Tholos-Hunt Syndrome

Syndrome of the superior orbital fissure, pathological ophthalmoplegia - all this is nothing more than Tholos Hunt syndrome, which is a lesion of structures in the superior orbital fissure. The process usually involves the orbital vessels (arterial and venous), nerve fibers (oculomotor, trochlear, abducent nerves, as well as the first branch of the trigeminal nerve) and the nearby cavernous sinus. The disease can be classified as a relatively rare and rather difficult pathology in diagnosis. [1]

Epidemiology

Tholos Hunt syndrome was described not so long ago: about 70 years ago. This was done by the Spanish doctor of neurology E. Tolos. Several years later, the work was supplemented by an Englishman, Doctor of Ophthalmology W. Hunt. The names of the research doctors became the basis for the name of the syndrome.

Tholos Hunt syndrome is found with equal frequency in both men and women. Pathology is usually one-sided and is noted equally often on the left or right side. Bilateral syndrome is possible, but occurs only in isolated cases.

The average age of the sick is 50 years. In general, Tholos Hunt syndrome can be recorded at the age of 15-85 years. Most of the patients belong to the elderly age category: the development of the disease is facilitated by multiple cardiovascular disorders, as well as age-related changes in tissues.

The most common symptom of the disease is the manifestation of a classic migraine attack: a person has a sudden throbbing headache on one side, "shooting" or "twisting", with irradiation into the orbit. Since the typical specific symptomatology of Tholos Hunt syndrome is absent, the pathology is often called "neurological chameleon": the diagnosis is complex, requiring differentiation from many other diseases.

Patients with Tholos Hunt syndrome are periodically found in different countries of the world, without any territorial or seasonal characteristics. The incidence rate is 0.3-1.5 cases per 1 million population. [2]

Causes tholos-Hunt syndrome

In the course of identifying the causes of the development of Tholos Hunt syndrome, scientists discovered the following facts:

• in most cases, the disease was provoked by immune inflammation of the outer wall of the cavernous sinus;
• in some cases, the causes were vascular malformations, tumor processes in the brain (primary and secondary forms), localized cranial pachymeningitis, orbital myositis, periarteritis nodosa and thrombus formation in the cavernous sinus;
• In about 30% of patients, it is not possible to establish the cause of the disorder, therefore, the diagnosis of idiopathic Tholos Hunt syndrome was made.

Let's consider these alleged reasons in more detail.

• The autoimmune development of the syndrome is associated with both hypothermia and recent infectious pathologies, and with deep stresses. The autoimmune form of the disease is characterized by: acute onset, recurrent course, high efficiency of glucocorticosteroid therapy. This form of the disease is more common in men.
• Vascular malformations often occur in decompensated arterial hypertension. More often women are ill. The disease begins acutely, the pain is moderate, with virtually no manifestations of exophthalmos and chemosis.
• Among the tumor processes that can lead to the development of Tholos Hunt syndrome, primary brain tumors, metastatic tumors with primary foci in the lungs, bronchi, prostate, or metastases of cutaneous melanoma were more common.
• Localized cranial pachymeningitis causes an acute onset of the syndrome in the absence of cerebral and meningeal signs, without exophthalmos. The diagnosis is confirmed morphologically by biopsy.
• Orbital myositis causes a subacute onset, with intense pain and exophthalmos, pronounced chemosis and double vision.
• Cavernous sinus thrombosis provokes the development of total ophthalmoplegia. The diagnosis is confirmed by magnetic resonance imaging.
• Periarteritis nodosa can cause the development of Tholos Hunt syndrome a few months after the onset of the disease.

The autoimmune mechanism in most cases underlies the formation of pathology, which has been proven by many experts. The following factors, in particular, indicate an autoimmune character:

• recurrent course;
• dysimmune disorders;
• protein-cell dissociation in cerebrospinal fluid and an increased content of pro-inflammatory cytokines in cerebrospinal fluid and serum. [3]

Risk factors

Scientists have not yet figured out the exact cause of the appearance of Tholos Hunt syndrome. But they managed to identify certain factors influencing the development of such a violation:

• Genetic predisposition to autoimmune diseases in general. If one of the family members is sick or is sick with an autoimmune disorder, then other relatives may have similar or other pathologies with a similar development mechanism. This factor is still an assumption that requires additional research and evidence.
• Environmental factors, including dietary habits, environmental conditions, water quality, industrial hazards, etc.
• Severe stressful situations, frequent stresses and psycho-emotional upheavals, powerful hormonal changes (including pregnancy, menopause, etc.).
• Long-term chronic infectious diseases, including hepatitis, herpesvirus infection, cytomegalovirus, etc.
• Hypothermia, radiation, other strong irritants and damaging factors.

