Ann Otol 85: 19i6
TEMPORAL BONE HISTOPATHOLOGY OF OSTEOPETROSIS FUMIRO SUGA, JOHN
R.
M.D.
LINDSAY,
CHICAGO,
M.D.
ILLINo:s
SUMMARY - The histopathology of the temporal bone of an eight and one-half-year-old girl with osteopetrosis (Albers-Schonberg disease) was studied to evaluate the pathogenesis of its frequent complications in hearing and facial nerve function. The patient was blind and had acute otitis media, but facial paralysis was not noted. Although the size of the temporal bone pyramid was markedly increased due to enormously thickened periosteal layer, changes in the endosteal and endochondral layers were less marked. Exostotic growth of periosteal bone was seen in the middle ear wall, and the tympanic cavity appeared to be narrowed. At the oval window region, the facial nerve was pushed down towards the stapes due to extreme overgrowth of periosteal bone of the epitympanum, and the superstructure of the stapes was imbedded deeply into the dislocated facial nerve and had strongly compressed it. Although the footplate was free from ankylosis, the crus of the stapes appeared to be immobilized because it was lodged in the facial nerve. Such changes appeared to be the pathogenesis of one form of facial nerve paralysis and conductive hearing loss associated with osteopetrosis.
Osteopetrosis, also known as AlbersSchonberg disease, is a hereditary disease characterized by a generalized increase in bone density. The otological interest has been drawn to aural complications associated with this disease. Although the most frequent neural complication is optic nerve atrophy, hearing impairment and facial nerve paralysis also are often associated with osteopetrosis.v?
facial nerve at the stylomastoid foramen, demonstrated by x-ray. Surgical observations of the ear with osteopetrosis are rare. Jones and Mulcahy" reported a 26-year-old female who had conductive hearing loss associated with osteopetrosis. The patient had a severe bony narrowing of the left external auditory meatus and a slight narrowing of the right external auditory meatus. Audiometry revealed a moderate conductive hearing loss on the left and a slight conductive loss on the right. Reconstructive surgery of the left external auditory meatus was performed, but the patient's hearing did not improve. An exploratory tympanotomy revealed a narrowing of the tympanic cavity, an incus enveloped in bone and displaced to a lower position, and discontinuity of the incudostapedial joint. The horizontal portion of the facial nerve, the oval window, and the superstructure of the stapes were completely replaced with bone.
Klintworth" examined neurological symptoms of six osteopetrosis patients. He found hearing impairment in all six cases and facial palsy in five. Hearing impairment associated with osteopetrosis has been attributed to the narrowing of the external auditory meatus," the overgrowth of bone within the middle ear and inner ear," and cochlear nerve constriction in the petrous bone." Wolford" reported facial paralysis associated with osteopetrosis in five generations of the same family. He attributed the cause of the facial paralysis to encroachment by thickened bone on the
From the Section of Otolaryngology, University of Chicago, Chicago Illinois. Histopathological studies in this report were supported in part by the A~erican Otological Society, Inc., the E. F. Andrews Foundation, and NIH Grant No. NS-03358-12. 15
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Hamersma7 reported five cases with hearing loss and facial palsy associated with osteopetrosis. The hearing loss was conductive in type in two cases, mixed type in two, and absent in one case. Frequent attacks of facial palsy occurred in four cases. Surgery was attempted in one case to improve hearing, but it was found that stapes mobilization was not possible due to narrowing of the oval window niche. The mastoid segment of the paralyzed facial nerve was surgically decompressed in two cases, but facial palsy recurred in both. There are two histopathological reports of temporal bones with osteopetrosis. Altmann" studied the histopathology of the temporal bone of a 13-month-old infant. Unfortunately, although examination had revealed that this patient had bilateral optic nerve atrophy, otological examinations had not been performed. Altmann described various structural changes of the bone such as the widened periosteal layer of the labyrinthine capsule with markedly narrowed marrow spaces. He found a mushroom-shaped bulging of the facial nerve from a large dehiscence of the facial nerve canal at the oval window region, but he did not find evidence to explain the pathogenesis of frequent hearing impairment associated with osteopetrosis. Myers and Stool" reported the temporal bone pathology of a two and one-half-year-old female who had osteopetrosis, optic nerve atrophy, and hearing impairment. They observed that the endochondral layer showed a striking change. Aside from otitis media, however, there were no significant pathological changes in the cochlea or cochlear nerve. Although there was no history of facial paralysis, they found a herniation of a part of the facial nerve in the horizontal segment, similar to that found in Altmann's" case. Because such studies as those mentioned above present a rather conflicting picture of temporal bone pathology and have shown only minor histopathological evidence of hearing impairment, it seems useful to present a case
of osteopetrosis to supplement the information on temporal bone histopathology and otological complications associated with this disease. CASE REPORT
An eight and one-half-year-old female was first admitted to a hospital at the age of three weeks with a history of fine muscular twitchings of both arms and legs arising eight days after a completely normal birth. The patient's breathing was strident, but no x-ray evidence of bone disease was recognized at that time. When the patient was six months old another x-ray had been taken for thymic size, and an osteopetrotic condition of the bone structure was noted. The entire skeleton was then examined, and all the bones were found to be involved. A review of previous films showed that these changes were already present in the x-ray taken when the patient was three weeks old. When the patient was eight months old, it became apparent that she was blind. An adenoidectomy was performed when the patient was ten months old in an attempt to improve her breathing. At that time, the patient was slightly anemic and showed a marked enlargement of her head. A pneumoencephalogram added cerebral atrophy to the established diagnosis of osteopetrosis and bilateral primary optic nerve atrophy. Since then, the patient had numerous admissions to the hospital and x-rays showed increased osteopetrosis. At the age of three and one-third years, the patient developed acute pUrltlent otitis media of the left ear associated with an upper respiratory infection. With the progress of osteopetrotic changes, thickening of the long bones of the lower extremity, poor muscular tone, and faulty coordination became apparent. At the age of seven years, her head was severely enlarged, measuring 66 em in circumference. At the age of eight and one-half-
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Fig. 1. Horizontal section of the right temporal bone through the ampulla of the superior semicircular canal shows extreme increase in the density of bone and in the breadth of the pyramid. Changes are most severe in the periosteal layer involving an extreme reduction of marrow spaces. The mastoid is not pneumatized, and the antrum area is filled with compact bone (H. and E. stain).
