Staged endovascular and surgical management of vertebral arteriovenous fistula with ruptured aneurysm and pseudoaneurysm in neurofibromatosis type 1 complicated by fatal reperfusion injury: illustrative case

Abstract

BACKGROUND

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with diverse systemic manifestations. Severe vertebral vascular complications are uncommon, and the combination of a vertebral arteriovenous fistula, ruptured aneurysm, and pseudoaneurysm is extremely rare and life-threatening. Management of these complex malformations remains challenging. Moreover, postoperative brainstem reperfusion injury after combined endovascular and surgical treatment has been poorly reported, and its clinical hazards are often underestimated.

OBSERVATIONS

This case involves a 41-year-old female with clinically confirmed NF1 and a positive family history. She presented with a progressive cervical mass and left upper limb neurological deficits. CT angiography and digital subtraction angiography confirmed the vascular lesions. The patient underwent staged endovascular embolization and open resection. Imaging verified complete lesion occlusion and relieved mass compression. Nevertheless, she developed cerebral hyperperfusion syndrome postoperatively and died of delayed fatal brainstem reperfusion injury on postoperative day 10.

LESSONS

Staged endovascular surgical treatment is a viable option for complex NF1-related vertebral vascular lesions. Chronic hypoperfusion from arterial steal increases reperfusion injury risk, requiring strict perioperative monitoring. Routine vascular screening is recommended for NF1 patients to detect hidden vascular lesions and facilitate early intervention.

https://thejns.org/doi/10.3171/CASE26583

Neurofibromatosis (NF) is a group of autosomal dominant genetic disorders characterized by the aberrant differentiation of neural crest cells. NF1 is present predominantly during childhood and is characterized by key clinical features such as the presence of six or more café-au-lait macules distributed across the body, freckling in the axillary or inguinal regions, and the development of multiple neurofibromas. Furthermore, NF1 is often associated with complex multisystem abnormalities, including optic pathway gliomas and scoliosis. NF1 may affect multiple organ systems, but vertebral artery aneurysm rupture is extremely rare. The diagnosis and management of NF1 are often delayed because of nonspecific symptoms. Clinicians should maintain a high index of suspicion for vascular lesions in NF1 patients who exhibit a progressively enlarging neck mass in conjunction with symptoms such as limb weakness, numbness, and pain.^1,2

This report describes a patient with NF1 initially presenting with a neck mass accompanied by neurological dysfunction. Subsequent clinical and pathological examinations confirmed the presence of a left vertebral artery arteriovenous fistula, the rupture of a vertebral artery aneurysm, and the formation of a secondary pseudoaneurysm. This report describes the clinical features, diagnosis, and treatment and emphasizes the importance of perioperative risk assessment and monitoring.

Illustrative Case

Medical History

A 41-year-old female patient was admitted to our hospital with a progressively enlarging left cervical mass, accompanied by weakness, numbness, and pain in the left upper extremity for more than 1 month. One month before her admission, she noticed a firm, nontender mass on the left side of her neck, approximately the size of an egg. During the following weeks, the mass continued to increase in size, and the weakness, numbness, and pain in the left upper extremity gradually worsened, although she was still able to move her fingers and perform daily activities. Numbness was distributed mainly in the forearm and hand distal to the left wrist joint, whereas pain was prominent in the left shoulder, neck, and lateral upper arm. As the mass enlarged, she gradually developed dysphagia and dyspnea, accompanied by ptosis of the left upper eyelid. CT angiography (CTA) of the head and neck performed at another hospital suggested a ruptured left vertebral artery aneurysm with pseudoaneurysm formation.

The patient had a lifelong history of multiple light brown macules distributed over the body surface, which had increased in size and number with age, accompanied by scattered small cutaneous nodules. Importantly, she had a positive family history: her mother and daughter also exhibited similar skin manifestations and were clinically diagnosed with NF1.

Physical Examination

General physical examination revealed numerous café-au-lait macules of varying sizes across the body, concentrated especially around the umbilicus. Spinal scoliosis was also observed. A palpable mass measuring approximately 12 × 8 cm was found on the left side of the neck. The mass was nontender, nonmobile, firm in texture, and without surface ulceration or erythema. Synchronous pulsation with the radial artery was detected, and a blowing vascular murmur was heard on auscultation (Fig. 1).

FIG. 1.

Clinical manifestations of NF1. A and B: Left cervical mass measuring approximately 12 × 8 cm. C: Multiple café-au-lait macules of varying size and pigmentation, with scattered small dermal nodules on the abdominal wall. D: Ptosis of the left upper eyelid.

