Vascular Lesions of the Central Skull Base Region Philip R. Chapman, MD*, Siddhartha Gaddamanugu, MD†,‡, Asim K. Bag, MD*, Nathan T. Roth, MD*, and Surjith Vattoth, MD* The arterial and venous structures of the central skull base region form complex anatomical relationships with each other and with adjacent osseous and neural structures. Vascular structures including the cavernous sinuses and internal carotid arteries can be displaced, encased, or invaded by neoplastic, inflammatory, or infectious lesions of the central skull base. Consequently, the vascular structures have a unique role in determining the imaging appearance, clinical significance, and therapeutic options of lesions occurring in the central skull base. This article briefly reviews the basic anatomy of the cavernous sinus and the relationship of the internal carotid artery to the cavernous sinus and central skull base. The major imaging features of some common vascular lesions, including skull base aneurysm, carotid-cavernous fistula, and cavernous sinus thrombosis are presented. Semin Ultrasound CT MRI 34:459-475 C 2013 Elsevier Inc. All rights reserved.

T

he vascular structures of the central skull base region have a determinate role in the imaging appearance, clinical significance, and therapeutic options for lesions occurring in the central skull base. Vascular structures including the cavernous sinuses and internal carotid arteries can be displaced, encased, or invaded by neoplastic, inflammatory, or infectious lesions of the central skull base. Macroadenomas and meningiomas, for example, can invade the cavernous sinus, encase the internal carotid, and prevent complete surgical resection. Such involvement can lead to catastrophic clinical consequences including cranial neuropathies, hemorrhage, or stroke, thus exposing the patient to the considerable risks of surgical intervention. In addition, there are intrinsic lesions of the vasculature that can affect the central skull base region including congenital anomalies, aneurysms, carotid-cavernous fistula (CCF), and cavernous sinus thrombosis (CST). This article reviews the basic anatomy of the vascular structures of the central skull base with an emphasis on the internal carotid artery (ICA). The pertinent imaging features of common

Project Editor: Suzanne Byan-Parker. Tel.: þ1-205-934-4274; þ1-205-4823229 (mobile). E-mail: [email protected]. *Department of Radiology, Section of Neuroradiology, University of Alabama at Birmingham, Birmingham, AL. †Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL. ‡Veteran’s Affairs Medical Center, Birmingham, AL. Address reprint requests to Philip R. Chapman, MD, Department of Radiology, Section of Neuroradiology, Jefferson Towers N424, 619 19th St South, Birmingham, AL 35249-6830. E-mail: [email protected]

0887-2171/$-see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.sult.2013.09.003

vascular lesions have been presented previously. These lesions carry their own unique challenges in diagnosis, treatment, and selection of appropriate imaging modalities. Unenhanced computed tomography (CT) scans can be used effectively to evaluate for hemorrhage involving the central skull base region. Routine contrast-enhanced CT studies may be useful in detecting a soft tissue mass and can assess vascular involvement to some degree. However, it may be difficult to distinguish soft tissue enhancement from intravascular enhancement on scans from routine CT-enhanced studies. In the past, it was not uncommon for neurosurgeons to intervene for a presumed neoplasm, only to find an aneurysm. A CT angiogram (CTA) of the head using helical scan techniques is the study of choice for evaluating the intracranial arteries. Because of its high spatial and temporal resolution, CTA is uniquely helpful in evaluating vascular structures near the skull base. The use of magnetic resonance imaging (MRI) to assess vascular lesions accurately can be particularly challenging, depending on the individual sequences used and whether intravenous gadolinium is administered. Vascular lesions can create variable appearances on MRI depending on the size, flow direction, pulsatility, flow velocity, and degree of thrombosis. MR angiography (MRA) of the intracranial arteries can be performed with or without intravenous contrast and can provide highquality visualization of the intracranial arteries, including the proximal arteries at the skull base. MR venography can be performed with phase contrast or postgadolinium 459

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460 techniques and can be useful for identifying flow in the major dural sinuses.

Vascular Anatomy of Central Skull Base The cavernous sinuses are paired venous sinuses on either side of the sella that have intricate relationships with the orbit, multiple cranial nerves (CNs), the pituitary gland, and the internal carotid arteries. The ICA and CN VI pass through the intrinsic sinusoids of the cavernous sinus. The CNs III, IV, and V1 and V2 are partly contained within the walls of the cavernous sinus. The internal carotid arteries are major structures within the central skull base region. Anatomically, the ICA can be divided into segments based on structural relationships and named branch arteries. In 1996, Bouthillier et al1 described a 7-segment classification system for the ICA. From proximal to distal, these include (1) the cervical, (2) the petrous, (3) the lacerum, (4) the cavernous, (5) the clinoid, (6) the ophthalmic, and (7) the communicating segments. All but the cervical segment are intimately related to the central skull base region (Fig. 1). The medial or distal portion of the petrous segment approaches the central skull base region as it travels through the petrous apex.2 The distal petrous segment of the internal carotid is incompletely surrounded by bone. The posteromedial, anterolateral, and inferior walls are usually solid. Of these 3, the posteromedial wall is the most developed. The superior covering or roof of the distal petrous canal is largely deficient of bone and is covered by dura.

