May. 04, 2021
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Carotid-cavernous fistulas are abnormal connections between the cavernous sinus and the internal carotid artery, external carotid artery, their branches, or both. There are 2 broad categories of carotid-cavernous fistulas—direct and indirect—each of which has a markedly different clinical presentation. In this article, the author discusses the clinical presentation, pathogenesis, and methods of diagnosis for this disease entity. This article provides an in-depth review of the current treatments for carotid-cavernous sinus fistulas, including the endovascular repair via transarterial or transvenous embolization.
• Carotid-cavernous sinus fistulas are communications between the cavernous sinus and the carotid arterial system.
• “Direct” carotid-cavernous sinus fistulas are abnormal communications between the internal carotid artery and the cavernous sinus, whereas “indirect” carotid-cavernous fistulas are aberrant connections between the branches of either the internal or external carotid arterial system or both and the cavernous sinus.
• “Direct” carotid-cavernous sinus fistulas are typically caused by head trauma or a ruptured cavernous carotid aneurysm and present in a dramatic fashion with proptosis, ophthalmoplegia, and loss of vision. “Indirect” or “dural” carotid-cavernous fistulas typically present in elderly women with hypertension in a more subtle fashion. Most of the time, both types of carotid-cavernous sinus fistulas can be closed successfully with modern neuro-interventional techniques.
Carotid-cavernous fistulas are abnormal communications between the cavernous sinus and the carotid arterial system, which includes the internal carotid artery, external carotid artery, and their meningeal branches. Historically, carotid-cavernous fistulas have been classified into 2 broad categories: direct and indirect. “Direct” or “high flow” carotid-cavernous fistulas are defined as direct connections between the internal carotid artery and cavernous sinus, whereas “indirect” or “dural” carotid-cavernous fistulas are characterized by connections between the meningeal branches of the internal carotid artery or external carotid artery and the cavernous sinus. A more specific anatomical-angiographic classification for carotid-cavernous fistulas was proposed by Barrow and colleagues who differentiated between 4 types of carotid-cavernous fistulas (06). Type A is a direct fistula between the cavernous internal carotid artery and cavernous sinus and is most often caused by a traumatic tear in the arterial wall or a rupture of an cavernous carotid aneurysm.
Type B is a fistula between meningeal branches of the internal carotid artery and cavernous sinus. Type C is a fistula between meningeal branches of the external carotid artery and cavernous sinus. Type D is a fistula between meningeal branches of both the internal carotid artery and external carotid artery and the cavernous sinus.
Thus, the traditional “direct” carotid-cavernous fistula is equivalent to a Type A carotid-cavernous fistula, whereas “indirect” (or “dural”) carotid-cavernous fistulas encompass Types B, C, and D. This classification gives the treating physician a more precise anatomical guideline on which treatment can be based.
The clinical manifestations of a carotid-cavernous fistula can be predicted by the structures within the cavernous sinus that are affected by the fistula. Therefore, a carotid-cavernous fistula may present with palsies of cranial nerves III, IV, V1, V2, or VI. In addition, retrograde venous flow may cause orbital and ocular venous congestion, resulting in proptosis, chemosis, arterialized venous loops on the sclera, increased intraocular pressure with subsequent glaucomatous vision loss, and engorgement of the extraocular muscles resulting in further restriction of eye movement. The acuteness of the presentation will depend mainly on whether the carotid-cavernous fistula is “direct” (type A) or “indirect” (type B, C, or D). Direct fistulas present with more dramatic symptoms due to the larger volume of blood that is being shunted. In a series of 98 consecutive patients presenting with direct carotid-cavernous fistulas from 1979 to 1992, the most common symptom was a prominent orbital bruit in 80%, proptosis in 72%, chemosis in 55%, isolated ipsilateral abducens palsy in 49%, retro-orbital pain or headaches in 24%, ophthalmoplegia in 23%, and vision loss in 17% (51).
A rare but important clinical manifestation is intracranial hemorrhage, which may develop in 5% of direct carotid-cavernous fistula patients. Interestingly, about 2% of these types of intracranial hemorrhages can present with life-threatening nosebleeds (87). Another rare but serious sequela of a direct carotid cavernous fistula is brainstem venous congestion, which may result in reduced consciousness, facial numbness, dysarthria, and gait ataxia (14).
