Search Results

You are looking at 1 - 10 of 12 items for

  • Author or Editor: Irene Meissner x
Clear All Modify Search
Full access

Vini G. Khurana, Irene Meissner and Fredric B. Meyer

Object

Anecdotal evidence exists for at least two subpopulations of intracranial saccular aneurysms; those that form rapidly and rupture when small and those that enlarge slowly and are particularly prone to rupture when they are 10 mm or more in diameter. The goal in this study was to determine if there was genetic evidence to support the classification of intracranial saccular aneurysms as “rupture-prone” or “rupture-resistant” lesions.

Methods

The authors prospectively obtained and analyzed clinical and genetic data in a cohort of 197 individuals composed of 58 patients with ruptured intracranial saccular aneurysms, 49 with unruptured aneurysms, and 90 healthy community volunteers. Based on recent studies supporting an increasingly relevant role for the critical vasomodulatory protein endothelial nitric oxide synthase (eNOS) in aneurysm pathobiology, the authors assayed blood from all 197 participants to determine and compare their eNOS genotypes.

The eNOS gene intron 4 27–base pair variable-number tandem-repeat polymorphism was significantly overrepre-sented in persons with ruptured intracranial saccular aneurysms compared with community volunteers (p <0.002). When comparing eNOS genotypes among patients with ruptured or unruptured aneurysms, an approximately 10-fold increase in the odds of presenting with brain aneurysm rupture was found among individuals with multiple variant eNOS alleles (p = 0.004).

Conclusions

Uniquely, the authors have identified a set of eNOS gene variations whose presence indicates patients with intracranial saccular aneurysms that are more prone to rupture. The authors conclude that if these findings are reproducible in the setting of a large multicenter study, then in addition to known anatomical factors, a rapid and cost-effective genetic screening tool will become available to clinicians as an aid to predicting rupture risks in patients presenting with unruptured intracranial aneurysms.

Restricted access

R. Loch Macdonald

Full access

Vini G. Khurana, Douglas J. Fox, Irene Meissner, Fredric B. Meyer and Robert F. Spetzler

✓ Considerable evidence links cerebral vasospasm to the decreased bioavailability of endothelial nitric oxide synthase (eNOS) after aneurysmal subarachnoid hemorrhage (SAH). In recent studies from the cardiology literature, researchers have suggested that a genetic predisposition to coronary vasospasm might develop as the result of a T-786C single nucleotide polymorphism (SNP) in the eNOS gene. The authors of this study attempted to determine if there may be a similar genetic predisposition toward cerebral vasospasm.

The authors prospectively identified 28 patients with Fisher Grade 3 SAH from a group of 51 consecutive patients with ruptured intracranial saccular aneurysms. Genomic DNA was isolated from a peripheral blood sample obtained with permission from each patient. Gene microarray technology was used to assay the samples for the presence and distribution of certain key eNOS gene polymorphisms. Clinical, radiological, and genomic data were analyzed. The finding of eNOS T-786C SNP could be used to significantly differentiate between the presence and severity of cerebral vasospasm (p = 0.04).

The findings from this preliminary study support similar findings in the coronary vasospasm literature as well as the hypothesis that a predisposition toward cerebral vasospasm may be related partially to genetic factors, which needs to be confirmed in a larger study. Such gene-based information may be important in rapidly identifying patients at increased risk of vasospasm after SAH, independent of their Fisher grade. In this article, the authors review key studies in this area.

Restricted access

Jonathan A. Friedman, Fredric B. Meyer, Douglas A. Nichols, Robert J. Coffey, L. Nelson Hopkins, Cormac O. Maher, Irene D. Meissner and Bruce E. Pollock

✓ The authors report the case of a man who suffered from progressive, disseminated posttraumatic dural arteriovenous fistulas (DAVFs) resulting in death, despite aggressive endovascular, surgical, and radiosurgical treatment.

This 31-year-old man was struck on the head while playing basketball. Two weeks later a soft, pulsatile mass developed at his vertex, and the man began to experience pulsatile tinnitus and progressive headaches. Magnetic resonance imaging and subsequent angiography revealed multiple AVFs in the scalp, calvaria, and dura, with drainage into the superior sagittal sinus. The patient was treated initially with transarterial embolization in five stages, followed by vertex craniotomy and surgical resection of the AVFs. However, multiple additional DAVFs developed over the bilateral convexities, the falx, and the tentorium. Subsequent treatment entailed 15 stages of transarterial embolization; seven stages of transvenous embolization, including complete occlusion of the sagittal sinus and partial occlusion of the straight sinus; three stages of stereotactic radiosurgery; and a second craniotomy with aggressive disconnection of the DAVFs. Unfortunately, the fistulas continued to progress, resulting in diffuse venous hypertension, multiple intracerebral hemorrhages in both hemispheres, and, ultimately, death nearly 5 years after the initial trauma.

