Thrombolytic therapy in vertebrobasilar dolichoectasia patients with acute posterior circulation cerebral infarction: a case series analysis

Abstract

Vertebrobasilar dolichoectasia (VBD) is a rare cerebrovascular condition marked by elongation and dilation of the vertebral and basilar arteries. Patients with VBD often have strokes in the posterior circulation, but the safety and efficacy of intravenous thrombolysis (IVT) in this population are not well established. We report two cases of acute posterior circulation infarction in VBD patients who received IVT with tenecteplase. Patient 1 was a 56-year-old man. He received IV tenecteplase (0.25 mg/kg) one hour after arrival, and his deficits resolved (NIHSS 0) by the end of infusion with no hemorrhagic complications. He remained stroke-free at 1 year on dual antiplatelet therapy and statin.Patient 2 was a 39-year-old man. He received IV tenecteplase 78 min after arrival and similarly recovered to NIHSS 0 with no bleeding. He was asymptomatic at 3 months but had a recurrent cerebellar stroke at 6 months due to poorly controlled hypertension and hyperlipidemia. These cases suggest that IVT can be effective in VBD-related stroke, but emphasize the importance of aggressive risk factor management.

Introduction

Vertebrobasilar dolichoectasia is an uncommon dilative arteriopathy that can lead to posterior circulation ischemic events.It is often associated with older age and chronic hypertension.Reported prevalence of VBD is low (approximately 0.06%–5.8% in population studies) [1], although it is more frequently identified in patients evaluated for cerebrovascular symptoms. Pathologically, VBD involves degeneration of the arterial media and elastic lamina, resulting in thinning and tortuosity of the basilar artery. The basilar artery is generally considered dolichoectatic when its diameter exceeds 4.5 mm [2]. Clinically, patients with VBD may present with ischemic stroke in the posterior circulation, intracranial hemorrhage, or cranial nerve compression syndromes. Because data are limited, it is unclear whether standard acute stroke therapies apply in VBD. In particular, the influence of VBD on IVT outcomes has not been widely studied. We describe two patients with VBD and acute posterior circulation infarction treated with IVT, to inform clinical practice in this special population.

Case presentation

Case 1

A 56-year-old man was admitted to our hospital with the chief complaint of “dizziness and right ear hearing loss for 3 hours.” He denied a history of hypertension, diabetes mellitus, heart disease, or other relevant conditions. Upon admission, head computed tomography (CT) revealed, “No obvious abnormal density areas were observed in the cerebral parenchyma at all levels; the ventricular system was normal, and midline structures were midline.” Head magnetic resonance imaging (MRI) combined with magnetic resonance angiography (MRA) showed “scattered punctate hyperintensities on diffusion-weighted imaging (DWI) with decreased apparent diffusion coefficient (ADC) values in the brainstem and right cerebellum; fusiform dilatation was noted in the mid-segment of the basilar artery, while no stenosis or aneurysmal protrusions were found in the remaining internal carotid arteries or vertebral arteries.” Based on these findings(Fig. 1A and H), the patient was diagnosed with vertebrobasilar dolichoectasia (VBD) complicated by acute posterior circulation ischemic stroke. Given that the patient was within the intravenous thrombolysis time window and had no contraindications, the benefits and risks of intravenous thrombolysis with tenecteplase were explained to his family, who subsequently provided informed consent for the treatment. Pre-thrombolysis positive signs included horizontal nystagmus, right limb ataxia, a National Institutes of Health Stroke Scale (NIHSS) score of 1, and no pathological reflexes were elicited. The patient arrived at the hospital at 09:48 and received intravenous thrombolysis with tenecteplase (0.25 mg/kg) at 10:48, with a door-to-needle time (DNT) of 60 min. Post-thrombolysis examination showed improved horizontal nystagmus, an NIHSS score of 0, and a modified Rankin Scale (mRS) score of 0. A follow-up head CT at 24 h post-thrombolysis showed no hemorrhage. During hospitalization, the patient received symptomatic and supportive treatments, including therapies to promote blood circulation, scavenge oxygen free radicals, and improve collateral circulation, along with dual antiplatelet therapy (aspirin combined with ticagrelor) and lipid-lowering/plaque-stabilizing therapy with atorvastatin calcium tablets.Follow-up evaluations at 3 months, 6 months, and 1 year after discharge showed no disease recurrence or other functional impairments.

