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06 February 2024: Articles  New Zealand

an Underrecognized Cause of Petrous Apicitis Presenting with Gradenigo Syndrome: A Case Report

Rare disease

Zaid Ibrahim ORCID logo1ABCDEF*, Shivani Fox-Lewis2E, Jason A. Correia13AE

DOI: 10.12659/AJCR.942652

Am J Case Rep 2024; 25:e942652

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Abstract

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BACKGROUND: With the advent of antibiotics, petrous apicitis (PA), inflammation of the petrous temporal bone, has become a rare complication of otitis media. Even more uncommon is Gradenigo syndrome (GS), a result of PA, characterized by a triad of otitis media or purulent otorrhea, pain within the regions innervated by the first and second division of the trigeminal nerve, and ipsilateral abducens nerve palsy. Recent literature has demonstrated increasing reports of Fusobacterium necrophorum isolated in cases of GS.

CASE REPORT: A 21-year-old man presented with otalgia, reduced hearing, and severe headache. Examination revealed right-sided purulent otorrhea, anesthesia within the trigeminal nerve distribution, and an ipsilateral abducens nerve palsy. F. necrophorum was isolated from an ear swab and a blood culture. Computed tomography and magnetic resonance imaging (MRI) demonstrated otomastoiditis, PA, cavernous sinus thrombosis, and severe stenosis of the petrous internal carotid artery. He was treated with intravenous benzylpenicillin, underwent a mastoidectomy and insertion of a ventilation tube, and was started on a 3-month course of dabigatran. Interval MRI showed improved internal carotid artery caliber, persistent petrous apex inflammation, and normal appearance of both cavernous sinuses. Follow-up clinical review noted persistent abducens and trigeminal nerve dysfunction.

CONCLUSIONS: We identified 190 cases of PA; of these, 80 presented with the classic Gradenigo triad. Fusobacterium sp. were cultured in 10% of GS cases, making them the most frequent isolates. Due to the fastidious nature of F. necrophorum, it may be underrepresented in the historical literature, and we recommend that empiric antibiotics cover anaerobic organisms.

Keywords: Fusobacteria, Fusobacteriaceae Infections, Fusobacterium necrophorum, Otitis Media, Otitis Media, Suppurative, Petrositis

Background

Otitis media (OM) is one of the most common infectious diseases. With the advent and widespread use of antibiotics, life-threatening complications of OM, such as petrous apicitis (PA), have become very rare. In 1937, it was estimated that PA occurred once in every 300 cases of OM [1]. Today, the incidence is likely less than 2 in every 100 000 cases of OM [2]. PA is caused by medial propagation of middle ear infection to the petrous apex of the temporal bone, where the trigeminal ganglion and abducens nerve, passing through the Dorello canal, reside [3]. Therefore, inflammation within the petrous apex can cause deep pain within the regions inner-vated by the first and second division of the trigeminal nerve and an ipsilateral abducens nerve palsy. When seen with OM/ purulent otorrhea, this is referred to as the Gradenigo triad, or Gradenigo syndrome (GS), first described by Giuseppe Gradenigo in 1904 [4]. Patients with PA rarely present with GS. In 1907, Gradenigo [5] suggested that only 42% of patients present with the classic triad.

Almost all individuals have pneumatized mastoid cells. Comparatively, one-third of adults have a pneumatized petrous apex. In these cases, there is a clear route for the middle ear infection to propagate medially to the petrous apex [6]. Therefore, these patients are at risk of developing PA and GS following OM. With a non-pneumatized petrous apex, the infection can occur directly through bony destruction, extension through fascial planes, or hematogenous spread [3,7]. These pathophysiologic processes offer insight into the 1-week to 3-month interval between the onset of OM and cranial nerve dysfunction [3]. If untreated, PA can lead to life-threatening complications, such as meningitis, empyema, cerebral abscess, or venous sinus thrombosis [3] with compression of the adjacent internal carotid artery (ICA); if severe, this can cause cerebral infarction. Immunocompromised patients are at significant risk of developing recurrent OM [8] and its life-threatening complications, including PA and GS. A literature review in 2018 suggested a mortality rate of 2.6% in GS cases [9].

F. necrophorum is an anaerobic, non-spore-forming, non-mo-tile, gram-negative bacillus [10]. It is a commensal of the upper respiratory tract with high virulence, as leukotoxin production leads to apoptosis of phagocytes [11]. It causes necrobacillosis, strictly defined as sepsis, due to F. necrophorum. However, the term is often synonymously used with Lemierre syndrome (septic thrombophlebitis of the internal jugular vein) [10]. F. necrophorum is known to cause platelet aggregation, possibly due to lipopolysaccharide release [12], increasing the risk of cerebral sinus thrombosis [13]. Interestingly, in recent reports of PA and GS, F. necrophorum appears to be an emerging pathogen [3,10,13–15]. Infrequent reports in the historical literature may be due to the fastidious nature of the organism, strictly growing under anaerobic conditions [16]. Here, we report a case of PA presenting with GS secondary to F. necrophorum and discuss the literature and treatment options.

