Introduction

Tolosa-Hunt syndrome (THS), a type of ophthalmoplegia, is a condition that affects the eye muscles. THS causes orbital pain and inhibits cranial nerves, such as the oculomotor, leading to limited eye movement.¹ In the majority of cases, it is primarily the third (oculomotor), fourth (trochlear) and sixth (abducens) cranial nerves which are compromised. As a result, there is restricted eye movement and motor function in the eye. 

The most common form of treatment is administering corticosteroids to reduce inflammation that inhibits nerve function. This is linked with positive patient outcomes in general. However, it is important that high doses are administered consistently to prevent recurrence. In cases of relapse, corticosteroids, which act through the glucocorticoid receptor (GR), have still been effective in treating THS.²

The general prevalence of THS is not well documented. However, the majority of cases are benign in countries such as Qatar and is not a result of inflammation. Although steroids do help in benign cases, they are more effective at acting through the GR to reduce inflammation.⁽³⁾ This article will focus on how steroids treat THS and the response to steroid treatment. Future directions on steroid treatment for THS will also be explored.

Pathophysiology of Tolosa-Hunt syndrome

THS involves several underlying mechanisms. Initially, the cavernous sinus and orbital apex become inflamed, which leads to painful ophthalmoplegia. A hallmark of THS is granulomatous inflammation, when immune cells form large clumps called granulomas. These granulomas cause paralysis in the aforementioned nerves and compromised muscle function in the eyes.⁴ Notably, before the onset of ophthalmoplegia, involvement of the third, fourth and sixth cranial nerves leads to retrobulbar pain. Inflammation of nerves, such as the optic nerve, leads to pain in the areas behind the eye and makes it painful for those affected to move their eyes, which further exacerbates the pain.⁵

There are different techniques and methods to diagnose this condition. However, this is difficult at times as the pathology is similar to some other conditions. The main symptoms observed are periorbital pain, unilateral (one eye) and ophthalmoplegia in serious cases. Headaches, fatigue and back pain are common in THS patients. Nerve palsies are an important feature of THS, which allows this disease to be diagnosed effectively.⁶

Techniques such as magnetic resonance imaging (MRI) are used to assess the inflammation in the cavernous sinuses, orbital apex and other affected regions.⁷ Computer tomography (CT) scans are also an effective imaging technique to detect THS.⁸ THS has been referred to as a diagnosis which involves exclusion, meaning that other conditions with similar symptoms have to be assessed before a diagnosis of THS is made. This is because granuloma formation and other symptoms present themselves in other diseases.⁹

Role of steroids in THS management

Steroids are very important when managing the symptoms of THS. Corticosteroids are used to reduce inflammation by acting through the glucocorticoid receptor. This works by glucocorticoids binding to this receptor, leading it to dimerise. Then it activates the transcription of anti-inflammatory genes and factors, such as GILZ, and inhibits the transcription of pro-inflammatory genes and factors, such as IL-6 and NF-kB.¹⁰ As glucocorticoids prevent pro-inflammatory gene transcription, this inevitably leads to a suppressed immune system, meaning that the body is less effective at countering certain illnesses.¹¹

It is important to control factors, such as the dosage of corticosteroids. For example, in doses below 30 milligrams per day is considered too low to outweigh the risks associated with taking steroids. Furthermore, the duration of the cycle can vary as well, but many successful outcomes occur when steroids are taken for a prolonged period of time.¹² There are cases where high doses are tapered, which is when the dosage is gradually reduced, is shown to be effective as well and this leads to shorter treatment courses.¹³

Clinical response to steroid treatment

There are certain responses to steroids when they are used to treat THS cases. Pain relief tends to vary with some patients having greatly reduced pain and some not necessarily recovering or doing so very slowly. There is also a similar trend regarding the resolution of cranial nerve function. However, steroids are used to reduce pain and 

eventually restore nerve function through inflammation reduction.¹⁴ Patient symptoms can be relieved through steroid treatments. However, this needs to be studied more over time as some symptoms tend to reappear when steroid administration is stopped.¹⁵ There are many different reasons as to why treatment responses are variable, such as treatment timings, dosage, and severity of THS symptoms, all of which influence patient responses to steroid treatment.¹²

Challenges and complications

There are some issues associated with steroid treatment that must be considered when managing THS. The short-term effects of glucocorticoid therapy include hyperglycaemia, which is when blood glucose levels are higher than normal. In addition to this, many patients experience hypertension alongside mood changes due to the overall neuropsychological effects associated with corticosteroid use. Pancreatitis is also prevalent in some cases. 

The long-term effects include osteoporosis, in which bones become weaker, and insufficient functioning of the adrenal glands, which can have many different side effects as hormones are produced in inadequate amounts. Ophthalmologic defects are also a potential issue, which will further exacerbate THS.¹⁶

Relapses remain a concern as well, despite the effectiveness of steroids in THS management. Relapses occur in 40% of cases after treatment in the months or years following a successful outcome. This suggests that steroids may not always provide long-term control. Relapses appear to be more common in younger patients, although further research is needed to confirm this trend. To manage recurrent THS, steroids alongside steroid-sparing agents may need to be administered over a long period of time.¹⁷

Alternative and adjunctive treatments

Steroids do not always work, which means that other alternative treatments must be utilised. Some patients who do not respond well to steroid treatment take immunosuppressive agents, such as methotrexate or azathioprine, which have shown positive results when steroids are ineffective. Other drugs, such as biologics are been used to reduce inflammation. In certain cases, radiation therapy has also been employed.¹⁸

To manage the pain, a structured approach is critical, particularly when patients present with ophthalmoplegia. Providing a caring environment for those affected is essential in managing this condition.¹⁹ Physical therapy is utilised to manage THS symptoms such as fatigue, neck pain and spasms, as many patients experience this alongside ophthalmoplegia.²⁰

Case studies and evidence-based insights

Many clinical studies have indicated that steroids are effective when treating THS. However, many people may need additional treatment such as biologics. Furthermore, recurrences are not out of the question. In some trials, a third of people experienced THS following treatment. However, symptoms can be relieved within a month when corticosteroids are used.²¹ Due to the overall success of corticosteroids, it remains the primary treatment for THS. However, other therapies, such as the previously mentioned immunosuppressive agents, are also effective in cases of treatment resistance or relapse.²²

Future directions and research needs

Further research on THS to improve diagnosis and treatment is needed. There are cases where THS is misdiagnosed therefore, a structured criterion to diagnose this disease needs to be put in place to prevent this in the future. As symptoms are similar to other diseases, there have been issues in assessing THS, which can improve over time.²³ Furthermore, specific biomarkers are currently under development to aid the diagnosis of THS given its impact on neurometabolism. As a result, diagnostic accuracy will inevitably improve in the years to come.²⁴ These advancements have also facilitated the development of more targeted and specific treatments, which are likely to enhance overall patient outcomes.²¹

Summary

To conclude, steroids are used in THS cases to reduce inflammation in the nerves that are affected, helping improve eye movement and impaired function. It acts through the glucocorticoid receptor and is largely a successful treatment method in the majority of cases. However, some patients do not respond well to corticosteroids, and treatment outcomes have been shown to be variable, leading to alternative therapies being used, such as immunosuppressive agents and biologics. It is of the upmost importance that those with THS have personalised treatment plans, with careful monitoring of steroid dosage and other contributing factors to ensure effective and safe management. Further research into the diagnosis and specialised treatment of THS is essential to improve patient outcomes. With the continued advancement of medical technology, both diagnostic methods and therapeutic options are expected to evolve, leading to more effective management in the near future.