Four variations of the mondini inner ear malformations as seen in microdissections

Am I Otalaryngol 5:242-257, 1984

Four Variations of the M o n d i n i Inner Ear Malformations as Seen in Microdissections LARS-GORANIOHNSSON,M.D.,*~r JOSEPHE. HAWKINS,JR., PH.D., D.Sc.,* ROLANDC. ROUSE, PH.D.,* AND THOMASC. KINGSLEY,M.D.r Four variations and degrees of severity of the Mondini malformation were found in the temporal bones from two neonates, one with congenital heart disease and the other with trisorny D, and from one teenager with leukemia: 1) short cochlea and normal vestibular organs; 2) short cochlea and persistent horizontal canal anlage; 3) markedly shortened cochlea with no modiolus, wide internal auditory meatus, and persistent horizontal canal anlage; 4) same as variation 3, but with persistent anlagen in all semicircular canals. Variations 3 and 4 were from the case of trisomy D, in which the left cochlea had a normal hair cell population but few nerve fibers, and the intraganglionic spiral bundle was displaced from Rosenthal's canal to the osseous spiral lamina. The right ear had no cochlear nerve fibers; the organ of Corti was present, but hair cells were unusually small. In the case of trisomy D, both ears showed subtotal loss of vestibular nerve fibers. Although the rudimentary cristae of the right ear had numerous hair cells, the macular hair cells were fewer and malformed. No hydrops was present.

The Mondini malformation was first described in 1791 by Carlo Mondini (Carolus Mundinus), a physician of Bologna, in his anatomic treatise on the ears of deaf-mutes. 1 Our study demonst_rates four variations of the malformation, as observed in microdissections and surface preparations. The abnormality is clinically important and can easily be diagnosed by conventional radiography, polytomography, and computerized tomographic scanning.2-8 The Mondini malformation may affect one or both ears and seems to represent several different stages of arrested labyrinthine development. Patients with this abnormality show varying degrees of hearing loss, but some may

Received August 3, 1983. Accepted for publication November 18, 1983. * Kresge Hearing Research Institute, Department of Otorhinolaryngology,University of Michigan Medical School, Anr~Arbor, Michigan, f Department of Otarhinolaryngalogy,UniversityCentral Hospital of Helsinki,Helsinki,Finland. ~:DepartmentofPathology,KennestoneHospital,Marietta, GEorgia. Supported by USPHS Research Grants NS-05065, N816236, NS-11672, NS-12706, and Program Grant NS-05785; by a grant from the ResearchFund of the AmericanOtological Society; and by the Finska L/ikaresiillskapetand the Paulo Sg/itio,Helsinki, Finland. Address correspondence and reprint requests to Dr, Hawkins: Kresge Hearing Research Institute, 1301 E, Ann Street, Ann Arbor, MI 48109.

have more or less normal hearing, The dysplasia occurs in association with such hereditary disorders as P e n d r e d ' s s y n d r o m e , a n e n c e p h a l y , 7 and other anomalies, e.g., trisomies or thalidom i d e - i n d u c e d e m b r y o p a t h i e s . 4 It also occurs sporadically with no known cause. M a l f o r m e d ears may have a b n o r m a l stapes with defective footplates and perilymphatic fistulae, which may be open or covered by membranes. This defect may result in recurrent otogenie meningitis. In cases of recurrent meningitis, M o n d i n i malformation w i t h a defective oval window should be suspected, s Schuknecht 9 believes that patients known to have the malformation should be counseled and forewarned of the possibility of this complication. No stapedial fistulae were observed in our study. Some surgeons advocate endolymphatic saccostomy or decompression in cases of Mondini malformation with progressive hearing loss, assuming that it would prevent further deterioration of hearing. I~ This notion appears to be based on the inference that Mondini dysplasia is associated with endolymphatic hydrops. Although distention of the saccule, the saccular duct, and the endolymphatic sac has been reported, 12a3 endolymphatic hydrops is not usually part of the Mondini dysplasia and was not demonstrated in this study. For extensive discussion of Mondini dysplasia, the reader is re-

242

JOHNSSONET AL. ferred to monographs and reviews on the sub-

ject.Q,13-1

We previously reported dysplasia of the vestibular portion of the labyrinth with and without accompanying cochlear malformations of the Mondini type. 17 The most common form of vestibular abnormality was persistence of the membranous horizontal canal anlage. In one of our specimens, the bony canal anlage enclosed a membranous ampulla and canal of normal shape. In most reports, the horizontal canal is cited as the most frequently grossly malformed inner ear structure. S'17-19 Altman Is indicated that malformations may occur in the pars superior of the inner ear without accompanying cochlear anomalies. The radiologist and the otologist should thus keep in mind that abnormal bony canals seen on radiographs can represent relatively harmless malformations and that the pouch-shaped bony anlage might contain a normal membranous canal and ampulla, It is debatable whether the isolated finding of a persistent canal anlage should be referred to as a Mondini malformation.6 Carlo Mondini's dissection in 17911 and the temporal bones in the Ibsen-Mackeprang collection3 have demonstrated the bony labyrinthine anomalies associated with this dysplasia. Bredberg 2~ reported the microdissection of a short and abnormally coiled cochlea in a fivemonth fetus. We report for the first time microdissections of postnatal temporal bones showing Mondini dysplasia malformations of both membranous and osseous labyrinths. METHODS