Case Report

A 21-year-old immunocompetent man with a 2-year history of recurrent middle ear infections following a right tympanic membrane perforation that occurred after an accident while surfing presented to the Emergency Department with a 1-month history of otalgia, otorrhea, and reduced hearing in his right ear despite a 14-day course of topical ciprofloxacin and oral amoxicillin/clavulanic acid. He developed a severe headache 24 h before his presentation to the hospital. Examination revealed purulent, malodourous right-sided ear discharge, anesthesia within the ophthalmic and maxillary distributions of the ipsilateral trigeminal nerve, and an ipsilateral abducens nerve palsy. He did not have clinical signs of meningism. Laboratory test results revealed a white blood count of 46.51 E+9/L, a neutrophil count of 35.21 E+9/L, and a C-reactive protein level of 49 mg/L. Broad-spectrum antibiotics (ceftriaxone, vancomycin, and metronidazole) were started immediately. F. necrophorum was isolated from a right ear swab and 1 of 2 sets of blood cultures taken on the day of admission (Figure 1). The isolate was susceptible to penicillin (minimal inhibitory concentration [MIC]: 0.016 mg/L), amoxicillin/clavulanic acid (MIC: 0.016 mg/L), and metronidazole (MIC: 0.06 mg/L). The antibiotic treatment was rationalized to intravenous benzyl-penicillin. Computed tomography (CT) of his temporal bone, cerebral angiography, and venography demonstrated otomastoiditis extending into the petrous apex (Figure 2). A gas and fluid collection affecting the Meckel cave and cavernous sinus with associated thrombosis was noted. This process extended into the right carotid canal, causing severe stenosis of the petrous portion of the ICA (Figures 3–6). No distal stenosis was noted. There was no associated cerebral infarction. Magnetic resonance imaging (MRI) confirmed the presence of PA associated with otomastoiditis (Figures 5, 6). The day following his hospital admission, he underwent an examination under anesthesia of both ears and a right-sided cortical mastoidectomy via a post-auricular incision. Within the external acoustic meatus, a copious sum of purulent material was seen, in addition to a thickened tympanic membrane, with a small posterior perforation. A ventilation tube was inserted into the perfo-ration to encourage adequate drainage of the middle ear. The left-sided external acoustic meatus and tympanic membrane appeared normal. Mastoid granulation tissue was sent for culture and revealed no growth. To manage his cavernous sinus thrombosis, he was placed on a 3-month course of dabigatran 150 mg, orally, twice daily. He was discharged with a 28-day course of intravenous benzylpenicillin 7.2 g per 24 h. Interval 3-month MRI demonstrated improved but persistent PA, with improved ICA caliber, normal appearance of both cavernous sinuses, and resolution of the previously seen trigeminal nerve enhancement (Figures 4–6). His 3-month clinical review noted improved hearing and reduced headache, with persistent abducens and trigeminal nerve dysfunction.

Discussion

PA is a potentially life-threatening complication of middle ear infection propagating to the petrous apex of the temporal bone, causing inflammation of adjacent cranial nerves, which can lead to GS. With the advent of antibiotics, PA and GS have become rare. GS has a reported incidence of 1% to 3.6% among those who have experienced complications from OM [17] and a suggested mortality rate of 2.6% [9].

The scarcity of PA and GS, lack of familiarity among clinicians, and delay between the onset of initial OM symptoms and cranial nerve signs suggestive of a petrous apex infection can lead to a delay in diagnosis of PA [3], increasing the risk of morbidity, as propagation of the infection can establish the classic Gradenigo triad or lead to life-threatening complications, such meningitis, empyema, cerebral abscess, or, as seen in our case, venous sinus thrombosis with compression of the adjacent ICA. Urgent neuro-imaging must be obtained to outline the extent of the disease and aid with operative planning, if indicated. CT will highlight the bony anatomy, whereas MRI can demonstrate the involvement of neurovascular structures and detect intracranial complications [3,17].

The management of PA has evolved with time. In 2017, Gadre and Chole reviewed the management of 44 cases of PA over 40 years (1971–2011), noting a significant reduction in the number of major surgical interventions performed (excluding tympanostomy, ventilation tube placement, and simple mastoidectomy). During the following periods, the percentage of patients that underwent major surgical intervention were as follows: 1971–1980, 50%; 1981–1990, 28.6%; 1991–2010, 15.4%; and 2001–2011, 12.5% [2]. In their review, 34 of the 44 patients (77.3%) underwent successful treatment of PA with antibiotics alone, with or without tympanostomy and ventilation tube placement [2], contradicting a review by Parsons and Strauss, who assert that surgical debridement of devitalized tissue is of the utmost importance in the management of osteomyelitis [18]. Concordantly, Henke et al found that in foot and digit osteomyelitis, aggressive surgical debridement improves wound healing, and antibiotic therapy alone was associated with reduced wound healing, less chance of limb salvage, and poor outcomes [19]. Gadre and Chole postulate that in contrast to other forms of osteomyelitis, petrous apex debridement in PA should not be a first-line treatment, as antibiotics alone can be sufficient, possibly due to the rich vascularity of the petrous apex. They also suggested a treatment algorithm in which antibiotics are the first-line treatment. If a patient worsens clinically following 24 to 48 h of treatment, major surgical intervention combined with antibiotics should be considered [2].

If major surgical intervention is warranted, important factors in determining the surgical approach to the petrous apex include the extent and location of disease, the anatomy of adjacent structures, whether the patient has serviceable hearing, and what the surgical team deems to be the shortest and least morbid route [2,20]. If a patient has impaired hearing ipsilateral to the lesion, a translabyrinthine or transcochlear approach can be considered. In cases in which hearing is preserved, approaches that tend to spare hearing include endoscopic endonasal, open anterior petrosectomy, middle cranial fossa, or transcanal infracochlear [21]. Complications range from cerebrospinal fluid leak, postoperative meningitis, damage to vascular structures, which can lead to bleeding and stroke, and hearing loss, vertigo, or facial nerve damage [20]. Given the results by Gadre and Chole [2] and the potential for morbidity, following a multidisciplinary review of the case described, we chose to avoid surgical debridement of the petrous apex.

