Confirmation of Tolosa-Hunt Syndrome via endoscopic

biopsy of inflammation surrounding the orbital apex Amy Li Richter MD, Masayoshi Takashima MD

Baylor College of Medicine Bobby R. Alford Department of Otolaryngology - Head and Neck Surgery

Objectives

Case Report

1) Review the criteria of diagnosing Tolosa-

Hunt Syndrome (THS), a rare cause of

painful ophthalmoplegia due to

idiopathic granulomatous inflammation

of the orbital apex or cavernous sinus.

2) Review the literature of THS and other

surgical techniques used previously in

the setting of THS.

• History of present illness: BH is a 41 year old male with 2 week history of decreased vision, left eye pain, pressure headache. No light perception from his left eye for 5 days.

• Surgical / social history: appendectomy, current 1/2 pack-per-day smoker, social drinker, no illicit drugs

• Vital signs: Temperature 100.3F

• Exam:

• Eyes: No light perception in left eye, afferent pupillary defect in left eye, paralysis of extraocular movements (total loss of cranial nerves III, IV, VI), right eye normal

• Neuro: Decreased sensation in left CN V2

• CBC, CMP, ESR, CRP, CSF, CTA, MRA, MRV all normal

• MRI demonstrated abnormal enhancement in left orbital apex and cavernous sinus with extension along left infraorbital nerve into the left inferior orbital and pterygopalatine fissures.

• CT demonstrated loss of fat planes in the left inferior orbital and pterygopalatine fissures and hyperostosis of the left sphenoid bone.

2004 THS International Headache Society criteria

A. One or more episodes of unilateral orbital pain

persisting for weeks if untreated

B. Paresis of one or more of the third, fourth and/or

sixth cranial nerves and/or demonstration of

granulomatous inflammation by MRI or biopsy

C. Paresis coincides with the onset of pain or follows

it within 2 weeks

D. Pain and paresis improve within 72h when

treated adequately with corticosteroids

E. Other causes have been excluded by appropriate

investigations

• One case per million per year, rare cause of painful ophthalmoplegia

• Nonspecific inflammation of orbital apex, septa and wall of cavernous sinus: lymphocyte and plasma cell infiltration, giant cell granulomas, and proliferation of fibroblasts

• Palsy of CN III, IV, VI, and superior divisions of CN V

• Differential diagnosis includes tumors, vasculitis, basal meningitis, sarcoid, diabetes mellitus, and ophthalmoplegic ‘migraine’

• MRI demonstrates inflammation in the cavernous sinus, superior orbital fissure or orbit in 92% of cases

• Diagnosis is a diagnosis of exclusion or demonstration of granuloma on MRI or granulomatous inflammation on histopathology

• Treatment with steroids; steroid type, dosage, administration method, and duration are variable

Imaging

Image 1. Coronal fat suppressed MRI.

Enhancement of extraocular muscles

at orbital apex and extension into

pterygopalatine fossa (arrow).

Image 2. Axial fat suppressed

MRI. Enhancement of extracranial

optical nerve extending into inferior

orbital fissure (arrow).

Image 3. Coronal CT with

contrast. Loss of fat planes in

pterygopalatine fossa at

sphenopalatine foramen (arrow).

Surgical Approaches

Background Pathology

Fig 1. Pterygopalatine fossa

• Biopsies performed of pterygopalatine fossa, pterygoid fossa, and sphenopalatine foramen

• Figure 1 demonstrates chronic inflammation with distorted lymphocytes (arrowhead) and plasma cells and fibrosis

• Figure 2 demonstrates chronic granulomatous inflammation with distorted lymphocytes surrounding fibrovascular bundles (arrowhead)

• Endonasal endoscopic biopsy of inflammatory tissue at pterygopalatine fossa and sphenopalatine foramen was performed within 72 hours to confirm chronic granulomatous inflammation and rule out infectious and neoplastic etiology.

• Steroids were initiated, and patient BH had resolution of his pain within 24 hours of starting high dose intravenous dexamethasone. He continued a several week course of oral steroids and continued to have gradual improvement of his ophthalmoplegia. At his one month follow up visit, he had significantly improved vision.

Fig 2. Pterygoid fossa

Discussion

Fig 3. Sphenopalatine artery Fig 4. Pterygoid fossa

Reference No Surgical

approach

Pathology

Tolosa.