years, the patient developed a high spiking temperature and purulent discharge from both ears. Shortly after, the patient went rapidly downhill, became lethargic, and died. The patient had no history of facial paralysis, and no audiometric examination had been performed. There was no known history of osteopetrosis in the patient's family. AUTOPSY REPORT
The most notable external feature was the enormous enlargement of the head, with a tremendous increase in its weight, due to the great thickening of all the bones of the head. The circumference of the head in the frontal occipital diameter was 67 em. The teeth were well developed, but they were widely separated due to an excessive growth of the mandible and the maxilla. Sections from ribs, sternum, fibula, and vertebrae showed varying degrees
of osseous overgrowth of dense bone containing in some places normal marrow, in others, only fatty tissue. The cortex of a rib was 2 mm thick and extremely dense. The bony trabeculae were also thickened and dense. In the cranium, the dura covering the hemispheres was unusually thickened without corresponding thinning of the falx. The leptomeninges were edematous and showed increased cellularity, mainly histiocytes. Blood vessels of the base of the brain were normal. The anterior part of the brain was disproportionately large on each side, while the temporal lobes appeared short. A coronal section through the frontal lobes revealed extreme hydrocephalus. There was hydrops of the third ventricle, the floor of which was of paper-like thickness. The cerebellum and brain stem were small as compared with the hemispheres.
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Fig. 2. Mushroom-shaped projection of new bone has grown out from the periosteal bone bordering the middle ear space. The deeper staining connective tissue (arrow) in the lining membrane of the middle ear space shows increased osteoid tissue suggesting an active process of pathologic bone formation (H. and E. stain; X90).
The anterior limbs of the optic chiasm were small, and the optic tracts on both sides had been reduced to the thickness of a coarse linen thread. However, the cranial nerves posterior to the II nerve appeared normal in size. The olfactory tracts were not strikingly reduced in size. In serial sections through the basal ganglia of both sides, the most definite change was complete absence of the optic tracts and the lateral geniculate bodies on both sides. mSTOPATHOLOGY
Only the right temporal bone was obtained for histopathological examination. The temporal bone was fixed with formalin, decalcified, embedded in celloidin, and horizontally sectioned in series. Every tenth section was stained and studied with a light microscope. Otic Capsule. The most striking change of the temporal bone was the abnormally dense character of the bone
and the greatly increased breadth of the pyramid (Fig. 1). The periosteal layer was enormously thickened, while the thickness of the endochondral layer and the endosteal layer appeared normal. The overgrowth of the periosteal bone was most marked bordering the cranial cavity but was also severe along the lateral surface bordering the middle Ear space. The overgrown bone had a lamellar-like structure and a fairly uniform pink-staining reaction for H. and E. The thickening of bone generally appeared diffuse but continuous, maintaining a smooth periosteal surface. In addition to the generalized diffuse overgrowth of the periosteal bone, there were mushroom-shaped projections of new bone which had grown out from the periosteal bone bordering the middle ear space (Fig. 2). These projections consisted of a concentric, circular, lamellar-type structure developed from
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Fig. 3. Many of the globular outgrowths of bone have arisen from the periosteal layer bordering the middle ear space (H. and E. stain; X32).
a base containing a small blood vessel. The surface adjacent to such exostotic overgrowth of bone showed a more active process of pathologic bone formation. In such areas, osteoid was observed in the lining membrane of the middle ear cavity, into which the periosteum merged. Similar broad-based, exostotic-type bone was present in the other areas of the periosteal layer bordering the middle ear space. Many of the globular outgrowths of bone had arisen from the surface of the periosteal layer, each presenting an orderly lamellar-type structure around a central vessel and stained uniformly pink with H. and E. (Fig. 3). Many lacunae of the surface layer of the globular bone were empty. The periosteum was smooth, and osteoblasts and osteoclasts were not seen on the surface of these exostotic projections. The mastoid was not pneumatized and the antrum area was filled with compact bone. The marrow spaces in the mastoid portion were extremely
narrowed by dense lamellar type of bone with pink-stain reaction to H. and E. The narrow marrow space was surrounded by a layer of dark-blue stained deposits and contained a blood vessel and fine connective tissue. In some areas there was only enough space to contain the small vessel. A few fatty marrow spaces were seen, but hematopoietic marrow was not noted in the mastoid bone. There was no active osteoblastic or osteoclastic activity in the mastoid, the bone appearing to be in a quiescent phase. In the petrous portion of the temporal bone, the marrow cavity was nearly obliterated by plexus-like bone and early lamellar-like bone with bluestaining reaction to H. and E. These types of bone were distinct from the trabeculae which were widened by dense pink-stained bone with a fairlv orderly arrangement of fibers. In general, however, the lamellar-like structure of periosteal bone was rather poorly developed as compared to nor-
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Fig. 4. The periosteal layer of the otic capsule is abnormally dense. Marrow spaces are absent. The endochondral layer is normal in thickness. The skein-like layer is abnormally dense. Remnants of cartilaginous matrix vary in size. The globuli ossei are frequent, many showing an unusually broad base. Endosteal layer appears normal (H. and E. stain; X69).
