Occurrence of fatal vertebrobasilar dolichoectasia after occlusion of unilateral internal carotid artery

Abstract

Background

Vertebrobasilar dolichoectasia (VBD) is a rare cerebrovascular disorder. The natural history of patients with VBD is generally poor, and current treatments do not appear to provide significant clinical benefit. Therefore, understanding the underlying mechanisms of VBD and implementing appropriate strategies in advance are particularly important.

Case presentation

In the first case, a 15-year-old boy initially presented in July 2020 with recurrent mild nausea and vomiting. He was diagnosed with left internal carotid artery (ICA) occlusion secondary to a giant fusiform aneurysm, along with a cerebellar arachnoid cyst. The patient received conservative treatment but did not adhere to the recommendation for regular follow-up. In August 2023, he developed hydrocephalus and severe brainstem compression caused by VBD. Ventriculoperitoneal (V-P) shunting failed to prevent rapid clinical deterioration, which eventually led to fatal intracranial hemorrhage. The second case involved a 9-year-old boy who initially presented in June 2013 with hydrocephalus and underwent V-P shunting. In June 2020, he was diagnosed with right ICA dolichoectasia during an evaluation for neck discomfort and subsequently underwent ligation of the right ICA. In March 2022, he experienced an acute onset of altered consciousness, and neuroimaging confirmed brainstem compression due to VBD. Considering the high anesthetic risk and the limited potential benefit of further surgical intervention, treatment was withdrawn, and the patient ultimately died of brainstem infarction.

Conclusions

These cases highlight the importance of close monitoring in pediatric patients with ICA occlusion, given the associated risk of VBD. Further research into the pathogenesis of VBD, particularly in pediatric patients, is essential to develop more effective preventive and therapeutic strategies.

Background

Vertebrobasilar dolichoectasia (VBD), characterized by pathological elongation, dilation, and tortuosity of the vertebrobasilar system, is a rare cerebrovascular condition with unclear epidemiology. Current estimates of VBD prevalence remain inconsistent: some studies report an incidence below 0.05% in the general population [1], while others describe detection rates of 2.06% in first-ever stroke cohorts [2]. Clinically, VBD presents with a range of neurological complications, including ischemic events in the posterior circulation, intracranial hemorrhage, and neurovascular compression syndromes affecting the brainstem or cranial nerves, all of which contribute to high morbidity and mortality.

Long-term studies indicate a poor prognosis for patients with VBD, with event-free survival rates decreasing to 54.1% at 5 years, 39.5% at 10 years, and 23.5% at 15 years [3]. Both surgical and endovascular interventions have shown limited effectiveness in halting disease progression. Surgical intervention carries exceptionally high risks due to the lesion’s proximity to the brainstem and insufficient collateral circulation, with existing literature documenting mortality rates exceeding 50% in such cases [4]. Endovascular approaches continue to struggle with safety-efficacy equilibrium: flow diversion embolization carries a 40.9% complication risk versus merely 10% occlusion rates achieved by braided stents in our previous study [5]. These findings underscore the urgent need for a deeper understanding of the underlying mechanisms to inform preventive strategies. The existing clinical evidence has established associations between vertebrobasilar dolichoectasia and several hereditary disorders [6]. However, the exact pathophysiological mechanisms of VBD remain unclear. This report presents two pediatric cases of de novo VBD secondary to unilateral internal carotid artery (ICA) occlusion and discusses possible mechanisms and management strategies based on a review of the existing literature.

