Pretreatment with a dual antiplatelet and anticoagulant (APAC) reduces ischemia-reperfusion injury in a mouse model of temporary middle cerebral artery occlusion-implications for neurovascular procedures.

BACKGROUND: Several neurovascular procedures require temporary occlusion of cerebral arteries, leading to ischemia of unpredictable length, occasionally causing brain infarction. Experimental models of cerebral ischemia-reperfusion injury have established that platelet adhesion and coagulation play detrimental roles in reperfusion injury following transient cerebral ischemia. Therefore, in a model of cerebral ischemia-reperfusion injury (IRI), we investigated the therapeutic potential of a dual antiplatelet and anticoagulant (APAC) heparin proteoglycan mimetic which is able to bind to vascular injury sites. METHODS: Brain ischemia was induced in mice by transient occlusion of the right middle cerebral artery for 60 min. APAC, unfractionated heparin (UFH) (both at heparin equivalent doses of 0.5 mg/kg), or vehicle was intravenously administered 10 min before or 60 min after the start of ischemia. At 24 h later, mice were scored for their neurological and motor behavior, and brain damage was quantified. RESULTS: Both APAC and UFH administered before the onset of ischemia reduced brain injury. APAC and UFH pretreated mice had better neurological and motor functions (p < 0.05 and p < 0.01, respectively) and had significantly reduced cerebral infarct sizes (p < 0.01 and p < 0.001, respectively) at 24 h after transient occlusion compared with vehicle-treated mice. Importantly, no macroscopic bleeding complications were observed in either APAC- or UFH-treated animals. However, when APAC or UFH was administered 60 min after the start of ischemia, the therapeutic effect was lost, but without hemorrhaging either. CONCLUSIONS: Pretreatment with APAC or UFH was safe and effective in reducing brain injury in a model of cerebral ischemia induced by transient middle cerebral artery occlusion. Further studies on the use of APAC to limit ischemic injury during temporary occlusion in neurovascular procedures are indicated.

Posterior condylar canal dural arteriovenous fistula: anatomical, symptomatological, and therapeutic considerations in comparison with hypoglossal canal dural arteriovenous fistula.

BACKGROUND: Posterior condylar canal dural arteriovenous fistulas (dAVFs) are extremely rare. METHODS: We report a case series and literature review of posterior condylar canal dAVFs and discuss similarities and differences between posterior condylar and hypoglossal canal dAVFs with respect to the related vascular anatomy, angioarchitecture of the fistula, presentation, and treatment. RESULTS: Four cases of posterior condylar canal dAVF were identified at our institutions and six cases were identified in the literature. Posterior condylar canal dAVFs were predominantly frequent in relatively young women. All patients presented with pulsatile tinnitus. There was no history of hemorrhage as there was no cortical venous reflux. This is different from hypoglossal canal dAVFs which can present with myelopathy or hemorrhage from cortical venous reflux. Transvenous embolization was safe and eliminated the symptoms. Palliative transarterial embolization can be an option to mitigate the symptoms, although there is a potential risk of cranial nerve palsy or lateral medullary stroke. CONCLUSIONS: Posterior condylar canal dAVFs are generally benign lesions. However, intolerable tinnitus may require intervention. Transvenous embolization is effective and safe.

Acute evacuation of 54 intracerebral hematomas (aICH) during the microsurgical clipping of a ruptured middle cerebral artery bifurcation aneurysm-illustration of the individual clinical courses and outcomes with a serial brain CT/MRI panel until 12 months.

