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Ultrastructure of the vestibular sensory organs in delayed endolymphatic hydrops
Am J Otolaryngol 10:336341,1989
Ultrastructure of the Vestibular Sensory Organs in Delayed Endolymphatic Hydrops YUJI YAKU, MD, ANDATSUSHI KOMATSUZAKI, MD
Vestibular sensory organs were examined ultrastructurally
in two cases of delayed endolymphatic hydrops. The patients, two women, 27 and 16 years of age, suffered profound sensory hearing loss in childhood and experienced severe, recurrent vertigo. Specimens were obtained by a translabyrinthial vestibular nerve transection. We studied the utricular macula and the lateral and posterior cristae in one case, and the utricular macula, the anterior and posterior cristae, and the vestibular ganglion in the other. The otoconia and the otoconial membrane, the sensory epithelia, and the vestibular ganglion appeared fairly normal. Although the entire vestibular end organs were not studied in these cases, it was surprising that the ultrastructural findings did not conclusively identify vestibular end organ pathology as the cause of the vertigo attacks. AM J OTOLARYNGOL 10:336-341. 0 1989 by W.B. Saunders Company. Key words: delayed endolymphatic hydrops, vestibular sensory epithelia, vestibular ganglion, ultrastructure.
incidence of this condition compared with Meniere’s disease. Clinical symptoms are similar to those of severe unilateral Meniere’s disease, so it is of interest to study ultrastructurally the vestibular sensory organs in delayed endolymphatic hydrops and to compare the findings.
Delayed endolymphatic hydrops, a clinical entity that can be differentiated from Meniere’s disease, was first reported simultaneously by Nadol et al1 and Wolfson and Leiberman’ in 1975, and was specified by Schuknecht3s4 in 1976 and 1978. Typically, patients with this disease suffer profound sensory hearing loss in one ear, usually from infection, trauma, or unknown origin, and then, several years later, develop recurrent episodic vertigo from the same ear. However, as in Meniere’s disease, nothing is known about the pathogenesis of this disease. Although the ultrastructural features of the vestibule in Meniere’s disease have been mentioned in a few studies,5-1’ those in delayed endolymphatic hydrops, to our knowledge, have not been reported. This must, at least in part, be due to the low
MATERIALS AND METHODS Specimens from two patients suffering from severe unilateral delayed endolymphatic hydrops were studied. The relevant clinical data, gathered shortly before surgery, are shown in Table 1. Both patients suffered profound sensorineural hearing loss (case no. 1 in the left ear and case no. 2 in the right) discovered incidentally during childhood. Frequent episodic vertigo, consisting of rotatory dizziness, began in patient no. 1 at 25 years of age and in patient no. 2 at 14 years of age. The duration of these symptoms was 1.7 and 2 years, respectively. Spontaneous and positional nystagmus were noted during attacks of vertigo in both cases. There were no symptoms or signs indicative of CNS involvement. Caloric responses in both cases were within normal limits. Radiographic examinations of the temporal bone, including tomography and computed tomography scanning of the
Received July 25, 1988, from the Department of Otolaryngology, Head and Neck Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan; and the Department of Otolaryngology, Toho University, Tokyo. Accepted for publication March 24, 1989. Address correspondence and reprint requests to Yuji Yaku, MD, Department of Otolaryngology, Head and Neck Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi 320, Japan. 0 1989 by W.B. Saunders Company. 0196-0709/89/1005-0004$5.00/0
336
YAKUANDKOMATSUZAKI TABLE 1. CASE No.
AGE AT TIME OF OPERATION
1
27
2
16
Clinical Data of the TWODelayed Endolymphatic Hydrops Cases PRQFOUND HEARING Loss
DURATION OF SYMPTOMS
SPONTANEOUS OR POSITIONAL NYSTAGMUS
Left
1.7
None
Right
2.0
None
inner ear, internal acoustic canal, and C-P angle, were normal. Considering these clinical findings and referring to the criteria proposed by Schuknecht,4 we diagnosed delayed endolymphatic hydrops. Because both patients experienced severe and recurrent episodic vertigo, a condition which medical treatment had failed to remedy, translabyrinthine vestibular neurectomy was indicated in both cases. During the operation, the utricular maculae and ampullar cristae were gently removed from the fully opened vestibules. In case no. 2, the vestibular ganglion was also obtained. Specimens were immediately immersed in 2.5% glutaraldehyde in 0.1 mol/L phosphate buffer, postfixed in 1% osmium tetroxide in the same buffer, dehydrated through graded ethyl alcohol, and embedded in epoxy resin. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a JEM 1200 EX electron microscope. Although considerable effort was taken to avoid any crushing of the specimens, some sustained traumatic damage, making them unsuit-
Figure I.
