Management of extracranial carotid artery aneurysm.

INTRODUCTION: Aneurysms of the extracranial carotid artery (ECAA) are rare. Several treatments have been developed over the last 20 years, yet the preferred method to treat ECAA remains unknown. This paper is a review of all available literature on the risk of complications and long-term outcome after conservative or invasive treatment of patients with ECAA. METHODS: Reports on ECAA treatment until July 2014 were searched in PubMed and Embase using the key words aneurysm, carotid, extracranial, and therapy. RESULTS: A total of 281 articles were identified. Selected articles were case reports (n = 179) or case series (n = 102). Papers with fewer than 10 patients were excluded, resulting in the final selection of 39 articles covering a total of 1,239 patients. Treatment consisted of either conservative treatment in 11% of the cases or invasive treatment in 89% of the cases. Invasive treatment comprised surgery in 94%, endovascular approach in 5%, and a hybrid approach in 1% of the patients. The most common complication described after invasive therapy was cranial nerve damage, which occurred in 11.8% of patients after surgery. The 30 day mortality rate and stroke rate in conservatively treated patients was 4.67% and 6.67%, after surgery 1.91% and 5.16%. Information on confounders in the present study was incomplete. Therefore, adjustments to correct for confounding by indication could not be done. CONCLUSIONS: This review summarizes the largest available series in the literature on ECAA management. The number of ECAAs reported in current literature is scarce. The early and long-term outcome of invasive treatment in ECAA is favorable; however, cranial nerve damage after surgery occurs frequently. Unfortunately, due to limitations in reporting of results and confounding by indication in the available literature, it was not possible to determine the optimal treatment strategy. There is a need for a multicenter international registry to reveal the optimal treatment for ECAA.

Evaluation of genetic risk loci for intracranial aneurysms in sporadic arteriovenous malformations of the brain.

BACKGROUND: In genome-wide association studies (GWAS) five putative risk loci are associated with intracranial aneurysm. As brain arteriovenous malformations (AVM) and intracranial aneurysms are both intracranial vascular diseases and AVMs often have associated aneurysms, we investigated whether these loci are also associated with sporadic brain AVM. METHODS: We included 506 patients (168 Dutch, 338 American) and 1548 controls, all Caucasians. Controls had been recruited as part of previous GWAS. Dutch patients were genotyped by KASPar assay and US patients by Affymetrix SNP 6.0 array. Associations in each cohort were tested by univariable logistic regression modelling, with subgroup analysis in 205 American cases with aneurysm data. Meta-analysis was performed by a Mantel-Haenszel fixed-effect method. RESULTS: In the Dutch cohort none of the single nucleotide polymorphisms (SNPs) were associated with AVMs. In the American cohort, genotyped SNPs near SOX-17 (OR 0.74; 95% CI 0.56-0.98), RBBP8 (OR 0.76; 95% CI 0.62-0.94) and an imputed SNP near CDKN2B-AS1 (OR 0.79; 95% CI 0.64-0.98) were significantly associated with AVM. The association with SNPs near SOX-17 and CDKN2B-AS1 but not RBBP8 were strongest in patients with AVM with associated aneurysms. In the meta-analysis we found no significant associations between allele frequencies and AVM occurrence, but rs9298506, near SOX-17 approached statistical significance (OR 0.77; 95% CI 0.57-1.03, p=0.08). CONCLUSIONS: Our meta-analysis of two Caucasian cohorts did not show an association between five aneurysm-associated loci and sporadic brain AVM. Possible involvement of SOX-17 and RBBP8, genes involved in cell cycle progression, deserves further investigation.

Risk factors in patients with perimesencephalic hemorrhage.

