Unruptured Cerebral Aneurysms

2 Unruptured Cerebral Aneurysms


Min S. Park, M. YasharS. Kalani, and Michael F. Stiefel


Abstract


The management of unruptured cerebral aneurysms is a fundamental component of most neurointerventional practices. The decision to observe these lesions or offer treatment is predicated on the risk of future rupture of the cerebral aneurysm over the expected remaining lifetime of the patient. The natural history data on unruptured cerebral aneurysms rely on several landmark papers that are well quoted throughout the medical literature; however, it is important to delve closely into the original papers to better understand these results and their limitations. In addition, it is important to have a solid understanding of the evidence that might support neurointerventional management of cerebral aneurysms.


Keywords: cerebral aneurysm, natural history, rupture rate, clipping, coiling, flow diversion


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


2.2.1 History of Present Illness


A 48-year-old non-Japanese, non-Finnish man presents for initial evaluation after discovery of two incidental cerebral aneurysms on magnetic resonance imaging and angiography (MRI/ A) for work-up of a several-year history of cluster-type headaches. He has an extensive history of smoking and alcohol use. He denies any significant neurological complaints including seizures, loss of consciousness, numbness, weakness, or speech/vision difficulty


Past medical history: Denies history of polycystic kidney disease, collagen vascular disease, prior subarachnoid/intracranial hemorrhage, or hypertension.


Past surgical history: Previous laparoscopic cholecystectomy.


Family history: Denies history of cerebral aneurysms.


Social history: 30 pack/year smoking history.


Review of systems: As per the above.


Neurological examination: Unremarkable.


Imaging studies: See figures.


Fig. 2.1a, b: MRA brain of a 4.5 * 4.5 mm right middle cerebral artery aneurysm and a cerebral angiogram of an irregular 8×4 mm left posterior communicating artery aneurysms. Both aneurysms had associated daughter sacs/dome irregularities.


2.2.2 Treatment Plan


The patient agreed to treatment of the incidental aneurysms after he discontinued the use of cigarettes. The recommendation was made for coil embolization of the left posterior communicating artery aneurysm followed by surgical clipping of the right middle cerebral artery aneurysm because of the angiomorphology and accessibility of the respective aneurysms.


2.2.3 Follow-up


The patient did very well after the initial embolization of the posterior communicating artery aneurysm, which had a small residual neck (Raymond 2 occlusion) after the treatment. He underwent uncomplicated clipping of the right middle cerebral artery aneurysm several months later. At his 2-year follow-up visit, he was doing well with a stable, small residual neck of the coiled left posterior communicating artery aneurysm on an MRA brain. Additionally, there was no evidence of recurrence of the right middle cerebral artery aneurysm on computed tomography angiograms of the head.


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 year5 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?


a) 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 rupture8 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


b) 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.


c)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?


a)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


b) 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.


c) 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).


2.5 Landmark Papers


Wiebers DO, Whisnant JP, O’Fallon WM. The natural history of unruptured intracranial aneurysms. N Engl J Med 1981,304 (12):696-698.


Any discussion of landmark papers on the natural history of unruptured cerebral aneurysms must include the work of Dr. David 0. Wiebers and his collaborators at the Mayo Clinic and Mayo Foundation in Rochester, Minnesota.1 In 1981, they reported on the natural history of 65 patients (22 men and 43 women) with 81 unruptured saccular aneurysms documented by cerebral angiography from 1955 to 1975, who did not undergo surgical treatment and were followed up for a minimum of 5 years after diagnosis or until death. Thirty-six of the patients had angiograms performed due to neurological symptoms (mass effect-like symptoms, ischemic symptoms, and/or headaches), whereas 29 patients had symptoms that were unrelated to the aneurysm.


Over the course of the follow-up period, eight patients experienced aneurysmal rupture, with seven of the eight dying as a result of the intracranial hemorrhage. Wiebers et al performed a multivariate analysis to determine whether patient-related (age, sex, presence of hypertension) and/or aneurysm-related (size, location, number, multilobulated aneurysms, symptoms other than hemorrhage) factors were predictive of future rupture. Their analysis indicated that aneurysm size greater than 10 mm was the most predictive of future rupture. Indeed, four aneurysms between 10 and 20 mm ruptured and four aneurysms greater than 20 mm ruptured, whereas no aneurysms below 10 mm in size ruptured. In addition, four patients with aneurysms ruptured within 21/2 months from the initial diagnosis had a mean aneurysm size of 30 mm. The other four patients whose aneurysms ruptured at a later time had a mean size of only 15.7 mm. The authors also noted that aneurysms were unlikely to cause symptoms of mass effect unless they were at least 8 mm in size.