PURPOSE: In aneurysmal intracerebral hemorrhage (aICH), our review showed the lack of the patient's individual (i) timeline panels and (ii) serial brain CT/MRI slice panels through the aICH evacuation and neurointensive care until the final brain tissue outcome. METHODS: Our retrospective cohort consists of 54 consecutive aICH patients from a defined population who acutely underwent the clipping of a middle cerebral artery bifurcation saccular aneurysm (Mbif sIA) with the aICH evacuation at Kuopio University Hospital (KUH) from 2010 to 2019. We constructed the patient's individual timeline panels since the emergency call and serial brain CT/MRI slice panels through the aICH evacuation and neurointensive care until the final brain tissue outcome. The patients were indicated by numbers (1.-54.) in the pseudonymized panels, tables, results, and discussion. RESULTS: The aICH volumes on KUH admission (median 46 cm3) plotted against the time from the emergency call to the evacuation (median 8 hours) associated significantly with the rebleeds (n=25) and the deaths (n=12). The serial CT/MRI slice panels illustrated the aICHs, intraventricular hemorrhages (aIVHs), residuals after the aICH evacuations, perihematomal edema (PHE), delayed cerebral injury (DCI), and in the 42 survivors, the clinical outcome (mRS) and the brain tissue outcome. CONCLUSIONS: Regarding aICH evacuations, serial brain CT/MRI panels present more information than words, figures, and graphs. Re-bleeds associated with larger aICH volumes and worse outcomes. Swift logistics until the sIA occlusion with aICH evacuation is required, also in duty hours and weekends. Intraoperative CT is needed to illustrate the degree of aICH evacuation. PHE may evoke uncontrollable intracranial pressure (ICP) in spite of the acute aICH volume reduction.

Transarterial Embolization of Dural Arteriovenous Fistulas: Conventional, Pressure Cooker, and Microballoon Catheter Embolization Techniques.

BACKGROUND AND OBJECTIVES: Dural fistulas are abnormal connections between dural arteries and intracranial veins treated mainly endovascularly in most settings. The aim was to examine a single-institution experience of microballoon catheter transarterial embolization (TAE) of dural arteriovenous fistulas (dAVFs) and compare it with other TAE techniques. METHODS: We retrospectively identified all dAVFs treated at our institution between 2017 and 2022 with microballoon, conventional, and pressure cooker TAE. We studied occlusion and retreatment rates, treatment-related complications, and radiation doses. RESULTS: During the study period, 66 patients underwent 75 TAE procedures to treat 68 dAVFs: 47 conventional TAE, 14 pressure cooker TAE, and 14 microballoon TAE. Median age of the study population was 63 years with 32% females. The most common dAVF location was the transverse sinus and 20% of dAVFs presented with hemorrhage. At 3-month follow-up, stable complete occlusion of the dAVF was seen in 72% (n = 34) after conventional TAE, 79% (n = 11) after pressure cooker TAE, and 86% (n = 12) after microballoon TAE. Retreatment was required in 19% (n = 9) after conventional TAE, 7% (n = 1) after pressure cooker TAE, and 7% (n = 1) after microballoon TAE. Treatment-related complications occurred in 17% (n =) after conventional TAE, 29% (n = 4) after pressure cooker TAE, and 7% (n = 1) after microballoon TAE. CONCLUSION: In our experience, microballoon TAE of dAVFs resulted in better initial and 3-month angiographic outcomes and required less retreatment than conventional TAE. Microballoon TAE also resulted in fewer treatment-related complications than other techniques. In our experience, microballoon TAE is a reliable and safe endovascular technique to treat dAVFs.

Prevalence of pre-eclampsia in 265 patients with an intracranial aneurysm, 393 female relatives versus a control cohort: A case-control study.

