Fatal Triad of Subarachnoid Hemorrhage, Cervical Hematoma, and Upper Airway Obstruction in a Patient With Neurofibromatosis Type 1: A Case Report

Abstract

BACKGROUND:

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, characterized by neurocutaneous lesions. NF1 has a high degree of clinical variability, which can include multiple neoplasia as well as cutaneous, vascular, osseous, and cognitive features. When vascular involvement occurs, NF1 can lead to aneurysms or arteriovenous malformations, which may rupture and cause life-threatening complications.

CASE SUMMARY:

We present a case of primary subarachnoid hemorrhage, complicated by spontaneous and rapidly progressing hemorrhage from the left subclavian artery resulting in upper airway obstruction and hypoxia in a patient with NF1. Treatment of this patient included surgical airway management, emergency hematoma evacuation, and vascular reconstructive surgery. Close collaboration between radiology, vascular surgery, and anesthesiology was essential to prevent patient’s death.

CONCLUSIONS:

Awareness of rare diseases such as NF1 is essential in critical care settings. Patients presenting with café-au-lait spots or cutaneous neurofibromas are at risk of vascular complications due to vascular fragility. This case of dual bleeding sources and airway obstruction from a neck hematoma underscores the need for interdisciplinary management. The role of proactive vascular screening in critically ill NF1 patients remains uncertain. Future approaches may incorporate advanced imaging and biomarker development to better stratify vascular risk and guide individualized care.

KEY POINTS

Question: Do patients with neurofibromatosis type 1 (NF1) require special considerations during critical illness, particularly with regard to vascular complications?

Findings: Our patient experienced a fatal triad of complications during treatment: first, a subarachnoid hemorrhage; second, a cervical hematoma; and resulting in third, upper airway obstruction with hypoxia.

Meanings: This case report highlights the importance of maintaining high vigilance for vascular complications in critically ill patients with NF1. The role of proactive screening for undetected vascular pathology is open for discussion.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder, affecting approximately one in 3000 individuals (1). It is characterized (Fig. 1) by a triad of skin symptoms (axillary hyperpigmentation, café-au-lait spots, and Lisch nodules), along with multiple neurofibromas. Although there is no curative treatment, patients face increased mortality primarily due to malignancies or complications directly related to NF1 (2).

Figure 1.

Clinical characteristics of neurofibromatosis type 1. Gastrointestinal stromal tumor created in BioRender.

NF1 results from mutations in the NF1 gene on chromosome 17q11.23 (3), leading to reduced or absent neurofibromin, a protein involved in cell growth regulation. Its deficiency contributes to tumor formation and, in rare cases (< 3%), vascular abnormalities (4). Vascular involvement may include stenosis, aneurysms, arteriovenous malformations, or fistulae (5). Immunological studies have shown NF1 expression in vascular endothelial cells, suggesting a direct role in vessel integrity (6).

Despite its potential severity, vascular NF1 complications remain poorly understood and underreported. Cerebrovascular changes may be life threatening. The combination of cerebral and peripheral vascular events is exceptionally rare but carries a high risk of mortality. Such complex presentations require prompt diagnosis and interdisciplinary management. Improved understanding of NF1-related vasculopathy is essential for identifying at-risk patients and preventing catastrophic outcomes.

CASE DESCRIPTION

A 47-year-old female presented with sudden onset of holocephalic headaches, nausea, and vomiting. She had a history of NF1 and a presumed arteriovenous fistula that had been treated more than 10 years earlier. No additional comorbidities were known, particularly no coagulation disorders or relevant medications. At the time of admission, the patient exhibited mild dysarthria and had a Glasgow Coma Scale (GCS) of 13. Patient’s vital signs were stable with an increased blood pressure of 190/80 mm Hg.

Cranial CT including a CT angiography confirmed the clinically suspected diagnosis of subarachnoid hemorrhage (SAH) caused by a cerebral aneurysm of the left posterior communicating artery (Fig. 2).

Figure 2.

