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.
View Image | 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 ner.... |
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.[2] THS affects males and females equally. And, as stated, although rare in children it is important to keep this condition in the differential diagnosis.[32]
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.
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The diagnosis of Tolosa-Hunt syndrome is usually one of exclusion.
CBC count, erythrocyte sedimentation rate (ESR), electrolytes with glucose, thyroid function tests, fluorescent treponemal antibody (FTA), antinuclear antibody (ANA), lupus erythematosus (LE) preparation, antineutrophil cytoplasmic antibody (ANCA), serum protein electrophoresis, Lyme titre, angiotensin-converting enzyme (ACE) level, and HIV titre are helpful in eliminating other processes. This level of evaluation is required to exclude other conditions, which can have significant morbidity associated.
Cell count and differential, protein, glucose, fungal and/or bacterial cultures, Gram stain, cytology, and opening pressure of CSF are helpful in eliminating conditions mimicking Tolosa-Hunt syndrome; a mild (lymphocytic) pleocytosis within the spinal fluid may occur in patients with Tolosa-Hunt syndrome.
Anti-GQ1b antibodies may be helpful in distinguishing early, painless Tolosa-Hunt syndrome from Miller Fisher syndrome.
MRI[6] of the brain and orbit with and without contrast, magnetic resonance (MR) angiography or digital subtraction angiography (DSA), and CT scan of the brain and orbit with and without contrast may all be useful (see the images below). Inflammatory changes in the cavernous sinus, superior orbital fissure, and/or orbital apex are typically observed on high-resolution contrast-enhanced imaging. In the authors' experience, thin-slice high–magnetic field MRI of the cavernous sinus region, including coronal sections with and without contrast and fat-suppressed cuts of the orbital regions, is the modality of choice. These changes are not specific for Tolosa-Hunt syndrome and may also be present in neoplastic conditions of the cavernous sinus. Enlargement of the optic nerve or external ocular muscles has been described, emphasizing the continuum with idiopathic orbital inflammatory disorders.[31]
Note that findings on all imaging studies may be normal in some cases of Tolosa-Hunt syndrome.
Narrowing of the internal carotid artery within the cavernous sinus may be identified on angiography. Note that these changes are not specific to Tolosa-Hunt syndrome.
MRI with 3-dimensional constructive interference in steady state (3D CISS) provides an enhanced picture within the cavernous sinus. This type of imaging may assist with future diagnoses of TSH, but it is not yet used routinely.[7]
View Image | 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 ner.... |
View Image | Coronal T1-weighted MRI with (below) and without (above) enhancement demonstrates left cavernous sinus fullness consistent with Tolosa-Hunt syndrome (.... |
Biopsy of the lesion may be required to confirm the diagnosis. The technical difficulty of cavernous sinus region biopsies usually mitigates for a trial of steroids; nonetheless, biopsy may be needed to exclude neoplasm or if symptoms are progressing, atypical, or recurrent.
Biopsy reveals nonspecific granulomatous or nongranulomatous inflammation. This is histologically indistinguishable from the pathology of orbital pseudotumor, and these diseases may exist along a continuum.
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; indeed, 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[8] has been employed.
Surgical extirpation is not generally a feasible treatment of Tolosa-Hunt syndrome; the primary value of surgical intervention is a histopathologic diagnosis.
Neuro-ophthalmology evaluation is helpful to confirm the diagnosis and to exclude other etiologies of presenting symptoms. Consultation with a neurosurgeon may be useful in cases requiring biopsy.
Steroids are used to treat the inflammation of Tolosa-Hunt syndrome. Pain relief usually occurs rapidly, ie, within 24-72 hours.[9] Continue treatment at the initial dose for a short time (ie, 7-10 d) after pain resolves, then taper gradually. If no response to steroid therapy has occurred within 72 hours, the diagnosis of Tolosa-Hunt syndrome should be reevaluated.
If a patient is unable to tolerate steroid therapy, other immunosuppressive therapy may be considered.
Clinical Context: May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.
Clinical Context: Antimetabolite used to treat many autoimmune processes. The mode of action is not known; this drug does interfere with DNA synthesis.
Clinical Context: Immunosuppressive agent that works primarily on T cells. Works very slowly; may require 6-12 mo of trial prior to effect. Up to 10% of patients may have idiosyncratic reaction disallowing use. Do not allow WBC count to drop below 3000/µL or lymphocyte count to drop below 1000/µL.
Supervise a tapering schedule for the steroids and monitor for steroid-related adverse effects. Because the diagnosis of Tolosa-Hunt syndrome is often made clinically without histopathologic confirmation, vigilance must be maintained for the possibility of alternative masquerading diagnosis.
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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.
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.
Coronal T1-weighted MRI with (below) and without (above) enhancement demonstrates left cavernous sinus fullness consistent with Tolosa-Hunt syndrome (THS). The imaging features are nonspecific and must be placed into the context of the history, examination, and clinical course to avoid misdiagnosis of infiltrating, infectious, or neoplastic cavernous sinus processes. Image courtesy of Eric Eggenberger, DO.
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.
Coronal T1-weighted MRI with (below) and without (above) enhancement demonstrates left cavernous sinus fullness consistent with Tolosa-Hunt syndrome (THS). The imaging features are nonspecific and must be placed into the context of the history, examination, and clinical course to avoid misdiagnosis of infiltrating, infectious, or neoplastic cavernous sinus processes. Image courtesy of Eric Eggenberger, DO.