A systemic review by Loh, Phua, and Shaw found that in un-complicated cases of acute mastoiditis, conservative treatment with antibiotics alone or with myringotomy with or without ventilation tube insertion is as effective as mastoidectomy in producing favorable long-term outcomes [22]. In contrast, a review of 262 cases of acute mastoiditis by Gelbart et al found that 94.7% (18/19) of acute mastoiditis cases caused by F. necrophorum developed complications, the most common being a subperiosteal abscess, compared with 15.6% (38/243) of acute mastoiditis caused by an alternate organism. All cases caused by F. necrophorum required surgical intervention. Comparatively, only 15.6% of cases not caused by F. necrophorum required surgery. Additionally, cases caused by F. necrophorum required significantly longer periods of hospitalization [23]. Ulanovski et al reported 43 cases of F. necrophorum mastoiditis, with higher inflammatory markers, more severe clinical presentations, and a greater incidence of intracranial and extracranial complications, compared with cases of mastoiditis secondary to other organisms [24]. Similarly, Yarden-Bilavsky et al identified 7 cases of acute mastoiditis secondary to F. necrophorum. All cases were complicated by subperiosteal abscess formation, had significantly elevated inflammatory markers, and 4 were complicated by an extradural abscess. All cases required mastoidectomy with ventilatory tube insertion [25]. Bakhos et al reviewed the management of 31 patients with a subperiosteal abscess secondary to acute mastoiditis. They found that conservative management with postauricular puncture or tympanostomy tube placement with antibiotics is an effective alternative to cortical mastoidectomy. Of the 16 cases, only 1 failed conservative management, requiring cortical mastoidectomy. The organism isolated was F. necrophorum [26]. Gelbart et al, Ulanovski et al, and Bakhos et al, all conclude that mastoiditis caused by F. necrophorum appears to have a more aggressive and complicated clinical course, and mastoidectomy should be strongly considered [23,24,26]. The patient we described underwent neuro-imaging, demonstrating right-sided mastoiditis (Figures 2, 5) and cultures positive for F. necrophorum (Figure 1); in line with the reviewed literature, he was treated with antibiotics and underwent a right-sided cortical mastoidectomy, with ventilation tube insertion into a small tympanic membrane perforation. In the days following the cortical mastoidectomy, the patient showed no signs of clinical deterioration. Therefore, surgical debridement of the petrous apex was not undertaken.

As discussed, Gadre and Chole assert that the first-line treatment of PA should be empiric broad-spectrum antibiotics with effective central nervous system penetrance. They suggest using ceftriaxone, vancomycin, and metronidazole [2], the same empiric regime used in our case, to cover a broad range of microorganisms that may be causing PA or to account for the possibility of a polymicrobial infection, frequently seen in head and neck infections [27]. Among the studies we reviewed, highlighted in greater detail later in this discussion, we identified 19 polymicrobial PA infections (Table 1). Pseudomonas aeruginosa was the most common isolate in polymicrobial infections (37%), with Staphylococcus aureus being the second most common (32%). Consistently, P. aeruginosa was the most common isolate among the 190 cases of PA we identified in our literature review (14.21%) and the most common isolate in the study by Gadre and Chole (53.3%), who reviewed 44 cases of PA over 40 years [2]. This information suggests that antipseudomonal and anti-staphylococcal antibiotics with effective central nervous system penetrance are used when treating PA with empiric antibiotics. Despite having some activity against P. aeruginosa, ceftriaxone is not recommended for treating pseudomonal infections [28]. Therefore, clinicians should consider using an alternate empiric antibiotic with strong activity against P. aeruginosa.

Antimicrobial agents can then be adjusted depending on the organisms isolated. In the case we have described, F. necrophorum was isolated from a single blood culture and a swab from ear discharge and was susceptible to penicillin (MIC: 0.016 mg/L); a second blood culture and intraoperative specimens revealed no growth. With microbiological evidence suggesting our patient did not have a polymicrobial infection and the data regarding the isolate’s antibiotic sensitivities, the patient’s antibiotics were changed to intravenous benzylpenicillin, administered for 7 days as an inpatient, and a further 28 days after discharge. Consistently, a review by McLaren, Cohen, and El Saleeby [17] suggested a treatment duration of 4 to 6 weeks to be sufficient.

The most common pathogens associated with OM are Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae [29]. This trend is not observed among reports of PA and GS [17]. Frequently, a pathogen is not isolated [30–70]. Interestingly, in recent reports of these conditions, F. necrophorum appears to be an emerging pathogen [3,10,13–15]. In 2020, McLaren, Cohen, and El Saleeby [17] identified 65 pediatric cases of PA, 45 presenting with GS, and 21 had positive cultures, 4 of which isolated F. necrophorum.

Similarly, recent studies have reported an increasing incidence of head and neck infections, including mastoiditis caused by F. necrophorum [23,24,71–73]. Gelbart et al reported a series of 149 cases of acute mastoiditis with an identified organism, 13% a result of F. necrophorum, showing a 7-fold increase in incidence from 2.8% in 2012 to 20.4% in 2015 [23]. Ulanovski et al reported 43 cases of F. necrophorum mastoiditis, 50% of which were culture-negative. The rest were identified through 16srRNA polymerase chain reaction (PCR) sequencing [24]. Over 11 years, Le Monnier et al identified 25 cases of F. necrophorum acute OM, 10 of which developed mastoiditis; 60% of the cases were diagnosed in the last 4 years of the study, and like the study by Ulanovski et al [24], PCR was used to identify F. necrophorum when cultures were negative [72]. The first report of F. necrophorum isolated in a case of GS in the English literature was in 2003 [10], in keeping with the organism’s fastidious nature. It appears that increased reports of F. necrophorum in head and neck infections are a consequence of improved anaerobic culture techniques and new molecular diagnostic methods, often used when cultures are negative and are therefore valuable when antibiotics have been started prior to cultures being sent to the laboratory [24,73]. Therefore, F. necrophorum is possibly underrecognized in the historical PA and GS literature.