Case no. I. Otoconia from the utricle.
CALORIC RESPONSE Slightly reduced Normal
PURE TONE AVERAGE (500 TO 2,000 Hz) (nW
110 (scale out) 110 (scale out)
able for ultrastructural studies. The utricular macula and the lateral and posterior cristae in case no. 1 and the utricular macula, the anterior and posterior cristae, and the vestibular ganglion in case no. 2 were successfully removed. RESULTS Case No. 7 LJtricuIar macula. The otoconia and otoconial membrane could be observed. The otoconia were roundish and hexagonal in shape. Their internal structure consisted of an electron lucent core and fine fibrous content (Fig 1). Two layers, the marginal zone and the medial zone, were clearly distinguished in the otoconial membrane. The marginal zone was composed of electron-dense material and the medial zone was composed of an electron-lucent substance, as has been described in normal otoconia (Fig 2j.l’ These findings indicated that the otoconia and otoconial membrane of the utricle in case no. 1
Figure 2. Case no. 1. Suprastructure of the utricle. Otoconia (0), marginal zone (Ma], and medial zone (Me) of the otoconial membrane.
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were fairly intact. The sensory epithelium, including types I and II sensory cells and supporting cells, showed a normal structure (Fig 3). The surface structure of these cells also appeared normal, with sensory hairs protruding from the sensory cells and microvilli from the supporting cells (Fig 2). Afferent and efferent nerve endings (an afferent nerve ending formed a nerve chalice on a type I sensory cell) remained normal, and synaptic bodies were occasionally observed (Figs 3 and 4). Vacuolization of the cytoplasm was rarely seen in the type I sensory cell (Fig 5). Myelinated nerves below the sensory epithelium appeared normal. Lateral and posterior cristae. The sensory regions of the cristae consisted of fairly normal type I and II sensory and supporting cells, with normal-looking sensory hairs projecting from the sensory cells and microvilli from the supporting cells (Fig 6). Afferent and efferent nerve endings and myelinated nerve fibers below the sensory epithelium also appeared normal (Fig 6) and synaptic bodies were also occasionally encountered.
ENDOLYMPHATIC
Figure 4. Case no. 1. Synaptic cell in the utricle (arrowheads].
boutons Afferent
HYDROPS
on type II sensory nerve ending (A).
Utricular macula. The otoconia and otoconial membrane could not be examined because they were lost during the surgical procedure. The sensory epithelium contained normallooking sensory cells which were interspersed
among the evidently normal supporting cells (Fig 7). In addition, the surface morphology of the sensory epithelium, sensory hairs, and microvilli appeared normal (Fig 7). Afferent and efferent nerve endings as well as innervating myelinated nerve fibers in the subepithelial region appeared intact and normal in both number and appearance.
Figure 3. Case no. 1.Horizontal section of type I (I) and type II (II) sensory cells in the utricle.
Figure 5. Case no. 1. Vesiculated the utricle.
Case No. 2
American Journal of Otolaryngolog 338
IY
type I sensory
cell [V) in
YAKU AND KOMATSUZAKI
Figure 6. Case no. 1. Sensory epithelium of the posterior crista. Type I [I) and type II (II) sensory cells.
Figure 8. Case no. 2. Sensory epithelium of the anterior crista. Type I (I) and type II (II) sensory cells and supporting cells.
Anterior and posterior cristae. The sensory epithelia of both cristae showed a fairly normal cytoarchitecture. Type I and II sensory cells, supporting cells, and afferent and efferent nerve endings, including nerve chalices, showed no pathologic changes (Fig 8). Myelinated nerve fi-
bers below the sensory regions also remained normal (Fig 9). Neurons of the vestibuVestibular ganglion. lar ganglion were present in large numbers and showed variations in size. Almost all neurons were unmyelinated and were surrounded by a single layer of Schwann cell cytoplasm. Al-
Volume
Figure 7. Case no. 2. Sensory epithelium of the utricle. Type I sensory cells (I), type II sensory cells (II], and supporting cells (S).