BACKGROUND AND PURPOSE: Smoking and hypertension are risk factors for aneurysmal subarachnoid hemorrhage (aSAH), whilst excessive alcohol consumption is less consistently linked with aSAH. Perimesencephalic hemorrhage (PMH) is a benign subset of non-aneurysmal subarachnoid hemorrhage. The exact cause of PMH is unknown, and its risk factor profile may help to elucidate the pathogenesis. The influence of smoking, hypertension and excessive alcohol consumption on the occurrence of PMH was studied. METHODS: Seventy-nine patients admitted with a PMH to the University Medical Center Utrecht were studied. As controls 574 persons were selected from five different general practices in the referral region of the University Medical Center Utrecht. All participants filled in a questionnaire about smoking habits, the presence of hypertension and alcohol consumption before their hemorrhage. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to assess the association of risk factors and PMH, and multivariable logistic regression was used to adjust for possible confounding by age and sex. RESULTS: Adjusted ORs for the occurrence of PMH were 1.7 (95% CI 1.0-2.8) for smoking cigarettes, cigars, pipes or any combination of these, 1.1 (95% CI 0.6-2.0) for hypertension and 1.1 (95% CI 0.5-2.1) for excessive alcohol consumption. CONCLUSIONS: Similar to aSAH, smoking is a risk factor for PMH and excessive alcohol consumption is not. In contrast to aSAH, hypertension is not a risk factor for PMH. This implies that the pathophysiological mechanisms causing PMH might be slightly different from those causing aSAH.

Time trends in outcome of subarachnoid hemorrhage: Population-based study and systematic review.

BACKGROUND: Treatment of aneurysmal subarachnoid hemorrhage (SAH) has changed substantially over the last 25 years but there is a lack of reliable population-based data on whether case-fatality or functional outcomes have improved. METHODS: We determined changes in the standardized incidence and outcome of SAH in the same population between 1981 and 1986 (Oxford Community Stroke Project) and 2002 and 2008 (Oxford Vascular Study). In a meta-analysis with other population-based studies, we used linear regression to determine time trends in outcome. RESULTS: There were no reductions in incidence of SAH (RR = 0.79, 95% confidence interval [CI] 0.48-1.29, p = 0.34) and in 30-day case-fatality (RR = 0.67, 95% CI 0.39-1.13, p = 0.14) in the Oxford Vascular Study vs Oxford Community Stroke Project, but there was a decrease in overall mortality (RR = 0.47, 0.23-0.97, p = 0.04). Following adjustment for age and baseline SAH severity, patients surviving to hospital had reduced risk of death or dependency (modified Rankin score > 3) at 12 months in the Oxford Vascular Study (RR = 0.51, 0.29-0.88, p = 0.01). Among 32 studies covering 39 study periods from 1980 to 2005, 7 studied time trends within single populations. Unadjusted case-fatality fell by 0.9% per annum (0.3-1.5, p = 0.007) in a meta-analysis of data from all studies, and by 0.9% per annum (0.2-1.6%, p = 0.01) within the 7 population studies. CONCLUSION: Mortality due to subarachnoid hemorrhage fell by about 50% in our study population over the last 2 decades, due mainly to improved outcomes in cases surviving to reach hospital. This improvement is consistent with a significant decrease in case-fatality over the last 25 years in our pooled analysis of other similar population-based studies.

Differences in risk factors according to the site of intracranial aneurysms.

BACKGROUND AND PURPOSE: Several risk factors for aneurysmal subarachnoid haemorrhage have been identified but it is not known whether some sites of aneurysms are linked to a specific risk factor. In a series of patients with aneurysmal subarachnoid haemorrhage, we compared risk factors according to the site of the ruptured aneurysm at the circle of Willis. METHODS: From our prospectively collected database of patients with aneurysmal subarachnoid haemorrhage admitted to our hospital between 2003 and 2007, we retrieved 304 patients with saccular aneurysms on the anterior communicating artery, middle cerebral artery, posterior communicating artery, basilar artery and vertebral artery. Risk factors (age, gender, smoking, no or excessive alcohol intake, hypertension and familial preponderance) were assessed per aneurysm location and compared with the anterior communicating artery as reference. We calculated odds ratios (ORs) and corresponding 95% CI. RESULTS: In comparison with aneurysms at the anterior communicating artery, those at the middle cerebral artery were less associated with age >55 years (OR 0.4; 95% CI 0.2 to 0.8), those at the posterior communicating artery were less associated with male gender (OR 0.4; 95% CI 0.2 to 0.9) and those at the basilar artery were more associated with no alcohol consumption (OR 5.8; 95% CI 1.1 to 29.9). CONCLUSION: Risk factors differ according to the site of aneurysm. This heterogeneity should be kept in mind in studies on the aetiology of aneurysms, such as genetic studies.

Natural history, epidemiology and screening of unruptured intracranial aneurysms.

