International Journal of Pediatric Otorhinolaryngology 77 (2013) 12191221

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International Journal of Pediatric Otorhinolaryngology

journal homepage: www.elsevier.com/locate/ijporl

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 A B S T R A C T

Article history: Tolosa-Hunt syndrome is an idiopathic chronic granulomatous inammatory process commonly
Received 13 February 2013 involving the cavernous sinus and the orbit [1]. Symptoms include unilateral eye pain, ophthalmoplegia,
Received in revised form 5 April 2013 headache, and facial pain in the distribution of the upper divisions of the trigeminal nerve and are highly
Accepted 12 April 2013
responsive to steroid therapy. Gradenigo syndrome describes extension of a middle ear infection to the
Available online 14 May 2013
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
Keywords:
with unilateral eye pain, abducens palsy, headache, hearing loss and serous otitis media, who was
Tolosa-Hunt
Gradenigo
ultimately diagnosed with Tolosa-Hunt syndrome.
Otitis media 2013 Elsevier Ireland Ltd. All rights reserved.
Ophthalmoplegia

1. Case presentation intravenous (IV) vancomycin and meropenem after consultation

A 17 year-old girl presented to the emergency department
complaining of new-onset diplopia and progressively worsening
right-sided headache and facial pain in the distribution of cranial
nerves VI and V2. The patient was noted to have a one-year history
of right serous otitis media, unresponsive to several courses of oral
antibiotics, with a mixed hearing loss that had been detected one
month prior to her presentation in the emergency department. A
complete right abducens palsy and right serous otitis media were
observed on examination in the emergency department. There was
no evidence of an acute infection: the patient was afebrile, the
mastoid was non-tender, the tympanic membrane was not red or
bulging, and the middle ear effusion was not purulent. All other
cranial nerves were intact, including all branches of the facial
nerve, and light touch and pinprick sensation in all divisions of the
trigeminal nerve were intact bilaterally. Laboratory tests demon-
strated a white blood cell count of 11.7 K/mm, platelet count of
479 K/mm and normal hematocrit. A high-resolution computed
tomography (CT) scan showed mastoid and middle ear uid with
an opacied petrous apex that did not enhance with contrast. The
diagnosis of Gradenigo syndrome was made based on the
abnormal 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 of
admission, where tympanocentesis was performed and uid
tapped from the middle ear was sent for culture. A tympanostomy
tube 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).
with the infectious disease team. Gram stain of the middle ear uid
showed no evidence of organisms and no neutrophils. MRI study of
the brain with contrast was obtained due to concern for possible
intracranial extension of presumed infection. Post-gadolinium T1
imaging showed mild enhancement of the right petrous apex,
Meckels cave, and cavernous sinus (Fig. 1). A critical stenosis of the
distal right petrous and cavernous portion of the internal carotid
artery was identied on MR angiography (Fig. 2).
Given the severity of the carotid stenosis, concern was raised for
potential complication with a spontaneous cerebrovascular acci-
dent, so the patient was referred to interventional radiology for
conventional angiography and consideration of stenting or
angioplasty. The carotid stenosis was conrmed on angiography,
but due to a patent circle of Willis and excellent collateral ow, the
neurointerventional team elected not to perform stenting or
angioplasty. The carotid stenosis was deemed to be a chronic
change due to narrowing of the more proximal carotid artery
immediately past the carotid bifurcation (Fig. 1B). The rheumatol-
ogy service was consulted to evaluate the patient for large or
medium 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 all
other tests, including an anti-neutrophil cytoplasmic antibody
(ANCA), anti-nuclear antibody (ANA), angiotensin converting
enzyme (ACE) level, lumbar puncture, tuberculin puried protein
derivative (PPD), and chest radiograph, were normal.
The patient was discharged on home IV antibiotics. Although
the middle ear effusion resolved, the headache and abducens palsy
persisted. Ten days after discharge the patient returned for follow
up evaluation in the outpatient otolaryngology clinic, and we
consulted the rheumatology team again. The patient had not had

0165-5876/$ see front matter 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijporl.2013.04.023
1220 E. Slattery et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 12191221

