Septic Thrombosis of the Cavernous Sinuses

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, diagnosis, 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 sinuses, 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: https://jamanetwork.com/ on 09/26/2021 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 infected 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 involve 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: https://jamanetwork.com/ on 09/26/2021 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 in trigeminal nerve (cranial nerve V) proptosis, chemosis, ophthalmople- terms of elevated white blood cell dysfunction have been reported in less gia, fever, decreased vision, and counts and protein levels, is cul- than half of the patients. Internal oph- pain.12 However, bilateral eye in- ture positive in only approximately thalmoplegia, defined as paralysis of volvement, papilledema, decreased 20% of cases.8 Occasionally, fungi the iris and ciliary apparatus, results periocular sensation, dilated pu- such as Aspergillus and members of from dysfunction of parasympa- pils, marked systemic toxic effects, the Mucoraceae family may cause thetic nerve fibers carried through the and abnormal spinal fluid are much CST.9-11 cavernous sinuses and optic canals on more likely to be features of CST and the oculomotor (cranial nerve III) aid in differentiating the two con- CLINICAL PRESENTATION nerves or dysfunction of the sympa- ditions. Preseptal cellulitis, which thetic fibers that join them to form the does not cause proptosis and oph- Multiple clinical features varying in short ciliary nerves. As a result, the thalmoplegia, generally causes little frequency and severity have been re- pupils may be dilated from parasym- confusion. Orbital apex syndrome, ported, with some, such as septic in- pathetic paralysis or may be smaller a rare complication of sinusitis, re- farcts of other organs, becoming un- and immobile if both parasympa- sults from inflammation or infec- common since the availability of thetic and sympathetic fibers are in- tion involving 2 clefts in the bony antibiotic therapy. Another vari- volved. Sensory alteration within the posterior orbit: (1) the superior or- able in this condition is the timing distribution of the first division of the bital fissure, which transmits cra- of the onset of signs and symp- trigeminal nerve may present as hy- nial nerves III, IV, and VI and toms: patients with acute, fulmi- peresthesia or hypoesthesia possibly branches of the ophthalmic divi- nant disease will manifest most signs with a depressed corneal response. sion of cranial nerve V, and the su- and symptoms rapidly from the out- Diplopia, seizures, and hemiparesis perior ophthalmic vein, and (2) the set of illness, and patients with a are uncommon.3,6 optic canal, through which pass the more subacute course will evi- The clinical presentation may ophthalmic artery and optic nerve. dence the features listed in the Table be made even more complex as a re- This condition, compared with or- sequentially and over several days. sult of ischemic changes or exten- bital cellulitis, more typically causes

