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Irene Meissner, James Torner, John Huston III, Michele L. Rajput, David O. Wiebers, Lyell K. Jones Jr., Robert D. Brown Jr. and the International Study of Unruptured Intracranial Aneurysms Investigators

Object

Investigators conducting the International Study of Unruptured Intracranial Aneurysms, sponsored by the National Institutes of Health, sought to evaluate predictors of future hemorrhage in patients who had unruptured mirror aneurysms. These paired aneurysms in bilateral arterial positions mirror each other; their natural history is unknown.

Methods

Centers in the US, Canada, and Europe enrolled patients for prospective assessment of unruptured intracranial aneurysms. Central radiological review confirmed the presence or absence of mirror aneurysms in patients without a history of prior subarachnoid hemorrhage (SAH) (Group 1). Outcome at 1 and 5 years and aneurysm characteristics are compared.

Results

Of 3120 patients with aneurysms treated in 61 centers, 376 (12%) had mirror aneurysms, which are more common in women than men (82% [n = 308] vs 73% [n = 1992], respectively; p <0.001) and in patients with a family history of aneurysm or SAH (p <0.001).

Compared with patients with nonmirror saccular aneurysms, a greater percentage of patients with mirror aneurysms had larger (>10 mm) aneurysms (mean maximum diameter 11.7 vs 10.4 mm, respectively; p <0.001). The most common distribution for mirror aneurysms was the middle cerebral artery (34% [126 patients]) followed by noncavernous internal carotid artery (32% [121]), posterior communicating artery (16% [60]), cavernous internal carotid artery (13% [48]), anterior cerebral artery/anterior communicating artery (3% [13]), and vertebrobasilar circulation (2% [8]). When these patients were compared with patients without mirror aneurysms, no statistically significant differences were found in age (mean age 54 years in both groups), blood pressure, smoking history, or cardiac disease. Aneurysm rupture rates were similar (3.0% for patients with mirror aneurysms vs 2.8% for those without).

Conclusions

Overall, patients with mirror aneurysms were more likely to be women, to report a family history of aneurysmal SAH, and to have larger aneurysms. The presence of a mirror aneurysm was not an independent predictor of future SAHs.

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Wells I. Mangrum, John Huston III, Michael J. Link, David O. Wiebers, Robyn L. McClelland, Teresa J. H. Christianson and Kelly D. Flemming

Object. Vertebrobasilar nonsaccular intracranial aneurysms (NIAs) are characterized by elongation, dilation, and tortuosity of the vertebrobasilar arteries. The goal of this study was to define the frequency, predictors, and clinical outcome of the enlargement of vertebrobasilar NIAs.

Methods. Patients with vertebrobasilar fusiform or dolichoectatic aneurysms demonstrated on imaging studies between 1989 and 2001 were identified. In particular, patients who had undergone serial imaging were included in this study and their medical records were retrospectively reviewed. Prospective information was collected from medical records or death certificates when available. Both initial and serial imaging studies were reviewed. The authors defined NIA enlargement as a change in lesion diameter greater than 2 mm or noted on the neuroradiologist's report. A Cox proportional hazards regression was used to model time from diagnosis of the vertebrobasilar NIA to the first documented enlargement as a function of various predictors. The Kaplan-Meier method was used to study patient death as a function of aneurysm growth.

Of the 159 patients with a diagnosis of vertebrobasilar NIA, 52 had undergone serial imaging studies including 25 patients with aneurysm enlargement. Lesion growth significantly correlated with symptomatic compression at the initial diagnosis (p = 0.0028), lesion type (p < 0.001), and the initial maximal lesion diameter (median 15 mm in patients whose aneurysm enlarged compared with median 8 mm in patients whose aneurysm did not enlarge; p < 0.001). The mortality rate was 5.7 times higher in patients with aneurysm growth than in those with no enlargement after adjustment for patient age (p = 0.002).

Conclusions. Forty-eight percent of vertebrobasilar NIAs demonstrated on serial imaging enlarged, and this growth was associated with significant morbidity and death. Significant risk factors for aneurysm enlargement included symptomatic compression at the initial diagnosis, transitional or fusiform vertebrobasilar NIAs, and initial lesion diameter. Further studies are necessary to determine appropriate treatments of this disease entity once enlargement has been predicted or occurs.

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Kelly D. Flemming, David O. Wiebers, Robert D. Brown Jr., Michael J. Link, Hirofumi Nakatomi, John Huston III, Robyn McClelland and Teresa J. H. Christianson

Object. Nonsaccular intracranial aneurysms (NIAs) are characterized by dilation, elongation, and tortuosity of intracranial arteries. Dilemmas in management exist due to the limited regarding the natural history of this disease entity. The objective of this study was to determine the prospective risk of subarachnoid hemorrhage (SAH) in patients with vertebrobasilar NIAs.

Methods. All patients with vertebrobasilar fusiform or dolichoectatic aneurysms that had been radiographically demonstrated between 1989 and 2001 were identified. These patients' medical records were retrospectively reviewed. A prospective follow-up survey was sent and death certificates were requested. Based on results of neuroimaging studies, the maximal diameter of the involved artery, presence of SAH, and measurements of arterial tortuosity were recorded. Nonsaccular intracranial aneurysms were classified according to their radiographic appearance: fusiform, dolichoectatic, and transitional. Dissecting aneurysms were excluded. The aneurysm rupture rate was calculated based on person-years of follow up. Predictive factors for rupture were evaluated using univariate analysis (p < 0.05). One hundred fifty-nine patients, 74% of whom were men, were identified. The mean age at diagnosis was 64 years (range 20–87 years). Five patients (3%) initially presented with hemorrhage; four of these patients died during follow up. The mean duration of follow up was 4.4 years (692 person-years). Nine patients (6%) experienced hemorrhage after presentation; six hemorrhages were definitely related to the NIA. The prospective annual rupture rate was 0.9% (six patients/692 person-years) overall and 2.3% in those with transitional or fusiform aneurysm subtypes. Evidence of aneurysm enlargement or transitional type of NIA was a significant predictor of lesion rupture. Six patients died within 1 week of experiencing lesion rupture.