Fig. 1.

A-H: Patient 1 imaging. DWI/ADC show scattered punctate acute infarcts in the brainstem and right cerebellum. MRA demonstrates fusiform dilatation of the mid-basilar artery consistent with vertebrobasilar dolichoectasia, with no significant stenosis of the remaining vertebral or internal carotid arteries

Case 2

A 39-year-old man was admitted to the hospital with the chief complaint of dizziness for 2 h. His past medical history included hypertension and cerebral infarction. After admission, head computed tomography (CT) showed “no obvious abnormal density area in the cerebral parenchyma at all levels, a normal ventricular system, and a centered midline structure.” Head magnetic resonance imaging (MRI) demonstrated an acute infarction in the left cerebellar hemisphere within the posterior inferior cerebellar artery (PICA) territory, showing hyperintensity on diffusion-weighted imaging (DWI) with corresponding decreased apparent diffusion coefficient (ADC) values (Fig. 2A and D). Time-of-flight magnetic resonance angiography (TOF-MRA) revealed a markedly tortuous and ectatic vertebrobasilar system. At the vertebrobasilar (VB) junction, there was a focal high-grade stenosis with marked signal loss involving the distal intracranial vertebral artery segment(s), and the distal basilar artery was poorly visualized, which may reflect low-flow/turbulence distal to the VB junction lesion in the setting of dolichoectasia (Fig. 2E and F). Non-contrast CT showed no intracranial hemorrhage (Fig. 2G and H).The patient was considered to have vertebral basilar dolichoectasia (VBD) complicated with acute posterior circulation cerebral infarction. Since the patient was within the intravenous thrombolysis time window and had no contraindications, the family members were informed of the benefits and risks of intravenous thrombolysis with tenecteplase. After obtaining the family’s consent, intravenous thrombolysis was planned. Positive signs before thrombolysis included horizontal nystagmus and left limb ataxia; the National Institutes of Health Stroke Scale (NIHSS) score was 1, and no pathological reflexes were elicited. The patient arrived at the hospital at 15:05, and intravenous thrombolysis with tenecteplase (0.25 mg/kg) was performed at 16:23, with a door-to-needle time (DNT) of 78 min. Post-thrombolysis physical examination showed improvement of horizontal nystagmus, and the NIHSS score was 0; the modified Rankin Scale (mRS) score was 0. Head CT reexamination at 24 h after thrombolysis showed no hemorrhage. During hospitalization, the patient received symptomatic and supportive treatment, including promoting blood circulation, scavenging oxygen free radicals, improving collateral circulation, combined antiplatelet aggregation with aspirin and ticagrelor, and lipid-lowering and plaque-stabilizing treatment with atorvastatin calcium tablets.At the 3-month follow-up after discharge, no disease recurrence or functional impairment was observed. However, Six months after discharge from the hospital due to the first cerebral infarction, the patient suffered a disease recurrence and was readmitted with the chief complaint of “dizziness accompanied by tongue numbness for 1 day.” One day prior to admission, the patient developed sudden dizziness and tongue numbness without any identifiable predisposing factors, and the symptoms persisted without relief during the course. After admission, cranial computed tomography (CT) was performed, and the results revealed that no definite abnormal density lesions were observed in the cerebral parenchyma at all scanning levels, the ventricular system was normal in morphology, size, and position, and the midline structure was not shifted. Further cranial magnetic resonance imaging combined with magnetic resonance angiography (MRI + MRA) was conducted, which showed punctate abnormal signal foci in the left cerebellum and left parietal lobe, presenting with high signal intensity on diffusion-weighted imaging (DWI) and low signal intensity on apparent diffusion coefficient (ADC) maps, consistent with acute ischemic infarction foci. In addition, the distal segment of the basilar artery was blurred with poor visualization, and multiple focal luminal stenoses were detected in the main branches of the vertebral artery and internal carotid artery. Neurological physical examination revealed several positive signs, including horizontal nystagmus, limb and tongue paresthesia, and left-sided cerebellar ataxia. The patient’s National Institutes of Health Stroke Scale (NIHSS) score was 3 points, and pathological reflexes were not elicited.During re-admission, relevant indicators were rechecked, with the following results: triglycerides (TG): 2.54 mmol/L; low-density lipoprotein cholesterol (LDL-C): 3.65 mmol/L; blood pressure (BP): 168/92 mmHg. The patient reported irregular diet and poor BP control over the previous 3 months—specifically, the irregular diet was characterized by high intake of oil and salt. During this disease episode, the patient’s BP reached a maximum of 180/105 mmHg, and it was noted that the patient had not been taking antihypertensive medications regularly.

