Recurrent spontaneous cervical hemorrhage in a patient with neurofibromatosis type 1 requiring repeated endovascular embolization: illustrative case

Abstract

BACKGROUND

Neurofibromatosis type 1 (NF1) is a genetic disorder occasionally associated with vascular abnormalities, including arterial fragility and spontaneous rupture. Cervical hemorrhage related to NF1 is rare, yet potentially life-threatening, and its management presents significant challenges. Here, the authors report a rare case of NF1 complicated by recurrent spontaneous cervical hemorrhage requiring repeated endovascular embolization.

OBSERVATION

A 67-year-old man with NF1 presented with acute cervical swelling without a history of trauma. CT revealed a large cervical hematoma causing tracheal deviation, and CT angiography showed active extravasation from a branch of the thyrocervical artery. Emergency endovascular embolization using n-butyl-2-cyanoacrylate achieved hemostasis. The following day, recurrent hemorrhage developed from branches of the transverse cervical and internal thoracic arteries, necessitating repeat endovascular embolization. After the second intervention, no further bleeding occurred, and the patient recovered with supportive care.

LESSONS

In patients with NF1, cervical hemorrhage may recur early from a vascular territory distinct from the initially treated lesion. Even after a technically successful embolization, close early surveillance is required.

https://thejns.org/doi/10.3171/CASE26354

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by neurofibromas and café-au-lait macules. NF1 is also known to be associated with Lisch nodules, skeletal dysplasia, and a variety of CNS neoplastic lesions, most notably optic pathway gliomas and pilocytic astrocytomas.^1–3 Vascular abnormalities may also occur and include arterial stenosis, aneurysm formation, dissection, and spontaneous rupture. The reported prevalence of NF1-associated vasculopathy is relatively low, at 0.4%–6.4%;⁴ however, these complications can result in sudden, life-threatening hemorrhage.⁵

Here, we report a rare case of NF1 complicated by recurrent spontaneous cervical hemorrhage requiring repeated endovascular embolization. This case highlights important clinical considerations regarding the pathophysiology of NF1-associated hemorrhage, the potential limitations and risks of endovascular treatment, and the need for vigilant surveillance following initial hemostasis.

Illustrative Case

A 67-year-old man, under follow-up in respiratory medicine for multiple lung nodules and chronic obstructive pulmonary disease, with a history of diagnosed NF1 with café-au-lait macules and neurofibromas, presented to the emergency department with acute neck swelling and no history of trauma (Fig. 1A). CT showed a large cervical hematoma and tracheal deviation secondary to compression (Fig. 1B). Although oxygen saturation was preserved on arrival, the cervical swelling exhibited progressive enlargement. CT revealed marked tracheal deviation secondary to the hematoma, while contrast-enhanced CT demonstrated active extravasation, consistent with ongoing hemorrhage. Airway management was anticipated to be challenging owing to the progressive diffuse cervical swelling, mild restriction in neck extension, and potential for further tracheal deviation with continued hematoma expansion. Consequently, a tracheostomy was performed by the otolaryngology team prior to endovascular intervention. Three-dimensional CT angiography (CTA) revealed active extravasation from a branch of the thyrocervical artery (Fig. 1C). No additional vascular malformations requiring treatment were identified within the imaging field. Two contrast-enhanced CT examinations performed prior to the initial embolization covered the entire cervical region. At that time, no definitive additional bleeding source or vascular lesion requiring treatment was detected within the examined field. An emergency angiographic study was subsequently performed.

FIG. 1.

A:Pretreatment photograph of the neck hematoma. B and C: Pretreatment CT angiograms of the neck showing extravasation of contrast from the right thyrocervical artery (arrow) and a large hematoma in the prevertebral space, beside the trachea and tracheal deviation due to pressure.

Using a right radial artery approach, we inserted a 4-Fr sheath. Angiography confirmed active bleeding from a branch of the thyrocervical artery (Fig. 2A). Embolization was performed using a Headway 17 microcatheter (Terumo) and a CHIKAI X014 (200 cm, Asahi Intec). The microcatheter tip was advanced to the bleeding branch of the thyrocervical artery, and embolization was achieved using 33% n-butyl cyanoacrylate (NBCA) (Fig. 2B).

FIG. 2.

A: Preembolization angiogram showing active extravasation from the right thyrocervical artery (arrow). B: Postembolization angiogram showing that extravasation from the right thyrocervical artery had disappeared.