Although no large vessels arise from the petrous segment, there are 2 potentially important small branches: the caroticotympanic branch and the vidian artery. The caroticotympanic branch arises from the horizontal segment and enters the middle ear through a small foramen. The importance of this branch lies in the formation of an aberrant ICA (described later). The vidian artery usually arises from the internal maxillary artery, but it can occasionally arise from the horizontal segment. Both branches are inconsistently visualized on conventional angiography studies. As the petrous segment exits the canal medially, it is partially surrounded by fibrocartilaginous tissue that is contiguous with the cartilage of the foramen lacerum. In this location, the artery courses above the cartilage-filled foramen lacerum but not through the foramen itself.3 The artery then begins to turn cephalad. The lacerum segment ends when the artery passes underneath a fibrous band, the petrolingual ligament. The cavernous segment begins as the artery passes beneath the petrolingual ligament.4 The cavernous segment is often redundant with its accentuated posterior and anterior turns, resulting in vertical or horizontal plane tortuosity. The artery initially ascends and then turns anteriorly to assume a horizontal course through the cavernous sinus. This posterior bend is the usual site of origin for the meningohypophyseal trunk. The horizontal portion of the cavernous ICA lies within a shallow groove along the lateral margin of the sphenoid bone— the carotid sulcus—which is occasionally dehiscent, allowing the internal carotid to protrude into the sphenoid sinus. The horizontal segment gives rise to the inferolateral trunk, which supplies small arterial branches to the intracavernous CNs and

Figure 1 The 7-segment classification system for the internal carotid artery. From proximal to distal, these include (1) the cervical (not shown), (2) the petrous, (3) the lacerum, (4) the cavernous, (5) the clinoid, (6) the ophthalmic, and (7) the communicating segments. All but the cervical segment are intimately related to the central skull base region.

Vascular lesions tentorium. Cranial nerve VI (abducens nerve) is just lateral and parallel to the horizontal portion of the cavernous ICA. Near the anterior margin of the cavernous sinus, the artery then turns cephalad and continues medial to the anterior clinoid segment. Along this vertical course, the ICA passes through 2 anatomically distinct dural rings, the proximal dural ring, which forms the true roof of the cavernous sinus anteriorly, and the distal dural ring. The clinoid segment is a short vertical segment medial to the anterior clinoid process that corresponds to the interdural segment of artery between the proximal and distal dural rings.5,6 These rings are not seen on routine cross-sectional imaging, but the expected location of these rings can be assessed. The optic strut, which forms the bony floor of the optic canal and connects the planum sphenoidale with the anterior clinoid process, forms the landmark.7 The proximal dural ring is attached to the inferolateral margin and the distal dural ring forms the superomedial margin of this strut. Aneurysms at this location are seldom confined to this very short segment and usually have either an extradural or a subarachnoid involvement. In general, no artery arises from this segment. The ophthalmic segment of the ICA is subarachnoid in location. It traditionally starts at the superior margin of the optic strut and ends at the origin of the posterior communicating artery (PCOM). The ophthalmic artery is its major branch. The terminal communicating segment of the ICA extends from the origin of the PCOM to the bifurcation of the ICA. It gives rise to the anterior choroidal artery—the last branch of the ICA before its bifurcation.

Aberrant Carotid Artery Aberrant ICA is a rare but very important developmental anomaly of the carotid artery that typically presents with pulsatile tinnitus. Normally, the initial ascending segment of the petrous ICA is inferior to the cochlea and is separated from

461 the tympanic cavity by a thin plate of bone (carotid plate). The caroticotympanic artery, a remnant of embryologic hyoid artery, arises from the petrous part of the ICA that enters into the tympanic cavity through the carotid plate to supply the medial wall in normal individuals.8 The inferior tympanic artery, a branch of the ascending pharyngeal artery, also supplies the medial wall of the tympanic cavity and anastomoses with the caroticotympanic artery after passing through the inferior tympanic canaliculus in the jugular spine. The aberrant ICA actually represents an enlarged inferior tympanic artery anastomosing with an enlarged caroticotympanic artery with underdevelopment of the cervical segment of the ICA. Consequently, the aberrant carotid artery enters the tympanic cavity through an enlarged inferior tympanic canaliculus and courses from the posteriorly located jugular spine to the carotid canal, through the medial wall of the tympanic cavity (Fig. 2). At first glance, on an unenhanced CT image of the temporal bone, the aberrant ICA may appear as a soft tissue lesion within the middle ear and could be mistaken for a glomus tympanicum tumor. On an axial CTA, it is easy to identify the aberrant course of the artery. It can be seen as an avidly enhancing tubular structure along the lateral margin of the cochlea that is contiguous with both the inferior tympanic canaliculus and the posterior margin of the petrous carotid canal.

Persistent Trigeminal Artery (PTA) The trigeminal artery, the largest of the fetal carotid-basilar communications, persists for the longest embryonic period and usually involutes after development of the PCOM. The exact causes of this primitive vessel’s persistence into adulthood are unclear. Genetic cause and maintenance of local hemodynamic balance have been postulated as reasons for persistence. PTA can originate from either the left or right side, most commonly from the posterior or lateral wall of the cavernous

Figure 2 Aberrant internal carotid artery. (A) Lateral CT scan through the left temporal bone demonstrates small petrous internal carotid artery canal (closed arrow) that protrudes posteriorly into the hypotympanum. An enlarged inferior tympanic canaliculus can be noted (open arrow). (B) Slightly higher, the aberrant vessel can be seen laterally along the cochlear promontory (open arrow).

