Cavernous sinus thrombosis

If there is a vascular blockage by a thrombus in the area of the cavernous sinus, located on the sides of the sella turcica, then they speak of thrombosis of the cavernous sinus. Pathology develops as a result of an inflammatory reaction - for example, with various infections. Cavernous sinus thrombosis is considered a rare disorder, and at the same time quite dangerous, since there is a significant risk of inflammation spreading to the area of cerebral structures. The disease is accompanied by impaired blood circulation in the brain, and if medical care is not provided, the patient may die. [1]

Early recognition of cavernous sinus thrombosis, which often presents with fever, headache, visual impairments such as periorbital edema and ophthalmoplegia, is critical to a good outcome. Despite modern treatment with antibiotics and anticoagulants, the risk of long-term effects such as vision, diplopia and stroke remains significant. [2], [3]

Epidemiology

Cavernous sinus thrombosis, as a pathology, has been known for a long time. The disease was described by several scientists from different times at once: in the 18th century it was done by the Irish surgeon-anatomist William Deese, and in the 19th century by the Scottish doctor, Professor Andrew Duncan.

The disease is considered rare: among adult patients, the distribution is about 3-4 cases per million of the population, and among pediatric patients (children and adolescents) - about 7 cases per million.

Cavernous sinus thrombosis is most common among people 20-40 years of age, more often women. [4]

Lethal outcomes are observed in 5-25% of cases. [5]

Causes of the cavernous sinus thrombosis

Cavernous sinus thrombosis always develops as a consequence of some other pathological process. In the origin of the disease, several disorders can become the primary source at the same time. Some experts believe that cavernous sinus thrombosis can occur on its own, however, many scientists are sure that there is a provoking cause in all cases, it is simply not always possible to determine it. [6]

Various infectious organisms can cause cavernous sinus thrombosis, although most are bacterial. Staphylococcus aureus can account for two-thirds of cases, and methicillin resistance should be considered. Other typical organisms include Streptococcus species (approximately 20% of cases), pneumococci (5%), gram-negative species such as Proteus, Hemophilus, Pseudomonas, Fusobacterium, Bacteroides, and gram-positive species such as Corynebacterium and Actinomyces. Some of them (Bacteroides, Actinomyces, Fusobacterium) are anaerobic. Fungal infection in cavernous sinus thrombosis is less common but may include aspergillosis (most common), zygomycosis (eg, mucormycosis), or coccidioidomycosis in immunocompromised individuals. Rare factors causing cavernous sinus thrombosis can include parasites such as toxoplasmosis, malaria and trichinosis, as well as viral causes such as herpes simplex, cytomegalovirus, measles, and hepatitis.

Most often, the disease is associated with the following root causes:

• Infectious and inflammatory reactions - in particular, infectious lesions of the upper respiratory tract and organs of vision (orbital phlegmon, furuncle, retrobulbar abscess, otitis media of various forms, sinusitis, meningoencephalitis, mastoiditis). In some cases, ARVI, fungal infection, and general blood poisoning become the "culprit".
• Non-infectious diseases of the central nervous system, which are accompanied by local damage to the brain tissue and venous sinuses - in particular, after neurosurgical operations, with traumatic brain injury, tumor processes (including metastatic).
• Hemodynamic disorders, lesions of the venous bed - for example, severe dehydration, cardiac insufficiency, antiphospholipid syndrome, prolonged catheterization with the formation of a thrombus in the central venous vessel, thrombophlebitis of the head localization.
• Connective tissue pathologies (systemic lupus erythematosus, "dry" syndrome, systemic vasculitis).
• Hormonal imbalance, including those associated with prolonged use of oral contraceptives, pregnancy, etc.
• Thrombophilia caused by congenital mutations or changes in the content of coagulation factor V, C and S-protein substances, prothrombin and antithrombin, homocysteine, as well as a lack of plasminogen or factor XIII. [7],  [8],  [9], [10]

Risk factors

The following factors contribute to the development of cavernous sinus thrombosis:

• autoimmune processes in the body (systemic lupus erythematosus, rheumatoid arthritis, etc.);
• hereditary tendency to form blood clots in the vessels;
• diabetes mellitus, especially its late stages;
• tumor formations of different etiology in the sinusoidal cerebral zone;
• infectious and inflammatory pathologies in the face and head (periodontitis, sinusitis, otitis media, mesotympanitis, etc.);
• cardiovascular diseases (heart rhythm disturbances, coronary heart disease, heart attacks);
• craniocerebral trauma, which are accompanied by a pinched sinus. [11]

Pathogenesis

The development of thrombosis of the cavernous sinus is due to the anatomical features of the venous cerebral mechanism: the veins of the brain do not have a muscular wall and a valve system. In addition, the cerebral veins are characterized by "branching". There are numerous anastomoses, and one venous vessel is able to pass through itself the blood coming from several arterial basins.