In contrast to the fulminant presentation of direct carotid-cavernous fistulas, indirect (“dural”) carotid-cavernous fistulas usually have a more subtle presentation due to the smaller volume of shunted blood. These patients are typically middle-aged or elderly women, although indirect carotid-cavernous fistulas can present in either sex or in any age group. Miller provides an elegant discussion of the clinical manifestations of indirect carotid-cavernous fistulas based on whether the indirect fistula drains posteriorly into the superior and inferior petrosal sinuses or anteriorly into the superior and inferior ophthalmic veins (59). In posteriorly draining indirect carotid-cavernous fistulas, there are usually no signs of orbital congestion such as proptosis or symptoms such as an orbital bruit. The lack of conjunctival vessel arterialization gives this type of indirect carotid-cavernous fistula the moniker “white-eyed shunt” (01). These fistulas are often asymptomatic and may present with sudden, isolated ocular motor nerve palsy and are almost always associated with ocular or orbital pain. The third nerve is the most commonly involved cranial nerve and can be complete with pupil involvement, incomplete with pupil involvement, or incomplete with pupil sparing. This presentation of isolated, pupil-involving third nerve palsy without orbital congestion is often initially misdiagnosed as being caused by a cerebral aneurysm or a microvascular palsy. However, the true diagnosis of a posterior-draining indirect carotid-cavernous fistula will be made after cerebral angiography.
In contrast, anterior-draining indirect carotid-cavernous fistulas usually produce orbital congestion and visual symptoms and are, therefore, more similar to direct carotid-cavernous fistulas. Thus, the patient with an anteriorly draining fistula may present with arterialization of the conjunctival vessels, proptosis, chemosis, ocular motor paresis, and orbital pain. Many patients with dural carotid-cavernous fistulas are initially misdiagnosed with “chronic conjunctivitis” because of the conjunctival injection; close inspection reveals the characteristic radial pattern of arterialization seen in carotid-cavernous fistula.
Vision loss occurs in approximately 30% of patients with anteriorly draining indirect carotid-cavernous fistulas and can be due to increased intraocular pressure, retinal vessel occlusion, ischemic optic neuropathy, or even proliferative retinopathy leading to tractional retinal detachment (59). Increased intraocular pressure also can be a result of angle closure from massive choroidal effusion (84). However, not all anteriorly draining indirect carotid-cavernous fistulas necessarily present with ocular or orbital signs. This finding is illustrated by Ikeda and colleagues who described a woman with an anteriorly draining indirect carotid-cavernous fistula presenting only with headache and isolated abducens nerve palsy. In this case, the presence of anastomoses between the superior ophthalmic vein and angular facial vein was thought to prevent pressure buildup in the superior ophthalmic vein, thus, the lack of ocular or orbital signs (40).
Another feature that distinguishes an indirect from a direct carotid-cavernous fistula is its waxing and waning nature. A high percentage of indirect carotid-cavernous fistulas will close or improve spontaneously, with rates as high as 60% (77). Spontaneous closure of an indirect fistula site may even occur in patients who present with florid clinical symptoms such as optic neuropathy and orbital congestion (13). Improvement is thought to be due to spontaneous thrombosis of the fistula site. Recurrences or changes in clinical symptoms may occur as these clots dissolve or migrate, thus, diverting blood flow to different areas.
A retrospective study of 47 patients with cavernous-carotid fistulae (26 indirect, 21 direct) revealed a similar percentage of headache and ophthalmic symptoms and signs (proptosis, conjunctival injection, ophthalmoparesis, chemosis, visual acuity loss) between the 2 groups (31). The average age of patients with indirect fistulae was 62 years, compared to 48 years for those with direct fistulae. Patients with indirect fistulae were more likely to have elevated intraocular pressure and fundus abnormalities; a bruit and history of trauma were significantly more common in patients with direct fistulae. Patients who presented with vision loss were 3 times more likely to have residual symptoms, independent of carotid-cavernous fistula classification.
The overall prognosis of a carotid-cavernous is fistula good, with over 80% experiencing complete cure after endovascular treatment (28). The primary source of mortality with indirect carotid-cavernous fistulas is intracerebral hemorrhage, which occurs rarely at a rate of approximately 1.8% per year in these patients (22). A large proportion (up to 60%) of indirect carotid-cavernous fistulas will close spontaneously or after diagnostic angiography alone, thus, obviating the need for intervention with its attendant risks (77; 15). Therefore, the treating physician may choose to closely observe a patient with an indirect carotid-cavernous fistula as long as the ocular symptoms remain mild and there are no neurologic symptoms. Although elevated intraocular pressure occurs commonly in indirect carotid-cavernous fistulas, it does not necessarily require intervention beyond medical management. In 1 series of 14 eyes, 9 had elevated intraocular pressure of which only 3 had unfavorable intraocular pressure control. Only 1 of these eyes required glaucoma surgery (41). However, the clinician must balance this conservatism with the fact that vision loss can result from other causes besides increased intraocular pressure. These other causes include irreversible ischemic optic neuropathy, proliferative retinopathy, and choroidal detachment and effusion (35). Obviously, if the patient develops uncontrollably high intraocular pressure, intractable exposure keratopathy from proptosis, unacceptable diplopia, or intracerebral hemorrhage, then closure of the fistula is warranted.
