Gradenigo Syndrome

Gradenigo syndrome is the triad of suppurative otitis media, deep retro orbital or facial pain from trigeminal irritation, and abducens (sixth) nerve palsy with diplopia. It is a sign of petrous apicitis.

It is rare, occurring in under 1% of complicated acute otitis media in the pre-antibiotic era and now far less. All three features are present in a minority of patients with petrous apicitis. Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae are the commonest organisms.

Pathophysiology.

Infection of the petrous apex inflames the dura at Dorello canal, where the abducens nerve passes beneath the petroclinoid ligament, and irritates the trigeminal ganglion in Meckel cave. Nearby sinus thrombosis and meningitis may follow.

Ear discharge, deep pain behind the eye or in the temple and face, horizontal diplopia worse looking toward the affected side, fever and headache. Facial palsy, vertigo and hearing loss are uncommon.

Red flags.

• Neck stiffness or confusion (meningitis).
• Proptosis or chemosis (cavernous sinus thrombosis).
• Facial or other cranial nerve palsies.
• Sepsis.

CT of the temporal bone shows petrous apex air cell opacification and bone erosion. Magnetic resonance imaging with contrast and venography shows apical inflammation, dural enhancement, abscess and venous sinus thrombosis. Send blood cultures and inflammatory markers, and swab discharge. Neuro ophthalmic examination documents the sixth nerve palsy.

Differential diagnosis.

• Petrous apex cholesterol granuloma.
• Skull base osteomyelitis.
• Cavernous sinus thrombosis.
• Skull base tumours.
• Tolosa-Hunt syndrome.
• Diabetic or microvascular sixth nerve palsy.

Start intravenous antibiotics at once with surgical drainage of the middle ear and mastoid (and the petrous apex if there is abscess or no improvement in 48 to 72 hours).

• Ceftriaxone: 2 g IV every 12 hours; maximum 4 g daily; usually 4 to 6 weeks in total; monitor renal function, liver tests and blood counts; no routine renal adjustment.
• Metronidazole: 500 mg IV or orally every 8 hours with ceftriaxone for the same duration; maximum 1.5 g daily; monitor neuropathy and liver tests; reduce to 500 mg every 12 hours in severe hepatic impairment.
• Vancomycin (added for suspected MRSA): load 25 to 30 mg/kg IV, then 15 to 20 mg/kg every 8 to 12 hours; target area under the curve 400 to 600; monitor levels and creatinine; extend the interval in renal impairment.
• Piperacillin-tazobactam (replacing ceftriaxone and metronidazole if Pseudomonas is isolated): 4.5 g IV every 6 hours; maximum 18 g daily; monitor renal function and blood counts; reduce for creatinine clearance under 40 mL/min.

The sixth nerve palsy usually recovers over weeks to months after the infection is controlled.

Monitoring. Daily neurological and eye movement examination; imaging at 4 to 6 weeks.

Referral and escalation. ENT, neurosurgery and ophthalmology urgently; critical care for sepsis.

Special groups. Children need weight based dosing: ceftriaxone 100 mg/kg daily (maximum 4 g).