Abstract

Background: Initial angiography may not identify a bleeding source in some subarachnoid hemorrhage (SAH) cases. We report an instructive case of initially angiogram-negative SAH where an anterior communicating artery aneurysm became apparent during treatment for vasospasm, subsequently requiring successful endovascular embolization.

Case Description: A woman in her 60s presented with diffuse SAH (Fisher group 3); initial computed tomography angiography (CTA) and digital subtraction angiography were negative for aneurysms. Symptomatic vasospasm developed on day 4, and treatment including cilostazol and fasudil was initiated. A repeat CTA on day 8 revealed the aneurysm.

Conclusion: This case underscores that even with negative initial angiography, an underlying aneurysm should be strongly suspected in patients with diffuse SAH or subsequent vasospasm. It highlights the critical importance of meticulous follow-up and appropriately timed, high-quality imaging re-evaluation, which can lead to accurate diagnosis and favorable outcomes.

Keywords: Cerebral aneurysm, Cerebral vasospasm, Delayed diagnosis, Endovascular treatment, Subarachnoid hemorrhage

INTRODUCTION

While ruptured cerebral aneurysms are the primary cause of subarachnoid hemorrhage (SAH), a significant challenge arises when initial angiography fails to identify a bleeding source. These angiogram-negative SAH scenarios necessitate persistent investigation, as an underlying aneurysm may become detectable on later examinations.[ 10 , 12 , 13 , 18 ] However, the optimal strategy for follow-up, including the timing and type of imaging re-evaluation, remains a critical discussion point for clinicians.

This creates a challenging diagnostic dilemma where the imperative to identify a life-threatening, treatable lesion must be balanced against the risks of repeated investigation, including radiation exposure. This clinical dilemma is particularly acute in patients with a nonperimesencephalic or diffuse hemorrhage pattern, where the risk of an underlying, occult aneurysm is substantially higher.[ 1 - 4 , 13 , 17 , 18 , 20 ] This elevated risk mandates a high index of suspicion and a proactive diagnostic strategy.

Here, we present an instructive case of angiogram-negative SAH where an anterior communicating artery (Acom) aneurysm, initially unvisualized by both computed tomography angiography (CTA) and digital subtraction angiography (DSA), became apparent during the active management of symptomatic cerebral vasospasm. This case highlights the educational value of maintaining a high index of suspicion for an occult aneurysm in patients with diffuse SAH and subsequent vasospasm. Furthermore, it underscores the importance of appropriately timed, high-quality imaging re-evaluation for accurate diagnosis and timely intervention. We aim to discuss the clinical decision-making process in this challenging situation, explore potential factors contributing to the delayed aneurysm visualization, and emphasize the practical lessons learned regarding follow-up strategies in such cases.

CASE REPORT

A woman in her 60’s with no significant medical history was transported to our hospital by ambulance due to the sudden onset of headache and vomiting. She arrived approximately 60 min after symptom onset. On arrival, she was conscious and alert with a Glasgow Coma Scale score of 15 and no focal motor deficits, corresponding to a World Federation of Neurosurgical Societies grade of 1. Head computed tomography (CT) performed within 10 min of her arrival revealed diffuse SAH corresponding to Fisher group 3, with thick hematoma deposition in the basal cisterns, bilateral Sylvian fissures, and the suprasellar cistern. Initial head CTA and DSA performed on the same day did not identify any definite aneurysms. Consequently, conservative management, including blood pressure control, was initiated for SAH of unknown origin [ Figure 1 ].

Figure 1:

Admission day (Day 0) imaging. (a) Plain axial computed tomography (CT) shows diffuse subarachnoid hemorrhage predominantly in the basal cisterns, bilateral Sylvian fissures, and the suprasellar cistern (Fisher group 3). (b) CT angiography reconstruction reveals no identifiable aneurysm. (c and d) Digital subtraction angiography with the right internal carotid artery injection (c: AP view, d: Lateral view) also shows no detectable aneurysm.

A follow-up head CT on the day after onset showed a small low-density area in the head of the right caudate nucleus, which was considered a small cerebral infarction [ Figure 2a ].

Figure 2:

Imaging findings on day 1 and day 4. (a) Axial computed tomography scan shows a small low-density lesion in the head of the right caudate nucleus (black circle). (b) Axial diffusion-weighted imaging demonstrates small foci of restricted diffusion in the left cerebral hemisphere, indicating early ischemia (white circle). (c) Magnetic resonance angiography shows diffuse vasospasm in the bilateral middle cerebral arteries (white arrows).

