Cavernous sinus syndrome is defined by its resultant signs and symptoms: ophthalmoplegia,

chemosis, proptosis, Horner syndrome, or trigeminal sensory loss. Infectious or noninfectious

inflammatory, vascular, traumatic, and neoplastic processes are the principal causes. Examples of
specific entities that may result in cavernous sinus syndrome are myriad and include carotid
artery aneurysms, carotid-cavernous fistulas (C-C fistulas) (see image below), tumors, and
Tolosa-Hunt syndrome, to name the most frequently discussed.

Carotid-cavernous fistula.

Pathophysiology
The cavernous sinuses are paired, venous structures located on either side of the sella turcica.
They receive venous tributaries from the superior and inferior orbital veins and drain into the
superior and inferior petrosal sinuses. The cavernous sinus contains the carotid artery, its
sympathetic plexus, and the oculomotor nerves (third, fourth, and sixth cranial nerves). In
addition, the ophthalmic branch and occasionally the maxillary branch of the fifth nerve traverse
the cavernous sinus. The nerves pass through the wall of the sinus while the carotid artery passes
through the sinus itself.
Cavernous sinus tumors
Cavernous sinus tumors are the most common cause of cavernous sinus syndrome. Tumors may
be primary or may arise from either local spread or as metastases. Examples of primary tumors
include meningiomas or neurofibromas. Examples of locally spreading tumors are
nasopharyngeal carcinoma or pituitary tumors. Metastatic lesions are most often from the breast,
prostate, or lung. Radiotherapy may offer transient relief, particularly in nasopharyngeal cancer.

Lateral extension of pituitary tumors may be treated with surgical resection and dopamine
agonists in the case of prolactinoma. Total resection of these lesions is challenging and attempted
only when the symptoms are disabling.[1]
Cavernous sinus aneurysms
Unlike intracranial aneurysms in other anatomic locations, carotid-cavernous aneurysms do not
involve a major risk of subarachnoid hemorrhage. However, their rupture can result in direct C-C
fistulas, which may lead to cerebral hemorrhage. These aneurysms, which are more frequent in
the elderly population, present with an indolent ophthalmoplegia. Although some patients suffer
minor disability and do not require treatment, endovascular occlusion of these lesions is often
successful and may be attempted in selected patients.[2]
Carotid-cavernous fistulas
C-C fistulas are of 2 types: direct and indirect. Direct fistulas occur if the carotid artery and
cavernous sinus are in continuity. They manifest with abrupt onset of proptosis, chemosis, visual
loss, and ophthalmoplegia. Indirect fistulas occur with communication between the cavernous
sinus and the branches of the internal carotid artery, external carotid artery, or both. They have a
more insidious presentation than direct fistulas, often with spontaneous resolution. Trauma or
aneurysm rupture is a common cause of carotid-cavernous fistulas. Interventional radiologists
can successfully treat all fistula types by endovascular occlusion techniques. Occasionally,
surgical treatment with carotid ligation is necessary; this sometimes is preceded by a superficial
temporal-to-middle cerebral bypass operation to ensure cerebral circulation after carotid ligation.
Frequency
In the US, approximately 5% of ophthalmoplegias are secondary to involvement of cranial
nerves in the cavernous sinuses. This is probably true worldwide.
Cavernous sinus aneurysms represent 5% of all intracranial aneurysms.

Mortality/Morbidity

Most of the lesions affecting the cavernous sinuses are treatable.

Metastatic cancer is a frequent cause of cavernous sinus syndromes, and the prognosis
depends on the specific tumor type.
Cavernous sinus septic thrombophlebitis mortality has decreased from 100% to 20% with

the implementation of improvement in diagnosis and therapeutics.

Cavernous sinus aneurysms and C-C fistulas can be treated successfully by endovascular

techniques.
Lateral extension of pituitary tumors, a common cause of this syndrome, can be treated

by surgical resection, radiation therapy in selected patients, and a dopamine agonist in the case of
prolactinoma.

