 34

40 II. Materials and Procedures: Participants in this study underwent approximately 90 minutes of non-invasive behavioral and electrophysiologic testing. All audiologic testing for this study was conducted by the investigator and co-investigator, Lisa Hilbert M.A., CCC-A at Children s Hospital Medical Center, Cincinnati. The equipment used for this study was the property of CCHMC. Frequency specific narrow band noise thresholds and speech perception testing was performed using a GSI 61 Audiometer, in conjunction with a compact disc player. This testing was completed in a sound proof booth at CCHMC. Speech Reception Thresholds (SRT) and Speech Awareness Thresholds (SAT) were obtained using standard age-appropriate spondaic word lists and administered via live-voice. Other standardized speech perception tests employed were the Lexical Neighborhood Test (LNT), the Multi-Syllabic Lexical Neighborhood Test (MLNT), and the Hearing in Noise Test (HINT). These are recorded tests administered through a compact disc player into the soundfield of the sound proof booth. Tympanometry was attained prior to audiologic testing using the Zodiac 901 Middle Ear Analyzer. Distortion Product Otoacoustic Emissions (DPOAES) were also completed using the Bio-Logic Scout Sport OAE System. The Perceived Benefits Questionnaire, as developed by Lisa Hilbert M.A., CCC-A, was completed by the child s accompanying parent. In addition, The Meaningful Auditory Integration Scale (MAIS) or the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) was verbally re-administered to the parent by the investigator. The investigators also administered the Ling-6 sounds to the children, at a conversational level, with no visual cues. Identification or detection of these 6 sounds was recorded. Each child was accompanied by his/her parent. Every attempt was made to obtain the maximum number of tests results for each child. However, some tests were omitted due to non- 35

41 compliance or physical inability. The investigator was not able to obtain tympanometry on one child and OAE s were not gathered for another three. In addition, speech perception tests were tailored individually to each child. That is, age-appropriate and language appropriate tests were selected for each participant. In addition, each child represented was at a different post-implant age, therefore their conditioning and performance abilities differ. III. Instrumentation The MAIS or the IT-MAIS was verbally re-administered to the parents by the investigator. These scales provide information about their child s consistency of cochlear implant use and their child s response to sound in everyday situations. The MAIS and the IT-MAIS were developed as a face valid measure of speech understanding in everyday situations, as there is often a discrepancy between a child's performance on structured auditory tests and listening behaviors in their natural environment. Performance is scored in terms of the total number of points accrued out of the 40 possible points. Each question has a potential of 0 (lowest) to 4 (highest) points. The Lexical Neighborhood Test (LNT) and the Multi-syllabic Lexical Neighborhood Test (MLNT), developed by Indiana University in 1995, are two recorded, open-set tests of word recognition. These tests include words that the child repeats, and have been used to assess recognition of individual words and phonemes in children who are cochlear implant candidates and users. The LNT and MLNT are based on the lexical characteristics of word frequency and neighborhood density, and include words found in the vocabularies of children age three to five. The LNT consist of monosyllabic words, excluding proper nouns, possesives, contractions. 36

42 plurals and inflected forms of words. Both a lexically easy and lexically hard list is available. The MLNT differs only by the fact that words are multi-syllabic. Results from these tests with pediatric cochlear implant users have shown that their lexicons appear to be organized into similarity neighborhoods, and these neighborhoods are accessed in open-set word recognition tests. Studies have shown that normal hearing three- and four-year old children are able to recognize all the words from these two open-set speech perception tests at very high levels of performance. Therefore, these results have been used as a benchmark for children with hearing impairments. Stimuli for the MLNT and LNT are presented at 70 db SPL. Responses are scored separately as the percent of words and phonemes correctly identified for the lexically easy words, for the lexically hard words and then for the test as a whole. Perceptually robust tests, such as these, can provide more reliable estimates of spoken word recognition than traditional tests in which stimulus variablity is pre-determined (i.e PB-K wordlist). The Hearing In Noise Test (HINT) tests speech recognition in the context of sentences. It is a pre-recorded, adaptive speech test administered both in quiet and in the presence of speech noise. This test uses common, simple sentences such as "How are you feeling?" or "The weather looks good today." HINT reliably and efficiently measures word recognition abilities to determine cochlear implant candidacy and to record outcome measures in this population. The HINT consists of 25 equivalent 10-sentence lists that may be presented in either condition to assess sentence understanding. The HINT test is first administered in quiet, using 2 lists of 10 sentences, scored for the number of words correctly identified. HINT in noise uses sentences administered at +10 signal to noise ratio. In the present study, only one child received the HINT, she is 11.9 years old has been a CI user for 8.6 years. 37

