Article: Unruptured Cerebral Aneurysms progression

Light shed on unruptured cerebral aneurysm course

Published on June 28, 2012 at 5:15 PM

By Eleanor McDermid

A large study in The New England Journal of Medicine offers new data on the natural course of unruptured cerebral aneurysms.

The study involves 5720 Japanese patients with 6697 aneurysms, making it even larger than the International Study of Unruptured Intracranial Aneurysms (ISUIA), although follow up is shorter so far, at 3 years.

"This is a very valuable study, in a difficult area to get good quality information," ISUIA co-investigator Andrew Molyneux (University of Oxford, UK) told MedWire News.

The latest findings, from Akio Morita (University of Tokyo, Japan) and fellow Unruptured Cerebral Aneurysm Study of Japan investigators, generally confirm those of ISUIA. Aneurysm rupture was rare overall, with 111 aneurysms rupturing during follow up, to give an annual rate of 0.95%. However, Molyneux noted that this rate is probably higher than would be found in European populations. The rupture rate would also have been influenced by the fact that 3050 aneurysms were treated during follow up.

As in previous studies, size was an important factor. Relative to aneurysms that were 3-4 mm in size, the rupture risk increased a significant 3.35-fold in those that were 7-9 mm, 9.09-fold in those that were 10-24 mm, and 76.26-fold in those that were 25 mm or larger. These associations were independent of baseline variables, including age and smoking status.

A new finding is that aneurysms in the anterior communicating artery were about twice as likely to rupture as those in the middle cerebral artery (MCA), as were those in the posterior communicating artery. In addition, aneurysms with a daughter sac had an increased rupture risk.

Molyneux suggested that the findings may encourage more treatment of unruptured mid-size and larger aneurysms, but a more conservative approach to small MCA aneurysms. And he added that the findings "provide additional confidence for doctors in explaining life time risk/benefit ratio of treatment."

However, Molyneux said that unruptured aneurysms detected incidentally may be very different to aneurysms detected only when they rupture, as the latter could, conceivably, form and rupture over a very short space of time. "This is an area where there remains considerable uncertainty in respect of advice to patients as to what best to do."

But the low rupture rate in the context of high aneurysm prevalence (about 32,000 per 1 million adults) means randomized trials of intervention versus conservative management will need huge numbers of patients to show an effect, and it can be difficult to accrue patients to a trial where the control option is no treatment.

"Sadly, it's a field that we'll probably never get grade 1 evidence in, so observational studies is the only thing we're going to have available," said Molyneux.

This is the same article with more basic statistics:

Brain Aneurysm Characteristics Predict Rupture

By Nancy Walsh, Staff Writer, MedPage Today
Published: June 27, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Size, location, and shape of cerebral aneurysms can help predict whether rupture is likely to occur, a Japanese study found.

Compared with aneurysms 3 to 4 mm in size, 7-to-9-mm lesions had a hazard ratio for rupture of 3.35 (95% CI 1.87 to 6, P<0.001), according to Akio Morita, MD, PhD, of the University of Tokyo, and colleagues.

And compared with lesions in the middle cerebral arteries, the hazard ratios were 2.02 (95% CI 1.13 to 3.58, P=0.02) for those in the anterior communicating artery and 1.90 (95% CI 1.12 to 3.21, P=0.02) for those in the internal carotid-posterior communicating artery, the researchers reported in the June 28 issue of the New England Journal of Medicine.

Aside from size and location of the aneurysm, the presence of a protrusion on the wall of the lesion, or "daughter sac," also was associated with increased risk of rupture (HR 1.63, 95% CI 1.08 to 2.48, P=0.02).

Incidentally identified cerebral aneurysms are not rarities, particularly among older adults, and the need for surgical intervention has remained controversial.

To explore the natural history of these lesions and determine potential risk factors that may be associated with rupture, Morita and colleagues undertook a prospective study in multiple centers in Japan, enrolling 5,720 patients who were found to have 6,697 aneurysms.

In most cases, patients were asymptomatic.

Two-thirds were women, mean age was 62.5, and mean aneurysm size was 5.7 mm.