462 segment of the ICA. It can have a medial course, through the dorsum sella, penetrating the dura near the clivus (Ohshiro’s medial type), or it can have a lateralized course, between the sensory roots of the trigeminal nerve and the lateral border of the sella, piercing the dura medial to the Meckel cave (Ohshiro’s lateral type).9 PTA joins the basilar artery between the anterior inferior cerebellar artery and the superior cerebellar artery. There can be variable branching patterns of PTA: pontine perforators, cerebellar branches, and meningohypophyseal trunk. Multiple variants of PTA have been described in the literature. Variant PTAs arise from the precavernous ICA and terminate in different cerebellar arteries instead of communicating with the basilar artery. Angiographically, PTA is classified as Saltzman type 1 (usual insertion at the basilar artery with absent PCOM) and Saltzman Type 2 (usual insertion at the basilar artery with fetal configuration of PTA). It is very important to identify a PTA on imaging as there several conditions that have been described in association with a PTA: (1) increased incidence of other vascular anomalies (absent common carotid artery (CCA) and ICA, hypoplastic basilar and vertebral arteries, and primitive otic arteries)10; (2) increased incidence of intracranial aneurysms (in approximately 14% of patients with PTA)10; (3) vertebrobasilar insufficiency and brainstem ischemia11; and (4) PTAcavernous sinus fistula.12

Aneurysms Intracranial aneurysms are relatively common, with a prevalence of 1%-5%. Although most aneurysms do not rupture and remain asymptomatic, aneurysm rupture is a significant problem affecting approximately 30,000 patients in the United States each year.13 Nonruptured aneurysms can create symptoms secondary to mass effect on adjacent structures. Aneurysms may be saccular, fusiform, dissecting, or mycotic in terms of morphology. Most aneurysms (85%) are saccular and occur at the circle of Willis,13 but they can occur anywhere along the intracranial ICA, typically at arterial branch points. Given the inclusion of the distal ICA segments (petrous to communicating) within the central skull base region, aneurysms represent a critical pathology in the region for the neuroimager.

Origins and Etiology Aneurysms that arise at or beyond the origin of the ophthalmic artery are, by definition, subarachnoid in location and can result in basilar subarachnoid hemorrhage. Paraclinoid aneurysms, depending on their relationship to the proximal and distal dural rings, may have components that are extradural, interdural, or subarachnoid.7 These aneurysms can produce subarachnoid hemorrhage if there is sufficient subarachnoid exposure. Aneurysms that occur in the petrous or cavernous segments are extradural and generally do not produce subarachnoid hemorrhage. In spite of a tendency to be asymptomatic, these lesions are often large—producing a mass effect upon adjacent soft tissue structures that may cause scalloping or erosion of the adjacent skull base.

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Petrous Segment ICA Aneurysms Skull base aneurysms of the petrous segment of the ICA rarely occur.14 Although most of these lesions are idiopathic and are thought to be congenital or developmental in origin, they may be posttraumatic (aneurysm or pseudoaneurysm), atherosclerotic, or infectious (mycotic) in origin. These aneurysms tend to be fusiform in morphology and occur in a younger age group compared with other aneurysms. Although most petrous ICA aneurysms are asymptomatic, they can lead to a variety of presentations depending on the size, location, and vector of expansion. Lesions larger than 2.5 cm are regarded as giant aneurysms.15 Petrous ICA aneurysms can lead to headache, cranial neuropathies, Horner syndrome, pulsatile tinnitus, and thromboembolic events.14 The eighth CN is most commonly affected, followed by the fifth, sixth, and seventh CNs. More medial aneurysms can encroach upon the cavernous sinus, resulting in cavernous sinus syndrome.15 The radiologic diagnosis of petrous ICA aneurysm is challenging, given the relative rarity of the lesion and its variable appearances on CT and MRI studies. The size, morphology, effect upon adjacent structures, degree and age of thrombosis, inflammatory response, calcification, luminal flow pattern (including velocity), and specific imaging technique can affect the appearance of the lesion.16,17 In general, as with most central skull base pathologies, we consider CT and MRI techniques (including CTA and MRA) to be complimentary in evaluating skull base lesions, especially when aneurysms are suspected. On unenhanced CT studies, an aneurysm of the petrous ICA may appear as a slightly hyperdense mass expanding the petrous apex, with bony scalloping of the carotid canal and petrosphenoid junction.18 As the lesion expands cephalad through the nonossified portion of the petrous apex roof, it meets with the dura and could mimic an invasive meningioma or other neoplasms such as chondrosarcoma. CT studies may demonstrate peripheral calcification in the wall of the aneurysm or linear calcification within chronic thrombus. If there is significant flow velocity within the aneurysm, conventional MRI may demonstrate typical vascular flow void within the aneurysm that is continuous with the parent vessel. Complex flow patterns are common and markedly heterogeneous signal patterns can be seen on T1- and T2-weighted images.16,18 Aneurysms with slow flow or significant thrombosis may not demonstrate classic flow void at all (Fig. 3). Furthermore, slow-flow aneurysms may demonstrate homogeneous central enhancement and may be more suggestive of a solid, soft tissue mass. A thrombus can cause a laminated or concentric pattern of variable signal intensities related to clot of differing ages.19 Occasionally, though a distinct flow void may not be identified with conventional sequences, a pulsation artifact along the phase-encoding axis provides a clue as to the vascular nature of the lesion (Fig. 4). CTA, MRA, or conventional angiography is often necessary to confirm the presence of an aneurysm. These techniques can better define the aneurysm neck and document its communication with the parent vessel, as well as evaluate the relationship with adjacent neurovascular structures.

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Figure 3 Left petrous ICA aneurysm mimicking a skull base mass. (A) Axial T1-weighted and (B) axial T2-weighted images show an expansile lesion in the left petrous apex. The hyperintensity on T2 might be suggestive of a chondrosarcoma. No definite flow voids are appreciated. (C) Axial postcontrast T1-weighted image shows diffuse enhancement of the lesion. (D) Coronal reformatted MIP image of a CTA shows that the left skull base mass is indeed a petrous ICA aneurysm. MIP, maximum intensity projection.

