International Journal of Pediatric Otorhinolaryngology 77 (2013) 1219–1221

Case report

Tolosa-Hunt syndrome masquerading as Gradenigo syndrome in a teenager

Eric Slattery, Andrew J. White *, Megan Gauthier, Luke Linscott, Keiko Hirose

Departments of Otolaryngology, Radiology and Pediatrics, Washington University, 660 South Euclid Avenue, Campus Box 8115, St. Louis MO 63110, USA

A R T I C L E I N F O

Article history:

Received 13 February 2013

Received in revised form 5 April 2013

Accepted 12 April 2013

Available online 14 May 2013

Keywords:

Tolosa-Hunt

Gradenigo

Otitis media

Ophthalmoplegia

A B S T R A C T

Tolosa-Hunt syndrome is an idiopathic chronic granulomatous inflammatory process commonly

involving the cavernous sinus and the orbit [1]. Symptoms include unilateral eye pain, ophthalmoplegia,

headache, and facial pain in the distribution of the upper divisions of the trigeminal nerve and are highly

responsive to steroid therapy. Gradenigo syndrome describes extension of a middle ear infection to the

petrous apex, with trigeminal pain and ophthalmoplegia, typically responsive to antibiotics and often

surgical drainage. We report a case of a 17 year-old girl with apparent Gradenigo syndrome, presenting

with unilateral eye pain, abducens palsy, headache, hearing loss and serous otitis media, who was

ultimately diagnosed with Tolosa-Hunt syndrome.

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1. Case presentation

A 17 year-old girl presented to the emergency departmentcomplaining of new-onset diplopia and progressively worseningright-sided headache and facial pain in the distribution of cranialnerves VI and V2. The patient was noted to have a one-year historyof right serous otitis media, unresponsive to several courses of oralantibiotics, with a mixed hearing loss that had been detected onemonth prior to her presentation in the emergency department. Acomplete right abducens palsy and right serous otitis media wereobserved on examination in the emergency department. There wasno evidence of an acute infection: the patient was afebrile, themastoid was non-tender, the tympanic membrane was not red orbulging, and the middle ear effusion was not purulent. All othercranial nerves were intact, including all branches of the facialnerve, and light touch and pinprick sensation in all divisions of thetrigeminal nerve were intact bilaterally. Laboratory tests demon-strated a white blood cell count of 11.7 K/mm, platelet count of479 K/mm and normal hematocrit. A high-resolution computedtomography (CT) scan showed mastoid and middle ear fluid withan opacified petrous apex that did not enhance with contrast. Thediagnosis of Gradenigo syndrome was made based on theabnormal ear exam, headache, pain, and ophthalmoplegia,although the symptom of severe eye and orbital pain was atypical.The patient was brought to the operating room on the night ofadmission, where tympanocentesis was performed and fluidtapped from the middle ear was sent for culture. A tympanostomytube was placed, and the patient was started empirically on

* Corresponding author. Tel.: +1 314 454 4033.

E-mail addresses: white@kids.wustl.edu, white_a@wustl.edu (A.J. White).

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http://dx.doi.org/10.1016/j.ijporl.2013.04.023

intravenous (IV) vancomycin and meropenem after consultationwith the infectious disease team. Gram stain of the middle ear fluidshowed no evidence of organisms and no neutrophils. MRI study ofthe brain with contrast was obtained due to concern for possibleintracranial extension of presumed infection. Post-gadolinium T1imaging showed mild enhancement of the right petrous apex,Meckel’s cave, and cavernous sinus (Fig. 1). A critical stenosis of thedistal right petrous and cavernous portion of the internal carotidartery was identified on MR angiography (Fig. 2).