Neurological examination revealed left-sided hyposmia and left upper eyelid ptosis. The pupils were round but anisocoric: the right pupil was 2.5 mm in diameter and the left was 2.0 mm. The muscle strength of the left upper extremity was 3/5, while that of the right upper extremity was 5/5. Left shoulder elevation was weakened, and left neck rotation was significantly restricted. Hyperalgesia to pinprick stimulation was present in the left upper extremity. The muscle strength of both lower extremities was approximately 5/5 (Fig. 1).

Imaging Findings

Preadmission head and neck CTA confirmed a ruptured aneurysm of the left vertebral artery with secondary pseudoaneurysm formation. After admission, a complete imaging evaluation including noncontrast CT, contrast-enhanced CT, CTA, and cervical and cervical spinal cord MRI was performed. The main findings were as follows: 1) The left vertebral artery was tortuous and dilated, with a saccular dilatation of 11 mm in the V1 segment. 2) A large saccular aneurysm was found in the V2 segment, with the ostium anterior to the vertebral artery. The aneurysm was approximately 70 × 69 mm in size, with mural filling defects and no obvious signs of dissection. 3) The lesion compressed and displaced the adjacent thyroid gland, cervical vascular structures, and soft tissue. 4) The left C5 intervertebral foramen was enlarged, and part of the pseudoaneurysm extended into the spinal canal, causing spinal cord compression. 5) Cervical kyphosis and local right scoliosis were observed, but no other significant abnormalities were detected (Fig. 2).

FIG. 2.

Preoperative vascular and spinal images. A and B:T2-weighted MR images showing compression of the cervical spinal cord by the aneurysm. C and D:Tortuosity and dilatation of the left vertebral artery, with saccular dilatation in the V1 segment (maximum diameter approximately 11 mm) causing compression and displacement of the adjacent thyroid gland, cervical vessels, and soft tissues. E and F: Large aneurysm (70 × 69 mm) arising from the V2 segment of the left vertebral artery, with its orifice located anterior to the vertebral artery.

Treatment

After multidisciplinary consultation involving neurosurgery, interventional radiology, anesthesiology, and other related specialties and after excluding surgical contraindications, a staged treatment plan was formulated based on the lesion characteristics and the patient’s general condition.

Stage 1: Endovascular Embolization of the Left Vertebral Artery

Stage 1 aimed to occlude the pseudoaneurysm in the proximal and distal segments, reduce sac pressure, and relieve neural compression.

Under general anesthesia, a 5-Fr vertebral artery catheter was inserted into the left V1 segment using a Loach guidewire. An Echelon 10 microcatheter was advanced to the proximal neck of the V2 pseudoaneurysm. A 10-mm × 34-cm detachable coil was initially deployed, followed by five additional coils to achieve dense packing. Afterward, 0.5 mL of Onyx glue was injected to reinforce the embolization. Postprocedural digital subtraction angiography (DSA) confirmed complete occlusion of the proximal segment.

Subsequently, the 6-Fr arterial sheath was replaced with an 8-Fr sheath. An intermediate catheter was inserted into the right V4 segment, and a microcatheter was advanced to the distal neck of the left V3 pseudoaneurysm via a contralateral transvascular approach. A 14-mm × 20-cm detachable coil was deployed, followed by six additional coils, and 1.0 mL of Onyx glue was injected to complete distal embolization.

Intraoperative DSA revealed a giant pseudoaneurysm in the V2 segment of the left vertebral artery with a size of approximately 13.1 × 10.1 × 9.5 mm. Antegrade blood flow in the left vertebral artery was severely blocked, with compensatory retrograde perfusion from the right vertebral artery to the left V3 segment. After embolization, complete occlusion of the proximal and distal ends of the pseudoaneurysm was confirmed. The left vertebral artery was no longer visible, and there was no contrast filling in the pseudoaneurysm. The basilar artery and posterior circulation vessels, which were not visualized preoperatively because of vertebral artery steal syndrome, were clearly visible after the procedure (Fig. 3).

FIG. 3.

Detailed analysis of vascular interventions. A:Digital subtraction angiogram confirming a giant pseudoaneurysm in the V2 segment of the left vertebral artery. B: Anterograde flow in the left vertebral artery is obstructed, with compensatory retrograde perfusion of the left V3 segment from the right vertebral artery. C and D: Dense embolization of the proximal pseudoaneurysm neck using detachable coils. E–G:Contralateral transvascular approach for dense coil embolization of the distal pseudoaneurysm neck. H–J: Postembolization angiograms showing complete occlusion of the left vertebral artery and pseudoaneurysm, with clear visualization of the basilar artery and posterior circulation.

Stage 2: Open Resection of the Pseudoaneurysm

The purpose of the procedure was to further resect the pseudoaneurysm wall, evacuate the intraluminal hematoma, completely relieve compression on surrounding tissues and the spinal cord, and obtain pathological specimens.

