Tolosa Hunt Syndrome
Patient #30 presented with retro-orbital pain and cranial nerve III, IV, and ophthalmic division of CN V involvement without other neurological signs or symptoms, localizing the responsible lesion to the cavernous sinus/superior orbital fissure. In no other part of the nervous system may these disparate cranial nerves, which are located intraparenchymally in the upper and lower midbrain and mid-pons, be affected without co-existent long-tract signs.
The cavernous sinus is a venous channel extending from the superior orbital fissure to the dorsum sella and functioning to drain blood from the orbit and deep, central portions of the brain. The cavernous sinus contains the carotid artery and oculosympathetic fibers that follow the carotid on their way to the pupillary fibers in the eye. In addition, cranial nerves III, IV, and the ophthalmic division of CN V travel beneath the dura in the lateral wall of the cavernous sinus. Cranial nerve VI runs through the inferior portion of the sinus immediately lateral to the internal carotid artery, and is, thus, one of two nervous structures (with the oculosympathetic fibers) that traverse the substance of the cavernous sinus (since the other structures run along the wall beneath a dural covering). Each of these structures then enters the superior orbital fissure on its way to innervate extraocular and pupillary muscles and provide sensation to the face. The maxillary portion of CN V traverses only the most posterior, inferior portion of the cavernous sinus before quickly exiting through foramen rotundum. The maxillary portion of CN V exits the skull through foramen ovale prior to entering the cavernous sinus.
The differential diagnosis of lesions affecting the cavernous sinus is large, including traumatic, vascular, infectious, inflammatory, neoplastic, and metabolic (diabetes mellitus) processes. The evaluation of patients with a superior orbital fissure/cavernous sinus syndrome is, therefore, oriented toward determining the underlying cause of the syndrome and rests heavily on neuroimaging. In this case, MRI showed an inflammatory process involving the right cavernous sinus. There were no signs suggestive of infection, and no clear underlying etiology could be identified. In the absence of an identifiable cause and a classic presentation of retro-orbital pain and cavernous sinus involvement in an otherwise healthy appearing patient, the diagnosis of Tolosa-Hunt syndrome was made. This is an idiopathic, granulomatous inflammatory process that involves the cavernous sinus/superior orbital fissure and is diagnosed by excluding other causes of the cavernous sinus syndrome.
The patient was treated with a five day course of intravenous Solumedrol followed by a tapering dose of oral prednisone. Within 24 hours he responded with a dramatic resolution of his retro-orbital pain and a gradual improvement in neurological deficits. This is typical of Tolosa-Hunt syndrome, which responds dramatically to steroid administration. The patient continues, however, to have mild residual diplopia, which has remained stable.
The Tolosa-Hunt Syndrome (THS) is a complex of periorbital or hemicranial pain associated with ipsilateral ophthalmoplegia, oculosympathetic dysfunction, and sensory loss in the first division of the trigeminal nerve. THS falls within the larger category of cavernous sinus/superior orbital fissure syndromes, and may consist of any of the above dysfunctions, with a varying severity. The etiology is an idiopathic granulomatous inflammatory process. The diagnosis, is therefore, made by exclusion.
The original criteria for this disorder included:
In 1988, W.E. Hunt and R.P. Brightman proposed a revision of the original criteria to include cases meeting all other criteria for THS, but showing involvement of V2, V3, or CN VII (which lie outside of the cavernous sinus). Their criteria, therefore, included cases "rarely involving structures outside the cavernous sinus". In addition, these authors downplayed the need for surgical exploration unless other diagnostic tools were unrevealing and there was no clinical response to steroids.
Tolosa-Hunt Syndrome is relatively rare, representing only 2.9 - 3.4% of cases of painful ophthalmoplegia. The age of onset varies from 3.5 to 75 years, with a peak in the fifth decade, and both sexes are equally affected. Usually pain either precedes or is concomitant with the ophthalmoplegia. The pain is generally located in the peri- or retro-orbital region, though it may involve the frontal or temporal regions as well. The pain is described as boring, lancinating, stabbing, and quite severe. Systemic symptoms (e.g., contralateral hemiparesis) have been described, but are rare (it is controversial whether these cases represented a truly idiopathic process).
There are many proposed causes of THS, including infections (e.g., syphilis, tuberculosis, bacterial periostitis) and inflammatory processes (including rheumatoid periostitis). To date, however, no clear etiology has been identified, and the diagnosis remains one of exclusion. The differential diagnosis is quite broad including the following:
Diagnostic testing is unrevealing by definition and is used primarily to exclude other clinical possibilities. Hematologic screens may show a mild leukocytosis or elevated ESR. Some patients may demonstrate elevated ANA or RF titers. CSF analysis may show a mild protein elevation or slight pleocytosis. Neuroimaging studies may be normal, but frequently show abnormal enhancing lesions in the cavernous sinus on MRI examination. Carotid angiography may show irregular narrowing of the carotid artery.
The clinical course of THS is variable. Spontaneous remissions may occur, but recurrences have been reported in up to 39% of cases and neurological deficits may persist. There is an almost universal response to corticosteroids, and this response is felt by many to be a diagnostic criterion. In most cases, the pain responds to corticosteroids within hours to days, but there is also frequently an improvement in the neurological symptoms. One must exercise caution in using the response to steroids as a diagnostic guide, however, since many diseases that affect the cavernous sinus/superior orbital fissure are steroid sensitive. In particular, lymphomas, chordomas, and giant cell tumors demonstrate an often dramatic response to this therapy. There are no definitive guidelines for the duration of steroid therapy, but severe, extensive pain, the severity of neurological deficits, and the presence of recurrences are used to guide therapy (generally toward longer courses and higher doses of steroids).
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