INTRODUCTION: The prevalence of unruptured intracranial aneurysms is around 2%; most of these aneurysms are small and located in the anterior circulation. Unruptured intracranial aneurysms may give rise to subarachnoid hemorrhage in the near or distant future and sometimes, these lesions warrant preventive intervention. STATE OF THE ART: Most studies, on risk of rupture, have methodological weaknesses; the overall risk of rupture found in follow-up studies is around 1% per year. Size is the most important risk factor for rupture, with smaller risks for smaller aneurysms. Other risk factors are site of the aneurysm (higher risk for posterior-circulation aneurysms), age, female gender, population (higher risks in Finland and Japan) and probably also smoking. For aneurysms smaller than 10mm, treatment carries a risk of around 5% of complications leading to death or dependence on help for activities of daily living. PERSPECTIVES: There are no good comparisons between clipping and coiling of unruptured aneurysms. The efficacy of coiling in the long-term is unsettled. Good-quality data are urgently needed to settle these questions. CONCLUSIONS: In deciding whether or not to treat an aneurysm, life expectancy is a pivotal factor; other important factors are size and site of the aneurysm.

Hypotension in anaesthetized patients during aneurysm clipping: not as bad as expected?

BACKGROUND: Patients with aneurysmal subarachnoid haemorrhage (SAH) often have disturbed autoregulation of cerebral blood flow. A reduction in systemic blood pressure during surgery may therefore lead to delayed cerebral ischaemia (DCI). To assess the incidence and severity of intra-operative hypotension, we performed a retrospective cohort study in 164 patients with recent SAH and surgical clipping of the aneurysm. METHODS: Intra-operative hypotension was defined in three levels of severity, as a decrease in mean arterial pressure (DeltaMAP) of more than 30%, 40% or 50% compared with the pre-operative pressure. For each patient the total amount of time with intra-operative hypotension was retrieved. Logistic regression analysis was performed to study the relation between intra-operative hypotension and the occurrence of DCI and poor outcome. RESULTS: A period with DeltaMAP>30% occurred in 128 patients (78%) with a median duration of this period of 105 min (25-75 per thousand 50-171 min). DeltaMAP>40% occurred in 88 patients (54%) and DeltaMAP>50% occurred in 22 patients (13%). In univariate analysis, DeltaMAP>50% was associated with poor outcome. After adjusting for age and World Federation of Neurological Surgeons grade, the association with poor outcome was no longer statistically significant [odds ratio (OR) 1.018; 95% CI 0.996-1.041]. CONCLUSION: Hypotension during surgical clipping of intracranial aneurysms occurred frequently. In our study population of patients mostly in good clinical condition, hypotension was not confirmed as an independent risk factor for DCI or poor outcome. Anaesthesia may have had a cerebral protective effect.

Natural history, epidemiology and screening of unruptured intracranial aneurysms.

The prevalence of intracranial aneurysms is 2.3% (95% CI, 1.7-3.1%); most of these aneurysms are small and located in the anterior circulation. Risk factors are age, female gender, smoking, hypertension, excessive use of alcohol, having one or more affected relatives with SAH and autosomal dominant polycystic kidney disease. Most studies on risk of rupture have methodological weaknesses; an important flaw is that observed risks are recalculated to yearly risks of rupture, assuming a constant risk of growth and rupture of aneurysms. In reality, it is much more likely that aneurysms have long periods of low risk and short periods of high risk of growth and rupture. The overall risk of rupture found in follow-up studies is around 1% per year. Size is the most important risk factor for rupture, with smaller risks for smaller aneurysms. Other risk factors are the site of the aneurysm (higher risk for posterior circulation aneurysms), age, female gender, population (higher risks in Finland and Japan) and, probably also, smoking. There are no good comparisons between clipping and coiling of unruptured aneurysms. Both treatment modalities have a risk of around 6% of complications leading to death or dependence of help for activities of daily living for aneurysms smaller than 10mm. These risks increase with larger size of aneurysms. For clipping, the risk seems to increase with age, for coiling this is less apparent. The efficacy of coiling on the long term is unsettled. In deciding whether or not to treat an aneurysm, life expectancy is a pivotal factor; other important factors are the size and the site of the aneurysm. If the aneurysm is left untreated, follow-up imaging may be considered to detect growth of aneurysms, but the frequency and effectiveness of repeated imaging are unknown.

Endothelial cell activation markers and delayed cerebral ischaemia in patients with subarachnoid haemorrhage.