mal temporal bone. The hematopoietic bone marrow had completely disappeared, and the rudimentary marrow cavity contained only the blood vessel and a few delicate connective tissue fibers. In the endochondral layer of the otic capsule, the layer of skein-like bone was wider and more dense in comparison to that of normal temporal bone of the same age, but the overall thickness of this layer appeared normal (Fig. 4). There were no marrow spaces in this layer. The fissura ante fenestram was large, while the fossula post fenestram was absent. The endosteum was well preserved and the endosteal layer was not thickened. There were a few incomplete fractures, probably not artificial, in the endosteal and endochondral layers, but there were no apparent lesions in the corresponding membranous structures. Middle Ear and Fallopian Canal. The tympanic membrane, malleus, and incus were missing from the specimen. The mucous membrane of the tympanic
cavity showed slight thickening, erosion, dilatation of blood vessels, and infiltrations of neutrophic polymorphonuclear leukocytes and small lymphocytes. As previously described, the medial wall of the middle ear cavity showed marked overgrowth of bone due to the osteopetrosis. The tympanic cavity appeared narrow due to the overgrowth of bone, but accurate measurement was not feasible because of the incomplete specimen. The Fallopian canal was surrounded by the thickened, dense bone and was somewhat narrow due to an overgrowth of periosteal bone of the canal wall, but there was no evidence of compression on the facial nerve in the Fallopian canal (Fig. 5). In the region of the oval window niche, wide portions of the anteromedial wall of the Fallopian canal were missing, and the facial nerve was exposed and pushed down towards the stapes. Such dislocation of the facial nerve appeared to be due to enormous overgrowth of periosteal bone of the epitympanum. The superstructure of the stapes was
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Fig. 5. Fallopian canal is surrounded by the thickened, dense bone, but there is no evidence of compression of facial nerve in its canal in this case. An incomplete fracture (arrow) of the labyrinthine capsule and the greater superficial petrosal nerve (C.S.P.N.) surrounded by the thickened bone are also seen (H. and E. stain).
imbedded deeply into the dislocated facial nerve and had compressed it to approximately one-half of the original size (Fig. 6). Although neural degeneration was not evident in this case, the marked compression of the facial nerve against the stapedial superstructure appeared capable of causing facial paralysis. The bone of the stapes did not show osteopetrotic change, and the footplate was free from ankylosis. However, the crus of the stapes was indented deeply into the facial nerve, possibly impeding movement.
Cochlea. The endosteum surrounding the membranous cochlea was not affected, and there was no new bone formation in the cochlear space. Bone in the spiral foraminous tract, the modiolus, and the osseous spiral lamina was unremarkable. The spiral ganglion and the peripheral nerve fibers were not degenerated. The internal auditory
meatus was elongated and somewhat narrowed due to the thickened periosteal bone, but evidence of cochlear nerve compression and degeneration was not found. The upper cochlear coils were artificially crushed, possibly due to unusual fragility of this bone. The epithelial and membranous structures of the cochlea were not examined in detail because of inadequate preservation. The round window and the cochlear aqueduct could not be satisfactorily studied.
Vestibule. The superior vestibular nerve canal and the singular foramen were slightly narrowed in their periosteal portions, but the superior vestibular nerve, posterior ampullar nerve, and Scarpa's ganglion were not degenerated. Although a few incomplete fractures were seen in the endosteal and endochondral layers of the labyrinthine capsule, there was no ossification in the vestibular and semicircular canal
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Fig. 6. Facial nerve is pushed down towards the stapes due to enormous overgrowth of periosteal bone in the epitympanal wall. The superstructure of the stapes is imbedded deeply (arrow) into the dislocated facial nerve and has compressed it to approximately one-half of the original size. The crus of the stapes appears to be immobilized ( H. and E. stain X(8).
