Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Retrograde Degeneration of the Cochlear Nerve H. Spoendlin To cite this article: H. Spoendlin (1975) Retrograde Degeneration of the Cochlear Nerve, Acta Oto-Laryngologica, 79:3-6, 266-275, DOI: 10.3109/00016487509124683 To link to this article: http://dx.doi.org/10.3109/00016487509124683
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 63
View related articles
Citing articles: 18 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [University of California, San Diego]
Date: 13 April 2016, At: 05:31
Acta Otolaryngol 79: 266-275, 1975
RETROGRADE DEGENERATION O F THE COCHLEAR NERVE
H. Spoendlin
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
From the Department of Otolaryngology, University of Zurich, Zurich, Switzerland
Abstract. Retrograde degeneration of the cochlear neurons has been studied in different types and degrees of peripheral cochlear damage such as acoustic trauma, intoxication, heredodegenerative deafness and others. It starts only when the peripheral dendrites to the inner hair cells are irreversibly damaged. About 10% of the neurons are not affected by retrograde degeneration. They correspond to the type I1 and I11 neurons, which also survive after transection of the cochlear nerve and are mainly associated with the outer hair cells. Cochlear damage due to vascular impairment usually leads to a complete loss of cochlear neurons. In hereditary abiotrophic deafness, neuronal degeneration is slower and its extent varies considerably according to the various genetic syndromes.
It is well known that retrograde degeneration occurs after destruction of the organ of Corti. The fact that an entire neuron degenerates when only the terminal portions of its dendrites are damaged is a peculiar phenomenon rather unique in the cochlear nerve. Especially in respect to electrical stimulation of totally deaf ears, it is important to know what induces this retrograde degeneration and how long and to what extent it proceeds under different pathological conditions. For this purpose we produced experimental damage of the end organ by acoustic trauma, intoxication with neomycine or direct surgical destruction and examined the cochlea after different surviving times from a few days up to one year using the bloc-surface technique (Spoendlin, 1974). In addition, the behaviour of the cochlear neurons in hereditary deafness in the deaf white cat and in some temporal bones of human cases with hereditary and acquired total deafness was studied. There have been discussions about the type of alterations in the organ of Corti which induce Acta Otolaryngol 79
retrograde degeneration. The crucial factor has been proposed to be the loss of inner hair cells (Bredberg, 1968), the collapse of the supporting elements of the organ of Corti (Schuknecht, 1953) or a direct damage to the cochlear nerve dendrites at the inner hair cells (Spoendlin, 1971). The total loss of outer hair cells over a greater length of the cochlear duct leads to the disappearence of the outer spiral fibres but it has no appreciable effect on the cochlear neurons in the osseous spiral lamina and in the spiral ganglion even after surviving times of one year, as long as the majority of inner hair cells are present (Figs. 1 and 2 A ) . The loss of the inner hair cells on the other hand is usually followed by a massive retrograde degeneration of the cochlear neurons, regardless of the presence or absence of the outer hair cells. The collapse of the supporting structures does not seem to be crucial for the initiation of degeneration, since complete retrograde degeneration is frequently seen in areas with in‘tact supporting structures (Fig. 2B). Although there is in general a good correlation between the number of destroyed inner hair cells and the degree of retrograde degeneration, we observed degeneration in areas with the inner hair cells present or no degeneration in areas with extensive loss of inner hair cells. This indicates that retrograde degeneration does not depend directly on the presence or absence of inner hair cells, but from some other factors. It is most likely the consequence of a direct damage to the peripheral unmyelinated segments of the cochlear neurons associated with the inner hair
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 267
Fig. I . Bloc-surface preparation (above) with corresponding schematic evaluation (below) of a guinea pig cochlea one year following acoustic overstimulation with 140 dB white noise for 20 min. In the upper half of the lower basal turn and in the upper basal turn, where the organ of Corti is completely gone (blank area) only 10% of
the cochlear nerve fibres in the osseous spiral lamina remain ( ). In the lower half of the lower basal turn ( A ) , where all outer hair cells are missing (......) but the inner there remains a full populahair cells are present (-), tion of nerve fibres in the osseous spiral lamina (100 %, see Fig. 2).
cells as inner radial fibres, which constitute about 95 yo of the entire cochlear neuron population (Spoendlin, 1969). It has been shown that these inner radiai fibres are particularly sensitive to many kinds of injury such as acoustic trauma (Spoendlin, 1971) and anoxia (Spoendlin, 1968), whereas the other nerve fibres are much more resistant. Irreversible damage initiating retrograde degeneration begins with excessive swelling of the fibres and ruptures of the axon membranes. This is frequently but not necessarily associated with a loss of inner hair cells or with a collapse of the supporting structures. The integrity of its peripheral terminal portion seems to be essential for the neuron to survive. Retrograde degeneration starts almost immediately after rupture of the inner radial fibres and proceeds within a few days through the osseous spiral lamina t o the spiral ganglion, where it is considerably delayed. After 3 weeks the great majority of nerve fibres in the osseous
spiral lamina have entirely disappeared but there is only a slight reduction of ganglion cells in the spiral ganglion. It is not before 3 months that degeneration of the ganglion cells has occurred on a larger scale and the number of ganglion cells is drastically reduced in a relatively short time. After 5 months only about 10 % of the normal ganglion cell population remain and this situation seems to be maintained (Fig. 3). After one year there are still about 10% of healthy looking ganglion cells present. When only the peripheral receptor is damaged, as in acoustic trauma, mechanical destruction, or intoxication with ototoxic antibiotics, retrograde degeneration never affects all neurons. 5-10 % of the neurons are always spared and resist retrograde degeneration. However, as soon as the cochlear blood supply is impaired or an infection affects the neurons directly, only very few or no neurons survive, resulting in a total loss of neurons. The next question concerns the type of neu-
18 - 752959
Acta Otolaryngol79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
268 H. Spoendlin
Fig. 2. (A) Elxtron micrascopic view of the or&an cf Corti from the lower half of the Iswer basal ttlri1 ( A ) of the cochlea in Fig. 1 . Although the outer hair cells are entirely missing ( x), the nerve fibres do not degenerate as long as the inner hair cells (iff) are present. The outward bending of the sensory hairs (Sf)of the Acta Otolaryngol79
i::ne; hair cell is a typical irr:v:rsible effect of the acoustical traumatisation. (B) The organ of Corti in the tipper basal turn 3 months after acoustic traumatisation. Here most outer hair cells (off) remain but the inner hair cells are missing ( x ) and the great majoiity of nerve fibres have degenerated (x).