BACKGROUND AND OBJECTIVES: There is emerging evidence on the connection between pre-eclampsia and saccular intracranial aneurysms (sIAs). Our aim was to study the prevalence of pre-eclampsia in sIA patients, their female relatives, and matched controls, and to examine familial sIA disease and familial pre-eclampsia in sIA patients' families. METHODS: We included all female sIA patients in the Kuopio Intracranial Aneurysm Patient and Family Database from 1995 to 2018. First, we identified the sIA patients, their female relatives, and matched population controls with the first birth in 1987 or later and studied the prevalence of pre-eclampsia. Second, all female sIA patients and all female relatives were analyzed for familial sIA disease and familial pre-eclampsia. Using the Finnish nationwide health registries, we obtained data on drug purchases, hospital diagnoses, and causes of death. RESULTS: In total, 265 sIA patients, 57 daughters, 167 sisters, 169 nieces, and 546 matched controls had the first birth in 1987 or later. Among them, 29 (11%) sIA patients, 5 (9%) daughters, 10 (6%) sisters, 10 (6%) nieces, and 32 (6%) controls had pre-eclampsia. Of all the 1895 female sIA patients and 12,141 female relatives, 68 sIA patients and 375 relatives had pre-eclampsia, including 32 families with familial pre-eclampsia. CONCLUSIONS: Pre-eclampsia was significantly more common in the sIA patients than in their matched controls. Familial sIA disease and familial pre-eclampsia co-occurred in seven families. Further studies of the mechanisms by which pre-eclampsia could affect the walls of brain arteries and increase the rupture risk in sIA disease are indicated.

Intraoperative intraarterial indocyanine green video-angiography for disconnection of a perimedullary arteriovenous fistula: illustrative case.

BACKGROUND: Intraarterial (IA) indocyanine green (ICG) angiography is an intraoperative imaging technique offering special and temporal characterization of vascular lesions with very fast dye clearance. The authors' aim is to demonstrate the use of IA ICG angiography to aid in the surgical treatment of a perimedullary thoracic arteriovenous fistula (AVF) in a hybrid operating room (OR). OBSERVATIONS: A 31-year-old woman with a known history of spinal AVF presented with 6 weeks of lower-extremity weakness, gait imbalance, and bowel/bladder dysfunction. Magnetic resonance imaging revealed an extensive series of flow voids across the thoracic spine, most notably at T11-12. After partial embolization, she was taken for surgical disconnection in a hybrid OR. Intraoperative spinal digital subtraction angiography was performed to identify feeding vessels. When the target arteries were catheterized, 0.05 mg of ICG in 2 mL of saline was injected, and the ICG flow in each artery was recorded using the microscope. With an improved surgical understanding of the contributing feeding arteries, the authors achieved complete in situ disconnection of the AVF. LESSONS: IA ICG angiography can be used in hybrid OR settings to illustrate the vascular anatomy of multifeeder perimedullary AVFs and confirm its postoperative disconnection with a fast dye clearance.

Long-term Risk of Epilepsy in Subarachnoid Hemorrhage Survivors With Positive Family History: A Population-Based Follow-up Study.

BACKGROUND AND OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke affecting the working-age population, where epilepsy is a common complication and major prognostic factor for increased morbidity in aSAH survivors. The objective of this analysis was to assess whether epilepsy in first-degree relatives is a risk of developing epilepsy after aSAH. METHODS: We used a region-specific database that includes all cases of unruptured and ruptured saccular intracranial aneurysm admitted to Kuopio University Hospital from its defined Eastern Finnish catchment population. We also retrieved data from Finnish national health registries for prescription drug purchases and reimbursement, hospital discharge, and cause of death and linked them to patients with aSAH, their first-degree relatives, and population controls matched 3:1 by age, sex, and birth municipality. Cox regression modeling and Kaplan-Meier survival curves were used for analysis. RESULTS: We examined data for 760 consecutive 12-month survivors of aSAH, born in 1950 or after, with a first aSAH from January 1, 1995, to December 31, 2018. Of the 760 patients (median age, 47 years; 53% female; median follow-up, 11 years), 111 (15%) developed epilepsy at a median of 7 months (interquartile range, 2-14 months) after admission for aSAH. Of the 2,240 population controls and 4,653 first-degree relatives of patients with aSAH, 23 (0.9%) and 80 (1.7%), respectively, developed epilepsy during the follow-up period. Among 79 patients with epilepsy in first-degree relatives, 22 (28%) developed epilepsy after aSAH; by contrast, among 683 patients with no epilepsy in first-degree relatives, 89 (13%) developed epilepsy after aSAH. Having at least 1 relative with epilepsy was an independent risk factor of epilepsy after aSAH (hazard ratio, 2.44; 95% CI 1.51-3.95). Cumulative 1-year rates by first-degree relationship were 40% with 1 or more children with epilepsy, 38% with 1 or more affected parents, 5% with 1 or more affected siblings, and 10% with no relatives with epilepsy. DISCUSSION: Patients who developed epilepsy after aSAH were significantly more likely to have first-degree relatives with epilepsy than those who did not develop epilepsy after the aSAH.