(REPRINTED) ARCH INTERN MED/ VOL 161, DEC 10/24, 2001 WWW.ARCHINTERNMED.COM 2673

Downloaded From: https://jamanetwork.com/ on 09/26/2021 visual loss and ophthalmoplegia out ernous sinus with lateral wall flat- ralysis of cranial nerves III, IV, and of proportion to or preceding signs tening or convexity rather than nor- VI; ptosis; and decreased visual acu- of anterior eye involvement, such as mal concavity, best visualized on ity. The patient died shortly there- proptosis and periorbital edema. Be- coronal images. In addition, multiple after secondary to respiratory ar- cause the optic nerve passes through irregular or single large filling defects rest, presumably from progressive the apex but not through the cav- within the enhancing cavernous si- infection of the central nervous sys- ernous sinus, impaired vision is nus are highly suggestive direct evi- tem. Permission for autopsy was de- more common with the orbital apex dence for thrombi. This is particularly nied. A biopsy sample from the eth- syndrome than with CST.13,14 the case when the filling defects are moid sinus obtained during an open Other more indolent or chronic irregular and do not correspond to the surgical procedure by the ear, nose, conditions may cause painful oph- anatomic course of neural struc- and throat service a few days be- thalmoplegia owing to involvement tures or a thrombosed intracavern- fore her death was unrevealing on of the cavernous sinuses, including ous section of the internal carotid ar- frozen sections but consistent with local or metastatic malignancy; asep- tery. They also must be differentiated mucormycosis on fungal stains of tic thrombosis resulting from trauma, from intracavernous fat deposits by permanent sections. myeloproliferative diseases, or dehy- size (thrombi usually Ͼ7 mm), den- Computed tomography per- dration; granulomatous disease, such sity, and signal intensity.21-24 formed with coronal images of the as tuberculosis or fungal infection, Indirect signs, related to con- paranasal sinuses on the eighth sarcoid, syphilis, or Tolosa-Hunt syn- comitant venous obstruction, con- hospital day revealed mucous re- drome; aneurysm of the internal ca- sist of dilation of the superior oph- tention cysts in both maxillary rotid artery; or carotid-cavernous thalmic vein, exophthalmos, soft sinuses, opacification of the eth- fistula. Other chronic diseases that tissue edema, and thrombi visual- moid sinuses, and mucosal thicken- may be confused with disease involv- ized in the veins and sinuses tribu- ing of the left sphenoid sinus. Pro- ing the cavernous sinuses are endo- tary to the cavernous sinus (supe- ptosis was present on the right side. crine exophthalmos and ophthal- rior ophthalmic vein and superior The superior ophthalmic veins did moplegic migraine.15-20 petrosal, inferior petrosal, and sig- not seem to be engorged. The cav- moid sinuses).21-24 ernous sinuses were poorly visual- DIAGNOSIS Magnetic resonance imaging ized owing to insufficient intrave- may be of greatest value either to re- nous contrast agent within the Before the availability of computed examine patients with nondiagnos- sinuses. Two days later, an MRI tomography (CT) or magnetic reso- tic CT scans or to further assess com- scan revealed mucosal thickening nance imaging (MRI), CST was di- plications involving the pituitary of the sinuses and diminished agnosed by its clinical features or at gland or extension of infection into enhancement in the right cavern- autopsy. Occasionally, cerebral an- adjacent meninges or brain.21,22 We ous sinus, accompanied by a right giography or the more definitive or- report a case of probable mucormy- cavernous internal carotid artery bital venography was performed, but cosis in which the organism seems signal void, which was smaller than it was accompanied, at least in the to have invaded the cavernous si- that seen on the left (providing pre- case of orbital venography, by the nuses from the paranasal sinuses to sumptive evidence for compression possibility of serious complica- illustrate these points. of the right internal carotid artery tions. It was difficult to puncture the by thrombus within the sinus). frontal veins in patients who were REPORT OF A CASE Another MRI the following day acutely ill with facial edema; in ad- revealed the additional finding of a dition, there was much concern that A 49-year-old woman with a his- new filling deffect in the left cav- orbital venography, accomplished by tory of diabetes mellitus was admit- ernous sinus (Figure 3). injecting contrast material under ted to the hospital and treated for pressure, may actually disseminate diabetic ketoacidosis, which was re- MANAGEMENT AND the infection or cause extension of versed by the second hospital day. TREATMENT the thrombosis.21 Her course was complicated by se- The availability of high-reso- vere gastritis and upper gastrointes- Management of patients with CST lution enhanced CT scans and, more tinal tract bleeding. On the seventh must also include treatment of pri- recently, MRI has remarkably im- hospital day, she complained of right mary infections, such as sinusitis, proved our ability to establish the di- eye pain and experienced rapid loss dental abscesses, and facial celluli- agnosis of CST using noninvasive of vision, accompanied by right eye- tis, and possible complications, in- technology. Although there is cur- lid edema, ptosis, and external and cluding brain abscesses, meningi- rently some debate regarding which internal ophthalmoplegia. Propto- tis, and extension to other venous of the two is the procedure of first sis was present the following day. sinuses. Initial antibiotic choice, choice, most experience is with high- Treatment initially was intrave- while awaiting culture results, might resolution CT performed with a slice nous ampicillin and sulbactam; on consist of nafcillin sodium, metro- thickness of 3 mm or less.22 Abnor- the ninth hospital day, high-dose nidazole, and ceftriaxone sodium or mal findings include those that are amphotericin B lipid complex was cefotaxime sodium to treat the pa- direct signs of CST, consisting of en- added. By the 11th hospital day, the tient for the most common organ- largement and expansion of the cav- left eye was also involved, with pa- isms associated with this disease.

(REPRINTED) ARCH INTERN MED/ VOL 161, DEC 10/24, 2001 WWW.ARCHINTERNMED.COM 2674

Downloaded From: https://jamanetwork.com/ on 09/26/2021 lateral blindness, seizures, hemiparesis, and hypopituitarism may be ob- served. The review by Southwick et al3 suggests that early anticoagulant therapy in patients with unilateral CST may also reduce mortality rates. Duration of anticoagulant therapy with warfarin sodium after initial heparin therapy is unknown, but 4 to 6 weeks has been suggested.30

