Gradenigo syndrome is a syndrome caused by the spread of infection and inflammation to the petrous apex of the temporal bone. It was reported in 1904 by the Italian otolaryngologist Giuseppe Gradenigo.
The classic triad consists of the following three findings:
However, the complete triad was present in less than 50% of Gradenigo’s original 57 cases 3). According to McLaren et al., the classic type is defined as “otitis media + abducens nerve palsy + trigeminal neuralgia + imaging evidence of petrous apicitis,” and the incomplete type as “two or more of the triad + imaging evidence of petrous apicitis” 6).
Epidemiology: the median age of onset is 12 years, with no sex predilection 3, 6). Before antibiotics, the complication rate of ear infections was 2.3–6.4%, but it has now markedly decreased to 0.04–0.15%. Mortality is reported as 2–2.6% in both children and adults 3, 6).
With the widespread use of antibiotics, the incidence of ear infection complications has decreased significantly. The current rate of ear infection complications is about 0.04–0.15%, and even literature reviews since 1990 report limited cases. The median age of onset is 12 years, and mortality is 2–2.6% 3, 6).
Yes. “Masked” cases have been reported where petrous apicitis progresses latently with minimal or absent ear symptoms due to inadequate antibiotic use 7). Adult cases presenting only with lateral rectus palsy also exist. Diagnosis requires keeping in mind that incomplete forms account for more than 50% of cases.
The most common cause of Gradenigo syndrome is untreated or inadequately treated acute otitis media (AOM). Infection spreads from the middle ear through the mastoid air cells and cell tracts to the petrous apex. Rarely, it can also be caused by cholesteatoma, chronic osteomyelitis, or non-infectious causes (lymphoma, hypertrophic pachymeningitis, epidural abscess).
The main causative organisms are listed below.
| Causative organism | Notes |
|---|---|
| Pseudomonas aeruginosa | Most common causative organism of petrous apicitis4) |
| Streptococcus pneumoniae | Main causative organism of pediatric AOM |
| Group A Streptococcus (Streptococcus pyogenes) | Common in children |
| Haemophilus influenzae | Common in children |
| Staphylococcus aureus | including MRSA |
| Escherichia coli | Adults and immunocompromised patients |
| Varicella-zoster virus | Rare cause in immunocompromised patients1) |
Diagnosis is based on the clinical triad, but note that incomplete forms are common. Diagnosis is made by combining at least two of abducens nerve palsy, facial pain, and ear symptoms with imaging findings of petrous apicitis (McLaren’s criteria for incomplete forms)6).
CT (Temporal Bone)
Evaluation of bone destruction: Detects bone destruction and soft tissue opacity in the petrous apex. Useful for assessing pneumatization and having a low false-positive rate.
Limitations: Destruction is detectable only after 30–50% of bone is demineralized, so early lesions may be missed5). Findings may appear nearly normal in early infection or after antibiotic treatment.
MRI (Brain and Temporal Bone)
Soft tissue evaluation: Depicts petrous apex lesions with low T1 and high T2 signal. Superior to CT in detecting involvement of nerves and vessels and intracranial complications5).
DWI: Restricted diffusion (high signal with low ADC) suggests abscess formation5).
Contrast-enhanced MRI: Ring enhancement indicates abscess, and dural thickening around Meckel’s cave suggests inflammatory spread to the trigeminal nerve 5, 6). Abnormal enhancement in the cavernous sinus reflects the mechanism of abducens nerve palsy.
The mainstay is long-term intravenous administration of high-dose broad-spectrum antibiotics. Since Pseudomonas aeruginosa is the most common causative organism of petrous apicitis, coverage for Pseudomonas aeruginosa is important when selecting antibiotics4). Before culture results are available, empiric therapy should include broad-spectrum antibiotics covering both gram-negative and gram-positive organisms, including Pseudomonas aeruginosa.
