Application of brain stem response in brain-injured children

Application of Brain Stem Response in Brain-Injured Children Yoshisato Tanaka, MD and Kimitaka Kaga, MD

The early components of the auditory evoked potential within 10 msec following an auditory stimulus are attributed to the brain stem auditory nuclei and pathways. In pediatric neurology the auditory brain stem response (ABR) can be applied to: 1) differential diagnosis of hearing impairment in young children including objective threshold measurement of hearing, 2) electrophysiological evaluation of maturation of the auditory pathways, 3) diagnosis of the site and/or extent of neurological diseases affecting the brain stem and 4) observation of a degenerating process of degenerative diseases in the centrdl nervous system. The paper is especially concerned with the application of ABR to severe neurological diseases in children including central auditory dysfunction, cerebral palsy, infantile spasm, adrenoleucodystrophy, anoxic brain damage and Down's syndrome. Value and limitation of ABR audiometry in the clinical practice were mentioned, and a special emphasis was placed on the fact that all types of auditory tests including behavioral, electrophysiological, and developmental tests are indispensable, because the ABR, like other indicators, also has its own limitation. Tanaka Y, Kaga K: Application of brain stem response in brain-injured children. Brain Dev 1980;2:45-56

The early components of auditory evoked potentials-those occurring within the 10 msec following an auditory stimulus-are attributed to the brain stem auditory nuclei and pathways [1, 2] . These components are called the "auditory brain stem response (ABR)" and have been used as a most exciting tool for detecting auditory dysfunction, especially in the brain stem region.

From the Department of Otolaryngology, Teikyo University School of Medicine, Tokyo. Received for publication: November 30, 1979.

Key words: Auditory brain stem response in children, development of auditory function, Down's syndrome, infantile spasm, adrenoleucodystrophy, kernicterus, auditory brain stem audiometry. Correspondence address: Dr. Yoshisato Tanaka, Department of Otolaryngology, Teikyo University School of Medicine, 11-1, Kaga 2-chome, Itabashi-ku, Tokyo, Japan.

Generators of ABR As shown in Fig 1, the ABR in humans generally consists of seven waves denoted by Roman numerals, I through VII, which present the various levels of the auditory pathways in the brain stem. It is known that there are some waveform variations even among normal subjects [3] . Depth recordings and lesion experiments in cat [1,2,4-10] as well as correlations made between abnormalities of some of the early auditory components and sites of brain stem pathology in humans [11,12] suggest that the neuronal generators of Waves I and II are the auditory nerve and cochlear nucleus, respectively. The sources of Waves III, IV, V, VI and VII are still disputed, as summarized in Table 1. As Jewett [7, 13] pointed out, in so far as the waves reflect the algebraic summation of the electrical activity originating from multiple generators, each having a complex cytoarchitecture, it may be safe to say that except for

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Fig 1 ABR for a normal adult showing seven positive peaks.

Wave I there cannot be a strict one-to-one correlation between different ABR components and different anatomic loci. Application of ABR to Pediatric Neurology

In pediatric neurology, ABR can be applied for various purposes, including: 1) Differential diagnosis of hearing impairments in young children, including measurement of hearing threshold; 2) Electrophysiological evaluation of maturation of the auditory pathways; 3) Diagnosis of the sites of neurplogical diseases affecting the brain stem; 4) Observation of the degenerating processes of degenerative diseases in the central nervous system. The following are criteria for ABR abnormalities collected from the literature; 1) Threshold elevation of Wave V; 2) Abnormal behavior of the Wave V latencyintensity curve [14] ; 3) Abnormal latency shift when the click repetition rate is increased [10] ; 4) Prolongation of the intervals between waves (interpeak latency) [15] ; 5) Reductions in the amplitude of the IVIV complex [15] ; 6) Abnormal wave-forms: However, the central nervous system is maturing throughout childhood, and this pro46 Brain & Development, Vol 2, No 1,1980

cess is observed even in the ABR, especially in the early stages of infancy. Accordingly, additional indices for evaluating the maturational changes in the brain stem are needed. The indices used for this purpose which appeared in the literature are: 1) Developmental changes of the ABR waveform [16, 17] ; 2) Shortening of the latency of Wave V with the increase of age [16,18,19] ; 3) Lowering of the Wave V threshold with the increase of age [20] ; 4) Growth of the amplitude of the waves with the increase of age [21] ; 5) Developmental changes resulting in shortening of peripheral transmission time and central transmission, or conduction time as a function of age [22,23] ; 6) Alterations in auditory brain stem recovery processes when rapid click rates are employed. Method

