Spontaneous carotid-cavernous sinus fistula with fibromuscular dysplasia: illustrative case

Abstract

BACKGROUND

A carotid artery cavernous sinus fistula (CCF) is an abnormal shunt of blood vessels, allowing blood to flow directly or indirectly from the carotid artery into the cavernous sinus. The most common cause of spontaneous CCF (s-CCF) is ruptured internal carotid-cavernous sinus aneurysms, while fibromuscular dysplasia (FMD) is rare. FMD is a rare, idiopathic, segmental, noninflammatory, and nonatherosclerotic disease of medium-sized arteries, characterized by abnormal cell proliferation and distortion of arterial wall architecture. The authors report the case of a patient with CCF with FMD.

OBSERVATIONS

The authors report the case of a young woman with s-CCF who was effectively treated with coiling and balloon compression. Subsequently, she was shown to have FMD susceptibility genes using single nucleotide polymorphism (SNP) testing in the follow-up phase.

LESSONS

The authors report the case of s-CCF caused by FMD in a young patient. SNP testing validated the existence of FMD susceptibility genes. The patient successfully recuperated following endovascular embolization therapy. For patients with s-CCF, the possibility of FMD should be considered, especially in young women with a family history.

https://thejns.org/doi/10.3171/CASE24622

Fibromuscular dysplasia (FMD) is a rare, idiopathic, segmental, noninflammatory, and nonatherosclerotic disease of medium-sized arteries, characterized by abnormal cell proliferation and distortion of arterial wall architecture.¹ FMD mostly affects systemic blood vessels, with the renal arteries being the most frequently impacted. The extracranial carotid arteries and vertebral arteries are commonly affected as well. When the internal carotid artery is involved, patients can present with headache, pulsatile tinnitus, transient ischemic attack, or stroke.² Here, we report the case of a patient with a carotid artery cavernous sinus fistula (CCF) caused by FMD.

Illustrative Case

This 26-year-old female with no history of trauma or special personal medical history presented with swelling in her right eye and reduced vision lasting more than 2 weeks. The patient’s mother had experienced similar symptoms 20 years previously but did not receive systematic treatment and died. The physical examination revealed a slight protrusion of the right eye, conjunctival redness, periorbital skin edema, absent light reaction, absent accommodation reflex, and inadequate eye movement. The results of the head CT, head MRI, head and neck CT angiography (CTA), digital subtraction angiography (DSA) studies all indicated a right carotid-cavernous fistula. During DSA, we noticed that the left renal artery was tortuous, with narrowing of the internal carotid artery, leading us to consider the possibility of CCF caused by FMD (Fig. 1).

FIG. 1.

A: Preoperative CT scan. B: Preoperative MR image. C: Preoperative CT angiogram. D: Preoperative digital subtraction (DS) angiogram, frontal view, of the left renal artery. E: Preoperative DS angiogram, lateral view, of the right internal carotid artery. F: Intraoperative DS angiogram. The white arrow indicates that the left renal artery was tortuous, the red arrows indicate the location of the fistula, and the blue arrow indicates superior ocular venous drainage.