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 269 ron which resists retrograde degeneration. In after retrograde degeneration following destrucnormal guinea pigs (Kellerhals et al., 1967; tion of the organ of Corti also represent mainly Spoendlin, 1971)and cats (Spoendlin, 1971; Ross, the innervation of the outer hair cells, whereas 1971) two different types of neuron are found in the nerve supply of the inner hair cells degenthe spiral ganglion: The great majority (type I) of erates (Fig. 4). It is an open question how much these exganglion cells are large and myelinated whereas perimental data in laboratory animals are apabout 10 % in the guinea pig and 5 76 in the cat plicable to the situation in the human. There is are smaller and unmyelinated (type 11) (Fig. 4). In the guinea pig one year following acoustical not much reason to believe that the human destruction of the organ of Corti, the majority cochlea would behave basically differently in of the surviving neurons are small and unmye- damage due to acoustic trauma or intoxication. linated, corresponding to the type I1 in the nor- Although antibiotic intoxication is still one of mal ganglion, whereas most of the type I cells the important causes of acquired total deafhave disappeared. A similar situation is found ness, genetic causes, infections and vascular disin the cat, where also practically all myelinated turbance play a by far more important role in type I ganglion cells degenerate and disappear the aetiology of total deafness and they are in the course of retrograde degeneration. The hardly reproducible in animal experiments. The histopathology of human temporal bones remaining 10% consist partly of type I1 cells with all their characteristics and partly of an- in persons who became totally deaf following other type of ganglion cell which resembles meningitis, bacterial labyrinthitis or head trauma closely the type I but is not myelinated (type reveals either a total bony obliteration of the 111) (Spoendlin, 1973). Surviving type I cells are cochlea without remaining neurons or, when the cochlear spaces are preserved, a total disexceptional. In the cat an interesting comparison between appearance of the organ of Corti and a practithe findings of retrograde degeneration after cally total loss of neurons (Fig. 5 A , B). destruction of the organ of Corti and the deViral labyrinthitis due to mumps or measles, generation pattern following transection of the on the other hand, affects mainly the endolymcochlear nerve in the inner acoustic meatus may phatic epithelial structures and spares the neugive some hints about the significance of the rons. Considerable retrograde degeneration of surviving neurons. In fact, the same type of the cochlear neurons seems to be rare following neurons (I1 and 111) resist degeneration after prenatal and of moderate degree following posttransection of the cochlear nerve (Spoendlin, natal infections (Lindsay, 1973). 1971, 1973, 1974) as in retrograde degeneration. A more complex situation is found in abioSince the organ of Corti does not degenerate trophic hereditary deafness, which represents a after section of the cochlear nerve it is seen that very important cause of total bilateral deafness the entire afferent nerve supply of the outer hair in man. Although histopathological information cells remains intact and almost all inner radial is rare, it seems that the degeneration process fibres, the afferent nerve supply of the inner hair usually begins as a cochleo-saccular degeneracells disappears. This means that essentially the tion within the endorgan or the stria vascularis afferent neurons for the outer hair cell system with varying degrees of secondary retrograde resist degeneration and that the type 11 and 111 degeneration of the cochlear neurons. Less frecells belong mainly to the neurons supplying the quently primary, almost total degeneration of outer hair cell system, whereas the type I cells the neurons in the presence of an intact endorgan belong to the neurons leading to the inner hair occurs, as shown in the temporal bones of two cells. Since we find the same type of neuron profoundly deaf persons suffering from Friedremaining after retrograde degeneration, it is reich’s disease (Spoendlin, 1974). In a number therefore most likely that the surviving neurons of cases of hereditary deafness with primary Acta Otolaryngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
270 H. Spoendlin
Acta Otolaryngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 271
Fig. 4. Schematic representation of the cochlear neurons in the cat. In the normal cat most ganglion cells arc large and myelinated of type I (I) and only few are small and unmyelinated of type TI (11). The efferent intraganglionic spiral bundle (e) consists of many myelinated and unmyelinated fibres; the inner radial fibres (iv) provide the afferent nerve supply of the iniiei hair cells whereas the
outer spiral fibres (OJ) are the afferent fibres to the outer hail cells. After destruction of the organ of Corti most type 1 cells degenerate and only type I1 and 111 cells remain. After sectlon of the VIII nerve the same type of ganglion cells survive together with the outer spiral fibres (as) and the afferent nerve endings at the outer hair cells. ~
Fig. 3. Spiral ganglion of the upper basal turn of a guinea pig cochlea: (A) Normal situation with a full set of densely packed myelinated type I ganglion cells and a few smaller unmyelinated type I1 ganglion cells (IT). The intraganglionic spiral bundle consists of densely packed efferent fibres (e). (B) Three weeks after complete acoustical destruction of the organ of Corti. In spite of degeneration of most fibres in the osscous spiral lamina only about 50% of the ganglion cells have disappeared.
