Glioma grade and post-neurosurgical meningitis risk.

BACKGROUND: Post-neurosurgical meningitis (PNM) constitutes a grave complication associated with substantial morbidity and mortality. This study aimed to determine the risk factors predisposing patients to PNM following surgery for low- and high-grade gliomas. METHODS: We conducted a retrospective analysis encompassing all patients who underwent glioma surgery involving craniotomy at Turku University Hospital, Turku, Finland, between 2011 and 2018. Inclusion criteria for PNM were defined as follows: (1) Positive cerebrospinal fluid (CSF) culture, (2) CSF leukocyte count ≥ 250 × 106/L with granulocyte percentage ≥ 50%, or (3) CSF lactate concentration ≥ 4 mmol/L, detected after glioma surgery. Glioma grades 3-4 were classified as high-grade (n = 261), while grades 1-2 were designated as low-grade (n = 84). RESULTS: Among the 345 patients included in this study, PNM developed in 7% (n = 25) of cases. The median time interval between glioma surgery and diagnosis of PNM was 12 days. Positive CSF cultures were observed in 7 (28%) PNM cases, with identified pathogens encompassing Staphylococcus epidermidis (3), Staphylococcus aureus (2), Enterobacter cloacae (1), and Pseudomonas aeruginosa (1). The PNM group exhibited a higher incidence of reoperations (52% vs. 18%, p < 0.001) and revision surgery (40% vs. 6%, p < 0.001) in comparison to patients without PNM. Multivariable analysis revealed that reoperation (OR 2.63, 95% CI 1.04-6.67) and revision surgery (OR 7.08, 95% CI 2.55-19.70) were significantly associated with PNM, while glioma grade (high-grade vs. low-grade glioma, OR 0.81, 95% CI 0.30-2.22) showed no significant association. CONCLUSIONS: The PNM rate following glioma surgery was 7%. Patients requiring reoperation and revision surgery were at elevated risk for PNM. Glioma grade did not exhibit a direct link with PNM; however, the presence of low-grade gliomas may indirectly heighten the PNM risk through an increased likelihood of future reoperations. These findings underscore the importance of meticulous post-operative care and infection prevention measures in glioma surgeries.

Prevalence of thoracic aortic aneurysms and dilatations in patients with intracranial aneurysms.

OBJECTIVE: The prevalence of intracranial aneurysms (IAs) is higher in patients with aortic aneurysms. However, there are lack of studies investigating prevalence of thoracic aortic aneurysms (TAAs) in patients with IAs. The objective of this study was to evaluate the prevalence and risk factors for thoracic aortic dilatations (TADs) and TAAs in patients with IAs. METHODS: We retrospectively reviewed data from 1777 patients with diagnosed IAs at our institution between 2006 and 2016. We included 411 patients with saccular IAs and available imaging studies (computed tomography or magnetic resonance imaging) of all thoracic aortic segments. TAD was defined according to age- and sex-matched normograms, and TAA as a diameter of greater than 4.0 cm. RESULTS: A total of 83 patients (20%) had TAD or TAA. The prevalence of TADs and TAAs were 18% (n = 74) and 8% (n = 31) without significant difference between unruptured and ruptured IAs (P = .7). Of the 74 patients with TAD, 22 (30%) had multiple TADs and 66% of the TADs located in the aortic arch. Older age (odds ratio [OR], 1.04; P = .006), rheumatic disease (OR, 4.73; P = .009) and alcohol abuse (OR, 4.77; P = .01) were significant risk factors for TAD/TAA. CONCLUSIONS: The prevalence of TADs and TAAs is considerably greater in patients with IAs compared with reports from the general population, suggesting that IAs might be associated with aortopathy and might share a similar pathogenetic background with TADs/TAAs. Especially patients with IAs and a history of rheumatic disease and/or alcohol abuse are at high risk for TADs/TAAs.

Temporal Trends in Healthcare Costs and Outcome Following ICU Admission After Traumatic Brain Injury.

