Cavernous Sinus Thrombosis

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Background

Cavernous sinus thrombosis (CST) was initially described by Bright in 1831 as a complication of epidural and subdural infections. The dural sinuses are grouped into the sagittal, lateral (including the transverse, sigmoid, and petrosal sinuses), and cavernous sinuses. Because of its complex neurovascular anatomic relationship, cavernous sinus thrombosis is the most important of any intracranial septic thrombosis.[1] Cavernous sinus thrombosis is usually a late complication of an infection of the central face or paranasal sinuses. Other causes include bacteremia, trauma, and infections of the ear or maxillary teeth. Cavernous sinus thrombosis is generally a fulminant process with high rates of morbidity and mortality. Fortunately, the incidence of cavernous sinus thrombosis has been decreased greatly with the advent of effective antimicrobial agents.

Pathophysiology

The cavernous sinuses are irregularly shaped, trabeculated cavities located at the base of the skull. The cavernous sinuses are the most centrally located of the dural sinuses and lie on either side of the sella turcica. These sinuses are just lateral and superior to the sphenoid sinus and are immediately posterior to the optic chiasm, as depicted in the image below. Each cavernous sinus is formed between layers of the dura mater, and multiple connections exist between the 2 sinuses.



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Anatomy of cross section of cavernous sinus showing close proximity to cranial nerves and sphenoid sinus.

The cavernous sinuses receive venous blood from the facial veins (via the superior and inferior ophthalmic veins) as well as the sphenoid and middle cerebral veins. They, in turn, empty into the inferior petrosal sinuses, then into the internal jugular veins and the sigmoid sinuses via the superior petrosal sinuses. This complex web of veins contains no valves; blood can flow in any direction depending on the prevailing pressure gradients. Since the cavernous sinuses receive blood via this distribution, infections of the face including the nose, tonsils, and orbits can spread easily by this route.

The internal carotid artery with its surrounding sympathetic plexus passes through the cavernous sinus. The third and fourth cranial nerves are attached to the lateral wall of the sinus. The ophthalmic and maxillary divisions of the fifth cranial nerve are embedded in the wall. The sixth cranial nerve follows a more medial course in close approximation to the internal carotid, as depicted in the image above.

This intimate juxtaposition of veins, arteries, nerves, meninges, and paranasal sinuses accounts for the characteristic etiology and presentation of cavernous sinus thrombosis (CST). CST is more commonly seen with sphenoid and ethmoid and to a lesser degree with frontal sinusitis.

Staphylococcus aureus accounts for approximately 70% of all infections. Streptococcus pneumoniae, gram-negative bacilli, and anaerobes can also be seen. Fungi are a less common pathogen and may include Aspergillus and Rhizopus species.

Epidemiology

Frequency

Occurrence of cavernous sinus thrombosis (CST) has always been low, with only a few hundred case reports in the medical literature. The majority of these date from before the modern antibiotic era. One review of the English-language literature found only 88 cases from 1940-1988.

Mortality/Morbidity

Prior to the advent of effective antimicrobial agents, the mortality rate from CST was effectively 100%. Typically, death is due to sepsis or central nervous system (CNS) infection. With aggressive management, the mortality rate is now less than 30%. Morbidity, however, remains high, and complete recovery is rare. Roughly one sixth of patients are left with some degree of visual impairment, and one half have cranial nerve deficits. These mortality and morbidity rates may be due to delayed diagnosis without prompt surgical drainage and antibiotic administration.

Age

All ages are affected, with a mean of 22 years.

History

The early signs and symptoms of cavernous sinus thrombosis (CST) may not be specific. A patient who presents with headache and any cranial nerve findings should be potentially evaluated for CST. The most common signs of CST are related to the anatomical structures affected within the cavernous sinus, as depicted in the image below.



View Image

Anatomy of cross section of cavernous sinus showing close proximity to cranial nerves and sphenoid sinus.

Patients generally have sinusitis or a midface infection (most commonly a furuncle) for 5-10 days. In as many as 25% of cases in which a furuncle is the precipitant, it will have been manipulated in some fashion (eg, squeezing, surgical incision).

The clinical presentation is usually due to the venous obstruction as well as impairment of the cranial nerves that are near the cavernous sinus.

