The Laryngoscope C 2015 The American Laryngological, V
Rhinological and Otological Society, Inc.
Histopathology of Idiopathic Lateral Skull Base Defects Aaron K. Remenschneider, MD, MPH; Elliott D. Kozin, MD; Hugh Curtin, MD; Felipe Santos, MD Objectives/Hypothesis: The objective of this study was to utilize techniques of otopathology to gain insight into the pathogenesis, sites of origin, and associated findings in idiopathic lateral skull base defects. Study Design: Histopathologic analysis of temporal bones from an otopathology repository. Methods: Specimens from a human temporal bone repository were investigated for clinical or otopathologic evidence of occult bony dehiscence indicating communication between the subarachnoid space and air cells of the temporal bone. Specimens were examined by light microscopy, organized by fistula site, and histopathologically described. Premortem patient demographics and clinical history was reviewed. Results: Specimens from 52 individuals met inclusion criteria. Three distinct fistula pathways were determined: transdural, labyrinthine, and perilabyrinthine. Transdural fistulae occur most commonly as the result of arachnoid granulations along the middle or posterior fossa dura (n 5 30) and are frequently incidental findings in specimens of older individuals (median age at death: 81 years). Labyrinthine fistulae (n 5 10) were noted with cochlear malformations when modiolar atresia permits cerebrospinal fluid (CSF) flow into a common intracochlear scala and oval window perilymphatic fistula results. Perilabyrinthine fistulae (n 5 7) were observed through three congenitally unfused tracts: the tympanomeningeal fissure, the petromastoid canal, or an extension of the subarachnoid space into the fallopian canal. Conclusions: Idiopathic lateral skull base defects occur in three distinct anatomic locations with consistent histopathologic findings. In the absence of clear radiographic localization, patient age and associated cochlear defects may assist in the determination of the site of CSF leak. These data have implications for surgical approaches of CSF fistula repair. Key Words: Cerebrospinal fluid leak, temporal bone pathology, arachnoid granulation, encephalocele, Mondini, scala communis, tympanomeningeal fissure, patent fallopian canal, petromastoid canal. Level of Evidence: NA Laryngoscope, 125:1798–1806, 2015
INTRODUCTION In contrast to acquired cerebrospinal fluid (CSF) leaks of the temporal bone, spontaneous CSF leaks are infrequently encountered and not well understood.1 CSF egress into the ear may arise from a defect in the middle or posterior fossa dura adjacent a bony dehiscence anywhere along the petrous pyramid. Active CSF leaks may be clinically obvious, presenting with a middle ear effusion, conductive hearing loss, and otorhinnorhea.2 In contrast, occult fistulae/defects may present with minimal signs and symptoms that only become apparent following a secondary intracranial complication, such as otogenic meningitis or seizure.3,4 Determining the etiology and location of lateral skull base fistulae is critical as it influences clinical deci-
From the Department of Otolaryngology (A.K.R., E.D.K., F.S.) and Department of Radiology H.C., Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and the Department of Otology and Laryngology (A.K.R., E.D.K., H.C., F.S.), Harvard Medical School, Boston, Massachusetts, U.S.A. Editor’s Note: This Manuscript was accepted for publication April 6, 2015. Presented orally at the Triological Society Combined Sections Meeting, Coronado, California, U.S.A., January 22–24, 2015. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Felipe Santos, MD, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114. E-mail: [email protected] DOI: 10.1002/lary.25366
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sion making, including the need for surgical repair. A detailed clinical history is of primary value as certain comorbid conditions, such as obesity, can provide significant insight into the etiology of the fistula.1,5–9 Although a thorough head, neck, otologic, and neurologic examination is necessary, such investigations frequently do not provide additional localizing information. Laboratory tests, such as b-2 transferrin, have a high specificity for CSF,10 but may not be readily obtainable and will not indicate the site of defect. Imaging studies including magnetic resonance imaging (MRI) and high-resolution computed tomography (CT) have sensitivities for localizing CSF leaks between 50% and 90%7,11,12; however, studies suggest that the sensitivity drops with decreasing defect size.12 Thus, if the fistulae are small, imaging may not readily provide information regarding the site of origin. As current diagnostic modalities may not consistently provide information as to the location of CSF leaks, knowledge of common sites for CSF fistulae of the temporal bone, especially in occult cases, is critical. In 1985, Neely first grouped clinical cases of spontaneous CSF effusion by the site of egress, based on their proximity to the otic capsule.13 Further refinement of this classification into transdural, labyrinthine, and perilabyrinthine fistulae greatly facilitates the understanding of their etiology, their stereotyped clinical features, their risk to the patient, and the appropriate method of surgical repair.
