Tolosa-Hunt syndrome presenting as persistent unilateral headache and painful ophthalmoplegia: A rare case report highlighting diagnostic challenges and therapeutic response

Abstract

Tolosa-Hunt syndrome (THS) is a rare idiopathic granulomatous inflammation of the cavernous sinus, superior orbital fissure, or orbital apex, presenting with painful ophthalmoplegia. The exact etiology remains unclear, but it is believed to be immune-mediated. Early diagnosis is essential, as prompt corticosteroid therapy results in rapid symptom resolution. This case report highlights the clinical presentation, diagnostic workup, and management of a patient with Tolosa-Hunt syndrome, emphasizing the role of neuroimaging in confirming the diagnosis and the efficacy of corticosteroid treatment. A 55-year-old male presented with a persistent right-sided headache for 2.5 months, accompanied by diplopia for 5 days. Neurological and ophthalmic examination revealed right-sided ptosis, restricted extraocular movements, and binocular diplopia. MRI findings demonstrated an asymmetric enlargement of the right cavernous sinus with inflammatory changes extending into the orbital apex and superior orbital fissure, confirming Tolosa-Hunt syndrome. The patient was treated with high-dose corticosteroids, leading to significant clinical improvement. Following corticosteroid therapy, the patient experienced rapid resolution of headache and improvement in ocular motility. Repeat MRI after 6 weeks showed a marked reduction in inflammation. There was no recurrence of symptoms upon gradual steroid tapering. Tolosa-Hunt syndrome should be considered in patients with unilateral headache and painful ophthalmoplegia. MRI plays a crucial role in diagnosis, and corticosteroids remain the mainstay of treatment, leading to excellent outcomes. Early recognition and intervention can prevent long-term complications and disability.

Background

Tolosa-Hunt syndrome (THS) is a rare idiopathic granulomatous inflammation affecting the cavernous sinus, superior orbital fissure, or orbital apex, leading to painful ophthalmoplegia [1]. First described by Tolosa in 1954 and later characterized by Hunt et al. [2], THS is now recognized as a distinct clinical entity classified under the International Classification of Headache Disorders (ICHD) as a cause of recurrent painful ophthalmoplegia. The exact pathophysiology remains unclear, but it is believed to involve an immune-mediated inflammatory process that leads to perivascular infiltration, thickening of the cavernous sinus walls, and compression of adjacent cranial nerves [3].

Patients with THS typically present with acute or subacute onset of unilateral periorbital pain, followed by cranial nerve involvement, most commonly affecting the oculomotor (CN III), trochlear (CN IV), and abducens (CN VI) nerves [4]. This results in ptosis, diplopia, and ophthalmoplegia. The pain is often severe, persistent, and poorly responsive to conventional analgesics. Systemic symptoms such as fever and weight loss are usually absent, distinguishing THS from infectious or neoplastic etiologies [4].

Magnetic resonance imaging (MRI) is crucial for diagnosis, often revealing enlargement and enhancement of the cavernous sinus, sometimes extending into the orbital apex and superior orbital fissure. This imaging feature helps differentiate THS from other causes of painful ophthalmoplegia, such as cavernous sinus thrombosis, neoplastic infiltration, or aneurysmal compression [5]. While cerebrospinal fluid (CSF) analysis and laboratory investigations are typically unremarkable, they are essential to exclude alternative diagnoses, including infections, malignancies, and systemic vasculitides such as granulomatosis with polyangiitis [6].

The hallmark of THS is a dramatic response to corticosteroids, with rapid symptom resolution within 24 to 72 hours of initiation. This therapeutic response is often considered a key diagnostic criterion. However, relapses are common, and long-term follow-up is required to monitor for recurrence and steroid dependency. Alternative immunosuppressive agents, such as methotrexate or azathioprine, may be considered in refractory cases [7]. Given its rarity and diagnostic complexity, THS often poses a clinical challenge, necessitating a high degree of suspicion. Early recognition and appropriate management are critical in preventing unnecessary interventions and ensuring optimal patient outcomes.

