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.
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.
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. THS affects males and females equally. And, as stated, although rare in children it is important to keep this condition in the differential diagnosis.
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.
Patients present with usually severe retro-orbital or periorbital pain of acute onset. This pain may be described as constant and "boring" in nature.
Diplopia related to ophthalmoparesis follows the onset of pain (in rare cases, the ophthalmoparesis precedes the pain, sometimes by several days). Patients may report visual loss. This is noted if the inflammation extends into the orbit to affect the optic nerve, and it is not a factor in disease limited to the cavernous sinus. Paresthesias along the forehead may be described if the first division of the trigeminal nerve is involved.
Tolosa-Hunt syndrome is most often unilateral, although bilateral cases have been described. The syndrome frequently mimics other conditions; a single characteristic that is pathognomonic for this process does not exist. As such, realizing that this is a diagnosis of exclusion becomes even more important. Many of the processes that are found within the differential diagnosis of Tolosa-Hunt syndrome can have significant associated morbidity if not diagnosed and treated appropriately.
Painful ophthalmoparesis or ophthalmoplegia is the hallmark of this syndrome.
In addition to the optic and trigeminal nerves (V1, rarely V2 distribution), any of the ocular motor nerves may be involved. The oculomotor and abducens nerves are most commonly affected. Evidence of incomplete third nerve palsy with or without pupillary sparing may be present. Conversely, inflammatory involvement of the sympathetic nerves passing through the interior of the cavernous sinus may produce Horner syndrome with miosis. The combination of unilateral oculomotor palsy and Horner syndrome increases the localization specificity for the cavernous sinus.
Ptosis may be observed related to oculomotor palsy. Lid swelling is more likely to occur with orbital disease rather than inflammation limited to the cavernous sinus. These changes have been misdiagnosed as a complication of sinusitis.
Mild proptosis and/or optic disc edema may be noted if the orbit is involved.
Evidence of trigeminal nerve involvement is suggested by loss of the ipsilateral corneal reflex.
The International Headache Society criteria for Tolosa-Hunt syndrome include the following:
- Episode(s) of unilateral orbital pain for an average of 8 weeks if left untreated
- Associated paresis of the third, forth, or sixth cranial nerves, which may coincide with onset of pain or follow it by a period of up to 2 weeks
- Pain that is relieved within 72 hours of steroid therapy initiation
- Exclusion of other conditions by neuroimaging and (not compulsory) angiography
Corticosteroids are the treatment of choice, usually providing significant pain relief within 24-72 hours of therapy initiation. Ophthalmoparesis usually requires weeks to months for resolution; ophthalmoparesis may not completely resolve in some cases depending on the degree of inflammation and the aggressiveness of therapy. For refractory cases, azathioprine (Imuran), methotrexate, or radiation therapy has been employed