Remenschneider et al.: Histopathology of Lateral Skull Base Defects
TABLE I. Transdural Defects. Patient Age at No. Death, yr
Defect
Site
Laterality
Clinically Apparent Leak During Life
Relevant Clinical History
1
50
Single arachnoid granulation
Middle fossa
Right
No
Normal hearing
2
89
Single arachnoid granulation
Posterior fossa
Left
No
Paget’s disease, diabetes
3 4
74 90
Multiple arachnoid granulations Single arachnoid granulation
Posterior fossa Middle fossa
Bilateral Left
No No
Malignant mesothelioma Mild to moderate hearing loss
5
77
Multiple arachnoid granulations
Middle fossa
Left
No
Cerebral hemorrhage
6 7
87 79
Multiple meningoencephaloceles Middle fossa Multiple arachnoid granulations Posterior fossa
Right Bilateral
Yes No
Died of otitic meningitis Unknown history
8
79
Multiple arachnoid granulations
Posterior fossa
Bilateral
No
Cerebral hemorrhage
9 10
92 77
Single arachnoid granulation Multiple arachnoid granulations
Posterior fossa Posterior fossa
Left Right
Unclear Yes
Fluctuating hearing loss Mild otitic meningitis
11
42
Single arachnoid granulation
Middle fossa
Right
Yes
Died of otitic meningitis
12 13
85 13
Single arachnoid granulation Single arachnoid granulation
Posterior fossa Middle fossa
Right Bilateral
No Yes
Mondini dysplasia Tuberous sclerosis
14
92
Single arachnoid granulation
Middle fossa
Right
Yes
Died of otitic meningitis
15 16
92 91
Single arachnoid granulation Single arachnoid granulation
Posterior fossa Posterior fossa
Left Left
No No
Fluctuating hearing loss Fluctuating hearing loss
17
98
Single arachnoid granulation
Posterior fossa
Right
No
Fluctuating hearing loss
18
94
Multiple arachnoid granulations
Middle and posterior fossae
Bilateral
No
19
64
Single arachnoid granulation
Posterior fossa
Right
No
Progressive hearing loss consistent with strial atrophy No otologic problems
20
74
Single arachnoid granulation
Middle fossa
Left
No
Otosclerosis with dead ear after stapedectomy
21
62
Bony defects, no arachnoid granulation
Middle fossa
Bilateral
No
Superior canal dehiscence
22 23
68 94
Single arachnoid granulation Single arachnoid granulation
Middle fossa Middle fossa
Right Right
No No
Bilateral SNHL Unknown history
24
99
Single arachnoid granulation
Petrous apex along superior petrosal sinus in both middle and posterior fossae
Bilaterally No
CSF contacts the fat of the petrous apex marrow
25
94
Single arachnoid granulation
Petrous apex along superior petrosal sinus in both middle and posterior fossae)
Bilaterally No
CSF contacts the fat of the petrous apex marrow
26
83
Single arachnoid granulation
Middle fossa
Left
No
Bilateral Meniere’s
27 28
63 55
Single arachnoid granulation Single arachnoid granulation
Right Left
No No
Pituitary dwarfism and severe SNHL Progressive bilateral hearing loss
29
81
Single arachnoid granulation
Posterior fossa Lateral to the internal carotid (middle fossa) Posterior fossa
Bilaterally Yes
Died of otitic meningitis
30
72
Single arachnoid granulation
Middle fossa
Left
No
No otologic history
31
85
Single arachnoid granulation
Middle fossa
Left
32
97
Single arachnoid granulation
Middle fossa
Right
Possible left Possible right
Late onset ipsilateral serous otitis media with tube placement Terminal acute otitis media with incus erosion
33
75
Single meningoencephalocele
Posterior fossa
Right
No
Right vestibular schwannoma, untreated
34
79
Single meningoencephalocele
Posterior fossa
Left
No
Endolymphatic hydrops in right ear
35
81
Single meningoencephalocele
Middle fossa
Right
Yes
Repaired defect transmastoid with cartilage at age 65 years with good effect
CSF 5 cerebrospinal fluid; SNHL 5 sensorineural hearing loss.
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Although recent studies have reviewed patient presentation and surgical repair of occult CSF leaks,2,7–9,14,15 few have investigated the temporal bone histopathologic findings and correlated them with premortem clinical history. We aimed to analyze cases of idiopathic transdural, labyrinthine, and perilabyrinthine skull base defects from a large temporal bone repository. By utilizing the techniques of otopathology, we hoped to gain better insight into the pathogenesis, site of origin, and associated defects of the temporal bone and lateral skull base.