Temporal bones from cases 1 and 2 were obtained at autopsy at the University of Michigan Hospital, as part of the material gathered for a large temporal bone collection. 21,22 The inner ear anomalies were found coincidentally. In case 3 trisomy D was identified, and the temporal bones were sent to us from the Springfield [Massachusetts) Hospital, because of suspected ear anomalies. The temporal bones were processed by microdissection and surface preparations. 2~ After fixation with 4 per cent paraformaldehyde solution, the inner ears were stained by perilymphatic perfusion with 1 per cent osmic acid. After the otic capsule covering the scala vestibuli, scala media, and vestibular organs was reduced to a thin shell, it was removed. The microdissections, immersed in 70 per cent alcohol, were transilluminated, examined, and photographed under the dissecting microscope. Coch-

lear hair cells were counted along the entire length of the basilar membrane, and the percentage of missing hair cells was calculated on the basis of the regular arrangement of three rows of outer hair cells. Cochlear length was measured at the habenula perforata. A sample of the organ of Corti with the osseous spiral lamina from the right ear in case 3 was embedded and cut into sections 3 p.m thick. The macular organs and horizontal canal crista in case 3 were critical-point-dried, and the neuroepithelium was examined by scanning electron microscopy. After dissection was completed, the modioli were decalcified, celloidin embedded, and sectioned for evaluation of ganglion cells and nerves. The ossicles from the right ear were decalcified, embedded in methacrylate, and sectioned. REPORT OF THREE CASES

The cases are described in order of increasing severity of the malformation. Case 1

A 14-year-old girl was admitted to the hospital with acute monocytic leukemia, pancytopenJa, and septicemia, Serum hepatitis was also suspected because of the serum bilirubin level of 5,2 mg/lO0 ml, and the patient was treated with antibiotics and blood transfusions. Before hospitalization, the leukemia had been treated with 6-mercaptopurine, 200 mg/day for six months, and then with methotrexate, 2.5 rag/day for three months. After two weeks in the hospital the patient ex~ perienced severe abdominal pain, became comatose, and died. At autopsy, extensive hemorrhage of the gastrointestinal tract was found, The changes in the liver indicated that the patient had had hepatitis. No anomalies were found at autopsy. The patient's parents reported that she had been hard of hearing in the left ear and believed that the hearing loss had been caused by measles at the age of 8 years. The left cochlear spiral was flatter than normal, and it also appeared to be shorter. The apical end was less coiled, and the helicotrema was much wider than in a normally shaped cochlea (Figs, 1 and 2). The right labyrinth was normal. In dissecting the cochlea, we consistently divide the spiral along an imaginary line tangential to the anterior margin of the round window and passing through the center of the helicotrema.23

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MONDINI INNER EAR MALFORMATION

Figure 1 (top). Normal left labyrinth from a 25-year-old subject. SL indicates spiral ligament; OC, organ of Corti; N, dense American network of radial fibers (intralaminar spiral fibers barely visible); H, helicotrema; DR, duatus reuniens; S, saccule with saccular duct (arrow); U, utricle; Sp, H_r, Pc, membranous canals with ampullae; OW, oval window; RW, round window niche. Journal Figure 2 (bottom). Case 1. Left cochlea (variation 1). The cochlea is slightly shorter than normal and less tightly coiled. It of Otolaryngology is characterized by a wide helicotrema (H); the presence of the organ of Corti (OC); and subtotal degeneration of the nerve fibers in the osseous lamina, with a few remaining in the apex. OW indicates oval window. Inset, close-up view of the lower basal turn, with a few nerve fibers (left of field) and scattered pigment cells (tap of field). Dark bands on the basilar membrane 244 represent inner and outer hair cells.

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The basilar m e m b r a n e and osseous spiral lamina are t h e n d i v i d e d into 7 major parts, referred to as the " h o o k , " B1/2, B1, M1/2, M1, A1/2, and A1 (B, M, and A r e p r e s e n t the basal, middle, and apical turns, respectively). By these criteria, no apical turn was p r e s e n t in the left ear. The cochlear length, h o w e v e r , was almost normal. The length of the basilar m e m b r a n e was 30.0 m m in the left ear and 31.47 m m in the right ear. The vestibular organs w e r e normal. T h e vestibular n e u r o e p i t h e l i a were flattened u n d e r a coverslip a n d studied as whole-mounts. The sensory cells c o u l d not be examined in detail, but the hair cell p o p u l a t i o n and the nerve network a p p e a r e d to be n o r m a l . There was a striking, n e u r a l type of degeneration in the left cochlea, whereas the nerve and hair cell p o p u l a t i o n s in the right cochlea were normal. The left ear h a d almost complete loss of nerve fibers in the osseous spiral lamina, with only a few radial fibers r e m a i n i n g in the apical e n d of t h e c o c h l e a (Fig. 2). A n e v e n s p a r s e r group of radial fibers r e m a i n e d in a small area in the lower half of the basal turn. Despite this severe loss of n e r v e fibers, there was only moderate loss of s e n s o r y cells (Fig. 3).