Given the patient’s suspected FMD, aneurysm dilation and stenosis were considered possible throughout the vasculature. To avoid iatrogenic pseudoaneurysm formation and minimize the risk of secondary injury by ensuring successful puncture on the first attempt, we used ultrasound guidance and the Seldinger technique to insert a 6-Fr arterial sheath into the femoral artery. On reaching the fistula, detachable coils were deployed to reduce fistula flow. Despite this, residual flow was observed. Subsequently, an EVAL (Kuraray Co. Ltd.) nonadhesive liquid embolic agent was used to occlude the fistula. Because precise occlusion is difficult to achieve without overfilling, a balloon occlusion catheter system was deployed promptly when angiography showed leakage of the embolic agent into the internal carotid artery, preventing excessive extravasation. Repeat angiography confirmed fistula closure, prompting immediate removal of the microcatheter and balloon. An intracranial stent was then deployed to compress the embolic agent against the vessel wall, preventing detachment and subsequent distal microvascular occlusion. Given the current lack of effective treatment for FMD lesions, no intervention was performed, and the patient was scheduled for follow-up. Postoperative DSA of the right internal carotid artery revealed normal venous drainage and adequate blood flow to the anterior and middle cerebral arteries. The DSA examination conducted 6 months postsurgery revealed satisfactory blood flow in all sections of the right internal carotid artery, the absence of any unusual drainage vein in the cavernous sinus, no reappearance of the fistula, and irregular narrowing of the right internal carotid artery interspersed with aneurysm-like dilation (Fig. 2). On the 1st day postoperatively, the patient reported pain relief compared with before, with a slight improvement in the protrusion and swelling of the right eye, and no intracranial murmur was heard at rest. The swelling and exophthalmos of the patient’s right eye completely disappeared 6 months after surgery (Fig. 3).

FIG. 2.

DSA of the right internal carotid artery revealed normal venous drainage and adequate blood flow to the middle cerebral arteries after surgery. The DSA examination conducted 6 months postsurgery revealed satisfactory blood flow in all sections of the right internal carotid artery, the absence of any unusual drainage vein in the cavernous sinus, no reappearance of the fistula, and irregular narrowing of the right internal carotid artery interspersed with aneurysm-like dilation. A: DS angiogram, frontal view, of the right internal carotid artery after surgery. B: DS angiogram, lateral view, of the right internal carotid artery after surgery. C: DS angiogram, frontal view, of the right internal carotid artery 6 months after surgery. D: DS angiogram, lateral view, of the right internal carotid artery 6 months after surgery.

FIG. 3.

Postoperative symptoms of right eye protrusion and swelling improved slightly. The swelling and exophthalmos of the patient’s right eye completely disappeared 6 months after surgery. A: The patient’s preoperative ocular symptoms. B: The patient’s postoperative ocular symptoms. C: The patient’s ocular symptoms 6 months after surgery.

One year later, the patient wanted to confirm whether she had FMD. A venous blood sample was collected for single nucleotide polymorphism (SNP) testing using EDTA anticoagulation. The patient was found to have the variant rs9349379 at the PHACTR1 locus, the variant rs11172113 at the LRP1 locus, and 4 variants at the LIMA1 locus: rs7301566, rs4459386, rs10783342, and rs12815871, as shown in Supplemental Table 1. The prevailing perspective is that genes such as PHACTR1, LRP1, ATP2B1, LIMA1, and COL5A1 are susceptible to FMD.^3,4 The test results are consistent with the prevailing view, providing additional evidence of FMD potentially leading to CCF genetically.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

We report the case of spontaneous CCF (s-CCF) caused by FMD in a young patient. SNP testing validated the existence of FMD susceptibility genes. While several cases of CCF caused by FMD have been reported in the English-language literature, this is the first instance in which SNP testing was used to validate the existence of FMD susceptibility genes. The patient successfully recuperated following endovascular embolization therapy. For patients with s-CCF, the possibility of FMD should be considered, especially in young women with a family history.

Lessons

The histological categorization of FMD is no longer applicable in clinical practice. Instead, FMD is classified into focal and multifocal based on cerebral angiography.¹ Focal FMD consists of a single concentric (less than 1 cm) or tubular (1 cm or more) stenosis and can occur in any part of the blood vessel. Multifocal FMD, in contrast, is an alternating area of stenosis and dilation, producing a typical “beaded appearance” that usually affects the middle and distal parts of the affected blood vessels.⁵ Multifocal FMD is the most common type, accounting for 90%, followed by focal FMD, accounting for the remaining 10%.⁶