43 The Central Institute of the Deaf (CID)W-22 test was used to obtain word discrimination scores on the 3 subjects. This is a phonetically balanced, open-set test for word recognition. There are four lists of 50 words each. They are made up of consonant-nucleus (CN), nucleusconsonant (NC) and consonant-nucleus-consonant (CNC) words. Words can be presented via tape, CD, or monitored live voice. Patients are asked to repeat words to the audiologist. Each word repeated correctly is valued at 2%, and scores are tallied as a percent-correct value. For the present study, the words were administered via live voice by the investigator and presented above the participants SRT. The Word Intelligibility by Picture Identification Test (WIPI) was used on one subject. The WIPI is a popular closed-response test which consists of 25 pages. Each page has 6 colored pictures representing an item named by a monosyllabic word. Four pictures represent a test item, while the other 2 serve to decrease probability of a correct guess. WIPI was developed for use with children with hearing impairment and can be used for children aged 4 years and older. The child is required to point to the correct picture at the prompting of the administrator. The administrator instructs the child to show me Each correct response is worth 4 percentage points. Distortion Product Otoacoustic Emissions (DPOAEs) were obtained for the frequencies 2000 Hz Hz, using the Bio-logic Scout Sport OAE System, in a sound proof booth. Stimuli consist of 2 pure tones at 2 frequencies (ie, f1, f2 [f2>f1]) and 2 intensity levels (ie, L1, L2). The Scout Sport is a diagnostic hand held unit which connects to a computer. The Scout software is then loaded into the computer and the user may set the test protocal; including stimulus intensity (L1 and L2), F2/F1 ratio, and test frequency range points. For the current 38

44 study, a setting of 65/55 db SPL L1/L2 was used. DPOAEs were considered to be present if the distortion product (DP) was at least 9 db above the noise floor across at least one octave. The Ling-6 sounds /m/, /u/, /i/, /a/, /sh/, and /s/ were administered to each child. Detection or identification of these sounds were reported by the investigator. The Ling-6 tests is an auditory only task administerd 3 feet away from the child. The investigator randomly administers each sound to the the child, with no visual cues. Detection of the sound is demonstrated when the child appropriately points to the correct picture representing the sound or develops another conditioned response. Identification of these sounds requires the child to repeat the sound back to the investigator. The Perceived Benefits Questionairre (PBQ), developed by Lisa Hilbert, M.A., CCC-A at CCHMC, determines the amount of benefit parents feel their children receive from the use of his/her cochlear implant device. Fifteen questions are asked regarding their child s usage and benefit from his/her CI. The answers are scaled from 1-5; 1 representing much worse, and 5 representing much imporved. Development of the Perceived Benefits Questionnaire may be helpful in measuring cochlear implant benefit in children who are not able to participate in standard testing. Please see Appendix A for the PBQ 39

45 Chapter 4 RESULTS/DISCUSSION: Previously, authors and clinicians have had reservations or have reported less than adequate outcomes regarding cochlear implants in cases of auditory neuropathy [18,20]. However, the current findings are in contrast to those authors. In the current study, all children showed some measure of improvement with the use of a cochlear implant. The qualitative and quantitative measure of benefit was clinically significant for this population of AN/AD children. Interestingly, our sample of subjects was quiet varied. It included children with neurological delays, physical handicaps, and also we encountered a set of siblings. Performance varied and was likely affected by additional handicapping conditions, age at implantation, duration of implant use, educational setting and/or communication mode. The investigator tabled the the performance outcome measures of audiometry, speech perception testing scores, otoacoustic emissions, and parent questionnaires (Table 4, Figure 4.1).Results of audiologic data (Figure 4.2) as well as the Perceived Benefits Questionnaire were comparable to results from children without AN/AD who have cochlear implants (Figure 4.3). Attempting a statistical analysis was not significant because of the small sample size and lack of a control group. In addition, individual audiologic data of the subset of AN/AD children was compared to the general population of pediatric patients receiving cochlear implants at this center (Table 5). It was the investigators intent to form a control group of non-an/ad children. Rather, a random, quasi-control group of 7 CI users who receive services from CCHMC was compiled. After analyzing this groups demographics, it was determined that the groups were indeed slightly matched, except for the participants sex. The non-an/ad group consisted of all females. However, the mean age of the non-an/ad group was 4 years 7 months and the mean length CI 40

