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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 24  |  Issue : 2  |  Page : 129-134

Management of unsafe type of chronic suppurative otitis media with extracranial complications at a tertiary care center


Department of ENT, GMC, Latur, Maharashtra, India

Date of Web Publication4-Sep-2018

Correspondence Address:
Dr. Vinod Tukaram Kandakure
Opp. Mamta Hospital, Mitra Nagar, Latur - 413 512, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/indianjotol.INDIANJOTOL_15_18

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  Abstract 


Chronic suppurative otitis media (CSOM) is a common disease in the developing countries and the complications associated with it still pose a major problem. Despite the reduction in the incidence of CSOM-related complications with the introduction of antibiotics, Gradenigo's syndrome, mastoid abscess, labyrinthine fistula, and other complications still do occur. Computed tomography scan is an inevitable part of diagnostic algorithm rendered when a patient with CSOM presents with complications. Otitis media although a common pathology,complications are rare and should be suspected when the picture is of torpid evolution with clinical worsening and manifestation of neurological signs. There is a need to emphasize the importance of accurate and early diagnosis followed by adequate surgical therapy with a multidisciplinary approach. Here, we look at such cases encountered at our institute and their management.

Keywords: Chronic suppurative otitis media, Gradenigo's syndrome, labyrinthine fistula, mastoid abscess


How to cite this article:
Kandakure VT, Khokle PD, Shah UR. Management of unsafe type of chronic suppurative otitis media with extracranial complications at a tertiary care center. Indian J Otol 2018;24:129-34

How to cite this URL:
Kandakure VT, Khokle PD, Shah UR. Management of unsafe type of chronic suppurative otitis media with extracranial complications at a tertiary care center. Indian J Otol [serial online] 2018 [cited 2018 Dec 13];24:129-34. Available from: http://www.indianjotol.org/text.asp?2018/24/2/129/240569




  Introduction Top


Chronic suppurative otitis media (CSOM) refers to a chronic inflammatory condition of the middle ear and mastoid cavity.[1],[2] There is acute inflammation of middle ear leading to irritation and then inflammation of the mucosa producing edema. Breakdown of the epithelium causes ulceration, subsequent infection and formation of granuloma/granulation tissue. Granuloma formation leads to the development of polyps in the middle ear.[1],[3] Factors influencing the development of complications are age, low socioeconomic status, virulence of the organism, immune compromised host, previous surgeries, fractures, fistulas, and cholesteatoma. The lack of awareness and ignorance further increases the chances of developing complications. The complications developed spread through various modes such as direct bone erosion, thrombophlebitis, preformed pathways, congenital bony defects, sutures of the skull that remains patent, old fractures-heal by fibrosis, defects caused by surgery, the oval and round windows, infection from the labyrinth. The extracranial complications which can be encountered in CSOM are acute mastoiditis, petrositis, facial nerve palsy, labyrinthitis, and discharging sinuses.[4] Despite the reduction in the incidence of CSOM related complications, they still pose a major problem. Although the number of unsafe type of CSOM patients referred to our institute is around 15–20/year, here, we look at few such cases encountered at our institute within a period of 1 week and their management.