A tracheostomy was performed, and the patient was ­transferred to the intensive care unit. The following day, a new swelling was observed in the shoulder region (Fig. 3A), and repeat 3D-CTA revealed extravasation from the transverse cervical artery (Fig. 3B and C). Urgent angiography confirmed active bleeding from branches of the transverse cervical and internal thoracic arteries (Fig. 4A). These bleeding sites were distinct from the initial culprit vessel identified on the first angiographic study. No evident vascular fragility or extravasation from these arteries had been observed during the initial angiographic assessment, suggesting either the presence of occult vascular vulnerability at presentation or interval development of a new bleeding point. Repeat embolization was performed using the same system, using 33% NBCA (Fig. 4B).

FIG. 3.

A: Photograph of the neck after endovascular embolization on postoperative day 1. Swelling in the shoulder area (arrow) developed and was accompanied by pain. B and C: CT angiograms of the neck showing another hematoma appeared in the right shoulder area and extravasation of contrast from the right transverse cervical artery (arrows).

FIG. 4.

A:Preembolization angiogram showing active extravasation from the right transverse cervical artery and the right internal thoracic artery (arrows). B: Postembolization angiogram showing that extravasation from the right transverse cervical artery and the right internal thoracic artery had disappeared.

Blood transfusions were administered as needed to address low hemoglobin levels. Following the second embolization, no further hemorrhagic events were observed. Follow-up contrast-enhanced CT performed 2 weeks later demonstrated no evidence of recurrent bleeding. The tracheostomy was successfully closed approximately 1 month later. No neurological deficits were identified, and the patient was discharged with a modified Rankin Scale score of 0 and full daily activities. He has since remained under outpatient follow-up without recurrent hemorrhage.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

NF1 results from mutations in the NF1 gene, which encodes neurofibromin and is located on the long arm of chromosome 17 (17q11.2). Reduced neurofibromin expression due to these genetic alterations impairs the inactivation of Ras-GTP, leading to constitutive activation of the downstream Ras-MAPK and PI3K-Akt-mTORC1 signaling pathways. Persistent activation of these pathways promotes the proliferation of several neoplastic lesions and contributes to the development of systemic pathological manifestations.⁶

Hemorrhagic complications in patients with NF1 have been reported across multiple anatomical regions, including the intracranial, thoracic, cervical, and peripheral soft tissues.^7–11 A review of previously reported cases of spontaneous bleeding in NF1 indicates that most cases involve a single hemorrhagic episode arising from a single vascular territory, frequently triggered by minor trauma, tumor-related bleeding, or spontaneous rupture of dysplastic arteries (Table 1).^7,8,10–13 In contrast, early recurrent hemorrhage requiring repeated intervention remains distinctly uncommon.

TABLE 1.

Literature review of spontaneous hemorrhage

Authors & Year	Clinical Presentation	Hemorrhage Location	Treatment	Rehemorrhage	Outcome at Last Reported FU
Baek et al., 20078	Spontaneous hemorrhage (tumor bleeding), n = 1	Lt back	Surgery	Yes (observation)	Skin necrosis present requiring debridement & skin grafting. Survived; discharged on hospital day 50
Hung et al., 201212	Spontaneous hemorrhage (sudden neck pain, swelling), n = 1	Lt thyrocervical artery	Pseudoaneurysm coil embolization	No	Survived; FU NR
Zhang et al., 20127	Spontaneous hemorrhage (tumor bleeding), n = 1	Second from 12th & 11th intercostal arteries	Embolization followed by resection	No	Survived; FU NR
Thacker & Hull, 201911	Spontaneous hemorrhage (pain, enlargement of lt calf), n = 1	Subperiosteal hemorrhage	Observation	No	Partial radiological resolution at 1 mo
Stephen et al., 202210	Spontaneous hemorrhage, n = 1	Lt maxillary artery	Coil embolization	No	Survived; discharged on postprocedural day 3
Wei et al., 202313	Acupuncture, n = 1	Subclavian artery	PVA embolization followed by resection	No	Survived; FU duration NR

FU = follow-up; NR = not reported; PVA = polyvinyl alcohol.

