TolosaâÂÂHunt syndrome is a rare disorder characterized by severe and unilateral headaches with orbital pain, along with weakness and paralysis (ophthalmoplegia) of certain eye muscles (extraocular palsies).
In 2004, the International Headache Society defined the diagnostic criteria, which included granuloma.
Symptoms are usually limited to one side of the head. In most cases, the individual affected will experience intense, sharp pain and paralysis of muscles around the eye. Symptoms may subside without medical intervention, yet recur without a noticeable pattern. Patients with this disorder describe it as almost like being stabbed in the head. The pain also comes from behind the eyes, forehead, and around the temple area. Not only is the disorder painful, but it is also severe.
In addition, affected individuals may experience paralysis of various facial nerves and drooping of the upper eyelid (ptosis). Other signs include double vision, fever, chronic fatigue, vertigo or arthralgia. Occasionally, the patient may present with a feeling of protrusion of one or both eyeballs (exophthalmos). Patients may lose their sight, and experience nausea and vomiting.
Tolosa-Hunt Syndrome should not be mistaken for idiopathic inflammatory orbital pseudotumor (IIPO). Both disorders have similar symptoms and respond similarly to steroid medications.
These may go for up to 8 weeks. Treatment can reduce the symptoms, but the disorder may recur. In one clinical case in 2019, a 14-year-old boy was admitted to the hospital as he exhibited severe headaches, but MRI scans showed no brain abnormalities. Over 4 weeks, the symptoms worsened, and the patient showed paralysis in the mouth region. After being given medications to alleviate the symptoms, symptoms came back after 8 weeks and the patient had to get hospitalized.
These also can return unpredictably, sometimes with months or years.
The cause of TolosaâÂÂHunt syndrome is not known. The disorder is thought to be, and often assumed to be, associated with inflammation of the areas behind the eyes (cavernous sinus and superior orbital fissure). These granulomatous inflammations involve lymphocytes, plasma cells, and multinucleate giant cells. Clinical cases have shown that the disorder consists of the inflammation of multiple cranial nerves, with the highest prevalence of ocular motor nerves. In some cases, it also involves the inflammation of sensory nerves, specifically the trigeminal nerves.
Tolosa-Hunt Syndrome is highly impacted by the inflammation of the cranial nerves, especially those that are located around the cavernous sinus. These include:
In some cases, inflammation can also impact other cranial nerves. These include:
A recent study involving a 14-year-old boy showed that the seventh cranial nerve has also been impacted, but not much is known about this one as compared to the other nerves.
Symptoms come from the International Classification of Headache Disorders which was done in 2013.
Due to the nature of the disorder, biopsy has been recommended as the best tool to assess whether a patient has the disorder or not.
TolosaâÂÂHunt syndrome is also diagnosed via exclusion, and as such, a vast amount of laboratory tests are required to rule out other causes of the patient's symptoms. These tests include a complete blood count (erythrocyte sedimentation rate, C-reactive protein, glucose, hemoglobin A1c, electrolytes, liver function tests), thyroid function tests and serum protein electrophoresis. Studies of cerebrospinal fluid (cell count and differential, cultures such as bacterial, fungal, viral, glucose, oligoclonal bands, opening pressure and protein) and serologic testing (angiotensin-converting enzyme, antinuclear antibody, anti-dsDNA, antimitochondrial antibody, antineutrophil cytoplasmic antibody, borrelia burgdorferi serology, HIV). may also be beneficial in distinguishing between TolosaâÂÂHunt syndrome and conditions with similar signs and symptoms.
MRI scans of the brain and orbit with and without contrast, magnetic resonance angiography or digital subtraction angiography and a CT scan of the brain and orbit with and without contrast may all be useful in detecting inflammatory changes in the cavernous sinus, superior orbital fissure and/or orbital apex. Inflammatory change of the orbit on cross-sectional imaging in the absence of cranial nerve palsy is described by the more benign and general nomenclature of orbital pseudotumor. Sometimes a biopsy may need to be obtained to confirm the diagnosis, as it is useful in ruling out a neoplasm. Other diagnoses to consider include craniopharyngioma, migraine and meningioma.