  Case Reports Top


Case 1

A 25-year-old male patient presented with a 5 days history of the left eye pain and diplopia, especially at left gaze. His medical history was insignificant except for recurrent episodes of otitis media. The patient also complained of pain and fullness sensation in his left ear for the past 10 days. Oral amoxicillin and clavulanic acid and topical (polymyxin B/neomycin/fludrocortisone) ear drops were prescribed by a general practitioner with the diagnosis of chronic otitis media. His symptoms worsened and hearing loss with constant pain in the left facial and retro-orbital areas began 5 days before presentation. On physical examination, the patient had left sixth cranial nerve palsy with no other cranial nerve abnormality [Figure 1]. Otoscopic examination revealed a congested bulging tympanic membrane. On admission, there were no meningeal signs and there were normal facial motility and no fever. Facial pain was localized in the first and second branch of the left trigeminal nerve. The left abducens nerve palsy was confirmed by the ophthalmologist. Clinical findings were compatible with the classic triad of petrous apicitis. Laboratory tests showed no significant abnormality. Intravenous (i.v) antibiotic treatment with amoxicillin-clavulanate (100 mg amoxicillin/kg/day i.v in two divided doses) was initiated. A computed tomography (CT) scan was done immediately which showed hypodense lesion involving left mastoid air cells, left mastoid antrum extending through aditus into middle air cavity. There were also features of the mild destruction of the bony margins of the petrous apex [Figure 2]. The mastoid antrum, the middle and inner ear structures and the brain parenchyma on the contralateral side were normal. A left radical mastoidectomy was done promptly with the elimination of the disease process; i.v treatment with the formerly mentioned antibiotic was continued for 3 weeks. Ten days after surgery, a partial recovery of the sixth nerve palsy was evident. The patient was discharged 3 weeks after the intervention with oral antibiotics (amoxicillin–clavulanic acid) for 1 week. On follow-up examination, 6 weeks after the surgical intervention, a significant recovery of the abducens nerve palsy was noted. The further ophthalmological examination was normal.
Figure 1: Preoperative ophthalmic evaluation showing left lateral rectus palsy

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Figure 2: High resolution computed tomography temporal bone showing hypodense lesion involving left mastoid air cells, left mastoid antrum extending through aditus into middle air cavity with features of mild destruction of the bony margins of petrous apex

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Case 2

A 12-year-old girl, presented with a history of upper respiratory tract infection of 2 weeks duration, with left otalgia and otorrhea. She was partially treated with oral antibiotics, but the symptoms persisted. Three days before presentation, the otalgia worsened and she developed a left postauricular swelling. The patient also denied any history of headache, photophobia, neck stiffness, or nausea to suggest meningitis. On examination, the patient was febrile with a temperature of 40°C. Otoscopic examination revealed purulent discharge in the left external ear canal. There was a diffuse left posterior auricular swelling measuring about 2 cm × 3 cm. The swelling was fluctuant and tender and the overlying skin was inflamed. Examination under the microscope revealed sagging of the posterosuperior wall of the external ear canal. The tympanic membrane showed granulations. She was started on broad spectrum i.v antibiotics with amoxicillin–clavulanate (1.2 g BID), ceftriaxone (1 g BID) urgent CT of the temporal bone that was performed, revealed abscess formation within the left postauricular region. It was also associated with gross soft-tissue opacification and destruction of mastoid air cells with soft-tissue extension in the middle ear with near complete erosion of ossicles with the breech in posterior lateral and medial wall mastoid with its extension in the external auditory canal (EAC) [Figure 3]. Left subperiosteal abscess with aggressive cholesteatoma was diagnosed. The patient was immediately planned for evacuation of abscess urgently. The surgical procedure went uneventfully. Pus culture and sensitivity was done which showed growth of Methicillin-resistant Staphylococcus aureus [Figure 4], sensitive to amikacin, vancomycin and linezolid. After 5 days of wet dressing and appropriate, i.v antibiotics, the wound was relatively clean. The patient subsequently underwent a left canal wall down mastoidectomy. Intraoperatively, there were granulations and cholesteatoma in the mastoid cavity, aditus, and attic. The sigmoid sinus as well as the tympanic segment of the facial nerve were exposed which were subsequently covered with soft tissue. i.v antibiotics were continued based on her culture reports and she was subsequently discharged on oral antibiotics. During the last visit following the surgery, she was well and the wound healed well.
Figure 3: High resolution computed tomography temporal bone showing gross soft tissue opacification and destruction of mastoid air cells with soft tissue extension in middle ear with near complete erosion of ossicles with breech in posterior lateral and medial wall mastoid with its extension in the external auditory canal

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Figure 4: Pus culture and sensitivity was done which showed growth of methicillin resistant Staphylococcus aureus