Case presentation

A 55-year-old male presented to the emergency department with a chief complaint of persistent headache for the past 2.5 months, which was associated with the recent onset of double vision in the right eye over the last 5 days. The headache was described as a constant, dull, and throbbing pain localized around the right periocular region, occasionally radiating to the forehead. The pain intensity had gradually increased over the past week, causing significant discomfort. The patient reported that the headache was unilateral, without any associated nausea, vomiting, or photophobia. He did not experience any fever, chills, or recent episodes of upper respiratory tract infection. Additionally, the patient described experiencing diplopia, which worsened with rightward gaze. He noted that reading and watching television had become increasingly difficult due to the presence of double vision. There was no history of trauma, head injury, or recent surgical interventions. He denied any associated symptoms such as dizziness, facial numbness, or limb weakness.

The patient had no significant past medical history. He denied any known chronic illnesses such as hypertension, diabetes mellitus, or prior neurological or ophthalmologic disorders. He had never experienced similar symptoms in the past. There was no history of tuberculosis, malignancy, or autoimmune diseases. His family history was unremarkable, with no reported cases of neurological disorders. The patient had no history of smoking, alcohol consumption, or illicit drug use. His occupation did not involve exposure to toxic substances or prolonged screen use that could contribute to his symptoms.

On general physical examination, the patient appeared well-nourished and in mild distress due to the headache. His vital signs were stable, with no signs of systemic illness such as fever, weight loss, or pallor. Neurological examination was performed to assess cranial nerve function and motor and sensory responses. Cranial nerve examination revealed notable involvement of the right oculomotor nerve (CN III) and trochlear nerve (CN IV). The patient exhibited mild ptosis of the right upper eyelid, along with restricted eye movements in the right eye. There was significant limitation of rightward gaze, with almost no lateral movement of the right eye when attempting to look towards the right. Vertical movements were also restricted, particularly upward gaze, leading to vertical diplopia. Binocular testing confirmed worsening diplopia on rightward gaze, consistent with extraocular muscle dysfunction.

Ophthalmic examination revealed a visual acuity of 6/12 in the right eye and 6/6 in the left eye. Pupillary reflexes were intact, with no afferent pupillary defect observed in either eye. Fundoscopic examination did not reveal any signs of papilledema, retinal hemorrhages, or optic nerve abnormalities. There were no signs of conjunctival congestion or proptosis. The left eye examination was unremarkable, with normal extraocular movements and no signs of cranial nerve dysfunction. Motor and sensory examinations of the limbs and trunk were normal, with preserved deep tendon reflexes. There was no evidence of muscle weakness, sensory deficits, or cerebellar dysfunction. Gait was normal, and there were no signs of ataxia or balance impairment.

An MRI of the brain with contrast was performed to investigate the underlying cause of the patient's symptoms. The imaging findings revealed asymmetric enlargement of the right cavernous sinus, with marked thickening and enhancement of the right cavernous dura. The inflammatory changes extended into the orbital apex, superior orbital fissure, and right tentorium cerebelli, which correlated with the patient's clinical symptoms. The lesion appeared as a localized mass, exhibiting contrast enhancement without any evidence of malignancy, aneurysm, or vascular abnormalities. These findings were characteristic of Tolosa-Hunt syndrome (THS). Based on the patient's clinical presentation, ophthalmic examination findings, and characteristic MRI features, a diagnosis of Tolosa-Hunt syndrome was established. This rare condition, characterized by painful ophthalmoplegia due to idiopathic granulomatous inflammation of the cavernous sinus, was confirmed due to the combination of unilateral periorbital pain, cranial nerve involvement, and the absence of other significant systemic or infectious causes Fig. 1.

Fig 1.

