Dr. Chaljub is an Associate Professor, Dr. Madamba is a Fellow, Dr. Hernandez is an Assistant Professor, and Dr. Guinto is a Professor in the Department of Radiology; Dr. Mandava is an Assistant Professor in the Department of Neurology; and Dr. Maiorell o is a Resident in the Department of Surgery, Section of Neurosurgery, and a Professor of Radiology, University of Texas Medical Branch, Galveston, TX. Dr. Pincus is a Radiologist in private practice in Virginia. Dr. Vrabec is an Associate Professor in the Department of Otolaryngology, Baylor College of Medicine, Neurosensory Center of Houston, Houston, TX.

Several vascular structures, the cranial nerves, the pituitary gland, and osseous structures sit in close proximity to each other in the cavernous sinus. Vascular, infectious, inflammatory, metastatic, and traumatic lesions in one of these structures can quickly spread to the other contiguous elements. Proper clinical recognition, appropriate imaging, and expeditious medical and/or surgical intervention can reduce morbidity and mortality. Undue delay in any aspect of this multimodality care could lead to disastrous consequences.

The carotid arteries and their intracavernous branches account for most of the pathology that leads to morbidity and mortality. The cranial nerves, on the other hand, may give the first clinical indication that something is amiss. ^1­5 The carotid arteries, cavernous sinus, and the minimally blood-brain-barrier­invested pituitary gland together lend themselves to be studied via different imaging modalities, each with its strengths and limitations.

Magnetic resonance (MR) imaging has supplanted computed tomography (CT) and cerebral arteriography for evaluating potential cavernous sinus lesions. ⁶ The noninvasive multiplanar capabilities of MR imaging along with superb soft-tissue contrast and MR angiography (MRA) enable MR to diagnose most cavernous sinus pathology. However, certain cavernous sinus vascular syndromes still benefit from traditional angiography for diagnosis, as well as multidisciplinary intervention.

Discussion in this article will be limited to vascular issues, such as carotid-cavernous (C-C) fistulas, cavernous sinus aneurysms, cavernous sinus thrombosis, and granulomatous inflammation of the cavernous sinus. The purpose of this pictorial essay is to describe the intricate anatomy of the cavernous sinus and the MR appearances of the normal anatomy and disease processes afflicting it. CT and angiographic correlation is provided where appropriate. Surgical considerations and approaches will be briefly discussed. All MR studies were performed on 1.5T units. Suggested MR protocols will be described.

Anatomy

The cavernous sinus is a venous space of the central skull base encased by a dural envelope. The superior dural wall extends from the planum sphenoidale to the clivus in conjunction with the diaphragm sellae. The medial wall is formed by the dura investing the pituitary gland. Dura from the floor of the middle cranial fossa and lateral wall of the sphenoid forms the inferior medial border. The lateral wall extends from the anterior and posterior clinoid processes to the middle cranial fossa. The anterior limit of the sinus is the superior orbital fissure, and the posterior border is the clivus. The interior of the sinus contains multiple septations. Blood flow is predominantly from the ophthalmic veins and pterygoid plexus. Intercavernous flow occurs through the connections anterior and posterior to the pituitary gland. Egress from the sinus is through the superior and inferior petrosal sinuses into the jugular system. ^7,8

The carotid artery traverses the sinus from inferior lateral to superior anterior. There are several arterial branches within the sinus, including the meningohypophyseal artery, inferolateral artery of the cavernous sinus, capsular artery, and, often, the ophthalmic artery. ¹

Cranial nerves III, IV, VI and VII are located within the lateral wall of the cavernous sinus. The abducens nerve (VI) enters the cavernous sinus through Dorello's canal and traverses the sinus within the lumen (Figure 1). The oculomotor (III) and trochlear (IV) nerves are located near the superior border, while the ophthalmic division of the trigeminal nerve occupies the inferior aspect. The maxillary division is more lateral and inferior to VI and exits this dural lining at the foramen rotundum. Many of these structures can be seen with MR or contrast-enhanced CT (Figure 2).

The cavernous sinus is best evaluated with contrast-enhanced MRI in the axial and coronal planes (Table 1). The cavernous sinus is concave medially and shows homogeneous enhancement other than the normal filling defects posteriorly and laterally secondary to the gasserian ganglion in Meckel's cave. MR imaging is superior to CT in evaluating disease afflicting the cavernous sinus except in the rare cases in which bony involvement is present, rendering both CT and MR imaging complementary. MR angiography is a noninvasive alternative to angiography to evaluate the cavernous carotid arteries. Angiography is reserved for diagnostic dilemmas and for minimally invasive endovascular procedures (only briefly discussed in this manuscript).

Vascular lesions

Carotid-cavernous fistula

Carotid cavernous fistulae can be spontaneous or traumatic, direct or dural and high-flow or low-flow. ¹⁰ A few of the spontaneous C-C fistula are believed to be secondary to connective tissue disorders. ^11,12 A distant history of trauma cannot be totally discounted in the spontaneous variety. The direct variety results from tears in the meningeal branches of the internal carotid artery (ICA) or the external carotid artery (ECA).