MATERIALS AND METHODS
Fig. 1. Coronal diagram showing various routes of cerebrospinal fluid fistula through the temporal bone. (1) Middle fossa transdural. (2) Labyrinthine via internal auditory canal (IAC) and oval window. (3) Patent tympanomeningeal fissure. (4) Widened fallopian canal. (5) petromastoid canal. Adapted with permission from Phelps.4 CochAq 5 cochlear aqueduct; EAC 5 external auditory canal; ET 5eustachian tube; JB 5 jugular bulb.
Temporal bone specimens included in this study are a part of the National Institute of Deafness and Other Communication Disorders’ National Temporal Bone, Hearing and Balance Pathology Resource Registry (The Registry). Specimens evaluated in the current study are all housed at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. The preparation and analysis of the bones have been previously described.16 In brief, the temporal bones were removed at autopsy and immediately fixed in 10% formalin solution. They were decalcified with
Fig. 2. Representative computed tomography scans of lateral skull base defects. Arrows indicate site of leak. (A) Posterior fossa arachnoid granulation. (B) Middle fossa meningoencephalocele. (C) Incomplete partition II, dilated apical cochlea and vestibule. (D) Patent tympanomeningeal fissure. (E) Widened fallopian canal.
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ethylenediaminetetraacetic acid and embedded in celloidin. Serial sectioning was performed in either the axial or vertical plane at a thickness of 20 mm, staining every tenth section with
hematoxylin and eosin. Stained sections were examined under light microscopy by expert otopathologists, with complete histologic and histopathologic features noted. Findings are recorded within The Registry and cataloged by key word. The Registry was queried for specimens that contained evidence of premortem CSF leak or histopathologically determined lateral skull base defects. Search terms utilized included: CSF leak, cerebrospinal fluid leak, CSF fistula, cerebrospinal fluid fistula, arachnoid granulation, Pacchionian body, encephalocele, meningoencephalocele, perilabyrinthine leak, Hyrtl’s fissure, tympanomeningeal fissure, petromastoid canal, patent fallopian canal, and cribose area. Cases were included in the analysis if there was evidence of an idiopathic and not secondarily acquired CSF fistula. Specimens with evidence of a fistula without clinical history of a leak were also included. Furthermore, cases with a documented clinical history of CSF otorrhea, otitic meningitis, or intracranial complications from a CSF leak were similarly included. Cases were excluded if the CSF fistula arose in the setting of chronic otitis media, trauma, cholesteatoma, previous surgery, or if there was another clear acquired cause. Specimens included in this study were organized into three distinct CSF fistula sites: transdural, labyrinthine, and perilabyrinthine. Transdural defects were defined as bony dehiscences with evidence of arachnoid granulation (AG) ingrowth, encephalocele/meningocele/meningoencephalocele, or direct dural contact with air cells from either the middle or posterior fossa. Labyrinthine defects were defined as the appearance of CSF in continuity with the scalae of the inner ear along with oval window abnormalities that could lead to a perilymphatic fistula. Perilabyrinthine defects were defined as congenital bony fistulae surrounding the otic capsule along three routes: a patent tympanomeningeal (Hyrtl’s) fissure, a widened petromastoid canal, or extension of the subarachnoid space into the fallopian canal. Given rarity of these data, each unique case’s features were made primary data for review. The age at death, histopathologic findings, site, laterality, evidence of CSF leak during life, and relevant clinical history were extracted. Descriptive analysis was performed. The Massachusetts Eye and Ear Computed Tomographic (CT) imaging library was searched for cases of lateral skull base defects with clinical CSF leaks. Available representative CT images from each category of fistula site were obtained.
RESULTS Search results revealed a total of 70 unique cases that included one or more terms listed above. Review of each case with application of inclusion and exclusion criteria netted a total of 52 separate cases for review. Clinical cases of occult CSF leak all contained an identifiable histologic defect of the lateral skull base. Of these, 35 were classified as transdural, 10 were labyrinthine, and seven were perilabyrinthine fistulae. The histologic
Fig. 3. (A) Low-power (23) view of a horizontal section along the axis of the internal auditory canal. The medial aspect of the canal at the porus acusticus demonstrates an arachnoid granulation of the posterior cranial fossa dura. (B) High-power (203) view of the arachnoid granulation reveals erosion into a mastoid air cell. (C) Low-power (1.253) view of a vertical section along the middle fossa floor demonstrates a distinct tegmental defect. There is associated glial tissue representing a 0.8-mm meningoencephalocele. This patient died of otitic meningitis.
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Age at Death
0 days
0 days
0 days
0 days
3 days
6 weeks
8 months
2 years
73 years
85 years
Patient No.