History
The signs and symptoms frequently found in patients with cavernous sinus lesions include visual
loss,

proptosis,

ocular

and

conjunctival

congestion,

elevation

of

ocular

pressure,

ophthalmoplegia, and pain. Various combinations of these symptoms may occur, which generally
are unilateral, but may be bilateral with neoplastic processes. Symptoms may be acute or slowly
progressive. Primary tumors are the most frequent neoplasm responsible for a cavernous sinus
syndrome.
Cavernous sinus tumors

Acute or slowly progressive ophthalmoplegia is the dominant presentation, with

diplopia being the most common symptom.

At times, painful diplopia is present.

Usually the patient has a preceding history of cancer. Occasionally, cavernous

sinus syndrome is the first manifestation of a systemic neoplasm.

Exophthalmos can be seen.

If the tumor is a pituitary adenoma, endocrine symptoms and visual field deficits
may be present.

Carotid-cavernous aneurysms

Patients frequently are elderly and present with subacute or chronic

ophthalmoplegia.

Rarely, they may have pain similar to that of trigeminal neuralgia.

Spontaneous rupture of a carotid-cavernous aneurysm leads to an abrupt onset of

a direct C-C fistula. This results in acute onset of massive exophthalmos with orbital,
ocular, and conjunctival chemosis, binocular diplopia, and visual loss.
Two types of C-C fistulas

Direct fistulas present with prominent acute symptoms.

Conversely, indirect fistulas are characterized by mild proptosis, chronic diplopia,

drooping of the lid, a red eye, arterialization of the conjunctival vessels, and visual loss.
The patient may report subjective "noises" in his or her head.
Cavernous sinus thrombosis

This is infrequent in the postantibiotic era.

It may occur as a complication of infection in the ethmoid, sphenoid, or frontal

sinuses or from midfacial, dental, or orbital infections.

Patients may present with sepsis or metastatic spread of septic emboli, most
commonly occurring in the lung. This presentation may appear as acute respiratory distress
syndrome (ARDS).

Retrobulbar pain, drooping of the upper eyelid, and diplopia may be the first
symptoms indicating the lesion's extension to the cavernous sinus.
Miscellaneous inflammatory lesions

These may involve the cavernous sinuses or the walls of the sinus.

Herpes zoster in its acute or chronic stage rarely causes pain, diplopia, and a
droopy eyelid in addition to the typical zoster blisters. In the chronic stage, a scar from the
acute lesion usually is found.

An idiopathic inflammation of the walls of the cavernous sinuses is referred to as

Tolosa-Hunt syndrome.

Sarcoid or Wegener granulomatosis may also predispose to cavernous sinus

syndrome.

Physical
Cavernous sinus lesions are characterized by the following signs:

Unilateral and isolated third, fourth, or sixth cranial nerve palsy

Combination patterns of ophthalmoplegia

Painful ophthalmoplegia

Proptosis (pulsating exophthalmos suggests a direct C-C fistula)

Ocular and cranial bruits

Conjunctival congestion; arterialization of conjunctival veins

Ocular hypertension

Optic disc edema or pallor; retinal hemorrhages

Anesthesia in the ophthalmic division of the trigeminal nerve (V1) and/or

decreased or absent corneal reflex and possibly anesthesia in the maxillary or V2 branch
Pupil in midposition and nonreactive if both sympathetics and parasympathetics

from the third nerve are affected

Cavernous sinus tumors

Metastatic

lesions

Isolated

or

combined

ophthalmoplegia,

painful

ophthalmoplegia, anesthesia in the ophthalmic nerve

Pituitary tumors - Isolated or combined ophthalmoplegia (lateral extension);

endocrine signs such as acromegaly, galactorrhea, and unitemporal or bitemporal visual field
defects

Primary intracranial tumors - Isolated or combined ophthalmoplegia and/or

primary aberrant regeneration of the third cranial nerve
Cavernous sinus aneurysms