OBJECTIVE: To assess temporal trends in 1-year healthcare costs and outcome of intensive care for traumatic brain injury in Finland. DESIGN: Retrospective observational cohort study. SETTING: Multicenter study including four tertiary ICUs. PATIENTS: Three thousand fifty-one adult patients (≥ 18 yr) with significant traumatic brain injury treated in a tertiary ICU during 2003-2013. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Total 1-year healthcare costs included the index hospitalization costs, rehabilitation unit costs, and social security reimbursements. All costs are reported as 2013 U.S. dollars ($). Outcomes were 1-year mortality and permanent disability. Multivariate regression models, adjusting for case-mix, were used to assess temporal trends in costs and outcome in predefined Glasgow Coma Scale (3-8, 9-12, and 13-15) and age (18-40, 41-64, and ≥ 65 yr) subgroups. Overall 1-year survival was 76% (n = 2,304), and of 1-year survivors, 37% (n = 850) were permanently disabled. Mean unadjusted 1-year healthcare cost was $39,809 (95% CI, $38,144-$41,473) per patient. Adjusted healthcare costs decreased only in the Glasgow Coma Scale 13-15 and 65 years and older subgroups, due to lower rehabilitation costs. Adjusted 1-year mortality did not change in any subgroup (p < 0.05 for all subgroups). Adjusted risk of permanent disability decreased significantly in all subgroups (p < 0.05). CONCLUSION: During the last decade, healthcare costs of ICU-admitted traumatic brain injury patients have remained largely the same in Finland. No change in mortality was noted, but the risk for permanent disability decreased significantly. Thus, our results suggest that cost-effectiveness of traumatic brain injury care has improved during the past decade in Finland.

High risk population isolate reveals low frequency variants predisposing to intracranial aneurysms.

3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2× increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42×10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17×10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87×10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08×-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87×10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases.

Accuracy of 837 pedicle screw positions in degenerative lumbar spine with conventional open surgery evaluated by computed tomography.

BACKGROUND: The spatial and directional accuracy of the positioning of pedicle screws in the lumbosacral spine with conventional open surgery assessed by computed tomography (CT) has been published in several studies, systematic reviews and meta-analyses with a short-term follow-up. Inaccurate pedicle screw insertion may cause neurologic symptoms and weakens the construct. METHODS: The data of 147 patients operated on with transpedicular screw fixation based on anatomical landmarks, supported by fluoroscopy, by a senior neurosurgeon in our clinic between 2000 and 2010 were analyzed retrospectively. The accuracy of the pedicle screw position was assessed by using postoperative CT images and graded in 2-mm increments up to 6 mm by two independent surgeons and partly by an independent radiologist. RESULTS: A total of 837 lumbosacral pedicle screws were inserted in 147 randomly selected patients by a senior neurosurgeon. A mean accuracy of 85.7% of the screws being inside the pedicles was identified by the surgeon observers, with 3.3% being perforated 4 mm or more outside the pedicles. Postoperative neurologic symptoms were observed on the side corresponding to the breach in an average of 25.9% of patients with pedicle perforations, and 89.2% of the misplaced screws were either medially or inferiorly inserted. CONCLUSIONS: Screw application reached a mean accuracy of 85.7% based on anatomical landmarks supported by fluoroscopy, warranting computer-assisted navigation for increased accuracy. Our results of 24 patients (16.3%) with the breached screws indicate that the direction of the breach may be more important than the absolute deviation in causing new neurologic symptoms.

Acute hormonal findings after aneurysmal subarachnoid hemorrhage - report from a single center.

PURPOSE: The aim was to assess anterior pituitary hormone levels during the acute phase of aneurysmal subarachnoid hemorrhage (aSAH) and analyze the possible association with the clinical condition and outcome. MATERIAL AND METHODS: Forty patients with aSAH whose aneurysm was secured by endovascular coiling were enrolled. Basal secretions of cortisol, testosterone, luteinizing hormone (LH), prolactin (PRL), and sex hormone binding globulin (SHBG) levels were measured up to 14 days after the incident. RESULTS: The main finding was that hypocortisolism was rare whereas testosterone deficiency was common in male patients. Furthermore, various other hormone deviations were frequent and there was wide interindividual variability. We found no association between delayed cerebral ischemia (DCI), outcome of the patients or aneurysm location, and hormone abnormalities, while both Hunt & Hess and Fisher grade were associated with low PRL levels. Hunt & Hess 5 was associated with low PRL concentration when compared to grades 1 (OR = 4.81, 95% CI 1.15-20.14, p = 0.03), 3 (OR 7.73, 95% CI 1.33-45.01, p = 0.02), and 4 (OR = 6.86 95% CI 1.28-26.83, p = 0.02). Fisher grade 4 was associated with low PRL concentration when compared to grades 3 (OR 3.37, 95% CI 1.06-10.73, p = 0.03) and 2 (OR 9.71, 95% CI 1.22-77.10, p = 0.04). CONCLUSION: Deviations from normal and huge interindividual differences are common in hormone levels during the acute phase of aSAH. Routine assessment of anterior pituitary function in the acute phase of aSAH is not warranted. During the follow-up in the outpatient clinic, hormone concentrations were not measured, which would have brought a more long-term perspective into our findings.

