Introduction

Tolosa-Hunt Syndrome (THS), named after Dr. Eduardo Tolosa and Dr. William Hunt, who first described this rare condition in 1954 and 1961, respectively, is known for causing pain around one eye, along with difficulty moving the eye, known as ophthalmoplegia.

It is also known as idiopathic orbital inflammation syndrome, and affects an insignificant number of people – about 1-2 per million, making it a rare condition recognised by the National Organisation for Rare Disorders (NORD) and one of the painful cranial neuropathies by the International Headache Society in its headache classification.

Studies show that THS results from an autoimmune response. This occurs when the body fights itself. Here, it targets and fights the space that houses the eyes and a specific area behind the eye known as the orbital space and cavernous sinus, triggering an inflammation. This inflammation leads to the compression of the cranial nerves (e.g., III, IV, VI and even trigeminal nerve V -- responsible for the eye, lower and upper jaw), in some while for others, the inflammation can result in numbness or tingling around the face.

A distinct feature of THS is that its symptoms can recur within a space of months or years and usually resolve when steroids are administered. THS can affect individuals of any gender and at any age.

People with THS experience problems with their eyes. To manage this condition, steroid medications are the drug of choice because of their activity in reducing swelling, leading to a period of relief.^1,2

How does THS present?

Symptoms experienced are usually for a short while and can resolve upon administration of Glucocorticoids within 2-3 days. Common symptoms include;

• Double vision.
• Swelling around the eyes.
• One-sided Headache (either the left or right side)
• One-sided Pain in the space/cavity that houses the eyes.
• Paralysis of the nerves that supply sensory functions to the brain, lower and upper jaws³

Diagnosis of THS

To diagnose THS, the diagnosis of exclusion method is used to rule out other conditions that present with similar symptoms, especially pain in the eyes. This is because diagnosing THS does not require a definitive test. To identify THS, physical examinations (e.g, understanding the patient’s symptoms), the use of imaging tools, Laboratory testing (e.g, Erythrocyte sedimentation rate), cerebrospinal fluid (CSF) studies, and administration of Glucocorticoids can be employed. 

A physical examination could be the physician observing the patient for one-sided eye pain and an unremarkable musculoskeletal or sensory response to rule out conditions such as Guillain-Barre syndrome and myasthenia gravis. 

Because THS affects the nerves behind the eye, doctors typically use imaging tests, like an MRI (Magnetic Resonance Imaging), to check for inflammation in areas like the cavernous sinus or the superior orbital fissure. An MRI can also help rule out other possible causes of similar symptoms, such as tumours, infections, or aneurysms. A Computerised Tomography (CT) can be performed to rule out ischemia-related conditions. 

To further diagnose THS, it is important to rule out cavernous sinus thrombosis, as this condition can develop due to infections or non-infectious causes like blood disorders (polycythemia or sickle cell disease), inflammation of blood vessels (vasculitis), pregnancy, dehydration, trauma, or recent brain surgery.

Aside from these, an Erythrocyte Sedimentation Rate (ESR) can help with a differential diagnosis. This test helps to detect inflammation, as the red blood cells settle quicker when there is an inflammation compared to when there is no inflammation, because of the presence of proteins.

Other differentials for diagnosis are Computed tomography (CT) of the head without contrast and CT scan of orbits with contrast. These imaging tests help with a detailed image of the blood vessels and their supply to the brain, assess acute conditions like bleeding within the brain and possible fractures, and assess the internal structure of the eyes.⁴

Why do we have a relapsing-remitting pattern with THS?

 A clear trait of THS is how it turns off and on, with times of strong pain and signs, then times when these signs calm down. The pain is because of swelling near the eyes, in a spot known as the cavernous sinus. This spot is key since it holds many brain nerves that help with eye movements and facial feeling — these are the cranial nerves III, IV, V and VI. It is impacted when certain immune cells, particularly macrophages, form clusters (granulomas) around the nerves, causing irritation and swelling.^5,6

The reasons for this OFF- and ON-pattern are unknown, but it might be that changes in the body's defence system can start times of swelling. When an ON time hits (ON period), people might feel a fast start of strong pain, often around the eyes or in the head, and problems like seeing double or trouble moving the eyes. These signs can stay for weeks to months. After one of these times, the signs might go away (OFF/REMISSION period) for a while, but they can come back again. People might face these ON and OFF times at different speeds. Some might have many ON times, while others might only have one or two in their whole life. Between each relapse can be months or years, again varying from patient to patient, making it challenging to predict when a new episode will arise. However, research suggests that nearly half of the patients treated for THS may have relapses, even over a 13 years period after initial diagnosis. This relapsing-remitting pattern is more common in children than adults.^7,8,9

The return of THS can be hard for those who have it. They may feel fine for a while, but then have sharp pain that harms their sight and makes daily life hard. We don't know why THS happens. It may start when the body's defence system wrongly hits the nerves in a key facial area, causing swelling.^10,11

How do we manage THS?

The aim in taking care of THS is to cut down on the bad signs, try to make the good times last longer, and push back the bad times. A drug called glucocorticoids is the top pick for treating THS, as it works well to hold back swelling. When inflammation is suppressed, there is ease with the pressure on the cranial nerves. So, the pain goes down, and things like eye movements and facial feel get back to normal.

One indicator in the diagnosis of THS is when patients feel relief or have their symptoms resolved within 24 to 72 hours. 

These Glucocorticoids come with lots of side effects, mainly if used too long or in high doses. They can raise blood sugar and blood pressure, make you put on weight, and even change your mood. Using them for a long time may cause thin bones, an increased risk of getting sick, and weak adrenal glands. A doctor decides the dose of Glucocorticoids based on how often the problem comes back and how bad the signs are, like headaches or swelling near the eyes. Examples of Glucocorticoids used are: Methylprednisolone and Prednisone. 

As with every dosage regimen of glucocorticoids, the medications are given at high dose for the first few days and then lowered gradually to reduce potential side effects over the next few days, weeks or even months, as symptoms resolve. 

Symptoms such as pain in and swelling around the eyes have been observed to improve in less than a week, while others, such as cranial nerve palsies, take about 2 to 3 months. 

In some cases where Glucocorticoids are contraindicated, ineffective, or to avoid possible side effects altogether, other treatment options, such as immunosuppressive medications (e.g., Azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, and infliximab) may be used as second-line therapy, but not without proof of THS using biopsy. 

 These drugs help by toning down the body's defence system to stop more swelling and help avoid dependence on steroids.^12,13

As a patient with THS, what can you do?

Once you get told you have THS, know that we don't know why it happens. While the onset of symptoms may disrupt your daily routines, ensure that to understand the symptoms. If you feel something new, talk to your doctor or nurse. Write down when you feel worse and better to help them take care of you. To not get hooked on Glucocorticoids, use them just as your doctor says.^14,15

Summary

Tolosa-Hunt Syndrome (THS) is a rare condition that affects 1 in a million persons, and its cause is unknown. It can cause sudden pain around the eye and difficulty moving it. This happens because the inflammation affects the nerves controlling vision and facial sensation. One distinct and challenging aspect of THS is its relapsing-remitting (OFF and ON) pattern, where symptoms come and go, with each pattern lasting for weeks or months.

Glucocorticoids (e.g., methylprednisolone and prednisone) are the drug of choice for the management of THS. These medications can reduce inflammation and relieve pain, with improvement often seen within 24 to 72 hours. While there is room for possible side effects, they can be managed. With ongoing care and support from your healthcare team, many patients find their symptoms well-controlled, and the prognosis is generally positive.