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Case 3

A healthy 26-year-old male presented to our hospital with chief complaints of progressively increasing right-sided hearing loss, tinnitus, and dizziness. Two weeks earlier, he had developed right-sided otalgia, middle ear fullness, and fever over 2 days and had been treated with antibiotics for 2 weeks. His history was insignificant except for recurrent episodes of otitis media which were neglected by the patient. Otoscopic examination revealed purulent ear discharge filling the right external ear canal, thus preventing the visualization of the tympanic membrane. A thorough examination of the ear under the microscope was undertaken, where keratinous debris and inflammatory polyps were seen over the tympanic membrane. The patient showed spontaneous, left-beating horizontal nystagmus. The patient was taken up for a high-resolution CT (HRCT) temporal bone where the right middle ear cavity was mostly occupied with soft tissue eroding all the ossicles as well as thinning of the tegmen plate [Figure 5] and [Figure 6]. Under the diagnosis of left cholesteatomatous chronic otitis media with the complication of labyrinthine fistula, the patient was instructed an absolute bed rest in a 30° head elevated position. A blood–brain barrier penetrating i.v antibiotic, and osmotic laxative were started. After resolution of dizziness, right canal-wall-down mastoidectomy was performed for complete removal of the cholesteatoma on the 7th day of admission. Intraoperatively, there was evidence of cholesteatoma encompassing the mastoid cavity, attic, and aditus with the erosion of the posterior wall of EAC. Furthermore, soft tissue around the lateral semicircular canal was observed without any leakage of perilymphatic fluid [Figure 7]. The tegmen plate was eroded with exposed dura. The dehiscence was covered by bone dust and muscle fascia. The patient was discharged from the hospital on the 8th postoperative day without any evidence of complications. On follow-up, the patient had complete resolution of the symptoms.
Figure 5: High resolution computed tomography temporal bone showing the right middle ear cavity was mostly occupied with soft tissue eroding all the ossicles as well as thinning of the tegmen plate

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Figure 6: High resolution computed tomography temporal bone showing erosion of bony wall of right lateral semi-circular canal

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Figure 7: Intra operative observation of labyrinthine fistula

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Case 4

A 14-year-old boy with history of chronic otitis media since childhood presented with left ear discharge for a 4 months duration. It was associated with severe otalgia. His pain was relieved intermittently with analgesics. At the same time, he also had reduced hearing on the same side which worsened over few weeks before the presentation. He gives a history of facial asymmetry 3 days before the presentation. He denied any history of vertigo or tinnitus, but there was a history of intermittent low-grade fever. There was no history of a headache, blurring of vision, or vomiting. There was no other significant history. On clinical examination, the patient was febrile. There was left-sided facial nerve palsy Grade IV (House-Brackmann grading system) [Figure 8]. There was no palpable neck node. All cranial nerves were intact except the facial nerve. There was no nystagmus and no neck stiffness. Rinne's test was positive on the right ear and negative on the left ear with the Weber's test lateralized to the left ear. Otoscopic examination revealed sagging of posterior wall of left EAC. The left tympanic membrane was not visualized due to the edematous EAC. The right ear was normal. The patient was promptly started on i.v antibiotics with injection amoxicillin–clavulanate (1.2 g BID) and metronidazole (500 mg BID). CT (HRCT-temporal bone) was then promptly taken up, which revealed the presence of destruction of mastoid air cells with soft-tissue opacification. There was an extension of soft tissue in the middle ear with ear ossicles embedded in it. Extension of soft tissue was seen in left EAC through a breech in mastoid [Figure 9]. Tympanic membrane was not visualized. He was put under emergency list for left mastoid exploration. The procedure and risk of facial nerve injury were explained to the patient. Intraoperative findings revealed an extensive cholesteatoma in the entire EAC with the erosion of the posterior wall. It was also seen encompassing the aditus, attic, and antrum along with the erosion of sigmoid sinus. The left facial nerve was otherwise normal. Postoperatively patient recovered well with minimal left ear discharge. His facial nerve palsy too had recovered at the 3 months follow-up.
Figure 8: Preoperative assessment of facial nerve showing Grade IV facial nerve palsy (House-Brackman grading system)

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Figure 9: High resolution computed tomography temporal bone revealed presence of destruction of mastoid air cells with soft tissue opacification and extension of soft tissue in the middle ear with ear ossicles embedded in it. Extension of soft tissue was seen in left external auditory canal through a breech in mastoid

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  Discussion Top


Chronic otitis media still prevails as one of the most common otological problems encountered worldwide, especially in the developing countries. Complications of otitis media may occur when the natural defensive barriers of the middle ear are penetrated, permitting infection to spread into adjacent structures.

