Cavernous Sinus Thrombosis

Danyelle Evans, M.D.
Joseph S. Kass, M.D., J.D.
Prashanth Krishnamohan M.B.B.S., M.D.

Basic Information

Definition

Cavernous sinus thrombosis (CST) is a late complication of either facial or paranasal sinus infection, resulting in thrombosis of the cavernous sinus and inflammation of its surrounding anatomic structures, including cranial nerves III, IV, V (ophthalmic and maxillary branch), and VI, and the internal carotid artery.

Synonyms

Cavernous sinus thrombosis (CST)
Intracranial venous sinus thrombosis or thrombophlebitis
Dural sinus thrombosis

ICD-10CM CODES
G08	Intracranial and intraspinal phlebitis and thrombophlebitis

Epidemiology & Demographics

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CST is rare in the post-antibiotic era.
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Before antibiotics the mortality rate was 80% to 100%.
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With antibiotics and early diagnosis, mortality rates have fallen to ∼20%.
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Reported morbidity rates have also declined from between 50% and 70% to about 20% to 30% with advances in imaging modalities and aggressive medical care.

Physical Findings & Clinical Presentation

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Can be either an acute and fulminant disease or an indolent and subacute presentation.
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Septic cases of CST commonly present with high-grade fever (picket fence pattern) and signs of sepsis.
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Headache, although not specific, is the most common presenting symptom and may precede fever and periorbital edema by several days. Elderly patients, however, may only demonstrate alteration in mental status without antecedent headache. The triad of unilateral or bilateral progressive chemosis, periorbital edema, and proptosis with headache is a classical presentation in patients with CST. These signs and symptoms are related to the anatomic structures affected within the cavernous sinus, notably cranial nerves III to VI, as well as impaired venous drainage from the orbit and eye.

Other common signs and symptoms include:

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Ptosis.
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Cranial nerve palsies (III, IV, V1, V2, VI).
1. 1.
  
  Ophthalmoplegia caused by involvement of cranial nerves III, IV, and VI is present in most cases. Sixth nerve palsy can occur early in some cases of septic CST, especially when originating from the sphenoid sinus owing to its anatomic proximity.
2. 2.
  
  Hypoesthesia or hyperesthesia of the ophthalmic and maxillary branch of the fifth nerve is common. Periorbital sensory loss and impaired corneal reflex may be noted.
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Papilledema, retinal hemorrhages, and decreased visual acuity progressing to blindness may occur from venous congestion within the retina.
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Pupil may be dilated and sluggishly reactive.
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Headache with nuchal rigidity and changes in mental status may occur if the infection spreads intracranially to the meninges and brain parenchyma.
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Infection can spread to the contralateral cavernous sinus through the intercavernous sinuses within 24 to 48 hours of initial presentation.
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Patients may also develop signs and symptoms of pituitary insufficiency.

Etiology

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CST most commonly results from contiguous spread of an infection from either the sinuses (sphenoid, ethmoid, or frontal) or the medial third of the face (areas around the eyes and nose that drain to the ophthalmic vein). Nasal furuncles are the most common facial infection to produce this complication. Less-common primary sites of infection include dental abscess, tonsils, soft palate, middle ear, or orbit (orbital cellulitis).
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CST also can result from hematogenous spread of infection to the cavernous sinus by the superior and inferior ophthalmic veins or through the lateral and sigmoid sinuses. Depending on the pressure gradients, infection can spread in a retrograde direction because the dural sinuses are valveless.
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Staphylococcus aureus is the most commonly identified pathogen, found in 60% to 70% of the cases.
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Streptococcus is the second leading cause.
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Gram-negative rods and anaerobes may also lead to CST.
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Rarely, Aspergillus fumigatus and mucormycosis cause CST.
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Risk factors for dural sinus thrombosis include venous hypercoagulable disorders, infections (see previous), trauma, malignancies, systemic inflammatory disorders, pregnancy, and dehydration.

Diagnosis

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The diagnosis of CST is made by clinical suspicion and confirmed by appropriate imaging studies.
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Proptosis, ptosis, chemosis, and cranial nerve palsy beginning in one eye and progressing to the other eye establish the diagnosis.

Differential Diagnosis

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Orbital or periorbital cellulitis.
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Internal carotid artery aneurysm or fistula.
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Cerebrovascular disease.
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Migraine headache.
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Allergic blepharitis.
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Thyroid ophthalmopathy.
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Orbital neoplasm.
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Meningitis.
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Epidural and subdural infections.
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Epidural and subdural hematoma.
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Subarachnoid hemorrhage.
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Acute angle-closure glaucoma.
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Trauma.

Workup

CST is a clinical diagnosis, with laboratory tests and imaging studies confirming the clinical impression.

Laboratory Tests

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Complete blood count, erythrocyte sedimentation rate, blood cultures, and sinus cultures help establish and identify an infectious primary source. Metabolic panel to look for electrolyte imbalances in cases of suspected pituitary involvement (DI/SIADH).
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Lumbar puncture (LP) helps to distinguish CST from more localized processes (e.g., sinusitis, orbital cellulitis). LP reveals inflammatory cells in 75% of cases. In half of these cases, the cerebrospinal fluid profile is typical for a parameningeal focus (high white blood cells with polymorphonuclear and/or mononuclear cells, normal glucose, normal protein, culture negative), and in one third may be similar to that of bacterial meningitis.