In our clinic, recordings in infants and young children are carried out while they are sleeping after administration of Trichloryl, 1 ml/kg by mouth. Subjects are placed in a supine position on a bed in a sound attenuated and electrically shielded room. Silver disc electrodes are attached at the center of the forehead near the hairline and to

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Wave II

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In Animals

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Wave I

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In Humans

Table 1 Generators of ABR components

Wave V

Inferior colliculus

Lateral lemniscus and inferior colliculus

Inferior colliculus

Inferior colliculus

Ventral nucleus of lateral lemniscus and preolivary region

Midbrain

Inferior colliculus or slightly rostral to it

Inferior colliculus

Inferior colliculus

Rostral pons or midbrain

Lateral lemniscus and inferior colliculus

Wave IV

Wave VII

Thalamus

Thalamus or auditory radiation

Not defined

Wave VI

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both mastoids. These electrodes are differentially amplified (Nihon Kohden RB-5, 1001000 Hz band pass) with the negative input corresponding to the test ear mastoid, the positive input to the forehead, and the non-test mastoid connected to the ground. The amplified responses are averaged by a computer (Nihon-Kohden ATAC 201) and graphically recorded on an X-V recorder. Auditory stimuli consist of three kiitds of click (one cycle segments of 3-kHz, I-kHz, and 500-Hz sine waves) processed by a signal generator (Dana Japan DA-502A), and are delivered to the ear through an attenuator and a TDH-39 earphone.

48 Brain

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Development. Vol 2, No 1, 1980

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obtained from patients with sensorineural hearing loss. B: Audiograms of the patients used. (Yamada et al. 1975114})

Differential Diagnosis of Hearing Impairment A differential diagnosis of conductive hearing loss and sensorineural hearing loss can be made in terms of abnormal behavior of the latencyintensity curve of Wave V [14]. The L-I curve is produced when the latency of Wave V is plotted as a function of auditory stimulus intensity. Fig 2 shows the range of L-I curves for normal adult listeners, indicated by the heavily dotted area, and the L-I curves for conductive hearing loss, which show horizontal shifts to the right. Fig 3 shows the L-I curves for sensorineural hearing loss which fall within the normal range at high stimulus intensities but show a marked deviation from normal at low intensities. The results indicate that differentiation and threshold determination of peripheral auditory pathologies can be made by ABR audiometry. ABR audiometry has been recognized as the

AUDITORY AGNOSIA CASE TN 2 Y ( Postepileptic)

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Fig 4 ABRs and auditory slow vertex responses (SVR) in a boy with auditory agnosia to clicks presented to the right ear. The ABR wave V threshold is approximately 25 dB (reference to the absolute click threshold level of normal hearing listeners). The audiogram indicates the threshold measured by COR audiometry.

most prormsmg procedure for assessing the hearing of difficult-to-test children. Fig 4 shows an example of a great value of ABR audiometry in such a child. The patient was a 2l-month-old boy who had a generalized seizure with auditory agnosia. The mother reported that following the epileptic attack her boy was unable to respond either to verbal commands or to environmental sounds. Neurological examinations showed that he was distractible and hyperactive, although he had started on anticonvulsants, with fairly good seizure control. He never responded to 500-Hz, I-kHz, or 2-kHz tones even at 90 dB, while the waveform and the Wave V threshold of the ABR to clicks were normal as shown in this figure. In this case it was suggested that the peripheral hearing organ as well as the auditory pathways at the brain stem level were intact, and the cause of hearing impairment was at a higher level of the central nervous system.

in age from 9 months to 6 years including an adult subject, were tested by ABR audiometry. The responses shown in Fig 5 are at a click intensity of 85 dB. The waveforms are all abnormal except for case 3, although there are marked individual differences. In cases 1 and 2 the ABR components are not identifiable. Initially, the patients were suspected to have severe hearing loss, but the follow-up studies demonstrated that they had normal hearing. Benda [24] found histopathological slowness of myelination as well as degenerative processes in certain areas of the brain and anomalies which are identical with those seen in myelodysplasia in the spinal cord. He concluded that the central nervous system of a baby with Down's syndrome is essentially immature. Considering the histoanatomical abnormalities reported by Benda, the ABR wave-form abnormalities observed in our patients with Down's syndrome may reflect the slow or pathological maturation of the brain stem.