Detection Rates and Trends of Asymptomatic Unruptured Intracranial Aneurysms From 2005 to 2019.

BACKGROUND AND OBJECTIVES: The trend in detection rates of asymptomatic unruptured intracranial aneurysms (UIAs) on brain computed tomography angiography/magnetic resonance angiography (CTA/MRA) is not well established. Our objective was to evaluate time trends in asymptomatic UIA detection rates on brain CTA/MRA between 2005 and 2019. METHODS: We conducted a retrospective study of all brain computed tomography/magnetic resonance scans (n = 288 336 scans in 130 621 patients) performed between January 2005 and December 2019 at a tertiary referral hospital. Patients who underwent brain CTA/MRA examinations were included (n = 81 261 scans in 48 037 patients). The annual detection rate of new UIA cases was calculated based on the first brain CTA/MRA imaging. Detection rates were compared between three periods and across different age groups. RESULTS: The number of first CTA/MRA examinations increased significantly from 2005 to 2009 (n = 12 190 patients) to 2010-2014 (n = 14 969 patients) and 2015-2019 (n = 20 878 patients) ( P < .001). The UIA detection rate also increased significantly from 1.7% in 2005-2009 to 2.5% in 2010-2014 and 3.4% in 2015-2019 ( P < .001). The UIA detection rate increased significantly from 2010-2014 to 2015-2019 (relative risk [RR], 1.33; 95% CI, 1.17-1.51), particularly in patients aged 60-69 years (RR, 1.29; 95% CI, 1.01-1.63), 70-79 years (RR, 1.71; 95% CI, 1.30-2.25), and >79 years (RR, 2.33; 95% CI, 1.56-3.47). Furthermore, the detection rate of <5-mm UIAs increased from 2010-2014 to 2015-2019 (RR, 1.51; 95% CI, 1.28-1.77). CONCLUSION: The detection rate of asymptomatic UIAs, particularly in elderly patients, has increased significantly over the past 15 years, coinciding with the increased use of CTA/MRA imaging. Furthermore, the size of the identified UIAs has decreased. These findings raise concerns about the management strategies for UIAs, indicating the need for further research.

Positive Correlation Between Thoracic Aortic Diameter and Intracranial Aneurysm Size-An Observational Cohort Study.

OBJECTIVE: To investigate the association between intracranial aneurysms (IAs) and thoracic aortic diameter. METHODS: This observational cohort study examined thoracic aortic diameters in patients with IA. Patients were categorized by IA size (<7 mm and ≥7 mm) and IA status (ruptured/unruptured) based on radiologic findings. We investigated the association between thoracic aortic diameter and IA size and status using binary and linear regression as univariate and multivariable analyses. RESULTS: A total of 409 patients were included. Mean age was 60 (±11.7) years and 63% were women. Thoracic aortic diameters were greater among patients who had an IA ≥7 mm versus IA <7 mm (P < 0.05). In the univariate analysis, the diameter of the ascending aorta (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.129 per 1 mm; P = 0.002), aortic arch (OR, 1.10; 95% CI, 1.04-1.15 per 1 mm; P < 0.001), and descending aorta (OR, 1.10; 95% CI, 1.03-1.16 per 1 mm; P = 0.003) were associated with IAs ≥7 mm. In the multivariable regression model, larger ascending aorta (OR, 1.09; 95% CI, 1.01-1.17 per 1 mm; P = 0.018), aortic arch (OR, 1.12; 95% CI, 1.02-1.22 per 1 mm; P = 0.013), and descending aorta (OR, 1.20; 95% CI, 1.08-1.33 per 1 mm; P < 0.001) were associated with ruptured IA. CONCLUSIONS: Greater thoracic aortic diameters are associated with a higher risk of IA being larger than 7 mm and IA rupture. Exploring the concomitant growth tendency in IA and thoracic aorta provides a basis for future considerations regarding screening and risk management.