Endovascular, surgical, and radiosurgical treatments are successful in curing most patients with DAVFs. The failure of multimodal therapy and the fulminant progression and disseminated nature of this patient's disease are unique.

Restricted access

Vini G. Khurana, Irene Meissner, Youvraj R. Sohni, William R. Bamlet, Robyn L. McClelland, Julie M. Cunningham and Fredric B. Meyer

Object. It is becoming apparent that the presence of certain genetic variations (polymorphisms) may increase the individual's susceptibility to cardiovascular diseases, even in the absence of a family history. We hypothesized that brain aneurysms more prone to rupture may be identified on the basis of an individual's genotype for endothelial nitric oxide synthase (eNOS), a critical vasomodulatory protein found to be increasingly relevant to the pathobiology of aneurysms.

Methods. Patients' clinical data were recorded prospectively. Genomic DNA was isolated from blood samples obtained from individuals presenting consecutively to the Mayo Clinic with ruptured (58 patients) or unruptured (49 patients) intracranial saccular aneurysms. Using polymerase chain reaction and gene microarray technology, the following eNOS genetic polymorphisms were studied: intron-4 27—base pair variable number of tandem repeats (27 VNTR); promoter single nucleotide polymorphism (T-786C SNP); and exon-7 SNP (G894T SNP).

Both groups of patients had similar demographic and clinical characteristics. For all three polymorphisms, variant alleles (p ≤ 0.003) and their corresponding genotypes (p ≤ 0.006) were found two to four times more frequently in patients with ruptured aneurysms than in patients with unruptured aneurysms. Strikingly, the odds ratio for presenting with a ruptured brain aneurysm among individuals demonstrating the copresence of all three variant alleles was 11.4 (95% confidence interval 1.7–75.9, p = 0.004).

Conclusions. The authors have uniquely identified a set of tandem eNOS gene variations whose presence can be used to identify patients with aneurysms likely to rupture. We believe that if this finding is reproducible in a large multicenter study, in addition to known anatomical factors a rapid and cost-effective screening tool will become available to clinicians as a genetic aid to predict the risks of rupture in patients presenting with unruptured intracranial aneurysms.

Restricted access

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.

Restricted access

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

Full access

Kelly B. Mahaney, Robert D. Brown Jr., Irene Meissner, David G. Piepgras, John Huston III, Jie Zhang and James C. Torner

Object

The aim of this study was to determine age-related differences in short-term (1-year) outcomes in patients with unruptured intracranial aneurysms (UIAs).

Methods

Four thousand fifty-nine patients prospectively enrolled in the International Study of Unruptured Intracranial Aneurysms were categorized into 3 groups by age at enrollment: < 50, 50–65, and > 65 years old. Outcomes assessed at 1 year included aneurysm rupture rates, combined morbidity and mortality from aneurysm procedure or hemorrhage, and all-cause mortality. Periprocedural morbidity, in-hospital morbidity, and poor neurological outcome on discharge (Rankin scale score of 3 or greater) were assessed in surgically and endovascularly treated groups. Univariate and multivariate associations of each outcome with age were tested.

Results

The risk of aneurysmal hemorrhage did not increase significantly with age. Procedural and in-hospital morbidity and mortality increased with age in patients treated with surgery, but remained relatively constant with increasing age with endovascular treatment. Poor neurological outcome from aneurysm- or procedure-related morbidity and mortality did not differ between management groups for patients 65 years old and younger, but was significantly higher in the surgical group for patients older than 65 years: 19.0% (95% confidence interval [CI] 13.9%–24.4%), compared with 8.0% (95% CI 2.3%–13.6%) in the endovascular group and 4.2% (95% CI 2.3%–6.2%) in the observation group. All-cause mortality increased steadily with increasing age, but differed between treatment groups only in patients < 50 years of age, with the surgical group showing a survival advantage at 1 year.

Conclusions

Surgical treatment of UIAs appears to be safe, prevents 1-year hemorrhage, and may confer a survival benefit in patients < 50 years of age. However, surgery poses a significant risk of morbidity and death in patients > 65 years of age. Risk of endovascular treatment does not appear to increase with age. Risks and benefits of treatment in older patients should be carefully considered, and if treatment is deemed necessary for patients older than 65 years, endovascular treatment may be the best option.

Restricted access

Robert D. Brown JR., John Huston III, Richard Hornung, DR.P.H., Tatiana Foroud, David F. Kallmes, Dawn Kleindorfer, Irene Meissner, Daniel Woo, Laura Sauerbeck, Joseph Broderick and for the Familial Intracranial Aneurysm (FIA) Investigators

Object

Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies.

Methods

The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression.

Results

Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006).

Conclusions

In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.