Rupture Risk Low for Small Cerebral Aneurysms

Pauline Anderson

June 06, 2017

Small intracranial aneurysms have a low risk for growth and rupture, and very small aneurysms have an even lower risk, although the quality of the evidence is not ideal, results of a new systematic review suggest.

"The evidence is poor, but we are making clinical decisions based on this very same evidence," lead author, Ajay Malhotra, MD, associate professor, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, told Medscape Medical News.

Many questions remain about optimal management of patients with small intracranial aneurysms, said Dr Malhotra.

"Should we follow them, and if we follow them, how frequently should we follow them, and for how long? What modality do we use to follow them? And how do we even define growth? "

The review was published online June 6 in the Annals of Internal Medicine.

As the quality and availability of imaging have improved in recent years, experts are diagnosing an increasing number of unruptured intracranial aneurysms (UIAs). An estimated 85% to 88% of these aneurysms are small, defined as less than 7 mm, said Dr Malhotra.

Research has suggested that more of these small aneurysms are rupturing than previously thought. Several recent papers looking at aneurysms that had ruptured found that up to about 25% of them were small.

The upshot is that clinicians are treating these small aneurysms more frequently. A recent survey found that a significant proportion of neurosurgeon respondents said they would routinely treat small aneurysms and that almost a third would treat them at least half the time, said Dr Malhotra.

The research shows that the rupture risk varies substantially according to risk factor burden. Aneurysms that grow or change in morphology have a greater propensity to rupture, and the initial aneurysm size is an important risk factor for growth.

Guidelines from the American Heart Association (AHA)/American Stroke Association (ASA) for managing UIAs that were updated in 2015 don't include specific recommendations for treating small aneurysms.

After searching various databases, researchers included 26 published case series and observational studies in their review. Seven studies were multicenter and the rest were single-center reports.  

Investigators estimated the annual growth and rupture rates and categorized findings according to aneurysm size: 0 to 3 mm, 0 to 5 mm, and 0 to 7 mm.

The review found that the annualized growth rate was less than 3% in all but one study for all three size categories. The "outlier" was a 2013 study by Chien and colleagues that reported annual growth rates of 11.64% for aneurysms 3 mm and smaller and 5.10% for those 5 mm and smaller.

The annualized rupture rates were 0% for the 0- to 3-mm size category, less than 0.5% for the 5-mm and smaller category, and less than 1% for the 7-mm and smaller category.

The authors noted that not all included studies assessed growth and rupture rates. Of the 26 articles, 10 reported both growth and rupture rates whereas 5 reported only growth rates and 11, only rupture rates.  

The authors also noted that the studies used various follow-up methods to measure rupture risk, including MRI, computed tomography, or cerebral angiography. Some studies did not specify follow-up methods.

Only 16 studies used consistent periodic angiographic follow-up to assess growth. And some studies reporting on growth did not clearly define aneurysm enlargement.

"None of the studies used a consistent imaging method for follow up, and not enough information is available regarding the frequency and duration of follow-up to derive conclusions," commented the authors.

The review highlights the variability in the definition of growth, commented Dr Malhotra. "We are not even looking at growth consistently, in the same way."

Standardization "Critical"

Using standardized methods to determine growth is "critical," the authors write. "This is especially important for small aneurysms, for which subtle changes in size must be above the spatial resolution of the imaging method used to define growth."

The authors pointed out the selection and reporting bias in the literature. Many studies in the review did not specify the criteria used to select patients for treatment or follow-up. Five studies reported that more than 20% of participants did not have complete follow-up data.

Also of note was that most studies had a mean follow-up of less than 5 years. The review included only one long-term follow-up study, with a mean follow-up of more than 20 years.

"The selection bias in that study was high, so we are unlikely to get any good studies on the natural outcome of these patients," commented Dr Malhotra.

An important limitation of most of the studies was selection bias in terms of higher-risk aneurysms being treated, said the authors. "Because growing aneurysms might have a higher risk for rupture and have been excluded, drawing strong conclusions about the correlation between growth and rupture is difficult."

As well, studies may have underestimated the rupture risk of growing aneurysms because of the long interval between follow-up scans and the possibility of growth before aneurysm rupture between scans, they write.

"Overall, the strength of evidence was very low quality for growth rates and low quality for rupture rates," the authors conclude.

The AHA/ASA recommends a first follow-up study at 6 to 12 months after initial discovery of a UIA, with subsequent follow-up yearly or every other year.  Dr Malhotra and his colleagues believe that future guidelines should consider specific follow-up imaging recommendations for small aneurysms, given their very low rupture rate and the poorly understood correlation between growth and rupture.

The review findings stress the need for neurologists to avoid treating all patients as one group, Dr Malhotra said in an interview. Aneurysm rupture is more likely in some patients, for example, those who smoke, those with hypertension, and those who have a family history of subarachnoid hemorrhage, he said.

"Some patients are at higher risk for rupture so they may need to be treated more aggressively, but routinely treating everyone, or continuing to image patients forever, is probably not a good strategy for all patients with small aneurysms."

Dr Malhotra and his team are working on further analyses that might help determine the most cost-effective management strategy for small UIAs.

Important Question

"The authors should be commended for their detailed review and attempts to define the risks of UIAs," Robert M. Starke, MD, University of Miami Miller School of Medicine, Florida, writes in an accompanying editorial.

"The question they aimed to answer is important, because most UIAs are smaller than 7 mm, but the poor quality of available data makes answering the question challenging."

Assessing growth rates of small aneurysms across studies is difficult because of variable definitions of growth and because of the use of diverse imaging techniques, Dr Starke notes.

Determining the risk for aneurysm rupture is as challenging as determining growth rate, he says. He adds that follow-up is another concern in the studies included in the review.

"One should not conclude from this study that small aneurysms have no risk for rupture but rather that experts are skilled at predicting which aneurysms are more likely to rupture," Dr Starke writes.

"Thus, all patients with aneurysms should be evaluated by an expert who can review associated risk factors and determine both the optimal follow-up plan (if any) and the need for treatment."

The consequences of management choices may be serious, says Dr Starke, noting that the mortality rate is approximately 50% in patients with a ruptured aneurysm.

Although ethical concerns likely will continue to preclude a randomized clinical trial, the new review "should prompt better prospective observational studies," Dr Starke concludes.

There was no targeted funding for this study. Dr Malhotra and Dr Starke have disclosed no relevant financial relationships.

Ann Intern Med. Published online June 6, 2017. Abstract, Editorial

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