On the basis of their results, the authors concluded that aneurysms less than 10 mm in size had a very low probability of subsequent rupture; however, patients with aneurysms > 10 mm in size should be treated as soon as possible. If aneurysms cause symptoms of mass effect after the initial diagnosis, then it likely indicates enlargement of the aneurysm to greater than 8 mm and, thus, portended a higher likelihood of rupture.


As one of the seminal works on the natural history of cerebral aneurysms, the article by Wiebers et al established the baseline to which all other papers would be compared. Unlike the later series by Juvela et al, there was no reported policy at Wieber et al’s institution to not treat incidental, unruptured aneurysms.3 This preselection of untreated, unruptured aneurysms potentially introduced an element of selection bias. No information was provided concerning those patients diagnosed with unruptured aneurysms who underwent elective treatment and, thus, were not available for this study. In addition, all of the follow-up was by communication (telephone interviews, records reviews, etc.) rather than by imaging. Thus, the authors were unable to discuss aneurysm growth as a risk factor; other than that the development of symptoms of mass effect over time would suggest aneurysm growth to at least 8 mm in size. The lack of significance of the other studied variables may be related more to the smaller sample size versus a lack of true significance.


juvela S, Porras M, Heiskanen O. Natural history of unruptured intracranial aneurysms: a long term follow-up study. J Neurosurg 1993;79(2):174-182.


Dr. Seppo Juvela and coauthors published another landmark paper in 1993 in which they followed 142 patients with 181 unruptured cerebral aneurysms in Finland.3 The basis of this study was an institutional/national policy prior to 1979 of not treating unruptured aneurysms. From 1956 to 1978, 142 patients (66 men and 76 women) with 181 aneurysms were followed up for a total of 1944 patient-years and, on average, 13.7 years per patient.


During the follow-up period, 27 of the 142 (19%) patients ultimately experienced a subarachnoid hemorrhage from an unruptured aneurysm with an approximate annual incidence of aneurysm rupture of 1.4%. The risk of rupture remained fairly constant over the decades of follow-up in their study with the observed cumulative risk of rupture of 32% at 30 years after diagnosis. Although Juvela et al did not find a definitive size cutoff to predict aneurysm rupture as in previous studies, they did note a linear relationship between the risk of rupture and aneurysm size.2 In addition, they found that all aneurysms which subsequently ruptured increased in size compared with the aneurysms that had not ruptured. De novo aneurysm formation was 2.2% per angiographic follow-up year.


On the basis of their findings, the authors recommended treatment of all cerebral aneurysms, irrespective of size, if technically feasible and if there were no contraindications to surgery from concurrent disease or advanced age.


Although this is easily considered one of the landmark papers on the natural history of unruptured cerebral aneurysms, there is one issue that limits the generalizability of the results. The majority of the patients included in this study had either a symptomatic aneurysm (6 of 142 patients) or a previous subarachnoid hemorrhage from an aneurysm rupture (131 of 142 patients). Only 5 of 142 patients had truly incidental aneurysms. Given the time period of the study (pre-1979) and the lack of advanced, noninvasive imaging studies at that time, this is hardly surprising; however, it does lead to questions concerning the selection bias of this particular cohort and whether their recommendations can be applied to truly incidental aneurysms (i.e., without a prior history subarachnoid hemorrhage). Unlike subsequent and previous studies concerning the natural history, there was no selection bias for treatment since all unruptured aneurysms were managed conservatively.


International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998,339 (24):1725-1733.


Perhaps one of the most controversial landmark papers on the topic of the natural history of unruptured aneurysms was published in 1998 in the New England Journal of Medicine.5 The International Study of Unruptured Intracranial Aneurysms (ISUIA) involved 2,621 patients in the United States, Canada, and Europe. The investigators retrospectively determined rupture risks in 1,449 patients with 1,937 unruptured aneurysms. About half of these patients (group 1, 727 patients) had no prior history of subarachnoid hemorrhage, while the other half (group 2, 722 patients) did. In addition, they followed up 1,172 patients prospectively who underwent surgical treatment to determine treatment-related morbidity and mortality.


