Ann P. Murchison
Jurij R. Bilyk
BASICS
DESCRIPTION
• Cavernous sinus thrombosis (CST) is a potentially life-threatening condition.
• The etiology of CST can either be septic, aseptic, or vascular.
• Septic CST is an infectious thrombophlebitis that develops as a sequela of head and neck infections. The most common sources include the paranasal sinuses (ethmoid and sphenoid), periodontal abscesses, parapharyngeal abscesses, facial infections (furuncles, boils), and middle ear infections (1)[C], (4)[C].
• In the pre-antibiotic era, septic CST was universally fatal. With current treatment mortality has been reduced to 30% (1)[C], (2)[C].
• Aseptic CST can occur from hypercoagulable states or direct injury from trauma or surgery.
• CST may also occur from a cavernous sinus arteriovenous fistula, typically fed by branches of the internal or external carotid arteries, or both.
EPIDEMIOLOGY
• The most common etiology of CST is vascular from a cavernous sinus fistula.
• CST is rare and there are no data on incidence.
RISK FACTORS
• Most patients presenting with bacterial septic CST are otherwise healthy individuals.
• In aseptic CST, risk factors include genetic or acquired prothrombotic conditions such as polycythemia, sickle-cell anemia, leukemia, antiphospholipid syndrome, Factor V Leiden, malignancy, oral contraceptives, and pregnancy.
• CST from a fistula typically occurs in two patient groups: Those with a history of head or neck trauma (typically younger males) and older patients with vasculopathic risk factors.
Genetics
• No specific genetic cause of CST is known.
• Genetic causes of hypercoagulable and immunosuppressed states apply when indicated.
GENERAL PREVENTION
• Prompt treatment of head and neck infections
• Genetic/hematologic testing in patients with family history of hypercoagulable conditions
• Control of vasculopathic risk factors
• Avoidance of head and neck trauma
PATHOPHYSIOLOGY
• Septic CST: The venous anatomy of the face is directly connected with the valveless veins of the skull base (orbit, pterygopalatine fossa, cavernous sinus), which then openly communicates with the deeper central venous sinuses. This facilitates infectious spread from superficial structures into the deeper venous plexuses (1)[C].
• Aseptic CST: Deformation of the sinus wall or turbulent flow within the sinus from trauma or surgery on adjacent tissue can cause thrombus formation (3)[C]. In hypercoagulable states, an error in the clotting cascade can prompt thrombosis.
• CST secondary to cavernous sinus fistula: An abnormal communication forms between the cavernous sinus and either the intracavernous internal carotid artery or a smaller caliber intracranial arterial branch. Thrombus may form because of the turbulent flow in the cavernous sinus or from spontaneous closure of the fistula (5)[C].
ETIOLOGY
• Head and neck infections
• Hypercoagulable states
• Vasculopathic
• Head and neck trauma
• Iatrogenic
COMMONLY ASSOCIATED CONDITIONS
See etiology
DIAGNOSIS
HISTORY
• The most common presenting symptom is headache. Focal neurologic deficits may be present. In cases of septic CST there is usually a history of a recent head or neck infection.
• Paranasal sinus infections have nonspecific symptoms. Ask directed questions about nasal congestion, purulent nasal discharge, a history of chronic sinusitis, and recurrent headaches
• Symptoms of other head and neck sources should be sought: Toothache, recent dental work, ear pain, sore throat, and facial furuncles
• Any predisposing immunosuppressive conditions, including diabetes, ketoacidosis, malignancy, chemotherapy, and primary or acquired immunodeficiency states
• History of hypercoagulability in the patient or family members
• Recent or distant head trauma
PHYSICAL EXAM
• For septic CST, highly variable and frequently indistinguishable from orbital cellulitis
• External ophthalmoplegia may or may not be present and may manifest from several etiologies
• Orbital congestion from decreased venous egress from the superior ophthalmic vein (SOV) into the cavernous sinus may cause a mechanical ophthalmoplegia
• Orbital inflammation from orbital cellulitis may result in external ophthalmoplegia.
• Cranial nerve paresis of III, IV, V1, V2, VI may be present from direct involvement of the cavernous sinus or orbital apex.
• Trigeminal dysfunction is highly atypical in pure orbital cellulitis. If present, this finding raises the possibility of septic CST.
