REVIEW ARTICLE Septic Thrombosis of the Cavernous Sinuses John R. Ebright, MD; Mitchell T. Pace, MD; Asher F. Niazi, MD eptic thrombosis of the cavernous sinuses (or cavernous sinus thrombophlebitis [CST]) is a dramatic and potentially lethal illness, which is still occasionally seen by clinicians. Before the availability of antimicrobial agents, mortality from CST was near 100%, but it markedly decreased to approximately 20% to 30% during the antibiotic era.1,2 Never- Stheless, the threat of death and serious morbidity continues to necessitate early recognition, diag- nosis, and treatment of CST to minimize risks to the patient. Accordingly, we reviewed the salient clinical features of this illness, with emphasis on newer aspects of diagnosis and treatment. Arch Intern Med. 2001;161:2671-2676 ANATOMY verse sinuses and internal jugular veins. In addition, the cavernous sinuses are con- Two cavernous sinuses are positioned on nected by emissary veins to the pterygoid either side of the sella turcica, which con- plexus, which is adjacent to the deep tains the pituitary gland (Figure 1). These muscles of the face, and also communi- sinuses are connected by intercavernous cates with the deep facial and inferior oph- sinuses located anterior and posterior to thalmic veins (Figure 2). the sella. As is true for all dural venous si- nuses, the cavernous sinuses are formed PATHOGENESIS by a separation of the layers of dura mater (specifically, the meningeal and perios- The dural sinuses and the cerebral and em- teal layers), with trabeculae from each layer issary veins have no valves, which allows crossing the spaces, giving them a reticu- blood to flow in either direction accord- lar or cavernous structure. Immediately be- ing to pressure gradients in the vascular low, separated by very thin bone, are the system. This fact and the extensive direct sphenoid sinuses. Of great clinical impor- and indirect vascular connections of the tance is the intimate relationship of cra- centrally located cavernous sinuses make nial nerves III, IV, V, and VI, which, ac- them vulnerable to septic thrombosis re- companied by the horizontal segment of sulting from infection at multiple sites. Si- the internal carotid artery, run through the nusitis, especially involving the sphe- lumen in the cases of the artery and ab- noid and ethmoid sinuses, seems to be the ducens nerve or through the outside lay- most common primary source of infec- ers of the cavernous sinuses’ lateral walls tion predisposing to CST. Infections aris- in the cases of the oculomotor, trochlear, ing at other locations, such as the face, and ophthalmic maxillary branches of the nose, tonsils, soft palate, teeth (lower and trigeminal nerves.4,5 upper), and ears, are less common pri- The cavernous sinuses extend from mary sources since antibiotic therapy has the superior orbital fissure in front back- become widely available. Orbital infection ward to the petrous portion of the tem- is rarely complicated by CST, although the poral bone. They receive blood from the ophthalmic veins drain directly into the superior ophthalmic and cerebral veins and orbits.6 the sphenoparietal sinuses and terminate The most common signs of CST are re- posteriorly in the superior and inferior pe- lated to damage of the nerves that traverse trosal sinuses, which drain into the trans- the cavernous sinuses (including the para- sympathetic and sympathetic nerves ac- From the Departments of Medicine (Drs Ebright and Niazi) and Radiology (Dr Pace), companying the oculomotor nerve and the Wayne State University School of Medicine and Detroit Medical Center, Detroit, Mich. internal carotid artery, respectively) and to (REPRINTED) ARCH INTERN MED/ VOL 161, DEC 10/24, 2001 WWW.ARCHINTERNMED.COM 2671 Downloaded from www.archinternmed.com at N/A, on November 5, 2007 ©2001 American Medical Association. All rights reserved. Third Ventricle Optic Chasm Internal Carotid Artery Oculomotor Nerve (III) Trochlear Nerve (IV) Pituitary Gland Internal Carotid Artery Abducens Nerve (VI) Ophthalmic Branch, Nerve V Cavernous Sinus Maxillary Branch, Nerve V Sphenoidal Sinus Nasopharynx Figure 1. Frontal section through the cavernous sinuses. Copyright 1997. Icon Learning Systems, LLC, a subsidiary of MediMedia USA Inc. Reprinted with permission from ICON Learning Systems, LLC, illustrated by Frank H. Netter, MD. All rights reserved.3 Superior face, or in a retrograde fashion from Sagittal lateral venous sinuses, ears, or teeth. Superior Sinus Ophthalmic It is possible that more indolent, sub- Vein acute cases arise from initially ster- Inferior ile thrombi that become infected af- Sagittal ter extending into the cavernous Sinus sinuses and that fulminant, acute cases result from rapid progression Inferior of an infected