Antti Lindgren

Irregular Shape of Intracranial Aneurysm Indicates Rupture Risk Irrespective of Size in a Population-Based Cohort

Background and Purpose— Size and shape of saccular intracranial aneurysms (sIA) reflect the condition of the sIA wall and were risk factors for rupture in previous follow-up studies. We investigated how well size or shape identify rupture-prone sIAs. Methods— In a population-based registry, we investigated the characteristics of ruptured sIAs treated in a single neurosurgical center (1980–2014). In addition to univariate analysis, logistic regression was used in multivariate analysis, and sensitivity and specificity of size or shape were calculated using receiver operating characteristic curves. Results— Ruptured sIAs were on average larger than unruptured sIAs (median, 7 versus 4 mm; P<0.000), but location and patient background affected the size at rupture. Of the ruptured sIAs, 38% were smaller than 7 mm and 18% were smaller than 4 mm. Of those sIAs that had ruptured at a small (<7 mm) size, 87% had an irregular shape. In multivariate analysis, irregular shape had the strongest association with presentation as ruptured sIA (odds ratio, 7.1; 95% confidence interval, 6.0–8.3), with better sensitivity (91%) and specificity (76%), in contrast to smoking (odds ratio, 0.7; 95% confidence interval, 0.6–0.9; sensitivity, 28%; specificity 57%) and Population, Hypertension, Age, Size of sIA, Earlier SAH from another sIA, Site of sIA score (odds ratio, 1.5; 95% confidence interval, 1.4–1.6). Conclusions— Irregular or multilobular shape is strongly associated with rupture in sIAs of all sizes and independent of location and patient background. Especially sIAs with irregular shape should be considered as high rupture risk lesions, even if small in diameter and in nonsmoking patients with low PHASES scores.

Hypertension predisposes to the formation of saccular intracranial aneurysms in 467 unruptured and 1053 ruptured patients in Eastern Finland

Abstract Objective. Hypertension associates with subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) when compared to matched controls or general population. Few series compare hypertension in unruptured sIA versus sIA-SAH, so its impact on the sIA disease remains uncertain. Methods. Kuopio sIA Database (www.uef.fi/ns) contains all cases of unruptured and ruptured sIAs admitted to Kuopio University Hospital from its Eastern Finnish catchment population. We compared the age-adjusted incidence of drug-treated hypertension in 467 unruptured and 1053 ruptured sIA patients admitted to Kuopio University Hospital from 1995 to 2007, using the national registry of prescribed medicines. Results. Antihypertensive medication was more frequent in the unruptured (73% versus 62%) with higher age-adjusted incidence. At sIA diagnosis, the sIA-SAH group had more often untreated hypertension (29% versus 23%). The size of unruptured sIAs increased with age at sIA diagnosis, independently of hypertension. Multiple sIAs, familial sIA, and sIA-SAH were not associated with hypertension in multivariate analysis. Results indicate that drug-treated hypertension associates with the formation of sIAs rather than their growth or rupture. Conclusion. Hypertension is highly prevalent in the carriers of unruptured sIAs when compared to those with ruptured sIA. Hypertension may associate with the sIA formation, and may predispose to the rupture of sIA if untreated.

ELAPSS score for prediction of risk of growth of unruptured intracranial aneurysms.

Objective: To develop a risk score that estimates 3-year and 5-year absolute risks for aneurysm growth. Methods: From 10 cohorts of patients with unruptured intracranial aneurysms and follow-up imaging, we pooled individual data on sex, population, age, hypertension, history of subarachnoid hemorrhage, and aneurysm location, size, aspect ratio, and shape but not on smoking during follow-up and family history of intracranial aneurysms in 1,507 patients with 1,909 unruptured intracranial aneurysms and used aneurysm growth as outcome. With aneurysm-based multivariable Cox regression analysis, we determined predictors for aneurysm growth, which were presented as a risk score to calculate 3-year and 5-year risks for aneurysm growth by risk factor status. Results: Aneurysm growth occurred in 257 patients (17%) and 267 aneurysms (14%) during 5,782 patient-years of follow-up. Predictors for aneurysm growth were earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, and shape of the aneurysm (ELAPSS). The 3-year growth risk ranged from <5% to >42% and the 5-year growth risk from <9% to >60%, depending on the risk factor status. Conclusions: The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

Type 2 Diabetes and Risk of Rupture of Saccular Intracranial Aneurysm in Eastern Finland