1
2
3
4
5
6
7
8
9
10
Right IP-II, left IP-II
Right IP-II, left IP- II
Right mild IP-II
Right IP-II, left IP-II
Left mild IP-II
Right IP-I, left IP-II
Left IP-II
Right mild IP-II
Right IP-II, left IP-II
Left IP-II
Cochleovestibular Malformation (Sennaroglu)
Both 1.5 turns, scala communis with imcomplete cribose bone
Both 2.0 turn cochlea, scala communis
2.5 turns, scala communis, absent cribose bone
1.0 turns, scala communis; 1.5 turns, scala communis
2.0 turns, scala communis
Common cavity; 1.5 turns, absent cribose bone
2.0 turns
2.0 turns, scala communis with intact cribose bone
Both 1.5 turns, scala communis with incomplete cribose bone
1.5 turns, rudimentary osseous spiral lamina
Cochlear Defect
Both dilated
Both dilated
Both normal
Both membranous
Normal, hypoplastic superior canal
Both dilated
Membranous, absent oval window
Fixed
Dilated
Common, dilated
Normal
Fixed
Absent oval window, fixed
Normal
Dilated
Both dilated
Both membranous
Normal
Dilated
Vestibule
Absent oval window
Stapes Footplate
TABLE II. Labyrinthine.
Both enlarged
Both enlarged
Normal
Both enlarged
Enlarged
None, enlarged
Enlarged
Enlarged
Both enlarged
Enlarged
Vestibular Aqueduct
Unknown
No
No
Probable
Possible
not-applicable
not-applicable
not-applicable
not-applicable
not-applicable
Clinically Apparent Leak During Life
Congenitally deaf, sparse records
Moderate hearing loss, died of myocardial infarction
Otopalatodigital syndrome, died of acute respiratory failure
Subacute otitis media and pulmonary consolidation seen at autopsy following septic death
Klippel-Feil syndrome, died of bronchopneumonia
Triplody 69XXY, died of cardiopulmonary failure Hydantoin syndrome (phenytoin toxicity)
Trisomy 13, died of cardiopulmonary failure
Born anencephalic
Trisomy 22, died of cardiopulmonary failure
Relevant Clinical History
TABLE III. Perilabyrinthine. Patient No.
Age at Death
Defect
Laterality
Clinically Apparent Leak During Life
Relevant Clinical History
1
8 weeks
Widened petromastoid canal confluent with subarcuate cell tract
Bilateral
Yes
Died from otogenic meningitis
2 3
11 weeks 2 years
Persistent tympanomeningeal fissure Widened petromastoid canal confluent with subarcuate cell tract
Right Left
Possible Possible
4
11 years
Persistent tympanomeningeal fissure
Left
No
Clear effusion right ear Bruton’s agammaglobulinemia, recurrent otitis media with seizures Progressive neurodegenerative disease
5
13 years
Extension of subarachnoid space into the fallopian canal
Bilateral
Yes
Mild meningitis
6
68 years
Widened petromastoid canal confluent with subarcuate cell tract
Right
Yes
Died from otitic meningitis
7
70 years
Persistent tympanomeningeal fissure
Right
No
Right vestibular schwannoma removed 22 years prior to death
description and clinical details of these results are featured in Tables I to III. Figure 1 displays identified pathways of CSF egress into the middle ear for each site. Representative CT scans demonstrating the identified routes for CSF leak are displayed in Figure 2. No CT images of a widened petromastoid canal resulting in CSF leak have been previously published or were identified in our imaging library.
subarachnoid space entering the internal canal through a defective fundal cribose area, which results in CSF in the scalae of the inner ear. Defects in the stapes footplate included aplasia, membranous footplate, and ankylosis (congenital stapes fixation). Of the 15 ears in 10 patients with such defects, 5/15 (33%) had membranous footplates, whereas 3/15 (18%) had a thickened footplate with apparent stapes fixation. Representative specimens are displayed in Figure 4.
Transdural Defects The mean age at death of patients in the temporal bone collection with transdural defects was 78 years, and the median was 81 years of age. Thirty of 35 cases (86%) were AGs, whereas 5/35 (14%) demonstrated bony defects without AG or meningoencephaloceles. Of the patients with AGs, 6/30 (20%) had multiple AGs, whereas the remainder had only one AG. Seventeen cases contained defects of the middle fossa floor, and 16 involved the posterior fossa plate; of these, three cases contained bony defects in both locations. Twenty-five of 35 patients (71%) did not have any history of active CSF leak or secondary complications such as otitic meningitis. The other 10 had documented meningitis or a clinical history or exam suggestive of a CSF oto/otorhinorrhea. Five patients (14%) died of otitic meningitis. Representative histopathologic specimens are featured in Figure 3.
Labyrinthine Defects Of the 10 cases of labyrinthine fistula identified in The Registry, all uniformly contained congenital modiolar defects. The classification of cochleovestibular malformation, configuration of the cochlea and vestibule, and the status of the vestibular aqueduct are detailed in Table II. The Sennaroglu classification was applied to each specimen.17 The median age at the time of death was
Rhinological and Otological Society, Inc.
