Alternative Treatment Options

C O N T E N T S

9.4Radiotherapy 284

9.5Surgery 287

References 289

With regard to the relatively high rate of spontaneous thrombosis of dural cavernous sinus fistulas (DCSFs) in some studies, a number of investigators consider conservative management the first line of treatment, especially if symptoms are mild, no cortical venous drainage is present and the angiographic evaluation reveals a low-flow shunt. This may include observing and following patients, while they are regularly examined by an ophthalmologist to monitor their visual acuity and IOP. Retroorbital pain may be treated with standard analgesics, diplopia may be coped with by using prism therapy and elevated IOP (if necessary) by administrating topical agents such as Latanoprost for a few weeks (Miller 2007). Worsening of symptoms may indicate an increase in AV shunting flow, but can be also part of the healing process that is accompanied by thrombosis of the CS and may involve the SOV to some degree. Administration of corticosteroids may help to cope with these symptoms and lessen their se-

verity (Sergott et al. 1987). This management may also be useful until elective endovascular treatment is scheduled.

If IOP continues to increase, exophthalmos progresses or chemosis develops, definite occlusion of the AV shunt becomes inevitable. Although conservative management with or without manual compression therapy is recommended by numerous investigators (Miller 2007; Grove 1984; Phelps et al. 1982; de Keizer 2003), glaucoma treatment may be insufficient and IOP can be difficult to control (Kupersmith et al. 1988).

While anticoagulation is used by some investigators to avoid postoperative thrombosis of the SOV and the central retinal vein, heparin is administered by others to control the thrombosis as part of the natural history of DCSFs. Bianchi-Marzoli et al. (1996) recently reported improvement in four patients after low-dose heparin administration, and deterioration in two other patients in whom the heparin was stopped. Yousry et al. (1997) observed an interesting case in which the AV shunt completely disappeared following systemic anticoagulation for 3 months. Other viable non-inva- sive options for conservative management include manual compression and controlled hypotension (see below).

9.1

Spontaneous Thrombosis

Early reports on spontaneous occlusion of CSFs include the monographs from Sattler (1930), Dandy (1937) and Hamby (1966), which reported 5.6%–10% occlusion rates. These relatively low numbers are presumably due to the inclusion of a large number of high-flow direct CCFs (Parkinson 1965, 1987).

Sattler (1930) reported that although he found occlusion in 18/322 cases (5.6%), this may be an underestimation, because in many treated and untreated cases, the outcome remained unknown. In two traumatic fistulas (0.6%), a slow regression of symptoms was seen without any therapeutic measure. The remaining 16 patients (10 traumatic and six spontaneous) underwent spontaneous thrombosis of the orbital veins, accompanied by severe inflammatory reactions.

Some data suggest that about 30% of the patients in all series show a spontaneous occlusion of the AV shunt, although the published material is quite heterogeneous (Tomsick 1997). For example, Nukui et al. (1984) and Sasaki et al. (1988) studied 20 and 26 patients, respectively, who were conservatively followed between 4 and 108 months (9 years). A regression of symptoms was noted in 18/20 (90%) and 19/26 (73%) cases, respectively, and was delayed in patients older than 60 years of age, in slow-flow fistulas and in cases with multiple draining veins. There was unfortunately no information on the anatomical outcome and whether disappearance of the symptoms correlated with complete angiographic occlusion. It appeared in these data that closure of the fistulas followed a pattern with a half-life of 18 months (Barcia-Salorio et al 2000).

Data on the “natural history” of DCSFs are in general incomplete, because some “spontaneous” occlusions occurred following cerebral angiography (Nukui et al. 1984; Sasaki et al. 1988; Takahashi et al. 1989; Newton and Hoyt 1970; Voigt 1978; Seeger et al. 1980), manual compression therapy (Kai et al. 2007), or in groups of patients undergoing transarterial embolizations (Kurata et al. 1998; Satomi et al. 2005).