On day 4, the patient developed acute neurological deterioration characterized by agitation and confusion, accompanied by motor aphasia. These new deficits were attributed to symptomatic cerebral vasospasm causing ischemia in the left middle cerebral artery (MCA) territory, a finding supported by subsequent magnetic resonance imaging (MRI).

MRI revealed diffuse vasospasm in both MCAs and scattered early ischemic lesions in the left cerebral hemisphere on diffusion-weighted image [ Figures 2b and c ]. Deciding the intensity of vasospasm treatment was challenging given that the bleeding source remained unidentified. After fully explaining the risk of rebleeding associated with antiplatelet therapy in the potential presence of an undetected aneurysm and obtaining informed consent from the patient’s family, treatment for cerebral vasospasm was initiated with fluid resuscitation, cilostazol (100mg/day), an antiplatelet agent and phosphodiesterase 3 inhibitor, and fasudil (90mg/day), a Rho-kinase inhibitor. Her restlessness and aphasia improved after the initiation of treatment. An MRI on day 5 showed no progression of vasospasm, although thick hematomas persisted in the basal cisterns and bilateral Sylvian fissures.

On day 8, a repeat CTA performed for re-evaluation of the bleeding source newly identified an aneurysm on the Acom, with a maximum diameter of 3 mm. Subsequent DSA confirmed the presence of a saccular Acom aneurysm that was not visible at onset [ Figure 3 ]. Emergent coil embolization was performed on the same day, achieving complete occlusion using a simple technique with a single catheter. The aneurysm was characterized as a small saccular type with a narrow neck. In addition, severe vasospasm was noted in the left MCA, necessitating percutaneous transluminal angioplasty using a balloon catheter [ Figure 4 ].

Figure 3:

Computed tomography angiography (CTA) and digital subtraction angiography (DSA) findings on day 8. (a) Computed tomography angiography reconstruction clearly visualizes a newly apparent anterior communicating artery (Acom) aneurysm (arrow). (b) 3D (three-dimensional) rotational DSA reconstruction confirms the Acom aneurysm (arrowhead). (c) For comparison, 3D rotational DSA reconstruction from Day 0 shows no aneurysm in the same location.

Figure 4:

Intraoperative findings during endovascular treatment. (a) Digital subtraction angiography (DSA) working projection demonstrates the Acom aneurysm (arrow). (b) Postprocedural DSA shows complete occlusion of the aneurysm after coil embolization. (c) DSA (anteroposterior view of left internal carotid artery injection) reveals severe vasospasm in the left middle cerebral artery territory (circle). (d) Significant improvement in vessel caliber is observed after percutaneous transluminal angioplasty using a balloon catheter.

The postoperative course was uneventful, with no rebleeding or complications. The patient was transferred to a rehabilitation hospital on day 20 and discharged home on day 47 with a modified Rankin Scale score of 0.

Written informed consent was obtained from the patient and her family for the publication of this case report and accompanying images.

DISCUSSION

Angiogram-negative SAH, where no aneurysm is identified on initial CTA or DSA, reportedly accounts for 10–30% of all SAH cases.[ 10 , 12 , 13 ] Among these, cases with a small amount of bleeding localized around the midbrain are termed perimesencephalic SAH (PM-SAH) [ 14 ]. Most PM-SAH cases are considered nonaneurysmal in origin and typically have a favorable prognosis.[ 12 ] However, in cases like the present one, characterized by nonperimesencephalic SAH (non-PM-SAH) patterns or diffuse hematomas, a certain number of reports describe aneurysms being identified on repeat imaging studies. In non-PM-SAH cases, the risk of vasospasm and mortality is higher than PM-SAH cases, and careful follow-up and re-evaluation are required.[ 10 , 12 , 13 , 15 , 18 ]

Delayed visualization of an initially occult aneurysm is often attributed to spontaneous lysis of an intra-aneurysmal thrombus formed at rupture, leading to recanalization. An alternative, or possibly concurrent, mechanism is the external compression of a small, thin-walled aneurysm by a thick surrounding hematoma, which can temporarily prevent its filling during angiography.[ 6 - 9 , 16 ] In our case, an Acom aneurysm, not detected by initial CTA or DSA, was visualized on CTA performed on day 8.

A particularly instructive finding in this case is the small infarction in the head of the right caudate nucleus, observed on day 1. The recurrent artery of Heubner (RAH), which typically originates from the A1-A2 junction in close proximity to the anterior communicating artery complex, is the primary vascular supply to this region. We postulate that the intra-aneurysmal thrombus, which initially prevented angiographic visualization of the aneurysm, also mechanically compromised the origin of the RAH, leading to this focal ischemic event. In retrospect, this “sentinel” infarct should be considered a key diagnostic clue, pointing directly to pathology within the Acom territory and further validating the need for vigilant follow-up imaging.