Histopathology of Idiopathic Lateral Skull Base Defects Aaron K. Remenschneider, MD, MPH; Elliott D. Kozin, MD; Hugh Curtin, MD; Felipe Santos, MD Objectives/Hypothesis: The objective of this study was to utilize techniques of otopathology to gain insight into the pathogenesis, sites of origin, and associated findings in idiopathic lateral skull base defects. Study Design: Histopathologic analysis of temporal bones from an otopathology repository. Methods: Specimens from a human temporal bone repository were investigated for clinical or otopathologic evidence of occult bony dehiscence indicating communication between the subarachnoid space and air cells of the temporal bone. Specimens were examined by light microscopy, organized by fistula site, and histopathologically described. Premortem patient demographics and clinical history was reviewed. Results: Specimens from 52 individuals met inclusion criteria. Three distinct fistula pathways were determined: transdural, labyrinthine, and perilabyrinthine. Transdural fistulae occur most commonly as the result of arachnoid granulations along the middle or posterior fossa dura (n 5 30) and are frequently incidental findings in specimens of older individuals (median age at death: 81 years). Labyrinthine fistulae (n 5 10) were noted with cochlear malformations when modiolar atresia permits cerebrospinal fluid (CSF) flow into a common intracochlear scala and oval window perilymphatic fistula results. Perilabyrinthine fistulae (n 5 7) were observed through three congenitally unfused tracts: the tympanomeningeal fissure, the petromastoid canal, or an extension of the subarachnoid space into the fallopian canal. Conclusions: Idiopathic lateral skull base defects occur in three distinct anatomic locations with consistent histopathologic findings. In the absence of clear radiographic localization, patient age and associated cochlear defects may assist in the determination of the site of CSF leak. These data have implications for surgical approaches of CSF fistula repair. Key Words: Cerebrospinal fluid leak, temporal bone pathology, arachnoid granulation, encephalocele, Mondini, scala communis, tympanomeningeal fissure, patent fallopian canal, petromastoid canal. Level of Evidence: NA Laryngoscope, 125:1798–1806, 2015
INTRODUCTION In contrast to acquired cerebrospinal fluid (CSF) leaks of the temporal bone, spontaneous CSF leaks are infrequently encountered and not well understood.1 CSF egress into the ear may arise from a defect in the middle or posterior fossa dura adjacent a bony dehiscence anywhere along the petrous pyramid. Active CSF leaks may be clinically obvious, presenting with a middle ear effusion, conductive hearing loss, and otorhinnorhea.2 In contrast, occult fistulae/defects may present with minimal signs and symptoms that only become apparent following a secondary intracranial complication, such as otogenic meningitis or seizure.3,4 Determining the etiology and location of lateral skull base fistulae is critical as it influences clinical deci-
From the Department of Otolaryngology (A.K.R., E.D.K., F.S.) and Department of Radiology H.C., Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and the Department of Otology and Laryngology (A.K.R., E.D.K., H.C., F.S.), Harvard Medical School, Boston, Massachusetts, U.S.A. Editor’s Note: This Manuscript was accepted for publication April 6, 2015. Presented orally at the Triological Society Combined Sections Meeting, Coronado, California, U.S.A., January 22–24, 2015. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Felipe Santos, MD, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114. E-mail: [email protected] DOI: 10.1002/lary.25366
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sion making, including the need for surgical repair. A detailed clinical history is of primary value as certain comorbid conditions, such as obesity, can provide significant insight into the etiology of the fistula.1,5–9 Although a thorough head, neck, otologic, and neurologic examination is necessary, such investigations frequently do not provide additional localizing information. Laboratory tests, such as b-2 transferrin, have a high specificity for CSF,10 but may not be readily obtainable and will not indicate the site of defect. Imaging studies including magnetic resonance imaging (MRI) and high-resolution computed tomography (CT) have sensitivities for localizing CSF leaks between 50% and 90%7,11,12; however, studies suggest that the sensitivity drops with decreasing defect size.12 Thus, if the fistulae are small, imaging may not readily provide information regarding the site of origin. As current diagnostic modalities may not consistently provide information as to the location of CSF leaks, knowledge of common sites for CSF fistulae of the temporal bone, especially in occult cases, is critical. In 1985, Neely first grouped clinical cases of spontaneous CSF effusion by the site of egress, based on their proximity to the otic capsule.13 Further refinement of this classification into transdural, labyrinthine, and perilabyrinthine fistulae greatly facilitates the understanding of their etiology, their stereotyped clinical features, their risk to the patient, and the appropriate method of surgical repair.