MORBIDITY AND MORTALITY

Mortality has decreased from 80% to 100% in the preantibiotic era to 20% to 30% since 1940. In addition, Yarington2 points to a de- crease in morbidity from 50% to 75% to only 22%. Nevertheless, the threat of temporary complications and long-term sequelae remains. In a review published early in the antibiotic era, Shaw7 described 60 patients treated with either sulfon- amides or penicillin: 53 recovered, but most (77%) had complications or long-term sequelae. Twenty-five patients had metastatic infection primarily involving the lungs, with abscesses, empyema, and pneumonia. Nine patients developed orbital ab- Figure 3. Magnetic resonance image of the cavernous sinuses, with a coronal (frontal), T1-weighted, scesses and 5 developed abscesses in postgadolinium image through the sella turcica, which reveals a bulging lateral wall of the cavernous sinus (thin arrow) and a large filling defect secondary to thrombus on the right side (curved arrow). The the brain. Prolonged cranial nerve left cavernous sinus demonstrates a small filling defect (large arrow) adjacent to the internal carotid flow dysfunction, especially of nerves III void secondary to thrombus from intercavernous spread. The black arrow indicates a portion of the and VI, were the most common long- pituitary gland. term sequelae; 5 patients developed unilateral blindness, and 4 had de- Vancomycin could be substituted for ticosteroids is not a well-supported in- creased visual acuity. Prominent fa- nafcillin if the risk of methicillin re- tervention in patients with CST. In a cial veins and spastic paresis of the sistance is high. Doses should be few patients, corticosteroid use may arm were also noted but were un- high, appropriate for critically ill pa- have contributed to improving cra- usual.7 A more recent review3 of 96 tients with intravascular and pos- nial nerve dysfunction3,26 or persis- patients treated since 1940 found 29 sible central nervous system infec- tent orbital congestion.27 Rarely, cor- to have long-term sequelae, includ- tions. The duration of antibiotic ticosteroid use may play a critical role ing oculomotor (cranial nerve III) therapy is not standardized, but 3 to in caring for patients with adrenal in- weakness in 16 (17%) of 95 pa- 4 weeks, consistent with manage- sufficiency secondary to ischemia or tients, blindness in 16 (17%), pitu- ment of other intravascular infec- necrosis of the pituitary gland.28,29 Full itary insufficiency in 2 (2%), and tions, such as endotheliitis or sup- anticoagulation using heparin, how- hemiparesis in 3 (3%). The cause of purative phlebitis, seems to be a ever, is possibly beneficial in select pa- blindness has been speculated to reasonable projection, especially if tients. Although no randomized con- be pressure on the retinal artery signs of inflammation, toxic ef- trolled studies have been conducted and vein at the orbital apex, arteri- fects, and fever have ceased during (and because of the infrequency of tis of the internal carotid artery, that period.25 this disease, probably never will be emboli to the retinal artery, or toxic Surgical drainage of the cavern- conducted), recent retrospective re- neuropathy of the optic nerve.31 ous sinus is almost never per- views provide some support for hep- Pituitary insufficiency, a rare but formed, but surgery may be essen- arin use in the absence of cortical ve- well-documented event, results tial for the management of primary nous infarction. Anticoagulant from either infarction or extension sinusitis or dental infection or com- therapy begun early (ie, within 7 days of infection into the sella turcica.29 plicating brain abscess, orbital ab- of hospitalization for CST) may re- Hemiparesis may be a consequence scess, or subdural empyema. Simi- duce morbidity rates in survivors.30 In of internal carotid artery occlusion, larly, reduction of inflammation and particular, a reduction in diplopia cerebral abscess, or cortical vein edema by administering systemic cor- from cranial nerve dysfunction, uni- thrombosis.30

