Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.

com/article/1146714-overview

This site is intended for healthcare professionals

News & Perspective

Drugs & Diseases
CME & Education
Specialty:
Edition: ENGLISH
DEUTSCH
ESPAOL
FRANAIS
PORTUGUS
Log In
Sign Up It's Free!
Edition: ENGLISH DEUTSCH ESPAOL FRANAIS PORTUGUS
Register Log In

1 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

2 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

3 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

No Results

4 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

No Results

News & Perspective Drugs & Diseases CME & Education

close
Please confirm that you would like to log out of Medscape. If you log out, you will be required to enter your username and
password the next time you visit. Log out Cancel

Tolosa-Hunt Syndrome
Author: Danette C Taylor, MS, DO, FACN; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN,
FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS more...

Updated: Sep 04, 2015

Background
Tolosa-Hunt syndrome (THS) is a painful ophthalmoplegia caused by nonspecific
inflammation of the cavernous sinus or superior orbital fissure. In 2004, the
International Headache Society provided a definition of the diagnostic criteria which
included granuloma.[1] See the image below.

5 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

MRI of a 40-year-old man with severe periorbital pain ocular sinister (OS; ie, left eye),
complete oculomotor nerve palsy OS, and partial abducens nerve palsy OS. Axial imaging
without (left) and with (right) enhancement demonstrates nonspecific fullness involving the left
cavernous sinus, consistent with Tolosa-Hunt syndrome within the context of the history.
Treatment with steroids produced complete resolution of symptoms. Image courtesy of Eric
Eggenberger, DO.

Pathophysiology
Nonspecific inflammation (noncaseating granulomatous or nongranulomatous)
within the cavernous sinus or superior orbital fissure is the cause of the constant
pain, which characterizes the onset of this disorder. Ophthalmoparesis or disordered
eye movements occur when cranial nerves III, IV, and VI are damaged by
granulomatous inflammation. Pupillary dysfunction may be present and is related to
injury to the sympathetic fibers in the cavernous portion of ICA or parasympathetic
fibers that surround the oculomotor nerve. Trigeminal nerve involvement (primarily
V1) may cause paresthesias of the forehead. Pathological involvement beyond the
cavernous sinus, superior orbital fissure, or apex of the orbit occurs rarely, and the
disorder is part of a continuum with idiopathic orbital pseudotumor, with which it
shares histopathologic features. Spontaneous remissions can occur; relapses may
occur in up to 40% of the patients.

Epidemiology
Frequency

Tolosa-Hunt syndrome (THS) is uncommon in both the United States and

internationally. The disorder is rare during the first 2 decades of life; in people older
than 20 years, it appears to have an even distribution. When THS occurs in children,
the course of the disorder appears to be similar to that experienced by adults.[2] THS
affects males and females equally.

Mortality/Morbidity

Tolosa-Hunt syndrome is not a fatal disorder; patients experience unilateral onset of

acute orbital pain and ophthalmoparesis, and the disorder may threaten sight if
untreated inflammation extends beyond the cavernous sinus to affect the optic
nerve.

Clinical Presentation

Contributor Information and Disclosures

Author
Danette C Taylor, MS, DO, FACN Medical Director, Movement Disorders Program, Beaumont Health; Clinical
Assistant Professor, Department of Neurology and Ophthalmology, Michigan State University College of
Osteopathic Medicine

Danette C Taylor, MS, DO, FACN is a member of the following medical societies: American Academy of
Neurology, American Osteopathic Association, International Parkinson and Movement Disorder Society, American
College of Osteopathic Neurologists and Psychiatrists, American Medical Association

Disclosure: Received honoraria from Allergan for speaking and teaching; Received honoraria from Teva
Pharmaceuticals for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Florian P Thomas, MD, PhD, Drmed, MA, MS Chairman, Neuroscience Institute; Director, Multiple Sclerosis
Center and Hereditary Neuropathy Center; Professor, Seton Hall-Hackensack-Meridian School of Medicine;
Editor-in-Chief, Journal of Spinal Cord Medicine