Remenschneider et al.: Histopathology of Lateral Skull Base Defects
TABLE I. Transdural Defects. Patient Age at No. Death, yr
Defect
Site
Laterality
Clinically Apparent Leak During Life
Relevant Clinical History
1
50
Single arachnoid granulation
Middle fossa
Right
No
Normal hearing
2
89
Single arachnoid granulation
Posterior fossa
Left
No
Paget’s disease, diabetes
3 4
74 90
Multiple arachnoid granulations Single arachnoid granulation
Posterior fossa Middle fossa
Bilateral Left
No No
Malignant mesothelioma Mild to moderate hearing loss
5
77
Multiple arachnoid granulations
Middle fossa
Left
No
Cerebral hemorrhage
6 7
87 79
Multiple meningoencephaloceles Middle fossa Multiple arachnoid granulations Posterior fossa
Right Bilateral
Yes No
Died of otitic meningitis Unknown history
8
79
Multiple arachnoid granulations
Posterior fossa
Bilateral
No
Cerebral hemorrhage
9 10
92 77
Single arachnoid granulation Multiple arachnoid granulations
Posterior fossa Posterior fossa
Left Right
Unclear Yes
Fluctuating hearing loss Mild otitic meningitis
11
42
Single arachnoid granulation
Middle fossa
Right
Yes
Died of otitic meningitis
12 13
85 13
Single arachnoid granulation Single arachnoid granulation
Posterior fossa Middle fossa
Right Bilateral
No Yes
Mondini dysplasia Tuberous sclerosis
14
92
Single arachnoid granulation
Middle fossa
Right
Yes
Died of otitic meningitis
15 16
92 91
Single arachnoid granulation Single arachnoid granulation
Posterior fossa Posterior fossa
Left Left
No No
Fluctuating hearing loss Fluctuating hearing loss
17
98
Single arachnoid granulation
Posterior fossa
Right
No
Fluctuating hearing loss
18
94
Multiple arachnoid granulations
Middle and posterior fossae
Bilateral
No
19
64
Single arachnoid granulation
Posterior fossa
Right
No
Progressive hearing loss consistent with strial atrophy No otologic problems
20
74
Single arachnoid granulation
Middle fossa
Left
No
Otosclerosis with dead ear after stapedectomy
21
62
Bony defects, no arachnoid granulation
Middle fossa
Bilateral
No
Superior canal dehiscence
22 23
68 94
Single arachnoid granulation Single arachnoid granulation
Middle fossa Middle fossa
Right Right
No No
Bilateral SNHL Unknown history
24
99
Single arachnoid granulation
Petrous apex along superior petrosal sinus in both middle and posterior fossae
Bilaterally No
CSF contacts the fat of the petrous apex marrow
25
94
Single arachnoid granulation
Petrous apex along superior petrosal sinus in both middle and posterior fossae)
Bilaterally No
CSF contacts the fat of the petrous apex marrow
26
83
Single arachnoid granulation
Middle fossa
Left
No
Bilateral Meniere’s
27 28
63 55
Single arachnoid granulation Single arachnoid granulation
Right Left
No No
Pituitary dwarfism and severe SNHL Progressive bilateral hearing loss
29
81
Single arachnoid granulation
Posterior fossa Lateral to the internal carotid (middle fossa) Posterior fossa
Bilaterally Yes
Died of otitic meningitis
30
72
Single arachnoid granulation
Middle fossa
Left
No
No otologic history
31
85
Single arachnoid granulation
Middle fossa
Left
32
97
Single arachnoid granulation
Middle fossa
Right
Possible left Possible right
Late onset ipsilateral serous otitis media with tube placement Terminal acute otitis media with incus erosion
33
75
Single meningoencephalocele
Posterior fossa
Right
No
Right vestibular schwannoma, untreated
34
79
Single meningoencephalocele
Posterior fossa
Left
No
Endolymphatic hydrops in right ear
35
81
Single meningoencephalocele
Middle fossa
Right
Yes
Repaired defect transmastoid with cartilage at age 65 years with good effect
CSF 5 cerebrospinal fluid; SNHL 5 sensorineural hearing loss.
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Although recent studies have reviewed patient presentation and surgical repair of occult CSF leaks,2,7–9,14,15 few have investigated the temporal bone histopathologic findings and correlated them with premortem clinical history. We aimed to analyze cases of idiopathic transdural, labyrinthine, and perilabyrinthine skull base defects from a large temporal bone repository. By utilizing the techniques of otopathology, we hoped to gain better insight into the pathogenesis, site of origin, and associated defects of the temporal bone and lateral skull base.
MATERIALS AND METHODS
Fig. 1. Coronal diagram showing various routes of cerebrospinal fluid fistula through the temporal bone. (1) Middle fossa transdural. (2) Labyrinthine via internal auditory canal (IAC) and oval window. (3) Patent tympanomeningeal fissure. (4) Widened fallopian canal. (5) petromastoid canal. Adapted with permission from Phelps.4 CochAq 5 cochlear aqueduct; EAC 5 external auditory canal; ET 5eustachian tube; JB 5 jugular bulb.