(REPRINTED) ARCH INTERN MED/ VOL 161, DEC 10/24, 2001 WWW.ARCHINTERNMED.COM 2675

Downloaded From: https://jamanetwork.com/ on 09/26/2021 CONCLUSIONS York, NY: Oxford University Press; 1994:325- 18. Lovel T, Marsan RE. Carotid cavernous fistula. 326. Angiology. 1974;25:231-236. 5. VanOverbeake JJ, Jansen JJ, Tulleken CAF. The cav- 19. Grayeli AB, Redondo A, Salama J, Rey A. Tuber- Although rare, CST remains a dra- ernous sinus syndrome: an anatomical and clini- culoma of the cavernous sinus: case report. Neu- matic and potentially lethal compli- cal study. Clin Neurol Neurosurg. 1988;90:311- rosurgery. 1998;42:179-181. cation of infections involving the si- 319. 20. Brismar G, Brismar J. Aseptic thrombosis of nuses, face, ears, and oral cavity. Early 6. DiNubile MJ. Septic thrombosis of the cavern- orbital veins and cavernous sinus. Acta Ophthal- ous sinuses. Arch Neurol. 1988;45:567-572. mologica. 1977;55:9-22. recognition and differentiation from 7. Shaw RE. Cavernous sinus thrombophlebitis: a re- 21. Berge J, Louail C, Caille JM. Cavernous sinus other diseases that can mimic it view. Br J Surg. 1952;40:40-48. thrombosis diagnostic approach. J Neuroradiol. coupled with aggressive medical and 8. Taylor PJ. Cavernous sinus thrombophlebitis. Br 1994;21:101-117. possible surgical intervention are key J Ophthalmol. 1957;41:228-237. 22. Schuknecht B, Simmen D, Yuksel C, Valavanis A. to reducing mortality rates and long- 9. Sekhar LN. Carotid-cavernous sinus thrombosis Tributary venosinus occlusion and septic cavern- caused by Aspergillus fumigatus. J Neurosurg. ous sinus thrombosis: CT and MRI findings. AJNR term sequelae. Recent improvements 1980;67:219-222. Am J Neuroradiol. 1998;19:617-626. in imaging, especially CT and MRI, 10. Estrem SA, Tully R, Davis WE. Rhinocerebral mu- 23. Ben-Uri R, Palma L, Kaveh Z. Case report: septic have contributed substantially to the cormycosis: computed tomographic imaging of thrombosis of the cavernous sinus: diagnosis with rapid diagnosis of this condition. cavernous sinus thrombosis. Ann Otol Rhinol the aid of computed tomography. Clin Radiol. Laryngol. 1990;99:160-161. 1989;40:520-522. 11. Dooley DP, Hollsten DA, Grimes SR, Moss J. In- 24. Ahmadi J, Keane JR, Segall HD, Zee CS. CT ob- Accepted for publication April 9, 2001. dolent orbital apex syndrome caused by occult mu- servations pertinent to septic cavernous sinus Corresponding author and re- cormycosis. J Clin Neuroophthalmol. 1992;12: thrombosis. AJNR Am J Neuroradiol. 1985;6:755- prints: John R. Ebright, MD, Division 245-249. 758. 12. Price CD, Hameroff SB, Richards RD. Cavernous 25. Zahllar M, Spector RH, Skoglund RR, Digby D, of Infectious Diseases, Harper sinus thrombosis and orbital cellulitis. South Med Nyhan WL. Cavernous sinus thrombosis. West J Hospital, 3990 John R, 4 Brush Cen- J. 1971;64:1243-1247. Med. 1980;133:44-48. ter, Detroit, MI 48201 (e-mail: jebright 13. Colson AE, Daily JP. Orbital apex syndrome and 26. Solomon OD, Moses L, Volk M. Steroid therapy @intmed.wayne.edu). cavernous sinus thrombosis due to infection with in cavernous sinus thrombosis. Am J Ophthal- Staphylococcus aureus and Pseudomonas aeru- mol. 1962;54:1122-1124. ginosa. Clin Infect Dis. 1999;29:701-702. 27. Friberg TR, Sogg RL. Ischemic optic neuropathy 14. Kronschnabel EF. Orbital apex syndrome due to si- in cavernous sinus thrombosis. Arch Ophthal- REFERENCES nus infection. Laryngoscope. 1974;84:353-371. mol. 1978;96:453-456. 15. Hunt WE, Meagher JN, LeFever HE, Zeman W. 28. Karlin FJ, Robinson WA. Septic cavernous sinus Painful ophthalmoplegia: its relation to indolent thrombosis. Ann Emerg Med. 1984;13:449-455. 1. Clune JP. Septic thrombosis within the cavern- inflammation of the cavernous sinus. Neurology. 29. Ivey KJ, Smith H. Hypopituitarism associated with ous chamber. Am J Ophthalmol. 1963;56:33-39. 1961;11:56-62. cavernous sinus thrombosis. J Neurol Neuro- 2. Yarington CT. Cavernous sinus thrombosis re- 16. Jellinek EH. The orbital pseudotumour syn- surg Psychiatry. 1968;31:187-189. visited. Proc R Soc Med. 1977;70:456-459. drome and its differentiation from endocrine ex- 30. Levine SR, Twyman RE, Gilman S. The role of 3. Southwick FS, Richardson EP, Swartz MN. Sep- ophthalmos. Brain. 1969;92:35-58. anticoagulation in cavernous sinus thrombosis. tic thrombosis of the venous dural sinuses. Medi- 17. Ryan MW, Rassekh CH, Chaljub G. Metastatic Neurology. 1988;38:517-522. cine (Baltimore). 1986;65:82-106. breast carcinoma presenting as cavernous sinus 31. Geggel HS, Insenberg SJ. Cavernous sinus throm- 4. Woodburne RT, Burkel WE. The head and neck. syndrome. Ann Otol Rhinol Laryngol. 1996;105: bosis as a cause of unilateral blindness. Ann Oph- In: Essentials of Human Anatomy. 9th ed. New 666-668. thalmol. 1982;14:569-574.

(REPRINTED) ARCH INTERN MED/ VOL 161, DEC 10/24, 2001 WWW.ARCHINTERNMED.COM 2676

Downloaded From: https://jamanetwork.com/ on 09/26/2021