- Kenneth S Shindler, MD, PhD
Kenneth S Shindler, MD, PhD
- Assistant Professor, Department of Ophthalmology
- University of Pennsylvania
The Tolosa-Hunt syndrome is a rare syndrome with an estimated annual incidence of one case per million per year . It is characterized by painful ophthalmoplegia (weakness of the eye muscles) and is caused by an idiopathic granulomatous inflammation of the cavernous sinus. This syndrome was first described in 1954, and its exquisite responsiveness to glucocorticoid treatment was recognized a few years later [2-4].
While considered a benign condition, permanent neurologic deficits can occur, and relapses are common, often requiring prolonged immunosuppressive therapy. Tolosa-Hunt syndrome must be carefully differentiated from more malignant diagnoses, a mandate challenged by the lack of a specific diagnostic test abnormality.
The Tolosa-Hunt syndrome is caused by an inflammatory process of unknown etiology. On histopathology, there is a nonspecific inflammation of the septa and wall of the cavernous sinus, with a lymphocyte and plasma cell infiltration, giant cell granulomas, and proliferation of fibroblasts [2,3]. The inflammation produces pressure and secondary dysfunction of the structures within the cavernous sinus, including cranial nerves III, IV, and VI, as well as the superior divisions of cranial nerve V.
While reports of intracranial extension of the inflammation exist , there are no reports of systemic involvement. Cases of Tolosa-Hunt syndrome have been reported in patients with other inflammatory disorders, such as systemic lupus erythematosus, but this may simply represent an association of the two autoimmune conditions . Cases of orbital inflammation may be the initial presentation of systemic inflammatory disorders such as sarcoidosis and Wegener's granulomatosis (table 1). (See "Neurologic sarcoidosis" and "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis".)
The Headache Classification Subcommittee of the International Headache Society describes the course and features of Tolosa-Hunt syndrome as "episodic orbital pain associated with paralysis of one or more of the third, fourth, and/or sixth cranial nerves which usually resolves spontaneously but tends to relapse and remit" .
- Iaconetta G, Stella L, Esposito M, Cappabianca P. Tolosa-Hunt syndrome extending in the cerebello-pontine angle. Cephalalgia 2005; 25:746.
- TOLOSA E. Periarteritic lesions of the carotid siphon with the clinical features of a carotid infraclinoidal aneurysm. J Neurol Neurosurg Psychiatry 1954; 17:300.
- HUNT WE, MEAGHER JN, LEFEVER HE, ZEMAN W. Painful opthalmoplegia. Its relation to indolent inflammation of the carvernous sinus. Neurology 1961; 11:56.
- Smith JL, Taxdal DS. Painful ophthalmoplegia. The Tolosa-Hunt syndrome. Am J Ophthalmol 1966; 61:1466.
- Calistri V, Mostardini C, Pantano P, et al. Tolosa-Hunt syndrome in a patient with systemic lupus erythematosus. Eur Radiol 2002; 12:341.
- Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33:629.
- Kline LB, Hoyt WF. The Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiatry 2001; 71:577.
- Colnaghi S, Versino M, Marchioni E, et al. ICHD-II diagnostic criteria for Tolosa-Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus. Cephalalgia 2008; 28:577.
- Zhang X, Zhou Z, Steiner TJ, et al. Validation of ICHD-3 beta diagnostic criteria for 13.7 Tolosa-Hunt syndrome: Analysis of 77 cases of painful ophthalmoplegia. Cephalalgia 2014; 34:624.
- Tessitore E, Tessitore A. Tolosa-Hunt syndrome preceded by facial palsy. Headache 2000; 40:393.
- Cakirer S. MRI findings in Tolosa-Hunt syndrome before and after systemic corticosteroid therapy. Eur J Radiol 2003; 45:83.
- de Arcaya AA, Cerezal L, Canga A, et al. Neuroimaging diagnosis of Tolosa-Hunt syndrome: MRI contribution. Headache 1999; 39:321.
- Sondheimer FK, Knapp J. Angiographic findings in the Tolosa-Hunt syndrome: painful ophthalmoplegia. Radiology 1973; 106:105.
- Inzitari D, Sità D, Marconi GP, Barontini F. The tolosa-Hunt syndrome: further clinical and pathogenetic considerations based on the study of eight cases. J Neurol 1981; 224:221.
- Adams AH, Warner AM. Painful ophthalmoplegia: report of a case with cerebral involvement and psychiatric complications. Bull Los Angeles Neurol Soc 1975; 40:49.
- Förderreuther S, Straube A. The criteria of the International Headache Society for Tolosa-Hunt syndrome need to be revised. J Neurol 1999; 246:371.
- Cakirer S. MRI findings in the patients with the presumptive clinical diagnosis of Tolosa-Hunt syndrome. Eur Radiol 2003; 13:17.