Temporal bone specimens included in this study are a part of the National Institute of Deafness and Other Communication Disorders’ National Temporal Bone, Hearing and Balance Pathology Resource Registry (The Registry). Specimens evaluated in the current study are all housed at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. The preparation and analysis of the bones have been previously described.16 In brief, the temporal bones were removed at autopsy and immediately fixed in 10% formalin solution. They were decalcified with
Fig. 2. Representative computed tomography scans of lateral skull base defects. Arrows indicate site of leak. (A) Posterior fossa arachnoid granulation. (B) Middle fossa meningoencephalocele. (C) Incomplete partition II, dilated apical cochlea and vestibule. (D) Patent tympanomeningeal fissure. (E) Widened fallopian canal.
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ethylenediaminetetraacetic acid and embedded in celloidin. Serial sectioning was performed in either the axial or vertical plane at a thickness of 20 mm, staining every tenth section with
hematoxylin and eosin. Stained sections were examined under light microscopy by expert otopathologists, with complete histologic and histopathologic features noted. Findings are recorded within The Registry and cataloged by key word. The Registry was queried for specimens that contained evidence of premortem CSF leak or histopathologically determined lateral skull base defects. Search terms utilized included: CSF leak, cerebrospinal fluid leak, CSF fistula, cerebrospinal fluid fistula, arachnoid granulation, Pacchionian body, encephalocele, meningoencephalocele, perilabyrinthine leak, Hyrtl’s fissure, tympanomeningeal fissure, petromastoid canal, patent fallopian canal, and cribose area. Cases were included in the analysis if there was evidence of an idiopathic and not secondarily acquired CSF fistula. Specimens with evidence of a fistula without clinical history of a leak were also included. Furthermore, cases with a documented clinical history of CSF otorrhea, otitic meningitis, or intracranial complications from a CSF leak were similarly included. Cases were excluded if the CSF fistula arose in the setting of chronic otitis media, trauma, cholesteatoma, previous surgery, or if there was another clear acquired cause. Specimens included in this study were organized into three distinct CSF fistula sites: transdural, labyrinthine, and perilabyrinthine. Transdural defects were defined as bony dehiscences with evidence of arachnoid granulation (AG) ingrowth, encephalocele/meningocele/meningoencephalocele, or direct dural contact with air cells from either the middle or posterior fossa. Labyrinthine defects were defined as the appearance of CSF in continuity with the scalae of the inner ear along with oval window abnormalities that could lead to a perilymphatic fistula. Perilabyrinthine defects were defined as congenital bony fistulae surrounding the otic capsule along three routes: a patent tympanomeningeal (Hyrtl’s) fissure, a widened petromastoid canal, or extension of the subarachnoid space into the fallopian canal. Given rarity of these data, each unique case’s features were made primary data for review. The age at death, histopathologic findings, site, laterality, evidence of CSF leak during life, and relevant clinical history were extracted. Descriptive analysis was performed. The Massachusetts Eye and Ear Computed Tomographic (CT) imaging library was searched for cases of lateral skull base defects with clinical CSF leaks. Available representative CT images from each category of fistula site were obtained.
RESULTS Search results revealed a total of 70 unique cases that included one or more terms listed above. Review of each case with application of inclusion and exclusion criteria netted a total of 52 separate cases for review. Clinical cases of occult CSF leak all contained an identifiable histologic defect of the lateral skull base. Of these, 35 were classified as transdural, 10 were labyrinthine, and seven were perilabyrinthine fistulae. The histologic
Fig. 3. (A) Low-power (23) view of a horizontal section along the axis of the internal auditory canal. The medial aspect of the canal at the porus acusticus demonstrates an arachnoid granulation of the posterior cranial fossa dura. (B) High-power (203) view of the arachnoid granulation reveals erosion into a mastoid air cell. (C) Low-power (1.253) view of a vertical section along the middle fossa floor demonstrates a distinct tegmental defect. There is associated glial tissue representing a 0.8-mm meningoencephalocele. This patient died of otitic meningitis.
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Age at Death
0 days
0 days
0 days
0 days
3 days
6 weeks
8 months
2 years
73 years
85 years
Patient No.
