2.1 Goals

1. 
   

   Review the literature that forms the basis of our understanding of the natural history of cerebral aneurysms.

   
   
2. 
   

   Critically analyze the literature on the natural history of cerebral aneurysms.

   
   
3. 
   

   Review the literature that supports treatment of unruptured cerebral aneurysms versus observation.

   
   
4. 
   

   Critically analyze more recent attempts to quantify the natural history of unruptured cerebral aneurysms and their treatment.

2.2 Case Example

2.3 Case Summary

1. 
   

   What would you report as the rupture risk of the unruptured cerebral aneurysms to this patient?

   
   

   The decision to treat an unruptured cerebral aneurysm is largely predicated on the perceived rupture risk of the aneurysm. We are attempting to improve the long-term outcomes for the patient by reducing the rupture risk of the aneurysm over the patient’s lifetime versus the immediate/short-term risk of the treatment.

   
   

   Our knowledge of the rupture rate of unruptured cerebral aneurysms has been developed over time by multiple landmark papers that are reviewed in this chapter. ^{1 , 2 , 3 , 4 , 5} Additionally, there are multiple factors (patient and aneurysm related) which can be taken into account in the decisionmaking process. Reported rupture rates can vary widely in the literature based upon the specific study and its methodology. For aneurysms of these sizes in this patient, the rupture rates can be quoted to be as low as < 0.05% per year ⁵ to as high as approximately 14.5% over 5 years. ⁴ There are multiple studies that would also place the rupture risk of unruptured cerebral aneurysms at around 1 to 1.5% per year. ^{3 , 6}

   
   
2. 
   

   What patient factors would you consider when deciding on your recommendations for observation or treatment of these unruptured cerebral aneurysms?

   
   
   
   
   1. 
      

      Age

      
      

      Since the risk of cerebral aneurysm rupture is life long, age is an important consideration when counseling patients for either observation or treatment. ⁷ A recent analysis of three large prospective cohort trials in Japan identified increasing patient age as an independent risk factor for aneurysm rupture ⁸ corroborating the results of an earlier published meta-analysis. ⁹ These results, however, are in contradiction to other studies that identified younger patient age as a risk factor for future aneurysm rupture. ^{3 , 10} In addition, certain methods of treatment may pose higher risks as patient’s age increases. ¹¹

      
      
   2. 
      

      Smoking

      
      

      Smoking appears to be one modifiable risk factor associated with an increased prevalence of unruptured cerebral aneurysms and, even possibly, with subsequent aneurysm rupture. ^{4 , 5 , 10} Whether or not smoking cessation improves the natural history, however, is unknown.

      
      
   3. 
      

      Multiplicity

      
      

      The presence of multiple aneurysms is found in upwards of 30% of patients with a diagnosis of cerebral aneurysms and may be associated with subsequent aneurysm growth, a strong marker for subsequent rupture. ^{3 , 5 , 6 , 12} However, other studies suggest that multiplicity of aneurysms is unrelated to future rupture risk. ¹³

   
   
3. 
   

   What aneurysm factors would you consider when deciding on your recommendations for observation or treatment of these unruptured cerebral aneurysms?

   
   
   
   
   1. 
      

      Size

      
      

      Size of an unruptured cerebral aneurysm has been extensively studied in relation to the risk of aneurysm rupture. ^{1 , 4 , 5 , 6 , 13} The size cutoff has been set at different levels by different studies. One centimeter was used in earlier studies with subsequent refinement to 7 mm in later studies. ^{1 , 4 , 5} In addition, investigators in Japan identified an increasing risk of rupture with increasing aneurysm size. ⁶

      
      
   2. 
      

      Vessel location

      
      

      Likewise, the location of the aneurysm has also been extensively studied in the literature. ^{4 , 5 , 6} Posterior circulation aneurysms have been posited to have a higher rupture rate than anterior circulation aneurysms. ^{4 , 5} Interestingly, these studies categorized posterior communicating arteries as posterior circulation aneurysms. The UCAS investigators also found differences in rupture risk based upon location, but only for anterior circulation aneurysms. ⁶ Aneurysms on the anterior or posterior communicating arteries had a higher rupture risk than aneurysms on the middle cerebral artery. There was no increased rupture risk with posterior circulation aneurysms.

      
      
   3. 
      

      Irregularity/daughter sacs

      
      

      Studies have identified aneurysm irregularities and/or presence of daughter sacs as an independent risk factor for subsequent aneurysm rupture. ⁶

   
   
4. 
   

   What would you recommend for the left posterior communicating artery aneurysm?

   
   

   Given the patient’s age, smoking history, size, location, and irregularity of the aneurysm, a strong argument can be made for treatment. Studies on the natural history of cerebral aneurysms have suffered from significant selection bias with inclusion of patients who were prescreened for observation over treatment. ^{1 , 4 , 5 , 6}

   
   

   Likewise, the method of treatment, either endovascular or surgical, is a decision to be made based upon the expert medical opinion of the practitioner(s) and the patient. Certainly, aneurysm-specific characteristics may preclude treatment by one method over another. In this instance, the aneurysm could be readily treated by either modality. After a lengthy discussion with the patient, he elected for endovascular treatment with balloon-assisted coil embolization. Also, the presence of a second aneurysm factored into the discussion with a strong desire to avoid bilateral open surgeries.

   
   
5. 
   

   What wouldyou recommend for the right middle cerebral artery aneurysm?

   
   

   In this instance, the patient ultimately elected for treatment of this aneurysm for reasons very similar to the ones previously stated. Observation was also a valid option given the smaller size and the location in the anterior circulation/middle cerebral artery. However, the patient’s young age and presence of a small daughter sac/dome irregularity weighed more heavily in the decision-making process. Unlike with the contralateral aneurysm, the middle cerebral artery aneurysm was wide necked, making coil embolization with or without adjunctive techniques a less attractive option. The use of flow diversion has been reported in this location, but the studies have largely been limited to smaller, retrospective, single-center series. In addition, younger patients may do better following surgical clipping than older patients with outcomes comparable to endovascular treatment. ⁴ Recurrence and retreatment rates following surgical clipping are also lower than with coil embolization.

   
   
6. 
   

   How would you follow-up these aneurysms with or without treatment?

   
   

   There are several methods of following up treated aneurysms with imaging studies: digital subtraction angiography, CT angiography, or MRA In this instance, we elected to follow up long term with both an MRA and CTA given the different treatment techniques.

2.4 Level of Evidence

Patients age: Given the patient’s relatively young age, treatment of aneurysms, including surgical clipping of the middle cerebral artery aneurysm, is reasonable (Class I, Level of Evidence B).

Smoking history: The patient’s extensive smoking history may present a risk for aneurysm development (Class I, Level of Evidence B).

Multiplicity of aneurysms: The patient has middle cerebral and posterior communicating artery aneurysms (Class I, Level of Evidence C).

Angiomorphology and location of the aneurysm: The posterior communicating artery aneurysm was highly irregular with associated daughter sacs (Class I, Level of Evidence C).

Treatment: Surgical clipping may be more durable than endo-vascular coiling but may be associated with higher procedural morbidity and mortality (Class IIB, Level of Evidence B).

Follow-up of aneurysm: With the small residual neck of the coiled aneurysm, periodic follow-up imaging studies should be performed. In this case, we elected to follow up with MRA studies, which demonstrated stability of the Raymond 2 aneurysm occlusion (Class I, Level of Evidence B).