(C) Three months after acoustical destruction of the organ of Corti. Most myelinated ganglion cells of type I arc gone. (D) One year after acousticaI destruction of the organ of Corti. 5-10% of the ganglion cells, mainly type I1 cells (11) and only few type I cells (I) remain without any signs of degeneration. Also the number of efferent fibres in the interganglion spiral bundle (e) is markedly reduced. Acta Otolaryngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
272 H. Spoendlin
Acta Otolavyngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 273 endorgan degeneration the secondary retrograde neuronal degeneration seems to be very much delayed or incomplete. Thus we observed one patient with Alport syndrome who was totally deaf for several years before death and two deafmute patients with Usher’s syndrome, whose cochleas revealed preservation of a fair number of neurons in spite of severe damage to or absence of the organ of Corti (Fig. 5C). Other cases of profound or total congenital hereditary deafness with very good preservation of cochlear neurons over many years have been reported by Lindsay (1973) and Gacek (1971). More precise information about this type of hereditary congenital deafness associated with pigment anomalies is: provided by histological studies in animals such as deaf mouse mutants (Deol, 1954; Gruneberg, 1956; Ernstson, 1971), the dalmatian dog (Lurie, 1948; Schuknecht et al., 1965; Anderson et al., 1968) and the deaf white cat (Bosher & Hallpike 1965; Mair, 1973). According to the studies of Mair in the deaf white cat, substantial degeneration of the spiral ganglion started only at the end of the first year of life and progressed continuously over the entire observation period of 8 years. Well preserved neuron populations as reported by Schuknecht and Anderson in the dalmatian dog are probably due to the young age (maximum 18 months) at which the animals were sacrificed and examined, before retrograde degeneration had taken place on a larger scale. Retrograde degeneration in hereditary cochleo-saccular degeneration certainly proceeds much more slowly than it does after de-
Fig. 5. (A) Cochlea of a patient who 48 years ago became deaf during bacterial meningitis. Complete bony obliteration of all cochlear spaces ( x ) and total loss of cochlear neurons. (B) Cochlea of a patient who became totally deaf as the consequence of a head blow 60 years ago. Total loss of sensory elements and practically total loss of cochlear neurons. Partial fibrous obliteration of the perilymphatic spaces. (C) Cochlea of a deaf-mute patient which died at the age of 20, who suffered from Usher’s syndrome with a positive family history. In spite of an entirely absent organ of Corti in all turns there is a fail number of remaining cochlear neurons ( N ) mainly in the upper turns.
struction of the organ of Corti by acquired factors. There is a considerable lag between the complete collapse of the organ of Corti which determines the hearing loss, and the retrograde neuronal degeneration. In the deaf white cat we find during a great part of adult life between 5-10% remaining ganglion cells similar to the situation in retrograde degeneration after experimental destruction of the organ of Corti. Even the type of the surviving cells might be the same, as far as can be judged from the available histopathological material. Only in the old animal do the surviving neurons also begin to show signs of degeneration, eidicr due to aging or to the hereditary deafness iactors.
CONCLUSIONS 1. Total deafness due to vascular impairment or bacterial labyrinthine infection is usually associated with a complete loss of neurons. 2, In deafness following viral labyrinthitis there is frequently a relatively good preservation of the cochlear neurons. 3. In cases of selective endorgan destruction (intoxication, acoustic trauma) retrograde degeneration is incomplete, leaving 5-10 % of neurons to survive, mainly associated with the outer hair cell system. 4. Congenital hereditary abiotrophic deafness presents a very variable situation with extensive retrograde degeneration in some cases (Waardenburg-Syndrom), relatively good preservation of neurons in other cases (Usher-Syndrom) and cases of primary neural degeneration and an intact endorgan. The time course of retrograde degeneration in hereditary deafness seems to be very slow and might vary considerably between the different syndromes. Even in cases of extensive retrograde degeneration a small percentage of neurons tend to survive over a long period of time. The behaviour of the cochlear neurons varies considerably according to type of cochlear damage in deafness and a careful individual appraisal Acta Otolaryngol 79
274 H. Spoendlin of every case is therefore essential to judge the usefulness of a possible electrical stimulation of the cochlear nerve by electrode implantation.
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
ZUZAMMENFASSUNG Die retrograde Degeneration der Cochlearisneuronen wurde nach cochlearen Schadigungen verschiedenen Ausmasses und verschiedener Art, wie akustischem Trauma, Intoxikation, heredodegenerativer Veranderung und anderen untersucht. Eine wesentliche neuronale Degeneration beginnt erst wenn die peripheren zu den inneren Haarzellen ziehenden Dendriten irreversibel geschadigt sind. Ca. 1 0 % der Neurone werden von der retrograden Degeneration nicht erfasst. Es sind dies Neuronen vom Typ 11 and 111, die auch nach Durchtren nung des Nervus cochlearis uberleben und im wesentlichen zum System der ausseren Haarzellen gehoren. Cochleaschaden infolge schwerer Durchblutungsstorungen fuhren in der Regel zu vollstandigem Verlust der Cochlearisneuronen. Bei heredodegenerativer Innenohrschwerhorigkeit verlauft die retrograde neuronale Degeneration langsamer und ihre Ausdehnung variert stark bei verschiedenen genetischen Syndromen.