Headache is the most common presentation symptom and usually precedes fevers, periorbital edema, and cranial nerve signs. The headache is usually sharp, increases progressively, and is usually localized to the regions innervated by the ophthalmic and maxillary branches of the fifth cranial nerve.

In some patients, periorbital findings do not develop early on, and the clinical picture is subtle.

Some cases of CST may present with focal cranial nerve abnormalities possibly presenting similar to an ischemic stroke.[2]

As the infection tracts posteriorly, patients complain of orbital pain and fullness accompanied by periorbital edema and visual disturbances.

Without effective therapy, signs appear in the contralateral eye by spreading through the communicating veins to the contralateral cavernous sinus. Eye swelling begins as a unilateral process and spreads to the other eye within 24-48 hours via the intercavernous sinuses. This is pathognomonic for CST.

The patient rapidly develops mental status changes including confusion, drowsiness, and coma from CNS involvement and/or sepsis. Death follows shortly thereafter.

Physical

Other than the findings associated with the primary infection, the following signs are typical for cavernous sinus thrombosis:

Periorbital edema may be the earliest physical finding.

Manifestations of increased retrobulbar pressure follow.

Signs of increased intraocular pressure (IOP) may be observed.

Hypoesthesia or hyperesthesia in dermatomes supplied by the V1 and V2 branches of the fifth cranial nerve.

Appearance of signs and symptoms in the contralateral eye is diagnostic of CST, although the process may remain confined to one eye.

Meningeal signs, including nuchal rigidity and Kernig and Brudzinski signs, may be noted.

Systemic signs indicative of sepsis are late findings. They include chills, fever, shock, delirium, and coma.

Causes

Most cases of septic cavernous sinus thrombosis (CST) are due to an acute infection in an otherwise healthy individual. However, patients with chronic sinusitis or diabetes mellitus may be at a slightly higher risk.

The causative agent is generally Staphylococcus aureus, although streptococci, pneumococci, and fungi may be implicated in rare cases.

Laboratory Studies

Cavernous sinus thrombosis (CST) is a clinical diagnosis and lab studies are seldom specific. Most patients exhibit a polymorphonuclear leukocytosis, often marked with a shift toward immature forms. Examination of the cerebrospinal fluid is consistent with either a parameningeal inflammation or frank meningitis. Blood culture results generally are positive for the offending organism.

One study by Misra et al showed that a D-dimer may be useful in patients with suspected cortical sinus venous thrombosis (CSVT).[4]

Imaging Studies

Historically, a number of techniques have been used to image cavernous sinus thrombosis (CST), including plain sinus radiography, carotid angiography, and orbital venography. In current practice, computed tomography (CT) scan or magnetic resonance imaging (MRI) with contrast is the modality of choice to confirm the diagnosis of CST and to differentiate it from alternatives such as orbital cellulitis, which may have a similar clinical presentation. The literature suggest using both CT and MRI, particularly diffusion weighted MRI; CT first (since it is generally faster and more available) and then MRI, especially if the CT is not definitive.[5, 6, 7, 8]

MRI with MR venogram (MRV) is the preferred imaging choice as the MRV will show the absence of venous flow in the affected cavernous sinus.

On noncontrast CT, thrombosis of the cavernous sinus can be appreciated as increased density. The introduction of intravenous contrast can reveal filling defects within the cavernous sinus as well as thickening of the superior ophthalmic vein. Nevertheless, CT scan findings may be subtle, and a negative CT scan cannot rule out CST reliably when the clinical suspicion is high.

Carotid angiography can demonstrate narrowing or obstruction of the intercavernous segment of the carotid artery. MRI and CT scan can also show this narrowing and/or obstruction of the carotid artery.

Procedures

Lumbar puncture may be helpful in distinguishing CST from more localized processes (e.g., sinusitis, orbital cellulitis). Lumbar puncture reveals inflammatory cells in approximately 75% of cases.

Emergency Department Care

The mainstay of therapy for cavernous sinus thrombosis is early and aggressive antibiotic administration. Although S aureus is the usual cause, broad-spectrum coverage for gram-positive, gram-negative, and anaerobic organisms should be instituted pending the outcome of cultures.