The main reported antibiotic regimens are shown below.
| Regimen | Main coverage | Source |
|---|---|---|
| Vancomycin + Ceftriaxone | MRSA + Gram-negative bacteria | 3) |
| Ceftazidime + Cefazolin | Pseudomonas aeruginosa + Gram-positive bacteria | 4) |
| Piperacillin/Tazobactam | Pseudomonas aeruginosa + broad spectrum | 2) |
| Benzylpenicillin + Clindamycin | Streptococcal type | 5) |
| Vancomycin + Cefepime | For immunocompromised patients | 1) |
Intravenous antibiotics are typically given for 2 to 6 weeks, followed by a switch to oral antibiotics3, 6). In children, 4 to 6 weeks of treatment is expected to result in complete resolution of symptoms. Radiographic improvement is also a criterion for discontinuing treatment.
Surgery is considered when there is no response to medical therapy, in cases of osteomyelitis requiring sequestrectomy, or when an abscess forms. Timely surgical decision-making is important to avoid permanent nerve palsy or death7).
Surgery is indicated when antibiotic therapy alone is insufficient, when sequestrectomy is needed for osteomyelitis, or when abscess formation is confirmed. The surgical approach is selected from mastoidectomy, infralabyrinthine approach, or petrosectomy depending on the extent of the lesion and the need for hearing preservation7).
Infection spreads from the middle ear to the mastoid air cells and then to the petrous apex. The mastoid air cells contain vascular-rich bone marrow and are prone to infection, reaching the petrous apex through pneumatized cell tracts. Routes of spread include direct invasion, the labyrinthine route via the round and oval windows, and hematogenous or thrombophlebitic routes.
The petrous apex is located between the inner ear and the clivus. It is divided into anterior and posterior parts by the internal auditory canal, with the anterior part more commonly involved in disease. The degree of pneumatization varies among individuals: 33% of normal temporal bones are pneumatized, 60% are spongy (filled with bone marrow), and 7% are sclerotic 5). Cases with a pneumatized petrous apex are more prone to forming routes for infection spread.
The course of the abducens nerve is as follows:
In Dorello’s canal, the abducens nerve is separated from the petrous apex by only a single layer of dura. Similarly, the trigeminal ganglion is located in Meckel’s cave, adjacent to the lateral side of the petrous apex3). Inflammation or abscess of the petrous apex can spread to the perineural spaces of these nerves, causing abducens nerve palsy and trigeminal neuralgia.
Widespread use of antibiotics partially suppresses inflammation. This prevents direct spread to the nerves, and incomplete forms, in which some of the classic triad do not appear, account for more than 50% of all cases7).
If Gradenigo syndrome is not treated or becomes severe, the main complications that may occur are as follows.
Horache et al. (2024) reported that in children, complete resolution of signs and symptoms of Gradenigo syndrome is expected within 4 to 6 weeks of treatment3). Recovery of abducens nerve palsy varies from 1 day to 10 days to several weeks depending on the report2, 3, 5, 6).
The majority achieve complete recovery with conservative antibiotic therapy. In some patients, neurological function may not fully recover. The major long-term sequela is hearing loss.
If left untreated, the condition can be fatal. Timely diagnosis and initiation of treatment greatly influence the prognosis.
Benavente K, et al. The risks of rejection vs. infection: Ramsay Hunt syndrome, Gradenigo syndrome, and varicella meningoencephalitis in a heart transplant patient. Eur Heart J Case Rep. 2023.
Li SB, et al. Incomplete Gradenigo Syndrome in a Patient With Mastoiditis and Lateral Sinus Thrombosis. J Neuro-Ophthalmol. 2023.
Horache K, et al. Insights into Gradenigo syndrome: Case presentation and review. Radiol Case Rep. 2024.
Tao BK, et al. Ceftazidime-Cefazolin Empiric Therapy for Pediatric Gradenigo Syndrome. Ann Otol Rhinol Laryngol. 2025.
Quesada J, et al. An unusual case of acute otitis media resulting in Gradenigo syndrome: CT and MRI findings. Radiol Case Rep. 2021.
Bonavia L, Jackson J. Gradenigo Syndrome in a 14-Year-old Girl as a Consequence of Otitis Media With Effusion. J Neuro-Ophthalmol. 2022.
Chowdhary S, et al. ‘Masked’ petrous apicitis presenting with lateral rectus palsy. BMJ Case Rep. 2021.