Following a review of the English literature using PubMed from 1938 to 2023, we found 97 case reports [3,10,13–15,17, 30–70,74–121]. The papers were sorted on PubMed using the query “F. necrophorum” or “fusobacterium” and “Gradenigo” or “Petrositis” or “petrous apicitis”. A total of 173 papers were found, and 97 were included in our review. Including our findings, we identified 190 cases of PA due to infection, 92 of which cultured an organism. Among the 190 cases of PA, 80 presented with the classic Gradenigo triad. The most common microbe cultured was P. aeruginosa, seen in 27 patients (14.21%). Interestingly, it only featured in 4 (5%) cases presenting with GS. Of the PA cases, 7 cultured F. necrophorum (3.68%), all of which presented with GS (8.75%), making it the most frequent isolate in the 80 GS cases identified. In 1 case of GS, F. nucleatum was isolated, bringing the total cases caused by Fusobacterium sp. to 8 (10%; Table 2).

The higher incidence of the Gradenigo triad among cases of PA caused by F. necrophorum may be due to the highly virulent nature of the organism [11], inciting a greater inflammatory response at the petrous apex leading to the characteristic cranial nerve palsies. An intense inflammatory process would also explain the aggressive and complicated clinical course seen in cases of mastoiditis caused by F. necrophorum.

Conclusions

It appears that F. necrophorum may be an underrecognized cause of PA presenting with GS. We report a further case of PA presenting with GS secondary to F. necrophorum. This case highlights that although PA and GS are rare, prompt recognition, with early neuro-imaging, is essential to confirm the diagnosis. Recent evidence suggests that mastoidectomy is the first-line treatment for mastoiditis secondary to F. necrophorum, given its aggressive and complicated clinical course. In contrast, petrous apex debridement for PA should be reserved for cases in which antibiotic therapy has failed. Although antimicrobial resistance in F. necrophorum is uncommon [122], we suggest that empiric antibiotics used to treat PA and GS cover anaerobes, P. aeruginosa, and S. aureus. We also suggest that routine anaerobic culture of samples are obtained.

Figures

Gram stain of Fusobacterium necrophorum isolated from blood culture, demonstrating characteristic pleomorphic gram-negative bacilli. Scale bar is 50 µm.Figure 1.. Gram stain of Fusobacterium necrophorum isolated from blood culture, demonstrating characteristic pleomorphic gram-negative bacilli. Scale bar is 50 µm. Axial computed tomography scan demonstrating otomastoiditis (lateral arrow) extending into the petrous apex where there is expansion with a gas and fluid collection (medial arrow).Figure 2.. Axial computed tomography scan demonstrating otomastoiditis (lateral arrow) extending into the petrous apex where there is expansion with a gas and fluid collection (medial arrow). Axial time-of-flight magnetic resonance angiography demonstrating severe narrowing of the petrous segment of the right internal carotid artery (ICA; left-sided arrow) and normal caliber of the petrous segment of the left ICA (right-sided arrow).Figure 3.. Axial time-of-flight magnetic resonance angiography demonstrating severe narrowing of the petrous segment of the right internal carotid artery (ICA; left-sided arrow) and normal caliber of the petrous segment of the left ICA (right-sided arrow). (A) Three-dimensional (3D) time-of-flight magnetic resonance angiography (MRA) demonstrating severe narrowing of the petrous and cavernous segments of the right internal carotid artery (ICA; 2 left-sided arrows). (B) 3D time-of-flight MRA 3 months after treatment demonstrating significantly improved caliber of the petrous and cavernous segments of the right ICA (2 left-sided arrows).Figure 4.. (A) Three-dimensional (3D) time-of-flight magnetic resonance angiography (MRA) demonstrating severe narrowing of the petrous and cavernous segments of the right internal carotid artery (ICA; 2 left-sided arrows). (B) 3D time-of-flight MRA 3 months after treatment demonstrating significantly improved caliber of the petrous and cavernous segments of the right ICA (2 left-sided arrows). (A) Axial post-gadolinium T1-weighted magnetic resonance imaging (MRI) during hospital admission demonstrating right-sided otomastoiditis (lateral arrow) with petrous apicitis and minimal contrast enhancement of the ipsilateral petrous internal carotid artery (ICA; medial arrow). (B) Axial post-gadolinium T1-weighted MRI 3 months after treatment demonstrating resolution of otomastoiditis (lateral arrow) and significantly improved ipsilateral petrous ICA caliber (medial arrow).Figure 5.. (A) Axial post-gadolinium T1-weighted magnetic resonance imaging (MRI) during hospital admission demonstrating right-sided otomastoiditis (lateral arrow) with petrous apicitis and minimal contrast enhancement of the ipsilateral petrous internal carotid artery (ICA; medial arrow). (B) Axial post-gadolinium T1-weighted MRI 3 months after treatment demonstrating resolution of otomastoiditis (lateral arrow) and significantly improved ipsilateral petrous ICA caliber (medial arrow). (A) Axial post-gadolinium T1-weighted magnetic resonance imaging (MRI) during hospital admission demonstrating right-sided cavernous sinus thrombosis with reduced ipsilateral cavernous internal carotid artery (ICA) caliber (left-sided arrow). (B) Axial post-gadolinium T1-weighted MRI 3 months after treatment showing resolution of cavernous sinus thrombosis with significantly improved ipsilateral cavernous ICA caliber (left-sided arrow).Figure 6.. (A) Axial post-gadolinium T1-weighted magnetic resonance imaging (MRI) during hospital admission demonstrating right-sided cavernous sinus thrombosis with reduced ipsilateral cavernous internal carotid artery (ICA) caliber (left-sided arrow). (B) Axial post-gadolinium T1-weighted MRI 3 months after treatment showing resolution of cavernous sinus thrombosis with significantly improved ipsilateral cavernous ICA caliber (left-sided arrow).