For direct carotid-cavernous fistulas, the prognosis is much graver in terms of both morbidity and mortality. In 1 series of 127 patients with direct carotid-cavernous fistulas, the mortality rate was 3.9%, whereas there were no fatalities for indirect carotid-cavernous fistulas. Additionally, the rates of intracerebral or subarachnoid hemorrhage (3.1% vs. 0%), life-threatening epistaxis (3.1% vs. 0%), and increased intracranial pressure (8.7% vs. 3.6%) were much higher for direct versus indirect carotid-cavernous fistulas. The authors note that subarachnoid hemorrhage from a direct carotid-cavernous fistula portends a particularly grim prognosis, with all 4 of these patients dying quickly (33).
History. A 47-year-old man was involved in a motor vehicle crash several months prior to evaluation. Since the crash, he had swelling and redness in the left eye. He started having pain in the eye when exposed to light. He went to the emergency department for evaluation.
Physical examination. The physical examination showed visual acuity of 20/40 bilaterally. He had gross proptosis and periorbital swelling of the left eye, and a thrill was present over the left eye. The intraocular pressure was 8 mm Hg in the right eye and 16 mm Hg in the left eye.
Diagnostic tests (angiography). A catheter angiogram revealed a direct carotid-cavernous sinus fistula located at the left proximal posterior genu and cavernous sinus. There was significant dilatation of the superior ophthalmic vein. There was so much shunting that there was little to no filling in the left hemispheric arteries. This was diagnosed as a type A carotid-cavernous sinus fistula.
Treatment. The fistula was treated from the arterial approach. Initially, a microcatheter was guided up the internal carotid artery and through the rent in the carotid to the superior ophthalmic vein. Multiple coils were then placed from distal to proximal in the superior ophthalmic vein. As the coils filled the superior ophthalmic vein, the shunting decreased and the arteries of the left hemisphere became visible. Once the ophthalmic vein was successfully coiled, a stent was placed in the internal carotid artery over the rent. This prevented coils from herniating into the parent vessel. Additional coils were then placed to occlude the cavernous sinus.
Outcome. The patient’s pain was significantly improved after the procedure, with decreased proptosis and chemosis. He had no restriction of extraocular movements, and the diplopia resolved.
Direct carotid-cavernous fistulas are usually secondary to trauma or a ruptured cavernous aneurysm. However, the exact mechanisms by which traumas can cause these fistulas is still debated. The exact cause of indirect carotid-cavernous fistulas is also controversial.
Direct carotid-cavernous fistulas are usually associated with some type of trauma or iatrogenic injury. The precise mechanism of direct carotid-cavernous fistula formation is uncertain. Some authors believe that these fistulas result from bony fractures tearing the intracavernous internal carotid artery from its dural attachment or from shearing of this vessel due to inertia (72). Others dispute the contribution of bony fractures and believe that direct carotid-cavernous fistulas are the result of increased intraluminal pressure that occurs from abrupt compression of the carotid arteries (eg, during sudden neck flexion). In their clinicopathologic study, Helmke and colleagues found no fractures of the bony walls surrounding the intracavernous internal carotid artery in human autopsy subjects. Rupture of the vessel occurred most often in the C4 segment of the internal carotid artery (27 of 42 patients) followed by the C2 (13 of 42 patients) and C3 (2 of 42 patients) segments. Because the C4 segment is free of the trabeculae of the cavernous sinus, Parkinson’s “tearing” hypothesis cannot completely account for fistula formation (37). Besides trauma, direct carotid-cavernous fistulas can occur spontaneously and may be the consequence of any entity that weakens the internal carotid artery vessel wall, including internal carotid artery aneurysm, Ehlers-Danlos syndrome (61), fibromuscular dysplasia (39), pseudoxanthoma elasticum (78), or osteogenesis imperfecta (26). Carotid-cavernous fistulas have been reported after surgery or endovascular intervention. Direct fistulae were reported after stent-assisted coil embolization of an intracavernous carotid aneurysm, mechanical thrombectomy for stroke, and after craniofacial surgery (15; 02; 94).