Imaging Studies

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MRI with gadolinium, including magnetic resonance angiography and magnetic resonance venogram (Fig. 1), is more sensitive than CT scan and is the imaging study of choice to diagnose CST. Findings may include deformity of the internal carotid artery within the cavernous sinus and an obvious signal hyperintensity within thrombosed vascular sinuses.

FIG.1

Superior sagittal sinus (SSS) thrombosis on magnetic resonance venogram (MRV).

Sagittal T1 magnetic resonance imaging (A) shows intermediate signal intensity in sagittal and straight sinuses (arrowheads). No flow is seen on MRV (B) in these vessels (arrowheads), which is consistent with thrombosis. Color Doppler evacuation (C) of the SSS in another 6-mo-old patient with suspected thrombosis demonstrated a patent SSS with normal draining cortical veins.

From Fuhrman BP, et al.: Pediatric critical care, ed 4, Philadelphia, 2011, Saunders.
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Noncontrast CT scan of the head and orbits may demonstrate increased density in the region of the cavernous sinus but has relatively low sensitivity. Contrast-enhanced CT scan may reveal underlying sinusitis, thickening of the superior ophthalmic vein, and irregular filling defects within the cavernous sinus; however, findings may be normal early in the disease course.

Treatment

Nonpharmacologic Therapy

Recognizing the primary source of infection (i.e., facial cellulitis, middle ear, and sinus infections) and treating the primary source expeditiously is the best way to prevent CST.

Acute General Rx

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Appropriate therapy should take into account the primary source of infection as well as possible associated complications such as brain abscess, meningitis, or subdural empyema.
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Broad-spectrum intravenous antibiotics are used as empiric therapy until a definite pathogen is found. Treatment should include vancomycin to cover hospital or community-acquired methicillin-resistant Staphylococcus aureus or resistant Streptococcus pneumoniae plus a third- or fourth-generation cephalosporin:
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  Vancomycin (1 g q12h with normal renal function) plus either ceftriaxone (2 g q12h) or cefepime (2 g q8 to 12h).
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  Metronidazole 500 mg IV q6h should be added if anaerobic bacterial infection is suspected (dental or sinus infection).
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Most experts recommend anticoagulation with heparin after the diagnosis is confirmed, unless surgical intervention is planned, or there is evidence of an expanding hematoma. Spontaneous intracranial hemorrhage should first be ruled out before initiating heparin therapy. Early heparinization has been suggested in patients with unilateral CST to prevent clot propagation. Coumadin therapy should be avoided in the acute phase of the illness, but should ultimately be instituted to achieve an INR of 2 to 3 and continued until the infection, symptoms, and signs of CST have either resolved or significantly improved. Retrospective case reports and case series have demonstrated a favorable outcome in terms of decreased mortality and morbidity in the anticoagulated patients.
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Steroid therapy is also controversial but may prove helpful in reducing cranial nerve dysfunction or when progression to pituitary insufficiency occurs. Corticosteroids should only be instituted after appropriate antibiotic coverage. Dexamethasone 10 mg q6h is the treatment of choice.
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Emergent surgical drainage with sphenoidotomy is indicated if the primary site of infection is believed to be the sphenoid sinus.

Chronic Rx

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Patients with CST are usually treated with prolonged courses (3 to 4 weeks) of IV antibiotics. If there is evidence of complications such as intracranial suppuration, 6 to 8 weeks of total therapy may be warranted.
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All patients should be monitored for signs of complicated infection, continued sepsis, or septic emboli while antibiotic therapy is being administered. Relapse of septic CST can occur after an initial improvement weeks after stopping antibiotic treatment.

Disposition

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CST can be a life-threatening, rapidly progressive infectious disease with high morbidity and mortality rates (30%) despite antibiotic use. Morbidity and mortality rates are increased in cases of sphenoid sinus infection.
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Complications of untreated CST include extension of thrombus to other dural sinuses, carotid thrombosis with concomitant strokes, subdural empyema, brain abscess, or meningitis. Septic embolization may also occur to the lungs, resulting in acute respiratory distress syndrome, pulmonary abscess, empyema, and pneumothorax.
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Thirty percent of treated patients develop long-term sequelae, including cranial nerve palsies, blindness, pituitary insufficiency, and hemiparesis.

Referral

If suspected, CST should be considered a medical emergency. Depending on source of infection, appropriate consultation should be made (i.e., ear-nose-throat, ophthalmology, and infectious disease).

Pearls & Considerations

Comments

CST is a medical emergency and should be suspected with progressing chemosis, proptosis, and cranial neuropathy in a patient with headaches with or without fever.

The anatomy of the cavernous sinus explains the clinical findings: The cavernous sinus lies just above and lateral to the sphenoid sinus and drains the middle portion of the face by the superior and inferior ophthalmic veins; cranial nerves III, IV, V, and VI pass alongside or through the cavernous sinus.

Ferri – Cavernous Sinus Thrombosis