Gradenigo’s and Vernet’s syndrome in an adult man with Candida mastoiditis

Abstract

The authors report a case of fungal otitis media complicated by extension of the infection into adjacent structures causing apical petrositis and subsequently involvement of the jugular foramen in a 71-year-old diabetic man. First described in 1907, Gradenigo’s syndrome is a serious but rare clinical triad of acute otitis media, unilateral pain in the distribution of cranial nerve V (trigeminal) and ipsilateral cranial nerve VI (abducens) palsy that commonly presents without all three features and is therefore often missed. In this report, our patient was initially misdiagnosed as having a diabetic cranial neuropathy, and later he developed Vernet’s syndrome. Despite aggressive surgical and medical management, he did poorly and died a few weeks later. Clinicians need to be aware of this serious and life-threatening complication of otitis media in high-risk individuals with diabetes or immunocompromised states, to allow early diagnosis and improved clinical outcomes.

Background

The classic triad of Gradenigo’s syndrome, synonymous with Gradenigo-Lannois syndrome, consists of suppurative otitis media, pain in the distribution of the trigeminal nerve and abducens nerve palsy.¹ Aetiology of trigeminal ganglion and abducens nerve involvement is presumed to be secondary to extradural inflammation at the petrous apex of the temporal bone due to suppurative otitis media via pneumatised air cell tracts, through vascular channels or as a result of direct extension through fascial planes. Further spread of infection may give rise to other complications including meningitis, intracranial abscess, prevertebral or parapharyngeal abscess, spread to sympathetic plexus around carotid sheath and spread to the skull base rarely involving the jugular foramen causing Vernet’s syndrome. Anatomically, the two jugular foramina in the skull base are formed anteriorly by the petrous portion of the temporal bone and posteriorly by the occipital bone and serve as a conduit for the internal jugular veins as well as cranial nerves IX (glossopharyngeal), X (vagus) and XI (accessory).² Although infectious, inflammatory and traumatic causes of Vernet’s syndrome have been reported, the more common aetiologies include congenital, vascular or neoplastic lesions.

Case presentation

A 71-year-old right-handed man with medical history significant for poorly controlled diabetes, hypertension, hyperlipidaemia, remote history of stroke with no reported residual deficits and chronic sinusitis, initially presented to the emergency department (ED) with 3 days of acute onset horizontal binocular diplopia. Initial examination revealed right sixth and partial third nerve palsies, without acute findings on a non-contrasted MRI brain. Additional workup of toxic, autoimmune and infectious aetiologies including a lumbar puncture was unrevealing and he was discharged with a diagnosis of diabetic cranial neuropathy due to microvascular ischaemia with recommendations to optimise neurovascular risk factors.

He re-presented to the ED 4 weeks later with progressive dysphagia, dysarthria, right otalgia and hearing loss. He was evaluated by the Otorhinolaryngology team who noted a peripharyngeal mass on examination, for which a CT of neck and soft tissues was obtained, revealing subtle effacement of bilateral pharyngeal recesses with heterogenous mucosal enhancement in addition to bilateral mastoid and middle ear effusions, worse on the right. He was initiated on broad spectrum antibiotics for mastoiditis and possible osteomyelitis.

Investigations

Contrasted MRI of the brain and orbits was repeated which showed enhancement of the right orbital apex with suspected involvement of the superior and inferior orbital fissures and their contents including cranial nerves III (oculomotor), IV (trochlear) and VI (abducens). In addition, pathological pachymeningeal enhancement along the undersurface of the right temporal lobe was also seen (figure 1). CT of the temporal bone confirmed right mastoiditis with concomitant osteomyelitis and a 0.5 cm focal bony defect in the roof of the middle cranial fossa, with communication to the intracranial compartment of the right middle cranial fossa (figure 2).

Figure 1.

MRI brain and orbits with enhancement of the right orbital apex with suspected involvement of the superior and inferior orbital fissures.

Figure 2.

CT temporal bone (A) revealing 0.5 cm focal bony defect in the roof of the glenoid fossa/middle cranial fossa, with communication to the intracranial compartment of the right middle cranial fossa as evidenced in MRI brain (B) with pathological pachymeningeal enhancement along the undersurface of the right temporal lobe.