Indirect carotid-cavernous fistulas usually occur spontaneously and insidiously in middle-aged to elderly women. Like direct carotid-cavernous fistulas, the precise etiology is controversial. Some investigators believe that indirect carotid-cavernous fistulas arise from rupture of the thin-walled dural arteries that normally cross the cavernous sinus (67). The currently favored theory is that these fistulas represent collateral anastomoses occurring after spontaneous venous thrombosis of vessels in the cavernous sinus and that these patients have a thrombotic tendency (85; 79). This may be the reason that dural fistulas are more common in women, and occur during pregnancy and the early postpartum period (89). Additionally, a congenital defect may play a role in indirect carotid-cavernous fistulas as these fistulas have been reported in infants without obvious additional risk factors (50; 29). Indirect carotid-cavernous fistulas can occur rarely with trauma, although this is more typical of direct fistulas.
The incidence of the various types of carotid-cavernous sinus fistulas is sparsely reported in the literature. Direct carotid-cavernous fistulas appear to be relatively rare, with an incidence ranging from 0.17% to 1.01% after traumatic brain and facial injury (83). However, this incidence appears to increase if one considers basilar skull fractures only. In their retrospective chart review of 312 patients with basilar skull fractures, Liang and colleagues found a 3.8% incidence of type A (direct) carotid-cavernous fistulas (52). Basilar skull fractures involving the middle cranial fossa were associated with the highest rate (8.3%) of direct carotid-cavernous fistulas compared to those involving the anterior (2.4%) and posterior (1.7%) cranial fossae. In another series of 100 consecutive direct carotid-cavernous fistulas, 76 were of traumatic origin, 22 occurred after a ruptured aneurysm, and 2 were iatrogenic. Motor vehicle accident (54 cases) and fall (10 cases) were the most common causes of trauma associated with direct carotid-cavernous fistulas in this series. Most of the trauma-related direct carotid-cavernous fistulas occurred in young men (57%; mean age of 36 years), whereas the ruptured aneurysm-related fistulas occurred predominantly in older women (77%; mean age of 54 years) (51). A report evaluated the incidence of direct carotid cavernous fistula formation after the placement of a flow diverter for treatment of a cavernous aneurysm. In this retrospective study, 11.5% of patients developed a direct cavernous carotid fistula within 2 weeks of treatment (80).
Intracranial dural arteriovenous fistulas account for 10% to 15% of all intracranial arteriovenous malformations (66). Of these, indirect carotid-cavernous fistulas account for approximately 12% and are the second most common type of intracranial dural fistula after those involving the transverse sigmoid sinus. No studies directly examining the incidence or prevalence of indirect carotid-cavernous fistulas were found. However, 1 study suggests that 0.1% of the United States population may have an arteriovenous malformation (12). Thus, at most 0.0018% (approximately 5400 people) of the United States population would be expected to have an indirect carotid-cavernous fistula.
Because most direct carotid-cavernous fistulas are caused by trauma, it is difficult to prevent their occurrence. Nonetheless, one should maintain a high level of suspicion for their presence when presented with a patient with severe head trauma and the typical neuro-ophthalmological signs. An iatrogenically related direct carotid-cavernous fistula can be prevented best by thorough knowledge of the patient’s carotid vasculature and medical history. For example, inadvertent creation of a direct carotid-cavernous fistula during transsphenoidal surgery for pituitary adenoma is more common in patients with a history of previous transsphenoidal surgery or radiation treatment. In these cases, it may be prudent to assess the patient’s unique vasculature with magnetic resonance or digital subtraction angiography before tumor resection. In this way, inadvertent direct carotid-cavernous fistula creation can be minimized during the operation (49).
Similarly, there is no proven way to reduce the incidence of indirect carotid-cavernous fistulas. However, because hypertension, atherosclerosis, and thrombophilia likely contribute to the genesis of indirect carotid-cavernous fistulas, measures aimed at reducing these risk factors seem sensible.
Because direct carotid-cavernous fistulas typically present with prominent orbital or ocular congestion, the main differential diagnoses include orbital processes such as thyroid eye (Graves) disease, idiopathic orbital inflammation (inflammatory orbital pseudotumor), orbital cellulitis, intraorbital tumor (eg, meningioma), or the various other causes of cavernous sinus syndrome (eg, carotid-cavernous thrombosis or Tolosa-Hunt syndrome). The main factor that distinguishes direct carotid-cavernous fistulas from these other entities is its typical association with acute, severe head trauma. In contrast, indirect carotid-cavernous fistulas present more insidiously, and their clinical manifestations may be overlooked or confused with benign entities such as conjunctivitis. One specific sign that distinguishes both direct and indirect carotid-cavernous fistulas from other disease entities is the presence of a characteristic orbital bruit. In almost all cases, the appropriate imaging study will clinch the diagnosis of a carotid-cavernous fistula. In the absence of imaging, the following pearls can help distinguish carotid-cavernous fistulas from other masqueraders:
Direct carotid-cavernous fistulas.