ABR in Down's Syndrome Seven children with Down's syndrome, ranging Tanaka et al: ABR in brain-injured children

49

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Fig 6 Chronological changes of the ABR waveform in a patient with infantile spasm. The stimulus intensity was 85 dB.

ABR in Infantile Spasm

ABR in Adrenoleucodystrophy [26]

Infantile spasm most commonly occurs between 3 and 8 months of age. This form of seizure indicates damage both to the cortex and to the diencephalon, with the discharging neurons located at the lower level [25]. Infants with this disease, associated with severe mental deterioration or retardation, behave as if profoundly deaf. In such a patient an abnormal ABR is occasionally observed as shown in Fig 6. In this patient the later components following Wave II were not visible at the first examination. This case suggests that there was some dysfunction at the lower level of the brain stem at this time, and, moreover, demonstrates that ABR audiometry is very effective for detecting the anatomic loci of pathology in this disease.

This is a progressive metabolic disease which results in the rapid degeneration of the central nervous system. Both demyelination of the white matter and hypermyelination of the gray matter in the brain have been associated with this disease. Initially, loss of hearing and/or vision is usually observed. The disease progresses rapidly until a degenerate state appears in its terminal stage. Our patient was a 6-year-old boy. He developed normally until 5 years old when external strabismus of the right eye was noted. Then, hearing and visual disorders began. When he first visited us, an examination of hearing acuity demonstrated that he had a moderate sensorineural hearing loss, a normal ABR with a threshold of 15 dB and normal slow vertex response, also with a threshold of 15 dB. He

50 Brain & Development, Vol 2, No 1,1980

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died of apnea at the age of 8 years. Fig 7 illustrates the progressive configurational changes of the ABRs as his general condition deteriorated. The first ABR was normal but the response changed to an abnormal pattern approximately I year after the first recording. Initially, there was lengthening of the wave V-I interpeak interval. This was followed by the disappearance of the later components as the disease progressed. Histologically, the autopsy disclosed, as the main alteration, extremely wide-spread demyelination of the white matter throughout the cerebrum. The histology of the brain stem revealed a marked neural disappearance and various kinds of degeneration of auditory nuclei and tracts including the cochlear nucleus, superior olivary complex, nuclei of lateral lemniscus, inferior colliculus, and medial geniculate body. The auditory nerves were observed to be demyelinated. On the other hand, vestibular nuclei, facial nuclei, and their nerves were not damaged. TIrls case indicated to us that ABR is a useful indicator for evaluating a degenerating process of a progressive degenerative disease of the central nervous system. ABR in Kernicterus It is known that many chidlren with cerebral

palsy caused by kernicterus have an associated sensorineural hearing loss. However, the anatomic site of the lesion in the auditory pathway has not been determined precisely. An animal experiment using a mutant animal model [27], which develops symptoms and signs resembling the human kernicterus syndrome, suggests that wide-spread areas of the central nervous system including the cochlear nucleus, inferior colliculus and cortical areas can be involved. We have tested 26 children suffering from kernicterus by ABR audiometry. Twenty-five of the 26 children had cerebral palsy and the remaining one, who had received an exchange transfusion at the earliest stage of icterus, was normal. Fig 8 shows ABRs to 85 dB clicks. The patients were classified into four groups by the degree of hearing loss: Group A, four children with ABR Wave V thresholds within 20 dB of normal; Group B, six with thresholds between 20 dB and 60 dB; Group C, seven with thresholds between 60 dB and 85 dB; and Group D, eight children who did not respond to 85 dB stimuli. The high ABR thresholds found in the subjects of groups B, C, and D may be best explained by damage of the cochlea [28]. However, we have some inconsistent cases who responded very well behaviorally to pure

Tanaka et al: ABR in brain-injured children

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tones and hwnan voices, although the ABR threshold was greatly elevated, as shown in Fig 9. Follow-up examinations demonstrated the patient had normal hearing acuity. The reason for the high ABR threshold in such a case is not clear, but it might be said that the abnormality of the ABR threshold may reflect a disturbance of synchronous discharges of the 52 Brain & Development, Vol 2, No 1,1980

brain stem auditory neurons in addition to th~ inner ear dysfunction. Gerull et al [29] suggested that myelination of the auditory pathway may be delayed by bilirubin precipitation in the cell bodies of cochlear and retrocochlear neurons, and Chisin et al [30] proposed that bilirubin damage of the cochlear neurons as well as central structures may interfere with

