Understanding Unruptured Brain Aneurysms: A Comprehensive Patient Guide

Table of Contents

• The Clinical Problem
• Risk Factors for Aneurysm Formation
• Natural History and Rupture Risk
• Diagnostic Imaging
• Risk Assessment and Treatment Decisions
• Conservative Treatment and Monitoring
• Interventional Treatment Options
• Patient Considerations and Quality of Life
• Clinical Recommendations
• Study Limitations
• Source Information

The Clinical Problem

Intracranial aneurysms are abnormal bulges or weak spots in the walls of brain arteries. They are the most common cause of nontraumatic subarachnoid hemorrhage, a type of bleeding in the brain that is associated with high mortality rates. This makes early detection and management of unruptured intracranial aneurysms (UIAs) critically important for patient safety.

A massive systematic review of 68 studies across 21 countries, involving 94,912 patients, found that the overall prevalence of UIAs is approximately 3.2% in the general population without other medical conditions. The prevalence is higher in certain groups, particularly women, people aged 30 years and older (with peak occurrence in the 50-59 age range), and those with a family history of UIAs, subarachnoid hemorrhage, hypertension, or autosomal dominant polycystic kidney disease.

Approximately 90% of these aneurysms are saccular (berry-shaped) and typically form at artery branch points in specific locations: the internal carotid artery, anterior and posterior communicating arteries, and middle cerebral artery. In the back of the brain (posterior circulation), they commonly occur at the basilar artery bifurcation and cerebellar artery branches. Up to 20% of patients with UIAs have multiple aneurysms.

Risk Factors for Aneurysm Formation

Risk factors for developing brain aneurysms are divided into modifiable (changeable) and nonmodifiable (unchangeable) categories. Understanding these factors is crucial for prevention and management.

Modifiable risk factors include:

• Cigarette smoking: A case-control study with 206 UIA patients and 574 controls identified smoking as an independent risk factor
• Hypertension (high blood pressure): The same study found hypertension to be another independent risk factor
• Heavy alcohol use: May also contribute to UIA formation

Interestingly, the research showed that hypercholesterolemia (possibly due to statin medication use) and regular physical exercise were associated with a decreased risk of aneurysm formation. A multicenter case-control study with 113 matched pairs demonstrated that risk factors work together synergistically - female smokers had four times the risk, while hypertensive female smokers had seven times the risk compared to nonsmoking women with normal blood pressure.

Nonmodifiable risk factors include:

• Female sex: Women have approximately twice the risk of men (2:1 ratio), especially after age 50, possibly due to hormonal factors
• Increasing age: Risk rises with age, particularly after 30
• Genetic predisposition: Family history significantly increases risk

A large systematic review and meta-analysis of 116,570 patients identified specific gene variations (CDK2NB, EDNRA, and SOX17) that contribute to aneurysm formation. These genes are involved in cell cycle regulation, vascular smooth muscle proliferation, and blood vessel maintenance.

Certain inherited conditions also increase risk, including autosomal dominant polycystic kidney disease, coarctation of the aorta, Ehlers-Danlos syndrome, glucocorticoid-remediable aldosteronism, moyamoya disease, and thoracic aortic aneurysms. A family history of UIA or subarachnoid hemorrhage increases the risk of aneurysm formation by a factor of 3.64 and raises the risk of rupture by a factor of 2.5. This risk can be as high as 17 times greater among smokers with hypertension.

Natural History and Rupture Risk

Understanding the natural course of unruptured aneurysms is essential for making treatment decisions. However, predicting exactly which aneurysms will rupture remains challenging with limited long-term data available.

Key factors that increase rupture risk include:

• Female sex
• Hypertension
• Smoking
• Large aneurysm size (≥7 mm)
• Irregular shape or "daughter sac" (small outpouching)
• Multiple aneurysms
• Location in the internal carotid or basilar artery
• Concurrent arteriovenous malformations

People with a family history of UIAs or subarachnoid hemorrhage tend to experience rupture at smaller aneurysm sizes and younger ages, often with worse outcomes than those with sporadic aneurysms.