1
2
3
4
5
6
7
8
9
10
Right IP-II, left IP-II
Right IP-II, left IP- II
Right mild IP-II
Right IP-II, left IP-II
Left mild IP-II
Right IP-I, left IP-II
Left IP-II
Right mild IP-II
Right IP-II, left IP-II
Left IP-II
Cochleovestibular Malformation (Sennaroglu)
Both 1.5 turns, scala communis with imcomplete cribose bone
Both 2.0 turn cochlea, scala communis
2.5 turns, scala communis, absent cribose bone
1.0 turns, scala communis; 1.5 turns, scala communis
2.0 turns, scala communis
Common cavity; 1.5 turns, absent cribose bone
2.0 turns
2.0 turns, scala communis with intact cribose bone
Both 1.5 turns, scala communis with incomplete cribose bone
1.5 turns, rudimentary osseous spiral lamina
Cochlear Defect
Both dilated
Both dilated
Both normal
Both membranous
Normal, hypoplastic superior canal
Both dilated
Membranous, absent oval window
Fixed
Dilated
Common, dilated
Normal
Fixed
Absent oval window, fixed
Normal
Dilated
Both dilated
Both membranous
Normal
Dilated
Vestibule
Absent oval window
Stapes Footplate
TABLE II. Labyrinthine.
Both enlarged
Both enlarged
Normal
Both enlarged
Enlarged
None, enlarged
Enlarged
Enlarged
Both enlarged
Enlarged
Vestibular Aqueduct
Unknown
No
No
Probable
Possible
not-applicable
not-applicable
not-applicable
not-applicable
not-applicable
Clinically Apparent Leak During Life
Congenitally deaf, sparse records
Moderate hearing loss, died of myocardial infarction
Otopalatodigital syndrome, died of acute respiratory failure
Subacute otitis media and pulmonary consolidation seen at autopsy following septic death
Klippel-Feil syndrome, died of bronchopneumonia
Triplody 69XXY, died of cardiopulmonary failure Hydantoin syndrome (phenytoin toxicity)
Trisomy 13, died of cardiopulmonary failure
Born anencephalic
Trisomy 22, died of cardiopulmonary failure
Relevant Clinical History
TABLE III. Perilabyrinthine. Patient No.
Age at Death
Defect
Laterality
Clinically Apparent Leak During Life
Relevant Clinical History
1
8 weeks
Widened petromastoid canal confluent with subarcuate cell tract
Bilateral
Yes
Died from otogenic meningitis
2 3
11 weeks 2 years
Persistent tympanomeningeal fissure Widened petromastoid canal confluent with subarcuate cell tract
Right Left
Possible Possible
4
11 years
Persistent tympanomeningeal fissure
Left
No
Clear effusion right ear Bruton’s agammaglobulinemia, recurrent otitis media with seizures Progressive neurodegenerative disease
5
13 years
Extension of subarachnoid space into the fallopian canal
Bilateral
Yes
Mild meningitis
6
68 years
Widened petromastoid canal confluent with subarcuate cell tract
Right
Yes
Died from otitic meningitis
7
70 years
Persistent tympanomeningeal fissure
Right
No
Right vestibular schwannoma removed 22 years prior to death
description and clinical details of these results are featured in Tables I to III. Figure 1 displays identified pathways of CSF egress into the middle ear for each site. Representative CT scans demonstrating the identified routes for CSF leak are displayed in Figure 2. No CT images of a widened petromastoid canal resulting in CSF leak have been previously published or were identified in our imaging library.
subarachnoid space entering the internal canal through a defective fundal cribose area, which results in CSF in the scalae of the inner ear. Defects in the stapes footplate included aplasia, membranous footplate, and ankylosis (congenital stapes fixation). Of the 15 ears in 10 patients with such defects, 5/15 (33%) had membranous footplates, whereas 3/15 (18%) had a thickened footplate with apparent stapes fixation. Representative specimens are displayed in Figure 4.
Transdural Defects The mean age at death of patients in the temporal bone collection with transdural defects was 78 years, and the median was 81 years of age. Thirty of 35 cases (86%) were AGs, whereas 5/35 (14%) demonstrated bony defects without AG or meningoencephaloceles. Of the patients with AGs, 6/30 (20%) had multiple AGs, whereas the remainder had only one AG. Seventeen cases contained defects of the middle fossa floor, and 16 involved the posterior fossa plate; of these, three cases contained bony defects in both locations. Twenty-five of 35 patients (71%) did not have any history of active CSF leak or secondary complications such as otitic meningitis. The other 10 had documented meningitis or a clinical history or exam suggestive of a CSF oto/otorhinorrhea. Five patients (14%) died of otitic meningitis. Representative histopathologic specimens are featured in Figure 3.
Labyrinthine Defects Of the 10 cases of labyrinthine fistula identified in The Registry, all uniformly contained congenital modiolar defects. The classification of cochleovestibular malformation, configuration of the cochlea and vestibule, and the status of the vestibular aqueduct are detailed in Table II. The Sennaroglu classification was applied to each specimen.17 The median age at the time of death was
