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Radiol Case Rep
Radiol Case Rep
Radiology Case Reports
1930-0433
Elsevier

S1930-0433(24)00789-1
10.1016/j.radcr.2024.08.002
Case Report
Insights into Gradenigo syndrome: Case presentation and review
Horache Kenza kenza.horache@gmail.com
⁎
Jidal Manal
ElOuali Ibtissam
Saouab Rachida
Elfenni Jamal
Radiology Department, Mohammed V military hospital of Rabat, Rabat, Morocco
⁎ Corresponding author. kenza.horache@gmail.com
03 9 2024
11 2024
03 9 2024
19 11 54425446
18 6 2024
31 7 2024
2 8 2024
© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Gradenigo syndrome (GS) is characterized by a triad of clinical features: abducens nerve palsy, retro-orbital pain, and otorrhea, arising as a complication of suppurative otitis media. Herein, we present a case of GS in a 15-year-old male patient, secondary to left otitis media. The patient exhibited fever, otorrhea, accompanied by diplopia, retrobulbar pain, and headache. Imaging studies demonstrated petrous bone destruction and inflammatory changes with opacification of petrous bone, mastoid cells and surrounding structures, confirming the diagnosis of GS. Treatment included intravenous antibiotics and anticoagulants, resulting in the resolution of symptoms and radiological improvement. GS, though rare, warrants prompt recognition and appropriate management to prevent severe complications. Diagnostic imaging plays a crucial role in evaluation, and treatment often involves prolonged antibiotic therapy and, in severe cases, surgical intervention. Understanding the clinical presentation and management strategies is essential for clinicians encountering this condition.

Keywords

Gradenigo syndrome
Petrous apicitis
Abducens nerve palsy
Retro-orbital pain
Otitis media
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pmcIntroduction

Gradenigo syndrome (GS) is a rare but clinically significant complication of suppurative otitis media, characterized by a classic triad of symptoms including abducens nerve palsy, retro-orbital pain, and otorrhea [1].

The syndrome typically arises due to apical petrositis, an inflammatory process affecting the petrous apex of the temporal bone. This region's proximity to critical neurovascular structures such as the abducens and trigeminal nerves renders them susceptible to compression and inflammation, leading to the characteristic clinical presentation. Although the incidence of GS has decreased with widespread antibiotic use, it remains crucial for clinicians to maintain a high index of suspicion, particularly in pediatric patients presenting with suggestive symptoms [2].

Herein, we present a case of GS in a 15-year-old male secondary to left otitis media, emphasizing the diagnostic challenges and therapeutic strategies essential for managing this condition effectively. The case underscores the role of diagnostic imaging, including CT and MRI, in confirming the diagnosis and guiding therapeutic interventions.

Understanding the clinical presentation, diagnostic modalities, and management principles of GS is paramount for clinicians encountering this rare yet significant condition. This article aims to enhance awareness and provide insights into the optimal management of Gradenigo syndrome, thereby contributing to improved patient outcomes.

Case report

We present a case of successfully treated Gradenigo syndrome in a 15-year-old male patient, which occurred as a complication of left otitis media.

The patient was admitted to the otorhinolaryngology department exhibiting symptoms of fever, otorrhea, and swelling of posterior part of the left ear, along with diplopia, retrobulbar pain, and headache. These symptoms emerged following a 3-week course of topical antibiotic treatment for left otitis media with effusion, which was subsequently confirmed to be positive for Streptococcus pyogenes.

Clinical examination revealed purulent discharge from the left ear, accompanied by erythema over the mastoid tip, and a sixth cranial nerve palsy with left tympanic perforation.

His vital signs were normal and no meningism or other cranial nerve palsy was identified.

Laboratory investigations demonstrated a white blood cell count of 15 × 10^9cells/L with 65% neutrophils, along with elevated levels of C-reactive protein (50 mg/L).

CT scan showed (Fig. 1):- Left-sided mastoiditis with opacification and fluid filled middle ear and petromastoid cells.

- Rim-enhancing lesion around the petrous apex.

- Rim-enhancing retropharyngeal lesion suggesting retropharyngeal abscess or necrotic retropharyngeal lymphadenopathy.

Fig. 1 CT scan showing: (A) opacification of the petromastoid left air cells and the middle ear (white arrow). (B) Rim enhancing lesion around the petrous apex (red arrow). (C) Rim enhancing retropharyngeal lesion (yellow arrow).

Fig 1:

MRI demonstrated (Fig. 2, Fig. 3):- Left-sided mastoid opacification (Fig. 2).

- FLAIR hyperintensity of the left petrous apex with hyperintensity on the diffusion weighted image and heterogeneous enhancement pattern, extending to surrounding tissue (Fig. 2, Fig. 3).

