Tolosa Hunt Syndrome

What is Tolosa Hunt syndrome?

Tolosa Hunt syndrome (THS) is a rare disease that is characterised by severe, usually unilateral headache around the eye and painful eye movements. This syndrome is very rare and has been documented to occur worldwide and at all ages. Also, males and females are equally affected ^[1]. The incidence per year is one case per million.

Causes

Tolosa Hunt syndrome is caused by inflammation process. The septa and wall of cavernous sinus becomes inflamed. The inflammation process puts pressure on the surrounding structures- cavernous sinus and cranial nerves III, IV, VI and a part of nerve V. the exact cause of inflammation is unknown but it is believed to be caused by an autoimmune process. Autoimmune disorders occur when the body’s natural defence mechanisms start to attack healthy tissue.

Other possible causes for THS might be generalized inflammation process and inflamed or/and constricted blood vessels of the head ^[2]. If you want to find out about other autoimmune disorders, read about periodic fever syndrome, antiphospholipid-antibody syndrome.

Symptoms

Patients usually complain about sudden onset of pain behind the eyes which is followed by painful and limited eye movements- ophtalmoplegia. In severe cases the eye is not able to move and look in different directions at all. Other symptoms include:

• Chronic periorbital headache
  • Pain can affect periorbital, retroorbital, frontal, temporal parts of the head
  • Pain is described as severe, stabbing in nature
• Double vision
• Optic disc upon examination can be swollen and pale
• Paralysis of cranial nerves III, IV, V, VI
• Protrusion of the eye
• Dropping of the upper eyelid (also see Lambert-Eaton syndrome)
• Impaired vision
• Nausea and vomiting might occur

All of the symptoms may resolve without any treatment but they are likely to reoccur ^[3].

Diagnosis

Diagnostic criteria

Since Tolosa Hunt syndrome is very rare, it might go undiagnosed. In order to make the diagnosis the following criteria must be met:

• Eye pain on one side of the head
• Pain persists for at least 8 weeks
• Damage to the III, IV, VI cranial nerves
• Pain is relieved within 48 hours after administrating steroids
• Other possible causes for pain are excluded ^[3]

Laboratory studies

There is a wide variety of tests that should be performed when THS is suspected. THS does not have any specific serum markers, but it is diagnosed by excluding other, potentially life threatening conditions. Laboratory tests that should be performed are:

• Complete blood count
• Erythrocyte sedimentation rate
• Blood electrolyte levels
• Thyroid function tests
• Treponemal antibody test
• Antinuclear antibody tests (ANA)
• Antineutrophil cytoplasmic antibody (ANCA)
• Lyme disease titre
• Angiotensin converting enzyme level
• HIV test
• Bacterial cultures
• Spinal tap- in Tolosa Hunt syndrome mild lymphocytic pleocytosis (abnormally large number) might occur
• Anti-GQ1b antibody test can help to distinguish THS from Miller Fisher syndrome, a subtype of Guillain-Barre syndrome ^[4].

Imaging studies

CT scanning can show asymmetry of the affected tissue- cavernous sinus can be enlarged. Contrast can also be enhanced in the affected area.

Secondary criteria on CT scan are narrowing of the internal carotid artery and extension towards the superior orbital fissure and apex of the orbit. Narrowing or the internal carotid artery can be seen in CT angiography, but these changes are not specific to THS.

MRI is better method to see inflammatory changes in the affected region. The signal intensity can be changed but it is not specific ^[5].

Other procedures

In order to confirm the diagnosis, biopsy of cavernous sinus tissue might be required. Since the cavernous sinus is not easy to access, usually trial of treatment with steroids is used. Biopsy can be performed if tumour is suspected. The biopsy reveals a non-specific granulomatous or non-granulomatous inflammation ^[4]. In histological examination epithelioid cells and occasional giant cells are seen. In some cases necrosis is observed. There is no data about any microorganisms that might cause this condition.

Differential diagnosis

• Trauma
• Lesions of the blood vessels:
  • Cavernous artery aneurism

• • Thrombosis
  • Carotid cavernous fistula
• Tumours
  • Pituitary adenoma
  • Meningioma
  • Giant cell tumour
  • Metastasis
• Giant cell arteritis
• Sarcoidosis
• Wegener’s granulomatosis
• Diabetic damage
• Migraine
• Orbital cellulitis (also see dry eye syndrome) ^[1,3,6]

Treatment

Medications

The method of choice for treating Tolosa Hunt syndrome is the use of corticosteroids. The use of steroids has not only therapeutic but also diagnostic value. Pain reliefs is usually acquired after 27-72 hours. If the eye movements have been impaired, it might take weeks or even moths to resolve. In some cases ophtalmoparesis might not completely resolve.

Corticosteroids, such as prednisone decreases inflammation. In the inflammation process capillary permeability is increased- prednisone takes action against this process, as well as supresses lymphocyte production of antibodies.

In some cases more aggressive medications are used, such as azathioprine, methotrexate or even radiation therapy ^[4,6].

Surgery

Surgery is mostly not indicated in Tolosa Hunt syndrome. In some cases surgical intervention is required to obtain a biopsy material ^[4,6].

Prognosis

The prognosis for patients suffering from THS is usually good. This condition might resolve without using drugs. Usually steroid treatment is used and most patients are responsive to treatment. In some cases complications due to prolonged use of steroids might occur.

Relapse of this condition has been observed in around 40% of cases that have been successfully treated. Usually relapse occurs on the same side as before. It has been observed, that patients who were treated with medications have lower risk of reoccurrence. In rare cases the process might spread and affect the optic nerve, causing the loss of vision ^[4,6].

References

1. General patient information: http://patient.info/doctor/tolosa-hunt-syndrome
2. Causes and pathophysiology: http://www.uptodate.com/contents/tolosa-hunt-syndrome
3. Symptoms: https://rarediseases.org/rare-diseases/tolosa-hunt-syndrome/
4. Diagnosis and prognosis: http://emedicine.medscape.com/article/1146714-workup#c4
5. Imaging: https://radiopaedia.org/articles/tolosa-hunt-syndrome-3
6. Detailed information for health care professionals: http://jnnp.bmj.com/content/71/5/577.full