Thyroid eye disease. Though thyroid eye disease may present with exophthalmos and limitation of ocular movement, it usually does so in a subacute manner and without trauma. In addition, it typically involves both eyes (although asymmetrically) with upper eyelid retraction being its hallmark. Chemosis and conjunctival injection are less common and not as prominent compared to direct carotid-cavernous fistulas (11).
Idiopathic orbital inflammation. This entity encompasses all nonspecific orbital inflammation that cannot be attributed to infection, tumor, or another identifiable cause. Signs and symptoms depend on which orbital structures are involved, ranging from a mild myositis to a severe orbital apex syndrome. It also may present acutely, subacutely, or chronically and, thus, may mimic both direct and indirect carotid-cavernous fistulas. Like a direct carotid-cavernous fistula, it usually presents unilaterally and can have severe orbital signs as well as severe scleral injection from scleritis. However, in contrast to a direct carotid-cavernous fistula, it is not typically associated with trauma or an orbital bruit. Idiopathic orbital inflammation is also exceptionally sensitive to corticosteroids unlike most of the entities listed in this differential (42).
Orbital cellulitis. This condition may also present with severe proptosis, eyelid edema, pain with extraocular eye movements, and vision loss. However, these patients usually develop their infection over several days and often have a history of upper respiratory infection, nasal congestion, or sinusitis preceding the orbital signs. In addition, these patients typically will have constitutional symptoms such as fever, decrease in appetite, or malaise. This entity typically will respond to the appropriate intravenous antibiotic (88).
Intraorbital tumor. The many types of intraorbital tumors also can present with proptosis, paralytic or restrictive ocular movements, and vision loss, especially if they involve the orbital apex. However, orbital tumors typically grow slowly over time; thus, their clinical features are usually more insidious. Corkscrew conjunctival vessels are not found with intraorbital tumors.
Vertebral-venous fistula. A case report describes a vertebral-venous fistula that presented with ocular symptoms attributable to a carotid cavernous fistula, but angiography demonstrated a vertebral-venous fistula. Although extremely rare, it should be kept in mind if carotid angiography is normal in a patient with symptoms consistent with a carotid cavernous fistula (32).
Indirect (“dural”) carotid-cavernous fistulas. In addition to the above differential diagnoses, indirect carotid-cavernous fistulas initially may be confused with simple ocular inflammation including blepharitis, conjunctivitis, episcleritis, or scleritis. However, indirect carotid-cavernous fistulas are not associated with discharge and will not resolve with topical antibiotics or anti-inflammatory medications. The conjunctival or scleral injection associated with these ocular inflammatory diseases can be discriminated from the typical radial, corkscrew vessels of carotid-cavernous fistulas. Lastly, cranial nerve palsies and other intracranial manifestations (eg, headache or transient ischemic attacks) occur frequently in indirect carotid-cavernous fistulas but not in these ocular inflammatory conditions.
The key to diagnosing a carotid-cavernous fistula is to suspect its presence based on the history and physical examination. Direct carotid-cavernous fistulas present with dramatic orbital signs in the context of severe head trauma, often with basilar skull fractures. It is important to ask the patient about a bruit. Patients often describe the bruit as a whooshing noise or a heart beat in their head. A stethoscope, placed over the eye or at the temple, can be used to seek out this rather specific sign. Arterialization of the conjunctival vessels occurs more frequently in carotid-cavernous fistulas compared to other orbital diseases. Indirect carotid-cavernous fistulas, especially those of the posteriorly draining variety, are more difficult to diagnose by history and physical examination alone. One should still suspect them in any middle-aged to elderly woman presenting with a spontaneous red eye, chemosis, isolated or multiple cranial nerve palsy, and mild orbital congestion (58). Misdiagnosis is common. A retrospective series of 24 patients with carotid cavernous fistula identified 2 patients misdiagnosed with cluster headache, 1 as an orbital fracture and 1 as thyroid eye disease (07).
Another office procedure that may help diagnose a carotid-cavernous fistula is measuring the ocular pulse amplitude. The ocular pulse amplitude is the difference between the maximum and minimum intraocular pressure during the cardiac cycle and can be calculated with any commercially available tonometer. One study showed an ocular pulse amplitude of more than 1.6 mmHg to be 100% sensitive and 93% specific in distinguishing carotid-cavernous fistulas from normal subjects or those with other orbital diseases. However, direct and indirect carotid-cavernous fistulas cannot be distinguished from each other by the ocular pulse amplitude (30). The ocular pulse amplitude has been shown to normalize after closure of the fistula by endovascular embolization (30; 46).