The natural history of these skull base aneurysms is associated with a thromboembolic stroke risk that is as high as 50% if left untreated. Treatment with ICA ligation is accompanied by up to 30% risk of stroke.20 Additional treatment options include endovascular ICA balloon occlusion, endovascular coil placement, covered stent, progressive iatrogenic ICA flow reduction to induce thrombosis in the aneurysm using a Selverstone clamp in the cervical ICA, or direct surgical treatment. Lateral skull base approach for repair of ICA aneurysms with cervical-to-petrous carotid artery bypass can be performed safely with durable and satisfactory results.21

Cavernous Segment ICA Aneurysms Aneurysms of the cavernous segment have similar pathogenesis and etiology as petrous aneurysms.22 Cavernous ICA

aneurysms occur predominantly in women. These lesions are often asymptomatic, and most are treated conservatively, as benign lesions.23 However, cavernous aneurysms can be large, accounting for 5% of all giant aneurysms,24 can produce symptoms related to local mass effect and thrombosis, and can occasionally rupture. Cavernous segment aneurysms generally present with headache, orbital pain, oculomotor palsy, and diplopia.23,24 When large, these lesions carry an increased risk of rupture. Rupture into the cavernous sinus can result in a CCF. However, rupture can also rarely extend to the subarachnoid space and the sphenoid sinus. Cavernous sinus aneurysms have general imaging features similar to those previously described for petrous apex aneurysms.22 Subsequently, they can have a variable appearance on CT and MRI studies. Lesions in this location tend to expand to the cavernous sinus, they may result in scalloping or dehiscence of the carotid sulcus of the sphenoid bone, and may extend medially into the sella (Fig. 5). Depending on the size, flow characteristics, and degree of thrombosis, a giant

Figure 4 Coronal postcontrast T1-weighted SE sequence with fat saturation in same patient as Figure 3. The aneurysm contains slow flow and there is homogeneous vascular enhancement of the lesion. A band of pulsation artifact (arrows) that extends through the lesion in the phase-encoding direction provides clue to the vascular nature of the lesion. SE, spin echo.

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Figure 5 A 52-year-old man presented with headache and double vision. (A) Axial T2-weighted image through the sella demonstrates a heterogeneous mass in the sella (arrow) associated with sellar expansion and marked T2 hypointensity in some regions, likely due to hemosiderin deposition within chronic mural thrombus. (B) Axial T2 image through upper sella demonstrates a heterogeneous lesion on the left (arrow). Areas of complex flow are demonstrated with variable T2 hypointensity. (C and D) Axial CTA source image and coronal reformatted image through the expanded sella show marked intraluminal enhancement within cavernous segment aneurysm laterally (long arrow) with medial and peripheral soft tissue density that does not enhance, consistent with mural thrombus (short arrow).

cavernous segment aneurysm might be confused with a skull base meningioma or pituitary adenoma on conventional imaging.17 Aneurysms that arise from the anterior aspect of the cavernous segment can project into the intradural subarachnoid space and thus can cause subarachnoid hemorrhage. al-Rhodan et al25 referred to these aneurysms as transitional cavernous aneurysms.

ophthalmic artery aneurysm and other non–branch point aneurysms (paraclinoid) of the intradural ICA medial to the anterior clinoid process.27 Clinoid and paraclinoid aneurysms are difficult to treat surgically given their proximity to the anterior clinoid process and the optic nerve and their complex dural relationships. Similar to the cavernous lesions, these aneurysms can enlarge and project medially into the sella (Fig. 6).

Clinoid and Ophthalmic Segment ICA Aneurysms

Carotid Cavernous Fistula

More distal ICA aneurysms of the clinoid and ophthalmic segments, namely the anterior clinoid process and the planum sphenoidale, can be associated with skull base erosion. Clinoid aneurysms arise from the interdural segment of the ICA, between the proximal and distal dural rings. As they enlarge, the fundus can extend intradurally and result in subarachnoid hemorrhage.26 Ophthalmic segment aneurysms include the

A carotid cavernous fistula (CCF) is an arteriovenous fistula resulting from abnormal communication between the carotid artery and the cavernous sinus. The arterial supply can arise from the cavernous ICA itself or from small dural branches of the ICA or external carotid artery (ECA). Barrow et al28 classified CCFs based on the origin of the arterial supply (Table 1).

Definition and Classification

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Figure 6 Nonruptured paraclinoid aneurysm in a 52-year-old woman with headache and diplopia. (A) Axial, unenhanced CT scan shows a slight hyperdense rounded mass (arrow) in the sella and suprasellar cistern, with CT image characteristics suggesting a macroadenoma. (B) CTA source image shows avid vascular enhancement of the lesion, confirming the presence of a large aneurysm arising from the paraclinoid right ICA. Scalloping of the right anterior clinoid process and planum sphenoidale (open arrows) is noted. Close inspection reveals a tiny jet of more hyperdense contrast at the ostium of the aneurysm just medial to the anterior clinoid process. (C) Coronal reformat from CTA shows large right paraclinoid ICA aneurysm expanding the sella and displacing the left A1 segment.