The aneurysms typically were larger in older patients. Lesions of 7 mm or greater were identified in only 18% of patients younger than 50, but in almost 40% of patients 80 and older (P<0.001).

The aneurysms were surgically repaired in 2,722 patients, at a median of 4 months after being discovered.

During 11,660 aneurysm-years of follow-up, there were 111 cases of rupture, for an annual risk of 0.95 (95% CI 0.79 to 1.15).

However, this may be an underestimate relating to case-selection bias, because patients were removed from the analysis at the time of surgical intervention, the researchers pointed out.

In 35% of cases, the rupture was fatal, and in an additional 29%, the patients were at least moderately disabled.

Lesions between 3 and 6 mm in size were not associated with an elevated risk for rupture, but the risk was exceedingly high for the largest aneurysms:

  • 10 to 24 mm, HR 9.09 (95% CI 5.25 to 15.74, P<0.001)
  • 25 mm or greater, HR 76.26 (95% CI 32.76 to 177.54, P<0.001)

However, while women appeared to have a higher risk of rupture, this was not statistically significant in the multivariate analysis (HR 1.54, 95% CI 0.99 to 2.42).

Unlike other studies, where smoking, hypertension, past subarachnoid hemorrhage, and multiple aneurysms were found to be risk factors, no significant association was seen in this cohort.

Possible explanations for a lack of association for these factors included changes in patterns of smoking and blood pressure treatment, small numbers of previous subarachnoid hemorrhages, and the statistical approach of measuring rates of rupture per aneurysm-years rather than per patient.

A limitation of the study was its inclusion of only Japanese patients, who have a higher incidence of subarachnoid hemorrhage compared with other groups.

The risk of rupture was higher in this study than in another cohort, the International Study of Unruptured Intracranial Aneurysms (ISUIA), which included mostly white patients.

Comparing the current study with ISUIA could provide further insight into the natural history of aneurysms, according to the researchers.

"The explanation for the difference in the risk of rupture between our cohort and the ISUIA cohort may be multifactorial rather than just genetic," they suggested.

The study and several of the authors have been supported by grants from Japanese Ministry of Health, Labor, and Welfare, the Japan Brain Foundation, and the National Cerebral and Cardiovascular Research Center of Japan.

One author has been an adviser to Kyowa Hakko Kirin, and another receives royalties for neurosurgical instruments from Mizuho Ika Kogyo.

From the American Heart Association:

Primary source: New England Journal of Medicine

Hi All,

Molyneux is not saying anything different to the advise given to me by the neuro surgeon's in London. Which was that Annies over 5mm should be treated and anything below monitored to see the rate of growth per year. Which is generally accepted to be less than one percent per year. Inaddition, the patient has the choice in respect of unruptured annies whether to have them treated or not. As this research shows, there is a bigger chance of the 7-9 and upwards catagories bleeding out. So the choice in the aforesaid catagories is do you get them treated or not and for most people this means can you go about your daily life with the knowledge that you have a time bomb in your head or do you do something about it. I know that I could not live day to day with that knowledge and I had mine treated. The yearly increase of less than 1% was irrelevant to me because at 8mm mine was already big enough to bleed out!

Nor to I think his final two comments are realistic because until CT scanning becomes more wide spead as a form of screening, the majority of people dont even know they have an Annie so the question of having it treated or otherwise will never arise!

Hi All,

I would like to see a study showing the effects of a bleed out on the first size catagory. This could be more insightful to help those with less than 7cm annies to decide to have them treated or monitored.

Hi Jennifer,

Below are two abstracts about small incidentally found (less than 10mm) aneurysms and treatment. If you would like to read the entire articles, please click on the Medscape link and join Medscape.

Small (< 10-mm) Incidentally Found Intracranial Aneurysms, Part 1

Reasons for Detection, Demographics, Location, and Risk Factors in 212 Consecutive Patients

Ioannis Loumiotis, M.D.; Anne Wagenbach, R.N., C.N.P.; Robert D. Brown Jr., M.D.; Giusepp e Lanzino, M.D.