REFERENCES Anderson, H., Henricson, B., Lundquist, P.-G., Wedenberg, E. & Wersall, J. 1968. Genetic hearing impairment in the Dalmatian dog. Acta Otolaryngol (Stockh), Suppl. 232, 1 . Bosher, S. K. & Hallpike, C. S. 1965. Observations on the histological features, development and pathogenesis of the inner ear degeneration of the deaf white cat. Proc R Soc B162, 147. Bredberg, G . 1968. Cellular pattern and nerve supply of the human organ of Corti. Acta Otolaryngol (Stockh), Suppl. 236, 1. Deol, M. S. 1954. The anomalies of the labyrinth of the mutants varitint-waddler, shaker-2 and jerker in the mouse. J Genet 52, 562. Ernstson, S. 1971. Cochlezr morphology in a strain of the waltzing guinea pig. Acta Otolaryngol (Stockh) 71, 469. Gacek, R. R. 1971. The pathology of hereditary sensorineural hearing loss. Ann Otol Rhinol Laryngol80,289. Griineberg, H. 1955-56. Hereditary lesions of the labyrinth in the mouse. Br Med Bull 11-12, 153. Kellerhals, B., Engstrom, H. & Ades, H. W. 1967. Die Morphologie des Ganglion spirale cochleae. Acta Otolaryngol (Stockh), Suppl. 226, 1. Lindsay, J. R. 1973. Profound childhood deafness. Inner Ear pathology. Ann Otol Rhinol Laryngol, Suppl. 5, 1. Lurie, M. H. 1948. The membranous labyrinth in the congenitally deaf Collie and Dalmatian dog. Laryngoscope 58, 279. Mair, I. W. S. 1973. Hereditary deafness in the white cat. Acta Otolaryngol (Stockh), Suppl. 314, 1. Acta Otolaryngol79
Ross, M. D. 1971. Fluorescence and electron microscopic observations of the general visceral, efferent innervation of the inner ear. Acta Otolaryngol (Stockh), Suppl. 286, 1. Schuknecht, H. F. 1953. Lesions of the organ of Corti. Trans A m Acad Ophthalmol Otolaryngol57, 366. Schuknecht, H. F., Igarashi, M. & Gacek, R. R. 1965. The pathological types of cochleo-saccular degeneration. Acta Otolaryngol (Stockh) 59, 154. Spoendlin, H. 1968. Ultrastructure and peripheral innervation pattern of the receptor in relation to the first coding of the acoustic message. In Hearing mechanisms in vertebrates (ed. A. V. S. de Reuck & J. Knight), pp. 89-1 19. Churchill, London. - 1969a. Innervation patterns in the organ of Corti of the cat. Acta Otolaryngol (Stockh) 67, 239. - 1971. Degeneration behaviour of the cochlear nerve. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 200, 275. - 1973. The innervation of the cochlear receptor. Proceeding of a Symposium on: Basic Mechanisms in Hearing, pp. 185-234. Academic Press, New York. 1973. Neuroanatomy of the cochlea. In Facts and model in hearing, Zwicker u. Terhardt (Springer-Verlag, Heidelberg). - 1974. Optic and cochleovestibular degenerations in hereditary ataxias. 11. Temporal bone pathology in two cases of Friedreich’s ataxia with vestibulocochlear disorders. Brain 97, 41. - 1974. The bloc surface technique for the evaluation of cochlear pathology. Arch Klin Exp Ohren Naseu2 Kehlkopfheilkd 208, 137. ~
H . Spoendlin, M.D. Dept. of Otolaryngology University of Zurich Zurich, 8006 Switzerland
DISCUSSION I . Friedmann: Is regeneration possible? Wardenburg syndrome-material on which figures are based. M. Lawrence; I noticed that the unmyelinated ganglion cells in the normal ganglion section had lobulated nuclei while in the ears in which these unmyelinated ganglion cells were the only cells remaining, the nuclei did not appear lobulated. Could there have been changed ganglion cells or was this appearance merely a matter of the particular section shown? M. Portmann: You show this degeneration of neurofibres after ototoxic aggression. How d o you explain the success of cochlear implant in such case? I saw on your slides a degeneration of efferent spiral bundle after acoustic trauma. Long ago I did the same sort of research and always found an intact spiral bundle after the destruction of the afferent system by acoustic trauma. How d o you explain this difference in our results? J. M. Sdnchez-Fernandez: I agree with Mr Lawrence and Mr Portmann about its importance by the clinical application in cochlear implants. Which is the limit in the time of the retrograde degeneration and in which
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneraton of the cochlear nerve level does it occur? Have you studied the central cochlear nucleus? Which are the initial ultrastructural findings of the retrograde degeneration in the myelin ganglion cells? G. Zecliner: By studying otosclerosis and inner-eardeafness 1 always found very few surviving ganglion cells with and without the organ of Corti. There was also a case where the focus arrived in tractus foraminosus in the meatus accusticus int. The organ of Corti was preserved but the ganglia cells were missing due to the destruction of nerve fibres by pressure. What is in your opinion the indication for cochlea implants, when mainly ganglion cells are missing in 95 %? C. R. Pfaltz: Would a similar type of retrograde degeneration also be expected in the vestibular nerve? H. Spoendlin (Reply) to I. Friedmann: The few remaining neurons after retrograde degeneration of the cochlear nerve lose only the most peripheral portion of the dendrites. Tye might have a certain regeneration capacity, which however does not help much, since the organ of Corti is entirely missing. I am well aware of the fact that you have studied the only available temporal bone of a case of Waardenburg syndrome. With the 5 % surviving neurons I am mainly referring to hereditary deafness associated with pigment anomalies in general. To Mr Lawrence: The surviving ganglion cells are of type I1 and 111. The type 111 cells have a tendency to prevail after retrograde degeneration. To Mr Porrmann: The decision whether a cochlear implant could be useful or not in a patient deafened as a consequence of antibiotic intoxication must rely on the question whether 5-10 % surviving neurons are sufficient for the transmission of complex acoustic messages. A
275
possible hint that very few neurons could be sufficient for useful hearing might be given by the example of the two cases of Friedreich’s disease of which we examined the temporal bones and where we found a primary degeneration of the cochlear neurons in the presence of an intact organ of Corti. Although only very few cochlear neurons were left at the lower end of the cochlea, the patients were not totally deaf. Not only the afferent cochlear neurons, but also, to our great surprise the efferent fibres in the interganglionic spiral bundle, undergo retrograde degeneration after long survival times following destruction of the organ of Corti. Even in areas where only the outer hair cells are gone there is a substantial reduction in the number of intraganglionic spiral fibres. To Mr Sanchez-Fernandez: The cochlear nucleus was not examined in our material. Degeneration of the cochlear neurons seems to proceed in the guinea pig and cat over 4-5 months. After longer survival times of one and two years we always find approximately the same number of surviving ganglion cells. To Mr Zechner: The reason that you found fewer surviving ganglion cells in human temporal bones in cases of profound inner ear deafness than we found in our experimentally induced inner ear deafness might be the additional effect of presbyacusis which probably also affects the surviving neurons after retrograde degeneration. To Mr Pflatz: The vestibular neurons seem to behave differently. After section in the inner acoustic meatus they show only minor degeneration and most neurons survive after destruction of the sensory epithelium by locally applied ototoxic antibiotics.