Veins of the brain are superficial and deep, they flow into the sinuses of the dura mater. In this case, the superficial network flows mainly into the superior sagittal sinus, and the deep one - into the large vein of the brain and the straight sinus.

Cavernous sinus thrombosis develops according to two mechanisms that determine the clinical picture of the lesion. According to the first mechanism, there is a blockage of cerebral venous vessels, which leads to cerebral edema and impaired venous blood flow. The second stage is an increase in intracranial pressure as a result of blockage of large venous sinuses. In a healthy person, cerebrospinal fluid passes from the cerebral ventricles through the subarachnoid space of the lower and upper lateral surfaces of the cerebral hemispheres, is absorbed in the arachnoid plexuses and flows to the superior sagittal sinus. With thrombosis of the cavernous sinus, venous pressure increases: as a result, the flow of cerebrospinal fluid is upset, an increase in intracranial pressure occurs. [12]

Symptoms of the cavernous sinus thrombosis

The degree of manifestation of the clinical picture in thrombosis of the cavernous sinus is different, depending on the root cause of the pathology, on the rate of increase in circulatory disorders, on the age and general health of the patient. [13]

In most patients, the first "bell" is pain in the head: sharp or growing, focal or diffuse, aching or intermittent, sometimes with nausea (up to vomiting). The infectious form of thrombosis is accompanied by an increase in headache in the supine position (for example, at night), an increase in body temperature and other signs of intoxication.

The eye pathological picture is manifested by swelling, pain when pressing on the periorbital region, general painful sensations in the eyeball. There is conjunctival edema, exophthalmos of varying intensity (usually bilateral). Patients complain of sudden blurred vision. [14] In some cases, it is possible to determine the venous cords in the upper eyelid by palpation. The main external signs: redness or cyanosis of the skin, swelling in the forehead and temples, cheeks and nasolabial triangle. A characteristic symptom is swelling of the mastoid area of the temporal bone.

General health can be impaired, from tinnitus to coma. In some patients, psycho-motor agitation is noted, which is especially typical for patients with heart attacks and strokes. In the future, a focal neurological picture manifests itself, represented by motor-sensitive aphasia, paresis and paralysis, and convulsive seizures. [15],  [16] Meningeal manifestations are less common.

The local neurological picture consists in drooping of the upper eyelid, motor limitation of the eyeball, deterioration of superficial sensitivity in the innervation of the damaged nerves. In some cases, strabismus is noted.

Stages

In its course, thrombosis of the cavernous sinus passes the stage of direct (first) and secondary (indirect) signs.

The first signs include:

• sudden deterioration of vision, up to and including its loss;
• protrusion of the eyeball anteriorly, with further displacement;
• swelling of the optic nerve and eyelids;
• intense pain in the neck, limitation of movement in this section;
• Strong headache. [17], [18]
• Indirect signs can be as follows:
• nausea to vomiting;
• high rates of body temperature;
• involuntary muscle twitching, mainly in the upper limbs and face;
• violations of the thought process, confusion. [19]

When indirect signs appear, there is a danger of developing a pre-coma and coma. Therefore, at the second stage, it is extremely important to provide the patient with emergency medical care.

Forms

Pathogenetically distinguish between aseptic (non-infectious) thrombosis of the cavernous sinus and infectious (septic) thrombosis. [20]

The aseptic form in clinical practice is somewhat more common and is due to:

• traumatic brain injury;
• complications during surgical (neurosurgical) interventions;
• tumor processes in the brain;
• violation of the patency of the internal jugular vein;
• complications of spinal and epidural anesthesia;
• hormonal imbalance;
• cardiac insufficiency, arrhythmias, heart defects;
• nephrotic syndrome; [21]
• severe dehydration;
• diseases of the blood coagulation mechanism;
• thrombophilia;
• liver diseases (cirrhosis), etc.

The infectious form, in turn, is microbial, viral, fungal. Such a pathology can be provoked by such violations:

• intracranial abscesses;
• microbial, viral, fungal infections;
• parasitic diseases.