MRI and CT scans are important for diagnosis, but should not be the sole form of diagnosis as they could potentially show other diseases (including tumors). These depend on the test coil, spatial, and temporal resolution of MRIs. The size of the lesion might not be detectable using MRIs if the lesions are not large enough. MRIs also have poorer temporal resolution, which makes it difficult to detect the timing of the lesions. In that case, it's recommended that patients do MRI follow-ups when the lesions develop over time. Additionally, other forms of diagnosis include vascular imaging such as digital subtraction angiography, CT angiography (CTA), and MRA.
There have been debates over the diagnosis. Yousem et al. 1990 showed that some patients with Tolosa-Hunt Syndrome have normal brain regions compared to some other patients in which they coined the term beginning Tolosa-Hunt Syndrome.
Differential diagnoses is as follows:
Treatment of TolosaâÂÂHunt syndrome includes immunosuppressives such as corticosteroids (often prednisolone) or steroid-sparing agents (such as methotrexate or azathioprine).
Radiotherapy has also been proposed as an addition. For patients to be given additional form of treatment, they need to perform follow up check ups.
Although there are known medications for patients, there is not much known about the instructions on administering the medications. Most medications given to patients with this disorder are based on other corticosteroids and other steroids, in which patients will be given a high dosage at first, and as it goes on, the dosage is decreased. Most patients will experience pain relief between 24âÂÂ72 hours after the medications are given, but these times depend on the type of symptoms that the patient is experiencing. Recurrences are common despite the alleviation of the symptoms. Additionally, depending on the severity of the disorder, not everyone responds the same way. Some patients may respond well to medications, while some patients may not need them at all. Doctors advise on proper diagnosis and evaluation.
TolosaâÂÂHunt syndrome typically has a good prognosis. Patients usually respond to corticosteroids, and spontaneous remission can occur, although movement of ocular muscles may remain damaged. Roughly 30âÂÂ40% of patients who are treated for TolosaâÂÂHunt syndrome experience a relapse.
Tolosa-Hunt syndrome affects all age groups, but most cases have been in adults aged 40âÂÂ50 years, with the average age being 41 years. There is no specific gender of the disorder, but most cases have shown a higher prevalence for males than females. Tolosa-Hunt Syndrome in the pediatric population is similar to that of adults. In addition, the cases have been found in multiple continents such as America, Europe, Asia, and Africa, thus, it is not known whether there are any differences between populations of different ethnic and racial makeup. Currently, there is about one case per million a year.
Some reports have shown that the disorder is more common in adults than children, but many other pediatric cases have been reported. Some indicate that diagnoses in children are more difficult than in adults due to children's difficulty in describing the disorder to doctors. This could be a problem when finding treatment for the disorder.
Tolosa-Hunt Syndrome was first recognized in 1954, when Dr. Eduardo Tolosa wrote a case study that involved inflammation of the tissues surrounding the arteries. The diagnostic tools were based on observations, as imaging and other forms of diagnosis were unavailable at the time. The patient he worked with had pain in their eyes and eye muscles. These symptoms were very similar to those of an aneurysm, with additional neurological symptoms. He found that this patient had inflammation on their carotid siphon, which can be found in the cavernous sinus.
Later on in 1961, Dr. William E. Hunt and colleagues investigated several cases involving this disorder. Similar to the case that Dr. Eduardo Tolosa was working with, the cases they dealt with involved pain around the eyes. These symptoms would last for days or weeks. Patients would get attacks from months or years at a time, with other neurological deficits.
Dr. Smith and Dr. Taxdal coined the name "Tolosa-Hunt Syndrome" after Dr. Hunt and Dr. Tolosa, who examined the very first cases dealing with the disorder in 1966. In their "Painful Ophthalmoplegia - The Tolosa-Hunt Syndrome" paper, they described a total of 5 cases involving this neurological disorder. All cases involved similar symptoms to the original findings. They found out that when patients were given systemic corticosteroids, the symptoms would be reduced.