Fig. 2.

A-H: Imaging findings of Patient 2 showing acute cerebellar infarction and vertebrobasilar dolichoectasia with severe stenosis at the vertebrobasilar junction. (A) ADC map demonstrating reduced ADC in the left cerebellar hemisphere (arrow). (B) DWI showing corresponding hyperintensity consistent with acute infarction in the left cerebellar hemisphere (arrow). (C–D) Axial MRI demonstrating an ectatic and tortuous basilar artery consistent with vertebrobasilar dolichoectasia. (E–F) TOF-MRA of the posterior circulation showing a markedly tortuous/ectatic vertebrobasilar system with focal high-grade stenosis and signal dropout at the distal intracranial vertebral artery segment(s) at the vertebrobasilar junction (arrowheads), with poor visualization of the distal basilar artery. (G–H) Non-contrast CT showing no intracranial hemorrhage

Discussion

Pathophysiological mechanisms and influencing factors of VBD

VBD is a complex vasculopathy characterized by elongation, tortuosity, and dilation of the vertebral and basilar arteries, often leading to significant hemodynamic and hemostatic changes [3]. The pathophysiological mechanisms underlying VBD are multifaceted, involving both congenital and acquired factors. Congenital predispositions, such as connective tissue disorders like Marfan syndrome and Ehlers-Danlos syndrome, are known to contribute to the structural weakening of arterial walls, leading to vessel elongation and dilation [4]. Acquired factors, particularly hypertension and atherosclerosis, play a critical role in the progression of VBD. Hypertension induces chronic stress on the arterial walls, exacerbating the degenerative changes in the internal elastic lamina and media, while atherosclerosis contributes to the thinning of the media and atrophy of smooth muscle cells [5]. These pathological alterations result in the characteristic elongation and tortuosity of the vertebrobasilar arteries, predisposing patients to complications such as thrombosis, microembolization, and brainstem compression [6]. This article analyzes two case reports. In the first case report, no hemorrhage occurred after thrombolysis; additionally, after discharge, with regular follow-up and effective control of risk factors, the patient exhibited a favorable clinical course during the 1-year follow-up, with no disease progression or recurrence of cerebral infarction. In the second case report, however, during the 6-month follow-up, poor control of risk factors such as blood pressure and blood lipids resulted in the recurrence of cerebral infarction. This data further confirms that hemodynamic disturbance caused by VBD is the core of its clinical manifestations. The abnormal flow dynamics within the ectatic arteries can lead to thrombus formation, which may embolize to distal vessels, causing transient ischemic attacks (TIAs) or posterior circulation infarctions [7]. Additionally, the mechanical compression of adjacent neural structures by the dilated arteries can result in cranial nerve deficits, brainstem dysfunction, and even hydrocephalus in severe cases [8]. The pathophysiology of VBD is further complicated by its association with other systemic conditions, such as diabetes mellitus, hyperlipidemia, and smoking, which exacerbate the underlying vascular pathology [9].