Carotid-cavernous fistulas can be classified more simply as either or indirect. Type A CCFs are labeled direct because of the direct communication between the ICA parent vessel and the cavernous sinus. CCFs arising from dural branches of the ICA or ECA or both are termed indirect.29,30 Direct CCFs are most commonly the result of trauma involving a skull base fracture with either bony ICA injury or shear injury from the dural attachments of the ICA at the foramen lacerum and anterior clinoid process.31,32 However, CCFs have been reported in the absence of a skull fracture.31 Less common causes of type A CCF are ruptured ICA aneurysm, arterial dissection, and iatrogenic trauma. The predisposing conditions include hypertension, atherosclerotic disease, fibromuscular dysplasia, and collagen vascular diseases such as Marfan syndrome or EhlersDanlos syndrome.33 The pathophysiology of indirect CCFs is not well understood. These lesions occur most often in the elderly, with a strong female predominance. Several factors have been associated with indirect CCF development including CST, diabetes, hypertension, pregnancy, thrombophlebitis, intracranial surgery, sinusitis, and trauma.30,33-35

Signs and Symptoms Manifestations for direct and indirect CCFs commonly include proptosis, conjunctival chemosis, orbital pain, reduced visual Table 1 Classification of Carotid-Cavernous Fistula Based on Arterial Supply Type

Arterial Supply

A B C D

Directly from the ICA Dural branches from the ICA Dural branches from the ECA Dural branches from both the ICA and ECA

acuity, and headache.35,36 Palsies of CNs III, IV, and VI may occur as a result of compression in the cavernous sinus.37 Direct CCFs tend to have a sudden onset of symptoms, whereas indirect CCFs present more insidiously. Intracranial hemorrhage, blindness, and death are serious complications that are more commonly seen with direct CCFs.34

Imaging In trauma settings, high-resolution CT imaging of the skull base using bone algorithm is the study of choice for diagnosing a skull base fracture, a common prelude to a direct CCF. Conventional, enhanced CT and MRI studies of the brain or orbits can demonstrate morphologic characteristics of both direct and indirect CCFs (Fig. 7).38,39 These include signs of orbital venous congestion, diffuse extraocular muscle enlargement, edema in retro-orbital fat, dilatation of the superior (and occasionally inferior) ophthalmic vein, and proptosis.29 Although these changes are typically unilateral, sufficient retrograde venous congestion can cause bilateral abnormalities. The orbital findings are nonspecific and other etiologies should be considered, including cellulitis, orbital pseudotumor, lymphoproliferative disorders, thyroid ophthalmopathy, and CST. Intracranial findings can also be seen on conventional images and comprise unilateral or bilateral cavernous sinus enlargement and engorged cortical veins including the sphenoparietal vein and petrosal sinuses. One of the most conspicuous features of CCFs on spin echo images is abnormal, epicarotid flow voids (indicative of high flow) within the cavernous sinus (Fig. 8).40-42

CTA and MRA Currently, CTA, using submillimeter helical acquisition parameters, offers the ability to study the intracranial arteries

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Figure 7 Direct CCF in a 27-year-old woman with serious head trauma. Originally presented following MVA 7 weeks earlier with left orbital and central skull base fractures. Now presents with right orbital chemosis and bruit to auscultation. (A) Axial CTA through the upper orbit demonstrates prominent superior ophthalmic vein (arrow), a nonspecific finding. (B) Axial CTA through the cavernous sinus demonstrates massive unilateral enlargement of the right cavernous sinus. The right internal carotid artery is difficult to distinguish from the dilated arterialized sinusoids (arrow) of the cavernous sinus that demonstrate similar contrast enhancement. (C) Axial T2-weighted MRI scan demonstrates multiple serpiginous flow voids within a markedly distended cavernous sinus on right (arrows), consistent with high-flow arteriovenous shunt. (D) 3D rendering of CTA-demonstrated vascular sinusoidal mass of the right cavernous sinus with prominent sphenoparietal and other cortical veins draining to right transverse sinus (arrows). MVA, motor vehicle accident.

in exquisite detail. Axial, CTA source images allow evaluation of the arteries at the skull base and the differentiation of arterial enhancement from adjacent venous and osseous structures. A unique advantage of CT angiography is its ability to demonstrate the arteries and their relationships to the sinuses and any skull base fracture. CTA also allows for the identification of a coexisting pseudoaneurysm or prolapse of the ICA into the sphenoid sinus. CTA and MRA can both demonstrate arterializations of the cavernous sinus and retrograde filling of the superior ophthalmic artery.40 Both offer the ability to identify the fistulous communication between the ICA and the

cavernous sinus, especially when source images are critically evaluated.43-45 Both CTA and MRA can identify enlarged ECA branches that provide CCF supply in indirect lesions (Fig. 8).

Digital Subtraction Angiography (DSA) DSA is still considered the gold standard for diagnosing and classifying CCFs. It may be the only imaging modality that can identify small or relatively slow-flow fistulae, especially the indirect lesions, which often demonstrate multiple small arterial inputs (Fig. 9).35,40,46 The internal and external carotid

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Figure 8 Indirect CC fistula in a 72-year-old woman with left orbital exopthalmos and conjunctival chemosis. (A) T2-weighted MRI demonstrates an enlarged left SOV (arrow) with prominent flow void. (B) T2-weighted image through central skull base region demonstrates prominent varix (arrow) at the anterior cavernous sinus-SOV junction. (C) MRA demonstrates arterialized flow within the enlarged SOV (open arrows) as well as an enlarged internal maxillary artery (closed arrows) indicating prominent external carotid artery contribution to the fistula. (D) Source image from the MRA at the level of the skull base demonstrates prominent internal maxillary artery in pterygopalatine fossa (long arrow), prominent artery in foramen ovale (short arrow), and an enlarged middle meningeal artery within the foramen spinosum (arrowhead). CC, carotid-cavernous; SOV, superior ophthalmic vein.

arteries, as well as the vertebral arteries, can be selectively catheterized to evaluate each vessel’s contribution to the CCF. Early filling of the cavernous sinus and adjacent venous structures, including the superior ophthalmic vein, is pathognomonic. If rapid opacification of the cavernous sinus hinders visualization of the fistulous tract because of fast flow, vertebral artery injection with compression of the ipsilateral common carotid artery can be performed (Huber maneuver).47,48 This maneuver results in slower fistula opacification through a patent PCOM. Compression of the ipsilateral common carotid performed during ipsilateral ICA injection (the MehringerHieshima maneuver) is also useful. DSA is generally necessary before specific treatment options can be chosen.