Empiric antibiotic therapy should include a penicillinase-resistant penicillin plus a third- or fourth-generation cephalosporin. If dental infection or other anaerobic infection is suspected, an anaerobic coverage should also be added.

IV antibiotics are recommended for a minimum of 3-4 weeks.

Controversy exists on the use of anticoagulation for cavernous sinus thrombosis. Because of the rarity of this syndrome, no prospective trials have been performed on the use of anticoagulation for CST. Some retrospective studies have shown a decrease in mortality and clot propagation by anticoagulation. A Cochrane review found two small trials involving 79 patients who were treated with anticoagulants. Limited evidence suggests anticoagulant drugs are probably safe and may be beneficial for people with sinus thrombosis.[9] Therefore, anticoagulation with heparin should be considered since the goal is to prevent further thrombosis and to reduce the incidence of septic emboli. One review suggests that low-molecular weight heparin (LMWH) is superior to unfractionated heparin (UFH).[10] Heparin is contraindicated in the presence of intracerebral hemorrhage or other bleeding diathesis.

Locally administered thrombolytics have also been used in the treatment of CST. However, use of thrombolytics should be considered experimental and only for severe refractory cases.[1]

Corticosteroids may help to reduce inflammation and edema and should be considered as an adjunctive therapy. They should be instituted after antibiotic coverage. When the course of CST leads to pituitary insufficiency, however, corticosteroids definitely are indicated to prevent adrenal crisis. Dexamethasone or hydrocortisone should be considered.

Surgery on the cavernous sinus is technically difficult and has never been shown to be helpful. The primary source of infection should be drained, if feasible (eg, sphenoid sinusitis, facial abscess). It is important to recognize the infected sphenoid sinus early and to prevent spread of the infection to the cavernous sinus.

Consultations

If drainage is indicated, make arrangements for intensive care and request the appropriate surgical consultation.

An infectious disease consultation should be considered in choosing the proper antibiotic coverage for the CST.

Medication Summary

Antibiotic therapy ideally is started after appropriate cultures but should not be delayed if difficulties exist in obtaining specimens. Antibiotics selected should be broad-spectrum, particularly active against S aureus, and capable of achieving high levels in the cerebrospinal fluid. With the recent increased prevalence of community-acquired MRSA, the emergency physician should consider additional coverage with intravenous antibiotics, such as vancomycin, if MRSA infection is suspected.

However, a case report and literature review by Naesens et al of community-acquired MRSA infections of the central nervous system, including cavernous sinus thrombosis, showed that patients treated with linezolid had a better outcome than those treated with vancomycin.[11]

Oxacillin (Bactocill)

Clinical Context:  A bactericidal antibiotic that inhibits cell wall synthesis. Used in treatment of infections caused by penicillinase-producing staphylococci. May be used to initiate therapy when staphylococcal infection is suspected.

Ceftriaxone (Rocephin)

Clinical Context:  Alternate antimicrobial choice. Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms than earlier generation cephalosporins. By binding to 1 or more penicillin-binding proteins, arrests bacterial cell wall synthesis and inhibits bacterial growth.

Metronidazole (Flagyl)

Clinical Context:  Additional anaerobic coverage. Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Usually employed in combination with other antimicrobial agents (except when used for Clostridium difficile enterocolitis, in which monotherapy appropriate).

Chloramphenicol (Chloromycetin)

Clinical Context:  Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

Vancomycin

Clinical Context:  Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes.

To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients diagnosed with renal impairment.

Used in conjunction with gentamicin for prophylaxis in penicillin allergic patients undergoing gastrointestinal or genitourinary procedures.

Class Summary

Empiric broad-spectrum coverage for gram-positive, gram-negative, and anaerobic organisms is necessary. Therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

In cases of suspected MRSA infection, vancomycin should be added for additional coverage.

Heparin

Clinical Context:  Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse thrombus but able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Various dosing nomograms available.

Class Summary

Unfractionated IV heparin and fractionated low-molecular-weight SC heparins are the 2 options in anticoagulation therapy.

Hydrocortisone (Solu-Cortef, Westcort)

Clinical Context:  DOC due to its mineralocorticoid activity and glucocorticoid effects. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Useful in management of inflammation caused by an immune response.

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli. When the course of CST leads to pituitary insufficiency, corticosteroids definitely are indicated to prevent adrenal crisis.