46 use was 2 years 7 months, which is identical to the AN/AD group. The type of implant utilized by all 14 patients was not a factor in the results of this study. The audiologic results, including PTA and SAT/SRT, were compared between the two groups. In addition, the PBQ and the MAIS/IT-MAIS were contrasted, as these are important qualitative scales of benefit in a clinical setting. I. AN/AD Results: The pure tone average of all of the subjects was substantially affected in a positive manner with the use of a cochlear implant (Table 4). Prior to implantation, the severity of hearing loss among the subjects ranged from moderate to profound. Following implantation, the mean pure tone average for the six subjects was 33.6 db; with a range of 23.3 db 66 db. Subject 3 and 5 provided the best frequency specific narrow band noise thresholds; each had a threshold of 23.3 db. Subject 5 has been a cochlear implant user for 8.6 years and subject 3 has been implanted for 2 years. The poorest threshold, 66 db, was obtained for subject 6. Although subject 6 has been a CI user for 2 years 10 months, she does not consistently attend aural rehabilitation and employs total communication, with an emphasis on manual communication. Subject 6 s family participation in the CCHMC post implant program was poor. According to the PTA and SAT/SRT results; 6 of the 7 participants (86%) were considered to be in the slight-mild hearing loss range, 1 subject (14%) had showed a moderate hearing loss Postoperatively, all the children have shown substantial improvement in speech awareness (SAT and/or SRT) (Table 5). The mean SAT/SRT was 28.3 db, again classifying the children in the mild hearing loss range. Subject 3 had the best SRT at 15 db, while subject 6 again performed poorly, obtaining a 50 db SAT. It is important to note the PTA and SAT of subject 4. Subject 4, who is the brother of Subject 5, is autistic and is both developmentally and 41

47 socially delayed. He was a CI user for 5 years 8 months. Although it had been impossible to obtain speech perception testing on subject 3 for the last few years, his thresholds and SAT (30 db) indicate that he was a successful CI user. Another multi-handicapped participant, subject 7, who had no identifiable language, also performed well for speech awareness. His SAT was 20 db, which indicates he too was receiving qualitative benefit from a cochlear implant. The MAIS/IT-MAIS was completed by the subject s parent and reports the child s awareness of acoustic information in everyday situations. This is completed pre-operatively by all parents at CCHMC. Post-operatively, the majority of scores on the MAIS/IT-MAIS showed consistency of CI use and appropriate response to everyday speech. The test is scored on a scale of 0-5, with a total of 40 possible points. The range of scores was between Some questions which parents scored lower regarded their child s inability to discriminate between voices (who were not parents) when the speaker was not visible. Encouraging scores were compiled for questions regarding the child s independency with the device and his/her ability discriminate between speech and non-speech. All parents reported that their child s communication and interaction in everyday situations is significantly affected by the use of a CI. Open and Closed-Set word discrimination scores were also promising for this group of children. The CID W-22 was administered to three children and the WIPI was given to one child. Subject 4,6 and subject 7 could not be tested due to behavioral noncompliance; no speech perception scores were obtained for theseof these children. The ability to obtain speech data for subjects 4 and 7 was precluded by autism and physical handicaps. However at age 5 years 5 months, subject 6 is known to have frequent violent outbursts and temper tantrums. The investigator noted lack of parental discipline as well. Therefore, the speech perception abilities of subject 6 were unknown. Of the children who were tested, the results were very good. Scores 42