Figure 9. Case no. 2. Subepithelial of the posterior crista.
myelinated
nerve fibers
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5
1989 339
DELAYED ENDOLYMPHATIC HYDROPS
though lamellae of rough endoplasmic reticulum were sometimes slightly dilated, the nucleus and other cytoplasmic organelles, including mitochondria, lysosomes, and Golgi complexes, appeared normal (Fig 10). Lipofuscin granules and multivesicular bodies were frequently observed in the cytoplasm, but they were always few in number. The vestibular ganglion contained numerous myelinated nerve fibers. Many of them remained intact, but a partial dissociation of axons from the myelin sheath, as well as splitting and disorganization of the myelin lamellae, were sometimes observed (Fig 11). These findings were considered preparation and/or fixation artifacts. The axons in these states showed an increase in cytoplasmic filaments and were observed to be somewhat more electron-dense in comparison to normal axons. To our regret, we could not diagnose delayed endolymphatic hydrops on the basis of the histologic appearance of the vestibules because the vestibular endorgans showed no definite ultrastructural signs that they were affected by the hydrops. Since their neurectomies, both patients have experienced dramatic and complete relief from their symptoms. DISCUSSION
Due to the difficulty of obtaining fresh specimens from normal human vestibular organs for
American Journal of Otolaryngol 340
09Y
Figure 10. Case no. 2. A neuron in the vestibular ganglion. The nucleus (N) contained a conspicuous nucleolus. Nuclei of Schwann cell [S).
Figure 11. Case no. 2. Degenerating myelinated nerve fibers in the vestibular ganglion. Partial dissociation of the axon from the myelin sheath (+). splitting (arrowheads), and disorganization (*) of the myelin lamellae. These findings were considered to be due to preparation and/or fixation artifacts. Intact axons [I).
electron microscopy, knowledge about the ultrastructural morphology of the normal vestibular organ in humans is limited. Ultrastructural studies of the vestibular sensory organs have been performed mainly in Meniere’s disease, because in the translabyrinthine approach to eighth nerve transection, used in advanced cases of Meniere’s disease, it is possible to obtain fresh vestibular organs. Several ultrastructural changes, possibly attributable to Meniere’s disease, have been reported in the vestibular sensory organs, including the epithelia of the macula and cristae. These changes include the loss of sensory cilia, the accumulation of fat droplets, vesiculation and/or vacuolation in the cytoplasm of the sensory and supporting cells, and cystic degeneration between the sensory cell and the nerve chalice.5-‘0.‘3~14 However, with advances in the procedures used to obtain and process histologic material, these findings, in the view of a number of authors, have come to be considered artifacts of degenerative change due to aging.g**1 Moreover, it has recently been reported that the vestibular sensory epithelia in Meniere’s disease are fairly normal morphologically.” Yet, it seems equally reasonable to suppose that some degenerative changes exist in the vestibular organs in cases of Meniere’s disease, as surgically treated
YAKU AND KOMATSUZAKI
patients have usually suffered from this disease for a long time. Both cases of delayed endolymphatic hydrops in this study had fairly normal vestibular sensory organs in both maculae and cristae. Although rare sensory cells of the utricular macula in case no. 1 showed vesiculation in the cytoplasm, especially type I sensory cells, the otoconia and the otoconial membrane and the cells of other sensory epithelia in both cases did not present any ultrastructural changes, such as have been noted in previous pathologic reports of Meniere’s disease. The cytoplasmic vesiculation of sensory cells in the utricular macula in case No. 1 was considered to be an age-related finding analogous to the findings in Meniere’s disease.6z*1 The fact that the vestibular sensory epithelia of these two cases of delayed endolymphatic hydrops exhibited remarkably normal cytoarchitecture could be attributed, at least in part, to their relatively young ages, 27 and 16 years. It has been commonly accepted that a possible explanation for hydrops in this disease is a disorder of the endolymphatic system which comprises the resorption of endolymph,4 but nothing absolute is known about the pathogenesis of the disease. However, if the hydrops did affect the vestibular sensory organs in these two cases, it did not cause morphologic changes in the vestibular sensory epithelia in the relatively short, Z-year period. In addition, no general degeneration was observed in the vestibular ganglion of case no. 2. Although some myelinated nerves certainly showed splitting and/or disorganization of the myelin sheath and an increase of cytoplasmic filaments in the axon; the vestibular neurons, Schwann cells, and many of the myelinated nerves appeared normal. Furthermore, with the finding that the subepithelial myelinated nerve fibers innervating the sensory epithelia of the utricular macula and cristae were intact, it was hypothesized that the changed myelinated nerves in the vestibular ganglion were preparation and/or fixation artifacts, as described in the eighth cranial nerve biopsy.15
Although the entire vestibular end organs were not studied in these cases, it was surprising that the ultrastructural findings did not conclusively identify vestibular end organ pathology as the cause of the vertigo attacks. Nonetheless, it is clear that a pathologic process somewhere in the vestibular system underlies these attacks. Acknowledgment. We are grateful to Dr T Kanda (Department of Otolaryngology, Chiba University) for his valuable advice. We also wish to thank N. Nakamura for his technical assistance.