Concomitant Rupture of an Intracranial Aneurysm and a Dural Arteriovenous Fistula: Clinical Image.

A patient in his 50s presented with postcoital severe headache. Computed tomography revealed a subarachnoid hemorrhage but also a subdural hematoma at the left convexity. Computed tomography angiography revealed a large irregular anterior communicating artery aneurysm but also cortical serpiginous vessels suggestive of a vascular malformation adjacent to the subdural hematoma in the left convexity. Digital subtraction angiography confirmed the ruptured aneurysm but also revealed a Borden 3 type dural arteriovenous fistula on the left convexity. The fistula had arterial supply mostly from middle meningeal artery branches and venous drainage directly to a left cortical vein adjacent to superior sagittal sinus. Ruptured aneurysm was treated with coiling. The ruptured fistula was treated in the same session with transarterial Onyx embolization. The patient had a favorable outcome. Our case is an important reminder for all clinicians treating patients with intracranial hemorrhages on the necessity of fully reviewing all available preoperative imaging.

Should individual timeline and serial CT/MRI panels of all patients be presented in acute brain insult cohorts? A pilot study of 45 patients with decompressive craniectomy after aneurysmal subarachnoid hemorrhage.

PURPOSE: Our review of acute brain insult articles indicated that the patients' individual (i) timeline panels with the defined time points since the emergency call and (ii) serial brain CT/MRI slice panels through the neurointensive care until death or final brain tissue outcome at 12 months or later are not presented. METHODS: We retrospectively constructed such panels for the 45 aneurysmal subarachnoid hemorrhage (aSAH) patients with a secondary decompressive craniectomy (DC) after the acute admission to neurointensive care at Kuopio University Hospital (KUH) from a defined population from 2005 to 2018. The patients were indicated by numbers (1.-45.) in the pseudonymized panels, tables, results, and discussion. The timelines contained up to ten defined time points on a logarithmic time axis until death ([Formula: see text]; 56%) or 3 years ([Formula: see text]; 44%). The brain CT/MRI panels contained a representative slice from the following time points: SAH diagnosis, after aneurysm closure, after DC, at about 12 months (20 survivors). RESULTS: The timelines indicated re-bleeds and allowed to compare the times elapsed between any two time points, in terms of workflow swiftness. The serial CT/MRI slices illustrated the presence and course of intracerebral hemorrhage (ICH), perihematomal edema, intraventricular hemorrhage (IVH), hydrocephalus, delayed brain injury, and, in the 20 (44%) survivors, the brain tissue outcome. CONCLUSIONS: The pseudonymized timeline panels and serial brain imaging panels, indicating the patients by numbers, allowed the presentation and comparison of individual clinical courses. An obvious application would be the quality control in acute or elective medicine for timely and equal access to clinical care.

The Woven EndoBridge for intracranial aneurysms: Radiological outcomes and factors influencing occlusions at 6 and 24 months.