The radiographic evaluation of a carotid-cavernous fistula will likely begin with noninvasive imaging such as CT, CT angiography, MRI, MR angiography, or transcranial Doppler ultrasound. A CT scan is usually the initial imaging study that is performed in patients with acute head trauma and may heighten the clinician’s suspicion for the presence of a carotid-cavernous fistula. In the case of direct carotid-cavernous fistulas, a CT scan will show proptosis of the involved globe, expansion of the cavernous sinus and superior ophthalmic vein, possible enlargement of the extraocular muscles, and any suspicious skull fractures (77). Magnetic resonance imaging has similar diagnostic utility to CT in finding signs suggestive of a carotid-cavernous fistula, but MRI is less sensitive in localizing bony fractures. An abnormal cavernous sinus flow void is a sign specific to MRI in the diagnosis of carotid-cavernous fistulas. In 1 study of indirect carotid-cavernous fistulas, CT found a dilated superior ophthalmic vein in all involved sides whereas MRI found this sign in 9 of 12 fistulas. MRI also found an abnormal flow void in the cavernous sinus in 11 of 12 patients with indirect carotid-cavernous fistulas (91).
For direct visualization of a carotid-cavernous fistula, CT angiography is increasingly being used in the initial localization and characterization of carotid-cavernous fistulas ever since its utility for this purpose was described in 2000 (23). In 1 study, CT angiography was found to be equivalent to traditional angiography and superior to MRA in determining the size and location of carotid-cavernous fistulas. This advantage was even greater in diagnosing direct carotid-cavernous fistulas involving the C4 segment of the internal carotid artery (ie, the most commonly involved segment) (16). Benson and colleagues reviewed 18 consecutive patients with a carotid-cavernous fistula and CTA imaging to find the most sensitive and specific imaging features of the carotid-cavernous fistula (09). Early enhancement and dilatation of the superior ophthalmic vein had 100% sensitivity. Arterial-phase contrast in the cavernous sinus had 88.9% sensitivity. 4D CTA is being increasingly used to diagnose neurovascular problems. MRA also can directly visualize a carotid-cavernous fistula but is less likely to delineate the small arterial feeder vessels or cortical venous drainage routes compared to traditional angiography (81). A report suggested that 4D flow MRI may be useful in providing a quantitative analysis of flow velocity and volume using time-resolved phase-contrast MRI for preoperative evaluation of a direct carotid cavernous fistula (64).
Other noninvasive imaging modalities that might aid in the diagnosis of carotid-cavernous fistulas are transcranial and transorbital color Doppler and carotid duplex ultrasonography (18; 19). These techniques can be used to measure the flow characteristics of both indirect and direct fistulas preoperatively. They may be even more important in helping to diagnose indirect carotid-cavernous fistulas when CT and MRI miss the signs of these fistulas. For example, results from a color Doppler ultrasound might help the clinician decide whether or not to perform invasive conventional angiography. Additionally, Doppler ultrasonography can give information regarding the collateral capacity of the circle of Willis before an intervention is undertaken as well as to judge whether an intervention was successful (47). Orbital color Doppler ultrasound (OCDUS) is another noninvasive test that, if negative, can rule out an anterior-draining carotid-cavernous fistula (92).
The gold standard for the diagnosis of both direct and indirect carotid-cavernous fistulas is catheter angiography. Angiography will provide the anatomic foundation on which to formulate a treatment plan. Both types of carotid-cavernous fistulas will require selective angiography to determine the exact location of the fistula and to delineate the possibly multiple feeder vessels and drainage pattern before treatment can commence. Kannath and colleagues studied 37 patients with 3-dimensional rotational angiography and were able to identify the fistulous connection prior to treatment (45). It is important to detail the venous drainage of the cavernous sinus in carotid-cavernous fistulas. If the cavernous sinus is draining superiorly into the cortical veins, the fistula should be treated emergently to prevent intracerebral hemorrhage and possible hemiparesis. Selective angiography also details the route (ie, transarterial or transvenous) by which the fistula can be closed, whether the fistula is being fed bilaterally, and the capacity of the circle of Willis (25). A common regimen that answers these questions includes selective injections of both internal carotid arteries and external carotid arteries, the ipsilateral vertebral artery, the ipsilateral ascending pharyngeal artery, middle and accessory meningeal arteries, and proximal and distal internal maxillary arteries (56). Botsford and Shankar evaluated the use of DSA-Dynavision in treatment of carotid-cavernous fistulas. In their retrospective study of only 8 patients, they found that using the DSA-Dynavision in treatment planning allowed more precision in their treatment and reduced the time of treatment (10).