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A 5-day-old b o y d i e d of c y a n o t i c congenital h e a r t disease. Various c o c h l e a r a n d v e s t i b u l a r anomalies were f o u n d at autopsy. T h e left cochlea s h o w e d a m a l f o r m a t i o n a l m o s t i d e n t i c a l to that in the left ear of case 1 (Fig. 4), a n d the cochlear malformation i n the right ear was similar but less p r o n o u n c e d . Hair cell p o p u l a t i o n s were n o r m a l in both ears. T h e c o c h l e a r spiral in case 2 a n d a n o r m a l c o c h l e a are s h o w n in Figure 5, left a n d right, respectively. T h e n e r v e n e t w o r k i n b o t h c o c h l e a s was normal, except that a f e w e x a m p l e s of an unusual f a r m of l o c a l i z e d absence of the m y e l i n sheath were observed in the osseous spiral lamina near the l o w e r e n d of the basal turn of both ears (Fig. 5, left). M y e l i n s h e a t h s of the radial n e r v e fibers had d e g e n e r a t e d in the i m m e diate vicinity a r o u n d short stretches of clearly s e e n c a p i l l a r i e s c r o s s i n g t h e s e fibers. T h i s c r e a t e d the a p p e a r a n c e of l i g h t , t r a n s l u c e n t paths m e a n d e r i n g t h r o u g h the d a r k n e r v e network. This finding, the cause of w h i c h is unk n o w n , is described in greater detail in a n o t h e r report. 24

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MONDINI INNER EAR MALFORMATION

Figure 4. Case 2. Left labyrinth (variation 2). The cochlea is shorter than normal (27.7 mm) and less coiled. H indicates wide helicotrema. Persistent horizontal canal anlage with crista (C} is present. U indicates small macula utriculi with two large vessels beneath it; Po, posterior canal and ampulla (superior canal is normal, but not visible),

American Journal of

Otola ryngology 246

In both ears, the horizontal canal was grossly malformed, with a persistent anlage (Fig. 4). The membrane did not form a semicircular canal or ampulla but was shaped like an open p o u c h with a crista and neuroepithelium bulging from the utricle. The surrounding otic capsule had the same shape and formed a bony cavity extending from the vestibule. The macula utriculi was approximately two thirds of normal size. In the left ear, the membranous wall of the saccule was collapsed over a large area, and it was attached to the otoconial membrane. The saccular duct was filled with a proteinaceous mass and was apparently occluded. In two areas, abnormal growth of the membranous walls of the vestibular organs was observed. A small, balloon-shaped membranous structure was attached to the outer surface of the medial side of the utricle. Capillaries were seen in the wall of this structure. From the membranous ampulla of the posterior semicircular canal, a similar, but smaller, structure was formed by invagination of the ampullary wall into the utricle. These epithelial cysts appeared

to be similar to those that we 25 and others is have observed in hereditary deafness. The vestibular n e u r o e p i t h e l i a were e x a m i n e d in the same fashion as in case 1, and hair cell and nerve populations appeared normal. Case 3

An infant was stillborn with numerous congenital malformations to a gravida III, para H, 27year-old woman. Although chromosomal studies were not performed, the pattern of anomalies was characteristic of trisomy 1 3 - 1 5 . Major externally visible deformities were anophthalmos, c o m p l e t e m i d l i n e cleft lip a n d palate, malformed, low-set ears, and absent eyebrows. Polydactyly was not present. Of the major internal anomalies, the brain findings were the most characteristic: slight m i c r o c e p h a l y (225 g); arhinencephaly; partial agenesis of the corpus callosum; atrophy of the optic tract, chiasma, and nerves; and atrophy of the posterior two thirds of the lateral ventricles. The heart was severely

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Figure 5, Top, Case 2, Osseous lamina and the organ of Corti dissected from the left ear. The cochlea is short (27.7 ram) and less coiled, with wide helicotrema. Pericapillary demyelinization is visible (arrows). The almost total absence of intralaminar spiral fibers is normal for this age group. DR indicates ductus reuniens; SL, spiral ligament. Bottom, the organ of Corti and the osseous lamina from the right ear of a 19-year-old subject. Length (33.6 ram), coiling, and helicotrema size are normal. A dense network of radial fibers is present, with numerous intralaminar spiral fibers (arrow). S indicates stria vascularis.

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MONDINI INNEREAR MALFORMATION

Figure 6. Case 3. Malformed ossieles from the right ear. The malleus (m) and incus (1) are fused. The abnormal malleoincudal joint separates the incudal short process (Isp) from the fused bones. The long process is partly aplastic and fibrous (darkly stained, cut). The stapes (S) has anterior crus only.

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anomalous, and other findings included agenesis of the left kidney, cortical tubular cysts in the right, and undescended testes with hypospadies. LEFT EAR. This ear had less pronounced gross anomalies than the right. Middle ear anomalies. The bulk of the malleus and the incus body were fused, and both bones were abnormal in shape. The malleoincudal joint was abnormal, such that the short process was separated from the two fused bodies of the ossicles (Fig. 6 shows similar changes in the right ear). The stapes was normal in shape. A thin strand of tissue, probably the remnant of the stapedial artery, passed between the crura. 26 The facial nerve was not enclosed in a bony canal. Rather, its v e r t i c a l p o r t i o n was surr o u n d e d by cartilage and connective tissue. The chorda tympani had a n o r m a l middle ear course. The facial nerve with the soft tissue surrounding it was easily dissected from the middle ear. After

its removal, two adjacent, s m o o t h l y contoured pits were uncovered in the bone posterior to the oval w i n d o w . The u p p e r one w a s c o n n e c t e d with a groove above the oval w i n d o w , in w h i c h the tympanic portion of the facial nerve was located. Cochlear anomalies. The cochlea was malformed, with the first half of the basal turn m u c h less curved than usual. The remaining p o r t i o n of the cochlear spiral was shorter than n o r m a l and much flatter. Only 1 1/2 turns were present, and the total length of the cochlea was 25.5 ram. There was a short i n t e r s c a l a r s e p t u m corresponding to the apical end of the cochlea, b u t no modiolus had developed. The peculiar shape of the cochlea caused the distance between the oval w i n d o w and the upper end of the basal t u r n to be much greater than in a n o r m a l l y s h a p e d cochlea (Fig. 7). The hair cell population, w h i c h was well preserved and easily countable, was almost normal.