PURPOSE: To identify factors influencing short- and mid-term radiological outcomes of intracranial aneurysms (IAs) treated with the Woven EndoBridge (WEB). METHODS: A total of 112 patients were treated for IAs with the WEB in at our institution between 2013 and 2020. Patients with 6- and/or 24-months follow-up data were included in the study. Aneurysm occlusion was evaluated using the Raymond-Roy occlusion classification (RR). RR 1 and RR 2 were considered as adequate outcomes, while RR 3 inadequate. RESULTS: Data were available for 91 patients (56 females, 62%) at 6 months and 62 of those patients (39 females, 58%) at 24 months. The adequate occlusion (RR 1/RR 2) rate was 89% (n = 81/91) at the 6-months follow-up and 91% (n = 56/62) at the 24-months follow-up. The treatment-related morbidity rate was 4% (n = 4/91), and mortality rate was 1% (n = 1/91). The predictor for inadequate occlusion at the 6-months follow-up was the lobular shape of an aneurysm (p = .01). The aneurysm's height (p = .02), maximal diameter (p = .001), width (p = .002), aspect ratio (p = .03), dome-to-neck ratio (p = .04), and lobular shape (p= .03) were predictive factors for inadequate occlusion at 24 months. All the thrombosed aneurysms (n = 3) showed unfavorable radiological outcomes and required re-treatment within 24 months. None of the patient-related factors were significant. CONCLUSIONS: The WEB provides favorable occlusion rates and low complications for both ruptured and unruptured wide-necked IAs. Unfavorable radiological outcomes after WEB treatment may be related to aneurysm morphology and size.

Duplication of the internal maxillary artery: Anatomical and clinical considerations.

Duplication of the internal maxillary artery (IMAX) results from a failed regression of either the embryological superficial or deep ring and is reported to be exceedingly rare. We present a patient with this rare anatomical variant who was treated by endovascular technique in the clinical context of an acute oropharyngeal hemorrhage.

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.

Risk factor management matters more than pharmaceutical cyclooxygenase-2 inhibition in the prevention of de novo intracranial aneurysms.

BACKGROUND AND PURPOSE: Pathophysiological studies of saccular intracranial aneurysm (sIA) disease have shown that inflammation plays a crucial role in sIA development. Pharmaceutical inhibition of COX-2-PGE2-NF-κB signaling (COX-2, cyclooxygenase-2; PGE2, prostaglandin E2; NF-κB, nuclear factor κB) has been shown in animal models to inhibit sIA formation and progression suggesting that use of medication inhibiting COX-2 could reduce intracranial aneurysm formation also in patients. METHODS: The impact of COX-2 inhibition on de novo sIA formation was studied in two cohorts: in a previously described angiographically followed cohort of 1419 sIA patients and in a cohort of 117 sIA patients treated with stenting or stent-assisted embolization. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database. Data on the use of anti-inflammatory medications and hospital diagnoses were obtained from national registries. Risk factors were identified by univariate and multivariate analyses. RESULTS: De novo sIA patients were younger and more often smokers. Use of COX-2 selective inhibitors or nonsteroidal anti-inflammatory drugs did not significantly reduce de novo sIA formation, but the percentage of patients with de novo sIA formation was smaller in patients with prescribed regular acetylsalicylic acid medication (1.1% vs. 3.6%). In the multivariate analysis, however, neither acetylsalicylic acid use nor other type of pharmaceutical inhibition of COX-2 reduced the formation of de novo sIAs. The risk was mostly affected by age, smoking history and irregular usage of antihypertensive medication regardless of used COX-2 inhibition level. CONCLUSION: For the prevention of de novo sIA formation, risk factor management with focus on cessation of smoking and treating hypertension adequately seems more important than pharmaceutical COX-2 inhibition.

Use of antihypertensive medication and formation of de novo intracranial aneurysms.

BACKGROUND AND PURPOSE: Hypertension is a risk factor for subarachnoid hemorrhage and is also considered a risk factor for saccular intracranial aneurysm (sIA) formation. However, there is little direct evidence that antihypertensive medication will reduce sIA formation. METHODS: The impact of antihypertensive medication on de novo sIA formation was studied in an angiographically followed cohort of 1419 patients. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database, and data on the purchases of antihypertensive medication were obtained from a national registry. Univariate and multivariate analyses were used to investigate the risk factors. RESULTS: Of the 966 sIA patients who were prescribed with antihypertensive medication, 841 patients used the medication regularly; 20 of them had de novo sIA. One hundred and twenty-five patients used the medication irregularly and 12 of them developed de novo sIAs. Four hundred and fifty-three patients did not use antihypertensive medication even though 27 of them had a diagnosis of hypertension, and 10 of them developed de novo sIAs. In the multivariate analysis antihypertensive medication did not significantly reduce de novo sIA formation (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.84-3.06). Age at primary diagnosis (HR: 0.95, 95%: CI 0.93-0.98) and smoking history (HR: 5.53, 95% CI: 2.77-11.05) were significant risk factors for de novo sIA formation. Also, irregular usage of antihypertensive medication was a significant risk factor (HR: 3.84, 95% CI: 1.59-9.29) for de novo sIA formation. CONCLUSIONS: Antihypertensive agents were not associated with a reduction of de novo sIA formation, but irregular use of antihypertensive agents was associated with an increased risk of de novo sIA formation.

Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons With a Family History for Subarachnoid Hemorrhage.

BACKGROUND: Persons with a positive family history of aneurysmal subarachnoid hemorrhage are at increased risk of aneurysmal subarachnoid hemorrhage. Preventive screening for intracranial aneurysms (IAs) in these persons is cost-effective but not very efficient. We aimed to develop and externally validate a model for predicting the probability of an IA at first screening in persons with a positive family history of aneurysmal subarachnoid hemorrhage. METHODS: For model development, we studied results from initial screening for IA in 660 prospectively collected persons with ≥2 affected first-degree relatives screened at the University Medical Center Utrecht. For validation, we studied results from 258 prospectively collected persons screened in the University Hospital of Nantes. We assessed potential predictors of IA presence in multivariable logistic regression analysis. Predictive performance was assessed with the C statistic and a calibration plot and corrected for overfitting. RESULTS: IA were present in 79 (12%) persons in the development cohort. Predictors were number of affected relatives, age, smoking, and hypertension (NASH). The NASH score had a C statistic of 0.68 (95% CI, 0.62-0.74) and showed good calibration in the development data. Predicted probabilities of an IA at first screening varied from 5% in persons aged 20 to 30 years with two affected relatives, without hypertension who never smoked, up to 36% in persons aged 60 to 70 years with ≥3 affected relatives, who have hypertension and smoke(d). In the external validation data IA were present in 67 (26%) persons, the model had a C statistic of 0.64 (95% CI, 0.57-0.71) and slightly underestimated IAs risk. CONCLUSIONS: For persons with ≥2 affected first-degree relatives, the NASH score improves current predictions and provides risk estimates for an IA at first screening between 5% and 36% based on 4 easily retrievable predictors. With the information such persons can now make a better informed decision about whether or not to undergo preventive screening.

Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

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.

Finnish flow diverter study: 8 years of experience in the treatment of acutely ruptured intracranial aneurysms.

BACKGROUND: Flow diversion of acutely ruptured intracranial aneurysms (IAs) is controversial due to high treatment-related complication rates and a lack of supporting evidence. We present clinical and radiological results of the largest series to date. METHODS: This is a nationwide retrospective study of acutely ruptured IAs treated with flow diverters (FDs). The primary outcome was the modified Rankin Scale (mRS) score at the last available follow-up time. Secondary outcomes were treatment-related complications and the aneurysm occlusion rate. RESULTS: 110 patients (64 females; mean age 55.7 years; range 12-82 years) with acutely ruptured IAs were treated with FDs between 2012 and 2020 in five centers. 70 acutely ruptured IAs (64%) were located in anterior circulation, and 47 acutely ruptured IAs (43%) were blister-like. A favorable functional outcome (mRS 0-2) was seen in 73% of patients (74/102). Treatment-related complications were seen in 45% of patients (n=49). Rebleeding was observed in 3 patients (3%). The data from radiological follow-ups were available for 80% of patients (n=88), and complete occlusion was seen in 90% of aneurysms (79/88). The data from clinical follow-ups were available for 93% of patients (n=102). The overall mortality rate was 18% (18/102). CONCLUSIONS: FD treatment yields high occlusion for acutely ruptured IAs but is associated with a high risk of complications. Considering the high mortality rate of aneurysmal subarachnoid hemorrhage, the prevention of rebleeding is crucial. Thus, FD treatment may be justified as a last resort option.