The Case

A 69-year-old male presents to the emergency department for evaluation of diplopia. Three days prior, he had developed left-sided periorbital and ocular aching pain. He then noticed decreased peripheral vision on the left. The patient denies worsening pain with extraocular muscle movement. He also denies photosensitivity, eye redness, discharge, flashing lights, floaters, or a curtain or veil over his vision. He hasn’t experienced headache, temple pain, jaw claudication, or fever, and there are no other neurological symptoms, such as extremity numbness, weakness, or slurred speech. He denies any recent trauma.

On physical examination, he is afebrile, and his vital signs are within normal limits. His ocular exam is notable for the following:

• Left eye: ptosis, weak adduction, no abduction
• Pupils: 3 mm bilaterally and reactive to light
• Visual acuity: right eye 20/30, left eye 20/25, no afferent pupillary defect

The remainder of his examination is normal.

The patient undergoes an MRI of the brain and orbits, which reveals an increased T2 signal with enhancement involving the left lateral rectus muscle and intraconal fat (orbital compartment) extending into the orbital apex and left cavernous sinus.

The patient’s MRI revealed an increased T2 signal with abnormal enhancement within the left lateral rectus muscle and intraconal fat extending into the orbital apex and left cavernous sinus.
Ethan Sterk

He is admitted to the neurology service, and subsequent workup includes the following tests: erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, antineutrophil cytoplasmic antibody, rapid plasma reagin, double-stranded DNA antibody, Lyme polymerase chain reaction, angiotensin-converting enzyme (ACE), and anti-smooth muscle antibody. They are all negative. Also, cerebrospinal fluid (CSF) testing is remarkable for a glucose of 99, a protein of 93, and one white blood cell. CSF cultures are negative; ACE and Lyme antibodies are also negative. Ophthalmology is consulted, and the patient is diagnosed with Tolosa-Hunt syndrome.

Discussion

Tolosa-Hunt syndrome is rare, with an estimated incidence of one case per million per year. It is characterized by painful ophthalmoplegia and is caused by an idiopathic granulomatous inflammation of the cavernous sinus. The inflammation produces pressure and secondary dysfunction of the structures within the cavernous sinus, including cranial nerves III, IV, and VI, as well as the superior divisions of cranial nerve V.^1–5 Diplopia results from cranial mono- or polyneuropathy. Patients may present at any age. Men and women are affected at the same frequency.⁴

Most patients who present with painful ophthalmoplegia will not have Tolosa-Hunt syndrome. The syndrome of painful ophthalmoplegia may be caused by any process exerting a mass effect on the cavernous sinus. These

(click for larger image) Table 1: Causes of Painful Ophthalmoplegia

include a primary intracranial tumor, lymphoma, other local or distant metastatic tumors, aneurysm, carotid-cavernous fistula, carotid dissection, cavernous sinus thrombosis, infection, vasculitis, and sarcoidosis (see Table 1). Of these conditions, tumors and vascular conditions are the most common. In addition to these structural, compressive lesions, painful ophthalmoplegia can also be caused by ophthalmoplegic migraine, giant cell arteritis, or a diabetic cranial nerve palsy.

The diagnosis of Tolosa-Hunt syndrome is based upon the clinical presentation in conjunction with neuroimaging results and a clinical response to corticosteroids. Laboratory tests and lumbar puncture are also recommended. The specific diagnostic criteria recommended by the International Headache Society are:²

• Unilateral headache
• Granulomatous inflammation of the cavernous sinus, superior orbital fissure, or orbit, demonstrated by MRI or biopsy
• Paresis of one or more of the ipsilateral third, fourth, and/or sixth cranial nerves
• Evidence of causation demonstrated by both:
  • Headache has preceded oculomotor paresis by <2 weeks or developed with it.
  • Headache is localized around the ipsilateral brow and eye
• Symptoms not accounted for by an alternative diagnosis

Glucocorticoid administration has diagnostic as well as therapeutic utility.3 Rapid resolution of pain, within 24 to 72 hours, helps to confirm suspected Tolosa-Hunt syndrome. Improvement of cranial nerve deficits and regression of MRI abnormalities over the subsequent two to eight weeks provide further confirmation of the diagnosis.⁶ A suggested regimen is prednisone 80 to 100 mg daily for three days. If pain has resolved, then taper prednisone to 60 mg, then to 40 mg, 20 mg, and 10 mg in two-week intervals. A small group of patients will require other immunosuppressive medications either to limit the complications of corticosteroid use or to keep the disorder in remission. Typically, such patients will require biopsy confirmation of the diagnosis.⁷

The prognosis for most patients is favorable. However, some patients follow a relapsing-remitting course requiring prolonged corticosteroid or other immunosuppressive therapy, and a few have permanent cranial nerve deficits.

Dr. Sterk is associate professor of emergency medicine at Loyola University Chicago–Stritch School of Medicine..

References

1. Iaconetta G, Stella L, Esposito M, et al. Tolosa-Hunt syndrome extending in the cerebello-pontine angle. Cephalalgia. 2005;25(9):746-750.
2. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808.
3. Colnaghi S, Versino M, Marchioni E, et al. ICHD-II diagnostic criteria for Tolosa-Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus. Cephalalgia. 2008;28(6):577-584.
4. Kline LB, Hoyt WF. The Tolosa-Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71(5):577-582.
5. Zhang X, Zhou Z, Steiner TJ, et al. Validation of ICHD-3 beta diagnostic criteria for 13.7 Tolosa-Hunt syndrome: analysis of 77 cases of painful ophthalmoplegia. Cephalalgia. 2014;34(8):624-632.
6. Cakirer S. MRI findings in Tolosa-Hunt syndrome before and after systemic corticosteroid therapy. Eur J Radiol. 2003;45(2):83-90.
7. Shindler KS. Tolosa-Hunt syndrome. UpToDate websitet. Accessed Nov.9, 2018.