Acta Otolaryngol 79
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Retrograde Degeneration of the Cochlear Nerve H. Spoendlin To cite this article: H. Spoendlin (1975) Retrograde Degeneration of the Cochlear Nerve, Acta Oto-Laryngologica, 79:3-6, 266-275, DOI: 10.3109/00016487509124683 To link to this article: http://dx.doi.org/10.3109/00016487509124683
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 63
View related articles
Citing articles: 18 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [University of California, San Diego]
Date: 13 April 2016, At: 05:31
Acta Otolaryngol 79: 266-275, 1975
RETROGRADE DEGENERATION O F THE COCHLEAR NERVE
H. Spoendlin
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
From the Department of Otolaryngology, University of Zurich, Zurich, Switzerland
Abstract. Retrograde degeneration of the cochlear neurons has been studied in different types and degrees of peripheral cochlear damage such as acoustic trauma, intoxication, heredodegenerative deafness and others. It starts only when the peripheral dendrites to the inner hair cells are irreversibly damaged. About 10% of the neurons are not affected by retrograde degeneration. They correspond to the type I1 and I11 neurons, which also survive after transection of the cochlear nerve and are mainly associated with the outer hair cells. Cochlear damage due to vascular impairment usually leads to a complete loss of cochlear neurons. In hereditary abiotrophic deafness, neuronal degeneration is slower and its extent varies considerably according to the various genetic syndromes.
It is well known that retrograde degeneration occurs after destruction of the organ of Corti. The fact that an entire neuron degenerates when only the terminal portions of its dendrites are damaged is a peculiar phenomenon rather unique in the cochlear nerve. Especially in respect to electrical stimulation of totally deaf ears, it is important to know what induces this retrograde degeneration and how long and to what extent it proceeds under different pathological conditions. For this purpose we produced experimental damage of the end organ by acoustic trauma, intoxication with neomycine or direct surgical destruction and examined the cochlea after different surviving times from a few days up to one year using the bloc-surface technique (Spoendlin, 1974). In addition, the behaviour of the cochlear neurons in hereditary deafness in the deaf white cat and in some temporal bones of human cases with hereditary and acquired total deafness was studied. There have been discussions about the type of alterations in the organ of Corti which induce Acta Otolaryngol 79
retrograde degeneration. The crucial factor has been proposed to be the loss of inner hair cells (Bredberg, 1968), the collapse of the supporting elements of the organ of Corti (Schuknecht, 1953) or a direct damage to the cochlear nerve dendrites at the inner hair cells (Spoendlin, 1971). The total loss of outer hair cells over a greater length of the cochlear duct leads to the disappearence of the outer spiral fibres but it has no appreciable effect on the cochlear neurons in the osseous spiral lamina and in the spiral ganglion even after surviving times of one year, as long as the majority of inner hair cells are present (Figs. 1 and 2 A ) . The loss of the inner hair cells on the other hand is usually followed by a massive retrograde degeneration of the cochlear neurons, regardless of the presence or absence of the outer hair cells. The collapse of the supporting structures does not seem to be crucial for the initiation of degeneration, since complete retrograde degeneration is frequently seen in areas with in‘tact supporting structures (Fig. 2B). Although there is in general a good correlation between the number of destroyed inner hair cells and the degree of retrograde degeneration, we observed degeneration in areas with the inner hair cells present or no degeneration in areas with extensive loss of inner hair cells. This indicates that retrograde degeneration does not depend directly on the presence or absence of inner hair cells, but from some other factors. It is most likely the consequence of a direct damage to the peripheral unmyelinated segments of the cochlear neurons associated with the inner hair
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 267
Fig. I . Bloc-surface preparation (above) with corresponding schematic evaluation (below) of a guinea pig cochlea one year following acoustic overstimulation with 140 dB white noise for 20 min. In the upper half of the lower basal turn and in the upper basal turn, where the organ of Corti is completely gone (blank area) only 10% of
the cochlear nerve fibres in the osseous spiral lamina remain ( ). In the lower half of the lower basal turn ( A ) , where all outer hair cells are missing (......) but the inner there remains a full populahair cells are present (-), tion of nerve fibres in the osseous spiral lamina (100 %, see Fig. 2).
cells as inner radial fibres, which constitute about 95 yo of the entire cochlear neuron population (Spoendlin, 1969). It has been shown that these inner radiai fibres are particularly sensitive to many kinds of injury such as acoustic trauma (Spoendlin, 1971) and anoxia (Spoendlin, 1968), whereas the other nerve fibres are much more resistant. Irreversible damage initiating retrograde degeneration begins with excessive swelling of the fibres and ruptures of the axon membranes. This is frequently but not necessarily associated with a loss of inner hair cells or with a collapse of the supporting structures. The integrity of its peripheral terminal portion seems to be essential for the neuron to survive. Retrograde degeneration starts almost immediately after rupture of the inner radial fibres and proceeds within a few days through the osseous spiral lamina t o the spiral ganglion, where it is considerably delayed. After 3 weeks the great majority of nerve fibres in the osseous
spiral lamina have entirely disappeared but there is only a slight reduction of ganglion cells in the spiral ganglion. It is not before 3 months that degeneration of the ganglion cells has occurred on a larger scale and the number of ganglion cells is drastically reduced in a relatively short time. After 5 months only about 10 % of the normal ganglion cell population remain and this situation seems to be maintained (Fig. 3). After one year there are still about 10% of healthy looking ganglion cells present. When only the peripheral receptor is damaged, as in acoustic trauma, mechanical destruction, or intoxication with ototoxic antibiotics, retrograde degeneration never affects all neurons. 5-10 % of the neurons are always spared and resist retrograde degeneration. However, as soon as the cochlear blood supply is impaired or an infection affects the neurons directly, only very few or no neurons survive, resulting in a total loss of neurons. The next question concerns the type of neu-
18 - 752959
Acta Otolaryngol79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
268 H. Spoendlin
Fig. 2. (A) Elxtron micrascopic view of the or&an cf Corti from the lower half of the Iswer basal ttlri1 ( A ) of the cochlea in Fig. 1 . Although the outer hair cells are entirely missing ( x), the nerve fibres do not degenerate as long as the inner hair cells (iff) are present. The outward bending of the sensory hairs (Sf)of the Acta Otolaryngol79
i::ne; hair cell is a typical irr:v:rsible effect of the acoustical traumatisation. (B) The organ of Corti in the tipper basal turn 3 months after acoustic traumatisation. Here most outer hair cells (off) remain but the inner hair cells are missing ( x ) and the great majoiity of nerve fibres have degenerated (x).