Diagnostic Imaging

UIAs are typically diagnosed using computed tomographic angiography (CTA) or magnetic resonance angiography (MRA). These imaging methods are often performed incidentally during routine screening of high-risk patients or when evaluating symptoms such as chronic headaches, dizziness, vision problems, or neurological symptoms.

CTA and MRA are preferred for routine screening because they're highly sensitive and noninvasive. Digital subtraction angiography remains the gold standard for detailed imaging, providing superior visualization of aneurysm features, detecting very small aneurysms, and facilitating treatment planning. It's typically used when there's high clinical suspicion despite normal CTA and MRA findings, or for pretreatment planning.

Patients undergoing these imaging procedures should be evaluated for potential contraindications, such as risk of contrast nephropathy (kidney damage from dye), and counseled about possible adverse effects including radiation exposure (with CTA), nephrotoxic effects, and rare complications with digital subtraction angiography such as thromboembolic events, infection, or vessel injury.

Risk Assessment and Treatment Decisions

Managing UIAs requires a multidisciplinary approach and shared decision-making between patients and healthcare providers. Several scoring systems have been developed to help assess rupture risk and guide treatment decisions.

The PHASES score (Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid hemorrhage, and Site of aneurysm) was developed from a meta-analysis of six prospective cohort studies involving 10,272 UIAs in 8,382 patients followed for 1-21 years. This score estimates the 5-year risk of aneurysm rupture:

• Score ≤2: 0.4% risk (95% CI, 0.1-1.5)
• Score of 5: 1.3% risk (95% CI, 0.8-2.4)
• Score of 10: 5.3% risk (95% CI, 3.5-8.0)
• Score ≥12: 17.8% risk (95% CI, 15.2-20.7)

The overall 1-year risk of UIA rupture using PHASES was 1.4% (95% CI, 1.1-1.6), and the 5-year risk was 3.4% (95% CI, 2.9-4.0). However, the PHASES score has limitations - it doesn't include known risk factors like smoking, family history, or aneurysm shape, and it hasn't been validated in prospective studies.

Other important studies have provided additional insights:

• The International Study of Unruptured Intracranial Aneurysms found annual rupture risks as low as 0.05% for small anterior circulation aneurysms (<10 mm) in patients without previous subarachnoid hemorrhage
• Risks increased to 1% annually for aneurysms ≥10 mm and up to 6% for those ≥25 mm
• Patients with previous subarachnoid hemorrhage had higher annual risks (~0.5%), even for small aneurysms
• The Japanese Unruptured Cerebral Aneurysm Study showed annual rupture risks of 0.54% for aneurysms <7 mm, increasing to 1-2% for aneurysms ≥7 mm, especially in the posterior circulation

The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was developed by 69 experts through a Delphi consensus process and incorporates treatment-related risk factors to personalize management. Other scoring systems include a Finnish model that uses only four variables (age, smoking, aneurysm diameter, and location) and a Japanese model from the UCAS study that includes age, sex, hypertension, aneurysm size, location, and presence of a daughter sac.

For monitoring aneurysm growth, the ELAPSS score (Earlier subarachnoid hemorrhage, Location of aneurysm, Age, Population, and Size and Shape of aneurysm) was developed from pooled data of 10 cohorts to assess the risk of UIA growth within 3 or 5 years. This helps guide follow-up imaging intervals, particularly for identifying patients with higher growth risk who may need more frequent monitoring.

Conservative Treatment and Monitoring

For asymptomatic patients with small (<7 mm) incidental UIAs, conservative management is typically recommended due to their low rupture risk. This approach focuses on modifying risk factors known to contribute to aneurysm growth.

Key components of conservative management include:

• Smoking cessation: Complete stopping of tobacco use
• Blood pressure control: Maintaining normal blood pressure levels
• Patient education: Understanding the condition, risks, and warning signs
• Shared decision-making: Active participation in treatment choices

Patients should be informed about the risks of subarachnoid hemorrhage, recognize warning signs like thunderclap headache ("the worst headache of my life") and cranial nerve palsies, know when to seek immediate medical attention, and understand the importance of long-term follow-up.

Research shows that uncontrolled hypertension is associated with a 6.1 times higher risk of aneurysm growth compared to patients without hypertension, and 3.9 times higher risk compared to those with controlled hypertension.