(A) Axial T1-weighted MR image showing an enlarged right cavernous sinus, mildly hypointense to grey matter. (B) Coronal T1-weighted MR image demonstrating the same enlargement of the right cavernous sinus. (C) Axial postcontrast T1WI fat-suppressed image showing enhancement of abnormal soft tissue extending through the superior orbital fissure into the orbital apex. (D) Coronal postcontrast T1WI fat-suppressed image revealing hyperenhanced thickening of the right temporal dura, tentorium, and right orbital apex.

Discussion

Tolosa-Hunt syndrome (THS) is a rare idiopathic granulomatous inflammation of the cavernous sinus, superior orbital fissure, or orbital apex, leading to painful ophthalmoplegia. First described by Tolosa in 1954 and later expanded by Hunt in 1961, THS is now classified under the International Classification of Headache Disorders (ICHD) as a distinct entity characterized by severe periorbital pain, cranial nerve palsies, and rapid response to corticosteroids [1]. The exact etiology remains unclear, but it is believed to be immune-mediated, resulting in nonspecific granulomatous inflammation of the affected structures [8].

In this case, the patient presented with a 2.5-month history of headache localized to the right periocular region, followed by acute onset of diplopia due to cranial nerve involvement. The presence of unilateral painful ophthalmoplegia, particularly with oculomotor (CN III) and trochlear (CN IV) nerve dysfunction, aligns with the classical presentation of THS. The most common differential diagnoses for such a presentation include cavernous sinus thrombosis, meningioma, pituitary apoplexy, carotid-cavernous fistula, and infectious or neoplastic etiologies [9]. However, the absence of systemic signs, progressive worsening of symptoms, and characteristic MRI findings supported the diagnosis of THS.

Neuroimaging, particularly contrast-enhanced MRI, is the gold standard for diagnosing THS. Typical findings include enlargement and enhancement of the cavernous sinus, superior orbital fissure, or orbital apex, often with asymmetric thickening of the dura [10]. Our patient's MRI revealed asymmetric enlargement of the right cavernous sinus with inflammatory extension into the orbital apex and tentorium cerebelli, consistent with previously reported imaging characteristics of THS [11]. Although biopsy remains the definitive method for confirming granulomatous inflammation, it is rarely performed due to the invasiveness and excellent clinical response to corticosteroids [12].

The mainstay of THS treatment is high-dose corticosteroids, which lead to rapid symptom resolution in most cases. The mechanism behind this dramatic response is thought to be the suppression of granulomatous inflammation within the cavernous sinus [13]. Our patient experienced significant improvement within days of initiating corticosteroid therapy, with near-complete resolution of headache and diplopia over the subsequent weeks. This response further reinforced the diagnosis of THS. However, relapse is observed in up to 30%-40% of cases, necessitating close follow-up and, in some cases, long-term immunosuppressive therapy [14].

Despite the rarity of THS, early diagnosis is crucial to prevent unnecessary interventions and long-term complications. Given the potential overlap with other cavernous sinus pathologies, clinicians should maintain a high index of suspicion when evaluating patients with unilateral headache and painful ophthalmoplegia. A thorough neurological examination, targeted neuroimaging, and response to corticosteroid therapy remain the key pillars in diagnosing and managing THS effectively.

Conclusion

In conclusion, Tolosa-Hunt syndrome is a rare yet important differential diagnosis in patients presenting with unilateral headache and painful ophthalmoplegia. This case highlights the significance of recognizing its characteristic features, including persistent periorbital pain, cranial nerve involvement, and radiological evidence of cavernous sinus inflammation. Early diagnosis is crucial, as prompt corticosteroid therapy leads to rapid symptom resolution and prevents complications. The patient's dramatic response to steroids further reinforced the diagnosis, emphasizing the inflammatory nature of the condition. Given the potential for recurrence, long-term follow-up is essential to monitor for relapses and assess the need for extended immunosuppressive therapy. Increased awareness among clinicians can lead to timely intervention, ultimately improving patient outcomes in cases of Tolosa-Hunt syndrome.

Patient consent

Written informed consent was obtained from the patient for the publication of this case report.