• Bilateral orbital cellulitis is very uncommon. Conversely, sequential bilateral septic CST manifesting as bilateral orbital congestion is common. Therefore, “bilateral orbital cellulitis” should immediately raise the suspicion of septic CST (4)[C].
• Dental caries/abscess
• Pharyngeal erythema, edema, or abscess
• Signs of middle ear infection
• Facial cellulitis, furuncle, or boil
• Signs of orbital congestion and possible cellulitis are often present: Eyelid edema and erythema, exophthalmos (proptosis), chemosis, external ophthalmoplegia, afferent pupillary defect, optic nerve swelling, retinal venous congestion or tortuosity (see also section on orbital cellulitis)
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Initial lab tests for suspected septic CST
• Complete blood count with differential
• Coagulation profiles (PT/PTT/INR)
• Blood cultures
• Culture of the inciting infectious nidus
• Lumbar puncture: If signs of meningitis
Follow-up & special considerations
Suspected septic CST is a medical emergency. Admit for immediate intravenous antibiotic therapy and further workup.
Imaging
Initial approach
• Detecting CST on imaging is difficult and clinical suspicion often guides the radiologist in finding the subtle changes. The first study obtained is usually a CT scan, as it is readily available. Frequently, indirect signs of CST are more readily identifiable. Any enlargement of the SOV, unilaterally or bilaterally, raises the suspicion of CST. With contrast injection, a heterogeneous filling of the venous plexus within the cavernous sinus is suggestive of CST.
• Imaging is also important in identifying occult sources of infection such as ethmoid and sphenoid sinusitis, mastoiditis from middle ear infection, odontogenic abscess, and parapharyngeal abscess.
• MRI may be a useful adjunct to CT.
• Septic CST is frequently a clinical diagnosis. Neuroimaging is helpful for confirmation of the diagnosis and identification of an occult infectious nidus; however, because of the lack of absolute sensitivity, it should never be used exclusively to rule out the possibility of septic CST.
• In CST from a fistula, initial orbital color Doppler may show reversal of flow in the SOV.
• If CST from a cavernous sinus fistula is suspected, a six-vessel (both internal and external carotid arteries, both vertebral arteries) arteriogram is recommended for elucidation of abnormal flow and to assess for the presence of posterior cortical venous outflow, which increases the risk for hemorrhagic stroke (5)[C].
Follow-up & special considerations
• Close clinical follow-up is mandated.
• If the neurologic/ophthalmologic exams deteriorate, repeat imaging should be performed to rule out progression of CST to intracranial abscess formation, meningitis, or hemorrhagic stroke.
Diagnostic Procedures/Other
Lumbar puncture if signs of meningitis are present.
Pathological Findings
• Pathologic specimens are rarely taken from the cavernous sinus.
• Culture of infectious nidus: Bacteria are the most common cause with Staphylococcus aureus in 69% and Streptococcus sp in 17%. Fungal infections with Mucor and Aspergillus sp also occur (1)[C].
DIFFERENTIAL DIAGNOSIS
• Orbital cellulitis
• Carotid cavernous fistula
• Dural sinus fistula
• Orbital apex syndrome
• Idiopathic orbital inflammatory syndrome
• Idiopathic granulomatous cavernous sinus inflammation (Tolosa-Hunt syndrome)
TREATMENT
MEDICATION
First Line
• Septic CST: Broad-spectrum intravenous antibiotics with a third generation cephalosporin and vancomycin are started initially (1)[C]. The antibiotic regimen is tailored once a specific pathogen has been identified. Since antibiotic sensitivity takes several days, potential resistance should be covered during empiric therapy.
• If fungal organisms are suspected, systemic antifungal therapy should be started empirically.
• Aseptic CST: Anticoagulation should be initiated in hypercoagulable states. Hemorrhagic stroke is a risk regardless of anticoagulation (2)[C], (3)[C].
• If a cavernous sinus arteriovenous malformation is suspected, anticoagulation should be avoided and angiography should be performed.
Second Line
• Septic CST: Anticoagulation may be offered to the patient based on indirect evidence.
• Anticoagulation has been shown to have some benefit in the treatment of aseptic central venous sinus thrombosis.