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 269 ron which resists retrograde degeneration. In after retrograde degeneration following destrucnormal guinea pigs (Kellerhals et al., 1967; tion of the organ of Corti also represent mainly Spoendlin, 1971)and cats (Spoendlin, 1971; Ross, the innervation of the outer hair cells, whereas 1971) two different types of neuron are found in the nerve supply of the inner hair cells degenthe spiral ganglion: The great majority (type I) of erates (Fig. 4). It is an open question how much these exganglion cells are large and myelinated whereas perimental data in laboratory animals are apabout 10 % in the guinea pig and 5 76 in the cat plicable to the situation in the human. There is are smaller and unmyelinated (type 11) (Fig. 4). In the guinea pig one year following acoustical not much reason to believe that the human destruction of the organ of Corti, the majority cochlea would behave basically differently in of the surviving neurons are small and unmye- damage due to acoustic trauma or intoxication. linated, corresponding to the type I1 in the nor- Although antibiotic intoxication is still one of mal ganglion, whereas most of the type I cells the important causes of acquired total deafhave disappeared. A similar situation is found ness, genetic causes, infections and vascular disin the cat, where also practically all myelinated turbance play a by far more important role in type I ganglion cells degenerate and disappear the aetiology of total deafness and they are in the course of retrograde degeneration. The hardly reproducible in animal experiments. The histopathology of human temporal bones remaining 10% consist partly of type I1 cells with all their characteristics and partly of an- in persons who became totally deaf following other type of ganglion cell which resembles meningitis, bacterial labyrinthitis or head trauma closely the type I but is not myelinated (type reveals either a total bony obliteration of the 111) (Spoendlin, 1973). Surviving type I cells are cochlea without remaining neurons or, when the cochlear spaces are preserved, a total disexceptional. In the cat an interesting comparison between appearance of the organ of Corti and a practithe findings of retrograde degeneration after cally total loss of neurons (Fig. 5 A , B). destruction of the organ of Corti and the deViral labyrinthitis due to mumps or measles, generation pattern following transection of the on the other hand, affects mainly the endolymcochlear nerve in the inner acoustic meatus may phatic epithelial structures and spares the neugive some hints about the significance of the rons. Considerable retrograde degeneration of surviving neurons. In fact, the same type of the cochlear neurons seems to be rare following neurons (I1 and 111) resist degeneration after prenatal and of moderate degree following posttransection of the cochlear nerve (Spoendlin, natal infections (Lindsay, 1973). 1971, 1973, 1974) as in retrograde degeneration. A more complex situation is found in abioSince the organ of Corti does not degenerate trophic hereditary deafness, which represents a after section of the cochlear nerve it is seen that very important cause of total bilateral deafness the entire afferent nerve supply of the outer hair in man. Although histopathological information cells remains intact and almost all inner radial is rare, it seems that the degeneration process fibres, the afferent nerve supply of the inner hair usually begins as a cochleo-saccular degeneracells disappears. This means that essentially the tion within the endorgan or the stria vascularis afferent neurons for the outer hair cell system with varying degrees of secondary retrograde resist degeneration and that the type 11 and 111 degeneration of the cochlear neurons. Less frecells belong mainly to the neurons supplying the quently primary, almost total degeneration of outer hair cell system, whereas the type I cells the neurons in the presence of an intact endorgan belong to the neurons leading to the inner hair occurs, as shown in the temporal bones of two cells. Since we find the same type of neuron profoundly deaf persons suffering from Friedremaining after retrograde degeneration, it is reich’s disease (Spoendlin, 1974). In a number therefore most likely that the surviving neurons of cases of hereditary deafness with primary Acta Otolaryngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
270 H. Spoendlin
Acta Otolaryngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 271
Fig. 4. Schematic representation of the cochlear neurons in the cat. In the normal cat most ganglion cells arc large and myelinated of type I (I) and only few are small and unmyelinated of type TI (11). The efferent intraganglionic spiral bundle (e) consists of many myelinated and unmyelinated fibres; the inner radial fibres (iv) provide the afferent nerve supply of the iniiei hair cells whereas the
outer spiral fibres (OJ) are the afferent fibres to the outer hail cells. After destruction of the organ of Corti most type 1 cells degenerate and only type I1 and 111 cells remain. After sectlon of the VIII nerve the same type of ganglion cells survive together with the outer spiral fibres (as) and the afferent nerve endings at the outer hair cells. ~
Fig. 3. Spiral ganglion of the upper basal turn of a guinea pig cochlea: (A) Normal situation with a full set of densely packed myelinated type I ganglion cells and a few smaller unmyelinated type I1 ganglion cells (IT). The intraganglionic spiral bundle consists of densely packed efferent fibres (e). (B) Three weeks after complete acoustical destruction of the organ of Corti. In spite of degeneration of most fibres in the osscous spiral lamina only about 50% of the ganglion cells have disappeared.