JOHNSSON ET AL.

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Figure 7. Case 3. Top, left labyrinth (variation 3). The cochlea is shorter (25.5 mm) and less coiled than normal. The distance from the oval window (OW) to the second turn is unusually long. Hz indicates persistent horizontal canal anlage; Sp, superior; Po, normal posterior canals and ampullae; U, small macule utriculi; and RW, round w~ndaw niche. Bottom, osseous lamina and the organ of Corfi from this ear, Abnormal coiling, sparse network of radial fibers, and abnormal location of the intraganglionic spiral bundle in the osseous lamina are evident. Four bundles can be seen entering the lamina to take a spiral course (arrow}.

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MONDINI INNER EAR MALFORMATION

Figure 8. Case 3. Right ear (variation 4). Coiling is abnormal, as in the left ear. Notice the complete absence of nerve fibers in the osseous lamina. OC indicates organ of Corti. In the upper half turn, numerous blood vessels cross beneath basilar membrane (cf,, Fig. 7). Sp, Hz, and Po indicate persistent anlagen for canals; U, macula utriculi.

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Mild loss of outer hair cells was f o u n d in the 4t o 8-mm area. (The hair cell p o p u l a t i o n in the first 3 m m of t he region of the h o o k could not be evaluated because of dissection artifacts.) The tectorial m e m b r a n e was normal. Neuroanatomic anomalies. Innumerable radial n e r v e fibers, al t hough far fewer than in a n e w b o r n i n f a n t , w e r e p r e s e n t i n the osseous spiral lamina, and t h e y appeared to have thinner my elin sheaths than n o r m a l for this age group (Fig. 7). Only a few single intralaminar spiral fibers w e r e present, but this is a n o r m a l finding, since th e s e fibers are not well d e v e l o p e d in infants. In c h i l d r e n older t h a n 2 or 3 years of age and in adults, m a n y of the radial fiber bundles e m e r g i n g f r o m the m o d i o l n s s w erve to take a spiral course in the osseous spiral lamina. T h e y thus f o rm m ul t i pl e parallel bundl e s that course l o n g i t u d i n a l l y for h a l f a t u r n or m o r e b e f o r e turning radially again toward the habenula perforata 21 (cf. Fig. 5, bottom). In Figure 7 (top) t w o t h i c k bundles and two t h i n n e r b u n d l e s of spiral fibers can be seen enter in g t h e os s eous s pi r a l l a m i n a in t h e u p p e r

port i on of t he basal t u r n before taking a spiral course along the modiolar margin of the osseous spiral lamina. Nerve fibers from n u m e r o u s bundies of radial fibers take a spiral course and join this spiral bundle. Several nerve fibers can be s e e n l e a v i n g t he b u n d l e a n d taking a radial course to the organ of Corti. T h e majority of the spiral fibers, h o w e v e r , c o n t i n u e t o w a r d t h e apical end of the cochlea, where the bundle divides into several fascicles that take an oblique spiral course to the organ of Corti. This bundle a p p a r e n t l y c o r r e s p o n d s to t h e intraganglionic spiral bundle. ' As m ent i oned earlier, this ear had no modiolus and no canal of Rosenthal, and the internal auditory meatus was short and wide. The cochlear nerve d i v i d e d inside the meatus into five to seven branches, w h i c h fanned out toward the osseous spiral lamina. The c o c h l e a r ganglion cells were t h u s located inside the auditory canal. Vascular anomalies. N u m e r o u s vessels c r o s s e d the b a s i l a r m e m b r a n e r a d i a l l y in all turns to join the vessels of the scala t y m p a n i portion of the spiral ligament (Figs. 7 and 8). In the

JOHNSSON ET AL.

Figure 9. Case 3. Right ear (variation 4}. Membranous labyriath dissected away. Scala tympani and vestibule with canal anlagen (Sp and Po) are displayed, lined with blood vessels. RW indicates round window niche (cf. Fig. 8).

basal turn, these vessels were even more numerous than those seen in fetuses. 27 Most of the vessels came d i r e c t l y from the osseous spiral lamina. Others w e r e br a nc he s of the inner or outer spiral vessel. Otherwise, the vasculature was normal, having characteristics pr evi ous l y described in newborns, i.e., dense capillary beds with some vessels larger than those in adults. 27 There was no obvious strial atrophy. Anomalies of the vestibular organs. The m a l f o r m a t i o n of t h e h o r i z o n t a l s e m i c i r c u l a r canal was similar to that in case 2. A membranous p o u c h bulged from the vestibule, and a bony pouch from the utricle (Fig. 7, top). The macula utriculi was about two thirds of normal size. The neuroepithelium of the vestibular organs, as s t u d i e d by s c a n n i n g e l e c t r o n m i c r o s c o p y , showed severe loss of sensory cells in all organs, indicated by a reduction in the num ber of ciliary tufts on the epithelium. RIGHT EAR. This was the most strikingly anomalous ear. Middle ear anomalies. T h e m i d d l e ear anomalies were almost identical with those of the left ear, but the ossicular chain was more malformed on this side (Fig, 6), The malleus and the incus body, both abnormal in shape, were