1954

1 Transfrontal

intradural,

autopsy

Negative; non-

specific periarterial

granulation

Hunt et al.

1961

1 Transfrontal

parasellar

Nonspecific

inflammation

Lakke.

1962

1 Frontotemporal

craniotomy

Nonspecific

inflammation

Schatz.

1972

2 Frontotemporal

craniotomy to

cavernous

sinus

Chronic

inflammation,

plasma cells,

fibrosis; chronic

granulomatous

lesion

Campbell et

al. 1987

1 Autopsy Vasculitis and

nongranulomatous

inflammation

Goadsby et

al. 1989

1 Craniotomy Retroorbital

granuloma

Brown et al.

1990

1 Sublabial

transseptal

sphenoidotomy

Nonspecific

inflammation

Yousem et

al. 1990

3 Unspecified

cavernous

sinus biopsy

Nonspecific

inflammatory

change

Lance.

1991

1 Unspecified Lateral cavernous

sinus granuloma

Montecucco

et al. 1993

1 Unspecified Mononuclear cells

noncaseating

granuloma

Wasmeier

et al. 2002

2 Transfrontal

biopsy of

medial rectus;

transorbital

exploration

Granulocytic

myositis;

granulomatous

inflammation at

orbital apex

References Brown J, Moster M, Kenning J, et al. The Tolosa-Hunt syndrome: A case report.

Otolaryng Head Neck. 1990;102;402-4.

Campbell R, Okazaki H. Painful ophthalmoplegia (Tolosa-Hunt variant): Autopsy

findings in a patient with necrotizing intracavernous carotid vasculitis and

inflammatory disease of the orbit. Mayo Clinic Proc. 1987;62:520-6.

Goadsby P, Lance J. Clinicopathological correlation in a case of painful

ophthalmoplegia: Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiat.

1989;52:1290-3.

Hunt W, Meagher J, LeFever J. Painful ophthalmoplegia: its relation to indolent

inflammation of the cavernous sinus. Neurology. 1961;11:56-62.

Kline L. The Tolosa-Hunt syndrome. Surv Ophthalmol. 1982;27:79-95.

Lakke JPWF. Superior orbital fissure syndrome. Arch Neurol. 1962;7:289-300.

Lance J. Solved and unsolved headache problems. Headache. 1991;31:439-

45.

Montecucco C, Caporali R, Pacchetti C, et al. Is Tolosa-Hunt syndrome a limited

form of Wegener’s granulomatosis? Br J Rheumatol. 1993;32:640-1.

Schuknect B, Sturm V, Huisman TAGM, et al. Tolosa-Hunt syndrome: MR

imaging features in 15 patients with 20 episodes of painful ophthalmoplegia.

Eur J Radiol. 2009;69:445-53.

Schatz N, Farmer P. THS: The pathology of painful ophthalmoplegia. In: Smith

JL, et al. Neuro-ophthalmology Vol 6. St. Louis: Mosby Co. 1972;102-12.

Tolosa E. Periarteritic lesions of the carotid siphon with the clinical features of a

carotid infraclinoidal aneurysm. J Neurol Neurosurg Psychiat. 1954;17;300-2.

Yousem D, Atlas S, Grossman R, et al. MR imaging of Tolosa-Hunt syndrome.

Am J Roentgenol. 1990;154:167-70.

Diagnostic Criteria

Operative Biopsy

Disclosure

It is the policy of Baylor College of Medicine (Baylor) that the provider

and faculty / presenters disclose any significant financial or other

relationships with commercial companies whose products may be

discussed in the activity, or the commercial supporters, if any. Baylor

also requires that faculty disclose any unlabeled use or investigational

use (not yet approved for any purpose) of pharmaceutical and medical

device products. Amy Richter, M.D., and Masayoshi Takashima, M.D.

reported nothing to disclose.

• Historically, THS has been a diagnosis of exclusion. There are only 14 documented cases with histologic diagnosis, of which only one biopsy in vivo was performed via transnasal approach (sphenoidotomy) and only 50% demonstrated granuloma formation or granulomatous inflammation. Most cases of THS are confirmed by symptoms and granuloma on imaging.

• Endonasal endoscopic biopsy of the peri-orbital apex proved to be a safe, low risk procedure to confirm THS and rule out dangerous causes of painful ophthalmoplegia, including malignancy.