Pathogenesis

The etiological mechanism of the development of Tholos Hunt syndrome has not been completely disclosed. The decisive importance is attributed to autoimmune reactions. Many scientists assume that viral and microbial infections, stressful situations, radiation only act as a provoking factor. There is no strong evidence of the relationship between the ingestion of pathogens and the development of Tholos Hunt syndrome. However, there are suspicions about the involvement of cytomegalovirus in the autoimmune process, which contributes to the formation of granulomas. [4]

The pathogenetic scheme is due to the appearance of a local granulomatous inflammatory process in the zone of the outer wall of the cavernous sinus, infraclinoid or supraclinoid part of the internal carotid artery, which leads to its narrowing. An important role is played by the disorder of the humoral and cellular immune defense. The humoral side of the syndrome is associated with the increased formation of antineutrophilic cytoplasmic antibodies that act against the enzymes proteinase-3, myeloperoxidase, and a specific membrane protein capable of binding endotoxins. Presumably, cytoplasmic antibodies stimulate the existing neutrophils, as a result of which they attack the target organs, in particular, the inflammatory process develops in the outer wall of the cavernous sinus.

Cellular changes also play a role in the development of Tholos Hunt syndrome. This is evidenced by the dominance of T-lymphocytes, macrophages and plasma cells in granulomas.

There is information about highly active endothelial structures and anti-inflammatory cytokines, which indicates a tendency of the disease process to become chronic.

In isolated cases, focal necrotic changes were noted in the area of the outer wall of the cavernous sinus.

Symptoms tholos-Hunt syndrome

The symptomatology characteristic of Tholos Hunt syndrome appears abruptly and unexpectedly for the patient himself. The main symptoms are:

• Severe pain in the area of the orbits, extremely unpleasant, boring, spreading from the frontal region to the brow ridges, to the eyes and further throughout the head.
• Doubling in the eyes, which is found following the onset of pain. It becomes extremely difficult for a person to visually concentrate and consider an object.
• Disorder of the motor function of the eyeball, or the so-called ophthalmoplegia, mainly unilateral. It can manifest itself to varying degrees, which depends on the severity of the pathological process and on the extent of the lesion.
• Conjunctival edema.
• Displacement of the eyeball anteriorly (exophthalmos, "bulging" eyes).
• Deviation of the visual axis of one eyeball to the side, strabismus, which is characteristic of unilateral nerve damage.
• General deterioration of health, a slight increase in temperature, weakness, irritability.

The clinical picture gradually progresses, the symptoms change and worsen, but they can disappear as abruptly as they appeared. However, in the absence of the necessary therapy, Tholos Hunt syndrome again reminds of itself with a relapse.

Neurological symptoms are due to the localization of the disease process. The pain appears as a result of irritation of the first branch of the trigeminal nerve, passing near the trunk of the oculomotor nerve, and is noted in the orbit, forehead, temple, base of the nose. The intensity of pain is different: from moderate to severe.

Possible atypical symptoms, which are characterized by the absence of pain. This can be observed when the lesion is localized before the fifth pair enters the cavernous sinus.

Oculomotor disorders usually manifest themselves as double vision during direct gaze.

If the painful process is localized in the zone of the apex of the orbit, then neurological manifestations are often found in combination with disorders of the visual analyzer. As a result, edema or atrophy of the optic nerve head appears, and central scotoma is often noted. Possible exophthalmos (bulging), chemosis (conjunctival edema), the occurrence of which is caused by infiltrative changes in retrobulbar tissue and difficulties with venous outflow from the orbit.

First signs

Since Tolos Hunt syndrome has not been sufficiently studied to date, scientists continue to clarify the possible mechanisms for the development of this pathology. Taking into account the criteria outlined by the International Neurological Society, the diagnosis of Tholos Hunt syndrome is justified in the presence of granulomas of the outer wall of the cavernous sinus, detected during an MRI of the brain or biopsy.

The list of signs that are accepted as diagnostic criteria for the syndrome is as follows:

• "Picking" or "twisting" pain in one eye socket with the subsequent development of muscle paralysis (ophthalmoplegia);
• combined lesions of the oculomotor nerves, the first branch of the trigeminal nerve and the periarterial nerve plexus;
• an increase in the clinical picture for several days (or within 1-2 weeks);
• the possibility of spontaneous remission (in some cases - with residual preservation of defects);
• the likelihood of a repeated exacerbation of the syndrome, months or years later;
• unchanged systemic picture, no lesions outside the carotid sinus;
• the presence of a positive effect from corticosteroid therapy.