Low and Borderline Ankle-Brachial Index Is Associated With Intracranial Aneurysms: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: A low ankle-brachial index (ABI) has been linked to systemic inflammation and an elevated risk of cardiovascular events, most notably myocardial infarction and stroke. Intracranial aneurysms (IAs) share similar risk factors with other cardiovascular diseases. However, the association between low ABI and IAs has not been sufficiently investigated. Our objective was to investigate the potential connection between ABI values and the prevalence of unruptured IAs. METHODS: This retrospective cohort study reviewed 2751 patients who had ABI measurements at a public tertiary hospital from January 2011 to December 2013. Patients with available cerebrovascular imaging or a diagnosis of ruptured IA were included in the study (n = 776) to examine the association between ABI and saccular IAs. The patients were classified into 4 groups: low ABI (≤0.9, n = 464), borderline ABI (0.91-0.99; n = 47), high ABI (>1.4, n = 57), and normal ABI (1.00-1.40; n = 208). RESULTS: The prevalence of IAs was 20.3% (18.1% unruptured IAs) in the low ABI group, 14.9% (12.8% unruptured IAs) in the borderline ABI group, 7.0% (5.3% unruptured IAs) in the high ABI group, and 2.4% (1.9% unruptured IAs) in the normal ABI group (P < .001). There were no significant differences in the prevalence of ruptured IAs between the ABI groups (P = .277). Sex- and age-adjusted multinomial regression, including clinically relevant variables, revealed that low ABI (odds ratio [OR], 13.02; 95% CI, 4.01-42.24), borderline ABI (OR, 8.68; 95% CI, 2.05-36.69), and smoking history (OR, 2.01; 95% CI, 1.07-3.77) were associated with unruptured IAs. CONCLUSION: The prevalence of unruptured IAs was 9-fold higher in the low ABI group and nearly 7-fold higher in the borderline ABI group when compared with the normal ABI group. ABI measurements could be clinically relevant for identifying individuals at higher risk of IAs and may help guide screening and preventive strategies.

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol.

INTRODUCTION: Positron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored. Our objective is to investigate feasibility of PET imaging using 18F-FDG and 68Ga-DOTANOC tracers to evaluate arterial wall inflammation in UIA. METHODS AND ANALYSIS: This PET imaging feasibility study will enrol patients scheduled for surgical treatment of UIA. The study subjects will undergo PET imaging of the intracranial arteries within 1 month before planned surgery. The imaging protocol includes 18F-FDG PET MRI, MRA with gadolinium enhancement, and 68Ga-DOTANOC PET CT. The study will also involve preoperative blood samples, intraoperative cerebrospinal fluid (CSF) samples, and aneurysm sac biopsy. Planned sample size is at least 18 patients. Primary outcome is uptake of 18F-FDG or 68Ga-DOTANOC in intracranial arterial aneurysms compared with contralateral normal vessel as maximum standardised uptake value or target-to-blood pool ratio and correlation of uptake of 18F-FDG or 68Ga-DOTANOC to aneurysm histological findings. Secondary outcomes include estimating the correlations between uptake of 18F-FDG or 68Ga-DOTANOC and histological findings with blood and CSF miRNA-levels, arterial wall enhancement in gadolinium enhanced MRA, aneurysm size and shape, smoking, hypertension, and location of the aneurysm. ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of the Hospital District of Southwest Finland, Finnish Medicines Agency Fimea, and Turku University Hospital. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04715503.

Incidence, surgical eligibility and outcome of spontaneous intracerebral haemorrhage in Southwest Finland - A retrospective study.

Introduction: Spontaneous intracerebral haemorrhage (sICH) is a major cause of morbidity and mortality. Large-scale trials have shown neutral outcomes for surgical interventions. The recent trial suggested functional benefits from surgical intervention. Surgical treatment for sICH is likely increasing. Research question: To determine the incidence of sICH in Southwest Finland, standardized to the European population, and to identify the proportion of large sICH patients eligible for surgery based on previously published trial criteria. We also examined factors associated with outcomes, including the effects of anticoagulant and antithrombotic medications. Material and methods: A retrospective clinical study identified 596 ICH cases treated at Turku University Hospital (2018-2019), of which 286 were supratentorial sICHs. Variables were analysed using a t-test, chi-squared or Fisher's exact test. A multivariate logistic modelling was performed to evaluate outcome differences. Results: The sICH incidence was 29.9/100,000 persons per year, with the highest European population age and sex standardized rates in individuals over 80 years old (110/100,000 males, 142/100,000 females). The incidence of sICH patients meeting surgical criteria was 2.7/100,000 persons per year. Out of 286 patients, 26 were eligible for surgery and had unfavourable outcomes (p = 0.0049). Multivariate analysis indicated a significant decrease in favourable outcomes with warfarin (p = 0.016, OR 0.42) and direct-acting anticoagulants (DOACs) (p = 0.034, OR 0.38), while antithrombotic medications showed no significant effect. Discussion and conclusion: We identified comparable incidence of sICH as European average. A small proportion of sICH cases were identified to be candidates for surgical intervention. Anticoagulants were associated with increased risk of unfavourable outcomes.