BACKGROUND: Endothelial cell activation may be connected with the pathogenesis of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). AIM: To assess the relationship between serial concentrations of circulating markers of endothelial cell activation (soluble intercellular adhesion molecule-1, soluble platelet selectin (sP-selectin), soluble endothelial selectin, ED1-fibronectin, Von Willebrand Factor (VWF) and VWF propeptide) and development of DCI. METHODS: 687 blood samples were collected from 106 consecutive patients admitted within 72 h after onset of SAH. Changes in levels were analysed in the last sample before and in the first sample after the onset of DCI (n = 30), and in subgroups with DCI occurring within 24 h after treatment of the aneurysm (n = 12) or unrelated to treatment of the aneurysm (n = 18). Patients without DCI (n = 56) served as controls. RESULTS: Concentrations of sP-selectin, but not of the other markers, were found to increase considerably after DCI unrelated to treatment of the aneurysm (increase 25 ng/ml, 95% CI 8 to 43), whereas they tended to decrease in the control patients without DCI (decrease 13 ng/ml, 95% CI -28 to 2.4). Surgery was found to profoundly influence the levels of the markers irrespective of the occurrence of DCI. CONCLUSION: The rise in sP-selectin level during DCI is suggested to be the result of platelet activation, as levels of the other markers of endothelial cell activation were not increased after DCI unrelated to treatment. Whether a causal role of platelet activation is implicated in the development of DCI should be determined in further studies in which the relationship between concentrations of markers and treatment is taken into account.

Corticosteroid use and risk of aneurysmal subarachnoid haemorrhage.

OBJECTIVES: Corticosteroids can induce hypertension and inhibit collagen synthesis in the blood vessel wall. Deficiencies in collagen have been found in intracranial aneurysms. Therefore use of corticosteroids could be a risk factor for intracranial aneurysms and aneurysmal subarachnoid haemorrhage (SAH). We investigated the relationship between the systemic use of corticosteroids in the past and the occurrence of aneurysmal SAH. METHODS: We compared the systemic use of corticosteroids (oral or intravenous) in the past between a consecutive series of 1158 patients with aneurysmal SAH and a control group consisting of 1019 patients diagnosed with a primary central nervous system (CNS) tumour. We discriminated between definite use of corticosteroids defined as use mentioned in the medical record and possible use defined as note in the medical record of a disease that may be treated with corticosteroids. We calculated odds ratios (OR) with corresponding 95% confidence intervals (CI) and adjusted for age and sex by means of logistic regression analyses. RESULTS: Twenty (1.7%, 95% CI 1.1-2.7) of the SAH patients and eight (0.8%, 95% CI 0.3-1.5) of the controls had used systemic corticosteroids (OR: 2.22; 95% CI 0.97-5.05; p-value 0.058; adjusted OR 2.23; 95 % CI 0.97-5.15; p-value 0.059). For definite plus possible use the OR was 1.67 (95% CI 1.09-2.54; p-value 0.016) and the adjusted OR 1.52 (95% CI 0.99-2.33; p-value 0.055). CONCLUSIONS: Patients with aneurysmal SAH more often have used systemic corticosteroids in the past than controls. This may suggest that the use of corticosteroids is a risk factor for aneurysmal SAH.

Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome.

OBJECTIVE: To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH). METHODS: Concentrations of soluble (s) intercellular adhesion molecule-1, sE-selectin, sP-selectin, ED1-fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression. RESULTS: Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations. CONCLUSIONS: Concentrations of sICAM-1, sP-selectin, sE-selectin, and ED1-fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation.

Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms.

Intracranial aneurysms have long been considered a once in a lifetime event. Nevertheless, patients who survive after subarachnoid haemorrhage (SAH) may be at risk for new aneurysms. In a cohort of patients with clipped aneurysms, we studied the yield of screening in the years after the SAH and we tried to identify risk factors for formation of new aneurysms as well as for enlargement of aneurysms that were already present at the time of the SAH. We screened 610 patients who had been admitted between 1985 and 2001 for SAH by means of CT-angiography. Risk factors were evaluated by Cox regression analyses. With screening we detected 129 aneurysms in 96 (16%) patients, after a mean interval of 8.9 years. Of these, 24 (19%) were located at the site of the previously ruptured and clipped aneurysm and 105 (81%) at a site remote from the clip site. Of the aneurysms at a remote site 59 could be compared with the initial (CT)-angiogram. Of these, 19 were truly de novo (32%) and 40 (68%) were already visible in retrospect. Of the 53 aneurysms that were followed over time 13 (25%) had enlarged. Risk factors for aneurysm formation and growth were presence of multiple aneurysms at time of SAH (HR 3.2, 95% CI 1.2-8.6), current smoking (HR 3.8, 95% CI 1.5-9.4) and hypertension (HR 2.3, 95% CI 1.1-4.9). These results suggest that intracranial aneurysms should not be considered as a single event in a lifetime but rather as a continuous process. Patients with a previous SAH have a substantial risk for new aneurysm formation and enlargement of untreated aneurysms. Screening these patients might be beneficial, especially in patients with multiple aneurysms, hypertension and a history of smoking. The risks and benefits of screening, however, should be carefully weighed, for example, in a decision model.

Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in The Netherlands.

BACKGROUND: There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. METHOD: In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. CONCLUSIONS: In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

Psychosocial impact of screening for intracranial aneurysms in relatives with familial subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In families with > or =2 relatives with intracranial aneurysms (IAs), screening for IAs in asymptomatic first-degree relatives is often recommended. We assessed the long-term psychosocial impact of such screening. METHODS: We identified all persons with IA (screen-positives) and matched them for age and sex with 2 controls without IA (screen-negatives) from hospital-based registers of familial IA. Persons underwent telephone interviews using questionnaires that covered the areas of psychosocial impact of screening, health-related quality of life (HRQoL), and mood. Data were compared between screen-positives and screen-negatives, and with reference populations. RESULTS: Overall, 105 persons from 33 families with IA were included, of whom 35 were screen-positive and 70 were screen-negative. Of the screen-positives, 12 (44%) had reduced their work and 23 (66%) had experienced changes in > or =1 area of independence, self-esteem, future outlook, or personal relationships. In contrast, only 1 (2%) screen-negative person had stopped working and 12 (17%) others had experienced changes in their self-esteem, future outlook, or relationships. Screen-positives had lower HRQoL compared with screen-negatives and the reference population, whereas both screen groups had higher mean depression scores than the reference population. Despite these effects, only 3 persons regretted participating in screening. CONCLUSIONS: Although screening for IA is an important preventative strategy in high-risk individuals, it is associated with considerable psychosocial effects, both positive and negative. Greater awareness of such outcomes, and appropriate intervention where necessary, would appear to be a necessary component of IA screening programs.

Genes and outcome after aneurysmal subarachnoid haemorrhage.

OBJECTIVES: Initial and secondary ischaemia are important determinants of outcome after subarachnoid haemorrhage (SAH). Cerebral ischaemia is a potent stimulus for expression of genes that may influence recovery.We investigated whether functional polymorphisms in the apolipoprotein E (APOE), insulin-like growth factor-1 (IGF-1), tumor necrosis factor-A (TNF-A), interleukin-1A (IL-1A), interleukin-1B (IL-1B), and interleukin-6 (IL-6) genes are related with outcome after aneurysmal SAH. METHODS: Genotyping of the polymorphisms was performed in a consecutive series of 167 patients with aneurysmal SAH. The risk of a poor outcome was analysed with logistic regression with adjustment for prognostic factors for outcome after SAH, using the homozygotes for the wild type alleles as a reference. RESULTS: Patients carrying any IGF-1 non-wild type allele had a lower risk of a poor outcome (OR 0.4, 95% CI 0.2-1.0), while carriers of the TNF-A non-wild type allele had a higher risk (OR 2.3, 95% CI 1.0-5.4). We could not demonstrate an association with outcome for APOE (APOE epsilon4 OR 0.4, 95% CI 0.1-1.2; APOE epsilon2 OR 0.7, 95% CI 0.2-2.4), IL-1A (OR 1.8, 95% CI 0.8-4.0), IL-1B (OR 0.7, 95% CI 0.3-1.5) and IL-6 (OR 0.7, 95% CI 0.3-1.8) polymorphisms. CONCLUSIONS: Variation in some genes that are expressed after cerebral ischaemia may partly explain the large differences in outcome between patients with aneurysmal SAH. SAH patients homozygote for the IGF-1 wild type allele or carriers of the TNF-A non-wild type allele have a higher risk of poor outcome. Additional studies in other populations are needed to assess the generalisability of our results.

Characteristics of intracranial aneurysms in patients with familial subarachnoid hemorrhage.