Complications and consequences

Cavernous sinus thrombosis can cause many complications. It should be borne in mind that the earlier the patient seeks a doctor and begins to take treatment, the less likely there will be adverse consequences. Early consequences include heart attack, cerebral edema, and focal seizures. [22] Among the long-term consequences, the following most often occur:

• serous inflammation of the arachnoid meninges (arachnoiditis);
• deterioration of vision;
• anisocoria (pupils of different sizes);
• paralysis of the abducens nerve, which is responsible for contraction of the lateral rectus muscle involved in the external rotation of the eye;
• drooping of the eyelid;
• cerebrovascular accident, stroke;
• hormonal disturbances from the hypothalamic-pituitary mechanism. [23]

A particular danger is cavernous sinus thrombosis in childhood, as it can cause impaired intellectual development and various nervous disorders. Often such deviations significantly affect the further quality of life of the child. [24], [25]

The incidence of death due to thrombosis of the cavernous sinus is about 20%.

The likelihood of re-thrombosis development depends on many factors - in particular, on the completeness of the recovery period, on the implementation of all medical recommendations. The rehabilitation period is usually long and lasts several months. After completing the main treatment course and transferring the patient to outpatient treatment, it is important to observe maximum rest, not to burden the body with physical activity, not to overeat, smoke  [26] or drink alcohol. Medication support at this stage is prescribed by the doctor on an individual basis. [27]

Diagnostics of the cavernous sinus thrombosis

The diagnosis of cavernous sinus thrombosis can be called difficult, primarily due to the absence of specific signs of pathology. Differential diagnosis is often placed in the first place, and the presumptive diagnosis is deduced by excluding other possible pathologies.

The diagnostic scheme for suspected cavernous sinus thrombosis consists in the following procedures:

• Collection of information about the disease, examination and questioning of the patient. The primary survey is conducted by a neuropathologist: he carefully examines the complaints, specifies the time of the onset of unpleasant symptoms, finds out the presence of other symptoms and concomitant pathologies. After that, he performs physical diagnostics to determine the external signs of the violation.
• Checking the neurological status. In many patients with thrombosis of the cavernous sinus, pupillary and corneal reflexes are inhibited, there is a decrease or loss of sensitivity in the eyelid zone, forward displacement of the eyeball (protrusion), paralysis of the eye muscles, strabismus. The spread of the inflammatory process to the structures of the brain reveals itself as bulbar disorders, central paresis and paralysis, and positive meningeal signs.
• Examination by an ophthalmologist. Examination sometimes reveals severe conjunctival edema, loss of visual fields in the form of partial blindness (hemianopsia). The ophthalmologist determines the fuzzy contours of the optic nerve head, dilated veins of the fundus. [28]

Further, the patient undergoes such laboratory tests:

• a general blood test (for thrombosis of the cavernous sinus, neutrophilic leukocytosis, increased ESR, low hemoglobin level, moderate type of lymphopenia, less often thrombocytopenia are characteristic);
• general urine analysis;
• examination of cerebrospinal fluid (with thrombosis of the cavernous sinus, there is an increased level of protein, the presence of blood cells, less often - the cerebrospinal fluid is unchanged).

Instrumental diagnostics are most often presented by X-ray,  [29] computed tomography and magnetic resonance imaging. [30]

MRI in T1 mode visualizes a thrombus as a zone with the intensity of the brain parenchyma, and in T2 mode - as a hypointense zone. In subacute course, all modes demonstrate an increase in the magnetic resonance signal in the thrombosed area. [31]

Cavernous sinus thrombosis on CT has the appearance of an area with increased density. Hepodense foci, narrowed cerebral cisterns and ventricles are found. Against the background of the use of contrast imaging, a thrombus of the cavernous sinus is seen, as well as a symptom of "empty delta", characterized by the absence of contrast accumulation in the blocked area of the venous sinus. [32], [33]

Differential diagnosis

If cavernous sinus thrombosis is suspected, differential diagnosis is required with general and ophthalmic diseases, in particular, with the following:

• A septic condition that proceeds independently of the primary focus. The patient is examined for bacteremia.
• Thrombosis of the sigmoid sinus, which becomes a complication of otogenic diseases.
• Thrombophlebitis of cerebral venous vessels, with typical repeated intult-like attacks, migration of focal lesions, rapid disappearance of neurological symptoms. Sharp head pains, vomiting, bradycardia, stagnation of the optic discs, spinal hypertension with local convulsive seizures are also characteristic. 
• Orbital pathologies, including phlegmon of the orbit, retrobulbar hemorrhage, sarcoma and other disorders accompanied by exophthalmos. The presence of infection and neurologic signs are indicative of cavernous sinus thrombosis. With swelling and pain in the eye area, decreased vision, phlegmon of the orbit can be suspected. Additionally, X-ray diagnostics are performed.