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threshold is lower than the ABR threshold in this patient.

their nonnal function and explain the absence of a response. At all events, the latter case suggests that a result observed by ABR audiometry must be carefully evaluated when the ABR threshold is high. Umitation of ABR Audiometry in Clinical Practice

As many workers have pointed out, ABR audiometry is undoubtedly a promising method of evaluating the function of the auditory pathway from the peripheral organ through the brain stem, and can offer the neurologist and otologist as well as the neurosurgeon an aid for the diagnosis and management of disorders affecting the brain stem. However, it must be remembered that ABR is nothing more than a physiological attribute, while the indicator used for behavioral audiometry is psychological. 1bis means that ABR audiometry cannot take the place of conventional behavioral audiometry in a strict sense. Therefore, the evaluation of hearing and determination of asite of lesion in the brain stem must never be made solely by the use of ABR audiometry. Developmental Test of Auditory Function [31] We have mentioned earlier that the developmental changes of the ABR behavior as a function of age can be observed at the early stages of childhood. However, there is one more

important aspect to be evaluated in terms of developmental neurology, namely the development of auditory behavior during infancy. Unfortunately, until recently, there was no developmental auditory test available for clinical use. Thus, we attempted to develop a scale of expected milestones of behavioral auditory function during the first year of life [31] . The data used for the devel0.pment of the test were collected from 194 normal-hearing infants ranging from birth to 15 months of age. As shown in Table 2 the scale consists of a checklist of 45 items which are placed on a developmental continuum. The testing procedure is very simple: Mothers are asked to check auditory responses of their own infant or young child at home using the scale prior to audiological examinations. Fig 10 illustrates a developmental profIle of auditory function designed for use in a followup study. The numbers on the oblique line correspond to those of the items of the developmental scale. In the normal infant the auditory function develops along this oblique line, but if the development is retarded, the developmental curve is shifted to the right as shown in this figure. The patient shown in this figure was born prematurely, severely mentally retarded, and with associated blindness. His behavioral auditory threshold was fairly high, but ABR Wave V thresholds were within normal limits.

Tanaka et al: ABR in brain-injUred children

53

Table 2 Developmental scale of auditory function in infancy (information to be obtained from the mother) Newborn period 1. A normal infant is startled in response to a sudden noise (Moro reflex). 2. He blinks in response to a sudden noise (auropalpebral reflex). 3. When sleeping he opens his eyes in response to a sudden noise. Two months 4. He is startled with extension of extremities and fingers in response to a sudden noise. 5. When sleeping he opens his eyes or begins to cry in response to a sudden loud noise. 6. When eyes are open he shuts his eyes on hearing a sudden loud noise. 7. When crying he reduces his activity or ceases to cry in response to a soft voice. 8. He makes a rudimentary head tum toward a voice (or a rattle). Three months 9. When sleeping he blinks or moves limbs in reo sponse to a sudden sharp noise (Moro reflex gradually disappears). 10. He is awakened from sleep by a sudden noise such as a child's shout, sneeze or noise made by a vacuum cleaner. 11. He smiles and vocalizes in response to a pleasing voice. Four months 12. When sleeping he blinks or moves his f'mgers on a sudden noise, but the generalized motor reaction has disappeared (Moro reflex absent or a rudimentary form). 13. He smiles and turns his face (or his eyes) toward an interesting sound such as a radio, a click of a switch, or a commercial on the television. 14. He looks anxious in response to an angry voice, while he is delighted by a soft voice. Or he feels comfortable or uncomfortable with a song or music. Five months 15. He pays attention to (or tUl'Il6 his head toward) various noises and sounds of daily life such as door slams, bells, rattles, sounds from a radio or television, etc. 16. He turns his head slowly when you call him by name. 17. He turns his head directly toward a human voice, especially his mother's voice (He discriminates between familiar and strange voices). 18. He turns his head directly toward the direction of an unexpected, strange or newly experienced sound. Six months 19. He turns his head toward the tick of an alarm clock close to his ear. 20. He identifies his parents' voices and his own recorded voice. 21. He is scarred by a sudden unfamiliar, loud noise and clings to the parent or begins to cry. Seven months 22. He watches your face while you talk or sing to him.