References 1. Nadol JB, Weiss AD, Parker SW: Vertigo of delayed onset
after sudden deafness. Ann Otol 1975; 84:841-846 2. Wolfson RJ, Leiberman A: Unilateral deafness with subsequent vertigo. Laryngoscope 1975; 85:1762-1766 3. Schuknecht HF: Pathouhvsiologv of endolvmuhatic hvdrops. Arch Otorhinc&ryngo~l976; 212?!5&262 * 4. Schuknecht HF: Delayed endolymphatic hydrops. Ann Otol 1978; 87:743-748 5. Colman BH, Friedman I, Wright JLW: Meniere’s disease. Electron microscopy of the vestibular ganglion and end organs after ultrasound. Acta Otolaryngol 1975; 79:189-196 6. Hilding DA, House WF: An evaluation of the ultrastructural findings in the utricle in Meniere’s disease. Laryngoscope 1963; 74:1135-1148 7. Ireland PE, Farkashiby J: Electron microscopic studies of Meniere’s disease: Twelve fresh specimens taken at operation. Trans Am Acad Ophthalmol Otolaryngol 1963; 6728-36 8. Litton WB, Lawrence M: Electron microscopy in Meniere’s disease. Arch Otolaryngol 1961; 74:52-59 9. Rosenhall U, Engstrom B, Stahle J: Macula utricle in four cases with Meniere’s disease. Acta Otolaryngol 1977; 84:307-316 10. SBnchez-Fernandez JM, Marco J: Ultrastructural study of the human utricular macula and vestibular nerve in Meniere’s disease. Acta Otolaryngol 1975; 79:180-188 11. Ylikoski J, Collan Y, Palva T: Vestibular sensory epithelium in Meniere’s disease. Arch Otolaryngol 1979; 105:486-491 12. Lim DJ: The development and structure of the otoconia, in Friedmann I, Ballantyne J (eds): Ultrastructural Atlas of the Inner Ear. London, Butterworths. 1984. DD Al 245-269 13. Pietrantoni L, Iurato S: Some initial electron-microscope investigations of a case of Meniere’s disease. Acta Otolaryngol 1960; 52:15-26 14. Friedmann I, Cawthorne T, McLay K, et al: Electron microscopic observation on the human membranous labyrinth with particular reference to Meniere’s disease. J Ultrastruct Res 1963; 9:123-138 15. Collan Y, Ylikoski J. Palva T, et al: Artifact in eighth cranial nerve biopsy. Acta Otolaryngol 1980; 89:71-75
Volume
10
Number September
5
1989 341
Ultrastructure of the Vestibular Sensory Organs in Delayed Endolymphatic Hydrops YUJI YAKU, MD, ANDATSUSHI KOMATSUZAKI, MD
Vestibular sensory organs were examined ultrastructurally
in two cases of delayed endolymphatic hydrops. The patients, two women, 27 and 16 years of age, suffered profound sensory hearing loss in childhood and experienced severe, recurrent vertigo. Specimens were obtained by a translabyrinthial vestibular nerve transection. We studied the utricular macula and the lateral and posterior cristae in one case, and the utricular macula, the anterior and posterior cristae, and the vestibular ganglion in the other. The otoconia and the otoconial membrane, the sensory epithelia, and the vestibular ganglion appeared fairly normal. Although the entire vestibular end organs were not studied in these cases, it was surprising that the ultrastructural findings did not conclusively identify vestibular end organ pathology as the cause of the vertigo attacks. AM J OTOLARYNGOL 10:336-341. 0 1989 by W.B. Saunders Company. Key words: delayed endolymphatic hydrops, vestibular sensory epithelia, vestibular ganglion, ultrastructure.
incidence of this condition compared with Meniere’s disease. Clinical symptoms are similar to those of severe unilateral Meniere’s disease, so it is of interest to study ultrastructurally the vestibular sensory organs in delayed endolymphatic hydrops and to compare the findings.