Treatment Direct CCFs usually require treatment because of the large, associated fistulous communication.34 Endovascular treatment options for CCFs include embolization and stenting. Embolization or occlusion of the fistula can be performed transarterially, through detached balloons, or transvenous embolization.46-48 The inferior petrosal sinus or the superior ophthalmic vein is usually selected for transvenous embolization. If appropriate, a covered stent can be placed across the site of the fistulous communication in the ICA. If these treatment routes are not feasible, forfeit of the involved interval part of the artery with coils or balloons can be performed if the patient has the sufficient vascular supply to the ipsilateral cerebral

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Figure 9 A 69-year-old woman with Type D indirect CCF presents with left orbital proptosis and diplopia. (A) Coronal enhanced CT scan through the orbits demonstrates an enlarged and enhancing superior ophthalmic vein (arrow) on the left. There is subtle enlargement of the extraocular muscles compared with the right side. (B) Axial T2-weighted image through the sella demonstrates abnormal serpiginous flow voids in the medial compartment of the left cavernous sinus (arrow). (C) DSA with left internal carotid injection, AP view, shows no appreciable early filling of the left cavernous sinus. (D) Right internal carotid artery injection, AP view, reveals early contralateral filling of the left cavernous sinus through tiny racemose dural feeders. (E) Lateral view from left external carotid injection demonstrates early filling of the left cavernous sinus and retrograde filling of superior ophthalmic vein through numerous small dural arteries. AP, anteroposterior.

hemisphere from either the posterior communicating or anterior communicating indicating arteries. This can be confirmed by a balloon occlusion test. The success rate for closing direct CCFs in patients is high, ranging from 85%-99%.34,47,48 Indirect CCFs are often more difficult to treat owing to the presence of multiple fistulous communications. They have generally developed slowly and have had time to recruit a number of dural feeders. Occasionally, indirect CCFs have spontaneously resolved without intervention.29,47 Other indirect CCFs are successfully treated with conservative management, and intermittent ECA compression can also be attempted.29,49 Endovascular embolization is typically attempted for persistent indirect CCFs, with surgical intervention used in refractory cases.30,37

to infections and is localized to the face, sinuses, orbits, oral cavity, temporal bone, and skull base. Sphenoethmoidal sinusitis is considered the most common primary source of infection, with Staphylococcus aureus and Streptococcus species accounting for most microbe-proven cases. Septic CST can occasionally occur in the setting of distant infection and bacteremia.52,53 Local infections can cause CST either by direct extension, as with invasive sinusitis, or by septic thromboembolism through venous tributaries. The cavernous sinuses and adjacent venous structures (including emissary veins through the osseous skull base) are valveless and allow antegrade and retrograde transmission of infectious organisms when local immunologic response fails to contain the infection.51,53

CST

Signs and Symptoms

Pathophysiology CST is considered a rare phenomenon. Aseptic thrombosis can occur in the setting of trauma, surgery, underlying vascular lesion such as aneurysm or CCF, or in hypercoagulable states.50,51 In most cases, CST is septic, occurring secondary

CST can present with a number of signs and symptoms based on the location of primary infection, particular microorganism, immunologic status, and response to treatment. Most patients exhibit signs of fever and retro-orbital headache. Patients can present with unilateral or bilateral proptosis and chemosis related to venous congestion with or without thrombosis of the

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Figure 10 A 22-year-old man with bilateral periorbital cellulitis and opthalmoplegia. (A and B) Axial postcontrast venous phase images through the orbits and skull base demonstrate bilateral filling defects in the superior ophthalmic veins (short arrows) and bilateral, slightly asymmetric filling defects (thin arrows) in the cavernous sinuses consistent with bilateral thrombus. (C) Coronal postcontrast image demonstrates typical normal enhancement within the cavernous carotid arteries bilaterally as well as enhancement of the lateral walls. Interposed between these structures are amorphous filling defects consistent with thrombus. (D) Coronal postcontrast image slightly more posteriorly demonstrates internal filling defects in the cavernous sinuses (thin arrows). The appearance of the left Meckel cave with normal peripheral dural enhancement (short arrow) should be noted.

superior ophthalmic vein. As thrombophlebitis expands the cavernous sinus, there is inflammation, mechanical pressure, and probably ischemia in the CNs, hence CN palsies are common, producing external ophthalmoplegia.51-54 Sympathetic fibers along the intracavernous carotid are also involved, leading to ptosis and papillary constriction. Most patients present with unilateral symptoms but thrombophlebitis often extends through the intercavernous veins resulting in bilateral manifestations. Advanced cases can result in blindness, meningitis, stroke, and death. Historically, CST was considered a grave prognosis, often leading to death. There has been considerable improvement in early recognition and treatment of the disease, so the morbidity has been reduced significantly, now ranging from 23%-50%.53-55