fused. The short process of the i ncus was separated from the ossicular mass by an abnormal malleoincudal joint, as in the left ear, The long process of the incus was i n c o m p l e t e l y developed, and only a thin strand of soft tissue connected it to the stapes. The stapes was anomalous in shape, and onl y the anterior crus was present, A small, but pat ent , s t a p e d i a l artery passed just behind the crus, Histologic sections of the essicles showed that there was poor cartilaginous development, with poor resorption of the existing cartilage and insufficient ossification of all bones. Cochlear anomalies. T h e c o c h l e a r malformations were similar to those of t h e left ear. The vestibular organs were even less d e v e l o p e d than on the opposite side, with no semicircular canals present and only an anlage of each in the form of a p o u c h (Figs. 8 and 9}. The cochlea was identical in shape to that of the left ear, but it was shorter (21.3 mm). As in the left ear, a short i n t e r s c a l a r s e p t u m was present. The major difference was the absence of auditory nerve fibers in this ear. There were no nerve fibers in the osseous spiral lamina, and no nerve was seen entering the cochlea. As in the opposite ear, the modiolus had not been formed. The internal auditory canal was short and wide

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MONDINI INNER EAR MALFORMATION

Figure 10, Case 3. Right ear. a, Cross section of the organ of Corti in the apical half of the cochlea (normal tectorial membrane removed). Under the reticular lamina are four malformed, minute outer hair cells. The inner hair cells appear less abnormal. b, Reticular lamina, upper end of basal turn. IHC indicates inner hair cells; IP, head plates of inner pillar cells; OHC, four to fi-~e irregular rows of outer hair cells, with pale, rounded cuticular plates [phase contrast).

Americon Journal

of Otolaryngology 252

and contained only one nerve, with numerous ganglion cells and proximal fibers but only a few distal fibers supplying the macula sacculi. The organ of Corti was poorly preserved, but the pattern of the reticular lamina appeared to be normal. Cuticular plates of hair cells were pale and rounded. No stereocilia were seen in surface preparations (Fig. 10a), but cross sections of a 1.5-ram sample from the upper half of the spiral showed the presence of outer hair

cells. They were highly abnormal in appearance and made no contact with the Deiters' cells below them. Their stereocilia were also minute. The inner hair cells, on the other hand, appeared to be less abnormal (Fig. 10a). Vestibular anomalies. No semicircular canals had formed. Two smaller p o u c h e s extending from the utricle clearly represented the anlagen for the superior and horizontal canals and their ampullae, and a larger pouch corre-

JOHNSSON ET AL.

sponded in location to the posterior canal and ampulla. The shape of these structures, and the corresponding malformations of the otic capsule, are seen in Figures 8 and 9. Each of the three membranous anlagen contained small, flat, oval islands of neuroepithelium that clearly represented rudimentary cristae. The macula utriculi was oval and about half of the normal size. Each crista anlage had a planum semilunatum containing p o p u l a t i o n s of predominantly dark osmiophilic ceils, with a few light cells among them. In the wall of the utricle, a similar arrangement of numerous dark osmiophilic cells was observed, interspersed with a few lightly stained cells. These cells represented the "dark" and "light" cells seen in the normal labyrinth. No otoconial membrane was found in either macula. The o t o c o n i a m a y have been lost because of long storage in formalin and alcohol. However, since no gelatinous layer was present, aplasia of macular suprastructures could have been responsible. Aplasia of otoconia has been described, but in those cases the gelatinous layer was still present, zB No cupulae were seen on the rudimentary cristae, but they may have been lost in the process of dissection. Scanning electron microscopic observations of vestibular neuroepithelia. Examination of the surface of the macula sacculi showed a markedly reduced n u m b e r of ciliary tufts (Fig. 11a). Some of the cilia were longer than usual and were apparently fused. Where the epithelium had been fractured, n u m e r o u s hair cells were seen, some without stereocilia. Interconnecting strands were seen at the basal ends of the sensory ceils, probably representing nerve fibers and their endings (Fig. 11b). No cilia could be identified with certainty on the utricular surface. Cell boundaries of the reticular lamina were swollen. Several large craterlike openings were seen, but it was not clear whether they were artifacts or represented the in r i v e condition. T h e y did, however, permit a v i e w b e n e a t h the reticular lamina, w h i c h showed numerous hair cells of both types I and II (Fig. 12). The density of ciliary tufts in the crista anlage was almost normal. Many of the cilia appeared to be fused, b u t it could not be determined whether this was due to autolysis or maldevelopment. DISCUSSION

The cases described clearly represent different stages of arrested inner ear development. Case 1