Delayed endolymphatic hydrops, a clinical entity that can be differentiated from Meniere’s disease, was first reported simultaneously by Nadol et al1 and Wolfson and Leiberman’ in 1975, and was specified by Schuknecht3s4 in 1976 and 1978. Typically, patients with this disease suffer profound sensory hearing loss in one ear, usually from infection, trauma, or unknown origin, and then, several years later, develop recurrent episodic vertigo from the same ear. However, as in Meniere’s disease, nothing is known about the pathogenesis of this disease. Although the ultrastructural features of the vestibule in Meniere’s disease have been mentioned in a few studies,5-1’ those in delayed endolymphatic hydrops, to our knowledge, have not been reported. This must, at least in part, be due to the low
MATERIALS AND METHODS Specimens from two patients suffering from severe unilateral delayed endolymphatic hydrops were studied. The relevant clinical data, gathered shortly before surgery, are shown in Table 1. Both patients suffered profound sensorineural hearing loss (case no. 1 in the left ear and case no. 2 in the right) discovered incidentally during childhood. Frequent episodic vertigo, consisting of rotatory dizziness, began in patient no. 1 at 25 years of age and in patient no. 2 at 14 years of age. The duration of these symptoms was 1.7 and 2 years, respectively. Spontaneous and positional nystagmus were noted during attacks of vertigo in both cases. There were no symptoms or signs indicative of CNS involvement. Caloric responses in both cases were within normal limits. Radiographic examinations of the temporal bone, including tomography and computed tomography scanning of the
Received July 25, 1988, from the Department of Otolaryngology, Head and Neck Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan; and the Department of Otolaryngology, Toho University, Tokyo. Accepted for publication March 24, 1989. Address correspondence and reprint requests to Yuji Yaku, MD, Department of Otolaryngology, Head and Neck Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi 320, Japan. 0 1989 by W.B. Saunders Company. 0196-0709/89/1005-0004$5.00/0
336
YAKUANDKOMATSUZAKI TABLE 1. CASE No.
AGE AT TIME OF OPERATION
1
27
2
16
Clinical Data of the TWODelayed Endolymphatic Hydrops Cases PRQFOUND HEARING Loss
DURATION OF SYMPTOMS
SPONTANEOUS OR POSITIONAL NYSTAGMUS
Left
1.7
None
Right
2.0
None
inner ear, internal acoustic canal, and C-P angle, were normal. Considering these clinical findings and referring to the criteria proposed by Schuknecht,4 we diagnosed delayed endolymphatic hydrops. Because both patients experienced severe and recurrent episodic vertigo, a condition which medical treatment had failed to remedy, translabyrinthine vestibular neurectomy was indicated in both cases. During the operation, the utricular maculae and ampullar cristae were gently removed from the fully opened vestibules. In case no. 2, the vestibular ganglion was also obtained. Specimens were immediately immersed in 2.5% glutaraldehyde in 0.1 mol/L phosphate buffer, postfixed in 1% osmium tetroxide in the same buffer, dehydrated through graded ethyl alcohol, and embedded in epoxy resin. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a JEM 1200 EX electron microscope. Although considerable effort was taken to avoid any crushing of the specimens, some sustained traumatic damage, making them unsuit-
Figure I.
Case no. I. Otoconia from the utricle.
CALORIC RESPONSE Slightly reduced Normal
PURE TONE AVERAGE (500 TO 2,000 Hz) (nW
110 (scale out) 110 (scale out)
able for ultrastructural studies. The utricular macula and the lateral and posterior cristae in case no. 1 and the utricular macula, the anterior and posterior cristae, and the vestibular ganglion in case no. 2 were successfully removed. RESULTS Case No. 7 LJtricuIar macula. The otoconia and otoconial membrane could be observed. The otoconia were roundish and hexagonal in shape. Their internal structure consisted of an electron lucent core and fine fibrous content (Fig 1). Two layers, the marginal zone and the medial zone, were clearly distinguished in the otoconial membrane. The marginal zone was composed of electron-dense material and the medial zone was composed of an electron-lucent substance, as has been described in normal otoconia (Fig 2j.l’ These findings indicated that the otoconia and otoconial membrane of the utricle in case no. 1
Figure 2. Case no. 1. Suprastructure of the utricle. Otoconia (0), marginal zone (Ma], and medial zone (Me) of the otoconial membrane.