References:

1.. Myerson MC, Suppuration of the petrous pyramid some views on its surgical management: Arch Otolaryngol, 1937; 26; 42-48

2.. Gadre AK, Chole RA, The changing face of petrous apicitis – a 40-year experience: Laryngoscope, 2018; 128; 195-201

3.. Jacobsen CL, Bruhn MA, Yavarian Y, Gaihede ML, Mastoiditis and Gradenigo’s syndrome with anaerobic bacteria: BMC Ear Nose Throat Disord, 2012; 12; 10

4.. Gradenigo G, [About circumscript leptomeningitis with spinal symptoms and about paralysis of the abducens nerve of otic origin.]: Archiv für Ohrenheilkunde, 1904; 62; 255-70 [in German]

5.. Gradenigo G, [About paralysis of the abducens nerve of otitis.]: Archiv für Ohrenheilkunde, 1907; 74; 149-87 [in German]

6.. Jackler RK, Parker DA, Radiographic differential diagnosis of petrous apex lesions: Am J Otol, 1992; 13; 561-74

7.. Motamed M, Kalan A, Gradenigo’s syndrome: Postgrad Med J, 2000; 76; 559-60

8.. Wilson NW, Hogan MB, Otitis media as a presenting complaint in childhood immunodeficiency diseases: Curr Allergy Asthma Rep, 2008; 8; 519-24

9.. Gore MR, Gradenigo’s ayndrome: A review: Ann Med Health Sci Res, 2018; 8; 220-24

10.. Piron K, Gordts F, Herzeel R, Gradenigo syndrome: A case-report: Bull Soc Belge Ophtalmol, 2003; 290; 43-47

11.. Narayanan S, Stewart GC, Chengappa MM: Infect Immun, 2002; 70; 4609-20

12.. Horose M, Kiyoyama H, Ogawa H, Shinjo T: Vet Microbiol, 1992; 32; 343-50

13.. Heshin-Bekenstein M, Megged O, Peleg U, Gradenigo’s syndrome: Is fusobacterium different? Two cases and review of the literature: Int J Pediatr Otorhinolaryngol, 2014; 78; 166-69

14.. Cundiff JG, Djalilian HR, Mafee MF, Bilateral sequential petrous apicitis secondary to an anaerobic bacterium: Otolaryngol Head Neck Surg, 2006; 135; 969-71

15.. Bergsma P, Kunz S, Kienle AL, Brand Y, Case report: petrous apicitis and otogenic thrombosis of the cavernous sinus in a 10-Year-old boy: Front Surg, 2021; 8; 667817

16.. Johannesen K, Dessau R, Heltberg O, Bodtger U: Eur Clin Respir J, 2016; 3; 30287

17.. McLaren J, Cohen MS, El Saleeby CM, How well do we know Gradenigo? A comprehensive literature review and proposal for novel diagnostic categories of Gradenigo’s syndrome: Int J Pediatr Otorhinolaryngol, 2020; 132; 109942

18.. Parsons B, Strauss E, Surgical management of chronic osteomyelitis: Am J Surg, 2004; 188; 57-66

19.. Henke PK, Blackburn SA, Wainess RW, Osteomyelitis of the foot and toe in adults is a surgical disease: Conservative management worsens lower extremity salvage: Ann Surg, 2005; 241; 885-92

20.. Savasta S, Canzi P, Aprile F, Gradenigo’s syndrome with abscess of the petrous apex in pediatric patients: What is the best treatment?: Childs Nerv Syst, 2019; 35; 2265-72

21.. Li KL, Agarwal V, Moskowitz HS, Abuzeid WM, Surgical approaches to the petrous apex: World J Otorhinolaryngol Head Neck Surg, 2020; 6; 106-14

22.. Loh R, Phua M, Shaw CL, Management of paediatric acute mastoiditis: Systematic review: J Laryngol Otol, 2018; 132; 96-104

23.. Gelbart M, Bilavsky E, Chodick G: Pediatr Infect Dis J, 2019; 38; 12-15

24.. Ulanovski D, Shavit SS, Scheuerman O: Int J Pediatr Otorhinolaryngol, 2020; 138; 110324

25.. Yarden-Bilavsky H, Raveh E, Livni G: Int J Pediatr Otorhinolaryngol, 2013; 77; 92-96

26.. Bakhos D, Trijolet JP, Morinière S, Conservative management of acute mastoiditis in children: Arch Otolaryngol Head Neck Surg, 2011; 137; 346-50

27.. Roscoe DL, Hoang L, Microbiologic investigations for head and neck infections: Infect Dis Clin North Am, 2007; 21; 283-304

28.. Richards DM, Heel RC, Brogden RN, Ceftriaxone: A review of its antibacterial activity, pharmacological properties and therapeutic use: Drugs, 1984; 27; 469-527

29.. Massa HM, Cripps AW, Lehmann D, Otitis media: Viruses, bacteria, biofilms and vaccines: Med J Aust, 2009; 191; S44-49

30.. Adams WS, A fatal case of otitic cerebellar abscess with contralateral petrositis: Proc R Soc Med, 1938; 31; 1431-44

31.. Bridgewater DL, A case of petrositis: Br Med J, 1944; 2; 470-71

32.. Ogilvie KR, Two cases of petrositis and Gradenigo’s syndrome, treated by conservative surgery and penicillin: J Laryngol Otol, 1945; 60; 445-48

33.. Horowitz S, Gradenigo’s syndrome and report of two cases: J Laryngol Otol, 1948; 62; 639-47

34.. Nako A, Recovery from petrositis associated with meningitis after penicillin treatment: Acta Otolaryngol, 1949; 37; 153-60

35.. Adams WS, A case of petrositis in childhood reviewed fourteen years later: J Laryngol Otol, 1950; 64; 642-44

36.. Gillespie FD, Gradenigo’s syndrome. Report of a case: Va Med Mon (1918), 1962; 89; 501-2

37.. Nicol WF, Petrositis. Report of an unusual case: Ann Otol Rhinol Laryngol, 1964; 73; 255-64

38.. Hilding DA, Petrous apex and subarcuate fossa maturation: Laryngoscope, 1987; 97; 1129-35

39.. Murakami T, Tsubaki J, Tahara Y, Nagashima T, Gradenigo’s syndrome: CT and MRI findings: Pediatr Radiol, 1996; 26; 684-85