Routine monitoring typically involves noninvasive CTA or MRA imaging every 6 months until the aneurysm is stable, then annually for 2-3 years, and less frequently thereafter if no changes are observed. The frequency may be increased for higher-risk aneurysms.

Interventional Treatment Options

For higher-risk aneurysms (typically ≥7 mm in diameter located in the anterior circulation), intervention may be recommended. The two main approaches are endovascular treatment and surgical clipping.

Endovascular techniques are minimally invasive procedures performed through blood vessels. These include:

• Coiling: Inserting tiny platinum coils into the aneurysm to promote clotting
• Flow diversion: Using specialized stents to redirect blood flow away from the aneurysm

Endovascular approaches are associated with lower perioperative risks but higher risks of aneurysm recurrence requiring retreatment.

Surgical clipping involves a craniotomy (opening the skull) to place a tiny clip across the aneurysm neck, isolating it from circulation. This provides more durable results but carries greater procedural risks, including those associated with open brain surgery.

The choice between these approaches depends on multiple factors including aneurysm size, location, shape, patient age, overall health, and surgeon expertise. The article emphasizes that treatment decisions should be individualized through shared decision-making between patients and their healthcare team.

Patient Considerations and Quality of Life

Living with an unruptured intracranial aneurysm can cause significant anxiety and psychological distress for patients. The knowledge that you have a potential time bomb in your head can profoundly affect quality of life, daily activities, and mental health.

Important considerations for patients include:

• Psychological support: Seeking counseling or support groups to manage anxiety
• Patient education: Fully understanding your specific condition and risks
• Shared decision-making: Being an active participant in treatment choices
• Adherence to monitoring: Keeping regular follow-up appointments and imaging studies
• Lifestyle modifications: Implementing changes to reduce risk factors

Healthcare providers should address these psychological aspects and provide appropriate resources and support to help patients cope with the emotional burden of living with a UIA.

Clinical Recommendations

Based on the comprehensive evidence presented, the author provides these clinical recommendations for managing unruptured intracranial aneurysms:

1. Risk assessment: Use validated scoring systems like PHASES to estimate rupture risk and guide management decisions
2. Modifiable risk factors: Implement aggressive management of hypertension and complete smoking cessation
3. Imaging: Use CTA or MRA for initial detection and monitoring; reserve digital subtraction angiography for complex cases or treatment planning
4. Conservative management: Recommend for small (<7 mm), incidental anterior circulation aneurysms with focus on risk factor modification and regular monitoring
5. Intervention consideration: Consider for higher-risk aneurysms (≥7 mm, posterior circulation, symptomatic, or with high-risk features)
6. Treatment approach: Choose between endovascular techniques (lower procedural risk but higher recurrence) and surgical clipping (higher procedural risk but more durable) based on individual patient and aneurysm factors
7. Psychological support: Address patient anxiety through education, support, and shared decision-making
8. Long-term monitoring: Establish regular follow-up protocols based on individual risk profiles

Study Limitations

While this article provides comprehensive guidance based on current evidence, several limitations should be acknowledged:

The PHASES score, while useful, has not been validated in prospective studies and omits known risk factors such as smoking, family history, and aneurysm shape. Most data comes from observational studies rather than randomized controlled trials, which limits definitive conclusions about optimal management strategies.

There is significant variation in rupture risk estimates between different studies and populations, particularly between Japanese and Western cohorts. This suggests that ethnic and genetic factors may play important roles that aren't fully captured in current risk assessment models.

Long-term data beyond 5-10 years is limited for both natural history and treatment outcomes, making truly long-term predictions challenging. Additionally, most studies have focused on anatomical and clinical factors, with less attention to quality of life and psychological impact, which are crucial considerations for patients.

Source Information

Original Article Title: Clinical Practice: Unruptured Intracranial Aneurysms
Author: Christopher S. Ogilvy, M.D.
Publication: The New England Journal of Medicine
Publication Date: June 19, 2025
Volume and Issue: 2025;392:2357-66
DOI: 10.1056/NEJMcp2409371

This patient-friendly article is based on peer-reviewed research originally published in The New England Journal of Medicine. It has been converted to make complex medical information accessible to patients while preserving all scientific data, statistics, and findings from the original publication.