Isolated or combined ophthalmoplegia

Painful ophthalmoplegia

Decreased pain sensation in the V1 ophthalmic division

Carotid-cavernous fistulas

Direct - Unilateral massive proptosis, pulsating exophthalmos, lid congestion,

conjunctival chemosis, orbital congestion, ocular hypertension, visual loss, optic neuropathy,
optic disc edema, retinal hemorrhages, retinal venous congestion, and loud ocular and cranial
bruit
Indirect - Similar signs and symptoms of lesser severity; occasionally, isolated

ophthalmoplegia, particularly if the fistula drains posteriorly

Cavernous sinus thrombosis

Generally speaking, primary infectious process involving paranasal sinuses and/or

orbital cellulitis
In addition to local and systemic signs of infection, the following may be seen:

Isolated or combined ophthalmoplegia

Painful ophthalmoplegia

Orbital congestion, lid chemosis, proptosis

Visual loss, optic disc edema (unilateral)

Signs of meningeal irritation

Miscellaneous cavernous sinus lesions

Tolosa-Hunt syndrome - Isolated or combined, painful ophthalmoplegia

Herpes zoster - Acute zoster ophthalmicus, typical skin lesion, and keratitis

Sarcoidosis - Systemic signs, uveitis, ophthalmoplegia, facial diplegia

Causes
Metastatic tumors

Breast

Prostate

Lung
Localized spread of tumor

Nasopharyngeal

Pituitary
Primary intracranial tumors

Meningiomas

Neurofibromas

Chondromas (less common)

Trauma (including postsurgical)

Carotid-cavernous aneurysms

Carotid-cavernous fistulas

Cavernous sinus thrombosis

Miscellaneous inflammatory syndromes

Herpes zoster

Tolosa-Hunt syndrome

Sarcoidosis

Diagnostic Workup
Patients in whom cavernous sinus lesions are suspected should undergo thin-section multiplanar
imaging studies of the orbit and the sellar/parasellar region. Precontrast and postcontrast scans
are advisable. CT scan offers better visualization of bone and calcium. However, MRI provides
better detail of all soft tissues contained in the sinuses, the expected signal void of the normal
carotid artery, and its relation to the surrounding structures. See the image below.

A T1-weighted, coronal MRI.

Orbital views are necessary to exclude a disease process primarily involving the cavernous
sinuses with concomitant compromise of the orbital apex. Conversely, primary orbit and
paranasal sinus disorders frequently may involve the cavernous sinuses. Visualization of the

superior and inferior orbital veins is helpful to diagnose increased venous pressure. Once
imaging is obtained and reviewed in light of clinical findings, further investigation can be
pursued to determine a specific diagnosis.
Cavernous sinus tumors

In the case of metastatic tumors, diagnosis of the primary neoplasm generally precedes
the cavernous sinus syndrome.

A lumbar puncture with cytologic examination may be helpful.

If a primary neoplasm of the nasopharynx is suspected, a biopsy may be needed.

In the case of pituitary tumors with lateral extension, tumor resection may be necessary.

Rarely, a biopsy of the cavernous sinus tumor is needed for diagnosis.

Cavernous sinus aneurysms

As MRI and/or magnetic resonance angiography (MRA) are often specific, cerebral
angiography generally is not required to make a diagnosis.

Perform angiography if balloon occlusion of the aneurysm is planned.

Carotid-cavernous fistulas

The dramatic clinical presentation and MRI and/or MRA of direct fistulas leave little
doubt regarding the diagnosis.

By contrast, indirect fistulas, particularly those draining in the petrosal sinuses, are

associated with subtle findings and possibly a normal MRI and/or MRA. See the images below.

This patient is a 55-year-old woman who originally had symptoms of eye pain and pulse
synchronous tinnitus on the left. She was found to have an indirect left carotid cavernous sinus
fistula and underwent successful coiling of the fistula. This picture shows her after the procedure,
as she had developed left eye chemosis and diplopia. A left lateral rectus paralysis was present on
examination. In this case, the probable causes of the ophthalmoplegia could be mass effect or
occlusion of the vasa nervorum supplying the sixth cranial nerve, which travels in the adventitia
of the carotid artery. Here, the prognosis is excellent, and the authors have seen several cases
with improvement within 4-8 weeks after coiling. Early phase of the post-fistula coiling
angiogram of the patient shown above. Coils can be appreciated at the cavernous portion of the
carotid artery.Later filling phase of the angiogram for the patient shown above. Note that coiling
has prevented anomalous filling of the cavernous sinus fistula.