(C) Three months after acoustical destruction of the organ of Corti. Most myelinated ganglion cells of type I arc gone. (D) One year after acousticaI destruction of the organ of Corti. 5-10% of the ganglion cells, mainly type I1 cells (11) and only few type I cells (I) remain without any signs of degeneration. Also the number of efferent fibres in the interganglion spiral bundle (e) is markedly reduced. Acta Otolaryngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
272 H. Spoendlin
Acta Otolavyngol 79
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneration of the cochlear nerve 273 endorgan degeneration the secondary retrograde neuronal degeneration seems to be very much delayed or incomplete. Thus we observed one patient with Alport syndrome who was totally deaf for several years before death and two deafmute patients with Usher’s syndrome, whose cochleas revealed preservation of a fair number of neurons in spite of severe damage to or absence of the organ of Corti (Fig. 5C). Other cases of profound or total congenital hereditary deafness with very good preservation of cochlear neurons over many years have been reported by Lindsay (1973) and Gacek (1971). More precise information about this type of hereditary congenital deafness associated with pigment anomalies is: provided by histological studies in animals such as deaf mouse mutants (Deol, 1954; Gruneberg, 1956; Ernstson, 1971), the dalmatian dog (Lurie, 1948; Schuknecht et al., 1965; Anderson et al., 1968) and the deaf white cat (Bosher & Hallpike 1965; Mair, 1973). According to the studies of Mair in the deaf white cat, substantial degeneration of the spiral ganglion started only at the end of the first year of life and progressed continuously over the entire observation period of 8 years. Well preserved neuron populations as reported by Schuknecht and Anderson in the dalmatian dog are probably due to the young age (maximum 18 months) at which the animals were sacrificed and examined, before retrograde degeneration had taken place on a larger scale. Retrograde degeneration in hereditary cochleo-saccular degeneration certainly proceeds much more slowly than it does after de-
Fig. 5. (A) Cochlea of a patient who 48 years ago became deaf during bacterial meningitis. Complete bony obliteration of all cochlear spaces ( x ) and total loss of cochlear neurons. (B) Cochlea of a patient who became totally deaf as the consequence of a head blow 60 years ago. Total loss of sensory elements and practically total loss of cochlear neurons. Partial fibrous obliteration of the perilymphatic spaces. (C) Cochlea of a deaf-mute patient which died at the age of 20, who suffered from Usher’s syndrome with a positive family history. In spite of an entirely absent organ of Corti in all turns there is a fail number of remaining cochlear neurons ( N ) mainly in the upper turns.
struction of the organ of Corti by acquired factors. There is a considerable lag between the complete collapse of the organ of Corti which determines the hearing loss, and the retrograde neuronal degeneration. In the deaf white cat we find during a great part of adult life between 5-10% remaining ganglion cells similar to the situation in retrograde degeneration after experimental destruction of the organ of Corti. Even the type of the surviving cells might be the same, as far as can be judged from the available histopathological material. Only in the old animal do the surviving neurons also begin to show signs of degeneration, eidicr due to aging or to the hereditary deafness iactors.
CONCLUSIONS 1. Total deafness due to vascular impairment or bacterial labyrinthine infection is usually associated with a complete loss of neurons. 2, In deafness following viral labyrinthitis there is frequently a relatively good preservation of the cochlear neurons. 3. In cases of selective endorgan destruction (intoxication, acoustic trauma) retrograde degeneration is incomplete, leaving 5-10 % of neurons to survive, mainly associated with the outer hair cell system. 4. Congenital hereditary abiotrophic deafness presents a very variable situation with extensive retrograde degeneration in some cases (Waardenburg-Syndrom), relatively good preservation of neurons in other cases (Usher-Syndrom) and cases of primary neural degeneration and an intact endorgan. The time course of retrograde degeneration in hereditary deafness seems to be very slow and might vary considerably between the different syndromes. Even in cases of extensive retrograde degeneration a small percentage of neurons tend to survive over a long period of time. The behaviour of the cochlear neurons varies considerably according to type of cochlear damage in deafness and a careful individual appraisal Acta Otolaryngol 79
274 H. Spoendlin of every case is therefore essential to judge the usefulness of a possible electrical stimulation of the cochlear nerve by electrode implantation.
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
ZUZAMMENFASSUNG Die retrograde Degeneration der Cochlearisneuronen wurde nach cochlearen Schadigungen verschiedenen Ausmasses und verschiedener Art, wie akustischem Trauma, Intoxikation, heredodegenerativer Veranderung und anderen untersucht. Eine wesentliche neuronale Degeneration beginnt erst wenn die peripheren zu den inneren Haarzellen ziehenden Dendriten irreversibel geschadigt sind. Ca. 1 0 % der Neurone werden von der retrograden Degeneration nicht erfasst. Es sind dies Neuronen vom Typ 11 and 111, die auch nach Durchtren nung des Nervus cochlearis uberleben und im wesentlichen zum System der ausseren Haarzellen gehoren. Cochleaschaden infolge schwerer Durchblutungsstorungen fuhren in der Regel zu vollstandigem Verlust der Cochlearisneuronen. Bei heredodegenerativer Innenohrschwerhorigkeit verlauft die retrograde neuronale Degeneration langsamer und ihre Ausdehnung variert stark bei verschiedenen genetischen Syndromen.
