Cavernous sinus thrombosis overview

# Overview

# Historical Perspective
Cerebral sinus thrombosis was first discovered by Ribes a french physician, in 1825. Ribes discovered the cavernous sinus thrombosis during an autopsy of a 45-year-old patient with headaches, epileptic seizures and delirium. The first postpartum cerebral sinus thrombosis first discovered by John Abercrombie, a Scottish physician, in a 24-year-old woman who developed headache and seizures 2 weeks after an unremarkable delivery In 1828. A subsequent autopsy revealed thrombosis of the superior sagittal sinus and cortical veins.

# Classification
The Jefferson classification and  Ishikawa classification have been used to localize cavernous sinus lesions.  Based upon the location of the intracranial orifice of the optic canal and the entry of the maxillary nerve into the cavernous sinus, lesions may be classified in the Ishikawa and the Jefferson classification scheme into three groups: Anterior lesions, middle lesions and posterior lesions. Although more patients could be classified using the Ishikawa classification, there is no advantage of Ishikawa classification over Jefferson with regard to determination of etiology of cavernous sinus lesions.

# Pathophysiology
The cavernous sinus which is a true dural venous sinus, is irregularly shaped, trabeculated cavity in the base of the skull. The cavernous sinus receives blood via the superior and inferior ophthalmic veins through the Superior orbital fissure and superficial cortical veins. The Cavernous sinus is connected to the basilar plexus of veins posteriorly. There are some important nerves and arteries pass through the cavernous sinus, include: The internal carotid artery (carotid siphon), cranial nerve III, cranial nerve IV, cranial nerve V branches and cranial nerve VII. Infection from the face may reach the cavernous sinus through its many anastomotic connections, with severe consequences. The cavernous sinus drains by two larger channels, the superior and inferior petrosal sinuses, ultimately into the internal jugular vein via the sigmoid sinus, also draining with emissary vein to pterygoid plexus. These sinuses are just lateral and superior to the sphenoid sinus and are immediately posterior to the optic chiasm. Each cavernous sinus is formed between layers of the dura mater, and multiple connections exist between the 2 sinuses. It is understood that the main cause of cavernous sinus thrombosis is bacterial infections. Staphylococcus aureus may account for two-thirds of cases of cavernous sinus thrombosis. Other typical organisms include: streptococcus species (approximately 20% of cases), pneumococcus (5%),gram-negative species such as Proteus, hemophilus, pseudomonas, fusobacterium, bacteroides and gram-positive species such as Corynebacterium and Actinomyces. In cavernous sinus thrombosis, a blood clot develops in the sinus cavernous structure to prevent the infection from spreading to brain, but it often blocks the blood flow out of the brain. Septic cases of cavernous sinus thrombosis are usually caused by central facial infections, especially within the danger triangle of the face (from the corners of the mouth to the bridge of the nose). The main sources of infection include: Mastoiditis, otitis media, abscess, cellulitis,sinusitis and dental infections or procedures. The other rare causes of cavernous sinus thrombosis include: fungal infections, severe head injuries, autoimmune conditions such as lupus and pregnancy.

# Causes
It is understood that the main cause of cavernous sinus thrombosis is bacterial infections. Septic cases of cavernous sinus thrombosis are usually caused by central facial infections, especially within the danger triangle of the face (from the corners of the mouth to the bridge of the nose). Common causes of cavernous sinus thrombosis may include: Staphylococcus aureus (two-thirds of cases) and Streptococcus species (approximately 20% of cases). Less common causes of cavernous sinus thrombosis include: Pneumococcus, Staphylococcus lugdunensis endocarditis, gram-negative species such as Proteus, hemophilus, Pseudomonas, Fusobacterium, Bacteroides, gram-positive species, Fungal infections, severe head injuries, autoimmune conditions such as lupus and Pregnancy. The main sources of infection in cavernous sinus thrombosis include: Mastoiditis, Otitis media, Abscess, cellulitis, Sinusitis, dental infections or procedures and endocarditis.

# Differentiating cavernous sinus thrombosis from Other Diseases
Cavernous sinus thrombosis must be differentiated from other diseases that cause severe headache, pain with eye movements, high fever, proptosis, periorbital swelling, and ophthalmoplegia, such as orbital cellulitis, acute Angle-Closure Glaucoma, intracranial tumors and, carotid cavernous fistula and tolosa-Hunt syndrome.

# Epidemiology and Demographics
The prevalence of cavernous sinus thrombosis is approximately 1.321.57 per 100,000 individuals worldwide. The mortality rate of cavernous sinus thrombosis is approximately 20%. The combination of anticoagulants with antibiotics in treatment of cavernous sinus thrombosis has significantly decreased the mortality rate of it. Patients of all age groups may develop cavernous sinus thrombosis. The incidence of cavernous sinus thrombosis significantly increases with age. women are more commonly affected by cavernous sinus thrombosis than men. The women to men ratio is approximately 3.75.3 to 1.

