Introduction

Tolosa-Hunt Syndrome is a rare condition that causes an individual pain around one eye (also known as unilateral) and restrictive movements of the affected eye. Ophthalmoplegia refers to the inability or restricted eye movement of the affected eye. This article will explore the signs of ophthalmoplegia that can be associated with Tolosa-Hunt Syndrome. 

Epidemiology 

Tolosa-Hunt Syndrome is commonly noted in individuals aged 41, it is considered very rare in younger individuals.¹ Moreover, there have been reports that although a majority of cases only impact an individual unilaterally, there are approximately 5% of cases that can impact individuals bilaterally (both eyes).^1,2 

Pathophysiology

Tolosa-Hunt Syndrome is caused by inflammation (also known as swelling) in a structure of the brain called the cavernous sinus.^1,2 The cavernous sinus is defined as a space that is located behind the two eyes in the head.³ It is a space that supports the drainage of blood from the brain and the face, and also holds cranial nerves that are responsible for eye movements, facial movements and sensation.³ In Tolosa-Hunt Syndrome, the underlying root cause of the inflammation in the cavernous sinus is not known. However, the inflammation can inadvertently put pressure on structures within the cavernous sinus (i.e. cranial nerves).^1,4 Out of the twelve cranial nerves in total, three cranial nerves are responsible for ocular movements (eye movements):⁴

• The third cranial nerve, known as the oculomotor nerve
• The fourth cranial nerve, known as the trochlear nerve
• The sixth cranial nerve, known as the abducens nerve

Any pressure on the third, fourth or sixth cranial nerves can cause pain or restrictions on eye movements, leading to ophthalmoplegia.^1,4 Furthermore, a branch (known as the ophthalmic branch) of the the fifth nerve, known as the trigeminal nerve can also be affected by the inflammation in the cavernous sinus.⁵ 

Signs and Symptoms

Tolosa-Hunt Syndrome causes a myriad of symptoms, including: 

Pain¹

• Sudden onset of severe pain that is usually described by individuals as a ‘sharp’, ‘shooting’, or ‘stabbing’ sensation either around and or behind the affected eye. This is known as orbital or periocular pain
• An individual can experience pain in the forehead and the temples. This is known as frontal and temporal pain
• Often, individuals can present up to one month in advance with pain related to the affected eye before the signs of ophthalmoplegia present

Ophthalmoplegia

• Individuals typically experience ophthalmoplegia in one eye when one or more of the nerves responsible for eye movements are affected.¹ The oculomotor nerve is impacted in approximately eighty per cent of cases, whereas the trochlear nerve is impacted in less than a third of individuals, and the abducens nerve is impacted in less than three-quarters of cases¹¹ 

Diplopia

• In Tolosa-Hunt Syndrome, an individual can experience diplopia (known as double vision) if the oculomotor nerve, the trochlear nerve and, or the abducens nerve is affected. Diplopia is the symptom that occurs when an individual’s eyes are misaligned causing the inability for an individual to maintain a singular image with both eyes open

Ptosis

• The oculomotor nerve is made of two branches. If the superior branch is affected, individuals may experience a ptosis (droopy eyelid)¹² 

Loss of sensation

• In Tolosa-Hunt Syndrome, the ophthalmic branch of the trigeminal nerve is affected in approximately a third of cases. If the nerve is affected, individuals can experience numbness of the forehead, scalp and cornea (the transparent layer at the front surface of the eye)¹¹

Pupil involvement

• In Tolosa-Hunt Syndrome, if the parasympathetic part of the oculomotor nerve is affected, then an individual can experience a dilated pupil (the black hole in the colored layer of an individual’s eye).¹⁵ This can prevent an individual’s ability to focus on close-by objects causing an individual to experience blurred vision
• In Tolosa-Hunt Syndrome, when the sympathetic nerves are affected, individuals can experience Horner's syndrome.¹⁵ This is where the pupil can be constricted, a ptosis and a decrease in sweating

Diagnosis

Individuals can be diagnosed with Tolosa-Hunt Syndrome through a combination of imaging, lab tests, and ophthalmic tests. 

Ocular motility examination 

A clinical team will conduct an ocular utility examination to assess the way an individual can move their eyes. During the examination, the individual is asked to follow a light with their eyes in different positions of gaze, and a member of the clinical team records how limited an individual’s eye movements may appear.¹³ 

Pupil examination

A clinical team can conduct an assessment on an individual’s pupils by shining a light and checking if the pupils react to the light.¹⁴

Imaging 

MRI with contrast or a CT scan can be used to detect if an individual has abnormal amounts of thickening of the cavernous sinus structure.¹⁰ 

Blood and Cerebrospinal fluid tests 

During the examination, if an individual is suspected to have Tolosa-Hunt Syndrome based on the imaging tests, a clinical team can also run a blood test or a cerebrospinal fluid study. If the individual is noted to have any abnormalities in these tests, then Tolosa-Hunt Syndrome can be excluded.² 

Reviewing steroid response

Often, clinical teams will use the response to medications as a way to confirm the diagnosis of Tolosa-Hunt Syndrome. High-dose steroids are used as the first line of treatment for individuals and usually show a dramatic improvement in pain within seventy-two hours.¹ 

Treatment

Typically, individuals are treated with steroids to improve symptoms and signs of Tolosa-Hunt Syndrome ^6. Whilst steroids are administered, an individual is monitored closely using imaging to support the reduction of the steroids appropriately.^6,9 

Moreover, for a small cohort of individuals, additional immunosuppressants are required to support the long-term effects of steroids.¹ In some cases, especially in the recurrence of Tolosa-Hunt Syndrome, some individuals may require radiotherapy to support the dependency on steroid use as a treatment.⁸

Prognosis

Tolosa-Hunt Syndrome symptoms and signs can be relieved significantly for individuals with steroid treatment. Individuals often respond within the first twenty-four to seventy-two hours.¹ However, it has been noted that signs such as eye movement recovery are typically much slower and occur more gradually and can take up to two months.⁷ Research shows that relapse of Tolosa-Hunt Syndrome can occur in 40% to 50% of individuals.⁶ Therefore, it is imperative that a full investigation be conducted to confirm a diagnosis on each occasion. 

Differential diagnosis

Ophthalmoplegia can be present as a sign in many conditions; therefore, it is imperative to diagnose the underlying root cause of the eye movement limitations. The following list can be considered for differential diagnoses for Tolosa-Hunt Syndrome:¹

Vascular and hemorrhagic conditions

• Cerebral Aneurysms
• Epidural Hematoma
• Cerebral Venous Thrombosis

Tumour-related conditions

• Benign brain tumours
• Malignant brain tumours
• Metastasis
• Meningioma
• Craniopharyngioma
• Central nervous system Lymphoma

Inflammatory conditions

• Polyarteritis Nodosa
• Neurosarcoidosis
• Tuberculous Meningitis
• Giant cell arteritis

Infectious conditions

• Varicella Zoster
• Lyme disease
• Central nervous system Whipple's disease

Autoimmune

• Systemic lupus erythematosus

Neurological Syndromes and other factors

• Cavernous Sinus Syndrome
• Diabetic Neuropathy
• Migraine

Summary

In conclusion, it is imperative to diagnose Tolosa-Hunt Syndrome as early as possible to ensure that an individual can be treated and their symptoms can be managed. Ophthalmoplegia is a common sign noted in the condition which can limit eye movements for an individual in the affected eye.