Brown, Robert D.

Object Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry. Results Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p < 0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p = 0.016). Conclusions Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.

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.

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.

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.

Background and Purpose— Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. Methods— Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case–control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. Results— A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3× weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18–0.87); reference group, no use of aspirin), patients in the “< once a month” group had an OR of 0.80 (95% CI, 0.31–2.05), and patients in the “> once a month to 2×/week” group had an OR of 0.87 (95% CI, 0.27–2.81; P =0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11–0.67; P =0.03) compared with those who never take aspirin. Conclusions— Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed.

Background and Purpose —There are few population-based data available regarding nursing home use after stroke. This study clarifies the use of a nursing home after stroke, as well as its dependence on stroke severity, in a defined population. Methods —All first stroke events among residents of Rochester, Minn, during 1987–1989 were ascertained, subtyped, and assigned Rankin disability scores (RS) before the event, at maximal deficit, and at specified intervals after stroke. Persons were followed from the date of stroke event to death, emigration from Rochester, or December 31, 1994, in complete community-based medical records and Minnesota Case Mix Review Program data tapes to determine nursing home residency before stroke and at 90 days and 1 year after stroke, proportion of survival days in a nursing home, and cumulative risk of admission to a nursing home. Results —There were 251 cases of first cerebral infarction, 24 intracerebral hemorrhages, and 15 subarachnoid hemorrhages among residents of Rochester during 1987–1989. The maximal deficit RS was 1 or 2 for 62 (25%), RS 3 for 72 (29%), and RS 4 or 5 for 117 (47%) of the cerebral infarct patients. Among patients surviving to 90 days or 1 year after cerebral infarction, 25% were in nursing home at 90 days and 22% at 1 year, respectively. Within these maximal deficit RS categories, the percentages of follow-up time spent in a nursing home during the first post–cerebral infarction year are as follows: RS 1 to 2, 4%; RS 3, 10%; and RS 4 to 5, 54%. Multivariate logistic regression revealed that increasing age and RS 4 to 5 at maximal deficit were independent predictors ( P <0.0001) of nursing home residency at 90 days and 1 year after stroke, whereas stroke type was not an independent predictor. At 1 year after cerebral infarction, the Kaplan-Meier estimates of proportion of people with at least 1 nursing home admission were 11% for RS 1 to 2, 22% for RS 3, and 68% for RS 4 to 5. Conclusions —This study provides unique population-based data regarding the short- and long-term use of a nursing home after stroke and its dependence on stroke severity. More than 50% of people with a severe cerebral infarction are in a nursing home 90 days and 1 year after the stroke, and by 1 year, nearly 70% will have required some nursing home stay. Age and stroke severity are independent predictors of nursing home residency after stroke.