The international consensus on the diagnosis of FMD explicitly states that the presence of an aneurysm, dissection, or tortuosity alone is insufficient to diagnose FMD, and the presence of at least one focal or multifocal arterial stenotic lesion is required for diagnosis.¹ At present, the gold standard for the diagnosis of FMD is still DSA, but DSA is limited to select patients with severe or complex vascular manifestations, such as aneurysms related to dissection, false aneurysms, or poorly controlled medications. The preferred imaging modality is noninvasive CTA or MR angiography in some high-volume centers with vast experience. Ultrasound can also be used as an examination tool, but there is not enough evidence to recommend one imaging method over any other.¹,⁵,⁶ In our case, DSA revealed tortuosity in the left renal artery and irregular narrowing of the right internal carotid artery interspersed with aneurysm-like dilation; the patient was diagnosed with FMD.

The etiology of FMD remains unclear, and current studies suggest that it is related to hormones, smoking, and genetic factors. A prospective case-control study from Italy detected strong progesterone receptor expression in the smooth muscle cell nuclei of 6 patients with renal FMD.⁷ Numerous studies have shown that smoking is a risk factor for FMD, as current smokers tend to be diagnosed with FMD at an earlier stage than nonsmokers.⁸,⁹ Hereditary factors can also influence the development of FMD, as a genome-wide association analysis found genes such as PHACTR1, LRP1, ATP2B1, and LIMA1 to be associated with FMD and to have similarities with common cardiovascular illnesses.³ In 2020, Richer and colleagues identified a novel susceptibility locus for FMD, COL5A1.⁴

The treatment of s-CCF caused by FMD is largely similar to that of general s-CCF; however, several crucial details warrant attention during the surgical procedure. In our case, considering the coexistence of FMD, we performed the puncture under ultrasound guidance to minimize the risk of secondary injury to the patient. Furthermore, given the possibility of dissecting aneurysms in the patient’s overall vasculature, once the catheter reached the C1 segment of the internal carotid artery, we used a microguidewire to carefully advance the microcatheter along the true lumen to the distal portion of the lesion, avoiding entry into the false lumen to prevent further vascular damage.

Spontaneous CCF is usually caused by arterial hypertension, atherosclerotic vascular disease, pregnancy, minor trauma, vascular disease, and collagen vascular disease. The pathogenesis of s-CCF induced by FMD is different from that of s-CCF in general, and s-CCF induced by FMD might be secondary to the patient’s underlying FMD lesions, which form weak areas in the cavernous sinuses. This section twists and turns, and with the constant onslaught of blood flow, the walls of the blood vessels gradually thin. This defect predisposes patients to form s-CCF after mild stress, such as coughing or Valsalva movements. The onset of s-CCF with significant symptoms facilitates earlier diagnosis in patients with such FMD compared to patients with a general diagnosis of FMD. Therefore, for young patients with s-CCF, the possibility of FMD cannot be ignored.¹⁰

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Y Jiang, Tan, L Jiang, Pan, Yang, Pang, Bao, Huang, Peng. Acquisition of data: Y Jiang, L Jiang, Yu, Pan, Yang, Pang, Bao, Huang, Peng. Analysis and interpretation of data: Yu, Pan, Yang, Pang, Bao, Huang, Peng. Drafting the article: Y Jiang, Tan, Yu, Pan, Yang, Pang, Bao, Huang, Peng. Critically revising the article: Y Jiang, Yu, Yang, Pang. Reviewed submitted version of manuscript: Y Jiang, Tan, Pang. Approved the final version of the manuscript on behalf of all authors: Y Jiang. Statistical analysis: Pang. Administrative/technical/material support: Pang. Study supervision: Y Jiang, Peng.

Supplemental Information

Online-Only Content

Supplemental Table 1. https://thejns.org/doi/suppl/10.3171/CASE24622.

Correspondence

Yong Jiang: The Affiliated Hospital of Southwest Medical University, Luzhou, China. jiangyong@swmu.edu.cn.