Introduction

Tolosa-Hunt syndrome (THS) is a rare disorder, which is part of the list provided by the National Organisation for Rare Disorders (NORD).^1,2 THS is synonymous with ophthalmoplegia (syndrome, painful or recurrent, as three separate terms).² Ophthalmology focuses on the eyes.³ Ophthalmoplegia involves eye muscle paralysis.⁴ Unfortunately, this disease is usually idiopathic,⁵ meaning that it does not have a known cause.⁶ THS patients present with persistent headaches, or what Dr Colin Tidy (2023) described as a ‘hemicranial or preorbital “gnawing’’ pain.⁸ 

As the symptoms of THS are not specific only to this disease, diagnosis follows a set of criteria from the International Classification of Headache Disorders (ICHD).⁸ The process requires exclusion due to other diseases involving painful ophthalmoplegia. Ensuring an accurate and early diagnosis allows for more immediate and effective treatment.⁹

Definition and pathophysiology

THS is known as an idiopathic orbital inflammatory disease.⁵ We will break this down below:

The term ‘idiopathic’, in this case, refers to the fact that the causes for THS are usually unknown.^6,7 It is linked to what is called non-specific granulomatous inflammation. To explain, the nonspecific immune system involves certain cells which gather at a site to fight against pathogens.¹⁰ Granulomas are benign clusters of immune cells and other tissue.¹¹ Inflammation is caused by the release of substances by immune system cells that widen the blood vessels and make them more “leaky.” The process continues, and more immune cells enter the site.¹⁰ Finally, the term ‘orbital’ refers to the eye socket, a small and bony structure that helps protect the eyeball.¹² The cavernous sinus (space behind the orbital that allows blood movement away from the brain) and the superior orbital fissure (an opening at the top of the orbit) are also places where idiopathic granulomatous inflammation may occur. ^5,13,14

The granulomatous inflammation can cause paralysis by affecting the cranial nerves.¹⁵ For example, the inflammation can put pressure on the cranial nerves III, IV and VI.⁷ It can also compress the superior divisions of cranial nerve V. The result is a severe periorbital headache and eye muscle paralysis (ophthalmoplegia).¹⁶ 

Primary symptoms

Pain

THS can cause a headache, which has been described as ‘gnawing’.⁸ These present periorbitally, referring to the tissues surrounding the orbit.^7,17 The headaches are severe and occur suddenly. They are also described as chronic and unilateral.² The unilaterality means the headache is localised to one side of the head.¹⁸  

Ophthalmoplegia

The pressure on the cranial nerves causes painful ophthalmoplegia.¹⁵ After the headache onset, paralysis of the eyes reduces eye movements. This is usually only applicable to one eye, rather than occurring in both, meaning that it is usually unilateral.^1,2 For example, a patient could present with severe left ophthalmoplegia and yet have no abnormality of movements with their right eye.⁵

Associated neurological signs

Several other symptoms may help to diagnose Tolosa-Hunt Syndrome, some of which have been added following recent presentations of THS.⁸ 

Ptosis

Ptosis is the drooping of the upper eyelid.¹⁹ It has previously helped to reveal THS,²⁰ serving as assistance in diagnosis, being a feature that may be looked for in a physical exam.²¹ This can occur as a result of the damage to cranial nerve III, also known as the oculomotor nerve. Normally, this nerve would support upper eyelid elevation ²²

Diplopia (Double vision)

Cranial nerve paralysis can also cause diplopia (double vision).²³ For example, it may be linked to damage to the functioning of the oculomotor nerve (cranial nerve III).³⁰ This means the patient is seeing two of the same image.²⁴ With one eye undergoing ophthalmoplegia, it may no longer look to the required focal point at the same time as the other eye. The eye misalignment can thus trigger double vision, making it appear as if there are two of the same image, separate.^24,25

Sensory impairment

During a physical exam, the patient’s facial sensation may be observed.²¹ It is possible that the superior divisions of the cranial nerve V may have been affected.¹⁶ The fifth cranial nerve is also known as the trigeminal nerve, and is responsible for a lot of facial sensory innervation.²⁶ One of the possible symptoms includes pain and loss of sensation in relation to the second branch of the trigeminal nerve.^27,28

Pupillary abnormalities

Patients have previously presented with pupil abnormalities. For example, pupil reaction to light may be sluggish or completely absent.²⁹ Normally, the expectation is that the pupil would shrink in response to light.³¹ The third cranial nerve (the oculomotor nerve) is connected to the pupil. As THS can impact the oculomotor nerve’s functioning, it may result in the pupils’ inability to react normally to light. One of the main functions of the oculomotor nerve is to constrict the pupil.³²

Systemic signs (Less common)

Systemic signs are symptoms that affect the body as a whole, instead of being focused on one part of the body or one organ.³³ For example, it is possible for THS to present with a fever, however, it is not as commonly described as the other previously mentioned symptoms, and is likely less definitive.^2,34 It is also possible that THS may occur in response to another autoimmune disease, as it has been previously documented with autoimmune inflammatory disorders, e.g. systemic lupus erythematosus.¹

A few others mentioned as potential systemic signs include:³⁵

• Backaches³⁵
• Cold feet³⁵
• Arthralgia³⁵
• Chronic fatigue³⁵
• Vertigo³⁵

Temporal profile

The symptoms of THS do not usually last in a chronic state. They mostly do not require intervention.² They may, however, recur randomly.² This tends to happen every few months or years.¹ Steroid treatment is known to improve the orbital pain, whilst glucocorticoids are the main method of treatment, improving symptoms dramatically.¹ 

Differential diagnosis

The International Headache Society (IHS) has set out the International Classification of Headache Disorders (ICHD).³⁶ Identifying THS is important, as it is not the only disease that can cause painful ophthalmoplegia.¹

Differential diagnosis refers to the selection of one diagnosis from a list of possible ones.³⁷ There is a long list of potential diseases with similar presentation.⁸ To name a few:

• Tumours (e.g. pituitary adenoma)⁸
• Infection (e.g. tuberculosis)⁸
• Migraine⁸
• Systemic Lupus Erythematosus (as mentioned earlier, an autoimmune inflammatory disorder)¹
• Diabetic Neuropathy¹
• Lyme Disease¹

Diagnostic tests and methods can help determine whether or not the presentation of symptoms is a result of the rare disease, THS. These include magnetic resonance imaging (MRI) and computed tomography (CT) scans, looking at the patient’s history in detail and carrying out a thorough clinical evaluation.²

Summary

Tolosa Hunt Syndrome is a rare disease which clinically presents in the form of, according to the IHS, a unilateral orbital or periorbital headache.³⁶ This is coupled with the painful ophthalmoplegic restrictions to the eyes. The disease is not consistent in its symptom presentation, as they may appear with gaps of months between. It is both possible and important to diagnose this disease, although there are several others that can present with similar symptoms. The correct diagnosis is beneficial to an individual’s healthcare as it helps to potentially explain to some extent what the patient is going through, and can help inform the decisions made by healthcare professionals going forward.^38,39 THS symptoms respond well to glucocorticoids, which are said to drastically reduce them.