VBD complicated with posterior circulation infarction

When VBD is complicated by posterior circulation cerebral infarction, the therapeutic approach must address both the acute ischemic event and the underlying vascular anomaly. Thrombolytic therapy, particularly intravenous thrombolysis (IVT), has been a cornerstone in the management of acute ischemic stroke. However, its efficacy in VBD-associated posterior circulation infarctions is limited by several factors. Firstly, the altered hemodynamics in ectatic arteries may impede the delivery of thrombolytic agents to the site of occlusion, reducing the likelihood of successful recanalization [10]. Secondly, the structural abnormalities of the arterial walls in VBD increase the risk of hemorrhagic complications, particularly intracerebral hemorrhage (ICH), which is a known adverse effect of thrombolytic therapy [11]. Despite these limitations, thrombolytic therapy remains a viable option in select cases, especially when administered within the early time window following symptom onset [12]. DeGeorgia et al. [13] reported a case of vertebrobasilar dolichoectasia (VBDE) complicated by luminal thrombosis treated with intravenous urokinase thrombolysis and conducted critical discussions on the efficacy and safety of this therapeutic approach. This study provides valuable references for clinical decision-making in similar patients, with particular emphasis on the potential risks that demand vigilance. For patients with vertebrobasilar dolichoectasia (VBDE) complicated by thrombosis who continue to experience recurrent ischemic symptoms despite adequate anticoagulation (with heparin or warfarin), intravenous thrombolysis can effectively lyse thrombi, improve vascular recanalization, and reduce the short-term risk of recurrent ischemic stroke. But it does require a strict, personalized evaluation of the risk-benefit ratio. Notably, VBDE is inherently characterized by congenital or hereditary structural abnormalities of the vascular wall, resulting in poor vascular stability. The thrombus may exert a “mechanical support” effect on the fragile vessel wall, and its removal via thrombolysis can significantly increase the risk of vascular rupture—which was the direct cause of death in this case. Additionally, transient detachment of microemboli during thrombolysis may trigger transient ischemic fluctuations (such as transient limb weakness and dysarthria observed in this patient). Furthermore, long-term anticoagulation after thrombolysis presents a clinical dilemma: while anticoagulation can prevent thrombus reaccumulation, it further elevates the bleeding risk; conversely, withholding anticoagulation may lead to recurrent ischemic events. Thus, this decision must be based on the individual trade-off between bleeding and ischemic risks and cannot be generalized uniformly.

Endovascular thrombectomy (EVT) has emerged as a promising alternative to thrombolytic therapy for posterior circulation infarctions, including those associated with VBD. EVT offers several advantages over IVT, including higher recanalization rates and a lower risk of hemorrhagic complications [14]. The mechanical removal of the thrombus directly addresses the underlying cause of the infarction, potentially leading to improved clinical outcomes. However, the efficacy of EVT in VBD patients is influenced by the anatomical complexity of the ectatic arteries, which may pose technical challenges during the procedure [15–16]. In Patient 2, the detection of severe stenosis at the vertebrobasilar (VB) junction has further complicated the pathophysiological mechanism underlying recurrent cerebral infarction. The coexistence of vertebrobasilar dolichoectasia (VBD) and VB junction stenosis may synergistically exacerbate hemodynamic disturbance: arterial tortuosity and dilatation caused by VBD already impairs blood flow velocity, while severe stenosis at the VB junction further reduces cerebral perfusion of the posterior circulation. Such dual vascular lesions are likely to significantly increase the risks of thrombosis and embolic events. Notably, reports of vertebrobasilar dolichoectasia (VBD) coexisting with severe stenosis at the vertebrobasilar (VB) junction are scarce. From an imaging perspective, it should be acknowledged that TOF-MRA can overestimate stenosis in the presence of low flow and complex/turbulent hemodynamics—both of which are common in dolichoectatic arteries—therefore, confirmatory vascular imaging (e.g., CTA, contrast-enhanced MRA, or DSA) would be valuable when the diagnosis is uncertain or when treatment decisions hinge on stenosis severity. Clinically, a high-grade VB junction lesion may represent a critical bottleneck for posterior circulation perfusion and may also serve as a nidus for in-situ thrombosis or artery-to-artery embolism, which could help explain the recurrent ischemic events observed in Patient 2. Consequently, management should be individualized with strict control of vascular risk factors, optimized antithrombotic strategy, and careful consideration of endovascular options in selected patients, while recognizing the technical complexity and potential risks of intervention in ectatic and tortuous vertebrobasilar anatomy.

