This article includes discussion of painful ophthalmoplegia, orbital inflammatory pseudotumor, orbital myositis, Tolosa-Hunt syndrome, orbital pseudotumor, and Tolosa-Hunt syndrome. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Orbital inflammatory pseudotumor is a condition that presents with orbit pain and variable degrees of proptosis, conjunctival injection, diplopia, and vision loss from optic nerve involvement. It is generally responsive to oral corticosteroids, which form the mainstay of treatment, but occasionally the disease is refractory and additional immunosuppressive agents or orbit radiation may be indicated. In this article, the author cites retrospective studies that help determine the utility of various imaging techniques and the response to corticosteroid treatment in arriving at a differential diagnosis of painful ophthalmoplegia.
• Orbital inflammatory pseudotumor refers to idiopathic inflammation in the orbit that may extend through the superior orbital fissure into the cavernous sinus, or may occur primarily in the cavernous sinus (Tolosa-Hunt syndrome) and extend into the orbit secondarily.
• If any specific infectious etiology is discovered, the process is not called orbital inflammatory pseudotumor but is named for the specific infection, eg, tuberculosis or fungi.
• Most cases respond promptly to high-dose (60 to 100 mg/day) prednisone, which should be continued for several weeks at high dose until ocular motility returns toward normal and then tapered to seek the lowest steroid dose that will maintain clinical remission.
• If the process responds to corticosteroids initially but breaks through repeatedly as the dose is tapered, consider the possibility of a lymphoma in the orbit and obtain tissue for pathologic examination, including cytology and other markers for neoplasm.
Historical note and terminology
The concept that orbital inflammatory pseudotumor and idiopathic inflammation in the cavernous sinus, or Tolosa-Hunt syndrome, are probably the same or closely related entities with different anatomic distributions developed relatively recently. The following paragraphs outline the development of our understanding of orbital inflammatory pseudotumor starting in the early part of this century, and then introduce the historic setting in which Tolosa-Hunt syndrome was established as a diagnostic entity. It is understandable that the pathology and immunology of orbital pseudotumor have been investigated much more intensively than those of Tolosa-Hunt syndrome because orbital tissue is relatively accessible for biopsy as compared with tissue from the cavernous sinus.
The idea that orbital inflammation could mimic neoplastic tumor in the orbit was introduced early in this century by Birch-Hirschfeld, who coined the term "pseudotumor" (Birch-Hirschfeld 1905). In the early 1940s, a distinction was drawn between cases in which the inflammation involves primarily the extraocular muscles and those in which the site of inflammation is primarily the orbital fat or other tissues (Dunnington and Berke 1943). The term "orbital myositis" was coined to describe those with primarily muscle involvement.
In the 1960s granulomatous inflammation in the orbit was found to be clinically and histopathologically distinct from other inflammatory orbital lesions. Nongranulomatous cases were subsequently divided into vasculitic (relatively uncommon) and nonvasculitic (more common) subgroups. During the 1960s and 1970s it was found that some individuals among those with a lymphocytic, nonvasculitic type of orbital lesion developed systemic lymphoma on follow-up. The question then arose whether these were really benign, nonneoplastic orbital lesions and the systemic disease independent, or whether the original orbital lesion was neoplastic and was not recognized as such at the time of presentation (Henderson 1994).
In the 1970s lymphocyte phenotyping revealed a functional difference between B and T lymphocytes that was morphologically indistinguishable. Individual cases were then further subdivided into "monomorphous types" with only B lymphocytes and "polymorphous types" having a mixture of B and T lymphocytes. It was thought that the monomorphous types had a greater likelihood than the polymorphous lesions of being clonally related to a single neoplastic lymphocyte line, and hence lymphomatous. However, it became apparent that the clinical behavior was not always predicted by the phenotypic mix of cells in the original lesion.
The next important development was the ability to recognize B lymphocyte production of "monoclonal" or "polyclonal" antibodies, the former favoring a neoplastic disorder. Names applied to the polyclonal group include "benign," "reactive," or "atypical lymphoid hyperplasia." Throughout the decade between 1980 and 1990, F A Jakobiec and D M Knowles II applied these laboratory advances to the diagnosis of orbital inflammatory pseudotumor (Knowles et al 1990; Henderson 1994).
In 1954 Eduardo Tolosa of Barcelona described a 47-year-old man with recurrent retro-orbital pain and dysfunction of the third, fourth, fifth, and sixth cranial nerves (Tolosa 1954). There had been a 3-year spontaneous remission between symptomatic episodes. The patient died a few days after an intracranial exploratory operation that had yielded no definite pathology. The autopsy, however, showed granulomatous inflammatory infiltration around the intracavernous portion of the internal carotid artery and adjacent cranial nerves.
In 1961 Hunt and colleagues reported 6 patients with orbital and brow pain along with various combinations of third, fourth, and sixth cranial nerve dysfunction on the same side (Hunt et al 1961). They reviewed Tolosa's pathologic material and judged that their patients had the same condition, although tissue samples had not been obtained. The rapid and dramatic relief of pain and ophthalmoplegia produced by systemic corticosteroid administration led these authors to conclude that their patients had the same inflammatory condition described by Tolosa.
Lakke from Utrecht reviewed clinically similar cases, calling them "superior orbital fissure syndrome," and presented pathologic material from a 47-year-old male patient with severe right retro-orbital pain followed by progressive ipsilateral ophthalmoplegia and ocular sympathetic involvement (Lakke 1962). At surgery, inflammatory tissue was found along the lateral wall of the cavernous sinus and the dura over the adjacent lesser wing of the sphenoid bone. His opinion was that these cases were all the same entity that Tolosa had documented pathologically and Hunt had described clinically. Further pathologic documentation was soon made available in 2 more cases of painful ophthalmoplegia (Schatz and Farmer 1972).
Lakke reviewed the literature describing an essentially similar painful ophthalmoplegia, without proptosis, ascribed most often to an inflammatory pachymeningitis from tuberculosis or syphilis, but often without laboratory or pathologic confirmation (Lakke 1962). Some cases may also represent sterile inflammatory reaction adjacent to paranasal sinus infection (Kretzschmar and Jacot 1939).
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