- Keane JR. Cavernous sinus syndrome. Analysis of 151 cases. Arch Neurol 1996; 53:967.
- Hung CH, Chang KH, Wu YM, et al. A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome. Cephalalgia 2013; 33:842.
- Wasmeier C, Pfadenhauer K, Rösler A. Idiopathic inflammatory pseudotumor of the orbit and Tolosa-Hunt syndrome--are they the same disease? J Neurol 2002; 249:1237.
- Goto Y, Hosokawa S, Goto I, et al. Abnormality in the cavernous sinus in three patients with Tolosa-Hunt syndrome: MRI and CT findings. J Neurol Neurosurg Psychiatry 1990; 53:231.
- Zournas C, Trakadas S, Kapaki E, et al. Gadopentetate dimeglumine-enhanced MR in the diagnosis of the Tolosa-Hunt syndrome. AJNR Am J Neuroradiol 1995; 16:942.
- Pascual J, Cerezal L, Canga A, et al. Tolosa-Hunt syndrome: focus on MRI diagnosis. Cephalalgia 1999; 19 Suppl 25:36.
- Schuknecht B, Sturm V, Huisman TA, Landau K. Tolosa-Hunt syndrome: MR imaging features in 15 patients with 20 episodes of painful ophthalmoplegia. Eur J Radiol 2009; 69:445.
- Kóbor J, Vörös E, Deák A. Magnetic resonance imaging in Tolosa-Hunt syndrome. Eur J Pediatr 2004; 163:753.
- Kwan ES, Wolpert SM, Hedges TR 3rd, Laucella M. Tolosa-Hunt syndrome revisited: not necessarily a diagnosis of exclusion. AJR Am J Roentgenol 1988; 150:413.
- Yousem DM, Atlas SW, Grossman RI, et al. MR imaging of Tolosa-Hunt syndrome. AJR Am J Roentgenol 1990; 154:167.
- Yeh YF, Hsieh FY, Chen ST, Ng SH. Magnetic resonance images of Tolosa-Hunt syndrome before and after steroid therapy. J Formos Med Assoc 1996; 95:572.
- Mandrioli J, Frank G, Sola P, et al. Tolosa-Hunt syndrome due to actinomycosis of the cavernous sinus: the infectious hypothesis revisited. Headache 2004; 44:806.
- Leijzer CT, Prevo RL, Hageman G. Meningioma presenting as Tolosa-Hunt syndrome. Clin Neurol Neurosurg 1999; 101:19.
- Esmaeli B, Ginsberg L, Goepfert H, Deavers M. Squamous cell carcinoma with perineural invasion presenting as a Tolosa-Hunt-like syndrome: a potential pitfall in diagnosis. Ophthal Plast Reconstr Surg 2000; 16:450.
- Sedwick LA, Kaufman DI, Fratkin J. Really painful double vision. Surv Ophthalmol 2000; 45:155.
- Haque TL, Miki Y, Kashii S, et al. Dynamic MR imaging in Tolosa-Hunt syndrome. Eur J Radiol 2004; 51:209.
- Sugano H, Iizuka Y, Arai H, Sato K. Progression of Tolosa-Hunt syndrome to a cavernous dural arteriovenous fistula: a case report. Headache 2003; 43:122.
- Zurawski J, Akhondi H. Tolosa-Hunt syndrome--a rare cause of headache and ophthalmoplegia. Lancet 2013; 382:912.
- Mormont E, Laloux P, Vauthier J, Ossemann M. Radiotherapy in a case of Tolosa-Hunt syndrome. Cephalalgia 2000; 20:931.
- Smith JR, Rosenbaum JT. A role for methotrexate in the management of non-infectious orbital inflammatory disease. Br J Ophthalmol 2001; 85:1220.
- O' Connor G, Hutchinson M. Tolosa-Hunt syndrome responsive to infliximab therapy. J Neurol 2009; 256:660.
- Foubert-Samier A, Sibon I, Maire JP, Tison F. Long-term cure of Tolosa-Hunt syndrome after low-dose focal radiotherapy. Headache 2005; 45:389.
- Furukawa Y, Yamaguchi W, Ito K, et al. The efficacy of radiation monotherapy for Tolosa-Hunt syndrome. J Neurol 2010; 257:288.
- Neigel JM, Rootman J, Robinson RG, et al. The Tolosa-Hunt syndrome: computed tomographic changes and reversal after steroid therapy. Can J Ophthalmol 1986; 21:287.
- CLINICAL FEATURES
- DIFFERENTIAL DIAGNOSIS
- DIAGNOSTIC EVALUATION
- Diagnostic criteria
- Magnetic resonance imaging
- Blood and CSF evaluation
- Response to glucocorticoids and further investigation
- Second-line treatments
- SUMMARY AND RECOMMENDATIONS