showed only mild malformation of both cochleas. In case 2 a similar unilateral malformation was present, in a d d i t i o n to a persistent horizontal canal anlage. Case 3 showed much more p r o n o u n c e d bilateral c o c h l e a r malformation than cases 1 and 2, with a persistent anlage of the horizontal canal in the left ear and arrested development of all vestibular organs (with the exception of the saccule) in the right ear. Anomalies of the semicircular canals are of clinical interest, since they could affect the horizontal canal response to caloric stimulation. In a pouch-shaped horizontal canal and ampulla in which the cupula is not enclosed by a membranous wall, the fluid movements caused by a caloric stimulus m a y not create a pressure gradient sufficient tO deflect the cupula. Thus, such an anomalous canal may not react to caloric stimulation, although it m a y respond to physiologic stimuli. 17 Certainly, an atresia of the membranous canal, such as that found in a normal ear from a teenager (Fig. 13), is likely to prevent or diminish a caloric response. The pouch-shaped lateral canal anlage could transmit the caloric stimulus to the utricle and the other ampullae, causing a bizarre caloric reaction. ~7 The semicircular canals first appear as flattened pouchings protruding from the ut~icle. 29-3! In a six-week embryo, the superior ridge has already become the superior semicircular canal. The t w o other antagen are successively transformed into the p o s t e r i o r and the horizontal semicircular canals. The canals attain maximum size in the same order. This sequence may explain the predominance of horizontal canal malformation, and it also indicates the gestational age at which semicircular canal aplasias occur. The shape of the m e m b r a n o u s and osseous wall enclosing the vestibular organs in the right ear of case 3 (Fig. 8) suggests arrested development before the sixth w e e k of fetal life {assuming a normal rate of development) and represents an even more severe malformation than that of the cochlea. The vestibular organs, which are phylogenetically the oldest part of the labyrinth, are more resistant to secondary nerve degeneration az and insults than is the cochlea, but they have a greater tendency for anomalies, la'17'18 The abnormal coiling of the cochlea can give the e r r o n e o u s i m p r e s s i o n of a considerably shortened organ. In case 1 (Fig. 2), the left cochlea had an abnormal shape, but the length of the basilar membrane was 30 ram. In the right ear, w h i c h had normal coiling, it was not much longer, i.e., 31.97 mm, In case 2, the lengths of the left and the right basilar membranes were

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MONDINI INNEREAR MALFORMATION

Figure 11. Case 3. a, Right ear. Scanning electron micrograph of macula sacculi. Reduced number of ciliary tufts, which are partly fused, b, Fractured area of macule sacculi displaying hair ceils, some of which lack cilia. Root-like structures at their bases probablyrepresent nerve fibers and endings,

American Journal of Otolaryngology 254

27.7 and 30.5 mm, respectively, which does correlate with the fact that the left ear had a more misshapen cochlea. In case 3, in which the cochlear anomalies were the most severe, the basilar membrane lengths were 25.5 and 21.3 mm for the left and right ears, r e s p e c t i v e l y . This is clearly less than the mean length (33.99 ram; SD, 1.22 ram) of 52 cochleas from adults in our collection. The mean difference between the two ears in case 3 was 1.22 m m (variance, 0.1 to 4.3 mm). The length of the cochlea in Bredberg's case of a five-month h u m a n fetus (by which time no further increase could be expected) was only 13 ram. 2~ The shape of the cochlear spiral in ears with Mondini malformations gives the impres-

sion that there is initially good growth of the basal turn, the lower end of w hi ch apparently serves as a growth center. 33 This growth is then interrupted, and the middle and apical turns fail to d e v e l o p , or t h e y d e v e l o p and coil insufficiently. The interscalar septa were present in all of the cochleas. Abnormal epi t hel i al cysts were obs e r v e d in t he v e s t i b u l a r s y s t e m in case 2, in which a saccule was partially collapsed and a saccular duct was occluded by a proteinaceous mass. This infant was 5 days old, and, presumably, the occlusion had not been of long duration. Abnormal epithelial growth of the labyrint h i n e m e m b r a n o u s walls in a s s o c i a t i o n w i t h

JOHNSSON ETAL. d e a f n e s s of t h e h e r e d i t a r y t y p e has b e e n described, 18,25 The e n d o l y m p h a t i c sac was not exa m i n e d in o u r cases, b u t n o h y d r o p s was present, T h e ear anomalies f o u n d in the stillborn tris o m y D infant with m u l t i p l e anomalies of other organs were in agreement w i t h the findings of previous investigators. 34 It s h o u l d be noted that the infant did have a normal brainstem, a probable prerequisite for n o r m a l d e v e l o p m e n t of the labyrinth. 35 Even so, considerable maturation of the inner ear n e u r o e p i t h e l i a can take place in anencephalics. 7 Tissue culture studies also indicate that an o t o c y s t - m e s e n c h y m e interaction affects t h e d e v e l o p m e n t a n d cpiling of the cochlea. 36 It is conceivable that the disturbances of ossification in the m i d d l e ear adjacent to the cochlea also contributed to labyrinthine malformations in this case. In the right ear, w h i c h h a d n o visible cochlear or utricular nerve fibers and no discernible fibers s u p p l y i n g the r u d i m e n t a r y cristae, the organ of Corti and the sensory cells of the macula utriculi and the cristae developed. The sensory cells of the organ of Corti were, however, grossly malformed, and the utricular sensory cells had no stereocilia. The n u m b e r of ciliary tufts on the horizontal crista, w h i c h was the only one exa m i n e d b y scanning electron microscopy, was almost normal, but the c o n d i t i o n of the hair cells was not explored. T h e saccule, w h i c h did receive some nerve fibers, was not m u c h better dev e l o p e d than the utricle. Our findings are similar to t h o s e of F r i e d m a n n et al., 7 w h o d e s c r i b e d

Figure 12. Case3. Right ear. Scanning electron micrograph of utricular macula with crater-like opening. Notice the swollen cell junctions of reticular lamina with a few fused stereocilia. Both types I and II hair cells are present. Rootlike structures (possibly neural remains) appear to be less numerous than in the macula sacculi (Fig, 11). w e l l - d e v e l o p e d n e u r o e p i t h e l i a l structures in ears w i t h the M o n d i n i m a l f o r m a t i o n despite total or partial absence of neural elements, These findings support recent observations that maturation of the auditory 37 and vestibular organs 38 in organ cultures can occur in the absence of nerve fibers or without close contact with them. W h e t h e r the m a l f o r m a t i o n of sensory cells in case 3 was due to the absence of nerve fibers and/

Figure 13. Lefthorizontal canal ampulla from a teenager with normal hearing, divided longitudinally, Notice the almost complete atresia of the canal. C indicates crista; PS, planum semilunatum.