- Rim-enhancement retropharyngeal lesion (Fig. 3).

Fig. 2 MRI of the brain: (A) Noncontrast coronal T2-weighted MRI demonstrating left mastoid opacification (white arrow). (B) FLAIR MRI shows hyperintensity suggestive of fluid within the petrous temporal bone (red arrow). (C) Post gadolinium contrast T1 axial shows ring-enhancing lesion at the petrous apex (red arrow). (D) The lesion with hyperintensity in axial diffusion-weighted image (DWI) (red arrow).

Fig 2:

Fig. 3 MRI showing Extensive and heterogenous enhancement in surrounding structures (A) (white arrow) with retropharyngeal lesion with hyperintensity in FLAIR (B) and rim enhancement (C) (red arrow).

Fig 3

On the basis of the radiological finding, a diagnosis of Gradenigo syndrome secondary to Streptococcus pyogenes was made.

Intra-venous antibiotic treatment including vancomycine and ceftriaxone was started immediately. The abducens nerve palsy resolved within 10 days following the initiation of intravenous antibiotics. After 6 weeks of intravenous and oral antibiotic therapy, a follow-up CT scan confirmed radiological resolution. It demonstrated significant improvement in the aeration of mastoid cells and the middle ear, along with resolution of the petrous lesion and retropharyngeal adenopathy (Fig. 4).Fig. 4 (A) Axial brain CT scan centered on the left petrous bone showing significant improvement in the aeration of mastoid cells and the middle ear (white arrow). (B and C) Axial contrast-enhanced brain CT scan demonstrating the resolution of retropharyngeal lymphadenopathy and petrous abscess (red arrows).

Fig 4:

Discussion

Gradenigo syndrome (GS), first documented by Guiseppe Gradenigo in 1907 [1,3], represents a rare but potentially life-threatening complication of untreated or partially treated otitis media [4]. Otitis media is a common infection usually managed effectively with antimicrobial therapy, and the incidence of intracranial complications is low, affecting only 0.04%-0.15% of cases [4]. In the discussed case, the patient received local antibiotic therapy to treat their otitis media, which could potentially explain the occurrence of Gradenigo's syndrome. Indeed, there is currently no strong evidence to support the use of topical antibiotics in children with acute otitis media and ear discharge, and the use of oral antibiotics is recommended [5].

GS tends to affect the pediatric population, with a median age around 12 years, without showing significant gender predilection [6]. Mortality rates in both pediatric and nonpediatric populations range between 2% and 2.6% [6].

The syndrome arises from the inflammation of the petrous apex, termed “petrous apicitis (PA),” likely originating in the middle ear and spreading to petrous apex of the temporal bone, resulting in localized osteomyelitis and reactive meningitis [1]. The petrous apex has critical proximity to vascular and neuronal structures [7]. Notably, the abducens nerve passes through the Dorello canal, situated medially to the petrous apex, towards the cavernous sinus [3,6], while the trigeminal nerve lies laterally to the petrous apex [6]. Since these nerves are only separated from the petrous apex by dura, they are easily affected by the inflammatory process [1].

GS typically presents as paralysis of the sixth cranial nerve, retro-orbital or maxillary pain in the distribution of the trigeminal nerve, and otorrhea [1]. However, not all patients with GS exhibit the complete triad of symptoms, leading to the identification of incomplete GS [7]. Actually, out of the original 57 cases described by Gradenigo, less than 50% presented with the complete triad [8]. Additionally, involvement of the seventh and eighth cranial nerves in GS has been described [9].

The prolonged duration of symptoms preceding presentation in patients with both classic and incomplete GS can be attributed to the gradual progression of otitis media spreading from the mastoid and petrous bone, and the subsequent development of CN VI palsy. This phenomenon elucidates why documented cases in the medical literature describe a time interval ranging from 1 week to 2-3 months from the onset of acute otitis media to the manifestation of the sixth nerve palsy [3]. Nonetheless, this observation likely highlights the limited awareness among primary care physicians regarding this rare yet serious condition. The sudden onset of abducens nerve palsy in a pediatric patient, accompanied by at least 1 additional sign or symptom from the original triad, should prompt clinicians to consider the possibility of this uncommon infection. The absence of otitis media with or without aural discharge, or the absence of trigeminal nerve pain, should not dissuade clinicians from actively pursuing a prompt diagnosis.

Diagnostic imaging, including CT and MRI, plays a crucial role in the evaluation of petrous apicitis and guides the appropriate surgical approach [3,6].

CT scans provide visualization of bony structures and mastoid air cell anatomy [2], while MRI is preferred for assessing neural and vascular involvement and potential intracranial spread [7].

