Pre-eclampsia, gestational diabetes and hypertensive disorders in patients with intracranial aneurysms: A case-control study.

BACKGROUND AND PURPOSE: The aim of this study was to define the prevalence of pre-eclampsia, gestational hypertension (HT), chronic HT, and gestational diabetes during pregnancy in a defined population of patients with saccular intracranial aneurysms (sIAs). METHODS: We included all patients with sIA, first admitted to the Neurosurgery Department of Kuopio University Hospital from its defined catchment population between 1990 and 2015, who had given birth for the first time in 1990 or later. The patients' medical records were reviewed, and clinical data were linked with prescription drug usage, hospital diagnoses and causes of death, obtained from nationwide registries. The prevalences of pre-eclampsia, other hypertensive disorders and gestational diabetes in patients were compared with a matched control population (n = 324). In addition, the characteristics of sIA disease in patients with pre-eclampsia were compared to those of sIA patients without pre-eclampsia. RESULTS: A total of 169 patients with sIA fulfilled the inclusion criteria. Of these, 22 (13%) had pre-eclampsia and 32 (19%) had other hypertensive disorders during pregnancy. In 324 matched controls who had given birth, the prevalence of pre-eclampsia was 5% (n = 15) and other hypertensive disorders were diagnosed in 10% (n = 34). There was no significant difference in prevalence of gestational diabetes (12% vs. 11%). Patients with sIA with pre-eclampsia more frequently had irregularly shaped aneurysms (p = 0·003). CONCLUSIONS: Pre-eclampsia was significantly more frequent in patients with sIA than in their population controls. Irregularly shaped aneurysms were more frequent in sIA patients with pre-eclampsia. Further studies are required to determine whether history of pre-eclampsia may indicate an elevated risk for sIA formation or rupture.

Saccular Intracranial Aneurysms in Children When Both Parents Are Sporadic or Familial Carriers of Saccular Intracranial Aneurysms.

BACKGROUND AND PURPOSE: To study the penetrance of saccular intracranial aneurysm (IA) disease in children when both parents carry the disease. PATIENTS AND METHODS: The Kuopio IA Patient and Family Database includes all 4,411 IA patients admitted to the Kuopio University Hospital from its defined Eastern Finnish catchment population since 1980. We fused IA database with hospital diagnoses for IA patients and their 46,021 relatives from a national registry to identify couples concordant for IA disease. Penetrance of IA disease and hypertension were studied in these families. RESULTS: A total of 3,659 IA patients had 1 or more children. In total, 18 couples concordant for the IA disease with a total of 48 children, all born healthy, were identified. Hypertension was diagnosed in 23 (64%) of the 36 parents, and 7 of the 12 sporadic-sporadic couples were concordant for hypertension. Six sporadic-sporadic couples were concordant for subarachnoid haemorrhage (SAH). None of the 24 children to the 12 sporadic-sporadic couples had been diagnosed with SAH or IA disease. Instead, 11 (46%) of the 24 children to the 6 familial-sporadic couples had a diagnosed with SAH or IA disease. CONCLUSIONS: Couples concordant for IA disease are uncommon but not exceedingly rare. Biparental sporadic exposure does not seem to increase the risk of a clinically diagnosed IA disease or SAH in the offspring. IAs were common in the children with biparental sporadic-familial exposure.

Development of the SAFETEA Scores for Predicting Risks of Complications of Preventive Endovascular or Microneurosurgical Intracranial Aneurysm Occlusion.

OBJECTIVE: Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics. METHODS: For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics. RESULTS: Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved <30 days, 140 (10.9%) had persisting neurological symptoms, and 6 died (0.5%)). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were: size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment; branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n=752), the c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points). CONCLUSIONS: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

Lack of impact of polycystic kidney disease on the outcome of aneurysmal subarachnoid hemorrhage: a matched case-control study.