Brain plasticity and neuroinflammatory protein biomarkers with circulating MicroRNAs as predictors of acute brain injury outcome - A prospective cohort study.

BACKGROUND: Brain recovery mechanisms after injuries like aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) involve brain plasticity, synaptic regeneration, and neuroinflammation. We hypothesized that serum levels of the p75 neurotrophic receptor (p75NTR) and associated signaling proteins, as well as differentially expressed (DE) microRNAs, could predict recovery outcomes irrespective of injury type. METHODS: A prospective patient cohort with ischemic stroke (IS, n = 30), aneurysmal subarachnoid hemorrhage (aSAH, n = 31), and traumatic brain injury (TBI, n = 13) were evaluated (total n = 74). Serum samples were collected at two post-injury intervals (early: 1-3 days, late: 4-8 days), and outcomes were assessed after three months using the modified Rankin Scale (mRS), categorizing outcomes as favorable (mRS 0-3) or unfavorable (mRS 4-6). Six proteins were measured using ELISAs: p75NTR, NGF, sortilin, IL1ß, TNFα, and cyclophilin. DE microRNAs were identified using DESeq2, and their target genes were predicted. Serum molecules between patients with differing outcomes were compared using a Kolmogorov-Smirnov test, 2-tailed t-test and multivariate linear discriminant analysis (LDA). RESULTS: Favorable (n = 46) and unfavorable (n = 28) outcome cohorts were balanced with age and sex (p = 0.25 and 0.63). None of the studied proteins correlated with age. Combinatory LDA of the six protein biomarkers indicated strong prognostic value for favorable outcomes (OR 2.09; AUC = 70.3%, p = 0.0058). MicroRNA expression changes over time were identified in the aSAH, TBI, and IS groups (p < 0.05, FDR corrected). Twenty-three microRNAs were commonly DE across all brain injury groups when comparing favorable and unfavorable outcomes (p < 0.05). LDA of four microRNAs targeting the studied proteins showed high prognostic accuracy (OR 11.7; AUC = 94.1%, p = 0.016). CONCLUSIONS: The combined prognostic microRNA and protein biomarker models demonstrated accurate outcome prognostication across diverse injury types, implying the presence of a common recovery mechanism. DE microRNAs were found to target the studied molecules, suggesting a potential mechanistic role in recovery. Further investigation is warranted to study these molecules in prognostication, as well as therapeutic targets for enhancing recovery.

Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries-A Prospective Cohort Study.

Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients' outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53-89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83-65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.

Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

BACKGROUND AND OBJECTIVES: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). METHODS: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. RESULTS: We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1/GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8). DISCUSSION: We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.

Stent-assisted embolization of recurrent or residual intracranial aneurysms.

INTRODUCTION: Intracranial stents have theoretical advantages in the treatment of wide-necked intracranial aneurysms, but the usability of intracranial stents in the retreatment of recurrent intracranial aneurysms is relatively unknown. In this study, we aim to evaluate the safety and efficacy of stent-assisted embolization in the retreatment of recurrent or residual intracranial aneurysms. METHODS: Retrospective evaluation was carried out for 55 consecutive patients (17 men and 38 women; mean age 51.5 years), with 56 recurrent or residual intracranial aneurysms electively retreated with stent-assisted embolization. RESULTS: The technical success rate was 91% (50/55 patients). Procedural complications were encountered with six patients (11%). Angiographic and clinical follow-up data were available for 51 patients (93%), with a mean follow-up period of 28.1 months. No rebleedings were encountered during the study period. The clinical outcome was favorable in 50 patients (91%), with a Glasgow Outcome Score of 4 (N = 14) or 5 (N = 36) at the end of the study period. Poor clinical outcome correlated with very large (>2 cm) total aneurysm size (P = 0.002), large (>10 mm) recurrent aneurysm size (P = 0.011), and occurrence of periprocedural complications (P < 0.001). CONCLUSION: Stent-assisted coil embolization is beneficial for the retreatment of wide-necked recurrent or residual intracranial aneurysms, but stability and permanent occlusion of the recurrent aneurysm is unlikely if the aneurysm exceeds 2 cm in diameter, the recurrent diameter of the aneurysm exceeds 10 mm, or if mass effect is present with the recurrent aneurysm.