40.. Somers TJ, De Foer B, Govaerts P, Chronic petrous apicitis with pericarotid extension into the neck in a child: Ann Otol Rhinol Laryngol, 2001; 110; 988-91

41.. Price T, Fayad G, Abducens nerve palsy as the sole presenting symptom of petrous apicitis: J Laryngol Otol, 2002; 116; 726-29

42.. Jagadeesan P, Madeswaran K, Thiruppathy SP, Gradenigo’s syndrome – a rare complication of otitis media: J Indian Med Assoc, 2002; 100; 669-70

43.. Park SN, Yeo SW, Suh BD, Cavernous sinus thrombophlebitis secondary to petrous apicitis: A case report: Otolaryngol Head Neck Surg, 2003; 128; 284-86

44.. Espay AJ, Bull RL, Petrositis in Ramsay Hunt syndrome with multiple cranial neuropathies: Arch Neurol, 2005; 62; 1774-75

45.. Koral K, Dowling M, Petrous apicitis in a child: Computed tomography and magnetic resonance imaging findings: Clin Imaging, 2006; 30; 137-39

46.. Hafidh MA, Keogh I, Walsh RM, Otogenic intracranial complications. A 7-year retrospective review: Am J Otolaryngol, 2006; 27; 390-95

47.. Zanation AM, Snyderman CH, Carrau RL, Endoscopic endonasal surgery for petrous apex lesions: Laryngoscope, 2009; 119; 19-25

48.. Rossor TE, Anderson YC, Steventon NB, Voss LM, Conservative management of Gradenigo’s syndrome in a child: BMJ Case Rep, 2011; 2011; bcr0320113978

49.. Loretan S, Duvoisin B, Scolozzi P, Unusual fatal petrositis presenting as myofascial pain and dysfunction of the temporal muscle: Quintessence Int, 2011; 42; 419-22

50.. Kong SK, Lee IW, Goh EK, Park SE, Acute otitis media-induced petrous apicitis presenting as the Gradenigo syndrome: Successfully treated by ventilation tube insertion: Am J Otolaryngol, 2011; 32; 445-47

51.. Lammers TH, Krieser DM, Unusual presentation of acute otomastoiditis with petrositis: J Paediatr Child Health, 2013; 49; E457-60

52.. Choi KY, Park SK, Petrositis with bilateral abducens nerve palsies complicated by acute otitis media: Clin Exp Otorhinolaryngol, 2014; 7; 59-62

53.. Plodpai Y, Hirunpat S, Kiddee W, Gradenigo’s syndrome secondary to chronic otitis media on a background of previous radical mastoidectomy: A case report: J Med Case Rep, 2014; 8; 217

54.. Karunakaran T, Kaneshamoorthy M, Harris R, Clivus erosions following Gradenigo’s syndrome-mastoiditis causing VI nerve palsy: BMJ Case Rep, 2016; 2016; bcr2016214604

55.. Kazemi T, acute otitis media-induced Gradenigo syndrome, a dramatic response to intravenous antibiotic: Iran J Otorhinolaryngol, 2017; 29; 165-69

56.. Jensen PV, Avnstorp MB, Dzongodza T, A fatal case of Gradenigo’s syndrome in Zimbabwe and the Danish-Zimbabwean ENT collaboration: Int J Pediatr Otorhinolaryngol, 2017; 97; 181-84

57.. Ghani S, Likeman M, Lyttle MD, New onset strabismus in association with ear pain: Arch Dis Child Educ Pract Ed, 2017; 102; 267-69

58.. Solms J, Evangelista M, Gourishankar A, A child with right ear pain and a gaze palsy: Clin Pediatr, 2017; 56; 1072-74

59.. Brunet-Garcia A, Barrios-Crispi MV, Faubel-Serra M, Carotid canal bone erosion. Gradenigo’s syndrome: Acta Otorrinolaringol Esp, 2018; 69; 246-47

60.. Al-Juboori A, Al Hail AN, Gradenigo’s syndrome and labyrinthitis: Conservative versus surgical treatment: Case Rep Otolaryngol, 2018; 2018; 6015385

61.. Özkaçmaz S, Acute otitis media associated with Gradenigo syndrome and transverse sinus thrombosis: A case report: J Int Med Res, 2019; 47; 1348-52

62.. Athapathu AS, Bandara ER, Aruppala AA, A child with Gradenigo syndrome presenting with meningism: A case report: BMC Pediatr, 2019; 19; 350

63.. Mancini AJ, Glassman RD, Chang YM, Headache in petrous apicitis: A case report of chronic migraine-like headache due to peripheral pathology: Headache, 2019; 59; 1821-26

64.. Brambilla A, Pasti M, Parri N, Sudden diplopia at a Pediatric Emergency Department: A case of Gradenigo syndrome in a child: Pediatr Emerg Care, 2019; 35; e236-37

65.. Demir B, Abuzaid G, Ergenc Z, Kepenekli E, Delayed diagnosed Gradenigo’s syndrome associated with acute otitis media: SAGE Open Med Case Rep, 2020; 8; 2050313 X20966119

66.. Chowdhary S, Alexander A, Thangavel S, Penubarthi LK, ‘Masked’ petrous apicitis presenting with lateral rectus palsy: BMJ Case Rep, 2021; 14; e244401

67.. Malic M, Milicic B, Gjuric M, Unrecognized petrous apicitis as a cause of long-lasting headache in a 5-year-old child: Case report: J Int Adv Otol, 2021; 17; 468-70

68.. Liu Y, Yeh PK, Lin YP, Sung YF, Steroid-responsive Gradenigo’s syndrome mimicking subdural hematoma: Cureus, 2021; 13; e19547

69.. Bano S, Nawaz A, Asmar A, Gradenigo’s syndrome presenting as IX and X cranial nerve palsy without clinically apparent ear infection: A case report and review of literature: eNeurologicalSci, 2022; 27; 100397