Several reports have documented life-threatening hemorrhage from major cervical or thoracic vessels in patients with NF1. Kettner et al. reported a case involving a patient who developed sudden laryngeal pain and cervical swelling, followed 2 hours later by airway obstruction that ultimately proved fatal despite resuscitative efforts; autopsy revealed mediastinal hemorrhage attributed to NF1-associated spontaneous bleeding.¹⁴ Okazaki et al. described a 52-year-old man without any notable trauma who presented to the emergency department with sudden left shoulder pain and periclavicular swelling and subsequently developed severe dyspnea 30 minutes later.¹⁵ Further evaluation revealed that hemorrhage from a ruptured left subclavian artery aneurysm had resulted in upper airway obstruction.¹⁵ Spontaneous bleeding or rupture of the subclavian, internal thoracic, occipital, internal carotid, and external carotid arteries has been reported as a cause of hemorrhage leading to airway compromise.^16–18

Reports indicate that only a few minutes can elapse between the onset of neck swelling or pain and the development of respiratory distress, underscoring the urgency of intervention.¹⁹ Airway deviation caused by the expanding hematoma has made conventional laryngoscopic intubation extremely difficult in several cases, necessitating surgical airway access or awake fiber-optic intubation. Therefore, it is essential to anticipate difficult intubation and prepare for surgical airway management.^15,16

In the present case, although the bleeding occurred spontaneously, there was a risk of airway obstruction during the initial episode, necessitating a tracheostomy. In cases of massive hemorrhage, secondary bleeding may be precipitated by compression of surrounding tissues or inflammation related to the initial event. Recurrent or multifocal bleeding even after successful hemostatic intervention has been described in previous reports, highlighting the systemic nature of NF1-associated vascular disease.²⁰ Therefore, the possibility of rebleeding should be considered.

Nevertheless, documented cases of rebleeding remain scarce. Baek et al.⁸ reported recurrent massive subcutaneous hemorrhage requiring surgical management, although subsequent bleeding was controlled conservatively. Peyron and Pollanen described a fatal case of acute retropharyngeal hemorrhage in which definitive hemostatic treatment could not be achieved before death owing to airway compromise.¹⁹ These reports suggest that hemorrhagic events in NF1 span a broad clinical spectrum, ranging from self-limited bleeding to rapidly fatal outcomes.

The present case is rare because of the sequential rupture of two distinct cervical vascular territories within a short interval, necessitating repeated emergency endovascular embolization. Unlike most previously reported cases, in which a single bleeding source is typically identified and treated, this case shows that NF1-associated hemorrhage may be multifocal and temporally progressive, even following technically successful initial embolization.

In NF1, reduced levels of neurofibromin are associated with an increased propensity for uncontrolled proliferation of spindle-shaped cells within the vascular wall, accompanied by dysplastic alterations of smooth muscle cells in both the intimal and medial layers. Consequently, NF1-associated vasculopathy is characterized by intimal hyperplasia, medial thinning, and fragmentation of elastic fibers, resulting in diffuse vessel wall fragility.⁵ Therefore, angiographically evident bleeding may represent only the most vulnerable sites at a given moment, while adjacent or remote vessels remain at risk of subsequent rupture. In the present case, it was speculated that mass effect and local inflammatory changes related to hematoma expansion may have contributed to the development of new bleeding, consistent with prior reports describing recurrent or multifocal hemorrhage in NF1.^8,21

Endovascular therapy offers rapid hemostasis and avoids the technical challenges of open surgery in fragile tissues.^12,13 In patients with NF1, bleeding primarily reflects vascular fragility rather than coagulation disorders, making surgical hemostasis difficult.^8,22 Therefore, endovascular treatment is likely to offer favorable outcomes and low invasiveness. It can be an appropriate option as the first-line treatment for bleeding and as a rescue therapy for recurrent bleeding.^12,23 Nevertheless, open management remains an important adjunctive option in selected situations. Early consultation with vascular surgery and other relevant surgical teams should be considered when hemorrhage arises from a major cervical or thoracic vessel, when selective catheterization is unsafe or unsuccessful, when hemostasis remains incomplete after embolization, when direct vascular reconstruction or proximal and distal vascular control may be required, or when hematoma evacuation or decompression is needed because of airway or compressive compromise. In patients with NF1, open surgical hemostasis may be particularly challenging because of vascular and soft tissue fragility; therefore, the decision to proceed with surgery should be made within a multidisciplinary framework rather than as an isolated stand-alone rescue maneuver.^5,21,24,25