The triad of sixth nerve palsy, pain in the distribution of the fifth nerve, and otitis media is known as Gradenigo syndrome.[5] The neurological manifestations of Gradenigo's syndrome are attributed to the involvement of the fifth and sixth cranial nerves that are only separated from the inflamed petrous apex by dura mater.[6],[7] The inflammatory process spreads from the base (mastoid and middle ear) of the pyramid-shaped os petrosum to its top (petrous apex). The spread of infection occurs through pneumatization, vascular channel or bone erosion. It can be seen as a complication of acute or chronic otitis media. Thus, infections in the petrous apex may be life-threatening due to the propensity to spread medially toward the meninges, cavernous sinus and brain. In our case, history and clinical findings are more consistent with otitis media as there was no ear discharge and tympanic membrane was intact. In imaging modalities, the CT scan of temporal bone has shown good results as it can give details of petrous apex, bone windows are more appropriate for bony erosion. In our case, CT scan showing bony erosion of mastoid and petrous apex was clearly evident. Magnetic resonance imaging (MRI) is better than CT scan to provide details of soft tissue and can identify any mass lesion and abscess formation.[8],[9] On T1-weighted MRI, inflammation of the petrous apex with peripheral enhancement of gadolinium is evident whereas T2-weighted MRI reveals high signal intensity.[10] For the clinical diagnosis of petrositis, the deep facial or ear pain appears to be the most useful symptom.[6] With the widespread use of antibiotics the symptoms may be masked, a high index of suspicion and early CT scan can prevent serious morbidity and mortality, like permanent nerve palsy and intracranial abscess. The management of petrositis has progressively changed from radical surgery in all cases of petrous apicitis to less extensive surgical interventions. Mastoidectomies without drainage of the petrous apex combined with i.v antibiotics. Some suggest an even more conservative approach without mastoid surgery.[11],[12]

Mastoid abscess, a destructive bacterial infection of the mastoid bone and air cell system, is relatively uncommon today since the advent of modern antibiotics. However, it remains a potentially serious condition due to the complications that can lead to intracranial sequelae. Even though subperiosteal abscess is the most frequent complication of mastoiditis, it is relatively less common in adults.[13] Most mastoid abscess patients are afebrile and lack systemic complaints.[14] Commonly, the patient develops otalgia or evidence of otitis media. Clinically, the retroauricular sulcus is obliterated, downward and outward protrusion of the auricle and postauricular swelling can be appreciated. The periosteum in this area is easily separated. When mucopus extends to this region, a subperiosteal abscess develops. Retroauricular fluctuance indicates a subperiosteal abscess. These features were present in our patient. Laboratory evaluation is usually not helpful.[14] Diagnosis is mainly by keeping a high index of suspicion, and urgent CT scan of the temporal bone is mandatory. Incision and drainage should be performed as soon as fluctuation appears. The incision should be in line with any future surgical incisions. Hilton's method is used to open all the abscess loculi and to achieve complete drainage of the pus. Modified radical mastoidectomy with canal wall down procedure is the most common surgical technique used for eradication of the disease. This ensures removal of extensive cholesteatoma and granulation tissue and frequent inspection of the cavity to rule out recurrence.

Labyrinthine fistula, in particular, is reported to rise from 3.6% to 13.9% of chronic otitis media with cholesteatoma, and known to affect the lateral semicircular canal most frequently.[15],[16],[17] Typical symptoms of labyrinthine fistula are positional vertigo, severe disequilibrium, and sensorineural hearing loss, collectively making it difficult to differentiate from benign paroxysmal positional vertigo or Meniere's disease. Confounding the distinction is the sensitivity of the fistula test, of which is reported to be between 30% and 60% at best.[18] HRCT of the temporal bone may help diagnose fistulas with sensitivity of 90%. Labyrinthine fistula is an aberrant connection between the perilymph-filled inner ear and air-filled middle ear, of which the perilymph leak results in the pathology of the vestibule and the cochlea. In most instances, the bony labyrinth is involved up to but not involving the endosteum so that the endosteum is merely separating the perilymphatic space from the matrix.[19],[20] Surgical management with a canal wall down mastoidectomy and sealing of the fistulous site is warranted in selected cases such as this one, for effective resolution of the symptoms.