Angiography-triggered occlusion was likely the underlying cause in the case of an AVF involving the IPS with symptoms mimicking a CSF, observed by the author. Following a bagatelle trauma, the 72-year-old gentleman developed right eye redness, chemosis and increasing diplopia due to 6th and 4th CN palsy. The DSA revealed a small arteriovenous shunt at the posterior CS, but mainly involving the IPS and exclusively supplied by bilateral dural branches of the APA. This patient, shown in Case Illustration XII, is one of the rare cases I have observed with a possibly related trauma in their history (see Sect. 5.2.5.). Due to a respiratory infection on initial admission, endovascular therapy had to be postponed and was rescheduled 6 days later. The angiogram at the beginning of this endovascu-

lar procedure showed a partial occlusion of the AV shunt, while the symptoms had regressed (Fig. 9.1). This occlusion was confirmed by a second control angiogram 3 months later, when the clinical exam demonstrated complete resolution of conjunctival engorgement and diplopia.

Such “spontaneous” occlusions of CSFs that follow intravascular contrast administrations have been described by several investigators (Seeger et al. 1980; Nishijima et al. 1985; Isfort 1967; Voigt et al. 1971; Yamamoto et al. 1995; Potter 1954; Parsons et al. 1954; Fromm and Habel 1965; Toennis and

Schiefer 1959).

Voigt et al. (1971) reported the spontaneous occlusion of a bilateral DSCF associated with cerebral angiography. The authors questioned the role of vasoconstrictor effect of the contrast medium triggering local thrombosis. They favored a theory of stasis following changes in pressure gradients during angiography. The role of general anesthesia was explained usually accompanied by a lowered systemic blood pressure. The latter theory has been considered by others as well (Potter 1954; Parsons et al. 1954) and reveals some evidence in fistula occlusions achieved by induced hypotension (see below) (de Miquel et al. 2005; Ornaque et al. 2003).

In 1980, Seeger et al. presented six patients with spontaneous occlusions. They discussed the role of contrast medium that likely induces thrombosis by direct interaction with the endothelium that causes aggregation of platelets and white blood cells, accelerating the clumping of erythrocytes and thrombosis.

Phelps et al. (1982), reporting the red eye shunt syndrome, observed six (32%) fistula occlusions. In this group, 7/19 patients (37%) underwent angiography, three of them (43%) obliterated soon after the exam. Spontaneous occlusions may be accompanied by exacerbation or regression of the symptoms, because a fresh thrombus in the CS may redirect AV shunting flow towards the SOV, increasing IOP. That is why a paradoxical increase of symptoms due to ongoing thrombosis can be seen in some of the patients (Seeger et al. 1980; Hawke et al. 1989; Grossman et al. 1985). Hawke et al. (1989) documented that a patient with initially isolated posterior drainage developed new ophthalmological symptoms after the IPS thrombosed. Kurata et al. (1993) emphasized that patients with singular SOV drainage and likely existing IPS thrombosis, demonstrated more significant chemosis and exophthalmos than those with more open efferent veins.

As already discussed by Sattler (1930), spontaneous occlusion of a CSF, if caused by thrombosis of the ophthalmic and the retinal veins, may cause visual loss when the fistula “heals” (Sergott et al. 1987; Knudtzon 1950; Miki et al. 1988; Suzuki et al. 1989). Choroidal effusion with increasing orbital congestion and cranial neuropathy due to uncontrolled spontaneous thrombosis may occur, leading to dramatic worsening of the symptoms.

When patients undergo TVO, transient aggravation of symptoms due to induced CS thrombosis affecting orbital veins may also occur. However, the amount of thrombus forming within the CS and potentially causing pseudoinflammatory deleterious effects is much larger during spontaneous occlusions. In addition, the elevated venous pressure is at least partially reduced as long as coils are effectively blocking the AV shunting flow. While aiming for this reduction of the venous pressure has priority during endovascular management, excessive thrombosis of the SOV and the central retinal vein must be avoided. Thus, anticoagulation for 48 h, even after complete transvenous coil packing of the CS, may be required (Kupersmith et al. 1988; Tomsick 1997).

The author utilized an anticoagulation regimen if embolization visibly accelerated thrombosis, or when a patient developed progressive symptoms or increasing intraocular pressure post procedure.

9.2

Manual Compression Therapy

The most widely used non-invasive conservative management of CSF patients is intermittent manual compression therapy (MCT). This involves a simple maneuver to reduce the arterial inflow and the venous outflow of CSF and was used by Scott in 1834 for diagnostic purposes. In 1846, Vanzetti from Padua communicated verbally a simple digital compression between heart and tumor, and taught the same from 1853 onwards.