Under general anesthesia, the patient was placed in the supine position with the head slightly rotated to the right. An approximately 8-cm-long oblique incision was made along the anterior border of the left sternocleidomastoid muscle. Blunt dissection was performed carefully to expose the aneurysm sac, where a pulsatile mass was palpated. A large-bore needle was used to aspirate dark red blood, confirming entry into the aneurysm cavity. The sac was then incised, and the thrombus was aspirated and irrigated with saline. A portion of the aneurysm wall was resected for pathological examination. Hemostasis was achieved using bipolar electrocoagulation and fibrin glue, and the incision was closed layer by layer (Fig. 4).

FIG. 4.

Intraoperative photographs. A and B: Opened aneurysm sac with embolization coils placed at both proximal and distal orifices. C: Debridement and meticulous hemostasis of the aneurysm sac; hemostatic agents and fibrin glue were applied.

Early Postoperative Recovery

Postoperative MRI showed nearly complete occlusion of the pseudoaneurysm, with a residual cavity of approximately 37 × 15 mm. Heterogeneous signal intensity with a gas-fluid level was observed, and no obvious enhancement was observed on contrast-enhanced images. The embolized left vertebral artery was not visualized. Pathological examination of the aneurysm wall revealed fibrous tissue with hyaline and myxoid degeneration, which was consistent with an aneurysm wall. The cavity contained a mixed thrombus (Fig. 5A–E).

FIG. 5.

Postoperative MR images. A–E:The left vertebral artery pseudoaneurysm is largely occluded, with a residual cavity measuring 37 × 15 mm that demonstrates a gas-fluid level and no significant enhancement. The embolized left vertebral artery is not visualized, and compression of the cervical spinal cord is relieved. F:Multiple dilated collateral veins are observed in the paravertebral region. Soft tissue density shadows are present in the subcutaneous tissue of the left chest wall, indicating potential effusion and extravasation.

Whole-exome sequencing was performed and revealed no pathogenic variants in the NF1 gene. Variants of uncertain clinical significance were identified in COL1A2 and RYR1.

Postoperative Complications and Outcomes

One week after surgery, the patient developed pain in the left neck, shoulder, axilla, and hypochondriac region, accompanied by recurrent vomiting. CT showed near-complete resolution of the pseudoaneurysm, local encapsulated gas accumulation, and multiple dilated collateral veins in the paravertebral region from the lower cervical to upper thoracic segments. Multiple patchy soft tissue shadows were seen in the left chest wall, indicating effusion and hemorrhage caused by increased pressure in branch vessels after left vertebral artery occlusion (Fig. 5F).

On postoperative day 7, the patient developed dizziness, nausea, and vomiting, suggesting cerebral hyperperfusion or reperfusion injury. On postoperative day 10, she suddenly developed right pupillary dilatation, loss of light reflex, tachypnea, apnea, and undetectable blood pressure and oxygen saturation. ECG showed ventricular fibrillation. Emergency resuscitation, which included endotracheal intubation, mechanical ventilation, chest compression, and vasoactive drugs, was performed. However, the patient’s condition did not improve, and she eventually died of brainstem hyperperfusion syndrome, progressive reperfusion injury, and multiple organ failure.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

The exact pathogenesis of vertebral artery lesions in patients with NF1 remains unclear. Three major mechanisms have been proposed: NF1 gene mutations leading to defective vascular structure, venous hypertension secondary to spinal deformities, and the combined effect of the above two factors.^1,3 Clinically, NF1-associated vascular lesions are easily misdiagnosed when patients only present with isolated neurological deficits. In individuals with NF1 complicated by spinal deformities, newly developed limb dysfunction strongly suggests underlying vascular malformations such as arteriovenous fistula; a progressively enlarging neck mass further indicates a ruptured aneurysm or pseudoaneurysm. Early imaging examinations, including CTA and DSA, are critical for obtaining a definitive diagnosis.⁴ Previous case series have demonstrated that NF1-related vertebral artery lesions occur predominantly in females and mostly involve the C2–6 segments, and arteriovenous fistula accounts for the majority of cases.⁵ According to our summary of reported cases, rupture is not uncommon, and delayed severe complications can lead to an overall mortality rate of approximately 11.1%.

Although modern genetic testing can detect most pathogenic NF1 variants, a negative genetic result cannot exclude the clinical diagnosis due to large-fragment deletions, splice-site or intron-exon boundary variants, and undetectable low-level mutations that are missed by conventional next-generation sequencing and multiple ligation-­dependent probe amplification.^6,7 Typical clinical manifestations, including multiple café-au-lait macules, a positive family history, and multiple neurofibromas, are sufficient to confirm the diagnosis of NF1.