Combined CT-angiography and digital substraction angiography (DSA) images obtained at admission and following the bleeding event. Acute subarachnoid hemorrhage diagnosed on an unenhanced axial CT scan (A). Selective catheter angiography of the left common carotid artery (B) revealed an aneurysm of the left posterior communicating artery as the source of hemorrhage (arrow); note the antegrade opacification of the basilar artery via the prominent anastomosis of the ipsilateral occipital and vertebral artery after parent vessel coil occlusion (arrowhead) of the left V2 segment (this finding reflects prior coil occlusion of the left vertebral artery, performed abroad years earlier, likely for treatment of an arteriovenous fistula; detailed procedural information is unavailable). A CT scan obtained 52 hr after admission showed a large left cervical hematoma (C), most likely secondary to rupture of the left suprascapular artery, a branch of the left subclavian artery (arrow in D).

The patient was admitted to the ICU after placing an external ventricular drain. A central venous line was placed under ultrasound guidance into the right internal jugular vein without any complications. The left internal jugular vein and the left subclavian vein were not punctured at any time. Super-selective transfemoral angiograms on the following day were obtained of both internal and external carotids as well as of the right vertebral artery confirming a posterior communicating artery aneurysm, which was successfully treated with platinum coil embolization without any periprocedural complications. Notably, the basilar artery was opacified via a prominent anastomosis between the ipsilateral occipital and vertebral arteries, consistent with prior parent vessel coil occlusion, most likely for treatment of an arteriovenous fistula. The ascending and deep cervical arteries had been killed using coil embolization over 10 years ago. No medical information was available on the previous event as this procedure was performed abroad before admission to our institution.

Following the intervention, the patient remained intubated and shortly sedated. We closely monitored the patient’s blood pressure, which consistently remained within the normal range. The patient was successfully weaned from mechanical ventilation, and extubation was carried out without complication. At that time, the patient was clinically stable and presented no neurologic deficits. Nimodipine, at a dosage of 60 mg six times a day, was initiated immediately upon admission for vasospasm prophylaxis.

Fifty-two hours postadmission, the patient developed significant left-sided neck swelling. Immediate CT angiography revealed active bleeding from the left suprascapular artery (Fig. 3). Rapidly, the neck hematoma led to complete airway compression and obstruction, resulting in dyspnea and hypoxia. Mask ventilation could be established after bedside hematoma relief, but both conventional laryngoscopy and advanced intubation techniques were not successful to secure the airway. A supraglottic airway device was not useful due to the hematoma progression. An emergency cricothyrotomy (5.5 mm tube via bougie) was performed. Immediate transfer of the patient to the operating room was critical, as the airway was temporarily placed, but ventilation remained limited. A surgical tracheotomy was initiated, ensuring a secured airway. This resulted in a significant improvement of the patient’s ventilation and oxygenation. The former bedside skin incision was explored, revealing a hematoma cavity from which blood clots were removed. After prolonged surgery and blood loss due to extensive hemorrhage, a bleeding branch of the subclavian artery was identified and securely ligated.

Figure 3.

Early post-treatment MRI and MRA demonstrated moderate vasospasm, while 12-day follow-up imageing shows marked vasospasm and associated infarcts. MRI with magnetic resonance angiography (A) and diffusion-weighted imaging (B) images 2 d after endovascular treatment depicting moderate vasospasm in the carotid terminus and the proximal middle cerebral artery (arrow in A). Control imaging 12 d after treatment shows massive vasospasm particularly in the proximal and distal middle cerebral and distal anterior cerebral artery on the left side (arrows in C) and corresponding infarcts in the corresponding territories (D).

During surgery, the patient experienced hemorrhagic shock with an estimated blood loss of 2000 mL, requiring massive transfusion, vasopressor support with up to 0.6 µg/kg/min of norepinephrine, and 1 international units/hr vasopressin.