spaces. The saccule was artificially distorted and the saccular macula showed autolysis. The superior and lateral semicircular canals and the utricle were normal. As far as could be evaluated, the posterior semicircular canal and the endolymphatic duct, incomplete as a specimen, did not indicate pathology. DISCUSSION
Previously reported studies of osteopetrosis have given entirely different histopathological descriptions of the temporal bone. Myers and Stool" reported that osteopetrotic changes occurred in the endochondral layer with the periosteal bone remaining normal, while Altmann" noted that the most marked change was in the periosteal layer of the temporal bone. In our material as well, osteopetrotic changes
were apparently most severe in the periosteal layer, although bone density was also increased in the endochondral layer. The thickness of the endosteal and endochondral layers of the temporal bone, as well as the size and contour of the labyrinthine spaces are already determined in the midfetal period of life. The periosteal bone continues to grow throughout childhood and is subject to active, but physiological, reconstruction. Pathological changes in osteopetrosis appear to be more marked in such continuously growing periosteal bone than in the more permanently established endosteal and endochondral bone. Actually, osteopetrosis seems to increase not only the density of bone, but also the size of the temporal bone pyra-
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mid, possibly narrowing the nerve canals. These factors appear largely responsible for many of the neurological complications observed in osteopetrosis. One important neurological facet, possibly a result of this process of osteopetrosis, is facial paralysis. Based on x-ray examinations, Wolford attributed this symptom to the narrowing of the stylomastoid foramen." However, in review of the recurrence of facial paralysis in all cases who received decompression surgery of the facial nerve of the mastoid segment," such an explanation remains in question. In previous histopathological observations of the temporal bone, both Altmann" and Myers and Stool" noted a large dehiscence of the Fallopian canal and a partial herniation of the facial nerve near the oval window. Our case also showed the similar dehiscence of the Fallopian canal and the dislocation of the facial nerve at the oval window region. Such exposure and dislocation of the nerve appears to have caused compression of the nerve due to its deep indentation by the superstructure of the stapes. This type of' nerve compression seems to be the pathogenesis of one form of facial nerve paresis associated with osteopetrosis. Although other portions of the Fallopian canal showed rather diffuse narrowing, no evidence of facial nerve compression was noted. However, it appears possible that such narrowing of the Fallopian canal may also be capable of causing facial nerve paralysis in the more advanced stage of osteopetrosis. Also associated with osteopetrosis may be impairment of hearing. Both conductive- and mixed-type hearing loss have been found.6.7 Surgical exploration of the middle ear revealed a narrowing of the tympanic cavity" and the oval window niche" and fixation of the stapes," but former histopathological studies have not described such abnormalities.s-? Although our observations of the middle ear structures were limited because of the incomplete specimen, we found marked exostotic overgrowth of periosteal bone of the median
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tympanic wall which presumably narrowed the middle ear cavity. In the extremely advanced stage of osteopetrosis, such overgrowth of bone into the middle ear cavity may disturb the movement of the auditory ossicles and result in conductive hearing loss. In addition to the exostotic overgrowth of the middle ear wall, movement of the superstructure of the stapes in our case appeared to be impeded by the facial nerve which enveloped the crura. Such impedance of stapedial movement may also produce conductive hearing impairment in osteopetrosis. Mixed-type hearing loss with elevated bone conduction thresholds have also been occasionally observed in osteopetrosis patients." Although the sensorineural component of such mixed-type hearing loss has been generally attributed to the overgrowth of bone within the inner ear! and the narrowing of the internal auditory meatus," no histopathological or surgical evidence has yet been found in the literature. The present case, at the age of eight and one-half years, already showed some narrowing of the internal auditory meatus, incomplete fractures of the labyrinthine capsule due to abnormal brittleness of the bone, and atrophy of the brain due to the thickened skull. Although we did not find any evidence of sensorineural degeneration in the inner ear in the present case, such changes in the inner ear and the brain may be a cause for sensorineural hearing loss in the very advanced stage of osteopetrosis. CONCLUSIONS
In the temporal bone with osteopetrosis, the overgrowth of bone and the increase in bone density were most marked in the periosteal layer. Such overgrowth of the periosteal bone caused the narrowing of the middle ear cavity, the Fallopian canal, and the internal auditory meatus. The facial nerve was exposed and displaced to a lower position at the oval window region due to enormous bony
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overgrowth in the epitympanum, and was deeply indented by the superstructure of the stapes.
Movement of the crus of the stapes appeared impeded by pressure from the displaced facial nerve.
Request for reprints should be sent to Fumiro Suga, M.D., Section of Otolaryngology, University of Chicago, 950 East 59th Street, Chicago, Illinois 60637. ACKNowLEDGMENT-vVe are grateful to Miss Ayako Hamamoto for her assistance. REFERENCES 1. Zetterstrom R: Osteopetrosis ( marble bone disease). Clinical and pathological review. Mod Probl Pediatr 3:488-508, 1957
6. Jones MD, Mulcahy ND: Osteopathia striata, osteopetrosis and impaired hearing. Arch Otolaryngol 87:116-118, 1968
2. Nelson WE: Textbook of Pediatrics. Philadelphia, W.B. Saunders Co., 1964 3. Klintworth GK: The neurologic manifestations of osteopetrosis, Albers-Schonberg's disease). Neurology (Minneap) 13:512-519, 1963 4. Hobbins SL: Pathology. Philadelphia, W.B. Saunders Co., 1967 5. Wolford NT: Facial paralysis associated with osteopetrosis (marble bone). J Pediatr 55:67-72,1959
7. Hamersma H: Osteopetrosis (marble bone disease) of the temporal bone. Laryngoscope 80: 1518-1539, 1970 8. Altmann F; Zur Anatomie und Klinik der Schlafenbeinveranderungen bei der Marmorknochenkrankheit (Albers-SchOnberg). Monatsschr Ohrenheilk Laryngorhinol 67: 1281-1308, 1933 9. Myers EN, Stool S: The temporal bone in osteopetrosis. Arch Otolaryngol 89:460-469, 1969
CONFERENCE ANNOUNCEMENT The Second International Conference on the Diagnosis and Treatment of Craniofacial Anomalies will be held at the New York University Medical Center, New York, New York on May 3-5, 1976. The Conference is organized under the auspices of the Educational Foundation of the American Society of Plastic and Reconstructive Surgeons. The Conference will focus on four major subject areas: orbitocephalic malformations, including orbital clefts and hypertelorism, craniofacial synostosis syndromes, mandibulofacial dyostosis (Treacher-Collins Syndrome) and craniofacial microsomia (maldevelopment of the first and second branchial arches). Emphasis will be placed on etiology, embryology, genetics, classification, pathology and the role of the different clinical specialties in the diagnosis and treatment of these anomalies. Special sessions will be devoted to associated speech and airway problems, helical deformities, audiology and middle ear surgery. For detailed information please write: John Marquis Converse, M.D., Institute of Reconstructive Plastic Surgery, 550 First Avenue, New York, New York 10016.
