Case Report: Tolosa-Hunt syndrome, a neuroinflammatory origin of painful ophthalmoplegia

Introduction

Tolosa-Hunt syndrome is a disease characterized by granulomatous inflammation affecting the cavernous sinus and/or superior orbital fissure. This inflammation leads to the compression of various cranial nerves and subsequent neuropathic symptoms. This condition was originally documented in 1954.¹ Tolosa-Hunt syndrome manifests as ptosis, discomfort in the orbital, periorbital, or hemicrania areas, and ophthalmoplegia (partial or full).² Typically, inflammation originates in the cavernous sinus and then extends towards the superior orbital fissure and orbital cavity. This condition presents as recurring episodic attacks, following a pattern of relapsing and remitting. According to reports, there are about one in a million cases affected by this disease annually.¹ Tolosa-Hunt Syndrome (THS) primarily affects the cavernous sinus and its nerves. The most commonly involved nerve is the oculomotor nerve (CN III), seen in about 80% of cases. The abducens nerve (CN VI) is affected in about 70% of cases. The trochlear nerve (CN IV) and branches of the trigeminal nerve (V1 and V2) can also be affected. If inflammation spreads to the orbital apex, it can impact the optic nerve (CN II), leading to visual symptoms. Inflammation may extend to affect other nerves such as the facial nerve (CN VII).¹

Here we describe a 35-year old male patient who presented to the hospital with headache and right eye pain. A magnetic resonance imaging (MRI) scan showed thickening in the cavernous sinus region. He was diagnosed as a case of Tolosa-Hunt syndrome after exclusion of all other potential diagnosis. This case report follows the CARE checklist.⁸

Case presentation

A 35-year-old Egyptian male patient, with no past medical history presented to the emergency department (ED) of Hamad hospital complaining of a four-day history of progressively increasing headaches associated with right eye pain and double vision. According to the patient, the headache mainly affected the right and frontal sides of the head and was associated with nausea and three episodes of non-bloody vomiting. He denied any recent history of head trauma, loss of consciousness, fever, neck stiffness, or photophobia.

In the ED, his vital signs were within normal limits. Physical examination revealed impaired abduction of the right eye with horizontal nystagmus on lateral gaze consistent with right abducens nerve palsy. Careful examination of both upper and lower extremities was unremarkable. No motor or sensory deficits were noted. Kernig’s and Brudzinski’s signs were negative. Examination of other systems was unremarkable.

The patient’s lab results, including a complete blood count and comprehensive metabolic panel, were within normal ranges. A computed tomography (CT) scan result showed subtle asymmetric thickening of the right cavernous sinus. However, given the strong clinical suspicion of Tolosa-Hunt syndrome, the radiologist recommended doing magnetic resonance imaging (MRI) scan of the head and orbital region. Following discussion with neurology team, the patient received painkillers and was admitted to the medical floor for further management. The neurology team recommended cerebrospinal fluid analysis (CSF), autoimmune, and vasculitis workups to narrow down the differential diagnoses.

Results of the MRI revealed an intensely enhanced soft tissue thickening in the right cavernous sinus region, slightly extending to the right orbital apex, which caused enlargement of the cavernous sinus and appeared isointense to the adjacent muscles on T1 and T2 (Figure 2).

Figure 1. Computed Tomography (CT) scan showing subtle asymmetrical thickening of the cavernous sinus.

Figure 2. Magnetic resonance imaging (MRI) showing enhancing soft tissue thickening in the right cavernous sinus region (red arrow).

Magnetic resonance imaging (MRI) showing enhancing soft tissue thickening in the right cavernous sinus region (red arrow). (A): Axial view. (B) Coronal view.

CSF analysis through Lumbar puncture (LP) was done and the opening pressure was 17, and while waiting for the results, the patient was started on oral prednisolone 60 mg for three days and then tapered off. The results of the CSF analysis showed no abnormalities which ruled out the possibility of TB and meningitis, and the results of the autoimmune and vasculitis workup also came back negative which ruled out the possibility of sarcoidosis. A diagnosis of Tolosa-Hunt Syndrome was made, and the patient was discharged on oral prednisolone at 60 mg with a follow-up visit to a neurology clinic after 6 weeks. Two weeks later, the patient presented to the ED again with a headache and right eye pain after his symptoms had initially improved. He was treated symptomatically as a known case of Tolosa-hunt syndrome and discharged on the same day.