• Two retrospective studies have concluded that there may be some benefit in decreasing morbidity and mortality.
• Hemorrhagic stroke is a risk of septic CST, with or without anticoagulation (1)[C].
ADDITIONAL TREATMENT
General Measures
All patients suspected of CST need admission.
Issues for Referral
Consult infectious disease, otolaryngology, ophthalmology, neurosurgery, and hematology when clinically indicated.
Additional Therapies
• Corticosteroids are necessary if pituitary insufficiency develops to prevent adrenal crisis.
• The use of corticosteroids to decrease edema caused by inflammation is controversial.
SURGERY/OTHER PROCEDURES
• The need for surgical intervention is dependent on the cause of CST.
• Septic CST: Drain source of infection
• Cavernous sinus fistula:
– Arteriography for diagnosis and possible intra-arterial closure
– A transvenous approach through the SOV may be helpful in selected cases (5)[C].
IN-PATIENT CONSIDERATIONS
Initial Stabilization
• Septic CST: Admit to ICU, close neurologic monitoring, intravenous antibiotic, and possible anticoagulation
• Cavernous sinus fistula with thrombosis: Admission for arteriography
• Aseptic CST: Admission for neurologic monitoring and anticoagulation
Admission Criteria
All suspected patients need admission.
IV Fluids
Hydration is important in all cases of CST.
Nursing
Close neurologic monitoring is needed.
Discharge Criteria
• Septic CST: Treatment and resolution of underlying cause, transition to oral antibiotics, and stable neurologic exam
• Aseptic CST: Stable neurologic exam with therapeutic oral anticoagulation
• CST secondary to fistula: Evidence of fistula closure either spontaneously or from intervention
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
• Septic CST: Depending on cause of infection follow-up with ophthalmology, oral surgery, or otolaryngology. Continue oral antibiotics for at least 14 days and possibly up to 6 weeks. Anticoagulation, if used, should be continued for a minimum of 2 weeks and up to 6 weeks (1)[C].
• Aseptic CST: Follow-up with hematology and internal medicine for therapeutic anticoagulation
• Instruct patients to contact health care providers if new or worsening symptoms develop.
Patient Monitoring
• Septic CST: Once underlying infection has resolved no continuous monitoring is necessary beyond 3 months unless cranial neuropathies persist.
• Within the first 3 months, there is a theoretical risk of recurrent infection from bacterial sequestration within the thrombus.
• A residual cranial neuropathy should be followed conservatively for at least 6 months to allow for improvement.
• Aseptic CST: Need lifelong monitoring to ensure anticoagulations remain therapeutic
• CST from fistula: Monitor for 3–6 months to assure that a fistula does not reform
DIET
Dietary restriction depends on the antibiotic and anticoagulation used.
PATIENT EDUCATION
• Obtain genetic/hematologic testing if there is a family history of thrombotic events.
• If there is a history of CST, contact health care provider immediately if new or recurrent neurologic symptoms develop.
PROGNOSIS
• Septic CST has a guarded prognosis, with an estimated mortality of 30%.
• 50% of patients who survive will be left with permanent neurologic sequelae (1)[C].
• Patients with CST secondary to fistula do well if the fistula is successfully closed.
COMPLICATIONS
• For all forms of CST:
– Cranial nerve palsy, including optic neuropathy with visual loss
– Pituitary insufficiency
– Hemorrhagic infarction
– Death
• For septic CST:
– Intracranial infections: Meningitis, encephalitis, and empyema formation
REFERENCES
1. Barahimi B, Murchison AP, Bilyk JR. Forget me not. Surv Ophthalmol 2010;26(4):295–297.
2. Stam J. Thrombosis of the cerebral veins and sinuses. New Engl J Med 2005;352:1791–1798.
3. Fisher C, et al. Cerebral venous sinus thrombosis in the emergency department: A retrospective analysis of 17 case and review of literature. J Emerg Med 2010;38(2):140–147.
4. Pavlovich P, Looi A, Rootman J. Septic thrombosis of cavernous sinus: Two different mechanisms. Orbit 2006;25:39–43.
5. Chaudhry IA, et al. Carotid cavernous fistula: Ophthalmological implications. Middle East Afr J Ophthalmol 2009;16(2):57–63.
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