Authors and Disclosures

Posted: 01/11/2012; Neurosurg Focus. 2011;31(6) © 2011 American Association of Neurological Surgeons

Abstract and Introduction


Object. The widespread use of imaging techniques for evaluating nonspecific symptoms (vertigo, dizziness, memory concerns, unsteadiness, and the like) and focal neurological symptoms related to cerebrovascular disease has led to increased identification of asymptomatic incidentally discovered unruptured intracranial aneurysms (UIAs). The management of these incidental aneurysms is controversial and many factors need to be considered. The authors describe reasons leading to diagnosis, demographics, and risk factors in a large consecutive series of patients with small incidentally found UIAs.
Methods. The authors prospectively evaluated 335 patients harboring 478 small (< 10-mm) UIAs between January 2008 and May 2011. Patients with known aneurysms, possibly symptomatic aneurysms, arteriovenous malformation–related aneurysms, patients with a history of subarachnoid hemorrhage from another aneurysm, and patients harboring extradural aneurysms were excluded from the analysis. Only truly incidental small aneurysms (272 aneurysms in 212 patients) were considered for the present analysis. Data regarding the reason for detection, demographics, location, and presence of potential risk factors for aneurysm formation were prospectively collected.
Results. There were 158 female (74.5%) and 54 male (25.5%) patients whose mean age was 60.6 years (median 62 years). The most common reason for undergoing the imaging study that led to a diagnosis of the aneurysms was evaluation for nonspecific spells and symptoms related to focal cerebrovascular ischemia (43.4%), known/possible intracranial or neck pathology (24%), and headache (16%). The most common location (27%) of the aneurysm was the middle cerebral artery; the second most common (22%) was the paraclinoid internal carotid artery (excluding cavernous sinus aneurysms). Sixty-nine percent of patients were current or prior smokers, 60% had a diagnosis of hypertension, and 23% had one or more relatives with a history of intracranial aneurysms with or without subarachnoid hemorrhage.
Conclusions. Small incidental UIAs are more commonly diagnosed in elderly individuals during imaging performed to investigate ill-defined spells or focal cerebrovascular ischemic symptoms, or during the evaluation of known or probable unrelated intracranial/neck pathology. Hypertension, smoking, and family history of aneurysms are common in this patient population, and the presence of these risk factors has important implications for treatment recommendations. Although paraclinoid aneurysms (excluding intracavernous aneurysms) are uncommon in patients with ruptured intracranial aneurysms, this location is very common in patients with small incidental UIAs.

Small (< 10-mm) Incidentally Found Intracranial Aneurysms, Part 2

Treatment Recommendations, Natural History, Complications, and Short-term Outcome in 212 Consecutive Patients

Ioannis Loumiotis, M.D.; Robert D. Brown Jr., M.D.; Roanna Vine, R.N.; Harr y J. Cloft, M.D., Ph.D.; David F. Kall mes, M.D.; Giusepp e Lanzino, M.D.

Authors and Disclosures

Posted: 01/16/2012; Neurosurg Focus. 2011;31(6) © 2011 American Association of Neurological Surgeons