The triad of chemosis, orbital bruit, and pulsatile exopthalmos has been classically associated with a C-C fistula. ^1,13 Radiologic diagnosis can be made by CT or MR showing the triad of exophthalmos, an enlarged and tortuous superior ophthalmic vein, and lateral bowing of the cavernous sinus (Figure 3). Conventional angiography may still be necessary to diagnose the etiology of the C-C fistula and, secondarily, to thrombose the fistula via coil or glue embolization. ^14,15 Treatment options and appropriate selection of these options remain controversial because spontaneous thrombosis of C-C fistula with resolution of symptoms often occurs. ^10,12,16 The low flow dural C-C fistulae were considered to be more likely to spontaneously thrombose. However, note should be made that a delay in addressing the C-C fistula and its complications in a timely manner may compromise the function of the eye. ^1,13 Embolization via the arterial system for the direct C-C fistulas or the venous system for the dural fistulas has been advocated. ^11,13,15

Cavernous sinus aneurysms

Cavernous sinus aneurysms of the carotid artery make up nearly 5% of all intracerebral aneurysms. ^2,17 For an unknown reason, women account for a great majority of the cases of cavernous carotid aneurysms. ^3,17,18 Etiologically, these aneurysms are catego-rized into idiopathic, traumatic, mycotic, secondary to radiation injury, and connective tissue disorders groups. Size-based classification has also been adopted: small (<1 cm), large (1 to 2.5 cm), and giant (>2.5 cm) aneurysms. ²

Ophthalmoplegia secondary to compression of cranial nerves III, IV, and VI, and retro-orbital pain and loss of sensation in V1 and V2 are common findings due to mass effect of the aneurysm. ^2,3,18 Embolic strokes emanating from intraluminal thrombus may give rise to symptoms corresponding to distal arterial territories. If the intrasinus aneurysm should rupture, a C-C fistula may result. On the other hand, if a giant aneurysm were to erode through or grow beyond the cavernous dura, rare progression to subarachnoid hemorrhage with concomitant sudden worsening of the neurological status can be seen. A flow void or heterogenous mass with flow voids by MR or rounded contrast enhancement by CT suggests the diagnosis (Figures 4 and 5). MR imaging with or without contrast can also suggest the diagnosis by showing a saccular mixed signal region secondary to slow flow and/or partial thrombosis along the cavernous carotid arteries. The cavernous carotid arteries are normally seen as round or tubular signal void regions. MR angiography can add complimentary information.

Conservative therapy may suffice for small carotid cavernous aneurysms. Large and giant aneurysms or patients with embolic events, mass effect on cranial nerves, and subarachnoid hemorrhage unquestionably require a joint neurosurgical/interventional approach. Drastic surgery (such as ligation of the proximal carotid artery, reconstruction of the carotid artery, and embolization of the aneurysm) has been suggested. ^17-19

Cavernous sinus thrombosis

Cavernous sinus thrombosis usually occurs as a complication of facial cellulitis or sinusitis. An immune compromised state and diabetic ketoacidosis are common risk factors for this condition. ^4,20,21 Rare cases of malignancy and trauma have also been associated with cavernous sinus thrombosis. ²²

Classic presenting findings include pain, chemosis, proptosis, and ophthalmoplegia. Involvement of the cavernous sinus is via thrombophlebitic spread of infection from both the superior and inferior ophthalmic veins, though direct extension from the sphenoid sinus is possible. Fungi of the mucor or the aspergillus classes are the common etiologic agents. ^4,20,21,23 A few bacterial cases such as staphylococcus aureus and pseudomonas aeruginosa have also been reported. ²⁴

MR imaging or CT with contrast can usually detect filling defects with the cavernous sinus (Figure 6) to suggest the diagnosis. ²⁰ If strong clinical suspicion exists, repeat imaging may sometimes be necessary, since early in the disease process both CT and MR may miss the diagnosis. Emergent initiation of medical therapy or surgical debridement may prevent lethal sequelae, such as formation of a brain abscess, stroke, and death. However, despite aggressive management, mortality continues to be high. ^4,20,21 Delay in obtaining confirmatory imaging studies or delivery of medical therapy and/or surgical intervention has traditionally resulted in high morbidity and mortality. While a brain abscess is due to contiguous spread, strokes are due to the involvement and thrombosis of one or both of the carotid arteries.

Inflammatory

Orbital pseudotumor is an encompassing inflammatory condition, which when limited to the cavernous sinus is known by the eponym Tolosa-Hunt syndrome. ^5,24,25 Tolosa-Hunt syndrome is generally accepted as granulomatous periarteritis of the carotid artery and its intracavernous branches. Patients describe steady unilateral orbital pain of several weeks' duration, followed by opthalmoplegia due to involvement of cranial nerves III, IV, and VI (Figure 7).

Intravenous or oral steroids can abate symptoms within 24 hours. Resolution of radiologically evident arteritis has also been reported. ²⁶ Radiologic studies in the form of CT, MRI/MRA, and, in rare instances, angiography, may be useful in differentiating orbital pseudotumor from other causes of orbital pain and opthalmoplegia. Mass lesions such as lymphoma, meningioma, chordoma, and other inflammatory conditions, such as sarcoid, have to be excluded first. ²⁵ Obtaining the correct radiologic study with an accurate clinical history may prevent unnecessary biopsies or other surgical interventions. The importance of radiologic studies in narrowing the differential diagnosis cannot be overstated, since lymphoid tumors, sarcoid, and inflammatory conditions can also be steroid-sensitive. Enhancement of the intraconal structures extending into the orbital apex and cavernous sinus can be easily detected by the multiplanar capabilities of MR, but may be difficult to differentiate from infection, metastasis, or lymphoma. Obtaining the pertinent medical history and correlating the clinical and radiographic findings is paramount in limiting and narrowing the diagnosis.

Conclusion

Nowhere is the adage The eye is the window into the brain more applicable than with cavernous sinus lesions. Although the patient's initial signs and symptoms may appear mundane, early recognition and identification of cavernous sinus pathology may avert significant morbidity and mortality. Treatment options vary from watchful waiting to aggressive combined medical, surgical, and endovascular interventions.