Imaging The radiologic literature on CST mainly consists of case reports and small series.56 Some debate exists as to whether CT or MRI

is most useful in diagnosing CST and its complications. As indicated for most central skull base processes, CT and MRI generally play complimentary roles. CT is readily available, offers fast acquisition, and is generally undertaken as the firstline study to evaluate a local head and neck infection. When infections are complicated by neurologic deterioration or cranial neuropathies, contrast-enhanced high-resolution images with thin slices (3 mm or less) are necessary to evaluate the orbital or central skull base.57 CT identifies the primary source of infection, as well as demonstrates bone erosion, soft tissue phlegmon, and abscess.52,53 Secondary signs of CST can be seen, these include orbital congestion, distension of the superior ophthalmic vein (with or without intraluminal thrombus), and exophthalmos (Fig. 10). The cavernous sinuses generally have concave lateral margins. With thrombophlebitis, there is intrinsic mass effect and expansion of the sinus so the lateral wall becomes flat or convex. This is best appreciated on the coronal view. If unilateral involvement predominates, contour asymmetry of the sinuses

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Figure 11 A 69-year-old woman with long-term steroid use developed sinusitis, fever, and opthalmoplegia. (A) Axial enhanced postcontrast CT through the cavernous sinuses depicts bilateral cavernous sinus filling defects, more obvious on the right (arrow). The lack of enhancement between enhancing lateral wall and internal carotid artery can be noted. (B) Axial T1-weighted image shows isointense soft tissue signal in the cavernous sinuses bilaterally, right (arrow greater than left). (C) Axial T2-weighted image shows heterogeneous, nonspecific signal (arrow) in the cavernous sinuses. (D) DWI shows diffusion restriction in the right cavernous sinus (arrow). (E and F) Axial postcontrast T1-weighted images demonstrate large irregular areas of hypoenhancement in the cavernous sinuses bilaterally (arrows).Such filling defects can be difficult to separate from ICA flow voids depending on sequences and slice orientation. (G) Coronal postcontrast T1-weighted image demonstrates large irregular filling defects (arrows) interposed between the enhancing lateral walls and enhancing pituitary margins. (H) Coronal postcontrast T1-weighted image slightly anterior to (G) shows more heterogeneous enhancement of the cavernous sinuses but with definite lateral wall convexity. DWI, diffusion-weighted imaging.

Figure 12 A 54-year-old woman presented initially with pneumonia and septicemia and was placed in the ICU. After 2 days, she developed severe bilateral periorbital swelling, proptosis, signs of periorbital infection, and blindness in the right eye. (A) Axial postcontrast MRI with fat saturation shows there is extensive inflammation of the retro-orbital soft tissues bilaterally and mild proptosis. The superior ophthalmic vein demonstrates linear filling defect consistent with thrombosis (arrows). (B) Axial postcontrast MRI with fat saturation demonstrates bilateral filling defects in the cavernous sinuses consistent with bilateral thrombosis. (C) Axial DWI image demonstrates high signal within the right optic nerve consistent with infarction (arrow). Patient recovered from systemic illness but was left with blindness in the right eye. DWI, diffusionweighted imaging; ICU, intensive care unit.

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Figure 13 A 54-year-old diabetic woman presented with sinusitis complicated by headache, right eye blindness, frozen globe, and right facial numbness secondary to invasive mucormycosis. (A) Coronal STIR image through the sinuses demonstrates marked opacification of the right maxillary sinus and the right ethmoid sinus. There is retro-orbital infiltration with enlargement of the medial rectus and superior oblique muscles (arrows). There is hyperintense signal within the optic nerve (short arrow) secondary to infarction. DWI (inset) demonstrates diffusion restriction on right optic nerve. (B) Coronal postcontrast fat-saturated image through the cavernous sinus shows lack of enhancement (arrows) within the sinus consistent with thrombosis as well as lack of enhancement of the wall indicative of obliterative angioinvasion. (C) Slightly more posteriorly, the absence of enhancement can be noted in the cavernous sinus as well as the perineural venous plexus of V3. (D) Coronal T2-weighted image through the cavernous sinus 3 days later demonstrates abnormal signal in the internal carotid artery (arrows) consistent with thrombosis. DWI of the brain (inset) reveals subsequent embolic strokes. DWI, diffusion-weighted imaging; STIR, short T1 inversion recovery.

is readily identified on the coronal view. If both sinuses are affected equally, detection based on contour alone becomes more difficult. The normal cavernous sinuses generally show symmetric enhancement, but the enhancement can be heterogeneous, revealing small focal and linear filling defects related to normal structures including the CNs as well as intracavernous fat.58 If a clot predominates in the sinus, multiple irregular filling defects would be identified centrally in the enlarged cavernous sinus (Fig. 11).56,58 The lateral wall of the sinus, when distended, often appears thickened and enhances conspicuously. If infection and inflammatory change (phlegmon) predominate, the sinus may demonstrate heterogeneous enhancement but would be less conspicuous than normal vascular enhancement. In addition to the superior ophthalmic vein thrombosis, filling defects can be seen in the adjacent tributaries as well as the sphenoparietal and inferior petrosal sinuses.58 Precontrast and postcontrast MRI of the orbits or skull base can demonstrate the local effects of soft tissue infection, including cellulitis, abscess, and phlegmon formation. As with CT, MRI readily demonstrates secondary orbital defects of

CST, including superior ophthalmic vein thrombosis (Fig. 12).53 Expansion of the lateral wall of the cavernous sinus can be easily identified. Acutely, CST appears as abnormal soft tissue of variable signal in the affected cavernous sinus. The MRI signature of subacute thrombus, T1 shortening (T1 hyperintensity), is less often visualized in cases of CST compared with other dural sinus thromboses. As with enhanced CT, postcontrast, T1-weighted images can reveal irregular central filling defects within the cavernous sinus in CST.59,60 T2-weighted images allow assessment of ICA flow void. The ICA can be narrowed secondary to infectious arteritis or vasospasm or can be thrombosed as well.58,61 MRI identifies meningeal enhancement to better advantage, and diffusionweighted imaging can assess for cerebral ischemia or optic nerve infarction.62,63