10
Volume Number September
5
1989 337
DELAYED
were fairly intact. The sensory epithelium, including types I and II sensory cells and supporting cells, showed a normal structure (Fig 3). The surface structure of these cells also appeared normal, with sensory hairs protruding from the sensory cells and microvilli from the supporting cells (Fig 2). Afferent and efferent nerve endings (an afferent nerve ending formed a nerve chalice on a type I sensory cell) remained normal, and synaptic bodies were occasionally observed (Figs 3 and 4). Vacuolization of the cytoplasm was rarely seen in the type I sensory cell (Fig 5). Myelinated nerves below the sensory epithelium appeared normal. Lateral and posterior cristae. The sensory regions of the cristae consisted of fairly normal type I and II sensory and supporting cells, with normal-looking sensory hairs projecting from the sensory cells and microvilli from the supporting cells (Fig 6). Afferent and efferent nerve endings and myelinated nerve fibers below the sensory epithelium also appeared normal (Fig 6) and synaptic bodies were also occasionally encountered.
ENDOLYMPHATIC
Figure 4. Case no. 1. Synaptic cell in the utricle (arrowheads].
boutons Afferent
HYDROPS
on type II sensory nerve ending (A).
Utricular macula. The otoconia and otoconial membrane could not be examined because they were lost during the surgical procedure. The sensory epithelium contained normallooking sensory cells which were interspersed
among the evidently normal supporting cells (Fig 7). In addition, the surface morphology of the sensory epithelium, sensory hairs, and microvilli appeared normal (Fig 7). Afferent and efferent nerve endings as well as innervating myelinated nerve fibers in the subepithelial region appeared intact and normal in both number and appearance.
Figure 3. Case no. 1.Horizontal section of type I (I) and type II (II) sensory cells in the utricle.
Figure 5. Case no. 1. Vesiculated the utricle.
Case No. 2
American Journal of Otolaryngolog 338
IY
type I sensory
cell [V) in
YAKU AND KOMATSUZAKI
Figure 6. Case no. 1. Sensory epithelium of the posterior crista. Type I [I) and type II (II) sensory cells.
Figure 8. Case no. 2. Sensory epithelium of the anterior crista. Type I (I) and type II (II) sensory cells and supporting cells.
Anterior and posterior cristae. The sensory epithelia of both cristae showed a fairly normal cytoarchitecture. Type I and II sensory cells, supporting cells, and afferent and efferent nerve endings, including nerve chalices, showed no pathologic changes (Fig 8). Myelinated nerve fi-
bers below the sensory regions also remained normal (Fig 9). Neurons of the vestibuVestibular ganglion. lar ganglion were present in large numbers and showed variations in size. Almost all neurons were unmyelinated and were surrounded by a single layer of Schwann cell cytoplasm. Al-
Volume
Figure 7. Case no. 2. Sensory epithelium of the utricle. Type I sensory cells (I), type II sensory cells (II], and supporting cells (S).
Figure 9. Case no. 2. Subepithelial of the posterior crista.
myelinated
nerve fibers
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5
1989 339
DELAYED ENDOLYMPHATIC HYDROPS
though lamellae of rough endoplasmic reticulum were sometimes slightly dilated, the nucleus and other cytoplasmic organelles, including mitochondria, lysosomes, and Golgi complexes, appeared normal (Fig 10). Lipofuscin granules and multivesicular bodies were frequently observed in the cytoplasm, but they were always few in number. The vestibular ganglion contained numerous myelinated nerve fibers. Many of them remained intact, but a partial dissociation of axons from the myelin sheath, as well as splitting and disorganization of the myelin lamellae, were sometimes observed (Fig 11). These findings were considered preparation and/or fixation artifacts. The axons in these states showed an increase in cytoplasmic filaments and were observed to be somewhat more electron-dense in comparison to normal axons. To our regret, we could not diagnose delayed endolymphatic hydrops on the basis of the histologic appearance of the vestibules because the vestibular endorgans showed no definite ultrastructural signs that they were affected by the hydrops. Since their neurectomies, both patients have experienced dramatic and complete relief from their symptoms. DISCUSSION
Due to the difficulty of obtaining fresh specimens from normal human vestibular organs for
American Journal of Otolaryngol 340
09Y
Figure 10. Case no. 2. A neuron in the vestibular ganglion. The nucleus (N) contained a conspicuous nucleolus. Nuclei of Schwann cell [S).