Case presentation

Case 1

A 15-year-old boy presented with recurrent mild nausea and vomiting in July 2020. Magnetic resonance imaging (MRI) revealed a cerebellar arachnoid cyst and a suspected thrombosed giant fusiform aneurysm of the left ICA (Fig. 1A). Subsequent computed tomography angiography (CTA) confirmed occlusion of the left ICA secondary to aneurysmal thrombosis (Fig. 1B) while the vertebrobasilar system demonstrated normal morphology (Fig. 1C). Conservative management was adopted, and annual follow-up was recommended due to the patient’s minimal symptoms and the generally benign course of cerebellar arachnoid cysts. However, the patient did not adhere to the recommended follow-up due to the COVID-19 pandemic. In August 2023, he presented to our hospital in a drowsy state. MRI revealed hydrocephalus (Fig. 1D). Further vessel wall MRI and CTA showed severe brainstem compression caused by VBD (Fig. 1E and G). His condition rapidly deteriorated, leading to deep coma. Repeat CT confirmed worsening hydrocephalus. Despite the high risk of aneurysm rupture due to changes in pressure gradients, emergency ventriculoperitoneal (V-P) shunting was performed to relieve symptoms. The patient’s condition improved significantly after surgery, returning to a drowsy state. Unfortunately, consciousness was lost again, and CT showed intracranial hemorrhage caused by aneurysm rupture (Fig. 1G). Although the medical team proposed salvage endovascular treatment via occlusion of the basilar artery, the plan was declined by the family. The patient eventually died from intracranial hemorrhage.

Fig. 1.

A Axial T2-weighted imaging showing a mass-like lesion along the course of the left internal carotid artery (ICA), consistent with thrombosed giant fusiform aneurysm (arrow), with a coexisting cerebellar arachnoid cyst also noted (✱). B CTA demonstrating occlusion of the left ICA (arrow), likely resulting from spontaneous thrombosis of the aforementioned aneurysm. C CTA revealing an intact normal basilar artery anatomy (arrowhead). D Axial T2-weighted image at temporal horn level showing obstructive hydrocephalus (Evans index = 0.34). (E, F) Axial (E) and sagittal (F) vessel wall MRI depicting dilated basilar artery with intramural thrombus encasing the true lumen (arrowheads), causing significant brainstem displacement and compression, especially in mesencephalon (G) CTA demonstrating occlusion of the left ICA (arrow) and vertebrobasilar dolichoectasia (arrowhead). H Non-contrast CT revealing subarachnoid hemorrhage and the ventriculoperitoneal (V-P) shunt (arrowhead)

Case 2

A 9-year-old boy initially presented with increased head circumference, irritability, and psychomotor developmental delay in June 2013. MRI revealed congenital communicating hydrocephalus (Fig. 2A), and V-P shunting was subsequently performed. After surgery, the patient’s irritability gradually improved, and his psychomotor development returned to near-normal levels. In July 2014, follow-up MRI confirmed complete resolution of the hydrocephalus (Fig. 2B). In June 2020, the patient presented with neck discomfort. Vessel wall MRI revealed a dilated lumen in the right internal carotid artery with hyperintense thrombus within the C5 segment (Fig. 2C and D). Angiography showed dolichoectasia involving the C1–C5 segments of the right ICA (Fig. 2E), slight dilation of the C3–C5 segments of the left ICA (Fig. 2F), and a normal vertebrobasilar artery structure (Fig. 2G). Due to the significant mass effect and high risk of rupture of the right ICA, along with negative results from the balloon occlusion test, right ICA ligation was performed (Fig. 2H). No ischemic symptoms were observed during the two-year follow-up. In March 2022, the patient developed a headache, which progressively worsened and was accompanied by impaired consciousness. Emergency CT revealed a high-density lesion anterior to the brainstem, indicating severe brainstem compression caused by VBD (Fig. 3). The patient’s level of consciousness declined rapidly within one day, progressing to deep coma. The medical team proposed a salvage decompressive surgery, explaining the high surgical risk and uncertain benefit. After thorough discussions with the patient’s family, treatment was discontinued. The patient ultimately died due to brainstem compression.

Fig. 2.

A Axial T2-weighted imaging showing communicating hydrocephalus. B Axial T2-weighted imaging demonstrating significant improvement in hydrocephalus following ventriculoperitoneal (V-P) shunting. C, D Axial (C) and sagittal (D) vessel wall MRI revealing intraluminal thrombosis and enhancing vessel wall lesions in the C5 segment. E–G Right common carotid angiogram (E) showing dolichoectasia involving the C1–C5 segments, left common carotid angiogram (F) indicating slight dilation in the C3–C5 segments, and right vertebral angiogram (G) showing normal vertebrobasilar artery morphology. (H) Right common carotid angiogram showing lack of visualization of the distal internal carotid artery after ligation

Fig. 3.