Given the severity of the carotid stenosis, concern was raised forpotential complication with a spontaneous cerebrovascular acci-dent, so the patient was referred to interventional radiology forconventional angiography and consideration of stenting orangioplasty. The carotid stenosis was confirmed on angiography,but due to a patent circle of Willis and excellent collateral flow, theneurointerventional team elected not to perform stenting orangioplasty. The carotid stenosis was deemed to be a chronicchange due to narrowing of the more proximal carotid arteryimmediately past the carotid bifurcation (Fig. 1B). The rheumatol-ogy service was consulted to evaluate the patient for large ormedium vessel vasculitis or other autoimmune conditions.Laboratory studies revealed an elevated erythrocyte sedimenta-tion rate of 49 mm/h and C-reactive protein of 16.7 mg/L, but allother tests, including an anti-neutrophil cytoplasmic antibody(ANCA), anti-nuclear antibody (ANA), angiotensin convertingenzyme (ACE) level, lumbar puncture, tuberculin purified proteinderivative (PPD), and chest radiograph, were normal.

The patient was discharged on home IV antibiotics. Althoughthe middle ear effusion resolved, the headache and abducens palsypersisted. Ten days after discharge the patient returned for followup evaluation in the outpatient otolaryngology clinic, and weconsulted the rheumatology team again. The patient had not had

Fig. 1. Contrast-enhanced T1-weighted images (A, B, C) and FLAIR images (D) obtained at time of initial presentation. (A) Enhancing soft tissue infiltrating the right cavernous

sinus. (B) Enhancing soft tissue extending into Meckel’s cave on the right. (C) Largest deposit of enhancing soft tissue (white open arrow) centered in the right carotid space,

causing severe narrowing of the right internal carotid artery (black arrow) and internal jugular vein. (D) Right mastoid effusion secondary to obstruction of the right

eustachian tube.

E. Slattery et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1219–12211220

significant improvement in eye pain or diplopia despite aggressivetreatment for infection, and cultures from the middle ear fluid hadnot grown any pathogenic organisms. After lengthy discussion, weelected to initiate treatment with high-dose prednisone (120 mg/day). Despite the patient’s negative laboratory tests, her angio-graphic findings raised the remote possibility that her symptomsresulted from an atypical vasculitis. She was maintained on high-dose prednisone for eight weeks after her follow up visit. Withinone week, the patient’s eye pain and headache improved, and herdiplopia slowly resolved. After recognizing the patient’s conditionto be steroid-responsive, re-examination of the MRI images led usto entertain the diagnosis of Tolosa-Hunt syndrome. Within two

Fig. 2. Cerebral angiogram performed at time of initial presentation. Frontal (A) and later

grade smooth stenosis of the petrous segment of the right ICA. White open arrows sho

months of immunosuppressive therapy, the patient’s abducenspalsy was completely resolved. The conductive component of herhearing loss had also resolved, although a high frequencysensorineural hearing loss persisted in the right ear. Two monthsafter her initial presentation, the MRI/MRA was repeated andshowed complete resolution of both the critical stenosis of theinternal carotid artery and the inflammatory mass that hadpreviously been identified in the orbital apex and cavernous sinus(Fig. 3B). She presented again 9 months after discontinuation of allimmunosuppresion with recurrent symptoms, and repeat scan(Fig. 3C) demonstrates recurrence of the soft tissue mass in theright carotid space with recurrent narrowing of the carotid artery.

al (B) views of the right internal carotid artery (ICA). Black open arrow shows high-

w smooth narrowing of the distal cervical segment of the right ICA.

Fig. 3. Contrast-enhanced T1-weighted images demonstrating temporal changes in the largest focus of enhancing soft tissue involving the right carotid space just lateral to

the right longus coli muscle. (A) Initial presentation. Large enhancing soft tissue lesion centered in right carotid space causing narrowing of the distal cervical portion of the

internal carotid artery and obliteration of the internal jugular vein. (B) 2 months later. Near complete resolution of the enhancing mass with mild residual enhancement and

narrowing of the right cervical internal carotid artery. (C) 11 months after initial presentation (8–9 months after discontinuation of prednisone). Recurrent soft tissue mass

centered in the right carotid space with recurrent narrowing of the cervical internal carotid artery. (D) Nearly two years after initial presentation. Complete interval resolution

of the soft tissue mass in the right carotid space.