# Risk Factors
Common risk factors in the development of cavernous sinus thrombosis include: Neoplasms, facial infections, sinusitis, otitis media, dental infections, sepsis, factor V Leiden mutation, Prothrombin G20210A mutation, antithrombin III deficiency, protein C or S deficiency, increased factor VIII, antiphospholipid antibody syndrome, hyperhomocysteinemia, heparin-induced thrombocytopenia, pregnancy, obesity, dehydration, autoimmune disease, uncontrolled diabetes, steroid use, chemotherapy, oral contraceptives or hormone replacement therapy and inflammatory bowel diseases. Less common risk factors in the development of cavernous sinus thrombosis include: Puerperium, fibrous thyroiditis, arterio-venous malformations and immunosuppression.

# Screening
Common risk factors in the development of cavernous sinus thrombosis include: Neoplasms, facial infections, sinusitis, otitis media, dental infections, sepsis, factor V Leiden mutation, Prothrombin G20210A mutation, antithrombin III deficiency, protein C or S deficiency, increased factor VIII, antiphospholipid antibody syndrome, hyperhomocysteinemia, heparin-induced thrombocytopenia, pregnancy, obesity, dehydration, autoimmune disease, uncontrolled diabetes, steroid use, chemotherapy, oral contraceptives or hormone replacement therapy and inflammatory bowel diseases. Less common risk factors in the development of cavernous sinus thrombosis include: Puerperium, fibrous thyroiditis, arterio-venous malformations andimmunosuppression.

# Natural History, Complications, and Prognosis
The symptoms of cavernous sinus thrombosis may vary depending upon the anatomical structures involved. The most common symptoms of cavernous sinus thrombosis include: Severe holocranial and bifrontal headache whit increasing severity, fever, Proptosis, Chemosis, external ophthalmoplegia, periorbital swelling and redness in one or both eyes. Other symptoms of cavernous sinus thrombosis include: Drooping eyelids, Decreased visual acuity, Vision loss or double vision, Inability to move the eye, periorbital sensory loss, pain or numbness around the face or eyes, fatigue, Seizures and Lethargy. Common complications of cavernous sinus thrombosis include: Death, bilateral blindness, Seizures, total ophthalmoplegia, Anisocoria, Meningitis, Intracerebral hemorrhage, Facial palsy, Hemiparesis, venous infarction, Ptosis and Hypopituitarism. Prognosis better as diagnosis is increasing made with imaging instead of autopsy, with mortality rates down from 100% to 6.5% in a recent review of 76 patients. Poor prognostic features include: Rapid progression, Coma, extremes of age, focal signs and symptoms, Hemorrhagic infarct and serious underlying cause.

# Diagnosis

## Diagnostic Study of Choice
Magnetic resonance imaging (MRI) with MR venography is the gold standard test for the diagnosis of cavernous sinus thrombosis. The following findings on performing MRI are confirmatory for cavernous sinus thrombosis: Absent flow void in T1 and T2 and signal characteristics vary depending on the age of the thrombus but will be abnormal. Contrast-enhancement or lack of is not a reliable indicator as organising thrombus can enhance. Diagnosis can generally be made on venography.

## History and Symptoms
Patients with cavernous sinus thrombosis may have a positive history of: Neoplasms, facial infections, sinusitis, otitis media, dental infections, sepsis, factor V Leiden mutation, Prothrombin G20210A mutation, antithrombin III deficiency, protein C or S deficiency, increased factor VIII, antiphospholipid antibody syndrome, hyperhomocysteinemia, heparin-induced thrombocytopenia, pregnancy, obesity, dehydration, autoimmune disease, uncontrolled diabetes, steroid use, chemotherapy, oral contraceptives or hormone replacement therapy and inflammatory bowel diseases. The symptoms of cavernous sinus thrombosis may vary depend on the anatomical structures involved. The most common symptoms of cavernous sinus thrombosis include: Severe holocranial and bifrontal headache whit increasing severity, fever, Proptosis, Chemosis, external ophthalmoplegia, periorbital swelling and redness in one or both eyes. Other symptoms of cavernous sinus thrombosis include: Drooping eyelids, Decreased visual acuity, Vision loss or double vision, Inability to move the eye, periorbital sensory loss, pain or numbness around the face or eyes, fatigue, Seizures and Lethargy.