REFERENCES Anderson, H., Henricson, B., Lundquist, P.-G., Wedenberg, E. & Wersall, J. 1968. Genetic hearing impairment in the Dalmatian dog. Acta Otolaryngol (Stockh), Suppl. 232, 1 . Bosher, S. K. & Hallpike, C. S. 1965. Observations on the histological features, development and pathogenesis of the inner ear degeneration of the deaf white cat. Proc R Soc B162, 147. Bredberg, G . 1968. Cellular pattern and nerve supply of the human organ of Corti. Acta Otolaryngol (Stockh), Suppl. 236, 1. Deol, M. S. 1954. The anomalies of the labyrinth of the mutants varitint-waddler, shaker-2 and jerker in the mouse. J Genet 52, 562. Ernstson, S. 1971. Cochlezr morphology in a strain of the waltzing guinea pig. Acta Otolaryngol (Stockh) 71, 469. Gacek, R. R. 1971. The pathology of hereditary sensorineural hearing loss. Ann Otol Rhinol Laryngol80,289. Griineberg, H. 1955-56. Hereditary lesions of the labyrinth in the mouse. Br Med Bull 11-12, 153. Kellerhals, B., Engstrom, H. & Ades, H. W. 1967. Die Morphologie des Ganglion spirale cochleae. Acta Otolaryngol (Stockh), Suppl. 226, 1. Lindsay, J. R. 1973. Profound childhood deafness. Inner Ear pathology. Ann Otol Rhinol Laryngol, Suppl. 5, 1. Lurie, M. H. 1948. The membranous labyrinth in the congenitally deaf Collie and Dalmatian dog. Laryngoscope 58, 279. Mair, I. W. S. 1973. Hereditary deafness in the white cat. Acta Otolaryngol (Stockh), Suppl. 314, 1. Acta Otolaryngol79
Ross, M. D. 1971. Fluorescence and electron microscopic observations of the general visceral, efferent innervation of the inner ear. Acta Otolaryngol (Stockh), Suppl. 286, 1. Schuknecht, H. F. 1953. Lesions of the organ of Corti. Trans A m Acad Ophthalmol Otolaryngol57, 366. Schuknecht, H. F., Igarashi, M. & Gacek, R. R. 1965. The pathological types of cochleo-saccular degeneration. Acta Otolaryngol (Stockh) 59, 154. Spoendlin, H. 1968. Ultrastructure and peripheral innervation pattern of the receptor in relation to the first coding of the acoustic message. In Hearing mechanisms in vertebrates (ed. A. V. S. de Reuck & J. Knight), pp. 89-1 19. Churchill, London. - 1969a. Innervation patterns in the organ of Corti of the cat. Acta Otolaryngol (Stockh) 67, 239. - 1971. Degeneration behaviour of the cochlear nerve. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 200, 275. - 1973. The innervation of the cochlear receptor. Proceeding of a Symposium on: Basic Mechanisms in Hearing, pp. 185-234. Academic Press, New York. 1973. Neuroanatomy of the cochlea. In Facts and model in hearing, Zwicker u. Terhardt (Springer-Verlag, Heidelberg). - 1974. Optic and cochleovestibular degenerations in hereditary ataxias. 11. Temporal bone pathology in two cases of Friedreich’s ataxia with vestibulocochlear disorders. Brain 97, 41. - 1974. The bloc surface technique for the evaluation of cochlear pathology. Arch Klin Exp Ohren Naseu2 Kehlkopfheilkd 208, 137. ~
H . Spoendlin, M.D. Dept. of Otolaryngology University of Zurich Zurich, 8006 Switzerland
DISCUSSION I . Friedmann: Is regeneration possible? Wardenburg syndrome-material on which figures are based. M. Lawrence; I noticed that the unmyelinated ganglion cells in the normal ganglion section had lobulated nuclei while in the ears in which these unmyelinated ganglion cells were the only cells remaining, the nuclei did not appear lobulated. Could there have been changed ganglion cells or was this appearance merely a matter of the particular section shown? M. Portmann: You show this degeneration of neurofibres after ototoxic aggression. How d o you explain the success of cochlear implant in such case? I saw on your slides a degeneration of efferent spiral bundle after acoustic trauma. Long ago I did the same sort of research and always found an intact spiral bundle after the destruction of the afferent system by acoustic trauma. How d o you explain this difference in our results? J. M. Sdnchez-Fernandez: I agree with Mr Lawrence and Mr Portmann about its importance by the clinical application in cochlear implants. Which is the limit in the time of the retrograde degeneration and in which
Downloaded by [University of California, San Diego] at 05:31 13 April 2016
Retrograde degeneraton of the cochlear nerve level does it occur? Have you studied the central cochlear nucleus? Which are the initial ultrastructural findings of the retrograde degeneration in the myelin ganglion cells? G. Zecliner: By studying otosclerosis and inner-eardeafness 1 always found very few surviving ganglion cells with and without the organ of Corti. There was also a case where the focus arrived in tractus foraminosus in the meatus accusticus int. The organ of Corti was preserved but the ganglia cells were missing due to the destruction of nerve fibres by pressure. What is in your opinion the indication for cochlea implants, when mainly ganglion cells are missing in 95 %? C. R. Pfaltz: Would a similar type of retrograde degeneration also be expected in the vestibular nerve? H. Spoendlin (Reply) to I. Friedmann: The few remaining neurons after retrograde degeneration of the cochlear nerve lose only the most peripheral portion of the dendrites. Tye might have a certain regeneration capacity, which however does not help much, since the organ of Corti is entirely missing. I am well aware of the fact that you have studied the only available temporal bone of a case of Waardenburg syndrome. With the 5 % surviving neurons I am mainly referring to hereditary deafness associated with pigment anomalies in general. To Mr Lawrence: The surviving ganglion cells are of type I1 and 111. The type 111 cells have a tendency to prevail after retrograde degeneration. To Mr Porrmann: The decision whether a cochlear implant could be useful or not in a patient deafened as a consequence of antibiotic intoxication must rely on the question whether 5-10 % surviving neurons are sufficient for the transmission of complex acoustic messages. A
275
possible hint that very few neurons could be sufficient for useful hearing might be given by the example of the two cases of Friedreich’s disease of which we examined the temporal bones and where we found a primary degeneration of the cochlear neurons in the presence of an intact organ of Corti. Although only very few cochlear neurons were left at the lower end of the cochlea, the patients were not totally deaf. Not only the afferent cochlear neurons, but also, to our great surprise the efferent fibres in the interganglionic spiral bundle, undergo retrograde degeneration after long survival times following destruction of the organ of Corti. Even in areas where only the outer hair cells are gone there is a substantial reduction in the number of intraganglionic spiral fibres. To Mr Sanchez-Fernandez: The cochlear nucleus was not examined in our material. Degeneration of the cochlear neurons seems to proceed in the guinea pig and cat over 4-5 months. After longer survival times of one and two years we always find approximately the same number of surviving ganglion cells. To Mr Zechner: The reason that you found fewer surviving ganglion cells in human temporal bones in cases of profound inner ear deafness than we found in our experimentally induced inner ear deafness might be the additional effect of presbyacusis which probably also affects the surviving neurons after retrograde degeneration. To Mr Pflatz: The vestibular neurons seem to behave differently. After section in the inner acoustic meatus they show only minor degeneration and most neurons survive after destruction of the sensory epithelium by locally applied ototoxic antibiotics.
Acta Otolaryngol 79