Florian P Thomas, MD, PhD, Drmed, MA, MS is a member of the following medical societies: Academy of Spinal
Cord Injury Professionals, American Academy of Neurology, American Neurological Association, Consortium of
Multiple Sclerosis Centers, National Multiple Sclerosis Society, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor
Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP,
MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of
Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University;
Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

6 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS
is a member of the following medical societies: American College of International Physicians, American Heart
Association, American Stroke Association, American Academy of Neurology, American Academy of Pain
Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians,
American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of
Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Additional Contributors
Eric R Eggenberger, MS, DO, FAAN Professor, Vice-Chairman, Department of Neurology and Ophthalmology,
Colleges of Osteopathic Medicine and Human Medicine, Michigan State University; Director of Michigan State
University Ocular Motility Laboratory; Director of National Multiple Sclerosis Society Clinic, Michigan State
University College of Human Medicine

Eric R Eggenberger, MS, DO, FAAN is a member of the following medical societies: American Academy of
Neurology, American Academy of Ophthalmology, American Osteopathic Association, North American Neuro-
Ophthalmology Society

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Biogen; Genzyme; Novartis; Teva
<br/>Received research grant from: Biogen; Genzyme; Novartis<br/>Received consulting fee from Biogen for
consulting; Received consulting fee from Teva for consulting; Received consulting fee from Acorda for consulting;
Received grant/research funds from Novartis for independent contractor; Received honoraria from Genentech for
speaking and teaching; Received honoraria from Genzyme for speaking and teaching.

Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author
Kenneth A Mankowski, DO to the development and writing of this article.

References

1. La Mantia L, Curone M, Rapoport AM, Bussone G, International Headache Society. Tolosa-Hunt syndrome:
critical literature review based on IHS 2004 criteria. Cephalalgia. 2006 Jul. 26 (7):772-81. [Medline].

2. Zanus C, Furlan C, Costa P, Cosentini D, Carrozzi M. The Tolosa-Hunt syndrome in children: a case report.
Cephalalgia. 2009. 29:1232-1237.

3. Lachanas VA, Karatzias GT, Tsitiridis I, Panaras I, Sandris VG. Tolosa-Hunt syndrome misdiagnosed as
sinusitis complication. J Laryngol Otol. 2008 Jan. 122(1):97-9. [Medline].

4. Colnaghi S, Versino M, Marchioni E, Pichiecchio A, Bastianello S, Cosi V, et al. ICHD-II diagnostic criteria
for Tolosa-Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus.
Cephalalgia. 2008 Jun. 28(6):577-84. [Medline].

5. [Guideline] The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004. Suppl
1:9-160. [Medline]. [Full Text].

6. 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 Mar. 53(3):231-4. [Medline].

7. Yagi A, Sato N, Taketomi A, et al. Normal cranial nerves in the cavernous sinuses: contrast-enhanced three-
dimensional constructive interference in the steady state MR imaging. AJNR Am J Neuroradiol. 2005 Apr.
26(4):946-50. [Medline].

8. Foubert-Samier A, Sibon I, Maire JP, Tison F. Long-term cure of Tolosa-Hunt syndrome after low-dose focal
radiotherapy. Headache. 2005 Apr. 45 (4):389-91. [Medline].

9. Cohn DF, Carasso R, Streifler M. Painful ophthalmoplegia: the Tolosa-Hunt syndrome. Eur Neurol. 1979.
18(6):373-81. [Medline].

10. Gimenez-Roldan S, Guillem A, Munoz L. [Long-term risk of relapses in Tolosa-Hunt syndrome]. Neurologia.
2006 Sep. 21(7):382-5. [Medline].

11. Barontini F, Maurri S, Marrapodi E. Tolosa-Hunt syndrome versus recurrent cranial neuropathy. Report of
two cases with a prolonged follow-up. J Neurol. 1987 Feb. 234(2):112-5. [Medline].