In case of infectious petrositis, lesions typically appear hypointense on T1-weighted and hyperintense in T2-weighted images. Abscess formation may present with a rim of gadolinium enhancement and hyperintensity on diffusion-weighted imaging [3]. Osteomyelitis typically appears as a hypointense lesion on T1-weighted images, distinguishable from normal bone marrow, which appears hyperintense on T1-weighted images [3,9].

Various conditions can mimic GS by presenting symptoms similar to the classical GS triad, without solely originating from petrous apicitis. These conditions include infections, inflammations, prothrombotic states and coagulopathies, Lemierre's syndrome, Tolossa-Hunt syndrome, and malignancies such as schwannoma, meningioma, chondroma, and chordoma [7,8].

Treatment of GS often involves drainage and extended courses of intravenous antibiotics, given that causative agents frequently include alpha and beta-hemolytic streptococcus species, Staphylococcus, Escherichia coli and Pseudomonas aeruginosa [6,8]; antibiotics should cover theses pathogens. Examples of such regimens include vancomycin, second or third generation cephalosporins, and fluoroquinolones [8]. Surgical intervention is reserved for severe cases involving abscess formation or osteomyelitis necessitating surgical debridement [10].

Steroid can be used to help reduce inflammation and facilitate the healing of the cranial nerves [11].

Patients with complications such as venous sinus thrombosis may be treated with anticoagulants, although the use of anticoagulants remains debatable [3].

Symptoms of GS typically resolve completely within an average period of 4 to 6 weeks in the pediatric cohort [6]. Potential sequelae of GS encompass a spectrum of complications, including meningitis, dural venous sinus thrombosis, labyrinthine fistula, intracranial abscess, skull base inflammation, facial nerve palsy, parapharyngeal abscess, Vernet's syndrome and hydrocephalus [2,12].

Conclusion

Gradenigo syndrome represents a rare yet clinically significant complication of otitis media. Prompt recognition and appropriate treatment, including antibiotics and, when necessary, surgical intervention, are essential for favorable outcomes. Diagnostic imaging is pivotal in confirming the diagnosis and guiding management. Continued awareness and understanding of Gradenigo syndrome are crucial for optimizing patient care and preventing severe complications.

Patient consent

Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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References

1 Ibrahim M Shah G Parmar H. Diffusion-weighted MRI identifies petrous apex abscess in Gradenigo syndrome J Neuroophthalmol 30 1 2010 34 36 10.1097/WNO.0b013e3181c5d0fd 20182204
2 Chan KC Chen SL. Diplopia in a child: Gradenigo syndrome is an unforgettable disease Ear Nose Throat J 102 2 2023 NP53 NP55 10.1177/0145561321989459 33507110
3 Jensen PV Hansen MS Møller MN Saunte JP. The forgotten syndrome? Four cases of Gradenigo's syndrome and a review of the literature Strabismus 24 1 2016 21 27 10.3109/09273972.2015.1130067 26979620
4 Bowman C Nakhla N Amedu V Patel P O’Connor C Houston A A rare complication of otitis media: Gradenigo’s syndrome successfully managed on outpatient antimicrobial therapy Clin Infect Pract 3–4 2020 100012 10.1016/j.clinpr.2019.100012
5 Venekamp RP Prasad V Hay AD. Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge? BMJ 352 2016 i308 10.1136/bmj.i308 26848130
6 Bonavia L Jackson J. Gradenigo syndrome in a 14-year-old girl as a consequence of otitis media with effusion J Neuroophthalmol 42 1 2022 e408 e409 10.1097/WNO.0000000000001278 34001731
7 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 132 2020 109942 10.1016/j.ijporl.2020.109942
8 Tornabene S Vilke GM. Gradenigo's syndrome J Emerg Med 38 4 2010 449 451 10.1016/j.jemermed.2007.08.074 18296009
9 Pedroso JL de Aquino CC Abrahão A de Oliveira RA Pinto LF Bezerra ML Gradenigo's syndrome: beyond the classical triad of diplopia, facial pain and otorrhea Case Rep Neurol. 3 1 2011 45 47 10.1159/000324179 21490711
10 Bozan N Düzenli U Yalinkilic A Ayral A Parlak M Turan M Gradenigo syndrome induced by suppurative otitis media J Craniofac Surg 29 7 2018 e645 e646 10.1097/SCS.0000000000004660 29894453
11 Jacob A Alsarhan A Nazir T Kherani S Bitar MA. Beyond Gradenigo syndrome: facial palsy and cavernous sinus involvement in a young teenage girl Otolaryngol Case Rep 22 2022 100396 10.1016/j.xocr.2022.100396 ISSN 2468-5488
12 Rossor TE Anderson YC Steventon NB Voss LM Conservative management of Gradenigo’s syndrome in a child BMJ Case Rep 2011 2011 bcr0320113978 10.1136/bcr.03.2011.3978