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

signicant improvement in eye pain or diplopia despite aggressive
treatment for infection, and cultures from the middle ear uid had
not grown any pathogenic organisms. After lengthy discussion, we
elected to initiate treatment with high-dose prednisone (120 mg/
day). Despite the patients negative laboratory tests, her angio-
graphic ndings raised the remote possibility that her symptoms
resulted from an atypical vasculitis. She was maintained on high-
dose prednisone for eight weeks after her follow up visit. Within
one week, the patients eye pain and headache improved, and her
diplopia slowly resolved. After recognizing the patients condition
to be steroid-responsive, re-examination of the MRI images led us
to entertain the diagnosis of Tolosa-Hunt syndrome. Within two
months of immunosuppressive therapy, the patients abducens
palsy was completely resolved. The conductive component of her
hearing loss had also resolved, although a high frequency
sensorineural hearing loss persisted in the right ear. Two months
after her initial presentation, the MRI/MRA was repeated and
showed complete resolution of both the critical stenosis of the
internal carotid artery and the inammatory mass that had
previously been identied in the orbital apex and cavernous sinus
(Fig. 3B). She presented again 9 months after discontinuation of all
immunosuppresion with recurrent symptoms, and repeat scan
(Fig. 3C) demonstrates recurrence of the soft tissue mass in the
right carotid space with recurrent narrowing of the carotid artery.

Fig. 2. Cerebral angiogram performed at time of initial presentation. Frontal (A) and lateral (B) views of the right internal carotid artery (ICA). Black open arrow shows high-
grade smooth stenosis of the petrous segment of the right ICA. White open arrows show smooth narrowing of the distal cervical segment of the right ICA.
 E. Slattery et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 12191221 1221

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 (89 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.

Immunosuppression was restarted, and repeat imaging two years
after presentation shows complete resolution (Fig. 3D).
2. Discussion
The rst case describing what is now known as Tolosa-Hunt
syndrome was published in 1954, where Tolosa described stenosis of
the 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 ipsilateral
ophthalmoplegia and spontaneous remission with recurrences over
a period of months to years without evidence of neurological ndings
outside of the orbit or cavernous sinus were established. Hunt added
the additional criteria of steroid responsiveness in a subsequent
paper published in 1961. The utility of MRI in identifying Tolosa-
Hunt syndrome has been integrated into the diagnostic criteria over
the last two decades [1,2]. Primary and secondary MRI ndings have
been described [3]. Primary ndings include the presence of
homogeneous cavernous sinus enhancement; local increase in
cavernous sinus size; and thickening and bulging of the dural
contour on certain MRI sequences (T1 with gadolinium) in the region
of Meckels cave, the cavernous sinus, and the orbital apex. Secondary
ndings include loss of dural contour, narrowing of the cavernous
portion of the internal carotid artery, and extension of soft tissue
enhancement into the superior orbital ssure with involvement of
the 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 orbital
apex, in part due to the formation of an inammatory pseudotumor
in this conned space. Upon review of the MRI studies in the case
presented above, the carotid artery and the structures of the
cavernous sinus do in fact appear compressed in the region of bright
enhancement, although this nding was not initially appreciated.
This patient demonstrates a case of mistaken identity. We
originally diagnosed an infectious complication of chronic otitis
media, Gradenigo syndrome (also referred to as petrous apicitis) and
characterized by middle ear infection extending to the petrous apex,
ear pain, and ophthalmoplegia. When the patients symptoms did
not improve despite aggressive antibiotic therapy, eye pain became
the predominant symptom, and severe carotid stenosis was noted
on MRA, we turned to other possible diagnoses. In retrospect,
perhaps the nal diagnosis of Tolosa-Hunt syndrome could have
been made at the outset, although the presence of an opacied
middle ear and mastoid ipsilateral to the patients ophthalmoplegia
led us to believe that the eye ndings were a result of pathology
within the temporal bone. The otolaryngology literature has
contributed little to the understanding of Tolosa-Hunt syndrome,
and while the temporal bone ndings and hearing loss in this patient
were likely unrelated to her presenting diagnosis, it would be helpful
to consider the possibility of Tolosa-Hunt syndrome in others who
present with new onset ophthalmoplegia, given the high prevalence
of otitis media in children and eagerness to attribute certain cranial
nerve decits to pathology centered in the middle ear. In this patient,
the source of her cranial nerve decit did not originate in the ear, but
at the orbital apex. Fortunately, her outcome was excellent once
immunosuppressive therapy was initiated.
References
[1] L.B. Kline, W.F. Hoyt, The Tolosa-Hunt syndrome, J. Neurol. Neurosurg. Psychiatry
71 (2001) 577582.
[2] The International Classication of Headache Disorders: 2nd edition. Cephalalgia
2004;24 Suppl 1:9-160.
[3] B. Schuknecht, V. Sturm, T.A. Huisman, et al., Tolosa-Hunt syndrome: MR imaging
features in 15 patients with 20 episodes of painful ophthalmoplegia, Eur. J. Radiol.
69 (2009) 445453.
[4] E. Tolosa, Periarteritic lesions of the carotid siphon with the clinical features of a
carotid infraclinoidal aneurysm, J. Neurol. Neurosurg. Psychiatry 17 (1954) 300302.