Outcome and survival of surgically treated acute subdural hematomas and postcraniotomy hematomas - A retrospective cohort study.

Background: The morbidity and mortality of acute subdural hematoma (aSDH) remains high. Several factors have been reported to affect the outcome and survival of these patients. In this study, we explored factors potentially associated with the outcome and survival of surgically treated acute subdural hematoma (aSDH), including postcraniotomy hematomas (PCHs). Methods: This retrospective cohort study was conducted in a single tertiary university hospital between 2008 and 2012 and all aSDH patients that underwent surgical intervention were included. A total of 132 cases were identified for collection of demographics, clinical, laboratory, and imaging data. Univariate and multivariable analyses were performed to assess factors associated with three-month Glasgow Outcome Scale (GOS) and survival at one- and five-year. Results: In this study, PCH (n = 14, 10.6%) was not associated with a worse outcome according to the 3- month GOS (p = 0.37) or one (p = 0.34) and five-year (p = 0.37) survival. The multivariable analysis showed that the volume of initial hematoma (p = 0.009) and Abbreviated Injury Scale score (p = 0.016) were independent predictors of the three-month GOS. Glasgow Coma Scale (GCS) score (p < 0.001 and p = 0.037) and age (p = 0.048 and p = 0.003) were predictors for one and five-year survival, while use of antiplatelet drug (p = 0.030), neuroworsening (p = 0.005) and smoking (p = 0.026) were significant factors impacting one year survival. In addition, blood alcohol level on admission was a predictor for five-year survival (p = 0.025). Conclusions: These elucidations underscore that, although PCHs are pertinent, a comprehensive appreciation of multifarious variables is indispensable in aSDH prognosis. These findings are observational, not causal. Expanded research endeavors are advocated to corroborate these insights.

Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.

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.

APOE4 predicts amyloid-ß in cortical brain biopsy but not idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-ß (Aß) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD). METHODS: 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aß (134 semiquantified by Aß plaques/mm2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others. RESULTS: The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aß plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%. CONCLUSION: In presumed NPH patients, APOE4 associates independently with the presence of Aß plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease. TRIAL REGISTRATION NUMBER: Kuopio NPH Registry (http://www.uef.fi/nph).

Increased relative risk of lung cancer in 2,904 patients with saccular intracranial aneurysm disease in eastern Finland.

BACKGROUND AND OBJECTIVE: To analyze the long-term incidence of cancer after the first diagnosis of saccular intracranial aneurysm (sIA) disease. METHODS: The Neurosurgery Department of the Kuopio University Hospital (KUH) solely serves a defined Eastern Finnish population. The Kuopio sIA database contains 2,904 consecutive sIA cases from 1980 to 2007, 618 unruptured (170 familial and 448 sporadic) and 2,286 ruptured aneurysmal subarachnoid hemorrhage (aSAH) cases (308 familial and 1,978 sporadic). They were followed for the incidence of cancer (Finnish Cancer Registry) until death (n = 1,176) or until December 31, 2008, giving a total of 26,844 person-years. Their standardized incidence ratios (SIRs) of different cancers were calculated as compared to the corresponding KUH population (year of follow-up, gender, age). RESULTS: Lung cancer after the first sIA diagnosis occurred in 30 of the 1,340 male patients [SIR = 2.0; 95% confidence interval (CI) = 1.4-2.9], and in 10 of the 1,564 female patients (SIR = 2.6; 95% CI = 1.2-4.7). Poisson regression analysis identified male gender and increasing diameter of the ruptured sIA as independent risk factors for lung cancer, while familial sIA disease, age at aSAH, site of ruptured sIA, or the presence of associated unruptured sIAs had no significant effect. CONCLUSIONS: Carriers of the sIA disease have an increased risk of developing lung cancer. Their long-term smoking habits after the sIA diagnosis should be elucidated for preventive purposes.