Cerebral angiography is the only way to arrive at the correct diagnosis.

Perform angiography to stage the fistula and document the anterior and posterior drainage
routes.

Cavernous sinus thrombosis

Imaging of the orbit and/or nasal sinuses is helpful in the search for a septic focus.

An aseptic thrombosis may be associated with conditions such as hypercoagulable states

and lymphoproliferative disorders.
A hematologic workup is indicated in these patients.

Miscellaneous inflammatory syndromes

Investigate additional systemic inflammatory and granulomatous processes after other common
causes have been excluded. These disorders can be screened by studies such as laboratory tests
and chest radiograph.
Tolosa-Hunt syndrome (an uncommon, idiopathic, inflammatory cavernous sinus

syndrome) may share a close etiologic link with orbital pseudotumor.

A nonspecific fibrotic inflammatory reaction and rarely a granulomatous

inflammation can occur, but biopsy is rarely used to establish the diagnosis.
A positive response to steroids is considered diagnostic, but false-positive

responses can occur in lymphoma and other parasellar neoplasms.

Biopsy of the cavernous sinuses entails a craniotomy, which is associated with morbidity.
Restrict a craniotomy to patients with a documented, progressive cavernous sinus syndrome.

cavernous sinus tumors

Metastatic lesions

Radiotherapy may offer transient improvement.

Nasopharyngeal carcinomas may be very radiosensitive, with a prolonged

remission following treatment.
Pituitary tumors

Prolactinomas may improve with oral dopamine agonists, or they may require

resection.

Gamma knife may be an adjunctive treatment for postoperative tumor residual or

recurrent tumor, and it may have a role as an alternative to open surgical treatment.
Cavernous sinus meningiomas

These lesions represent a major challenge for surgical resection, primarily because

of poor accessibility and the frequent encasement of the cavernous carotid artery.
Since these tumors are slow growing and difficult to resect, elderly patients or

those with minor symptoms probably should be observed expectantly without specific
treatment.

Radiotherapy may be offered to some patients, and some show improvement of

cranial nerve function after gamma knife treatment. Partial resection may be attempted in
others with disabling symptoms (eg, intractable pain, total ophthalmoplegia in a patient with
poor vision in the nonparetic eye).

Cavernous sinus aneurysms

Treat cavernous sinus aneurysms by endovascular balloon occlusion.
Carotid-cavernous fistulas

Treatment ideally consists of endovascular obliteration of the fistula with coils, although
some cavernous sinus dural AV fistulas may be observationally managed.

Access to the fistula may be transarterial; however, the transvenous approach has become
the mainstay of treatment, in some cases a combined surgical/endovascular approach can be used
with surgical exposure of the superior ophthalmic vein followed by fistula embolization. Several
venous approaches have been used, including the safest transfemoral approach; however, if this
is not feasible, a superior orbital vein or a percutaneous transorbital puncture to the cavernous
sinus can be used.[3]

Supraorbital vein dissection with placement of a catheter to access the cavernous sinuses
has been performed successfully.

Percutaneous transorbital access to the cavernous sinus followed by embolization.

Small indirect C-C fistulas may occlude either spontaneously or following diagnostic
angiography. If the clinical signs are mild, consider careful monitoring.

If intraocular pressure is elevated, antiglaucoma agents may be required.

Cavernous sinus thrombosis

High-dose antibiotic therapy should be directed against the most common pathogens,
such as S aureus and S pneumoniae, as well as gram-negative rods and anaerobes.

Anticoagulation in septic cavernous sinus thrombosis is controversial, but may hasten the
rate of recovery.

Drainage of any primary site of infection (eg, abscess, sinusitis) is advised.

Corticosteroids are not recommended.

Anticoagulation also may be helpful in aseptic patients.

Miscellaneous inflammatory syndromes

Inflammatory cavernous sinus syndromes may respond to treatment of the specific

systemic inflammation or vasculitic etiology.

Tolosa-Hunt syndrome responds well to a 3- to 6-month course of high-dose steroid

therapy that can be tapered slowly thereafter.