## Physical Examination
Physical examination of patients with cavernous sinus thrombosis is usually remarkable for high grade fever, Tachycardia with regular pulse, Tachypnea, low blood pressure with normal pulse pressure, Pallor of skin, Altered mental status, Periorbital edema (initially unilateral but typically bilateral), unilateral or bilateral exophthalmos, abnormal extra-ocular movements from third, fourth and sixth cranial neuropathy, non-reactive pupils to neither light nor accommodation (from paralysis of the iris and ciliary body), lid erythema, horner syndrome (ptosis, miosis, and anhidrosis), Chemosis, Ptosis, Proptosis (due to impaired venous drainage of orbit, painful eye movement, Papilledema, retinal hemorrhages, decreased visual acuity, Photophobia, pulsating conjunctiva, facial tenderness, impaired corneal reflex, blindness, stiff neck, Photophobia, Hyperreflexia, generalised weakness, downgoing plantar reflex, Ptosis and Hemiparesis.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of cavernous sinus thrombosis include: Neutrophilic-predominant leukocytosis, lumbar puncture may be used to detect possible meningitis, positive blood culture, metabolic acidosis, hypernatremia and elevated ESR and CRP.

## Electrocardiogram
There are no ECG findings associated with cavernous sinus thrombosis.

## X-ray
The x-ray usually is not used in diagnosis of cavernous sinus thrombosis as the MRI and CT scan have a very better diagnostic value.

## Echocardiography and Ultrasound
The echocardiography and ultrasound usually are not used in diagnosis of cavernous sinus thrombosis as the MRI and CT scan have a very better diagnostic value.

## CT scan
High-resolution contrast-enhanced CT scan is useful in the assessment of cases with clinical features of cavernous sinus thrombosis. In early stages of the disease the CT and MRI findings may be normal. Findings on CT scan suggestive of cavernous sinus thrombosis include: Irregular filling defects within the cavernous sinus, thickening of the superior ophthalmic vein, poor enhancement of the cavernous sinus, hypodensity in the region of the cavernous sinus, thickening and dilation of the superior ophthalmic vein and opacification of the paranasal sinuses and ethmoidal air cells.

## MRI
Magnetic resonance imaging (MRI) with MR venography is the gold standard test for the diagnosis of cavernous sinus thrombosis. The following findings on performing MRI are confirmatory for cavernous sinus thrombosis: Absent flow void in T1 and T2 and signal characteristics vary depending on the age of the thrombus but will be abnormal. Contrast-enhancement or lack of is not a reliable indicator as organising thrombus can enhance. Diagnosis can generally be made on venography.

## Other Imaging Findings
There are no other imaging findings associated with cavernous sinus thrombosis.

## Other Diagnostic Studies
There are no other diagnostic studies associated with cavernous sinus thrombosis.

# Treatment

## Medical Therapy
Cavernous sinus thrombosis is a medical emergency. Pharmacologic medical therapies for cavernous sinus thrombosis include antithombotic agents, antibiotics, and drugs such as mannitol, steroids and acetazolamide to decrease the intracranial pressure.  Empiric antimicrobial therapy for septic thrombosis of cavernous or dural venous sinus includes metronidazole plus either nafcillin or oxacillin with either ceftriaxone or cefotaxime. Generally, the preferred empiric regimen for the treatment of cavernous sinus thrombosis is (Vancomycin 3045 mg/kg IV q812h for 3-4 weeks OR Nafcillin 2 g IV q4h for 3-4 weeks OR Oxacillin 2 g IV q4h for 3-4 weeks) AND (Ceftriaxone 2 g IV q12h for 3-4 weeks OR Cefotaxime 812 g/day IV q46h for 3-4 weeks) AND Metronidazole 7.5 mg/kg IV q6h for 3-4 weeks. If the risk of MRSA is high,  vancomycin should be used instead of either nafcillin or oxacillin. Other pharmacologic therapies include antithrombotic agents (usually LMWH) to prevent clot formation, steroid therapy (e.g. Dexamethasone 10 mg q6h) for symptomatic relief, and mannitol and acetazolamide to reduce the elevated intracranial pressure. Antiepileptic therapy should be administered only if patients develop seizures.

## Interventions
Early endovascular therapy may help preserve vision in patients in patients with acute cavernous sinus thrombosis. Combination of medical and surgical interventions may be in management of cavernous sinus thrombosis. Endovascular therapy of cerebral venous thrombosis using approaches to intracranial recanalization include: Thrombolysis and thrombectomy. This interventions are not well described and there are few studies about this interventions. Successful recanalization of the bilateral cavernous sinuses and superior ophthalmic veins was achieved in some studies without complication.

## Surgery
Surgical intervention is not recommended for the management of cavernous sinus thrombosis.

## Primary Prevention
There are no established measures for the primary prevention of cavernous sinus thrombosis.

## Secondary Prevention
There are no established measures for the primary prevention of cavernous sinus thrombosis.