E. Slattery et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 1219–1221 1221

Immunosuppression was restarted, and repeat imaging two yearsafter presentation shows complete resolution (Fig. 3D).

2. Discussion

The first case describing what is now known as Tolosa-Huntsyndrome was published in 1954, where Tolosa described stenosis ofthe internal carotid artery as an integral component of the syndrome[4]. In this original paper, the diagnostic symptoms of severe,continuous retro-orbital pain preceding or coinciding with ipsilateralophthalmoplegia and spontaneous remission with recurrences overa period of months to years without evidence of neurological findingsoutside of the orbit or cavernous sinus were established. Hunt addedthe additional criteria of steroid responsiveness in a subsequentpaper published in 1961. The utility of MRI in identifying Tolosa-Hunt syndrome has been integrated into the diagnostic criteria overthe last two decades [1,2]. Primary and secondary MRI findings havebeen described [3]. Primary findings include the presence ofhomogeneous cavernous sinus enhancement; local increase incavernous sinus size; and thickening and bulging of the duralcontour on certain MRI sequences (T1 with gadolinium) in the regionof Meckel’s cave, the cavernous sinus, and the orbital apex. Secondaryfindings include loss of dural contour, narrowing of the cavernousportion of the internal carotid artery, and extension of soft tissueenhancement into the superior orbital fissure with involvement ofthe orbital apex. Ophthalmoplegia and carotid stenosis in Tolosa-Hunt syndrome are believed to be secondary to extrinsic compres-sion of nerves as they course through the cavernous sinus and orbitalapex, in part due to the formation of an inflammatory pseudotumorin this confined space. Upon review of the MRI studies in the casepresented above, the carotid artery and the structures of thecavernous sinus do in fact appear compressed in the region of brightenhancement, although this finding was not initially appreciated.

This patient demonstrates a case of mistaken identity. Weoriginally diagnosed an infectious complication of chronic otitismedia, Gradenigo syndrome (also referred to as petrous apicitis) andcharacterized by middle ear infection extending to the petrous apex,ear pain, and ophthalmoplegia. When the patient’s symptoms didnot improve despite aggressive antibiotic therapy, eye pain becamethe predominant symptom, and severe carotid stenosis was notedon MRA, we turned to other possible diagnoses. In retrospect,perhaps the final diagnosis of Tolosa-Hunt syndrome could havebeen made at the outset, although the presence of an opacifiedmiddle ear and mastoid ipsilateral to the patient’s ophthalmoplegialed us to believe that the eye findings were a result of pathologywithin the temporal bone. The otolaryngology literature hascontributed little to the understanding of Tolosa-Hunt syndrome,and while the temporal bone findings and hearing loss in this patientwere likely unrelated to her presenting diagnosis, it would be helpfulto consider the possibility of Tolosa-Hunt syndrome in others whopresent with new onset ophthalmoplegia, given the high prevalenceof otitis media in children and eagerness to attribute certain cranialnerve deficits to pathology centered in the middle ear. In this patient,the source of her cranial nerve deficit did not originate in the ear, butat the orbital apex. Fortunately, her outcome was excellent onceimmunosuppressive therapy was initiated.

References

[1] L.B. Kline, W.F. Hoyt, The Tolosa-Hunt syndrome, J. Neurol. Neurosurg. Psychiatry71 (2001) 577–582.

[2] The International Classification of Headache Disorders: 2nd edition. Cephalalgia2004;24 Suppl 1:9-160.

[3] B. Schuknecht, V. Sturm, T.A. Huisman, et al., Tolosa-Hunt syndrome: MR imagingfeatures in 15 patients with 20 episodes of painful ophthalmoplegia, Eur. J. Radiol.69 (2009) 445–453.

[4] E. Tolosa, Periarteritic lesions of the carotid siphon with the clinical features of acarotid infraclinoidal aneurysm, J. Neurol. Neurosurg. Psychiatry 17 (1954) 300–302.