70.. Nassrallah WB, de Tilly LN, Micieli JA, Case of petrous apicitis after COVID-19 infection: J Neuroophthalmol, 2022; 42; 10-97

71.. Brook I, Fusobacterial head and neck infections in children: Int J Pediatr Otorhinolaryngol, 2015; 79; 953-58

72.. Le Monnier A, Jamet A, Carbonnelle E: Pediatr Infect Dis J, 2008; 27; 613-17

73.. Megged O, Assous MV, Miskin H, Neurologic manifestations of Fusobacterium infections in children: Eur J Pediatr, 2013; 172; 77-83

74.. Weille FL, Superior petrosal and cavernous sinus thrombosis and basal petrositis; Observed as complication of destructive labyrinthitis with facial paralysis: Arch Otolaryngol, 1947; 45; 90-104

75.. Bradburn I, Mastoiditis, petrositis and lateral sinus thrombosis; Report of an unusual case: AMA Arch Otolaryngol, 1953; 57; 83-85

76.. Eby LG, Petrositis and lateral sinus thrombosis due to antibiotic-resistant infections: Laryngoscope, 1961; 71; 1165-85

77.. Hiranandani LH, Tuberculous petrositis. A case report: Laryngoscope, 1967; 77; 1723-28

78.. Hendershot EL, Wood JW, Bennhoff D, The middle cranial fossa approach to the petrous apex: Laryngoscope, 1976; 86; 658-63

79.. Kohut RI, Lindsay JR, Necrotizing (“malignant”) external otitis histopatho-logic processes: Ann Otol Rhinol Laryngol, 1979; 88; 714-20

80.. Chole RA, Donald PJ, Petrous apicitis. Clinical considerations: Ann Otol Rhinol Laryngol, 1983; 92; 544-51

81.. Stamm AC, Pinto JA, Cóser PL, Marigo C, Nonspecific necrotizing petrositis: An unusual complication of otitis in children: Laryngoscope, 1984; 94; 1218-22

82.. Kearns DB, Coker NJ, Pitcock JK, Jenkins HA, Tuberculous petrous apicitis: Arch Otolaryngol, 1985; 111; 406-8

83.. Horn KL, Erasmus MD, Akiya FI, Suppurative petrous apicitis: Osteitis or osteomyelitis? An imaging case report: Am J Otolaryngol, 1996; 17; 54-57

84.. 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

85.. Minotti AM, Kountakis SE, Management of abducens palsy in patients with petrositis: Ann Otol Rhinol Laryngol, 1999; 108; 897-902

86.. Fitzgerald DC, Nasopharyngeal abscess and facial paralysis as complications of petrous apicitis: A case report: Ear Nose Throat J, 2001; 80; 305-12

87.. Finkelstein Y, Marcus N, Mosseri R: Int J Pediatr Otorhinolaryngol, 2003; 67; 815-17

88.. Trimis G, Mostrou G, Lourida A, Petrositis and cerebellar abscess complicating chronic otitis media: J Paediatr Child Health, 2003; 39; 635-36

89.. Crossland GJ, De R, Higgins JN, Axon PR, Two stage management of petrositis with associated mycotic aneurysm of the intrapetrous carotid artery: J Laryngol Otol, 2005; 119; 479-82

90.. Lee YH, Lee NJ, Kim JH, Song JJ, CT, MRI and gallium SPECT in the diagnosis and treatment of petrous apicitis presenting as multiple cranial neuropathies: Br J Radiol, 2005; 78; 948-51

91.. Sethi A, Sabherwal A, Gulati A, Sareen D, Primary tuberculous petrositis: Acta Otolaryngol, 2005; 125; 1236-39

92.. Visosky AM, Isaacson B, Oghalai JS, Circumferential petrosectomy for petrous apicitis and cranial base osteomyelitis: Otol Neurotol, 2006; 27; 1003-13

93.. Sethi A, Sethi D, Mrig S, Coexistent acute pyogenic and tubercular petrous apicitis: A diagnostic dilemma: J Laryngol Otol, 2006; 120; 875-78

94.. Isaacson B, Mirabal C, Kutz JW, Pediatric otogenic intracranial abscesses: Otolaryngol Head Neck Surg, 2010; 142; 434-37

95.. Pollock TJ, Kim P, Sargent MA, Ophthalmic complications of otitis media in children: J AAPOS, 2011; 15; 272-75

96.. Dumas G, Schmerber S, Atallah I, Subacute tuberculous otitis media complicated by petrositis and meningitis: Rev Laryngol Otol Rhinol, 2012; 133; 221-24

97.. Colpaert C, Van Rompaey V, Vanderveken O, Intracranial complications of acute otitis media and Gradenigo’s syndrome: B-ENT, 2013; 9; 151-56

98.. Bhatt YM, Pahade N, Nair B, Aspergillus petrous apicitis associated with cerebral and peritubular abscesses in an immunocompetent man: J Laryngol Otol, 2013; 127; 404-7

99.. Chen PY, Wu CC, Yang TL, Gradenigo syndrome caused by nontuberculous mycobacteria: Audiol Neurootol, 2014; 19; 275-82

100.. Valles JM, Fekete R, Gradenigo syndrome: Unusual consequence of otitis media: Case Rep Neurol, 2014; 6; 197-201

101.. Jensen PV, Hansen MS, Møller MN, Saunte JP, The forgotten syndrome? Four cases of Gradenigo’s syndrome and a review of the literature: Strabismus, 2016; 24; 21-27

102.. Janjua N, Bajalan M, Potter S, Multidisciplinary care of a paediatric patient with Gradenigo’s syndrome: BMJ Case Rep, 2016; 2016; bcr2015214337

103.. Do Vale J, Mezhari I, Oker N, Roux D, Keep an ear to the ground, the answer’s behind: Intensive Care Med, 2016; 42; 440-42

