Acute suppurative otitis media is defined as a suppurative infection involving the mucosa of the middle ear cleft. By convention, it is termed acute if the infection is less than 3 weeks in duration. Obstruction of the eustachian tube seems to be the most important antecedent event in the pathophysiology of acute suppurative otitis media.[1,2] The majority of cases of acute suppurative otitis media are triggered by upper respiratory infections, which seed the middle ear cavity through the eustachian tube orifice. Infections involving the nasopharynx can infect the middle ear through the pharyngeal end of the eustachian tube. Most commonly, the infection is viral in origin; however, allergic symptoms may also play an important role in the pathogenesis. Pathogenic bacteria can secondarily infect the middle ear mucosa. The bacteria that commonly cause this disorder are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.[3] To become pathogenic, the bacteria must become adherent to the mucosal lining of the middle ear cavity. This is possible with prior viral infection of the middle ear mucosa. If the infection persists beyond a period of 2 weeks, then there is an associated thickening of the mucoperiosteum, especially in the air cells around the periantral area that lead to a blockage of the drainage from the antral cells. The trapped secretions in the mastoid air cell system cause intense pressure, venous stasis, and local acidosis. This acidosis causes dissolution of calcium from the bone, causing decalcification and coalescence of the mastoid air cell system. This condition is known as coalescent mastoiditis.[1] This stage is characterized by the emergence of otalgia and low-grade fever. Erosion of the outer mastoid cortex can lead to the formation of an abscess under the periosteum of the mastoid cortex.[1,2,3] Known complications include:
- Mastoiditis
- Petrositis or petrous apicitis (Gradenigo syndrome)
- Facial nerve palsy
- Meningitis
- Venous sinus thrombosis
Gradenigo syndrome, also known as petrous apicitis or apical petrositis, is a rare complication of suppurative otitis media, with only a few cases reported (mostly in the otolaryngology literature). The syndrome is a triad of sixth nerve palsy, pain in the distribution of the trigeminal nerve, and otitis media.[2] It was first described by Giuseppe Gradenigo in 1904; the incidence has since diminished with the advent of antibiotic use. In his original description of the disease, only 42% of the cases he described exhibited the classical triad. The neurologic manifestations of Gradenigo syndrome are attributed to the involvement of the fifth and sixth nerves, which are only separated from the inflamed petrous bone apex by the dura matter.[5] The temporal bone not only contains the organs for hearing, balance, and sound conduction, but it also contributes to the cranial vault and zygoma.[1] The temporal bones are situated at the sides and base of the skull and consist of five parts: the squama, mastoid, petrous, tympanic, and styloid process. The petrous portion, called the petrous pyramid, contains the otic and labyrinth. Superiorly, it forms the inferior surface of the middle cranial fossa. Posteriorly, it is bounded by the attachment of the tentorium cerebelli, and together with the mastoid portion it helps to form the anterior face of the posterior cranial fossa. At the petrous apex, there is a hiatus between the tentorium and the petrous that forms a canal for the fifth cranial nerve (Meckel cave). The sixth cranial nerve runs through a notch just below the posterior clinoid process (the medial attachment of the tentorium) and above the articulation of the petrous and sphenoid (Dorello canal).[1]
The inflammatory process spreads from the base (mastoid and middle ear) of the pyramid-shaped os petrosum to the top (petrous apex). This explains why the time interval between the onset of otitis media and the manifestation of cranial nerve dysfunction varies between 1 week and 2-3 months.[5] The complications of Gradenigo syndrome include the following:
- Meningitis
- Intracranial abscess
- Spread to the skull base and involvement of the ninth, tenth, and eleventh cranial nerves; known as Vernet syndrome
- Prevertebral/paravertebral/retropharyngeal abscess
- Spread to the sympathetic plexus around the carotid sheath.
- Labyrinthitis
- Venous sinus thrombosis
- Death
The differential diagnosis of Gradenigo syndrome includes tumors of the petrous apex, such as meningioma, sarcoma, trigeminal neuroma, or metastatic disease. Gradenigo syndrome in children usually results from an infectious etiology. The organisms causing Gradenigo's syndrome are often difficult to recover, and cultures from the middle ear and mastoid or petrous tissue may be negative; however, common organisms recovered include Group A Streptococcus, pneumococcus, Staphylococcus, Pseudomonas aeruginosa, and Mycobacterium tuberculosis.[3]
The evaluation of a patient with suspected Gradenigo syndrome should include neuroimaging. A reasonable initial imaging modality is a CT scan of the head with high resolution to provide detail of the petrous apex, as the test is widely available and can identify abnormalities in bony anatomy. MRI is superior, however, for demonstrating the CNS anatomy and meningeal enhancement, which makes it the ideal test to diagnose Gradenigo syndrome. MRA and/or MRV may be useful in evaluating sigmoid sinus pathology.
Treatment of Gradenigo syndrome must be initiated immediately. The underlying infection must be addressed in order to prevent further spread, complications, or permanent abducens nerve injury. The advent of the antibiotic era has facilitated the conservative management of a select cohort of patients with apical petrositis. It is now generally advocated that patients be treated with high-dose, broad-spectrum antibiotics and less-aggressive surgical procedures.[2] Surgical treatment involves a minimum of infectious decompression with myringotomy and ventilation tube placement. Tympanocentesis should be performed to allow for culture-directed intravenous antibiotic therapy. In patients with cranial nerve palsies, steroids have been used to speed recovery by reducing inflammation, edema, and nerve compression.[5]
The MRI of the patient in this case showed fluid collection in the left middle ear, mastoid air cells, and the petrous apex, which is consistent with the diagnosis of apical petrositis. This finding, in conjunction with retro-orbital pain, otorrhea, and ipsilateral sixth nerve palsies, led to the final diagnosis of Gradenigo syndrome. Her blood and CSF cultures were negative; however, the middle ear fluid culture showed Stenotrophomonas maltophilia sensitive to trimethoprim-sulfamethoxazole. Her antibiotic prescription was changed from meropenem to intravenous trimethoprim-sulfamethoxazole, and 6 days of intravenous dexamethasone was added to her regimen.
The patient started to show improvement on the third day of trimethoprim-sulfamethoxazole and steroid therapy. The sixth and seventh nerve palsies improved slowly, and a decrease in the ear discharge, headache, and left orbital pain were noted. She received both intravenous and oral trimethoprim-sulfamethoxazole for a total of 6 weeks, and she continued physiotherapy for the facial nerve palsy. A follow-up examination showed full recovery, and a repeat MRI a few months later showed full resolution.
Gradenigo syndrome should be considered in patients with suppurative otitis media who present with orbital/retro-orbital pain and/or cranial nerve palsies, especially palsy of the sixth nerve. Prompt otolaryngology consultation and initiation of antibiotic therapy are very important in curtailing the serious morbidity resulting from this condition.