A typical sign of cavernous sinus thrombophlebitis is bilateral exophthalmos with immobility of the eyeballs.

Treatment of the cavernous sinus thrombosis

Therapeutic procedures for thrombosis of the cavernous sinus can be different, depending on both the age of the patient and the intensity of pathological manifestations and the root cause of the disease. If drug therapy is ineffective, surgery is prescribed with further rehabilitation measures. [34]

The main focus of treatment is to restore the patency of the cavernous sinus. There are known facts of the successful use of thrombolysis, however, against its background, the risk of developing hemorrhages significantly increases. To date, anticoagulants, for example, low molecular weight heparins, are at the forefront of the treatment plan. [35] As experts point out, the use of direct anticoagulants at the acute stage of thrombosis significantly optimizes the prognosis and reduces the percentage of mortality and disability among patients. [36],

In case of infectious thrombosis of the cavernous sinus, antibiotic therapy is prescribed in high doses, with the use of drugs with extensive antibacterial activity - in particular, cephalosporins:

• Ceftriaxone in the amount of 2 g per day as an intravenous infusion;
• Meropenem, Ceftazidine 6 g per day as an intravenous infusion;
• Vancomycin 2 g per day intravenously.

Be sure to examine and act on the primary infectious focus: if necessary, resort to surgical assistance (the operation should not precede antibiotic therapy). [37]

After the acute stage of cavernous sinus thrombosis, indirect oral anticoagulants (Warfarin, Acenocoumarol) are prescribed, with an INR orientation in the range of 2-3. It is advisable to use direct anticoagulants until such indicators of the international normalized ratio are achieved. [38]

In the aseptic form of pathology, heparin is used in the amount of 2.5-5 thousand units in the form of intravenous or subcutaneous injections. The dosage is gradually increased to 70 thousand units per day. The therapy is continued until a positive symptomatic dynamics is achieved.

In addition to the main treatment, measures are taken to prevent the development of complications - for example, seizures or increased intracranial pressure. For this purpose, anticonvulsants are used, artificial ventilation of the lungs is performed (hyperventilation with (+) expiratory pressure), osmotic diuretics are prescribed. When taking diuretics, it should be borne in mind that excessive excretion of fluid can negatively affect the rheological qualities of the blood, which can aggravate the formation of blood clots. [39]

In some cases - in particular, with cerebral edema - glucocorticoids are used, although their effectiveness remains questionable.

With a particularly severe course of thrombosis of the cavernous sinus, with compression of the cerebral structures, according to indications, decompression is performed in the form of hemicraniotomy. [40]

Prevention

The main point of prevention of cavernous sinus thrombosis is the timely treatment of any infectious and inflammatory processes in the body, and especially those that affect the respiratory system. People with frequent respiratory diseases, chronic pathologies of the respiratory system should visit the attending physician for preventive purposes at least once every 6 months.

It is necessary to take measures to strengthen the vascular wall. It is important to eat healthy, natural foods, drink enough fluids daily, periodically take multivitamins at the discretion of the doctor.

One of the provoking factors of thrombosis is infectious processes in the body. In particular, viral, bacterial, and fungal infections can become dangerous. With the development of the disease, it is important to be treated in a timely and full-fledged manner, following all the doctor's recommendations. In no case should you complete the treatment without completing it, and even more so - independently prescribe and cancel medications, change the dosages prescribed by the doctor.

Forecast

The most favorable prognosis is for cases of cavernous sinus thrombosis detected at the early stages of development, subject to competent timely treatment. Drug therapy can stop the inflammatory process, eliminate a blood clot and restore normal blood circulation. Late diagnosis requires the appointment of more serious therapeutic measures. [41]

The most frequent complications of thrombosis are heart attacks and cerebral hemorrhages, cerebral edema. Such problems arise in about every second patient. Among the more rare complications are status epilepticus, pulmonary embolism. As a result of infectious inflammation, abscesses sometimes develop (including the liver, lungs, brain), purulent meningitis, and inflammatory processes in the lungs. [42], [43]

Thrombosis of the cavernous sinus is also dangerous because the pathological focus is located in close proximity to the structures of the brain. That is why it is important to seek medical help as early as possible in order to prevent the spread of the inflammatory reaction to brain tissues and blood vessels. [44] Timely diagnosis and treatment will help restore health and prevent the development of adverse complications.