Further Inpatient Care

Admission to intensive care unit is indicated.

Deterrence/Prevention

Patients should be educated that furuncles or abscesses (pimples) in the central portion of the face should not be manipulated without prior antibiotic coverage.

Complications

Complications may include the following:

Prognosis

Mortality rate is as high as 30%; the majority of survivors suffer permanent sequelae.

What is cavernous sinus thrombosis (CST)?What is the anatomy of the cavernous sinuses?How does infection spread to the cavernous sinuses?Which arteries and nerves are involved in the cavernous sinuses?Which anatomic features are relevant to the etiology of cavernous sinus thrombosis (CST)?Which bacteria are the cause of most infections associated with cavernous sinus thrombosis (CST)?How common is cavernous sinus thrombosis (CST)?What are the mortality and morbidity of cavernous sinus thrombosis (CST)?What are the age-related demographics for cavernous sinus thrombosis (CST)?What are the signs and symptoms of cavernous sinus thrombosis (CST)?What causes the symptoms associated with cavernous sinus thrombosis (CST)?What is the most common symptom of cavernous sinus thrombosis (CST)?When do periorbital symptoms occur in cavernous sinus thrombosis (CST)?Which condition has a similar presentation as cavernous sinus thrombosis (CST)?What patient complaints are associated with cavernous sinus thrombosis (CST)?What are the signs of treatment failure in cavernous sinus thrombosis (CST)?What are the signs of cavernous sinus thrombosis (CST)?What are the causes of cavernous sinus thrombosis (CST)?What are the differential diagnoses for Cavernous Sinus Thrombosis?What is the role of lab studies in the workup of cavernous sinus thrombosis (CST)?Which imaging studies are indicated in the workup of cavernous sinus thrombosis (CST)?What is the role of MRI in the workup of cavernous sinus thrombosis (CST)?What is the role of CT scanning in the workup of cavernous sinus thrombosis (CST)?What is the role of carotid angiography in the workup of cavernous sinus thrombosis (CST)?What is the role of lumbar puncture (LP) in the workup of cavernous sinus thrombosis (CST)?What is the mainstay of therapy for cavernous sinus thrombosis (CST)?What is in the recommended empiric antibiotic therapy for the treatment of cavernous sinus thrombosis (CST)?How long should IV antibiotics be used in the treatment of cavernous sinus thrombosis (CST)?Are anticoagulants indicated for the treatment of cavernous sinus thrombosis (CST)?Are thrombolytics indicated for the treatment of cavernous sinus thrombosis (CST)?What is the role of corticosteroids in the treatment of cavernous sinus thrombosis (CST)?Is surgery indicated in the treatment of cavernous sinus thrombosis (CST)?Which specialist consultations are indicated in the treatment of cavernous sinus thrombosis (CST)?Which antibiotics are recommended for the treatment of cavernous sinus thrombosis (CST)?Which medications in the drug class Corticosteroids are used in the treatment of Cavernous Sinus Thrombosis?Which medications in the drug class Anticoagulants are used in the treatment of Cavernous Sinus Thrombosis?Which medications in the drug class Antibiotic, Miscellaneous are used in the treatment of Cavernous Sinus Thrombosis?Where should patients with cavernous sinus thrombosis (CST) be treated?How can cavernous sinus thrombosis (CST) be prevented?What are the complications of cavernous sinus thrombosis (CST)?What is the mortality rate of cavernous sinus thrombosis (CST)?

Author

Rahul Sharma, MD, MBA, FACEP, Medical Director and Associate Chief of Service, NYU Langone Medical Center, Tisch Hospital Emergency Department; Assistant Professor of Emergency Medicine, New York University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Edward Bessman, MD, MBA, Chairman and Clinical Director, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Sanz Laniado Medical Center, Netanya, Israel

Disclosure: Nothing to disclose.

Additional Contributors

J Stephen Huff, MD, FACEP, Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

Disclosure: Nothing to disclose.

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Anatomy of cross section of cavernous sinus showing close proximity to cranial nerves and sphenoid sinus.

Anatomy of cross section of cavernous sinus showing close proximity to cranial nerves and sphenoid sinus.

Anatomy of cross section of cavernous sinus showing close proximity to cranial nerves and sphenoid sinus.