Once hemodynamic stability was achieved, we discontinued sedation and initiated weaning. Due to immediate presentation of generalized seizures an anti-epileptic IV therapy with levetiracetam (1000 mg two times a day) was started. To rule out hypoxic ischemic encephalopathy following the critical incident, cranial MRI (cMRI) was performed revealing constant SAH with newly present vasospasms, but no evidence of new infarction following extensive vessel repair. Neuron-specific enolase levels were slightly elevated (12–15 µg/L; cutoff 12.5 µg/L).

Within the next days, the patient remained at a reduced level of consciousness (minimum GCS of 6) and clinically presented with new right-sided hemiparesis. Repeated cMRI imaging after 9 and 17 days of the event revealed vasospasm-associated bihemispheric infarctions (left > right) in the middle and anterior cerebral artery territories, as well as a lacunar cerebellar infarction. The infarcts observed in imaging were typically associated with vasospasms, as confirmed by our neurologic specialists. We initiated hypertensive therapy to maintain a mean arterial pressure above 110 mm Hg. Daily transcranial Doppler monitoring revealed declining vasospasms over time.

Further rehabilitation therapy was continued in a neurologic rehabilitation facility from day 27 on after admission.

Eighteen months after the incident, the patient was still treated in a long-term specialized rehabilitation center. She was spontaneously breathing after decannulation and was mobilized into a wheelchair. Neurologically, she remained significantly impaired, with right-sided hemiparesis, but was awake and able to speak simple words. Efforts to reintroduce oral nutrition are ongoing. Overall, her neurologic status corresponds to a modified Rankin Scale score of 4.

Written informed consent was obtained from the patient’s authorized representative for publication of this case report. The report was prepared in accordance with the CAse REport guidelines for consensus-based clinical case reporting.

DISCUSSION

This case describes a patient with NF1 who presented with a rare combination of two separate potentially life-threatening vascular complications. First, a SAH from an aneurysm of the posterior communicating artery and a second hit by an acute spontaneous bleeding from the left suprascapular artery resulting in upper airway obstruction. To our knowledge, this fatal triad of complications has not previously been reported in an NF1 patient.

While vascular complications in NF1 are well documented, they remain relatively rare and often under-recognized (7–11). Acute airway obstruction due to acute hematoma has been previously described, and Tong et al (7) highlighted that spontaneous vessel rupture in the subclavian artery region occurs disproportionately often in NF1 patients.

Furthermore, literature review unveiled an association between patients with neurofibromatosis and complications from vascular involvement, including vascular stenosis, aneurysm formation, and vascular malformations (5). The pathogenesis is thought to involve Schwann cell infiltration of vessel walls leading to intimal thickening and degradation of the vascular media and elastic fibers, which predisposes to both stenosis and aneurysms (12). Aneurysm formation is also primarily driven by genetic disruption of vascular extracellular matrix (ECM) homeostasis and inflammatory signaling (13). In NF1, loss of neurofibromin leads to hyperactivation of these pathways, further accelerating aneurysm development through a shared cascade of ECM degradation, vascular inflammation, and smooth-muscle dysfunction (13). Future diagnostic approaches may integrate specific microRNAs that reflect fundamental molecular processes, such as ECM degradation and vascular inflammation, which contribute to disease severity and prognosis (14). Increasing evidence suggests that these biomarkers may assist in identifying high-risk patient subsets and enable more refined stratification for both diagnostic assessment and therapeutic intervention. Among these, microRNAs have demonstrated considerable potential as noninvasive indicators for monitoring aneurysm progression and predicting clinical outcomes (14). Overall, scientific literature is limited to individuality in the form of case reports, and general awareness for this special patient cohort appears to be missing (7, 9–11, 15, 16).

This unique case presents a life-threatening triad of two acute spontaneous bleedings, causing massive neck hematoma and consecutive airway compression. This patient’s rapid deterioration highlights the need for close monitoring in NF1 patients at high risk of vascular involvement. The co-occurrence of SAH, which may require arterial hypertension for the treatment of vasospasms, combined with undetected peripheral vascular fragility, raises concerns about optimal blood pressure management in such patients and emphasizes the importance of individualized care.