104.. Vitale M, Amrit M, Arora R, Lata J, Gradenigo’s syndrome: A common infection with uncommon consequences: Am J Emerg Med, 2017; 35; 1388-e1

105.. Dorner RA, Ryan E, Carter JM, Gradenigo syndrome and cavitary lung lesions in a 5-year-old with recurrent otitis media: J Pediatric Infect Dis Soc, 2017; 6; 305-8

106.. Taklalsingh N, Falcone F, Velayudhan V, Gradenigo’s syndrome in a patient with chronic suppurative otitis media, petrous apicitis, and meningitis: Am J Case Rep, 2017; 18; 1039-43

107.. Shapiro D, Vaiyani D, Horlbeck D, Pattishall S, Case 1: Otorrhea, otalgia, and blurry vision in an 11-year-old girl: Pediatr Rev, 2017; 38; 566

108.. Bozan N, Düzenli U, Yalinkilic A, Gradenigo syndrome induced by suppurative otitis media: J Craniofac Surg, 2018; 29; e645-46

109.. Rossi N, Swonke ML, Reichert L, Young D, Gradenigo’s syndrome in a four-year-old patient: A rare diagnosis in the modern antibiotic era: J Laryngol Otol, 2019; 133; 535-37

110.. Patel PD, Meybodi AT, Agarwalla P, Rapid recovery of cranial nerve deficits after anterior petrosal (Kawase) approach for medically refractory petrous apicitis: World Neurosurg, 2020; 140; 122-27

111.. Hodges J, Matsumoto J, Jaeger N, Wispelwey B, Gradenigo’s syndrome and bacterial meningitis in a patient with a petrous apex cholesterol granuloma: Case Rep Infect Dis, 2020; 2020; 8822053

112.. Chandran A, Sagar P, Monga R, Singh S, Unusual manifestation of Koch’s disease: Gradenigo-Lannois syndrome: BMJ Case Rep, 2020; 13; e236779

113.. Guimaraes GC, de Freitas PP, da Silva VA, Castilho AM, Conservative management of petrous apex abscess and Gradenigo’s syndrome in a diabetic patient: Case report and literature review: Clin Case Rep, 2021; 9; 742-46

114.. Isaac H, Liu A, Shibata SB, Hansen MR, Transmastoid and transtemporal drainage of petrous apicitis with otitis media: Ann Otol Rhinol Laryngol, 2021; 130; 314-18

115.. Sattarova V, Gencturk M, Lee MS, McClelland CM, Gadoxetate disodium-enhanced imaging of Gradenigo syndrome in end-Stage renal disease: J Neuroophthalmol, 2021; 41; e375-77

116.. Quesada J, Kong A, Tweddle E, An unusual case of acute otitis media resulting in Gradenigo syndrome: CT and MRI findings: Radiol Case Rep, 2021; 16; 3903-7

117.. Bonavia L, Jackson J, Gradenigo syndrome in a 14-year-old girl as a consequence of otitis media with effusion: J Neuroophthalmol, 2022; 42; e408-9

118.. Jin L, Liu S, Tan S, Petrositis caused by fluconazole-resistant candida: Case report and literature review: BMC Infect Dis, 2022; 22; 649

119.. Chan KC, Chen SL, Diplopia in a child: Gradenigo syndrome is an unforgettable disease: Ear Nose Throat J, 2023; 102; NP53-55

120.. Kehayov II, Angelova PM, Kitov BD: J Infect Dev Ctries, 2023; 17; 418-22

121.. Saldanha M, Nayar V, Augustine BA, Shenoy RD, Acute bacterial meningitis and petrous apicitis in a child with aplasia cutis congenita: A case report: J Int Adv Otol, 2023; 19; 355-59

122.. Schuetz AN, Antimicrobial resistance and susceptibility testing of anaerobic bacteria: Clin Infect Dis, 2014; 59; 698-705

Figures

Figure 1.. Gram stain of Fusobacterium necrophorum isolated from blood culture, demonstrating characteristic pleomorphic gram-negative bacilli. Scale bar is 50 µm.Figure 2.. Axial computed tomography scan demonstrating otomastoiditis (lateral arrow) extending into the petrous apex where there is expansion with a gas and fluid collection (medial arrow).Figure 3.. Axial time-of-flight magnetic resonance angiography demonstrating severe narrowing of the petrous segment of the right internal carotid artery (ICA; left-sided arrow) and normal caliber of the petrous segment of the left ICA (right-sided arrow).Figure 4.. (A) Three-dimensional (3D) time-of-flight magnetic resonance angiography (MRA) demonstrating severe narrowing of the petrous and cavernous segments of the right internal carotid artery (ICA; 2 left-sided arrows). (B) 3D time-of-flight MRA 3 months after treatment demonstrating significantly improved caliber of the petrous and cavernous segments of the right ICA (2 left-sided arrows).Figure 5.. (A) Axial post-gadolinium T1-weighted magnetic resonance imaging (MRI) during hospital admission demonstrating right-sided otomastoiditis (lateral arrow) with petrous apicitis and minimal contrast enhancement of the ipsilateral petrous internal carotid artery (ICA; medial arrow). (B) Axial post-gadolinium T1-weighted MRI 3 months after treatment demonstrating resolution of otomastoiditis (lateral arrow) and significantly improved ipsilateral petrous ICA caliber (medial arrow).Figure 6.. (A) Axial post-gadolinium T1-weighted magnetic resonance imaging (MRI) during hospital admission demonstrating right-sided cavernous sinus thrombosis with reduced ipsilateral cavernous internal carotid artery (ICA) caliber (left-sided arrow). (B) Axial post-gadolinium T1-weighted MRI 3 months after treatment showing resolution of cavernous sinus thrombosis with significantly improved ipsilateral cavernous ICA caliber (left-sided arrow).

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923