Figure 11. Case no. 2. Degenerating myelinated nerve fibers in the vestibular ganglion. Partial dissociation of the axon from the myelin sheath (+). splitting (arrowheads), and disorganization (*) of the myelin lamellae. These findings were considered to be due to preparation and/or fixation artifacts. Intact axons [I).
electron microscopy, knowledge about the ultrastructural morphology of the normal vestibular organ in humans is limited. Ultrastructural studies of the vestibular sensory organs have been performed mainly in Meniere’s disease, because in the translabyrinthine approach to eighth nerve transection, used in advanced cases of Meniere’s disease, it is possible to obtain fresh vestibular organs. Several ultrastructural changes, possibly attributable to Meniere’s disease, have been reported in the vestibular sensory organs, including the epithelia of the macula and cristae. These changes include the loss of sensory cilia, the accumulation of fat droplets, vesiculation and/or vacuolation in the cytoplasm of the sensory and supporting cells, and cystic degeneration between the sensory cell and the nerve chalice.5-‘0.‘3~14 However, with advances in the procedures used to obtain and process histologic material, these findings, in the view of a number of authors, have come to be considered artifacts of degenerative change due to aging.g**1 Moreover, it has recently been reported that the vestibular sensory epithelia in Meniere’s disease are fairly normal morphologically.” Yet, it seems equally reasonable to suppose that some degenerative changes exist in the vestibular organs in cases of Meniere’s disease, as surgically treated
YAKU AND KOMATSUZAKI
patients have usually suffered from this disease for a long time. Both cases of delayed endolymphatic hydrops in this study had fairly normal vestibular sensory organs in both maculae and cristae. Although rare sensory cells of the utricular macula in case no. 1 showed vesiculation in the cytoplasm, especially type I sensory cells, the otoconia and the otoconial membrane and the cells of other sensory epithelia in both cases did not present any ultrastructural changes, such as have been noted in previous pathologic reports of Meniere’s disease. The cytoplasmic vesiculation of sensory cells in the utricular macula in case No. 1 was considered to be an age-related finding analogous to the findings in Meniere’s disease.6z*1 The fact that the vestibular sensory epithelia of these two cases of delayed endolymphatic hydrops exhibited remarkably normal cytoarchitecture could be attributed, at least in part, to their relatively young ages, 27 and 16 years. It has been commonly accepted that a possible explanation for hydrops in this disease is a disorder of the endolymphatic system which comprises the resorption of endolymph,4 but nothing absolute is known about the pathogenesis of the disease. However, if the hydrops did affect the vestibular sensory organs in these two cases, it did not cause morphologic changes in the vestibular sensory epithelia in the relatively short, Z-year period. In addition, no general degeneration was observed in the vestibular ganglion of case no. 2. Although some myelinated nerves certainly showed splitting and/or disorganization of the myelin sheath and an increase of cytoplasmic filaments in the axon; the vestibular neurons, Schwann cells, and many of the myelinated nerves appeared normal. Furthermore, with the finding that the subepithelial myelinated nerve fibers innervating the sensory epithelia of the utricular macula and cristae were intact, it was hypothesized that the changed myelinated nerves in the vestibular ganglion were preparation and/or fixation artifacts, as described in the eighth cranial nerve biopsy.15
Although the entire vestibular end organs were not studied in these cases, it was surprising that the ultrastructural findings did not conclusively identify vestibular end organ pathology as the cause of the vertigo attacks. Nonetheless, it is clear that a pathologic process somewhere in the vestibular system underlies these attacks. Acknowledgment. We are grateful to Dr T Kanda (Department of Otolaryngology, Chiba University) for his valuable advice. We also wish to thank N. Nakamura for his technical assistance.
References 1. Nadol JB, Weiss AD, Parker SW: Vertigo of delayed onset
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Volume
10
Number September
5
1989 341