Cholesteatoma is a disease that can occur in the middle ear, mastoid bone, or petrous temporal bone. It is characterized by a tendency for bone erosion and recurrence. Once established in the middle ear, mastoid or petrous bone, cholesteatoma is destructive lesion that gradually expands and destroys adjacent structures leading to complications. These complications include subperiosteal abscess, mastoid abscess, petrositis, labyrinthitis, and facial nerve palsy. Intracranial complications ranging from meningitis, brain abscess, lateral sinus thrombosis, and extradural abscess can also occur. Facial nerve paralysis is uncommon, but significant complication of CSOM. It has decreased significantly with the use of newer diagnostic tools and effective antibiotics.[21] The mechanism of facial nerve paralysis is not fully understood. It is often associated with dehiscence in the  Fallopian canal More Details.[22] Some of the proposed etiologic factors may be osteitis, bone erosion, external compression, edema, and inflammation of the nerve by bacteria or neurotoxins.[23] Facial nerve paralysis due to chronic otitis media may present either abruptly or gradually. Gradual onset results most commonly due to compression from cholesteatoma. Patients with facial palsy as a result of chronic otitis media should be operated as early as possible regardless of the severity of facial dysfunction, the presence of cholesteatoma, type of onset, the age of the patient and any previous otologic surgical history. Modified radical mastoidectomy with canal wall down procedure is the most common surgical technique used for eradication of disease as well as facial nerve decompression. This ensures removal of extensive cholesteatoma and granulation tissue and frequent inspection of the cavity to rule out recurrence.[24] High surgical gain is defined as improvement in facial function by two or more grades by House-Brackman grading system after surgery.[21],[25] Good recovery is seen in cases of CSOM with short duration of onset of facial nerve paralysis, the absence of previous surgery, noncholesteatomatous inflammatory granulation tissue and a healthy bony labyrinth. Presenting complaints of the patient can help to arrive at a provisional diagnosis of an intracranial or intratemporal complication of CSOM. CT scan of temporal bone gives information regarding the extent of the disease and presence of bony erosion. In our patient, there was no risk factor for him to develop such a complication. We thought that his condition worsened due to inadequate antibiotic treatment he received previously, and much delay in presentation to our care. However with disease clearance by radical mastoidectomy, his condition improved significantly.


  Conclusion Top


Although the incidence of complications of CSOM has decreased in recent decades, it still remains high. Excessive use and misuse of antibiotic treatment may cause masked presentations,[26],[27] thereby reducing the chances of early diagnosis. It is critical that clinicians remain alert for clinical signs and symptoms that may indicate the onset of these potentially serious complications and be prepared to examine patients for the presence of more than one complication. Modern diagnostic techniques with appropriate medical and surgical treatment are necessary to reduce mortality. High level of awareness in patients too regarding these complications and utility of early clinical detection and the appropriate treatment modalities are required to achieve successful resolution of the disease process and the prevention of complications.

In the management of CSOM with extra-or intra-cranial complications,

”Never let the sun set without performing ear surgery on the patient.”

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Yorgancılar E, Yildirim M, Gun R, Bakir S, Tekin R, Gocmez C, et al. Complications of chronic suppurative otitis media: A retrospective review. Eur Arch Otorhinolaryngol 2013;270:69-76.  Back to cited text no. 1
    
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Hossain MM, Kundu SC, Haque MR, Shamsuzzaman AK, Khan MK, Halder KK, et al. Extracranial complications of chronic suppurative otitis media. Mymensingh Med J 2006;15:4-9.  Back to cited text no. 2
    
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Mostafa BE, El Fiky LM, El Sharnouby MM. Complications of suppurative otitis media: Still a problem in the 21st century. ORL J Otorhinolaryngol Relat Spec 2009;71:87-92.  Back to cited text no. 3
    
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Dubey SP, Larawin V. Complications of chronic suppurative otitis media and their management. Laryngoscope 2007;117:264-7.  Back to cited text no. 4
    
5.
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Gillanders DA. Gradenigo's syndrome revisited. J Otolaryngol 1983;12:169-74.  Back to cited text no. 7
    