The decision to initiate antiplatelet therapy for symptomatic vasospasm in the face of an unidentified bleeding source represented a significant clinical dilemma. Our institutional protocol for preventing delayed cerebral ischemia prioritizes aggressive medical management centered on clazosentan, an endothelin receptor antagonist. However, clazosentan is contraindicated in patients with an unsecured ruptured aneurysm due to the risk of rebleeding. Therefore, as an alternative strategy in this case, the decision was made to use a combination of an antiplatelet agent (cilostazol) and a Rho-kinase inhibitor (fasudil). After a thorough discussion with the patient’s family regarding the high risk of neurological decline from untreated vasospasm versus the potential, unquantified risk of re-bleeding from an occult aneurysm, a consensus was reached to proceed with treatment. While specific data on re-bleeding rates after initiating antiplatelet therapy in this precise context are scarce, the immediate and evident threat of vasospasm was deemed to outweigh the hypothetical risk of re-rupture. This decision highlights the need for individualized risk-benefit assessment in such challenging scenarios.

An interesting observation in this case is that the aneurysm became visible after the initiation of treatment with cilostazol and fasudil for cerebral vasospasm. Cilostazol possesses pleiotropic pharmacological effects, including inhibition of platelet aggregation through suppression of thromboxane A2 production and phosphodiesterase 3 inhibition as well as vasodilation and improvement of endothelial function. It has shown efficacy in suppressing cerebral vasospasm and delayed cerebral ischemia after SAH.[ 5 , 11 ] Theoretically, the antiplatelet effect of cilostazol could potentially contribute to the lysis of an intra-aneurysmal thrombus. However, there are currently no definitive reports demonstrating that antiplatelet therapy directly promotes thrombus lysis, recanalization, and visualization of aneurysms. Therefore, a causal relationship cannot be established based solely on the temporal association observed in this patient.

There is no universal consensus on the optimal timing and modality for repeat angiography in angiogram-negative, non-PM-SAH. The diagnostic yield of repeat angiography in angiogram-negative, non-PM-SAH has been a subject of numerous studies, with varied results [ Table 1 ]. Published protocols vary widely, with recommendations for repeat imaging ranging from an early phase within 7–14 days to a later phase at 2–3-month postonset. Some institutions employ a strategy of both early and late repeat angiography to maximize detection rates. The choice of modality, typically between CTA and DSA, also depends on institutional preference and the specific clinical scenario.[ 1 - 4 , 13 , 17 , 18 , 20 ] Our approach of re-imaging on day 8 falls within the early phase of these recommendations, prompted by the patient’s neurological deterioration from vasospasm, which significantly increased the pretest probability of an underlying aneurysm.

Table 1:

Summary of selected studies on the diagnostic yield of repeat angiography in nonperimesencephalic angiogram-negative subarachnoid hemorrhage.

Key learning points from this case:

Maintain a high index of suspicion for an occult aneurysm in angiogram-negative SAH, especially with diffuse bleeding patterns or subsequent vasospasm: even if initial comprehensive angiography (CTA and DSA) is negative, an underlying ruptured aneurysm should be strongly suspected in patients presenting with non-PM SAH patterns. The clinical course of diffuse SAH accompanied by vasospasm, as seen in our patient, further strengthens this suspicion and mandates continued diagnostic vigilance.

Limitations of this report include that it is a single case study, and therefore, the findings cannot be generalized. In addition, as previously mentioned, the causal relationship between antithrombotic agent administration and aneurysm visualization remains unclear; the observation is based solely on temporal correlation, and the precise mechanism underlying the delayed visualization of the aneurysm is unknown. Despite these limitations, the clinical course presented offers valuable insights and is instructive for managing similar challenging cases of angiogram-negative SAH.

CONCLUSION

This case underscores a critical lesson: in patients with angiogram-negative SAH, particularly with diffuse bleeding patterns or vasospasm, a high index of suspicion for an occult aneurysm must guide persistent diagnostic efforts. While the exact mechanism of delayed visualization, including any potential influence of vasospasm treatment, requires further elucidation, our experience highlights that meticulous clinical monitoring combined with appropriately timed, high-quality angiographic re-evaluation is paramount for accurate diagnosis, timely intervention, and ultimately, achieving favorable patient outcomes.

Ethical approval:

Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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