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TEMPORAL BONE HISTOPATHOLOGY OF OSTEOPETROSIS FUMIRO SUGA, JOHN
R.
M.D.
LINDSAY,
CHICAGO,
M.D.
ILLINo:s
SUMMARY - The histopathology of the temporal bone of an eight and one-half-year-old girl with osteopetrosis (Albers-Schonberg disease) was studied to evaluate the pathogenesis of its frequent complications in hearing and facial nerve function. The patient was blind and had acute otitis media, but facial paralysis was not noted. Although the size of the temporal bone pyramid was markedly increased due to enormously thickened periosteal layer, changes in the endosteal and endochondral layers were less marked. Exostotic growth of periosteal bone was seen in the middle ear wall, and the tympanic cavity appeared to be narrowed. At the oval window region, the facial nerve was pushed down towards the stapes due to extreme overgrowth of periosteal bone of the epitympanum, and the superstructure of the stapes was imbedded deeply into the dislocated facial nerve and had strongly compressed it. Although the footplate was free from ankylosis, the crus of the stapes appeared to be immobilized because it was lodged in the facial nerve. Such changes appeared to be the pathogenesis of one form of facial nerve paralysis and conductive hearing loss associated with osteopetrosis.
Osteopetrosis, also known as AlbersSchonberg disease, is a hereditary disease characterized by a generalized increase in bone density. The otological interest has been drawn to aural complications associated with this disease. Although the most frequent neural complication is optic nerve atrophy, hearing impairment and facial nerve paralysis also are often associated with osteopetrosis.v?
facial nerve at the stylomastoid foramen, demonstrated by x-ray. Surgical observations of the ear with osteopetrosis are rare. Jones and Mulcahy" reported a 26-year-old female who had conductive hearing loss associated with osteopetrosis. The patient had a severe bony narrowing of the left external auditory meatus and a slight narrowing of the right external auditory meatus. Audiometry revealed a moderate conductive hearing loss on the left and a slight conductive loss on the right. Reconstructive surgery of the left external auditory meatus was performed, but the patient's hearing did not improve. An exploratory tympanotomy revealed a narrowing of the tympanic cavity, an incus enveloped in bone and displaced to a lower position, and discontinuity of the incudostapedial joint. The horizontal portion of the facial nerve, the oval window, and the superstructure of the stapes were completely replaced with bone.
Klintworth" examined neurological symptoms of six osteopetrosis patients. He found hearing impairment in all six cases and facial palsy in five. Hearing impairment associated with osteopetrosis has been attributed to the narrowing of the external auditory meatus," the overgrowth of bone within the middle ear and inner ear," and cochlear nerve constriction in the petrous bone." Wolford" reported facial paralysis associated with osteopetrosis in five generations of the same family. He attributed the cause of the facial paralysis to encroachment by thickened bone on the
From the Section of Otolaryngology, University of Chicago, Chicago Illinois. Histopathological studies in this report were supported in part by the A~erican Otological Society, Inc., the E. F. Andrews Foundation, and NIH Grant No. NS-03358-12. 15
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Hamersma7 reported five cases with hearing loss and facial palsy associated with osteopetrosis. The hearing loss was conductive in type in two cases, mixed type in two, and absent in one case. Frequent attacks of facial palsy occurred in four cases. Surgery was attempted in one case to improve hearing, but it was found that stapes mobilization was not possible due to narrowing of the oval window niche. The mastoid segment of the paralyzed facial nerve was surgically decompressed in two cases, but facial palsy recurred in both. There are two histopathological reports of temporal bones with osteopetrosis. Altmann" studied the histopathology of the temporal bone of a 13-month-old infant. Unfortunately, although examination had revealed that this patient had bilateral optic nerve atrophy, otological examinations had not been performed. Altmann described various structural changes of the bone such as the widened periosteal layer of the labyrinthine capsule with markedly narrowed marrow spaces. He found a mushroom-shaped bulging of the facial nerve from a large dehiscence of the facial nerve canal at the oval window region, but he did not find evidence to explain the pathogenesis of frequent hearing impairment associated with osteopetrosis. Myers and Stool" reported the temporal bone pathology of a two and one-half-year-old female who had osteopetrosis, optic nerve atrophy, and hearing impairment. They observed that the endochondral layer showed a striking change. Aside from otitis media, however, there were no significant pathological changes in the cochlea or cochlear nerve. Although there was no history of facial paralysis, they found a herniation of a part of the facial nerve in the horizontal segment, similar to that found in Altmann's" case. Because such studies as those mentioned above present a rather conflicting picture of temporal bone pathology and have shown only minor histopathological evidence of hearing impairment, it seems useful to present a case
of osteopetrosis to supplement the information on temporal bone histopathology and otological complications associated with this disease. CASE REPORT
An eight and one-half-year-old female was first admitted to a hospital at the age of three weeks with a history of fine muscular twitchings of both arms and legs arising eight days after a completely normal birth. The patient's breathing was strident, but no x-ray evidence of bone disease was recognized at that time. When the patient was six months old another x-ray had been taken for thymic size, and an osteopetrotic condition of the bone structure was noted. The entire skeleton was then examined, and all the bones were found to be involved. A review of previous films showed that these changes were already present in the x-ray taken when the patient was three weeks old. When the patient was eight months old, it became apparent that she was blind. An adenoidectomy was performed when the patient was ten months old in an attempt to improve her breathing. At that time, the patient was slightly anemic and showed a marked enlargement of her head. A pneumoencephalogram added cerebral atrophy to the established diagnosis of osteopetrosis and bilateral primary optic nerve atrophy. Since then, the patient had numerous admissions to the hospital and x-rays showed increased osteopetrosis. At the age of three and one-third years, the patient developed acute pUrltlent otitis media of the left ear associated with an upper respiratory infection. With the progress of osteopetrotic changes, thickening of the long bones of the lower extremity, poor muscular tone, and faulty coordination became apparent. At the age of seven years, her head was severely enlarged, measuring 66 em in circumference. At the age of eight and one-half-
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Fig. 1. Horizontal section of the right temporal bone through the ampulla of the superior semicircular canal shows extreme increase in the density of bone and in the breadth of the pyramid. Changes are most severe in the periosteal layer involving an extreme reduction of marrow spaces. The mastoid is not pneumatized, and the antrum area is filled with compact bone (H. and E. stain).