On initial evaluation, soft tissue edema, or the presence of blood in the airway can complicate endotracheal tube placement, potentially requiring urgent and advanced surgical intervention. Similar situations may arise after carotid surgery, thyroid surgery, and other airway-related procedures (17). Airway management in cases of threatening neck hematoma and yet clinically stable patients should be promptly performed in spontaneously breathing patients using advanced intubation techniques including fibreoptic awake intubation. If progressive bleeding with consecutive compressive hematoma, and impending hypoxia may occur, Emergency Front-of-Neck Access seems to be the method of choice to save patients’ lives. This approach is also endorsed by the revised Canadian Airway Focus Group guidelines for difficult airway management (18).

Regarding the origin of this precarious bleeding situation, various factors could have played a pathophysiologic role. An iatrogenic vascular injury during the neuroradiological intervention of the aneurysm seems to be unlikely due to the bleeding manifestation 52 hours after the procedure and due to the absence of any technical difficulties (Fig. 4). Nevertheless, a minor vascular injury in a patient with fragile vessels cannot be completely excluded. Necessary therapeutic options for underlying SAH, such as hyperdynamic therapy to prevent vasospasms, seem to have had a contributory effect on the bleeding situation. Given the prior left V2 segment coil occlusion of the vertebral artery and the resulting anterograde basilar flow, it is possible that altered hemodynamic conditions contributed to the vessel rupture. Comparable mechanisms have been reported in the literature following altered hemodynamic and secondary stress on vessel walls, suggesting that disturbed flow dynamics may increase the risk of delayed rupture (19–22). From our point of view, two previously undiagnosed and separately bleeding vascular lesions in the context of the underlying NF1 (i.e., cerebral aneurysm and vascular lesion of the arm artery) are the best explanation, although the second bleeding event could not be specifically determined due to missing imaging of the specific region.

Figure 4.

Supplementary overview of angiographic, CT and MRI findings following endovascular treatment, including initial vascular imaging and post-treatment changes. Selective catheter angiography of the left common carotid artery showing successful treatment of the aneurysm with coil embolization (A). CT of the head and neck region, which showed no signs of a vascular pathology the day on the initial imaging (arrow in C). Diffusion-weighted MRI (B) image 2 d after endovascular treatment and control imaging 12 d after treatment showing cerebral infarction (D).

NF1-associated vasculopathy is mostly asymptomatic, with its overall incidence and spectrum remaining poorly understood. The incidence of vasculopathy in NF1 is estimated to range from 0.4% to 6.4%, while cerebrovascular vasculopathy occurs in approximately 2–5% of cases (4).

Given the potential for life-threatening complications, including stroke and aneurysm rupture, regular cardiovascular and neurologic screening is critical. Emerging biomarkers may help identify patients at risk and enable more precise stratification for diagnostic and therapeutic interventions. Although no formal guidelines exist for the critical care of NF1 patients, evidence suggests that vascular abnormalities can be effectively treated (23). Therefore, maintaining a low threshold for imaging is reasonable, particularly in high-risk situations such as known vascular involvement. Accordingly, the debate is open if the performance of a whole-body CT angiography can identify vascular lesions at risk of spontaneous bleeding. Consequently, identified lesions should then be evaluated by neuroradiologists for their location, bleeding risk, and potential for life-threatening complications. In these cases, a prophylactic treatment may help prevent catastrophic events in this vulnerable population.

CONCLUSIONS

In conclusion, patients with preexisting NF1 who present with café-au-lait spots or cutaneous neurofibromas are at risk of vascular involvement, which may lead to hemorrhage from spontaneous aneurysm rupture. The presented nearly fatal triad of two different bleeding sources and an acute airway obstruction due to neck hematoma, highlights the importance of interdisciplinary treatment approaches in life-threatening situations. Immediate performance of airway management algorithms, including surgical cricothyroidotomy, might be necessary and lifesaving. Proactive screening for vascular pathology in all critically ill NF1 patients has to be discussed.

ACKNOWLEDGMENTS

We thank the patient and her relatives for permission to publish this article and for their willing information during the follow-up of the case.