For ruptured vertebral artery aneurysms, complete occlusion of both the proximal and distal segments of the parent vessel is required to avoid retrograde perfusion and lesion recurrence.⁸ Consistent with mainstream strategies reported in previous cases, we adopted a staged embolization approach to achieve total lesion exclusion.⁸ In published cases of NF1-related vertebral artery diseases, endovascular embolization is the first-line treatment, and parent artery occlusion is widely applied in most patients.^1,3,9,10

Differential Diagnosis and Limitations

The diagnosis of cerebral hyperperfusion syndrome and subsequent brainstem reperfusion injury in this case was established primarily on clinical and temporal grounds rather than on definitive perfusion imaging. The onset of dizziness, nausea, and vomiting on postoperative day 7, followed by rapid neurological deterioration on day 10, is consistent with the typical time course of reperfusion injury in a chronic hypoperfusion scenario. Furthermore, the presence of severe preoperative vertebral steal syndrome with chronic brainstem ischemia represents a well-established risk factor for this complication. Notably, postoperative imaging demonstrated marked dilatation of the paravertebral collateral veins and soft tissue extravasation in the left chest wall (Fig. 5F), which indirectly supports a global hemodynamic shift with increased vascular permeability, consistent with hyperperfusion physiology.

With that in mind, it is important to consider several alternative diagnoses in the differential diagnosis. First, progressive posterior fossa infarction with cytotoxic edema and mass effect could present similarly, particularly given the abrupt neurological decline. Second, hemorrhagic transformation of a subclinical infarct or remote surgical site bleeding could also account for brainstem compression. Third, it is important to consider obstructive hydrocephalus due to edema in the posterior fossa as part of the differential diagnosis.

We acknowledge that the absence of dedicated intracranial perfusion imaging (CT perfusion or MR perfusion) is a notable limitation of this report. The patient’s rapid clinical deterioration and subsequent death precluded the completion of such studies. Definitive differentiation between hyperperfusion and progressive infarction would require quantitative perfusion parameters such as increased cerebral blood volume and cerebral blood flow. In the absence of such data, our diagnosis remains one of high clinical suspicion supported by indirect radiological and clinical evidence rather than definitive confirmation. This limitation underscores the importance of performing perfusion studies early in high-risk patients to facilitate timely diagnosis and intervention.

Lessons

Cerebral hyperperfusion syndrome and reperfusion injury are life-threatening complications after vertebrobasilar intervention, especially in patients with chronic brainstem ischemia and arterial steal syndrome. Long-term vascular hypoperfusion impairs cerebral autoregulation; rapid restoration of blood flow after revascularization triggers vascular injury, cerebral edema, and brainstem compression.^11,12 In our case, preoperative angiography confirmed severe chronic ischemia caused by steal syndrome. Although the posterior circulation perfusion was restored after staged treatment, the patient eventually died of delayed fatal cerebral hyperperfusion syndrome and reperfusion injury. Early warning signs such as dizziness and vomiting should be closely monitored during the postoperative period. Intracranial pressure management, anti-inflammatory and neuroprotective treatments, and 1–2 weeks of intensive surveillance are essential for high-risk patients.^11,12

Head and neck high-flow arteriovenous fistulas are strongly correlated with NF1 and intracranial aneurysms, and the vertebral artery is involved in most such cases. Typical manifestations include a pulsatile cervical mass, vascular murmur, and neurological deficits. Regular vascular screening, especially color Doppler ultrasound, is recommended for high-risk NF1 patients to achieve early diagnosis and intervention of life-threatening vascular complications.¹³

We report an extremely rare case of NF1 complicated by a left vertebral artery arteriovenous fistula, ruptured aneurysm, and pseudoaneurysm, in which the patient presented with a progressive cervical mass and neurological symptoms in the upper extremity. Staged endovascular embolization and open surgery resulted in complete lesion occlusion and successful decompression, but the patient died of a postoperative delayed fatal brainstem reperfusion injury. This case highlights the risk of severe vascular complications in NF1 patients, emphasizing the need for regular vascular screening, early diagnosis, multidisciplinary treatment, and rigorous perioperative monitoring. Individualized comprehensive management is crucial for improving the prognosis of such complex cases.

Acknowledgments

The Doubao large language model was used for English-language polishing, sentence simplification, and academic expression optimization of the manuscript. We independently verified all core clinical content, data analysis, and manuscript logic.

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: Zhang, Wu, Zhou. Acquisition of data: all authors. Analysis and interpretation of data: all authors. Drafting the article: Wu, Yang. Critically revising the article: Zhang, Wu. Reviewed submitted version of manuscript: Zhang, Wu. Approved the final version of the manuscript on behalf of all authors: Zhang. Study supervision: Zhang.

Correspondence

Wei Zhang: Guangdong Pharmaceutical University, Guangzhou, Guangdong, China. zw_gdpu@outlook.com.