Introduction

Type IV Ehlers-Danlos syndrome (EDS) is a rare genetic condition characterized by extreme fragility of blood vessel walls. The most common neurovascular complication is a spontaneous direct carotid-cavernous fistula (CCF) [1], usually manifested by progressive chemosis, proptosis, ophthalmoplegia and declining visual acuity that can lead to blindness [2]. The visual prognosis of these patients is determined largely by the size of the fistula [3]. Reflux into cerebral veins can cause haemorrhage.

Standard treatment of CCF is now endovascular embolization using balloons or coils [4]. However, owing to the extreme fragility of the blood vessels, this procedure carries a significant risk of complications [5]. Diagnostic angiography alone is associated with a mortality of over 10%, which doubles with endovascular manipulation [5]. We report a novel approach to this problem with open surgical access to neck vessels, allowing normal endovascular techniques to be deployed in relative safety.

Case report and technical notes

A 34-year-old woman with known type IV EDS developed severe left-sided headache while snorkelling. Intermittent retro-orbital pain and a feeling of fullness behind the left eye continued over the next few weeks, while she was treated for presumed sinusitis and conjunctivitis. Following this, there was increased redness and protrusion of the left eye. She presented to hospital with a rushing sound in the left ear, intermittent right arm weakness and an occasional difficulty in finding words. MRI revealed a left CCF, as evidenced by an enlarged left superior orbital vein and dilated cavernous sinus. Dilated leptomeningeal veins were noted over the left temporal lobe. Visual acuity was 6/6 in the left eye; the right eye was amblyopic, with an acuity of 6/18 as a result of childhood strabismus.

Because of the high risk of vascular damage from angiography, definitive investigation and treatment was deferred. (Her mother had died of an uncontrolled haemorrhage after varicose vein surgery.) Over the next 3 months, symptoms progressed. Acuity in the left eye deteriorated (from 6/6 to 6/9), with diplopia and conjunctival and retinal engorgement (Fig. 1a).

Fig. 1
figure 1

Colour photographs of a 34-year-old woman with type IV EDS and a left CCF, showing clinical appearances before (a) and 1 month after (b) management by occlusion of the fistula

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She then presented acutely with sudden-onset left frontal headache. CT revealed a left temporal haemorrhage, and the decision was made to proceed with invasive management and attempt closure of the fistula.

To avoid transfemoral arteriography, the carotid artery and jugular vein were exposed by direct neck dissection. Two endovascular sheaths were introduced (Fig. 2a). The wound was closed around the sheaths and the patient heparinized before transfer from theatre to the angiography suite (Fig. 2b). Angiography confirmed a large fistula between C4 and C5 portions of the left carotid siphon and the cavernous sinus (Fig. 3a). The fistula drained anteriorly into the superior orbital vein, posteriorly into the inferior petrosal sinus, across the midline into the contralateral cavernous sinus and retrogradely into the left superficial middle cerebral vein. There was no antegrade flow in the right internal carotid artery beyond the fistula. The right cerebral hemisphere was collateralized from the left via the anterior communicating artery.

Fig. 2
figure 2

Colour photographs taken in the operating theatre, demonstrating the direct neck dissection. Two endovascular sheaths were introduced (a), and the wound was then closed around the sheaths (b) prior to heparinization and transfer to the angiography suite

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Fig. 3
figure 3

CCF demonstrated by angiography, before arterial injection (a) and following the first session in the angiography suite (b). Normal antegrade flow in the internal carotid artery was restored after the second procedure (c)

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Using a wire-guided balloon catheter (Hyperglide, Micro Therapeutics, Irvine, Calif.) in the carotid siphon to prevent extrusion of coils through the fistula into the carotid artery, 21 Guglielmi detachable coils (GDC; Boston Scientific, Cork, Ireland) were deployed in the cavernous sinus via catheters threaded up through the inferior petrosal sinus (Fig. 3b). This produced a substantial reduction in the shunt, and the catheters and sheaths were removed. Haemostasis was achieved by manual pressure. The patient was kept sedated and ventilated overnight on the neurocritical care unit.

Following the procedure, the bruit was diminished. However, proptosis persisted and conjunctival oedema gradually worsened. Ocular movements were further restricted and the left pupil had become dilated. Five days following the first procedure, the patient was taken back to theatre, where a similar approach was adopted, exposing the neck vessels in theatre and then transferring to the angiography suite. Angiography confirmed substantial persistent flow through the fistula, including drainage into the left superior orbital vein. Using a balloon again to define and protect the carotid lumen at the level of the fistula, 14 further GDCs were packed into the left cavernous sinus until the fistula was occluded. Normal antegrade flow in the internal carotid artery was restored (Fig. 3c).The sheaths were removed and heparin continued for 24 h followed by low-dose aspirin to prevent thromboembolic complications. Within hours, conjunctival swelling had settled and vision in the left eye had started to improve. The bruit had disappeared and the eye movements were improving. The patient was discharged after 20 days as an inpatient, and at 1- and 6-month follow-up she was asymptomatic, with a normal visual acuity of 6/6 (Fig. 1b).