years, the patient developed a high spiking temperature and purulent discharge from both ears. Shortly after, the patient went rapidly downhill, became lethargic, and died. The patient had no history of facial paralysis, and no audiometric examination had been performed. There was no known history of osteopetrosis in the patient's family. AUTOPSY REPORT
The most notable external feature was the enormous enlargement of the head, with a tremendous increase in its weight, due to the great thickening of all the bones of the head. The circumference of the head in the frontal occipital diameter was 67 em. The teeth were well developed, but they were widely separated due to an excessive growth of the mandible and the maxilla. Sections from ribs, sternum, fibula, and vertebrae showed varying degrees
of osseous overgrowth of dense bone containing in some places normal marrow, in others, only fatty tissue. The cortex of a rib was 2 mm thick and extremely dense. The bony trabeculae were also thickened and dense. In the cranium, the dura covering the hemispheres was unusually thickened without corresponding thinning of the falx. The leptomeninges were edematous and showed increased cellularity, mainly histiocytes. Blood vessels of the base of the brain were normal. The anterior part of the brain was disproportionately large on each side, while the temporal lobes appeared short. A coronal section through the frontal lobes revealed extreme hydrocephalus. There was hydrops of the third ventricle, the floor of which was of paper-like thickness. The cerebellum and brain stem were small as compared with the hemispheres.
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Fig. 2. Mushroom-shaped projection of new bone has grown out from the periosteal bone bordering the middle ear space. The deeper staining connective tissue (arrow) in the lining membrane of the middle ear space shows increased osteoid tissue suggesting an active process of pathologic bone formation (H. and E. stain; X90).
The anterior limbs of the optic chiasm were small, and the optic tracts on both sides had been reduced to the thickness of a coarse linen thread. However, the cranial nerves posterior to the II nerve appeared normal in size. The olfactory tracts were not strikingly reduced in size. In serial sections through the basal ganglia of both sides, the most definite change was complete absence of the optic tracts and the lateral geniculate bodies on both sides. mSTOPATHOLOGY
Only the right temporal bone was obtained for histopathological examination. The temporal bone was fixed with formalin, decalcified, embedded in celloidin, and horizontally sectioned in series. Every tenth section was stained and studied with a light microscope. Otic Capsule. The most striking change of the temporal bone was the abnormally dense character of the bone
and the greatly increased breadth of the pyramid (Fig. 1). The periosteal layer was enormously thickened, while the thickness of the endochondral layer and the endosteal layer appeared normal. The overgrowth of the periosteal bone was most marked bordering the cranial cavity but was also severe along the lateral surface bordering the middle Ear space. The overgrown bone had a lamellar-like structure and a fairly uniform pink-staining reaction for H. and E. The thickening of bone generally appeared diffuse but continuous, maintaining a smooth periosteal surface. In addition to the generalized diffuse overgrowth of the periosteal bone, there were mushroom-shaped projections of new bone which had grown out from the periosteal bone bordering the middle ear space (Fig. 2). These projections consisted of a concentric, circular, lamellar-type structure developed from
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Fig. 3. Many of the globular outgrowths of bone have arisen from the periosteal layer bordering the middle ear space (H. and E. stain; X32).
a base containing a small blood vessel. The surface adjacent to such exostotic overgrowth of bone showed a more active process of pathologic bone formation. In such areas, osteoid was observed in the lining membrane of the middle ear cavity, into which the periosteum merged. Similar broad-based, exostotic-type bone was present in the other areas of the periosteal layer bordering the middle ear space. Many of the globular outgrowths of bone had arisen from the surface of the periosteal layer, each presenting an orderly lamellar-type structure around a central vessel and stained uniformly pink with H. and E. (Fig. 3). Many lacunae of the surface layer of the globular bone were empty. The periosteum was smooth, and osteoblasts and osteoclasts were not seen on the surface of these exostotic projections. The mastoid was not pneumatized and the antrum area was filled with compact bone. The marrow spaces in the mastoid portion were extremely
narrowed by dense lamellar type of bone with pink-stain reaction to H. and E. The narrow marrow space was surrounded by a layer of dark-blue stained deposits and contained a blood vessel and fine connective tissue. In some areas there was only enough space to contain the small vessel. A few fatty marrow spaces were seen, but hematopoietic marrow was not noted in the mastoid bone. There was no active osteoblastic or osteoclastic activity in the mastoid, the bone appearing to be in a quiescent phase. In the petrous portion of the temporal bone, the marrow cavity was nearly obliterated by plexus-like bone and early lamellar-like bone with bluestaining reaction to H. and E. These types of bone were distinct from the trabeculae which were widened by dense pink-stained bone with a fairlv orderly arrangement of fibers. In general, however, the lamellar-like structure of periosteal bone was rather poorly developed as compared to nor-
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Fig. 4. The periosteal layer of the otic capsule is abnormally dense. Marrow spaces are absent. The endochondral layer is normal in thickness. The skein-like layer is abnormally dense. Remnants of cartilaginous matrix vary in size. The globuli ossei are frequent, many showing an unusually broad base. Endosteal layer appears normal (H. and E. stain; X69).