Abstract and Introduction


Object. The management of incidental small unruptured intracranial aneurysms (UIAs) is controversial and many factors need to be considered in the decision-making process. The authors describe a large consecutive series of patients harboring small incidental intracranial aneurysms. Treatment strategy, natural history, complications, and short-term outcomes are presented.
Methods. Between January 2008 and May 2011, the authors prospectively evaluated 212 patients with 272 small (< 10-mm) incidental aneurysms. Treatment recommendations (observation, endovascular treatment, or surgery), complications of treatment, and short-term outcomes were assessed.
Results. Recommended treatment consisted of observation in 125 patients, endovascular embolization in 64, and surgery in 18. Six patients were excluded from further analysis because they underwent treatment elsewhere. In the observation group, at a mean follow-up of 16.7 months, only 1 patient was moved to the embolization group. Seven (6%) of the 125 patients in the observation group died of causes unrelated to aneurysm. Sixty-five patients underwent 69 embolization procedures. The periprocedural permanent morbidity and mortality rates in patients undergoing endovascular treatment were 1.5% and 1.5%, respectively (overall morbidity and mortality rate 3.0%). In the surgery group no periprocedural complications were observed, although 1 patient did not return to her previous occupation. No aneurysmal rupture was documented in any of the 3 treatment groups during the follow-up period.
Conclusions. A cautious and individualized approach to incidental UIAs is of utmost importance for formulation of a safe and effective treatment algorithm. Invasive treatment (either endovascular or surgery) can be considered in selected younger patients, certain "higher-risk" locations, expanding aneurysms, patients with a family history of aneurysmal hemorrhage, and in those who cannot live their lives knowing that they harbor the UIA. Although the complication rate of invasive treatment is very low, it is not negligible. The study confirms that small incidental UIAs deemed to be not in need of treatment have a very benign short-term natural history, which makes observation a reasonable approach in selected patients.

Hi Julie,

Thanks for the above. I found it interesting. I discovered by chance that I had a fusiform Annie on the right internal carotid artery when I went to see an ENT specialist for laryngitis which I had had for three months ( to long!). I had nothing wrong with my throat but the Annie was discovered. I did not have any of the symptoms described above. The only other thing I noticed was that my stress levels were reducing and on one or two occasions I told myself to calm down because I felt I was having a Stroke. There is a family history of Stroke in the female members of my family but in later years ie. ( in their 70's) In addition, I was a smoker for many years. At 55 I was considered as having a 50/ 50 chance of treatment. But I decided to go ahead for the reasons already given.

What I found most worrying is that all the research that I read was all doom and gloom! Even after the FDS, I was afraid and felt better after I had passed the 5 month risk period. Even now, I still dont know how long these FDS stent lasts, Does anyone?

Even when I left hospital I was told by the Registrar " Go home and enjoy what is left of your much shortened life" This really frightened me as I did not understand what he was talking about. I had had the treatment to prevent a bleed out.

In the UK they respond to events there is no monitoring as such as there is with other illnesses. This I found hard. Even when I had an MRI when I lost my sight, which later resolved; they could no see the Stent. This I found disconcerting. I am due my check Angio now (6 mths) and until I have it I wont know where I am. Treatment is not for the faint hearted.

At the end of the day, I felt that I was between a rock and a hard place and for me treatment was better than the prospect of a bleed out which I would not have survived. I am glad my Annie was found and I am pleased to have had it treated.

Neurosurgeons rely on people reading and understanding the research on annies before having the procedure but in reality few do because it is very complicated and we are often "blinded by science". The beauty of these groups is that they can help people to come through it human terms .

Hi Julie,

Reading the full article there appears to be a link between fat and fusiform annies. Do you have any information on this?

Hi Julie,

Thanks again for posting such informative studies.

I am very happy to read the conclusion that an individualized approach to treatment is needed. There is no approach that works for everyone. It’s also significant to read about the role that the patient’s fear plays in deciding whether to pursue invasive treatment.

When I had my angiogram earlier this year, I asked my neuro about his criteria for deciding when surgery should be performed. He told me that one of them was the “the level of fear of the patient”. This is consistent with the conclusions above.

Take care,


Hi Carol,

Very well put. But I would also add that if a person decides to go for treatment that they do their research and find the best surgeon they can who is experience in dealing with the particular type and location of the annie. This will give the peace of mind of a better outcome. What we have also learnt is that it is better to do something either monitor or treat. It is not an option to live in ignorant bliss and hope for the best. It is also important to make the life style changes that aid general health and reduce the risk factors for stroke.

Hi Jennifer,

I don't have any other info, but I'll keep my eyes open.


Hi Jennifer,

I agree with you. We should control what we can control, influence what we can and try not to get too stressed about the rest. :slight_smile:

Take care.


Hi Carole,

As usual wise words. Not always easy though. One thing at a time. My next thing is to loose weight. I quit smoking ( 8 months ago) and no alcohol. I also do the half hour walk every day. I will be a new women by the end of the journey!