Discussion

EDS is a heterogeneous group of connective tissue disorders affecting 1 in 500,000 to 1 in 5,000 individuals [6]. Its classification is based on clinical and pathological features, and has undergone repeated revisions as the basis of the underlying molecular defects is discovered. Currently, eight types are described: types I–VII and X [7]. Type IV EDS, also known as vascular or malignant type, represents 4% of EDS cases [8, 9] and is rare, with a prevalence estimated as 1 in 105 to 106. It is usually described as an autosomal dominant disorder, although there have been reports of it being inherited in a recessive fashion [10]. Type IV EDS is characterized by fragile blood vessels and visceral walls, due to a defect in the synthesis of type III collagen, which is usually found in abundance in the vascular tree. This defect is caused by mutations of the COL3A1 gene, which is located on chromosome 2 [6, 10]. Endovascular procedures are therefore hazardous.

Patients with type IV EDS present with ruptured blood vessels, aneurysms, dissections and fistulas, as well as spontaneous pneumothoraces and visceral rupture. The most common neurovascular complication of type IV EDS is a CCF [1]. In a series of 202 patients with type IV EDS reviewed by North et al. [9], intracranial haemorrhage was the most common neurovascular complication, accounting for 4% of cases. Because of potential complications, the diagnosis of type IV EDS should be considered in all patients with a CCF before proceeding to any surgery or endovascular intervention [11].

Cerebral angiography was pioneered by Moniz in 1927, and early techniques involved direct carotid puncture. Following the introduction of catheters allowing a transfemoral approach by Seldinger in 1953, cerebral angiography has become a safer procedure with fewer serious complications [12]. Direct carotid puncture is now reserved for difficult cases. An effective treatment for CCF only became possible with the development of endovascular balloons, which were first described in 1971 by Serbinenko [13]. Standard treatment for CCF is now endovascular, using one of two basic techniques. One technique requires arterial access, and a balloon can be passed through the fistula and inflated in the cavernous sinus to tamponade the defect. Alternatively, coils can be placed in the cavernous sinus from the arterial or venous approach. The latter method requires both venous and arterial access. In 1991, Guglielmi et al. [14] reported the development of a technique combining electrolysis and electrothrombosis, and GDCs have revolutionized intracranial endovascular procedures.

In type IV EDS, the fragility of the blood vessels renders the standard endovascular interventions very hazardous. CCFs in patients with type IV EDS are relatively rare, and few cases have been reported. Early reviews of the literature highlighted very high rates of morbidity and mortality [5]. The first case report was published in 1955. Francois et al. [15] had adopted a conservative approach, resulting in blindness. Surgical treatments included direct surgical repair [5], ocular enucleation [16] and ligation of carotid arteries [5]. The first successful occlusion of a CCF in type IV EDS by interventional neuroradiology was reported in 1988 [17]. Occlusion was achieved using a detachable balloon and a solidifying mixture of silicone to enable permanent distension of the balloon. Schievink et al. [5] reviewed a total of 17 cases of CCF in type IV EDS that had been reported prior to 1991. They concluded that diagnostic neuroangiography alone carried morbidity and mortality rates of 36% and 12%, respectively. The mortality rate increased to 24% when therapeutic, in addition to diagnostic, procedures were analysed. A further 35% died from vascular or visceral complications unrelated to endovascular intervention. More recent cases have been treated successfully with both balloon occlusion [18] and techniques utilizing GDCs [4, 19]. In 2000, Kanner et al. [4] reviewed 14 endovascularly treated CCFs. They found two perioperative deaths (14%) and occlusion of the fistula in nine patients (64%). However, in four of these patients the internal carotid artery was occluded. It has been suggested that in patients with type IV EDS, the usually safe and effective arterial approach to the CCF is contraindicated, because there is an increased risk of arterial dissection. It is considered safer to work from the venous side of the fistula when attempting occlusion in these patients [4, 20, 21]. It has also been proposed that GDCs are preferable to balloons in these patients, because they can be controlled more easily and are less traumatic [4].

In our patient, two separate procedures were required to occlude a direct, high-flow CCF successfully. That it required two attempts testifies to the size of the arteriovenous shunt, but also, to some extent, to the safety of the procedure. Both procedures involved carotid puncture, the first also utilizing a jugular approach. Both involved the use of GDCs. We opted for direct puncture of the carotid and jugular vessels in the neck, avoiding the risks of the usual transfemoral approach. We surmised that an open procedure would minimize the risk of carotid dissection or damage to the jugular vein, but that if a carotid dissection did occur, it might still be possible to reach the fistula and occlude it. In the event, we were able to occlude the fistula, leaving the internal carotid artery intact. This represents a novel approach which, to our knowledge, has not previously been used in the management of CCFs in EDS patients.