48 on the CID W-22 ranged from 84%-92%; each word correct is worth 4 percentage points. It should be noted that the highest score, 94%, was recorded for subject 2, who was the youngest of the participants at age 2.5. She had been a CI user for 1 year 1 month and attended an intensive deaf-oral preschool five mornings a week. However subject 1, age 5.2 had also been implanted for a year and he was unable to respond to the CID W-22 task. Instead, he was given the WIPI, and scored 88%. He had just recently entered the same deaf-oral school as subject 2, where he attended five full days a week. Phonemic discrimination, a more difficult task, was reported by the MLNT/LNT scores of 3 subjects. Open- set tests, such as these, are an important diagnostic yardstick for determining sensory aid benefit in these children because it indicates that they have established neural representations of words in their long-term lexical memory, which is fundamental to the development of spoken language. LNT scores for subject 3 and 5 were both 96% and the MLNT score for subject 2 was a 93%. These outcomes provide insight into the child s ability to follow conversational spoken words, in which the stimulus is variable. The MLNT/LNT scores reported here are consistent with the child s intensive post implant therapies and educational placements. The final speech perception test assessed the individuals ability to discriminate speech in the presence of background noise; a known nuisance for AN/AD children. This task, the HINT, was the most difficult and was only appropriate for 2 children. This test is given in both a quiet and noisy environment. Subject 3 scored a 94 % in quiet and 63% in noise. While subject 5 obtained a 57% in quiet and a 10 % in noise. Although subject 3 is the younger of the two, at age 5.6, both subjects were implanted around the same age ages 3.3 and 3.6. However, their educational placements were quite different. Subject 5, who had been a CI user for 8.6 years, was mainstreamed and had both a full time interpreter and FM system. Subject 5 used total 43

49 communication quite effectively. Subject 3 had been enrolled in an concentrated deaf oral school, with CI peers, for approximately 2 years. Subject 3 s environment also included a teacher-pupil ratio of better than one to four, soundfield amplification, and on-site audiologic services. As discussed, an interesting finding of AN/AD children is secondary loss of OAE s. To better understand this perplexing disorder, it is important to determine whether OAE s are lost naturally or as the result of hearing aid use. Understanding the maturing function of outer hair cells (OHC) in AN/AD children can also provide insight into the site of lesion in AN/AD. DOAE s were obtained on 4 of the subjects; 50% of this population had present emissions. Three of these children wore hearing aids on their non-implanted ear (subjects 1, 5, 2). Subjects 3 and 5 presented with weak, but present, DPOAE s in their non-implanted ear. Subject 2, who was also diagnosed with bilateral Enlarged Vestibular Aqueduct, did not have DPOAE s. However, prior to amplification, the presence of a DPOAE was only observed at one octave. The presence of OAE s in patients with AN/AD suggests that the cochlea has a normal balance of OHC s. Therefore, it is not surprising that patients with AN/AD have functional hearing disabilities similar to those with sensory losses. However, it is not clear if the OHCs which generate the OAE s provide any functional benefit, in terms of sensitivity or frequency resolution in those with AN/AD. It is crucial that OAE s be monitored frequently in AN/AD who are not implanted. Since OAE s may deteriorate without any change in pure-tone sensitivity, there may be a considerable risk that these children have inadequate amplification. As discussed, overamplification via hearing aids can cause a temporary or permanent threshold shift which may halt the habilitation of AN/AD children. 44

50 The introduction of the Perceived Benefits Questionairre (Appendix A) proved to be clinically pertinent and significant for this group of AN/AD children. The questionnaire was developed at CCHMC in hopes of developing more appropriate habilitation plans, counseling, and follow-up care. It was also thought that this method of scaling benefit would be useful in assessing children who are unable to complete objective testing. After reviewing the questionnaires, two main conclusions were determined. First, 100% of the parents in this study reported that their child received benefit from his/her CI. Perceived benefit was rated according to their child s increased social interaction abilities, improved communication abilities, and general independence after receiving the cochlear implant. Secondly, parents of this subset of children perceived benefit even when objective testing did not occur. This was especially seen in the multi- handicapped subjects. The parents of subject 7, whose spoken communication skills did not improve following his CI, raved that their son s quality of life improved post implant. Subject 7 is able to interact with family members and express his wants and needs. In addition, subject 4, although his language skills were still severely delayed, he has exhibited more independency and less stress since receiving his cochlear implant. It is important to discuss the individual results of subject 6. Audiologically, her postimplant test results indicated only marginal benefit with the use of a CI. An absent ABR and operating outer hair cells, as determined by the CM and DPOAES, confirmed an AN/AD diagnosis at age 1 year 8 months. Prior to implantation, there were no medical indicators to suggest this procedure would not result in the development of age appropriate communication abilities. However, since implantation, subject 6 has not been a consistent CI user and frequently does not attend aural rehabilitation as well as speech therapy. The fault may lay in the familial commitment and socioeconomic status. In addition, an oral communication mode is not 45