Discussion

Tolosa-Hunt syndrome stands as an uncommon entity of painful ophthalmoplegia, originating from non-specific inflammation within the cavernous sinus.

The National Organization for Rare Disorders (NORD) states that the disease typically emerges around the median age of 41 years, affecting both sexes.³ Our patient, however, was a 35-year-old male, which is relatively young in contrast to the average age of onset.

The specific etiology of the disease is not fully understood.² A non-specific granulomatous inflammation of the cavernous sinus with varying extension into the superior orbital fissure and orbital apex, along with infiltration of lymphocytes and plasma cells, is the primary characteristic of the disease. When patients present with symptoms of ophthalmoplegia and headache, it is necessary to rule out other malignant and autoimmune conditions, even though it is typically thought of as a benign condition. Understanding the differential diagnosis is more crucial to exclude other causes than it is to confirm the condition,⁴ as a requirement for the diagnostic criteria as per The International Classification of Headache Disorders (ICHD).

Tolosa Hunt’s Diagnostic criteria as per ICHD’s latest edition in 2018⁵ includes the following:

“A. Unilateral orbital or periorbital headache fulfilling criterion C

B. Both of the following:

   1. Granulomatous inflammation of the cavernous sinus, superior orbital fissure or orbit, demonstrated by MRI or biopsy

   2. Paresis of one or more of the ipsilateral cranial nerves III, IV and/or VI

C. Evidence of causation demonstrated by both of the following:

   1. Headache is ipsilateral to the granulomatous inflammation

   2. Headache has preceded paresis of the nerves III, IV and/or VI by 2 weeks, or developed with it

D. Not better accounted for by another ICHD-3 diagnosis”

Generally, MRI is a cornerstone in diagnosing pathologies of the cavernous sinus. In the case of Tolosa Hunt syndrome, the classical appearance is enhancing soft-tissue thickening of the cavernous sinus and superior orbital fissure that appears isointense to gray matter on T1-weighted images and iso- to hypointense on T2-weighted images.⁶

Our patient presented with a headache and right eye pain, and the physical examination showed a sixth (IV) cranial nerve palsy (Abducens nerve palsy). The results of the CT scan showed subtle asymmetric thickening of the right cavernous sinus. However, the radiology team recommended an MRI scan, as the clinical history and examination were highly suggestive of Tolosa-Hunt syndrome. The MRI results showed intensely enhanced soft tissue thickening in the right cavernous sinus region, slightly extending to the right orbital apex, which caused enlargement of the cavernous sinus and appears isointense to the adjacent muscles on T1 and T2. In addition, the results of the autoimmune, vasculitis, and CSF workups were all negative.

Since the disorder is inflammatory, high-dose glucocorticoids are the main course of therapy.¹ A progressive oral taper over a period of weeks is advised after an initial high-dose steroid therapy. Neuropathies may take months to resolve, requiring a longer steroid regimen. Neurological impairments may occasionally last a lifetime. Persistent MRI abnormalities should not affect the recommended length of therapy unless they show no regression because radiological improvement also takes time to resolve. Overall, 50% of individuals have a recurrence of the illness.⁷

After admission, our patient started prednisolone treatment with an initial dose of 60 mg for three days, followed by a tapering dose. He was discharged with a follow-up with a neurology clinic after 6 weeks. Two weeks later, he presented again to the ED with a headache and right eye pain, although his symptoms had initially improved with treatment. He was treated symptomatically and discharged on the same day.

Conclusions

Tolosa-Hunt syndrome is a very rare neuroinflammatory condition that presents as painful ophthalmoplegia. Thickening of the cavernous sinus on MRI images with a background history of ophthalmoplegia and headache is highly suggestive of Tolosa-Hunt syndrome. However, as the disease is a diagnosis of exclusion, it’s very crucial for clinicians to exclude other possible pathologies of painful ophthalmoplegia before establishing the diagnosis of Tolosa-Hunt syndrome.

Consent

Written informed consent for publication of their clinical details and clinical images was obtained from the patient.