54 Brain & Development, Vol 2, No 1,1980

23. When you call him by name he intentionally turns his head toward your voice. 24. He turns his head sensitively toward a radio or television.

Eight months 25. He turns his head toward a noise from the next room or a dog's bark from outdoors (He localises distant noises). 26. He watches our mouth and sometimes vocalises when you talk or sing to him. 27. He turns his eyes quickly toward the television at the beginning of a signatUre tune or a commercial. 28. He is startled or begins to cry on hearing a scolding voice or a sudden loud noise in the vicinity. Nine months 29. He is delighted when you imitate barking, mewing or neighing. 30. When he enjoys to vocalise, he imitates you if you make his own sounds. 31. He pulls back his hands or beings to cry when he is scolded. .32. He turns his head toward the tick of a watch near his ear. Ten months 33. He looks around in or creeps toward the direction of a noise from outdoors, such as the splash of a shower, the noise of an automobile in the street or in the yard. 34. He waves his hand when you say "bye-bye," or the creeps toward you when you say "come here." 35. He creeps toward you when you make a noise in the next room or call him from a distance. 36. He enjoys moving his limbs to music or your singing (He enjoys to listen to music). 37. He promptly turns his head toward a faint noise or sound which is made accidentally or unexpected. Eleven months 38. He imitates you when you say "rna rna" or "da da." 39. He turns his head toward you when you steal near him without attracting his attention and call him by name in a whisper. Twelve months 40. He dances or moves his body rhythmically to music. 41. He gives you what you want when you say "give

me ...." 42. He looks at what you ask him when you say "where is the ... ?) Thirteen-Sixteen months 43. He listens to or brings you attention to a noise or sound in the next room. 44. He responds to your simple verbal commands, such as "bring me a bow waw." 45. He points to his eye, nose, mouth and other parts of his body on your request.

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Summary Developmental aspects of the ABR in young children and the ABR abnormalities in some illustrative examples of children with various kinds of brain injury including hearing impairment, Down's syndrome, infantile spasm, adrenoleucodystrophy, and kernicterus were reported. In the literature there are also some reports of some autistic children and children with learning disorders having an abnormality in the ABR [13, 32,33] ,although corresponding cases have not been found in our clinic. In summary, it can be concluded that the ABR is a most effective indicator for evaluating maturational changes of the auditory neurons as well as detecting the site of lesion or dysfunction of the auditory system in the brain stem in terms of electrophysiology. However, in clinical practice, a special emphasis is placed on the fact that all types of auditory tests are indispensable, becasue the ABR, like other indicators, also has its own limitations.

Acknowledgments The authors extend their gratitude to Dr. Roger Marsh for his help in revising the English. References 1. Jewett DL, Romano MN, Eilliston JS. Human auditory evoked potentials: possible brain stem components detected on the scalp. Science 1970; 167:1517-8. 2. Lev A, Sohmer H. Sources of averaged neural responses recorded in animals and human subjects during cochlear audiometry (electrocochleogram). Arch Klin Exp Ohr-Nas-Kehlk opfbeilk 1972;201:79-90. 3. Chiappa KJ, Gladstone KJ, Young RR. Brain stem auditory responses. Studies of waveform variations in 50 normal human subjects. Arch NeuroI1979;36:81-7. 4. Ando I. The change of BSR by the section of the eighth nerve in cats. Audiol Japan (Tokyo) 1977; 20:733-6. 5. Ando 1. The experimental study of BSR (The change of BSR by the destruction of inferior colliculus). Audiol Japan (Tokyo) 1977;20:210-20. 6. Buchwald JLS, Huang CoM. Far-field acoustic

Tanaka et al: ABR in brain-injured children

55

7.

8. 9.

10.

11.

12.

13. 14. 15. 16.

17.