There is another similar diagnostic list of signs proposed in 2003. According to this list, Tholos Hunt syndrome is considered as a result of the growth of granulomatous tissue in the cavernous sinus, superior orbital fissure and orbital cavity:

• one or more episodes of unilateral painful attack in the orbital zone, which pass without treatment for a couple of weeks;
• damage to the cranial nerve (III, IV or VI) in the form of paresis, the presence of granulomas, confirmed by magnetic resonance imaging or biopsy;
• the appearance of paresis simultaneously with pain syndrome, or within 14 days after it;
• the disappearance of paresis and pain syndrome within 3 days from the start of corticosteroid therapy.

Forms

With Tolos Hunt syndrome, the left and right sides are affected with approximately equal frequency, therefore the pathology is divided into left-sided or right-sided.

The disease is mostly one-sided. Bilateral damage was noted only in extremely rare cases.

The clinical picture of the disease can develop through the following stages:

• acute or subacute, which occurs after a recent viral infectious disease, hypothermia, a strong increase in blood pressure, sometimes for no apparent reason;
• chronic recurrent, with a gradual increase in symptoms and periodic exacerbation.

In addition, Tholos Hunt syndrome can be:

• total, with damage to all the nerves that pass through the superior orbital fissure;
• incomplete, with involvement in the pathological process of the nerves of the VI, IV, III pairs and I branches of the V pair in various combinations.

In relation to the sinus, the anterior, middle and posterior forms of Tholos Hunt syndrome can be distinguished.

Complications and consequences

Tholos Hunt syndrome occurs with severe pain, which entails loss of sleep, disturbances in the emotional and mental sphere. Sick people become irritable, emotionally unstable. If the necessary treatment is not carried out, then against this background, the appearance of neurotic disorders is possible: depressive states, neurasthenia, and hypochondria develop. Working capacity significantly decreases, the patient becomes withdrawn.

A characteristic feature of Tholos Hunt syndrome is a recurrent course, which often occurs in autoimmune diseases. The duration of the remission period varies greatly: the maximum recorded asymptomatic duration was 11 years. After treatment, the risk of relapse is significantly reduced. If exacerbations do occur, then they differ in a less severe course.

Diagnostics tholos-Hunt syndrome

It often becomes difficult for doctors to immediately diagnose Tholos Hunt syndrome, as the symptoms are very similar to those of other more common diseases. In most cases, additional consultation is required from a number of narrow specialists: a neuropathologist, ophthalmologist, endocrinologist, oncologist, neurosurgeon, etc.

At the first stage, malignant diseases, aneurysms, meningitis, etc. Should be excluded.

Most often, Tholos Hunt syndrome is determined by the method of exclusion: the patient is given a number of tests that exclude other most likely diseases. The following tests are required:

• detailed picture of blood;
• study of the hormonal function of the thyroid gland;
• study of the level of total protein in the blood (to assess the quality of protein metabolism);
• analysis of cerebrospinal fluid.
• Instrumental diagnostics involves the implementation of such diagnostic procedures:
• magnetic resonance imaging of the brain and orbital region, with and without contrast;
• magnetic resonance angiography;
• digital subtraction angiography (intravenous subtraction angiography);
• computed brain and orbital tomography with and without contrast.

Gadolinium-enhanced MRI is the method of choice for assessing THS and can demonstrate abnormal increase and enhancement of CS passing through the superior orbital fissure into the apex of the orbit. Reported T1-weighted and T2-weighted MRI findings are extremely variable and non-specific. MRI plays a key role in diagnosis and helps to rule out other common CS-related lesions, avoiding the need for high-risk invasive procedures such as SC biopsy, the only way to obtain histopathological confirmation of this disease. [5]

These studies help to identify traces of inflammatory processes in the cavernous sinus, superior orbital fissure or orbital apex. Traces of inflammation in the orbital area in cross-sectional images with the absence of cranial nerve palsy are considered more benign in terms of prognosis.

Some patients with suspicion of Tholos Hunt syndrome are recommended to take a biopsy to exclude oncological processes.

Differential diagnosis

Clinical practice indicates that similar symptoms can be present in many somatic and neurological pathologies:

• with microbial, viral and fungal inflammatory processes that involve the meninges or the outer wall of the cavernous sinus;
• with tumor processes in the brain and orbit - for example, with pituitary adenoma, craniopharyngioma, neurinoma, meningioma of the wing of the sphenoid bone, with cerebral or orbital metastases;
• with vascular malformations - in particular, with venous-arterial aneurysms, carotid-cavernous fistulas, etc., as well as with dissection of branches of the internal carotid artery;
• with thrombosis, cystic formations of the cavernous sinus, lymphoma;
• with sarcoidosis, myositis of the orbit (eye muscles), Wegener's granulomatosis (granulomatosis with polyangiitis), ophthalmigraine, some blood pathologies.