mal temporal bone. The hematopoietic bone marrow had completely disappeared, and the rudimentary marrow cavity contained only the blood vessel and a few delicate connective tissue fibers. In the endochondral layer of the otic capsule, the layer of skein-like bone was wider and more dense in comparison to that of normal temporal bone of the same age, but the overall thickness of this layer appeared normal (Fig. 4). There were no marrow spaces in this layer. The fissura ante fenestram was large, while the fossula post fenestram was absent. The endosteum was well preserved and the endosteal layer was not thickened. There were a few incomplete fractures, probably not artificial, in the endosteal and endochondral layers, but there were no apparent lesions in the corresponding membranous structures. Middle Ear and Fallopian Canal. The tympanic membrane, malleus, and incus were missing from the specimen. The mucous membrane of the tympanic
cavity showed slight thickening, erosion, dilatation of blood vessels, and infiltrations of neutrophic polymorphonuclear leukocytes and small lymphocytes. As previously described, the medial wall of the middle ear cavity showed marked overgrowth of bone due to the osteopetrosis. The tympanic cavity appeared narrow due to the overgrowth of bone, but accurate measurement was not feasible because of the incomplete specimen. The Fallopian canal was surrounded by the thickened, dense bone and was somewhat narrow due to an overgrowth of periosteal bone of the canal wall, but there was no evidence of compression on the facial nerve in the Fallopian canal (Fig. 5). In the region of the oval window niche, wide portions of the anteromedial wall of the Fallopian canal were missing, and the facial nerve was exposed and pushed down towards the stapes. Such dislocation of the facial nerve appeared to be due to enormous overgrowth of periosteal bone of the epitympanum. The superstructure of the stapes was
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Fig. 5. Fallopian canal is surrounded by the thickened, dense bone, but there is no evidence of compression of facial nerve in its canal in this case. An incomplete fracture (arrow) of the labyrinthine capsule and the greater superficial petrosal nerve (C.S.P.N.) surrounded by the thickened bone are also seen (H. and E. stain).
imbedded deeply into the dislocated facial nerve and had compressed it to approximately one-half of the original size (Fig. 6). Although neural degeneration was not evident in this case, the marked compression of the facial nerve against the stapedial superstructure appeared capable of causing facial paralysis. The bone of the stapes did not show osteopetrotic change, and the footplate was free from ankylosis. However, the crus of the stapes was indented deeply into the facial nerve, possibly impeding movement.
Cochlea. The endosteum surrounding the membranous cochlea was not affected, and there was no new bone formation in the cochlear space. Bone in the spiral foraminous tract, the modiolus, and the osseous spiral lamina was unremarkable. The spiral ganglion and the peripheral nerve fibers were not degenerated. The internal auditory
meatus was elongated and somewhat narrowed due to the thickened periosteal bone, but evidence of cochlear nerve compression and degeneration was not found. The upper cochlear coils were artificially crushed, possibly due to unusual fragility of this bone. The epithelial and membranous structures of the cochlea were not examined in detail because of inadequate preservation. The round window and the cochlear aqueduct could not be satisfactorily studied.
Vestibule. The superior vestibular nerve canal and the singular foramen were slightly narrowed in their periosteal portions, but the superior vestibular nerve, posterior ampullar nerve, and Scarpa's ganglion were not degenerated. Although a few incomplete fractures were seen in the endosteal and endochondral layers of the labyrinthine capsule, there was no ossification in the vestibular and semicircular canal
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Fig. 6. Facial nerve is pushed down towards the stapes due to enormous overgrowth of periosteal bone in the epitympanal wall. The superstructure of the stapes is imbedded deeply (arrow) into the dislocated facial nerve and has compressed it to approximately one-half of the original size. The crus of the stapes appears to be immobilized ( H. and E. stain X(8).