12. Bruyn GW, Ferrari M, de Beer FC. Migraine, Tolosa-Hunt syndrome and pleocytosis. Correlation or
coincidence?. Clin Neurol Neurosurg. 1984. 86(1):33-41. [Medline].

13. Hunt WE. Tolosa-Hunt syndrome: one cause of painful ophthalmoplegia. J Neurosurg. 1976 May.
44(5):544-9. [Medline].

14. Johnston JL. Parasellar syndromes. Curr Neurol Neurosci Rep. 2002 Sep. 2(5):423-31. [Medline].

15. Kline LB. The Tolosa-Hunt syndrome. Surv Ophthalmol. 1982 Sep-Oct. 27(2):79-95. [Medline].

16. Kline LB, Hoyt WF. The Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001 Nov. 71(5):577-82.
[Medline].

17. Kobor J, Voros E, Deak A. Magnetic resonance imaging in Tolosa-Hunt syndrome. Eur J Pediatr. 2004 Dec.
163(12):753-4. [Medline].

18. Kwan ESK, Wolpert SM, Hedges TR III. Tolosa-Hunt revisited: Not necessarily a diagnosis of exclusion. Am
J Radiol. 1989. 71:932.

19. La Mantia L, Erbetta A, Bussone G. Painful ophthalmoplegia: an unresolved clinical problem. Neurol Sci.
2005 May. 26 Suppl 2:s79-82. [Medline].

20. Lane R, Davies P. Ophthalmoplegic migraine: the case for reclassification. Cephalalgia. 2010 Jun.
30(6):655-61. [Medline].

21. Lo YL, Chan LL, Pan A, Ratnagopal P. Acute ophthalmoparesis in the anti-GQ1b antibody syndrome:
electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi. J Neurol
Neurosurg Psychiatry. 2004 Mar. 75(3):436-40. [Medline].

7 of 8 01/11/2016 08.07
Tolosa-Hunt Syndrome: Background, Pathophysiology, Epidemiology http://emedicine.medscape.com/article/1146714-overview

22. Rehman HU. A woman with headache and ptosis. QJM. 2012 Jan 20. [Medline].

23. Roca PD. Painful ophthalmoplegia: the Tolosa-Hunt syndrome. Ann Ophthalmol. 1975 Jun. 7(6):828-34.
[Medline].

24. Schutta HS. Diseases of the dura mater. Joynt R, Griggs R, eds. Clinical Neurology. Philadelphia, Pa:
Lippincott, Williams & Wilkins; 1993. 34-44.

25. Smith JL, Taxdal DS. Painful ophthalmoplegia. The Tolosa-Hunt syndrome. Am J Ophthalmol. 1966 Jun.
61(6):1466-72. [Medline].

26. Sondheimer FK, Knapp J. Angiographic findings in the Tolosa-Hunt syndrome: painful ophthalmoplegia.
Radiology. 1973 Jan. 106(1):105-12. [Medline].

27. Spector RH, Fiandaca MS. The "sinister" Tolosa-Hunt syndrome. Neurology. 1986 Feb. 36(2):198-203.
[Medline].

28. Troost BT. Miller NR, Newman NJ, eds. Walsh & Hoyt's Clinical Neuro-Ophthalmology. Philadelphia, Pa:
Williams & Wilkins Company; 1998. 1727-29.

29. Vallat JM, Vallat M, Julien J, et al. Painful ophthalmoplegia (Tolosa-Hunt) accompanied by peripheral facial
paralysis. Ann Neurol. 1980 Dec. 8(6):645. [Medline].

30. Yousem DM, Atlas SW, Grossman RI, et al. MR imaging of Tolosa-Hunt syndrome. AJR Am J Roentgenol.
1990 Jan. 154(1):167-70. [Medline].

Medscape Reference 2011 WebMD, LLC

8 of 8 01/11/2016 08.07