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MONDINI INNEREAR MALFORMATION or to o t h e r m o r e p r i m a r y factors, s u c h as the tris o m y , is n o t k n o w n . T h e a b n o r m a l l y sparse n e t w o r k of radial fibers in the left ear i n case 3 w a s p r o b a b l y d u e to dev e l o p m e n t a l failure r e l a t e d to the t r i s o m y rather t h a n to d e g e n e r a t i o n d u r i n g g e s t a t i o n in this stillborn infant. The p r o m i n e n t b u n d l e of spiral fibers i n case 3 is b e l i e v e d to r e p r e s e n t the intraganglionic spiral bundle, which had grown anomalously into the osseous spiral lamina, probably because no modiolus had formed. T h e r e are few a l t e r n a t i v e e x p l a n a t i o n s for the p r e s e n c e of t h e s e f i b e r s i n the o s s e o u s s p i r a l lamina. T h e b u n d l e c o u l d n o t h a v e r e p r e s e n t e d the i n t r a l a m i n a r spiral fibers, w h i c h are p o o r l y d e v e l o p e d e v e n in n o r m a l infants. W h e n t h e y a p p e a r at 2 to 3 years of age, t h e y h a v e an entirely different o r g a n i z a t i o n , and t h e y are w i d e l y d i s t r i b u t e d in the o s s e o u s spiral lamina. 21 The spiral b u n d l e b e g a n its c o u r s e i n the m i d d l e of t h e b a s a l t u r n a n d r e c e i v e d n u m e r o u s contributions f r o m the b u n d l e s of radial fibers, w h i c h are g e n e r a l l y r e g a r d e d as afferent. This f i n d i n g l e n d s further s u p p o r t to o u r earlier p r o p o s i t i o n that the i n t r a g a n g l i o n i c spiral b u n d l e i n h u m a n s , unlike t h a t in g u i n e a pigs, is n o t d e r i v e d p r i m a r i l y f r o m t h e b u n d l e of O o r t b u t rather t h a t a m a j o r p o r t i o n of it c o n s i s t s of m y e l i n a t e d a f f e r e n t nerve fibers. 21 This n o t i o n does n o t e x c l u d e the p o s s i b l e p r e s e n c e of u n m y e l i n a t e d e f f e r e n t fibers a d j a c e n t to, or i n t e r m i n g l i n g with, the afferent fibers, 39 b u t n o n e w a s o b s e r v e d w i t h the staining t e c h n i q u e s u s e d i n this s t u d y . The s u b t o t a l lass of n e r v e fibers in t h e left ear in case 1, in w h i c h m o s t of the hair cells w e r e present, was p r o b a b l y d u e to a c h i l d h o o d disease, w h i c h m a y h a v e s e l e c t i v e l y affected the m a l f o r m e d c o c h l e a . M e a s l e s , w h i c h was susp e c t e d b y the p a t i e n t ' s p a r e n t s as a cause of the c h i l d ' s h e a r i n g loss, is k n o w n , h o w e v e r , to c a u s e a s e n s o r i n e u r a l t y p e of d e g e n e r a t i o n . 4~ A p u r e f o r m of n e u r a l d e g e n e r a t i o n as s e e n i n this ear is e x c e e d i n g l y rare. S t u d y of the M o n d i n i m a l f o r m a t i o n p r o v i d e s i m p o r t a n t i n f o r m a t i o n a b o u t the d e v e l o p m e n t of the h u m a n l a b y r i n t h . T h e s e n s o r y a n d n e u r a l m a l f o r m a t i o n s of b o t h ears in case 3 are particu l a r l y i n t r i g u i n g a n d s u g g e s t that n e u r o a n a t o m i c a s p e c t s of i n n e r e a r d e v e l o p m e n t s h o u l d be s t u d i e d w i t h p a r t i c u l a r a t t e n t i o n i n future cases. References

American Journal of Otolaryngology 256

1. Mondini C: Anatomica surdi nati sectio: de Bononiensi scientarum et artium institute atque academia commentari. Bononiae 7:419-431, 1791