The reported rupture rates for all patients were significantly lower than previously reported. Group 1 patients (no history of subarachnoid hemorrhage) had a rupture risk of< 0.05% per year for aneurysms smaller than 10 mm, whereas group 2 patients had a rupture risk of 0.5% per year for small aneurysms. For aneurysms > 10 mm in diameter, the rupture rates were still less than 1%, although the rupture rate for giant aneurysms (>25 mm) in group 1 was reportedly 6% in the first year. Overall, the rupture rate for all patients, 0.5% per year, was considerably lower than earlier reports. In addition, posterior circulation aneurysms were also noted to have a greater risk of rupture than those in other locations.


The prospective arm of the study also subdivided patients into two groups based on prior history of subarachnoid hemorrhage. The majority of the patients (996 of 1,172 patients) underwent surgical clipping of the aneurysm, with the remainder being treated by “various endovascular procedures.” The complications following surgery were considerably higher than previously reported, with combined morbidity and mortality in group 1 patients of 17.5% and 15.7% at 30 days and 1 year, respectively, and 13.6% and 13.1%, respectively, for group 2 patients.


Considering the identified risk of rupture and the combined morbidity and mortality for treatment, the ISUIA investigators stated that it would appear unlikely that the risks of treatment for aneurysms less than 10 mm would improve on the overall natural history of these aneurysms.


Following the publication of what has become known as ISUIA 1, a litany of complaints was voiced by the neurosurgical and neurointerventional community. Most notably, issues were raised concerning the selection bias inherent in these types of studies. Aneurysms that were considered unsuitable for observation were treated, either surgically or endovascularly, and were unavailable for the retrospective component of the study. Thus, the patients in the retrospective arm would include a preponderance of aneurysms that were deemed “safe” to follow. This resulted in several notable differences in various groups. For example, there was an underrepresentation of larger aneurysms in patients with prior subarachnoid hemorrhage and an overrepresentation of certain types of aneurysms for which most practitioners would not recommend treatment, for example, cavernous internal carotid artery aneurysms. In addition, questions were raised concerning the higher reported complication rates of treated aneurysms as well.


Wiebers DO, WhisnantJP, Huston J HI, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362(9378): 103-Uh


The follow-up study to the first ISUIA publication involved a prospective assessment of unruptured aneurysms of 4,060 total patients enrolled over a 7-year period (December 1991 to December 1998).4 Three groups of patients were involved: 1,692 patients were followed up in the observation arm, 1,917 had open surgery for treatment of their aneurysm, and 451 had endovascular repair. Similar to the original ISUIA publication, the observational arm was divided into two groups based on a prior history of subarachnoid hemorrhage from a separate aneurysm.4,5


In the natural history cohort, a total of 51 of 1,692 patients (3%) experienced a confirmed aneurysm rupture within the 5-year follow-up period. Another 36 patients who had both an aneurysm and another potential source for the hemorrhage were excluded from the analysis. This resulted in a more detailed report of 5-year cumulative rupture risks according to the size and location of the aneurysms ( Table 2.1). Although groups 1 and 2 were reported separately for aneurysms smaller than 7 mm, they were reported together in all other size categories because of the smaller numbers of patients.


The 5-year natural history of unruptured aneurysms in the observational cohort of what has become known as ISUIA 2 indicated a higher risk of rupture than was reported in ISUIA 1. However, the investigators still contended that aneurysms < 7 mm in size without a prior history of subarachnoid hemorrhage had an exceedingly low rate of rupture (0.1% per year). In addition, the ISUIA investigators included posterior communicating artery aneurysms in the posterior circulation cohort, a rather curious classification given most commonly held anatomical teachings.


The complication rate for open surgical treatment was also reportedly better than in the original study. Combined morbidity and mortality at 1 year in the surgical arm was 12.6% for group 1 patients and 10.1% for group 2 patients, whereas the same rates reported in the initial study were 15.7% and 13.1% for groups 1 and 2, respectively.4,5 Comparatively, the endovascular complication rates at 1 year were 9.8% and 7.1% for groups 1 and 2, respectively, despite having generally older patients, larger aneurysms, and more posterior circulation aneurysms compared with the surgical arm.


May 5, 2024 | Posted by in NEUROSURGERY | Comments Off on Unruptured Cerebral Aneurysms

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