CT demonstrating brainstem and cerebellar compression caused by VBD

Discussion

To our knowledge, these are the first reported cases of VBD emerging in temporal association with unilateral ICA occlusion. In both cases, the vertebrobasilar artery appeared entirely normal before or at the early stage of ICA occlusion. This chronological pattern raises the possibility that hemodynamic alterations following ICA occlusion could contribute to VBD pathogenesis. Theoretically, compensatory increases in vertebrobasilar flow to maintain cerebral perfusion might promote pathological remodeling. Animal studies conducted in rabbits support this hypothesis [7, 8]. Notably, Mežvinska P et al. documented a patient with a ruptured basilar artery aneurysm concomitant with left internal carotid artery hypoplasia, providing clinical corroboration for this hemodynamic mechanism [9]. A previous meta-analysis indicated that the risk of de novo aneurysm formation following carotid occlusion is 4.3% [10], which is higher than the 5-year cumulative incidence of aneurysm formation in patients treated with coiling (0.75%) [11]. This difference may reflect increased hemodynamic stress on collateral arteries after occlusion. While our cases demonstrate a temporal association between ICA occlusion and subsequent VBD development, the causative relationship requires cautious interpretation. In Case 1, the exact onset timing of ICA occlusion remains undetermined, limiting precise correlation with VBD progression. In Case 2, robust cross-flow through the anterior communicating artery (evidenced by negative balloon occlusion test) suggests hemodynamic stress on the posterior circulation may have been mitigated. Thus, we propose ICA occlusion as a potential contributor rather than a definitive cause, acting within a multifactorial framework that likely involves genetic predisposition and developmental vasculopathy.

Congenital factors and non-atherosclerotic factors likely play an important role in the development of VBD in pediatric populations like ours. The etiology of VBD remains poorly defined and is likely multifactorial, potentially involving both atherosclerotic (ASVD) and non-atherosclerotic (non-ASVD) pathways [6]. Established ASVD risk factors include hypertension, advanced age, and smoking history [1, 12, 13]. However, in pediatric cases such as those presented here, non-ASVD mechanisms are more likely to be central. These non-ASVD mechanisms encompass a broad spectrum. Polycystic kidney disease, an autosomal dominant disorder associated with dysregulation of the renin-angiotensin-aldosterone system and hypertension, has been linked to a higher risk of VBD [14]. Connective tissue disorders—such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome—are also recognized as risk factors due to their impact on vascular wall integrity and elasticity, which may predispose to arterial dilatatio [15–17]. Additionally, metabolic disorders such as Fabry disease [18] and late-onset Pompe disease [19] can lead to arterial dilation and tortuosity. This is attributed to deficiencies in specific metabolic enzymes (α-galactosidase and acid maltase, respectively), resulting in the accumulation of unmetabolized substrates within smooth muscle cells. This accumulation causes smooth muscle cell dysfunction and aberrant vascular remodeling. Although infectious etiologies—including syphilis, HIV, and varicella-zoster virus (VZV) infection—may contribute to vascular injury through documented mechanisms [6], serological testing for both syphilis and HIV-specific antibodies returned negative results in our two cases. Furthermore, complete varicella vaccination had been administered prior to disease onset. These findings collectively suggest a low probability of infectious factors playing a significant pathogenic role in these pediatric patients. In addition, somatic mutations in the platelet-derived growth factor receptor β(PDGFRB) gene have been identified in patients with fusiform aneurysms resembling VBD, suggesting a potential molecular mechanism [20]. Notably, microarray analysis of two affected pediatric siblings with carotid and vertebrobasilar dolichoectasia revealed a 1.5-Mb deletion at 6p25.3 spanning 15 genes, including FOXC1 - a gene implicated in vascular morphogenesis defects [21]. And previous reports have indicated that Foxc1-deficient mice exhibit severe congenital hydrocephalus [22]. Unfortunately, the clinical urgency precluded comprehensive genetic testing in our cases.