Gioppi, one of Vanzetti’s peers and a professor of ophthalmology in Padua, reported in 1856 a more defined technique (Gioppi 1858). He described a 42-year-old female with pulsating exophthalmos that developed after pregnancy, who was treated with 15 min of intermittent external compression. After 4 days, pulsation and bruit were diminished. After 6 days, a slight recovery of the complete vision loss was observed.

Gioppi suggested four different compression techniques: (1) from anterior to posterior between the two heads of the sternocleidomastoid muscles,

(2) using the 2nd, 3rd, and 4th finger of the left hand along the lateral margin and the thumb along the medial margin of the sternocleidomastoid muscle, while the right hand pushes the head to the involved side, (3) using the second finger at the anterior margin of the sternocleidomastoid muscle posteriorly and slightly lateral, and (4) slight compression against the larynx or trachea. While performing part of the compression therapy herself, Gioppi’s patient was not always able to grab the carotid and had to use his third technique.

Two years later, in Verona, Scaramuzza treated a patient using intermittent digital compression for no longer than 4–5 min, 5–6 times per day over 18 days. After the 3rd day, partial regression was noted. After 16 days, complete regression of the exophthalmus occurred, and after 26 days complete “healing” of the fistula was observed [reported by Vanzetti (1858)].

Sattler (1880) mentioned that carotid compression might be less effective in traumatic fistulas than in idiopathic cases (spontaneous CSFs). In 29 patients in which digital or instrumental carotid compression was performed, only four (14%) showed success. Despite these somewhat discouraging results, he suggested beginning treatment of pulsating exophthalmus with a compression method, either digital, using a mechanical instrument (Fig. 2.7) or via a tourniquet, as was utilized by Nelaton. In spontaneous (“idiopathic”) cases, such intermittent compression may already be sufficient to achieve improvement or cure. Bed rest and other measures to lower systemic blood pressure were also recommended. In 1924, Locke mentioned a rate of cure or improvement of 37% in 27 patients and 26.4% in 106 patients, respectively.

Manual compression therapy as a treatment option for CSFs has been advocated by numerous investigators as a minimally invasive procedure since. It was further supported by the encouraging experience reported by Halbach et al. in 1987. Patients with DCSFs were asked to compress their carotid arteries and jugular veins with their opposite hands while sitting for 10 s several times per hour. When tolerated, the compression was increased 30 s over a total of 4–6 weeks. Patients with angiographic evidence of cortical venous drainage were excluded. The authors achieved complete cure in 7/23 (30%) patients undergoing carotid jugular compression, while the

same group (Higashida et al. 1986) achieved occlusion of direct CCFs in eight of 48 patients (17%).

Since then, this occlusion rate (approximately one third) has been cited in numerous publications. Thus, manual compression therapy has been recommended as an adjunct or even alternate treatment option. In 1992, complete cure was reported in 34% of 53 patients (Halbach et al. 1992). Quite surprisingly, in the most recent report on DCSF patients from the same investigators, including all patients from 1986–2000, manual compression therapy was curative in only one patient (0.74%), while it was used as an adjunctive technique to endovascular treatment in 34%. This raises questions about its true efficacy. Unfortunately, no validation of its actual treatment effects exists to date.

Kai et al. (2007) studied a group of 23 patients, achieving complete resolution of symptoms in eight cases (35%). The authors identified lower ocular pressure, a shorter interval between symptom onset and compression treatment and venous drainage solely via the superior ophthalmic vein without involvement of the inferior petrosal sinus as factors that would favor a complete occlusion achievable by this technique. Because the patients in this group underwent MRI/MRA for FU, it is not clear in how many cases anatomical occlusions were indeed achieved. It is also known that resolution of ophthalmological symptoms may occur while the venous drainage is rerouted posteriorly towards cortical veins, in fact creating, a more dangerous lesion.

Manual compression therapy was performed in only four of the author’s patients, who were considered compliant. The therapy was performed as described previously. Although all patients reported some improvement over this period of time, none showed a notable reduction of the shunt flow in the control angiogram. In one patient, after 3 weeks compressing the SOV in the eye angle, an increase in symptoms occurred. All patients underwent subsequent endovascular therapy, which lead to complete anatomical and clinical cure.