The definitive treatment of any arterial-venous fistula is obliteration of the fistulous connection. There are 4 methods of treatment of carotid-cavernous sinus fistulas: conservative, endovascular, stereotactic radiation, and surgical. The type of the fistula often determines the treatment of choice. It is important to remember that there still are no randomized clinical trials evaluating the treatment or outcomes of carotid-cavernous sinus fistulas.
Closure of indirect carotid-cavernous fistulas may occur spontaneously or after diagnostic angiography alone with reported success rates as high as 47% to 60% (74; 77). Indirect fistulas will sometimes respond to conservative treatment with a trial of carotid compression (38; 34; 44). The patient is asked to manually occlude the affected carotid with the opposite hand for 10 seconds 3 times an hour while awake. The occlusion time is gradually increased: After the second day, the patient compresses the artery for 15 seconds 3 times an hour for 2 days, then 20 seconds 3 times an hour for 2 days, then 25 seconds 3 times an hour for 2 days, then 30 seconds 3 times an hour. This can also be attempted with direct fistulae, but due to the high flow nature of direct fistulae, carotid compression is less effective. The maneuver is thought to promote thrombosis and closure of the fistula. Previous studies have reported complete resolution of symptoms in 21% to 34% of indirect carotid-cavernous fistula patients (38; 34; 44).
Even without thrombosis or closure of the indirect carotid-cavernous fistula, a large number of patients will recover or experience significant improvement with conservative management alone. For example, 1 series found that 82% of patients (39 of 48) who were treated conservatively recovered or were significantly improved without invasive intervention (27). Of special importance is the presence or absence of retrograde cortical venous drainage as diagnosed by angiography. If this drainage pattern occurs, there is a much higher risk of intracerebral hemorrhage and patient mortality if the fistula is not closed urgently. One study found this risk to be increased by at least 30% (34).
Endovascular treatment has become the primary means of treating carotid-cavernous sinus fistulas with surgical intervention reserved for failures. Direct and indirect fistulae can be closed either by transarterial or transvenous routes, or a combination of both. The tools available to use during endovascular treatment include coils, stents, flow diverters, liquid embolics, particles, carotid sacrifice, detachable balloons (not available in the United States), and, most recently, a vascular micro plug that can be used for quick vessel occlusion (08). Combinations of all of the above can also be used with the objective being to close the fistulous connection.
Direct carotid-cavernous sinus fistulas are most commonly closed by a transarterial approach. The key is to locate the rent between the carotid and the cavernous sinus. Once this is located, a microcatheter can be passed through the rent, and the cavernous sinus is filled with coils to occlude the fistula. Sometimes a balloon or a stent may be needed to cover the rent while the coils are being placed to keep the coils out of the parent vessel (62). The rent can also be occluded with a covered stent if the vessel size and tortuosity allows. There have been reports of using flow diverters to treat direct carotid-cavernous sinus fistulas (93; 86; 76). Covered stents and flow diverters allow reconstruction of the vessel without occluding the sinus (48; 53; 68).
Another option in endovascular treatment of a direct carotid-cavernous sinus fistula is parent vessel sacrifice. Prior to sacrificing the vessel, it is important to make sure the collateral blood supply is sufficient to support perfusion of the brain. A trial balloon occlusion allows the assessment of the collateral vessels. With the patient awake, a balloon is blown up in the carotid artery near the rent. The balloon is left up for 15 minutes, during which time the patient is continuously examined. Five minutes into the test a nuclear medicine tracer is injected intravenously, and the patient is taken to nuclear medicine for a perfusion study at the end of the test. If the patient passes both the clinical exam and the nuclear medicine portion, then the vessel can be sacrificed with low morbidity. A type A carotid-cavernous fistula can be treated effectively and relatively safely with endovascular procedures. Chi and colleagues reported on a series of 172 patients with type A carotid-cavernous fistulas treated with an endovascular procedure (20). They reported a 94% occlusion rate with a 70% rate of preservation of the carotid artery. In the series, they had a 0.6% mortality and a 2.4% morbidity.
Indirect fistulae are more difficult to treat because there are usually multiple feeding vessels. The feeding arteries are often small, tortuous, and difficult to reach, even with a microcatheter. The transvenous approach is usually the access route of choice. The inferior petrosal sinus is often the most straightforward way to reach the cavernous sinus. If this is not an option, the superior petrosal sinus, basilar plexus, pterygoid plexus, the facial vein, or even a direct puncture of the dilated superior ophthalmic vein or percutaneous access to the facial vein with ultrasound guidance can be attempted (60; 56; 57; 96; 65; 24; 95; 55; 03). Coils, liquid embolics, or particles can be used to occlude the fistulous connection. Detachable balloons, once widely used to treat carotid cavernous fistulas, were removed from the U.S. market in 2003. In an attempt to determine the success of various endovascular treatments for indirect carotid-cavernous sinus fistula, Alexandre and colleagues reviewed patient records at 4 centers. Records were available for 267 patients; overall, obliteration was accomplished in 86.5%. An exclusively transvenous approach had the highest obliteration rate of 86.9%. A transvenous approach using coils only had the highest likelihood of achieving a cure. Complication rates were also decreased when only coils were used compared to liquid embolics alone or in combination with coils (04).