BACKGROUND: Compared with sporadic aneurysms, familial aneurysms rupture at an earlier age and are more often located at the middle cerebral artery. Other characteristics of familial aneurysms may also differ from sporadic aneurysms. The authors compared the size of ruptured aneurysms and the number of aneurysms between patients with familial subarachnoid hemorrhage (SAH) and those with sporadic SAH. METHODS: The authors included all patients with familial SAH admitted to the University Medical Center Utrecht (UMCU) and their first-degree relatives with proven aneurysmal SAH, including admissions elsewhere. As reference group the authors used a consecutive series of patients with sporadic SAH admitted to the UMCU from December 1995 to March 1997. Criteria for sporadic SAH were absence of a positive family history and exclusion of aneurysms in first-degree relatives by means of MR angiography. The authors dichotomized sizes of aneurysms into small (10 mm). Size and number of aneurysms between patients with familial SAH and sporadic SAH were compared with relative risks (RR) with corresponding 95% CI. RESULTS: The authors found 58 patients with familial SAH (48 with information on aneurysm size) and 88 patients with sporadic SAH. Twenty of 48 patients with familial SAH (41%) had large aneurysms, versus 17 (19%) with sporadic SAH (RR 2.1, 95% CI 1.2 to 3.6). Fifteen of 58 patients with familial SAH (26%) had multiple aneurysms, versus 9 (10%) with sporadic SAH (RR 2.5, 95% CI 1.2 to 5.4). CONCLUSIONS: Familial aneurysms are generally larger at time of rupture and more likely to be multiple than sporadic aneurysms. The development of large and multiple aneurysms may be related to genetic factors that determine defects of the arterial wall.

Risk factors for intracerebral hemorrhage in the general population: a systematic review.

BACKGROUND AND PURPOSE: Although data on some risk factors for intracerebral hemorrhage (ICH) already are beyond doubt, for other factors, the evidence is less clear. We performed a systematic overview of case-control and cohort studies on risk factors for ICH. METHODS: We searched MEDLINE, LILACS, EXTRAMED, and Pascal from 1966 to 2001 to identify studies. Studies were included if they met predefined methodological criteria. When possible, 2x2 tables were extracted and combined with the Mantel-Haenszel method. Summary odds ratios (ORs) were calculated for case-control studies, and summary relative risks (RRs) were found for cohort studies and for case-control and cohort studies combined. RESULTS: Fourteen case-control and 11 cohort studies were identified. We could not always combine the results of case-control and cohort studies. In cohort studies, the crude RR for age (every 10-year increase) was 1.97 (95% confidence interval [CI], 1.79 to 2.16). In case-control studies, the crude OR for high alcohol intake was 3.36 (95% CI, 2.21 to 5.12) and for hypertension was 3.68 (95% CI, 2.52 to 5.38). Two cohort studies showed an increasing risk of ICH with increasing degree of hypertension. In cohort and case-control studies combined, the crude RR for sex (male versus female) was 3.73 (95% CI, 3.28 to 4.25); for current smoking, 1.31 (95% CI, 1.09 to 1.58); and for diabetes, 1.30 (95% CI, 1.02 to 1.67). CONCLUSIONS: Risk factors for ICH appeared to be age, male sex, hypertension, and high alcohol intake. High cholesterol tends to be associated with a lower risk of ICH. We could not assess whether these risk factors are independent.

Attributable risk of common and rare determinants of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Smoking, hypertension, alcohol consumption, autosomal dominant polycystic kidney disease (ADPKD), and positive family history for subarachnoid hemorrhage (SAH) are well-known risk factors for SAH. For effective prevention, knowledge about the contribution of these risk factors to the overall occurrence of SAH in the general population is pivotal. We therefore investigated the population attributable risks of the risk factors for SAH. METHODS: We retrieved the relative risk and prevalence of established risk factors for SAH from the literature and calculated the population attributable risks of these risk factors. RESULTS: Drinking alcohol 100 to 299 g/wk accounted for 11% of the cases of SAH, drinking alcohol >/=300 g/wk accounted for 21%, and smoking accounted for 20%. An additional 17% of the cases could be attributed to hypertension, 11% to a positive family history for SAH, and 0.3% to ADPKD. CONCLUSIONS: Screening and preventive treatment of patients with familial preponderance of SAH alone will cause a modest reduction of the incidence of SAH in the general population. Further reduction can be achieved by reducing the prevalence of the modifiable risk factors alcohol consumption, smoking, and hypertension.