thrombus or septic Ophthalmic Cavernous Vein Sinus embolization from a primary in- fected focus.7 Irrespective of which mechanism is involved, the pres- ence of enlarging infected clots within Lateral a confined cavernous sinus spread- Intercavernous Sinus Sinuses ing via intercavernous sinuses to in- volve the opposite side is an omi- nous complication. Systemic effects from sepsis, local effects from direct Pterygoid Sigmoid Plexus Sinus injury to cranial nerves III through VI and impaired vascular drainage from the face and eyes, and possible exten- Internal Superior and sion into adjacent tissue, causing Jugular Vein Inferior Petrosal meningitis, subdural empyema, and Sinuses pituitary necrosis, together may re- Figure 2. Relationship of the cavernous sinuses to other dural sinuses and veins of the head and face. sult in an overwhelming and truly catastrophic illness. engorgement of the retinal and or- like sieves, trapping bacteria, em- MICROBIOLOGIC FINDINGS bital vessels caused by impaired ve- boli, and thrombi progressing from nous drainage. It has been specu- anterior infected sites involving the The most commonly identified lated that the trabeculated sinuses act nose, sinuses, or medial third of the pathogen in patients with CST con- (REPRINTED) ARCH INTERN MED/ VOL 161, DEC 10/24, 2001 WWW.ARCHINTERNMED.COM 2672 Downloaded from www.archinternmed.com at N/A, on November 5, 2007 ©2001 American Medical Association. All rights reserved. Nevertheless, most patients will de- sion of infection from the cavern- Frequency of Symptoms and velop fever, ptosis, proptosis, che- ous sinuses or primary site of Physical Abnormalities in Patients mosis, and external ophthalmople- infection to involve the adjacent vas- With Septic Thrombosis of the Cavernous Sinuses* gia during the course of their illness. cular structures or brain paren- External ophthalmoplegia, defined as chyma. Southwick et al3 reviewed the Abnormality Frequency, % paralysis of the extraocular muscles pathologic findings of 23 patients (in the case of CST, secondary to dys- who died or underwent surgery dur- Fever Ptosis function of cranial nerves III, IV, and ing the antibiotic era. Extension of Proptosis 80-100 VI, rather than direct involvement of the thrombosis to other venous si- Chemosis the extraocular muscles), usually in- nuses, including petrosal, inferior Cranial nerve palsies cludes all the extraocular muscles. sagittal, sigmoid, and lateral, was ob- Lethargy However, it may be more limited or served in 7 patients. Such exten- Headache present at least initially with only sion may not only worsen head- Periorbital swelling 50-80 Papilledema lateral rectus muscle palsy, espe- ache, obtundation, and papilledema Venous engorgement cially when disease spreads to the op- but may also result in additional Decreased visual acuity posite eye. Spread to the opposite findings, such as ear and neck pain, Sluggish or dilated pupil eye through the intercavernous si- odynophagia, dysphagia, hoarse- Periorbital sensory loss Ͻ50 nuses, usually within 24 to 48 hours ness, lateral-gaze nystagmus, sei- Decreased corneal reflex of the initial unilateral periorbital zures, and hemiplegia. In addition, Nuchal rigidity 7 Diplopia edema, is a common and character- the same authors noted 4 cases of Seizures Ͻ20 istic feature of CST. Less frequent, but pituitary necrosis due to contigu- Hemiparesis still seen in most patients, are mild ous spread of infection or ischemic papilledema (usually a late finding), damage, 11 cases of meningitis, and *Adapted from Southwick et al,3 copyright retinal venous engorgement, and al- 9 cases of brain abscess or subdural 1986. tered mental status consisting of leth- empyema, primarily in the fronto- argy or obtundation. Headaches, an parietal or temporal lobes.3 tinues to be Staphylococcus aureus, early symptom resulting from ei- identified in 60% to 70% of pa- ther sinusitis or CST, usually are fron- DIFFERENTIAL DIAGNOSIS tients. Less frequently identified are tal, temporal, or retro-orbital and streptococcal species, including may be accompanied by tearing. Cavernous sinus thrombophlebitis Streptococcus pneumoniae; gram- Violaceous edema of the upper lid is only 1 (albeit probably the most negative bacilli; and anerobes.3 Blood accompanying periorbital swelling dramatic) of many causes of pain- cultures are commonly positive (ap- also is common. ful ophthalmoplegia. The most com- proximately 70% of cases), espe- Decreased visual acuity, inter- mon condition mimicking acute CST cially in patients with acute, fulmi- nal ophthalmoplegia, and perior- is orbital cellulitis, which com- nant disease, whereas cerebrospinal bital sensory alteration secondary to monly causes periorbital swelling, fluid, abnormal in most patients