There are times when the tortuosity of the carotid vessels limits endovascular access to the fistula. In these cases, surgical exposure of the cervical carotid for access has been described (63; 82).
If endovascular treatment fails or is not possible, the fistula can be treated surgically. This is a more invasive strategy involving a posterior orbitotomy or a craniotomy to gain access to the cavernous sinus and close the fistula site directly (73; 77). The closure can be accomplished with a variety of materials, including sutures, clips, fascia, or acrylate glue. In 1 series of 19 patients who failed endovascular treatment, 100% of the carotid-cavernous fistulas were closed with direct surgery of the cavernous sinus (90). However, 3 patients (16%) required a bypass graft because the intracavernous internal carotid artery became trapped. In addition, direct surgery came with a significant rate (26%) of sacrifice of the internal carotid artery or bypass graft.
Another potential treatment for carotid-cavernous fistulas is stereotactic radiotherapy (ie, gamma knife radiosurgery or XKnife®). In this modality, radiation is precisely targeted on the main fistula site to thrombose and close it. The results are promising, with 1 group reporting a 90.9% closure rate for 22 indirect fistulas with no recurrences during a follow-up period ranging from 15 months to 14 years (05). However, fistula closure and clinical improvement occur more slowly with gamma-knife therapy compared to traditional endovascular approaches. In the aforementioned study, complete fistula closure took an average of 7.5 months, and symptom improvement took an average of 2.4 months. This latency is consistent with other similar studies (75; 69; 21). There also might be a difference in complication rates between different modalities of radiosurgery in closing indirect fistulas. In 1 study, XKnife® was associated with higher radiation doses being delivered to the lens, optic nerve, optic chiasm, and brainstem compared to gamma knife surgery (70). Stereotactic radiotherapy also has been used in an attempt to close posttraumatic direct carotid-cavernous fistulas. The rate of clinical improvement and fistula closure was much poorer for these direct fistulas, successful in only 1 of 3 cases in the Barcio-Salorio study (05). Park and colleagues reviewed their 7 year experience of the treatment with direct carotid-cavernous fistulas with stereotactic radiosurgery. This was a retrospective study reviewing 18 cases. Eighty-three percent of their patients had total obliteration of the fistula over 2 years (71).
Outcomes after treatment of carotid cavernous fistulae are good if the fistula can be disconnected. Angiographic occlusion of the fistula has been shown to predict good outcome (43). Hassan and colleagues evaluated 34 patients, 26 with a direct fistula and 8 with an indirect fistula (36). All patients showed complete recovery of their pretreatment symptoms. Only 1 patient (3%) had a complication. Common complications that can occur with treatment of carotid-cavernous fistulas include hemorrhage (either intracranial or if treatment is endovascular, at the groin site), new neurologic deficit, infection, recurrence, or endocrine dysfunction. Chen and associates reported a case of a patient developing syndrome of inappropriate antidiuretic hormone secretion after Onyx treatment of bilateral direct carotid-cavernous fistulas (17).
Patients with impaired renal function. Patients with known poor renal function are at higher risk for worsening of their renal function after endovascular treatment secondary to the intravenous contrast used during the procedure. In these cases, the risks and benefits must be weighed carefully and discussed with the patient and family.
Pregnancy may predispose patients to indirect carotid-cavernous fistulas by increasing the risk of thrombosis of the cavernous sinus vessels. This clotting may stimulate anastomoses in the cavernous sinus leading to indirect carotid-cavernous fistula formation. Toya and colleagues reported 2 cases of indirect carotid-cavernous fistulas that developed during pregnancy in young women in their twenties (89). One of the patients had an indirect carotid-cavernous fistula that disappeared after she terminated her pregnancy in the 12th week of gestation. The other patient developed the indirect carotid-cavernous fistula at the 28th week of pregnancy, but her symptoms gradually improved several weeks after delivery. In addition, the hemodynamic changes associated with pregnancy have been implicated in a case where a previously resolved direct carotid-cavernous fistula reopened (54). In this case, backflow to the cortical veins and an intracerebral hematoma led to hemiplegia.
Kim Rickert MD
Dr. Rickert of the Guthrie Clinic has no relevant financial relationships to disclose.See Profile
Steven R Levine MD
Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.See Profile
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