spaces. The saccule was artificially distorted and the saccular macula showed autolysis. The superior and lateral semicircular canals and the utricle were normal. As far as could be evaluated, the posterior semicircular canal and the endolymphatic duct, incomplete as a specimen, did not indicate pathology. DISCUSSION
Previously reported studies of osteopetrosis have given entirely different histopathological descriptions of the temporal bone. Myers and Stool" reported that osteopetrotic changes occurred in the endochondral layer with the periosteal bone remaining normal, while Altmann" noted that the most marked change was in the periosteal layer of the temporal bone. In our material as well, osteopetrotic changes
were apparently most severe in the periosteal layer, although bone density was also increased in the endochondral layer. The thickness of the endosteal and endochondral layers of the temporal bone, as well as the size and contour of the labyrinthine spaces are already determined in the midfetal period of life. The periosteal bone continues to grow throughout childhood and is subject to active, but physiological, reconstruction. Pathological changes in osteopetrosis appear to be more marked in such continuously growing periosteal bone than in the more permanently established endosteal and endochondral bone. Actually, osteopetrosis seems to increase not only the density of bone, but also the size of the temporal bone pyra-
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mid, possibly narrowing the nerve canals. These factors appear largely responsible for many of the neurological complications observed in osteopetrosis. One important neurological facet, possibly a result of this process of osteopetrosis, is facial paralysis. Based on x-ray examinations, Wolford attributed this symptom to the narrowing of the stylomastoid foramen." However, in review of the recurrence of facial paralysis in all cases who received decompression surgery of the facial nerve of the mastoid segment," such an explanation remains in question. In previous histopathological observations of the temporal bone, both Altmann" and Myers and Stool" noted a large dehiscence of the Fallopian canal and a partial herniation of the facial nerve near the oval window. Our case also showed the similar dehiscence of the Fallopian canal and the dislocation of the facial nerve at the oval window region. Such exposure and dislocation of the nerve appears to have caused compression of the nerve due to its deep indentation by the superstructure of the stapes. This type of' nerve compression seems to be the pathogenesis of one form of facial nerve paresis associated with osteopetrosis. Although other portions of the Fallopian canal showed rather diffuse narrowing, no evidence of facial nerve compression was noted. However, it appears possible that such narrowing of the Fallopian canal may also be capable of causing facial nerve paralysis in the more advanced stage of osteopetrosis. Also associated with osteopetrosis may be impairment of hearing. Both conductive- and mixed-type hearing loss have been found.6.7 Surgical exploration of the middle ear revealed a narrowing of the tympanic cavity" and the oval window niche" and fixation of the stapes," but former histopathological studies have not described such abnormalities.s-? Although our observations of the middle ear structures were limited because of the incomplete specimen, we found marked exostotic overgrowth of periosteal bone of the median
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tympanic wall which presumably narrowed the middle ear cavity. In the extremely advanced stage of osteopetrosis, such overgrowth of bone into the middle ear cavity may disturb the movement of the auditory ossicles and result in conductive hearing loss. In addition to the exostotic overgrowth of the middle ear wall, movement of the superstructure of the stapes in our case appeared to be impeded by the facial nerve which enveloped the crura. Such impedance of stapedial movement may also produce conductive hearing impairment in osteopetrosis. Mixed-type hearing loss with elevated bone conduction thresholds have also been occasionally observed in osteopetrosis patients." Although the sensorineural component of such mixed-type hearing loss has been generally attributed to the overgrowth of bone within the inner ear! and the narrowing of the internal auditory meatus," no histopathological or surgical evidence has yet been found in the literature. The present case, at the age of eight and one-half years, already showed some narrowing of the internal auditory meatus, incomplete fractures of the labyrinthine capsule due to abnormal brittleness of the bone, and atrophy of the brain due to the thickened skull. Although we did not find any evidence of sensorineural degeneration in the inner ear in the present case, such changes in the inner ear and the brain may be a cause for sensorineural hearing loss in the very advanced stage of osteopetrosis. CONCLUSIONS
In the temporal bone with osteopetrosis, the overgrowth of bone and the increase in bone density were most marked in the periosteal layer. Such overgrowth of the periosteal bone caused the narrowing of the middle ear cavity, the Fallopian canal, and the internal auditory meatus. The facial nerve was exposed and displaced to a lower position at the oval window region due to enormous bony
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overgrowth in the epitympanum, and was deeply indented by the superstructure of the stapes.
Movement of the crus of the stapes appeared impeded by pressure from the displaced facial nerve.
Request for reprints should be sent to Fumiro Suga, M.D., Section of Otolaryngology, University of Chicago, 950 East 59th Street, Chicago, Illinois 60637. ACKNowLEDGMENT-vVe are grateful to Miss Ayako Hamamoto for her assistance. REFERENCES 1. Zetterstrom R: Osteopetrosis ( marble bone disease). Clinical and pathological review. Mod Probl Pediatr 3:488-508, 1957
6. Jones MD, Mulcahy ND: Osteopathia striata, osteopetrosis and impaired hearing. Arch Otolaryngol 87:116-118, 1968
2. Nelson WE: Textbook of Pediatrics. Philadelphia, W.B. Saunders Co., 1964 3. Klintworth GK: The neurologic manifestations of osteopetrosis, Albers-Schonberg's disease). Neurology (Minneap) 13:512-519, 1963 4. Hobbins SL: Pathology. Philadelphia, W.B. Saunders Co., 1967 5. Wolford NT: Facial paralysis associated with osteopetrosis (marble bone). J Pediatr 55:67-72,1959
7. Hamersma H: Osteopetrosis (marble bone disease) of the temporal bone. Laryngoscope 80: 1518-1539, 1970 8. Altmann F; Zur Anatomie und Klinik der Schlafenbeinveranderungen bei der Marmorknochenkrankheit (Albers-SchOnberg). Monatsschr Ohrenheilk Laryngorhinol 67: 1281-1308, 1933 9. Myers EN, Stool S: The temporal bone in osteopetrosis. Arch Otolaryngol 89:460-469, 1969
CONFERENCE ANNOUNCEMENT The Second International Conference on the Diagnosis and Treatment of Craniofacial Anomalies will be held at the New York University Medical Center, New York, New York on May 3-5, 1976. The Conference is organized under the auspices of the Educational Foundation of the American Society of Plastic and Reconstructive Surgeons. The Conference will focus on four major subject areas: orbitocephalic malformations, including orbital clefts and hypertelorism, craniofacial synostosis syndromes, mandibulofacial dyostosis (Treacher-Collins Syndrome) and craniofacial microsomia (maldevelopment of the first and second branchial arches). Emphasis will be placed on etiology, embryology, genetics, classification, pathology and the role of the different clinical specialties in the diagnosis and treatment of these anomalies. Special sessions will be devoted to associated speech and airway problems, helical deformities, audiology and middle ear surgery. For detailed information please write: John Marquis Converse, M.D., Institute of Reconstructive Plastic Surgery, 550 First Avenue, New York, New York 10016.
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