51 completely supported by the family and manual communication is frequently employed. In addition, professionals question that the site of lesion in this particular patient may hinder the functional abilities of a cochlear implant. Post-implant, subject 6 did not display Neural Response Telemetry (NRT) activity. NRT is a CI feature used to measure how well the hearing nerve fibers in the cochlea respond to electrical stimulation. NRT assures professionals that the auditory nerve is responding to the stimulation provided by the implant. However, NRT is outside the scope of this paper. The degree of benefit and functional abilities subject 6 actually receives from the use of her CI is hard to determine at this time. II. AN/AD group vs. non-an/ad group results: Both qualitative and quantitative test results were compared for these two groups (Figures 4.3, 4.4). As discussed, they are not completely matched, but all 14 participants were CI users for the same mean length of time; 2.7 years. Both the PTA and SAT/SRT mean scores were quite comparable between the two groups. The mean SAT/SRT for the non-an/ad group (22 db) was slightly lower than the AN/AD group (24 db). Similarly, the PTA of the AN/AD group was db, while the non-an/ad mean group thresholds resulted in a 23.3 PTA. These measures do not prove a greater statistical benefit by either group. Also, benefit, as perceived by the child s parent was compared between these two groups. The mean score of the Perceived Benefit Questionnaire was slightly higher in the AN/AD population; while the mean MAIS/IT- MAIS was slightly lower than the CI control group. The development of the PBQ for this particular study proved helpful in comparing the benefit between the AN/AD children and the non-an/ad children. The mean score for the AN/AD group was slightly higher, 4.54, while the non-an/ad group averaged 4.16 out of 5 possible points. Parents of AN/AD children felt their 46

52 child s level of stress, the families stress level, and the child s family participation was much improved after cochlear implantation [Appendix A]. While the quasi-control group may have also expressed improvements in these areas, it was not of the same magnitude as the AN/AD group. These feelings expressed by the AN/AD parents may be reflective of the intense stress before implantation, when these families are searching for the appropriate management of this unique population. Thus, enforcing the need for professional agreement on the diagnosis, counseling, and management of AN/AD children. The only area in which the AN/AD group comprehensively reported a worse rating was for question 6; my child is accepting of wearing the device. According to this data, there was not a substantial benefit for either group. Rather the results indicate a comparable and positive benefit of cochlear implantation in AN/AD children as well as in the general SNHL population. III. Limitations Although this data is encouraging, this study is not without limitations. They include, the small sample size of this study. Participants are not representative of alternative communication modes and post implant treatment options. All of the individuals presented here, except one, were faithful to intensive follow-up care; including aural rehabilitation and a specialized oral education. This sample constitutes 24 % (8/34) of the total AN/AD population diagnosed at CCHMC. In the future it will be important to document the treatment and communication abilities of the 76% (26/34) of AN/AD children who have not received cochlear implants. In addition, these tests scores reflect progress following a relatively short duration follow-up, ranging from years. It is crucial to document the long term performance outcomes 47

53 measures in this population. The reader needs to be cautious about generalizing the results of this study. However, the investigator would predict that future research will mimic the strength of evidence presented here. IV. Direction for Future Research Clinical challenges for this AN/AD population include, identifying a site of lesion, developing appropriate diagnostic protocols, and providing the best possible habilitation. To accomplish this, electrophysiologic tests to measure neural synchrony and inner hair cell function prior to implantation need to be developed. Also, a more anatomically correct term for this diagnostic label should be reviewed. In addition to universal a diagnostic protocol, it will be important to document how AN/AD affects developmental speech and language milestones from infancy to early childhood. Also, genetic components and potential risk factors should continue to be researched in the AN/AD population. As CI s are becoming a more available treatment option for those with AN/AD it will be important to authenticate if CI s do indeed facilitate synchronous firing along the auditory pathway. Also, strategies, such as mapping and speech processing programs, need to be developed for this population. 48