The effect of compression therapy appears unpredictable, as there is no control on the change in the venous pressure or flow during this treatment. In fact, aggravation of symptoms such as retinal hemorrhage, induced by central retinal vein occlusion and hypoxic retinopathy preceding the spontaneous regression of spontaneous cavernous sinus fistulas has been reported (Miki et al. 1988).

One factor that may possibly influence the efficacy of manual compression therapy is the dependence of the cerebral venous drainage on the posture of the patient. Recent studies have shown that the internal jugular vein serves as a main drainage vessel only in the supine position. When standing, this function is mainly taken over by the vertebral venous plexus (Gisolf et al. 2004). Consequently, compression of the IJV when standing or sitting will likely be less effective.

Thus, until controlled data become available, it remains doubtful whether or not manual compression therapy is in fact effective as a single treatment modality. There is otherwise no question that reducing the flow and pressure within the AV shunting communication is a useful adjunctive therapy to both transarterial and transvenous occlusion techniques. If consequently performed by a cooperative patient, it may even be effective as a single (conservative) treatment modality in direct CCF (Spinnato et al. 1997).

Some investigators recommend the external compression of the SOV at the inner eye angle before the vein joins the angular vein (Locke 1924) or direct ocular compression (Isamat et al. 2000). Blocking the venous outflow in a case with anterior drainage may have similar untoward effects, causing either aggravation of ophthalmic symptoms or rerouting the venous flow and inducing cortical drainage.

Case Illustration XIII is an example in which manual SOV compression resulted in worsening of the symptoms (Fig. 9.2). The patient had to undergo subsequent transarterial embolization with particles to reduce the AV shunting.

9.3

Controlled Hypotension

Case Report VIII (Fig. 9.3.)

A 72-year-old woman presented with right chemosis, exophthalmos, glaucoma and loss of visual acuity of 0.05 in the right eye (09/17/1999). Performing manual carotid compressions, she felt subjectively better and had a visual acuity of 0.2 (09/29/1999). An angiogram was performed on 10/11/99, revealing a dural AVF of the left CS fed by the left meningohypophyseal trunk and draining into the right SOV. Ophthalmologically, there was a suspicion of a superior ophthalmic vein thrombosis and thus, low-molecular heparin was prescribed. Two weeks later, left retinal hemorrhages were found, and anticoagulation was suspended. Treatment of the AVF became necessary. Since embolization of the small ICA pedicle was considered dangerous, controlled hypotension was proposed. Her BP was lowered from 160/100 to 80/45, while the mean arterial pressure was maintained around 60 mmHg using propofol and nitroglycerine. After 8 min of hypotension, the patient suddenly noticed that her vision was clearer and better. In fact, her visual acuity improved over several days and was 0.4 in the RE and 0.5 in the LE at ophthalmologic FU 3 weeks later. The glaucoma treatment was stopped. The patient remained symptom free until 5 years later at the end of 2004.

The induction of controlled hypotension for occlusion of DCSFs is a new approach, which has not been widely communicated (de Miquel et al. 2001; 2005; Ornaque et al. 2003). The first description was from De Miquel et al. (2001), who reported eight consecutive patients with DAVFs, including two DCSFs who underwent 30 min of controlled hypotension using sodium nitroprussiate, esmolol and nitroglycerine. In four patients, the symptoms lessened; in two, angiography confirmed occlusion.

In 2003, Ornaque et al. reported a DAVF of the transverse sinus for which controlled hypotension was performed by lowering the blood pressure under general anesthesia utilizing propofol. The authors discovered the possible influence of low blood pressure on DAVF thrombosis and occlusion in a patient with hypovolemic shock due to massive hematoma after unsuccessful transfemoral embolization. A total of 13 patients were treated without general anesthesia using various blood pressure lowering drugs, including nitroglycerin, urapidil and nitroprussi-

ate. This group included spinal AVFs (n = 3), DAVFs (n = 2) and DCSFs (n = 8). In four patients (31%), complete occlusion was accomplished, in four others the symptoms improved, in five (over 38%), there were no changes. The mean arterial pressure was lowered to 50–60 mmHg for a duration of 30–45 min. The patient reported by the authors was a 48-year-old male

with a DAVF of the right transverse sinus initially undergoing partial embolization and was planned for surgery. Controlled hypotension during the general anesthesia using propofol for 90 min resulted in complete occlusion prior to surgical exploration. An arteriogram confirmed that the fistula remained closed for 15 days and during the following 6 months.