CTA and MRA CTA with its high–spatial resolution source images can fully evaluate the internal carotid arteries at the central skull base in

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472 the setting of invasive cavernous sinus infections and CST. In the early arterial phase, the integrity and patency of the arteries can be assessed with confidence. Care must be taken not to overinterpret CST on early arterial phase CTA images as the early sinus opacification is often variable and asymmetric. MRA is also useful in evaluating secondary effects upon the cavernous ICA, including arteritis, thrombosis, and pseudoaneurysm formation.64

Invasive Fungal Disease and Cavernous Sinus Thrombophlebitis Invasive fungal disease deserves special mention in the discussion of CST.65 Most commonly originating in the sinuses, invasive fungal species are prone to invade the orbit (including the orbital apex), the central skull base, and the

adjacent neurovascular structures.66 Mucor and Aspergillus account for a majority of the causative organisms. Both are considered angioinvasive because of their propensity to invade and damage vascular structures. This can result in cavernous sinus and other venous thrombosis, arterial thrombosis, and vascular breakdown leading to hemorrhage and thromboembolism.67,68 The clinical course can be fulminant, and early clinical and radiologic diagnosis is key to survival. Rhinocerebral mucormycosis is considered the most aggressive fungal infection and occurs in immunocompromised patients, most commonly in patients with poorly controlled diabetes with ketoacidosis.67 Patients present with facial pain and edema, and most develop severe ophthalmologic symptoms including proptosis, chemosis, ophthalmoplegia, and visual loss secondary to optic nerve involvement or central retinal

Figure 14 A 69-year-old patient with lymphoma and neutropenia developed invasive Aspergillus infection of the sinuses and subsequent cavernous sinus thrombophlebitis and ICA thrombus. (A) Axial T1-weighted image demonstrates mild enlargement of superior ophthalmic vein (open arrow) and soft tissue signal in the cavernous sinus. The normal flow void in the right ICA is absent. (B) MRA depicts occlusion of the right ICA (arrow). DWI (inset) reveals multiple strokes of the right MCA. (C) Coronal postcontrast fat-saturated image demonstrates mild enlargement of the right cavernous sinus with heterogeneous filling in lateral compartment. The right ICA is mildly enlarged and contains thrombus. (D) More anteriorly, the ICA is enlarged (arrow), presumably related to angioinvasion, weakening, and thrombosis. DWI, diffusion-weighted imaging; MCA, middle cerebral artery. ICA, internal artery thrombosis.

Vascular lesions artery occlusion (Fig. 13). Mucor also exhibits tropism for neural tissue and can progress along perineural pathways.69 Invasive aspergillosis (IA) most commonly affects patients with profound neutropenia, and the incidence of IA in patients with hematologic malignancies is increasing.68 Although mucormycosis preferentially affects the sinonasal region, only 5% of IA cases affect the sinuses and skull base. Similar to mucormycosis however, IA can result in progressive angioinvasive disease of the central skull base and cause CST and acute neurologic deterioration (Fig. 14).70,71

Treatment Early clinical recognition and radiologic confirmation is necessary to guide therapy to prevent severe consequences of CST. Early surgical intervention with debridement and drainage of the primary infection combined with long-term antibiotic therapy are mainstays of therapy.

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Cavernous Hemangioma of the Cavernous Sinus Cavernous hemangiomas account for 5%-13% of intracranial vascular malformations. These lesions typically occur over the cerebral hemispheres and often result in hemorrhage or seizures. Cavernous hemangiomas of the cavernous sinus are rare lesions that result in an expansile mass that infiltrates and obliterates the cavernous sinus. Cavernous hemangiomas of the cavernous sinus consist of densely packed vascular channels and are considered by most authors to represent benign vascular malformations rather than true neoplasms. However, they behave like neoplasms, gradually increasing in size, causing symptoms because of their mass effect upon adjacent neural structures. These lesions often encase the ICA without narrowing.72 With CT, there is conspicuous absence of intrinsic calcification or hyperostosis. On MRI studies, cavernous sinus hemangiomas are well-circumscribed masses, isointense on

Figure 15 A middle-aged patient with diplopia found to have large mass involving the central skull base, cavernous sinus, and sella. Given its T2 hyperintensity and diffuse enhancement, the lesion was thought to represent chordoma or chondrosarcoma. At surgery, a large highly vascular lesion was encountered and biopsy demonstrated hemangioma. (A) Axial T2-weighted image demonstrates large mass (white arrows) extending from the sella, through the cavernous sinus, and into left middle cranial fossa. The lesion encases but does not narrow cavernous ICA (black arrow). (B) Coronal enhanced MRI shows that the large well-marginated lesion enhances diffusely. (C and D) Axial postcontrast T1-weighted images demonstrate large homogeneously enhancing mass in the left cavernous sinus, encasing the ICA (black arrow) with remarkable lateral extension (arrows).

474 T1, markedly hyperintense on T2, and enhancing diffusely (Fig. 15). No intrinsic flow voids are demonstrated. These lesions can extend medially into the sella or laterally into the middle cranial fossa.73

Conclusion The cavernous sinuses and internal carotid arteries are critical vascular structures in the central skull base region. These structures can be displaced, encased, or invaded by neoplastic, inflammatory, or infectious lesions of the central skull base region. The secondary involvement of the vascular structures can play a key role in the clinical presentation, diagnosis, treatment, and outcome of central skull base lesions. In addition, intrinsic vascular lesions of the central skull base are routinely encountered in neuroradiologic practice. It is important that the radiologist recognize the important imaging features of these lesions.

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