54 Table 4: Aided Audiologic and Speech Perception Results of the AN/AD Group Pure Tone Average (db) Speech Awareness Threshold (SAT or SRT) MAIS or IT- MAIS Word Discrimination MLNT/LNT HINT DPOAE's PBQ Subject db SRT - 20 db 38/40 88 % (WIPI) CNT CNT Absent AU 4.53 Subject db SRT = 25 db 33/40 92% (CID W-22) 93% - MLNT CNT Absent AU 4.80 Subject db SRT db 40/40 88% (CID W-22) 96% - LNT 94% - quiet 63%-noise left ear present 5.00 Subject db SAT - 30 db 32/40 CNT CNT CNT CNT 4.80 Subject db SRT - 30 db 35/40 84% (CID W-22) 96% - LNT 57%-quiet 10%-noise right ear present 4.93 Subject 6 Subject dB SAT - 50 db 22/40 CNT CNT CNT CNT db SAT - 20 db CNT CNT CNT CNT /40 SAT = Speech awareness threshold, SRT = Speech Reception Threshold, MAIS/IT-MAIS = Meaningfull Auditory Index Scale (infant), MLNT = Multisyllabic Lexical Neighborhood Test, LNT = Lexical Neighborhood Test, HINT = Hearing in Noise Test, DPOAE = Distortion Product Otoacoustic Emissions (present or absent), PBQ = Perceived Benefits Questionairre CNT = could not test, CID W-1= Central Institute of the Deaf W-22, WIPI = Word Inteligibility by Picture Identificaiton Test 49

55 Table 5: Pre & Post Implant PTA and VAL/SRT Results for the AN/AD Group Name Pre-implant PTA Post-implant PTA Subject db 26.6 db Pre-implant VAL 105 db (NR) Post-implant VAL/SRT SRT - 20 db Subject 2 75 db 26.6 db 70 db SRT - 25 db Subject 3 90 db 23.3 db 65 db SRT db Subject 4 90 db 30.0 db 75 db VAL - 30 db Subject 5 95 db 23.3 db 80 db SRT - 30 db Subject 6 78 db 66.0dB 65 db VAL - 50 db Subject db 35.0 db 90 db VAL - 20 db PTA=pure tone average, VAL=voice awareness level, SRT=speech recognition threshold NR=no response 50

56 Figure 4.1 AN/AD Audiologic Data IT-MAIS/MAIS SAT/SRT Word discrim % PTA PBQ Subject 1 Subject 2 Subject 3 Subject 4 Subject 5 Subject 6 Subject 7 70 Figure 4.2 PTA and SRT scores SAT/SRT PTA Subject 1 Subject 2 Subject 3 Subject 4 Subject 5 Subject 6 Subject 7 51

57 Table 6: AN/AD group vs. non AN/AD Subject Characteristics Characteristics Age of child; mean (range) AN/AD group (N=7) 5.4 years ( ) Non AN/AD group (N=7) 4.7 years ( ) Sex of child; N (%) Age of child at stimulation; mean (range) Parent completing form: Mother Father 43% male 57% female 2.7 years (1 4.4) 57% 43% 0% male 100% female 2.7 years ( ) 86% 14% Device worn 29% ABC 57% Cochlear 14% Med El 14% ABC 86% Cochlear 0 % Med El Figure 4.3 Mean SRT/SAT & PTA for AN/AD vs. non-an/ad AN/AD SRT/SAT Non-AN/AD PTA Figure 4.4 Perceived Benefits Questionnaire - AN/AD group vs. non-an/ad group Auditory Neuropathy Mean PBQ Non-Auditory Neuropathy 52

58 Chapter 5 Conclusions All of the participants have shown considerable improvements in their sound detection, speech perception abilities, and communication skills. Concomitant disabilities did not affect the successfulness of cochlear implantation in this population. Age at stimulation was not a significant factor in audiologic results either. Rather, the determining factor of success and perceived benefit appears to be an appropriate and intensive post-implant habilitation program. This includes the concurrent participation and commitment of both the CI team and the families of these children. These data suggest that cochlear implantation is a viable treatment option and that AN/AD should not be considered a contraindication to implantation. In addition, the advent of the perceived benefits questionnaire was useful for the children who could not participate in standardized testing and should be considered valuable in other cochlear implant centers. It is important however to stress that the appropriate habilitation of each AN/AD child should be considered individually. 53

59 Appendix A. Perceived Benefits Questionnaire (PBQ) 54