Despite generally favorable outcomes associated with endovascular approaches, some important limitations must be acknowledged. In patients with NF1, diffuse vasculopathy and intrinsic vessel wall fragility may limit the durability of hemorrhage control achieved by embolizing an angiographically identified culprit vessel.^8,20 Moreover, catheter manipulation and embolic material deployment within dysplastic arteries have been reported to carry an inherent risk of additional vascular injury.²⁶ Consequently, even after technically successful embolization, careful clinical assessment and serial radiological evaluation are warranted to detect potential recurrent or secondary bleeding at an early stage. These considerations distinguish NF1-associated hemorrhage from many other head and neck embolization cases, such as traumatic, tumor-related, or iatrogenic hemorrhage, in which treatment is often directed toward a relatively isolated culprit lesion. In patients with NF1, cervical hemorrhage should be regarded as a manifestation of systemic and potentially multifocal vasculopathy rather than a single-vessel event. Consequently, complete angiographic occlusion of the initially identified bleeding branch does not exclude early subsequent hemorrhage from adjacent or remote dysplastic vessels. This distinction is clinically important when planning postprocedural surveillance and counseling patients and their families regarding the risk of early recurrence.^5,20,26

Intensive clinical and radiological surveillance remains mandatory during the acute phase, even after apparent hemostasis. Clinicians should maintain a low threshold for repeat imaging when new symptoms or swelling develop. Airway protection is particularly critical in cases of cervical hemorrhage.¹⁹ In this case, a tracheostomy was performed, which carried no complications and was deemed appropriate without hesitation. More specifically, in the acute phase after embolization, surveillance should include continuous airway and hemodynamic monitoring, serial physical examination of the neck and shoulder region, repeated hemoglobin assessment, and early ­contrast-enhanced CT or CTA when new pain, swelling, respiratory concerns, hemodynamic instability, or hemoglobin decline is observed. Repeat catheter angiography should be considered when CTA demonstrates active extravasation, when hematoma enlargement or transfusion requirement persists despite negative or equivocal noninvasive imaging, or when endovascular retreatment is planned. Retreatment should be considered for persistent or recurrent extravasation, newly detected pseudoaneurysms, progressive hematoma enlargement, ongoing transfusion requirements, or worsening airway compromise. Although evidence from cerebral aneurysm embolization cannot be directly extrapolated to NF1-associated cervical hemorrhage, prior work has emphasized that vascular lesions treated endovascularly require reliable follow-up because recurrent or residual lesions may otherwise remain untreated.²⁷ In the chronic phase, follow-up should include careful assessment of symptoms, physical findings, vital signs, and laboratory parameters, with prompt imaging if new symptoms, minor trauma, or mechanical stimulation occurs.

Lessons

Prompt airway assessment is essential in patients with NF1 who present with cervical hemorrhage, as airway compromise may progress rapidly with hematoma expansion. Even after successful initial embolization, a low threshold for repeat imaging should be maintained when new swelling, pain, or respiratory concern arises, as rebleeding may originate from a distinct vascular territory. When active bleeding or progressive hematoma is suspected, repeat catheter angiography should be considered for possible reembolization. Early multidisciplinary involvement, including vascular surgery consultation, should be considered when endovascular access is limited, hemostasis is incomplete, major-vessel reconstruction may be required, or surgical decompression is needed.

Acknowledgments

We sincerely thank the physicians in the Department of Otolaryngology–Head and Neck Surgery, Yokohama City University, for their support in the clinical management of this patient.

We thank Editage for English-language editing.

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: Akimoto, Shioda, Yamamoto. Acquisition of data: Akimoto, Shioda, Suenaga, Nakai. Analysis and interpretation of data: Shioda. Drafting the article: Akimoto, Shioda. Critically revising the article: Kawasaki, Suenaga, Tateishi, Nakai, Yamamoto. Reviewed submitted version of manuscript: Akimoto, Iida, Kawasaki, Suenaga, Tateishi, Nakai, Yamamoto. Approved the final version of the manuscript on behalf of all authors: Akimoto. Administrative/technical/material support: Nakai. Study supervision: Akimoto, Nakai, Yamamoto.

Correspondence

Taisuke Akimoto: Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Kanagawa, Japan. akimoto.tai.ss@yokohama-cu.ac.jp.