2. Everberg G: Investigations into unilateral total deafness and absence of vestibular function with a particular view to the x-ray appearance in the inner ear. Acta Otolaryngol 52:47-62, 1960 3. JensenJ: Malformations of the inner ear in deaf children. Acta Radial CSuppl 286}:1963 4. Terrahe K: Missbildungen des Innen und Mittelohres als Folge der Thalidomidembryopathie: Ergebnisse van RSntgenschichtuntersuchungen des Ohres. Fortschr Gab Rontgenstr Nuklearmed Erganzungsband 102:1429, 1965 5. Valvassori GE, Naunton RE, Lindsay JR: Inner ear anomalies: clinical and histopathological considerations. Ann Otol Rhinol Laryngol 78:929-938, 1969 6. Valvassori GE, Mafee MF, Dobben GD: Computerized tomography of the temporal bone. Laryngoscope 92:562-565, 1982 7. Friedman I, Wright JL, Phelps PD: Temporal bone studies in anencephaly. ] Laryngol Otol 94:929-944, 1980 8. Biggers WP, Howell NN, Fischer ND, et ah Congenital ear anomalies associated with otic meningitis. Arch Otolaryngol 97:399-401, 1973 9. Schuknecht HF: Mendini dysplasia: a clinical and pathological study. Ann Otol Rhinol Laryngol 69 (Suppl 65, part 1}:1980 10. Shea JJ, at ah Surgical attacks on fluctuant hearing loss, in Shambaugh GE ]r, Shea ]J (eds): Proceedings of the Shambaugh Fifth International Workshop on Middle Ear Microsurgery and Fluctuant Hearing Lass. Huntsville, Alabama, Strade Publishers, 1977, pp 477-483 11. Mangabeira-Albernaz PL, Fukuka Y, Chammas F, et ah The Mondini dysplasia: a clinical study. J Otolaryngol Relat Spec 43:131-152, 1981 12. Gussen R: Mondini type of genetically determined deafness. J Laryngol Otol 82:41-55, 1968 13. Paparella MM: Mondini's deafness: a review of histopathology. Ann eta] Rhino] Laryngol 89 (Suppl 67, part 2):1980 14. Mygind H: Obersicht fiber die pathologisch-anatomischen Ver~nderungen der GehGrorgane Taubstummer. Arch Ohrenheilkd 30:76-118, 1890 15. Illum P: The Mondini type of cochlear malformation: a survey of the literature. Arch Otolaryngo196:305- 311, 1972 16, Birth Defects: Original Article Series, in Gorlin RJ (ed): Morphogenesis and Malformation of the Ear. March of Dimes Defects Foundation, Vol. 16(4). New York, Alan R. Liss, 1980 17. ~ohnsson L-G: Degenerative changes and anomalies of the vestibular system in man. Laryngoscope 81:18821694, 1971 18. Altman F: Malformations, anomalies and vestigial structures of the inner ear. Arch Otolaryngol 57:591-692, 1953 19. Sando I: Discussion of inner ear anomalies: reply to Dr. Schuknecht. Birth Defects 16(4):73-82, 1980 20. Bredberg C: Cellular pattern and nerve supply of the human organ of Corti. Aeta Otolaryngol (Suppl 236):1968 21. Iohnsson L-G, Hawkins JE jr: Sensory and neural degeneration with aging, as seen in microdissections of the human inner ear. Ann Otol Rhinol Laryngol 81:179193, 1972 22. ]ohnsson L-G, Hawkins JE jr: Vascular changes in the human inner ear associated with aging. Ann Otol Rhinol Laryngol 81:364-376, 1972 23. Hawkins ]E jr, ]ohnsson L-G: Microdissection and surface preparations of the inner ear, in Smith CA, Vernon, JA (eds]: Handbook of Auditory and Vestibular Research Methods. Springfield, Illinois, Charles C Thomas, 1976, pp 5-52 24. ]ohnsson L-G, Hawkins JE jr: Perivascular demyeliniza-

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25. 26, 27. 28. 29. 30. 31.

32.

tion of cochlear neurons in two neonates. Acta Otolaryngol, in press Johnsson L-G, Rouse RC, Hawkins JE jr, et el: Hereditary deafness with hydrops and anomalous calcium phosphate deposits, Am ; Otolaryngol 2:284-298, 1981 ]ohnsson L-G, Kingsley TC: Herniation of the facial nerve in the middle ear, Arch Otolaryngol 91:598602, 1970 ]ohnsson L-C: Cochlear blood vessel pattern in the human fetus and postnatal vascular involution. Ann Otol R.hinol Laryngol 81:22-40, 1972 Wright CG, Hubbard DG, Graham [W: Absence of otoconia in a human infant. Ann Otol Rhinol Laryngol 88:779-783, 1979 Streetar GL: On the development of the membranous labyrinth and the acoustic and facial nerves in the human embryo. Am ] A n a t 6:139-167, 1906 Bast TH, Anson BJ: The Temporal Bone and the Ear. Springfield, Illinois, Charles C Thomas, 1949 Anson BJ, Davies J: Embryology of the ear: development anatomy of the ear, in Paparella MM, Shumrick DA (eds): Otolaryngology, vo[ I, ed 2., Philadelphia, WB Saundars Co, 1980, pp 3-25 Gacek RR: Afferent auditory neural system, in Graham

33. 34. 35, 36. 37. 38,

39. 40.

AB (ed): Sensorineura] Hearing Processes and Disorders. Boston, Little, Brown and Co, 1967, pp 4 9 - 5 9 Ruben R~: Development of the inner ear of the mouse: a radioautographic study of terminal mitoses. Acta OtoIaryngoI (SuppI 220}:1967 Sando S, Leiberman A, Bergstrom L, et al: Temporal bone histopathological findings in trisomy 13 syndrome. Ann Otol Rhinol Laryngol 84 (Suppl 21):1975 Deol MS: Inherited disease of the inner ear in man in the light of studies on the mouse. ] Mod Goner 5:137158, 1968 Li CW, McPhee J: Influences on the coiling of the cochlea. Ann Otol Rhinol Laryngol 88:280-287, 1979 Van De Water TR, Li CW, Ruben RJ, et ah Ontogenic aspects of mammalian inner ear development. Birth Defects 16(4):5-45, 1980 Anniko M, Nordemar H, van de Water TR: Embryogenesis of the inner ear: I, Development and differentiation of the mammalian crista ampullaris in vivo and in vitro. Arch Otorhinolaryngol 224:285-299, 1979 Gacek RR: The efferent cochlear bundle in man, Arch Otolaryngol 74:690-694, 1961 Lindsay JR: Profound childhood deafness', inner ear pathology. Ann Otol P,hinol Larynga] 82 (suppl 5]:197S

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