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Hardjasudarma M, Edwards RL, Ganley JP, Aarstad RF. Magnetic resonance imaging features of Gradenigo's syndrome. Am J Otolaryngol 1995;16:247-50.  Back to cited text no. 8
    
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Woody RC, Burchett SK, Steele RW, Sullivan JA, McConnell JR. The role of computerized tomographic scan in the management of Gradenigo's syndrome: A case report. Pediatr Infect Dis 1984;3:595-7.  Back to cited text no. 9
    
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Hitier M, Boutet C, Faure C, Abadie C, Moreau S. Radiology quiz case 2. Gradenigo syndrome caused by right petrous apicitis. Arch Otolaryngol Head Neck Surg 2010;136:201.  Back to cited text no. 10
    
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Marianowski R, Rocton S, Ait-Amer JL, Morisseau-Durand MP, Manach Y. Conservative management of Gradenigo syndrome in a child. Int J Pediatr Otorhinolaryngol 2001;57:79-83.  Back to cited text no. 11
    
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Goldstein NA, Casselbrant ML, Bluestone CD, Kurs-Lasky M. Intratemporal complications of acute otitis media in infants and children. Otolaryngol Head Neck Surg 1998;119:444-54.  Back to cited text no. 12
    
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Migirov L, Yakirevitch A, Kronenberg J. Mastoid subperiosteal abscess: A review of 51 cases. Int J Pediatr Otorhinolaryngol 2005;69:1529-33.  Back to cited text no. 13
    
14.
Tsai CJ, Guo YC, Tsai TL, Shiao AS. Zygomatic abscess complicating a huge mastoid cholesteatoma with intact eardrum. Otolaryngol Head Neck Surg 2003;128:436-8.  Back to cited text no. 14
    
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Turner B, Eynon-Lewis N. Systematic approach needed to establish cause of vertigo. Practitioner 2010;254:19-23, 2-3.  Back to cited text no. 15
    
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Palva T, Kärjä J, Palva A. Opening of the labyrinth during chronic ear surgery. Arch Otolaryngol 1971;93:75-8.  Back to cited text no. 16
    
17.
Kim CS, Choi BY, Hwang CH, Ahn SH, Park JB, Koo JW, et al. Clinical presentation and management of labyrinthine fistula in chronic otitis media with cholesteatoma. Korean J Otolaryngol Head Neck Surg 2002;45:1039-45.  Back to cited text no. 17
    
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Maitland CG. Perilymphatic fistula. Curr Neurol Neurosci Rep 2001;1:486-91.  Back to cited text no. 18
    
19.
Pfaltz CR. Complications of otitis media. ORL J Otorhinolaryngol Relat Spec 1982;44:301-9.  Back to cited text no. 19
    
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Gacek RR. The surgical management of labyrinthine fistulae in chronic otitis media with cholesteatoma. Ann Otol Rhinol Laryngol 1974;83:Suppl 10:1-19.  Back to cited text no. 20
    
21.
House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg 1985;93:146-7.  Back to cited text no. 21
    
22.
Ceylan A, Bayazit Y, Yilmaz M, Celenk F, Bayramoglu I, Uygur K, et al. Extracranial complications of chronic otitis media. Int Adv Otol 2009;5:51-5.  Back to cited text no. 22
    
23.
Kim J, Jung GH, Park SY, Lee WS. Facial nerve paralysis due to chronic otitis media: Prognosis in restoration of facial function after surgical intervention. Yonsei Med J 2012;53:642-8.  Back to cited text no. 23
    
24.
Samy RN, Gantz BJ. Surgery of the facial nerve. Glasscock, Surgery of the Ear. 5th ed. B.C. Decker Inc., Elsevier Ontario, 2003. p. 615.  Back to cited text no. 24
    
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Ikeda M, Nakazato H, Onoda K, Hirai R, Kida A. Facial nerve paralysis caused by middle ear cholesteatoma and effects of surgical intervention. Acta Otolaryngol 2006;126:95-100.  Back to cited text no. 25
    
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Chandrashekharayya SH. Complications of chronic suppurative otitis media- still a menace. Med Inn 2013;2:3-4.  Back to cited text no. 27
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]



 

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