Additionally, the long-term outcomes of EVT in VBD patients remain uncertain, necessitating further research to optimize patient selection and procedural techniques [17–18]. Some researchers have also pointed out the favorable safety and efficacy of large woven stents in the treatment of patients with vertebrobasilar dolichoectasia (VBD) [19]. However, other researchers have proposed that patients with compressive symptoms may not benefit from endovascular treatment; on the contrary, patients who have not yet developed compressive symptoms may benefit from endovascular treatment. Nevertheless, this still requires validation through long-term follow-up and large sample sizes [20].

Challenges in clinical diagnosis and treatment of VBD

The diagnosis of VBD remains challenging due to its nonspecific clinical presentation and the lack of awareness among clinicians [21]. Misdiagnosis or delayed diagnosis often results in suboptimal treatment, as conventional secondary preventive measures such as antiplatelet and lipid-lowering therapies are ineffective in addressing the underlying vascular pathology of VBD [22]. Moreover, the use of anticoagulants or thrombolytics in VBD patients carries a heightened risk of intracranial hemorrhage, further complicating treatment decisions [23]. The cases presented illustrate the limitations of current therapeutic strategies and emphasize the need for a tailored approach that considers the unique pathophysiology of VBD. Early recognition of VBD through advanced imaging techniques, such as high-resolution MRI, is crucial for timely intervention and improved outcomes [24]. Emerging therapies, such as targeted nanomedicine and ultrasound-assisted sonothrombolysis, offer promising avenues for improving thrombolytic efficacy and reducing complications in VBD-associated stroke [25]. For instance, cerium-based metal-organic frameworks (Ce-MOFs) encapsulated with mesenchymal stem cell membranes have demonstrated potent thrombolytic and antioxidant properties in preclinical models, providing a novel strategy for addressing the dual challenges of thrombosis and oxidative stress in VBD [26]. Furthermore, the use of microbubbles in conjunction with ultrasound has shown potential for enhancing clot dissolution and improving cerebral perfusion, offering a noninvasive alternative to traditional thrombolytic therapies [27]. The integration of TCM, particularly therapies aimed at “supplementing Qi and activating blood circulation,” represents a novel and complementary approach to managing VBD-associated stroke [28]. In the presented cases, the use of TCM formulations containing Qi-invigorating herbs such as Huangqi (Radix Astragalus Mongolici) and Danggui (Radix Angelicae Sinensis) was associated with improved cerebral perfusion and reduced recurrence of stroke. These herbs exhibit pharmacological properties that enhance blood flow, inhibit platelet aggregation, and protect vascular endothelium, addressing the underlying mechanisms of VBD [29]. The incorporation of TCM into the treatment regimen of VBD patients may provide a holistic approach that complements conventional therapies and improves long-term outcomes.

In conclusion, the pathophysiological mechanisms of VBD involve a combination of congenital and acquired factors that lead to significant structural and hemodynamic changes in the vertebrobasilar arteries. While thrombolytic therapy remains a treatment option for VBD-associated posterior circulation infarctions, its efficacy is limited by the unique challenges posed by the underlying vascular pathology. Endovascular thrombectomy offers a promising alternative, but its application in VBD patients requires careful consideration of the anatomical and clinical complexities. Future research should focus on refining therapeutic strategies to improve outcomes in this challenging patient population.

Author contributions

QH: Writing–original draft, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization. E-BZ: Data curation, Formal analysis, Writing – review & editing. M-QL: Data curation, Formal analysis, Writing – review & editing. G-lJ: Data curation, Writing – review & editing. L-ZQ: Writing – review & editing. H-JG: Data curation, Resources, Supervision, Writing – review & editing. H-yC: Writing – review & editing.

Funding

This work was supported in part by grants from the Research Project of Jilin Provincial Department of Education (JJKH20240692KD) and Research Fund of Yanbian University (Yanbian University Science and Technology Agreement No. 20 (2021) and Changbai Elite Talent Program (202434024).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The Ethics Committee of the Affiliated Hospital of Yanbian University has approved this research.

Consent for publication

We obtained signed written informed consent from the patient’s legal guardian to publish personal or clinical details in this study.

Competing interests

The authors declare no competing interests.