18. 19. 20.

response: origins in the cat. Science 1975;189: 382-4. Jewett DL. Volume conducted potentials in response to auditory stimuli as detected by averaging in the cat. Electroencephalogr Clin NeurophysioI1970;28:609-18. Koh M. Changes of BSR by destruction of superior olivary nuclei in cats. Audiol Japan (Tokyo) 1978;21 :645-52. Shinoda Y, Kaga K, Hink RF. Brain stem mapping and lesion study of the BSR in cats. Presented at the US-Japan Seminar on Auditory Responses from the Brain Stem, Honolulu, January 5-7,1979. Uchida T, Ichikawa G, Koh M. The changes of middle latency response after medial geniculate body destruction in cats. Audiol Japan (Tokyo) 1979;22:167-72. Sohmer H, Feinmesser M, Szabo G. Sources of electrocochleographic responses as studied in patients with brain damage. Electroencephalogr Clin NeurophysioI1975;28:609-18. Starr A, Hamilton A. Correlation between confIrmed sites of neurological lesions of far-fIeld auditory brain stem responses. Electroencephalogr Clin NeurophysioI1976;41:595-608. Jewett DL, Williston JS. Auditory-evoked far fIelds averaged from the scalp of humans. Brain 1971 ;94 :681-96. Yamada 0, Yagi T, Yamane H. Clinical evaluation of the auditory evoked brain stem response. Auris Nasus Larynx (Tokyo) 1975;2:97-105. Stockard n, Rossiter VS. Clinical and pathologic correlates of brain stem auditory response abnormalities. Neurology 1977;27:316-25. Salamy A, McKean CM, Buda FB. Maturational changes in auditory transmission as reflected in human brain stem potentials. Brain Res 1975;96: 361-6. Salamy A, McKean CM, Petett G, Mendelson T. Auditory brain stem recovery processes from birth to adulthood. Psychophysiology 1978;15: 214-20. Hecox L, Galambos R. Brain stem auditory evoked responses in human infants and adults. Arch OtolaryngoI1973;90:30-3. Schulman-Galambos C, Galambos R. Brain stem auditory evoked responses in premature infants. J Speech Hear Res 1975;18:456-65. Kaga K, Tanaka Y. The correlation of brain stem responses and behavioral audiometry in neonates, infants and adults. No To Hattatsu (Tokyo) 1978;10:284-90.

56 Brain & Development, Vol 2, No 1, 1980

21. Lieberman A, Sohmer H, Szabo G. Cochlear audiometry (electrocochleography) during the neonatal period. Dev Med Child Neurol1973 ;15: 8-13. 22. Salamy A, McKean CM. Postnatal development of human brain stem potentials during the fIrst year of life. Electroencephalogr Clin NeurophysioI1976;40:418-26. 23. Starr A, Amlie RN, Martin WHo Development of auditory function in newborn infants revealed by auditory brain stem potentials. Pediatrics 1977; 60:831-9. 24. Benda CEo Down's syndrome. In: Mongolism and its management. (Revised edition). New York: Grune & Stratton, 1969;134-65. 25. Menkes JH. Textbook of child neurology. Philadelphia: Lea & Febiger, 1974:431. 26. Kaga K, Tokoro Y, Tanaka Y. The progress of adrenoleucodystrophy as revealed by auditory brain stem evoked responses and brain stem histology. Arch Oto-Rhino-Laryngol (Berlin) (in press). 27. Jew JY, Sandquist D. CNS changes in hyperbilirubinemia. Functional implications. Arch Neurol 1976;36:149-54. 28. Kaga K, Kitazumi K, Kodama K. Auditory brain stem responses of kernicterus. Int J Pediatr Otorhinolaryngol1979;1 :255-64. 29. Gerull GM, Giesen M, Mrowinsk D. Quantitative Aussagen der Hirnstamm-audiometrie bei mittelohr-, kochlearen und retrocochlearen Horschaden, Laryngol RhinoI1978;57:54-62. 30. Chisin R, Perlman M, Sohmer H. Cochlear and brain stem responses in hearing loss following neonatal hyperbilirubinemia. Ann Otolaryngol 1978;88:352-7. 31. Tanaka Y, Shindo M, Kaga K. Developmental test of auditory function: its clinical use and application to early identification of hearing impairment. Audiol Japan (Tokyo) 1978;21:51-73. 32. Sohmer H, Student M. Auditory nerve and brain stem evoked responses in normal, autistic, minimal brain dysfunction and psychomotor retarded children. Electroencephalogr Clin Neurophysiol 1978;45 :515-24. 33. Stillman RD, Moushegian G, Pupert AL. Early tone-evoked responses in normal and hearingimpaired SUbjects. Audiology 1976 ;15: 10-22. 34. Yagi T, Kaga K. The effect of the click repetition rate on the latency of the auditory evoked brain stem response and its clinical use for a neurological diagnosis. Arch Oto-Rhino-Laryngol (Berlin) 1979;222:91-7.