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Background Aneurysms are one of the most common and yet devastating cerebrovascular diseases after rupture. Despite several decades of scientific advancements including the expansion of the endovascular capabilities and noninvasive imaging modalities, no medical treatment exists to date. This failure is likely largely attributed to the complex and multifactorial nature of aneurysm pathophysiology. Recent research has increasingly implicated vascular endothelial growth factor (VEGF) in the development and rupture of intracranial aneurysms. Regarded as one of the most potent inducers of angiogenesis, it is a key factor in vascular wall maintenance, inflammation, and regulation of vascular permeability. Whether abnormal VEGF expression is directly related to aneurysm development or acting merely as an acute phase reactant remains uncertain. No review of the current‐state‐of‐evidence on this topic exists yet. Methods and Results A systematic literature search was performed following PRISMA guidelines May 2024 that queried PubMed (1946–2024), Wiley Cochrane Library: Central Register of Controlled Trials (1898–2024), Thompson Reuters Web of Science: Citation Index (1900–2024), and Google Scholar (1946–2024). Inclusion criteria encompassed human and animal studies that investigated the relationship of intracranial aneurysm and VEGF. Several human and animal models revealed significantly elevated expression of VEGF in intracranial aneurysm tissue, along with greater levels in the cerebrospinal fluid and systemically. Overexpression has been shown to inhibit endothelial cell migration, proliferation, and induce cell apoptosis. Recently, genetic polymorphisms of VEGF have also been shown to significantly correlate with the presence of intracranial aneurysms, establishing the first genetic link between the two. Conclusions Despite lacking definitive evidence of a causal relationship, the wealth of supporting data substantiates VEGF as a promising topic for future investigation into aneurysm pathophysiology and as a potential therapeutic target.

Summary: Background: The few previous studies that have estimated the incidence of cerebral cavernous malformations (cavernomas) have reported incidence rates of 0.2–1.9/100,000 for diagnosed cavernomas. Our aim was to describe incidence trends of cavernomas by clinical presentation. Methods: We conducted a retrospective cohort study of cavernomas diagnosed at two university hospitals in Finland (Kuopio University Hospital, KUH and Tampere University Hospital, TAUH). Cavernoma diagnoses during 2004–2020 were identified from the KUH and TAUH Care registry databases and verified from medical records and diagnostic imaging studies. We calculated the age-standardized incidence rates using the European standard population and analysed incidence trend and changes in trend by sex, age group, and calendar year using Poisson regression. Findings: A total of 669 cavernoma diagnoses were identified during 2004–2020 in the combined KUH and TAUH population. The age-standardized incidence rate was 2.01/100,000 (95% confidence interval (CI) 1.85–2.16) for all cavernoma diagnoses, 1.25/100,000 (1.13–1.37) for asymptomatic, 0.75/100,000 (0.66–0.85) for symptomatic, and 0.46/100,000 (0.39–0.53) for ruptured cavernomas. No significant difference in the incidence of cavernoma diagnoses was seen between the KUH and TAUH populations or between the sexes. Incidence of cavernomas was highest at ages 40–59 years and low in those under 20 or over 80 years of age. Incidence of diagnosed cavernomas, especially asymptomatic, increased during the study period. Interpretation: In our population-based study, incidence of cavernomas was higher than previously reported and increased during the study period. The burden imposed by cavernomas on healthcare system is considerable and increasing. Funding: The Research Council of Finland, Kuopio University Hospital, Tampere University Hospital, and Wellbeing services county of Pirkanmaa.

Abstract Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state. Graphical abstract

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. Methods The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. Discussion Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. Trial registration ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Background The size of the saccular intracranial aneurysm (IA) has been used as the primary indicator for rupture risk. We investigated at which size IAs that rupture did so, and whether this size has significantly changed over time. Methods Patients treated for ruptured IAs were identified from the Aneurysm Database of the Tampere University Hospital. The size of the IA at the time of rupture was measured from computed tomographic angiography or digital subtraction angiography made to diagnose the aneurysm. Data for the clinical risk factors for rupture were collected from the patient's medical records. Results Of the 2545 patients with ruptured intracranial aneurysms (IAs) admitted, the size of the ruptured IA could be determined for 76% (1925 of 2545). Fifty‐one percent (984 of 1925) of the studied IAs ruptured at a size

BACKGROUND:Secondary hypertension is a serious form of hypertension, involving 5% to 10% of all hypertension patients. Hypertension is a risk factor of the saccular intracranial aneurysm (sIA) disease and subarachnoid hemorrhage from ruptured sIA (aSAH), but the impact of secondary hypertension on sIA disease is poorly known. In a defined Eastern Finnish sIA population we studied the prevalence of secondary hypertension and its impact on sIA disease phenotype. METHODS:We included 2704 consecutive sIA patients first admitted to Kuopio University Hospital from 1995 to 2014. Their clinical data from Kuopio Intracranial Aneurysm patient and Family Database was fused with prescription drug usage data, hospital diagnoses and causes of death, retrieved from nationwide registries. Medical records of hypertensive sIA patients were reviewed to confirm or exclude secondary hypertension. Prevalence of secondary hypertension and associated diagnoses were calculated. Logistic regression was used to identify clinical characteristics of sIA disease that associated with secondary hypertension. RESULTS:We identified 2029 (75%) sIA patients with hypertension and 208 (10%) of them had secondary hypertension. Most frequent conditions associated with secondary hypertension were kidney and renovascular diseases (45%), sleep apnea (27%) and hypothyroidism (19%); 46 (22%) of the 208 patients had more than one such condition. In multivariate logistic regression analyses of 1561 aSAH patients, secondary hypertension significantly associated with the number of sIAs (p = 0.003; OR 1.32; 95% CI 1.10-1.58) and male gender (p = 0.034; OR 1.59; 95% CI 1.04-2.43). CONCLUSIONS:Secodary hypertension was relatively common (10%) among hypertensive sIA patients. Secondary causes for hypertension should be taken into account in hypertensive sIA patients, especially in aSAH patients with multiple intracranial aneurysms. Further research is indicated to evaluate the impact of secondary hypertension on the long-term rupture risk of unruptured sIA carriers and long-term outcome after aSAH.

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.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.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.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.