OBJECTIVE: The authors set out to study whether autosomal dominant polycystic kidney disease (ADPKD), an established risk factor for intracranial aneurysms (IAs), affects the acute course and long-term outcome of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The outcomes of 32 ADPKD patients with aSAH between 1980 and 2015 (median age 43 years; 50% women) were compared with 160 matched (age, sex, and year of aSAH) non-ADPKD aSAH patients in the prospectively collected Kuopio Intracranial Aneurysm Patient and Family Database. RESULTS: At 12 months, 75% of the aSAH patients with ADPKD versus 71% of the matched-control aSAH patients without ADPKD had good outcomes (Glasgow Outcome Scale score 4 or 5). There was no significant difference in condition at admission. Hypertension had been diagnosed before aSAH in 69% of the ADPKD patients versus 27% of controls (p < 0.001). Multiple IAs were present in 44% of patients in the ADPKD group versus 25% in the control group (p = 0.03). The most common sites of ruptured IAs were the anterior communicating artery (47% vs 29%, p = 0.05) and the middle cerebral artery bifurcation (28% vs 31%), and the median size was 6.0 mm versus 8.0 mm (p = 0.02). During the median follow-up of 11 years, a second aSAH occurred in 3 of 29 (10%) ADPKD patients and in 4 of 131 (3%) controls (p = 0.11). A fatal second aSAH due to a confirmed de novo aneurysm occurred in 2 (6%) of the ADPKD patients but in none of the controls (p = 0.027). CONCLUSIONS: The outcomes of ADPKD patients with aSAH did not differ significantly from those of matched non-ADPKD aSAH patients. ADPKD patients had an increased risk of second aSAH from a de novo aneurysm, warranting long-term angiographic follow-up.

Association of Intracranial Aneurysms With Aortic Aneurysms in 125 Patients With Fusiform and 4253 Patients With Saccular Intracranial Aneurysms and Their Family Members and Population Controls.

Background Varying degrees of co-occurrence of intracranial aneurysms (IA) and aortic aneurysms (AA) have been reported. We sought to compare the risk for AA in fusiform intracranial aneurysms (fIA) and saccular intracranial aneurysms (sIA) disease and evaluate possible genetic connection between the fIA disease and AAs. Additionally, the characteristics and aneurysms of the fIA and sIA patients were compared. Methods and Results The Kuopio Intracranial Aneurysm Database includes all 4253 sIA and 125 fIA patients from its Eastern Finnish catchment population, and 13 009 matched population controls and 18 455 first-degree relatives to the IA patients were identified, and the Finnish national registers were used to identify the individuals with AA. A total of 33 fIA patients were studied using an exomic gene panel of 37 genes associated with AAs. Seventeen (14.4%) fIA patients and 48 (1.2%) sIA patients had a diagnosis of AA. Both fIA and sIA patients had AAs significantly more often than their controls (1.2% and 0.5%) or relatives (0.9% and 0.3%). In a competing risks Cox regression model, the presence of fIA was the strongest risk factor for AA (subdistribution hazard ratio 7.6, 95% CI 3.9-14.9, P<0.0005). One likely pathogenic variant in COL5A2 and 3 variants of unknown significance were identified in MYH11, COL11A1, and FBN1 in 4 fIA patients. Conclusions The prevalence of AAs is increased slightly in sIA patients and significantly in fIA patients. fIA patients are older and have more comorbid diseases than sIA patients but this alone does not explain their clinically significant AA risk.

Neurofibromatosis type 1 is not associated with subarachnoid haemorrhage.

BACKGROUND: The prevalence of intracranial aneurysms (IAs) has been proposed to be elevated in the patients with neurofibromatosis type 1 (NF1). Our aims were to determine the prevalence of NF1 in a large Finnish population based cohort of IA patients and, on the other hand, the occurrences of subarachnoid haemorrhage and unruptured intracranial aneurysms in a nationwide population-based cohort of NF1 patients and its matched ten-fold control cohort. METHODS: The Kuopio IA Database (www.kuopioneurosurgery.fi) includes all ruptured and unruptured IA cases admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population since 1980. In this registry-based study, we cross-linked the Kuopio IA database with the Finnish national registry covering all hospital diagnoses. The NF1 diagnoses of the 4543 patients with either saccular of fusiform IA were identified from 1969 to 2015 and verified from patient records. Our second approach was to analyze the occurrence of aneurysmal subarachnoid haemorrhage (aSAH) and unruptured IAs in a nationwide population-based database of 1410 NF1 patients and its ten-fold matched control cohort (n = 14030) using national registry of hospital diagnoses between 1987 and 2014. RESULTS: One NF1 patient was identified among the 4543 IA patients. Three verified IA cases (one unruptured IA and two aSAH cases) were identified in the cohort of 1410 NF1 patients, with similar occurrences in the control cohort. CONCLUSIONS: We found no evidence in our population-based cohorts to support the conception that NF1 is associated with IAs. Our results indicate that the incidence of aSAH is not elevated in patients with NF1. Further studies are required to confirm that there is no association between NF1 and unruptured IAs.