Case 2 illustrates the complex clinical decision-making associated with ICA dolichoectasia, a condition with limited consensus on optimal treatment. Peeters et al. recommend observation for extradural lesions in patients with stable neurological status, an intact sphenoid sinus, and no thromboembolic events, while surgical intervention is indicated in cases of intradural extension, aneurysmal progression, neurological decline, or recurrent embolic events [23]. Pico et al. suggest biannual or annual MRI/MRA surveillance for intracranial arterial dolichoectasia, reserving intervention for cases with enlargement greater than 2 mm [24]. In our case, treatment was complicated by the absence of robust natural history data and validated prognostic models in pediatric populations, limiting accurate assessment of therapeutic efficacy. Given the dolichoectatic involvement of the intracranial ICA with significant mass effect on adjacent neural structures, a high risk of rupture-induced hemorrhage, and strong family preference for definitive management, we proceeded with ICA occlusion.

Currently, there is no ideal treatment for VBD, particularly in patients experiencing severe brainstem compression due to mass effect. As the predominant therapeutic modality for VBD, endovascular treatment has demonstrated preliminary safety and efficacy [5, 25], but it may not be effective for patients with compressive symptoms [26]. Parent artery occlusion and flow diversion have shown efficacy in reducing aneurysm size and improving modified Rankin Scale (mRS) scores in patients with vertebrobasilar dissecting aneurysms associated with brainstem compression [27]. However, because VBD lesions often involve long segments of the basilar artery, parent artery occlusion is frequently impractical. Concurrently, the therapeutic outcomes for bilateral vertebral artery occlusion remain suboptimal. Sluzewski et al. documented 6 cases treated with balloon occlusion, among whom 3 patients achieved favorable outcomes while 3 succumbed during the mean 8.6-month follow-up period [28]. Flow diversion appears to be associated with higher complication rates in patients presenting with mass effect. Griessenauer et al. documented outcomes of 53 basilar artery dolichoectatic aneurysms treated with the Pipeline embolization device, where univariable logistic regression indicated that patients with neurological deficits had significantly elevated complication risks (p = 0.05) [29]. Similarly, Siddiqui et al. reported 7 symptomatic VBD cases undergoing flow diversion, with 4 fatalities and 1 severe disability (mRS = 5) at final follow-up [30]. Although microsurgical treatment may offer the most direct relief of mass effect, its application is hindered by the proximity of VBD lesions to the brainstem and the anatomical complexity of the vertebrobasilar system, resulting in high procedural difficulty and risk. Despite ongoing efforts by experienced neurosurgical teams to overcome these challenges, the outcomes of microsurgical intervention remain suboptimal [4, 31]. Therefore, it is essential to further clarify the mechanisms underlying the onset and progression of VBD and to implement preventive strategies and early interventions before the disease reaches an advanced stage.

Conclusion

We report two pediatric cases that underscore the potentially fatal emergence of VBD years after ICA occlusion—despite an initially normal vertebrobasilar system. This serves as a critical warning for vigilant long-term monitoring of posterior circulation in such patients. Furthermore, the roles of hemodynamic remodeling and genetic predisposition merit confirmation through large‑scale clinical studies and molecular investigations.

Abbreviations

CT

Computed tomography

CTA

Computed tomography angiography

HR-MRI

High-resolution magnetic resonance imaging

ICA

Internal carotid artery

MRI

Magnetic resonance imaging

V-P

Ventriculoperitoneal

VBD

Vertebrobasilar dolichoectasia

Authors’ contributions

H.H. and Z.J. wrote the main manuscript text. S.W. prepared Figs. 1 and 2. T.Z. and J.L. oversaw the clinical management. C.H. and H.Z. supervised the data analysis and critically revised the manuscript. All authors reviewed and approved the manuscript.

Funding

Supported by National Key Research and Development Program of China (No. 2016YFC130080), National Science and Technology Major Project (No. 2023ZD0504702), National Natural Science Foundation of China (No. 82471404).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

The whole study had been approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University and had therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from the patient’s legal guardian for publication of this case report and accompanying images.

Consent for publication

Written informed consent for publication of clinical details and any identifying images was obtained from the parents of both minor patients. All authors have approved the final manuscript and its submission to this journal.

Competing interests

The authors declare no competing interests.