Differential diagnosis involves the study of the possibility of the development of all these diseases, based on the results of a survey, examination, laboratory and instrumental studies.

Most often, Tholos Hunt syndrome has to be distinguished from such pathologies:

• blockage of the cavernous sinus by a thrombus;
• Rochon-Duvignot syndrome;
• retrosphenoidal space syndrome (Jacot's syndrome);
• paratrigeminal Raeder's syndrome;
• cranial polyneuropathy.

Treatment tholos-Hunt syndrome

Tholos Hunt syndrome responds well to treatment with an immunosuppressive course of corticosteroid hormonal agents. Such drugs are able to suppress the aggressive response of the immune system and its damaging effects on body tissues.

More often than other drugs, Prednisolone, Methylprednisolone, Cortisone are prescribed, or alternative drugs that have shown a positive effect in the treatment of known autoimmune pathologies. The benefits of steroids appear to be related to the antioxidant mechanism and / or the ability of such high doses to reduce edema and subsequent ischemia in the affected area. [6]

In addition to corticosteroids, the use of painkillers, anticonvulsants is appropriate. Comprehensive multivitamin preparations are required.

If you strictly follow all the prescriptions and recommendations of the attending physician, then the painful signs of Tolos Hunt syndrome are quickly stopped: patients notice a pronounced improvement in well-being on about the second or third day. In the overwhelming majority of cases, the ability to work remains. [7]

The optimal dosage and frequency of taking hormonal drugs are indicated on an individual basis. There is no generally accepted treatment regimen, since it is very difficult to organize placebo-controlled studies, which is associated with the low prevalence of the syndrome. Most often, high doses of corticosteroids are recommended, although there have been cases of effectiveness and rather small doses of drugs (for example, the use of Prednisolone in an amount of less than 0.5 mg / kg per day). To date, the average amount of Prednisolone used in Tholos Hunt syndrome is 1-2 mg / kg per day.

Approximate treatment regimen:

• Methylprednisolone (Solu-Medron 1000 as an intravenous drip infusion with 250 ml of isotonic sodium chloride solution and Panangin (10.0) daily for five days;
• Mildronate for the normalization of cellular metabolism, 500 mg intravenous jet injection daily for 10 days;
• Neuromidin to improve impulse transmission along neuromuscular fibers, 20 mg orally three times a day;
• Clonazepam to enhance the inhibitory effect on the transmission of nerve impulses and stimulation of benzodiazepine receptors, 2 mg orally, and / or Trileptal 150 mg orally at bedtime.

Perhaps the appointment of a prolonged course of glucocorticosteroid therapy using high doses of Prednisolone. [8]

Prevention

It is not possible to prevent the appearance of Tholos Hunt syndrome in advance. This is due, at least, to the fact that the reasons for the violation have not yet been clearly defined. If any painful signs are found - in particular, frequent pains in the frontal region and eye sockets, double vision and weakening of the eye muscles, then you should contact the appropriate specialist as soon as possible and carry out a complete diagnosis.

Secondary prevention is aimed at preventing relapse in patients with already diagnosed Tholos Hunt syndrome. Important points of preventive action are:

• regular medical consultations, diagnostic measures, dispensary supervision of specialists;
• periodic courses of corticosteroid therapy;
• strengthening and maintaining an adequate state of the immune system.

All patients need to try to avoid stressful situations, to timely treat any inflammatory processes in the body.

Forecast

The prognosis for Tholos Hunt syndrome is considered favorable. There is a good response to corticosteroid therapy, and spontaneous remission is common, although some patients have residual effects in the form of impaired function of damaged ocular muscles. In the absence of further treatment, the disease becomes recurrent. In treated patients, relapses occur in about 35% of cases. [9]

Upon completion of the therapeutic course, the ability to work is usually restored. However, this refers to a correctly diagnosed disease, and not to other pathologies that develop under the "mask" of a syndrome. [10]

Disability is noted only in rare cases. Only with documented frequent exacerbations is it possible to assign a third group of disability. In difficult cases, the patient is transferred to lightweight labor, which is not accompanied by visual stress. If Tholos Hunt's syndrome is persistent and recurrent, then the person is not recommended to drive vehicles, which is due to impaired motor function of the eyeballs and diplopia.