Conclusions. Risk of hemorrhage in patients harboring vertebrobasilar NIAs is more common in those with evidence of aneurysm enlargement or a transitional type of aneurysm and carries a significant risk of death.

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Thanh G. Phan, John Huston III, Robert D. Brown Jr., David O. Wiebers and David G. Piepgras

Object. The goal of this study was to determine the frequency of enlargement of unruptured intracranial aneurysms by using serial magnetic resonance (MR) angiography and to investigate whether aneurysm characteristics and demographic factors predict changes in aneurysm size.

Methods. A retrospective review of MR angiograms obtained in 57 patients with 62 unruptured, untreated saccular aneurysms was performed. Fifty-five of the 57 patients had no history of subarachnoid hemorrhage. The means of three measurements of the maximum diameters of these lesions on MR source images defined the aneurysm size. The median follow-up period was 47 months (mean 50 months, range 17–90 months).

No aneurysm ruptured during the follow-up period. Four patients (7%) harbored aneurysms that had increased in size. No aneurysms smaller than 9 mm in diameter grew larger, whereas four (44%) of the nine aneurysms with initial diameters of 9 mm or larger increased in size. Factors that predicted aneurysm growth included the size of the lesion (p < 0.001) and the presence of multiple lobes (p = 0.021). The location of the aneurysm did not predict an increased risk of enlargement.

Conclusions. Patients with medium-sized or large aneurysms and patients harboring aneurysms with multiple lobes may be at increased risk for aneurysm growth and should be followed up with MR imaging if the aneurysm is left untreated.

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Bryce Weir

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Editorial

Unruptured aneurysms

David O. Wiebers, David G. Piepgras, Robert D. Brown Jr., Irene Meissner, James Torner, Neal F. Kassell, Jack P. Whisnant, John Huston III and Douglas A. Nichols

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Robert D. Brown Jr., David O. Wiebers, James C. Torner and W. Michael O'Fallon

✓ The purpose of this study was to determine the symptoms at presentation and the incidence of intracranial hemorrhage (ICrH) caused by intracranial vascular malformations (IVMs) in a defined population. The authors used the Mayo Clinic medical records linkage system to detect all cases of IVM among residents of Olmsted County, Minnesota, during the period 1965 through 1992. Forty-eight IVMs were detected over the 27-year period. Twenty-nine of the 48 patients were symptomatic at presentation. The most common presenting symptom was ICrH, which was present in 20 patients, 69% of all symptomatic cases. Sixty-five percent of arteriovenous malformations (AVMs) presented with ICrH. The most common subtype of ICrH was intracerebral hemorrhage, which was found in nine of 20 patients; the second most common subtype was subarachnoid hemorrhage. The peak occurrence of hemorrhage was during the fifth decade of life. The age- and gender-adjusted occurrence of a first ICrH from an IVM among residents of Olmsted County, Minnesota was 0.82 per 100,000 person years (95% confidence interval 0.46–1.19). There was no increase in the detection of IVM-related ICrH throughout the study period. The 30-day mortality rate following ICrH was 17.6% for patients with an AVM and 25% for all patients with IVMs. This study provides unique data on symptoms at presentation and the incidence of ICrH and hemorrhage subtypes from IVMs on a population basis.

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Robert D. Brown Jr., David O. Wiebers and Douglas A. Nichols

✓ This long-term follow-up study of 54 patients clarifies the angiographic predictors of intracranial hemorrhage (ICH) and clinical outcome in individuals with unoperated intracranial dural arteriovenous fistulae (AVF's). All of these patients were examined at the Mayo Clinic between 1976 and 1989, and all available cerebral arteriograms were reviewed by a neuroradiologist. Follow-up information was obtained for 52 patients (96%) until death or treatment intervention, or for at least 1 year after diagnosis, with a mean follow-up period of 6.6 years.

Throughout this 6.6-year follow-up period, ICH related to dural AVF occurred in five of the 52 patients, for a crude risk of hemorrhage of 1.6% per year. The risk of hemorrhage at the time of mean follow-up examination was 1.8% per year. Angiographic examination revealed several characteristics that were considered potential predictors of ICH during the follow-up period. Lesions of the petrosal sinus and straight sinus had a higher propensity to bleed, although the small numbers in the series precluded a definite conclusion. A person suffering from a dural AVF with a venous varix on a draining vein had an increased risk of hemorrhage, whereas no hemorrhage was seen in the 20 patients without a varix (p < 0.05). Lesions draining into leptomeningeal veins had an increased occurrence of hemorrhage, although this increased risk was not statistically significant. Patients' initial symptoms were compared to those at follow-up evaluation. Pulsatile tinnitus improved in more than half of the 52 patients, and resolved in 75% of those showing some improvement. Individuals without a sinus or venous outflow occlusion at initial cerebral angiography were more likely to improve or remain stable (89%), whereas patients with an occlusion showed infrequent improvement (11%; p < 0.05).