Differential diagnosis

Other diagnoses considered in the differential included a vascular event such as stroke although given his progressive worsening, an infection or neoplastic process was more likely.

Treatment

Treatment of fungal otomastoiditis consists of three parts: control of underlying immunocompromise if present, surgical debridement of necrotic tissues and antifungal chemotherapy. Our patient underwent surgical debridement and a mastoid biopsy, cultures of which eventually revealed Candida parapsilosis. In addition to blood glucose optimisation, he was initiated on empiric broad spectrum antibiotics and antifungal agents on presentation, which were later narrowed to amphotericin and fluconazole based on tissue cultures.

Outcome and follow-up

In addition to aggressive medical management, the patient also required extensive supportive care including percutaneous endoscopic gastrostomy tube placement, after which he was discharged to a long-term acute care facility, where he unfortunately died several weeks later.

Discussion

The classic triad of Gradenigo’s syndrome was present in fewer than half of the 57 patients in Giuseppe Gradenigo’s original series¹ and arises as a complication of otitis media and mastoiditis involving the apex of the petrous temporal bone. Further spread of infection may give rise to other complications including meningitis, intracranial or prevertebral or parapharyngeal abscesses, spread to sympathetic plexus around carotid sheath and spread to the skull base causing Vernet’s syndrome. First described in 1917 by Vernet, clinical features include paralysis of the laryngeal muscles, loss of sensation to the posterior ipsilateral aspect of the tongue, loss of ipsilateral gag reflex, dysfunction of the accessory nerve and cerebral oedema secondary to intracranial venous congestion.

Confirmation of the diagnoses requires imaging. In Gradenigo’s syndrome, CT typically reveals petromastoid air cell opacification with possible bone destruction, and MRI shows inflammatory changes in petrous apicitis. Radioisotope bone scan reveals increased uptake in the petrous apex and hence aids localisation of the disease process. MRI with contrast is the investigation of choice in Vernet’s syndrome.

Increased susceptibility of certain groups of patients to develop Gradenigo’s syndrome is reported in diabetics and immunosuppressed patients on chronic steroids or with HIV. The most common organisms implicated are Pseudomonas and mycobacterium tuberculosis.³ Vernet’s syndrome may be secondary to a congenital, vascular, neoplastic, traumatic or inflammatory aetiology and causative viral and bacterial infections have been reported.² This is the first case reported of a fungal aetiology of Vernet’s syndrome.

Candida parapsilosis is a normal human commensal, first discovered in Puerto Rico in 1928 by Ashford⁴ from a diarrheal stool. Initially considered non-pathogenic,⁵ it is now recognised as an important, emerging nosocomial pathogen.^{5 6} C. parapsilosis is the most common non-C. albicans species of Candida and the second most common pathogen in superficial candidiasis after C. albicans.⁶ C. parapsilosis does not form true hyphae; it exists in either a yeast phase or pseudohyphal form. It is white, creamy and shiny in dextrose agar with an oval, round or cylindrical shaped cell. It appears smooth or cratered in its yeast form in contrast to a wrinkled or concentric phenotype in the pseudohyphae form.⁶

Successful treatment for candidiasis of the auditory canal has included intense debridement in combination with topical and systemic antifungals, despite which there is high morbidity and mortality associated with the diagnosis.⁷

Learning points.

• Gradenigo’s and Vernet’s syndromes are uncommon clinical presentations of cranial neuropathies but despite their rarity, both syndromes remain highly clinically relevant entities.

• The classic triad of Gradenigo’s syndrome consists of suppurative otitis media, pain in the distribution of the trigeminal nerve and abducens nerve palsy, but is present in less than half of patients.

• Common aetiologies of Vernet’s syndrome include congenital, vascular or neoplastic lesions, although traumatic, inflammatory and infectious causes have also been reported. Symptoms include paralysis of the laryngeal muscles, loss of sensation to the posterior ipsilateral aspect of the tongue, loss of ipsilateral gag reflex, dysfunction of the accessory nerve and cerebral oedema secondary to intracranial venous congestion.

• Elucidation of aetiology determines management and prognosis and thus morbidity and mortality.