OBJECTIVE Type 2 diabetes is a risk factor for other forms of stroke, but its association with subarachnoid hemorrhage (SAH) from ruptured saccular intracranial aneurysm (sIA) has remained unclear. RESEARCH DESIGN AND METHODS Kuopio Intracranial Aneurysm Database (www.uef.fi/ns) includes all ruptured and unruptured sIA cases from a defined catchment population in eastern Finland since 1980. We compared the age-adjusted incidences of type 2 diabetes in 1,058 ruptured and 484 unruptured sIA patients during 1994–2008, using the national registry of prescribed medicine purchases. RESULTS Of the 1,058 ruptured sIA patients, 43% were males and 57% females, with a median age at rupture of 51 and 56 years, respectively. From 1994 to 2008 or until death, 9% had been prescribed antidiabetes medication (ADM) with a median starting age of 58 years for males and 66 years for females. Of the 484 unruptured sIA patients, 44% were males and 56% females, with a median age at the diagnosis of 53 and 55 years, respectively, and 9% had used ADM, with a median starting age of 61 years for males and 66 years for females. The incidence of type 2 diabetes was highest in the age-group 60–70 years, with no significant differences between the ruptured and unruptured sIA patients. CONCLUSIONS Our study suggests that type 2 diabetes does not increase the risk of rupture of sIA, which is by far the most frequent cause of nontraumatic SAH.

Risk of Shunting After Aneurysmal Subarachnoid Hemorrhage: A Collaborative Study and Initiation of a Consortium.

Background and Purpose— Shunt dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) is a common sequela that may lead to poor neurological outcome and predisposes to various interventions, admissions, and complications. We reviewed post-aSAH shunt dependency in a population-based sample and tested the feasibility of a clinical risk score to identify subgroups of aSAH patients with increasing risk of shunting for hydrocephalus. Methods— A total of 1533 aSAH patients from the population-based Eastern Finland Saccular Intracranial Aneurysm Database (Kuopio, Finland) were used in a recursive partitioning analysis to identify risk factors for shunting after aSAH. The risk model was built and internally validated in random split cohorts. External validation was conducted on 946 aSAH patients from the Southwestern Tertiary Aneurysm Registry (Dallas, TX) and tested using receiver-operating characteristic curves. Results— Of all patients alive ≥14 days, 17.7% required permanent cerebrospinal fluid diversion. The recursive partitioning analysis defined 6 groups with successively increased risk for shunting. These groups also successively risk stratified functional outcome at 12 months, shunt complications, and time-to-shunt rates. The area under the curve–receiver-operating characteristic curve for the exploratory sample and internal validation sample was 0.82 and 0.78, respectively, with an external validation of 0.68. Conclusions— Shunt dependency after aSAH is associated with higher morbidity and mortality, and prediction modeling of shunt dependency is feasible with clinically useful yields. It is important to identify and understand the factors that increase risk for shunting and to eliminate or mitigate the reversible factors. The aSAH-PARAS Consortium (Aneurysmal Subarachnoid Hemorrhage Patients’ Risk Assessment for Shunting) has been initiated to pool the collective insights and resources to address key questions in post-aSAH shunt dependency to inform future aSAH treatment guidelines.

De Novo Aneurysm Formation in Carriers of Saccular Intracranial Aneurysm Disease in Eastern Finland

Background and Purpose— Formation of new (de novo) aneurysms in patients carrying saccular intracranial aneurysm (sIA) disease has been published, but data from population-based cohorts are scarce. Methods— Kuopio sIA database (http://www.uef.fi/ns) contains all unruptured and ruptured sIA patients admitted to Kuopio University Hospital from its Eastern Finnish catchment population. We studied the incidence and risk factors for de novo sIA formation in 1419 sIA patients with ≥5 years of angiographic follow-up, a total follow-up of 18 526 patient-years. Results— There were 42 patients with a total of 56 de novo sIAs, diagnosed in a median of 11.7 years after the first sIA diagnosis. The cumulative incidence of de novo sIAs was 0.23% per patient-year and that of subarachnoid hemorrhage from a ruptured de novo sIA 0.05% per patient-year. The risk of de novo sIA discovery per patient-year increased with younger age at the first sIA diagnosis: 2.2% in the patients aged <20 years and 0.46% in the patients aged between 20 and 39 years. In Cox regression analysis, smoking history and younger age at the first sIA diagnosis significantly associated with de novo sIA formation, but female sex, multiple sIAs, and sIA family did not. Conclusions— Patients aged < 40 years at the first sIA diagnosis are in a significant risk of developing de novo sIAs, and they should be scheduled for long-term angiographic follow-up. Smoking increases the risk of de novo sIA formation, suggesting long-term follow-up for smokers. Antismoking efforts are highly recommended for sIA patients.

Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case–Control Study

Background and Purpose— To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. Methods— The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. Results— The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2–3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. Conclusions— The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication.

Increased incidence of aneurysmal subarachnoid hemorrhage on Sundays and Mondays in 1,862 patients from Eastern Finland.

Background: Temporal patterns of aneurysmal subarachnoid hemorrhage (aSAH) from saccular intracranial aneurysm (sIA) were studied in a consecutive series of 1,862 patients. Methods: Neurosurgery of Kuopio University Hospital (KUH) solely serves a defined catchment population in Eastern Finland. Kuopio’s sIA database contains 1,596 sporadic and 266 familial patients admitted to KUH within 72 h from the onset of aSAH between 1980 and 2007. The distributions by the weekday of the onset of aSAH, admission to KUH, and occlusive therapy of the ruptured sIA were analyzed. Logistic regression was used to search for clinical variables (patients, sIA disease, clinical condition) that would independently correlate with each distribution. Results: The onset of aSAH occurred significantly most often (p < 0.001) on Sundays (n = 330) and Mondays (n = 309) and least frequently on Saturdays (n = 231). None of the clinical variables tested associated significantly and independently with the Sunday and Monday peaks. The admissions to KUH after aSAH were most frequent (p < 0.001) on Mondays (n = 331) and least frequent on Thursdays (n = 221) and Saturdays (n = 221). Overall, 1,655 patients underwent occlusive therapy, most frequently on Mondays (n = 318) and least frequently on Saturdays (n = 189) and Sundays (n = 197). Conclusions: Sundays and Mondays were the most frequent and Saturdays the least frequent days of aSAH in a defined Eastern Finnish population. We could not identify any etiology to this temporal pattern. Binge drinking is frequent in Finland, especially among young males, but age and gender did not correlate with the Sunday and Monday peaks.

Irregular Shape Identifies Ruptured Intracranial Aneurysm in Subarachnoid Hemorrhage Patients With Multiple Aneurysms

Background and Purpose— We investigated which aneurysm-related risk factors for rupture best discriminate ruptured versus unruptured saccular intracranial aneurysms (sIAs) in subarachnoid hemorrhage patients with multiple sIAs. Methods— We included 264 subarachnoid hemorrhage patients with a ruptured sIA and at least one additional unruptured sIA, from the Kuopio Intracranial Aneurysm database from 2003 to 2015. These patients had 268 ruptured and 445 unruptured sIAs. Angiograms of the 713 sIAs were reevaluated for multiple variables describing aneurysm shape. Multivariate generalized linear mixed models were used to calculate odds ratios with corresponding 95% confidence intervals for the independent risk factors for aneurysm rupture. Results— In the multivariate analysis, only sIA size (P<0.004) and irregular shape (P<0.000) independently associated with sIA rupture. As an independent risk factor, irregular shape showed the strongest association with rupture (odds ratio 90.3; 95% confidence interval, 47.0–173.5). The sIA location, flow angles, bottleneck factor, or aspect ratio were not significantly associated with rupture. Conclusions— Irregular shape may identify the ruptured sIA better than size in patients presenting with aSAH and multiple sIAs.

Epilepsy-associated long-term mortality after aneurysmal subarachnoid hemorrhage

Objective: To elucidate the epilepsy-associated causes of death and subsequent excess long-term mortality among 12-month survivors of subarachnoid hemorrhage from saccular intracranial aneurysm (SIA-SAH). Methods: The Kuopio SIA Database (kuopioneurosurgery.fi) includes all SIA-SAH patients admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The study cohort consists of 779 patients, admitted from 1995 to 2007, who were alive at 12 months after SIA-SAH. Their use of reimbursable antiepileptic drugs and the causes of death (ICD-10) were fused from the Finnish national registries from 1994 to 2014. Results: The 779 12-month survivors were followed up until death (n = 197) or December 31, 2014, a median of 12.0 years after SIA-SAH. Epilepsy had been diagnosed in 121 (15%) patients after SIA-SAH, and 34/121 (28%) had died at the end of follow-up, with epilepsy as the immediate cause of death in 7/34 (21%). In the 779 patients alive at 12 months after SIA-SAH, epilepsy was an independent risk factor for mortality (hazard ratio 1.8, 95% confidence interval 1.1–3.0). Conclusions: Comorbid epilepsy in 12-month survivors of SIA-SAH is associated with increased risk of death in long-term follow-up. Survivors of SIA-SAH require long-term dedicated follow-up, including identification and effective treatment of comorbid epilepsy to prevent avoidable deaths.