Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial.

BACKGROUND: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. METHODS: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. FINDINGS: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). INTERPRETATION: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. FUNDING: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.

Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). OBJECTIVE: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. METHODS: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18 F]FE-PE2I. RESULTS: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. CONCLUSIONS: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Zero-heat-flux thermometry over the carotid artery in assessment of core temperature in craniotomy patients.

Zero-heat-flux core temperature measurements on the forehead (ZHF-forehead) show acceptable agreement with invasive core temperature measurements but are not always possible in general anesthesia. However, ZHF measurements over the carotid artery (ZHF-neck) have been shown reliable in cardiac surgery. We investigated these in non-cardiac surgery. In 99 craniotomy patients, we assessed agreement of ZHF-forehead and ZHF-neck (3M™ Bair Hugger™) with esophageal temperatures. We applied Bland-Altman analysis and calculated mean absolute differences (difference index) and proportion of differences within ± 0.5 °C (percentage index) during entire anesthesia and before and after esophageal temperature nadir. In Bland-Altman analysis [mean (limits of agreement)], agreement with esophageal temperature during entire anesthesia was 0.1 (-0.7 to +0.8) °C (ZHF-neck) and 0.0 (-0.8 to +0.8) °C (ZHF-forehead), and, after core temperature nadir, 0.1 (-0.5 to +0.7) °C and 0.1 (-0.6 to +0.8) °C, respectively. In difference index [median (interquartile range)], ZHF-neck and ZHF-forehead performed equally during entire anesthesia [ZHF-neck: 0.2 (0.1-0.3) °C vs ZHF-forehead: 0.2 (0.2-0.4) °C], and after core temperature nadir [0.2 (0.1-0.3) °C vs 0.2 (0.1-0.3) °C, respectively; all p > 0.017 after Bonferroni correction]. In percentage index [median (interquartile range)], both ZHF-neck [100 (92-100) %] and ZHF-forehead [100 (92-100) %] scored almost 100% after esophageal nadir. ZHF-neck measures core temperature as reliably as ZHF-forehead in non-cardiac surgery. ZHF-neck is an alternative to ZHF-forehead if the latter cannot be applied.

Preoperative Magnetic Resonance Image Quality in Motion Disorder Patients Scheduled for Deep Brain Stimulation Surgery.

BACKGROUND: To obtain magnetic resonance (MR) images of good quality for accurate target localization in deep brain stimulation (DBS) surgery, sedation or anesthesia may be used, although their usefulness has not been proven. OBJECTIVE: To assess whether sedation or general anesthesia (GA) improve the quality of MR imaging (MRI). METHODS: The records of DBS procedures for Parkinson's disease (PD), dystonia, and essential tremor in our tertiary neurosurgical unit between January 2011 and June 2016 were reviewed. Adult patients with preoperative MR images were included. Patient records concerning MRI, surgery, adverse events, and clinical outcome were retrospectively scrutinized and analyzed. MR image quality was assessed by two independent radiologists. RESULTS: A total of 215 preoperative MR images for 177 DBS procedures were analyzed. The MRI sequences performed under GA were superior to those performed without anesthesia or under sedation (p < 0.01). Virtually all images captured under GA were of good quality, while the proportions among those captured with sedation or without anesthesia were <65%. Good image quality was not associated with better clinical outcome (>50% improvement in the Unified Parkinson's Disease Rating Scale III score) among patients with PD. CONCLUSION: GA was associated with better MRI sequences than intravenous sedation or no anesthesia.

Intensive care of traumatic brain injury and aneurysmal subarachnoid hemorrhage in Helsinki during the Covid-19 pandemic.

BACKGROUND: To ensure adequate intensive care unit (ICU) capacity for SARS-CoV-2 patients, elective neurosurgery and neurosurgical ICU capacity were reduced. Further, the Finnish government enforced strict restrictions to reduce the spread. Our objective was to assess changes in ICU admissions and prognosis of traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) during the Covid-19 pandemic. METHODS: Retrospective review of all consecutive patients with TBI and aneurysmal SAH admitted to the neurosurgical ICU in Helsinki from January to May of 2019 and the same months of 2020. The pre-pandemic time was defined as weeks 1-11, and the pandemic time was defined as weeks 12-22. The number of admissions and standardized mortality rates (SMRs) were compared to assess the effect of the Covid-19 pandemic on these. Standardized mortality rates were adjusted for case mix. RESULTS: Two hundred twenty-four patients were included (TBI n = 123, SAH n = 101). There were no notable differences in case mix between TBI and SAH patients admitted during the Covid-19 pandemic compared with before the pandemic. No notable difference in TBI or SAH ICU admissions during the pandemic was noted in comparison with early 2020 or 2019. SMRs were no higher during the pandemic than before. CONCLUSION: In the area of Helsinki, Finland, there were no changes in the number of ICU admissions or in prognosis of patients with TBI or SAH during the Covid-19 pandemic.

The focus of temperature monitoring with zero-heat-flux technology (3M Bair-Hugger): a clinical study with patients undergoing craniotomy.

In the noninvasive zero-heat-flux (ZHF) method, deep body temperature is brought to the skin surface when an insulated temperature probe with servo-controlled heating on the skin creates a region of ZHF from the core to the skin. The sensor of the commercial Bair-Hugger ZHF device is placed on the forehead. According to the manufacturer, the sensor reaches a depth of 1-2 cm below the skin. In this observational study, the anatomical focus of the Bair-Hugger ZHF sensor was assessed in pre- and postoperative CT or MRI images of 29 patients undergoing elective craniotomy. Assuming the 2-cm depth from the forehead skin surface, the temperature measurement point preoperatively reached the brain cortex in all except one patient. Assuming the 1-cm depth, the preoperative temperature measurement point did not reach the brain parenchyma in any of the patients and was at the cortical surface in two patients. Corresponding results were obtained postoperatively, although either sub-arachnoid fluid or air was observed in all CT/MRI images. Craniotomy did not have a detectable effect on the course of the ZHF temperatures. In Bland-Altman analysis, the agreement of ZHF temperature with the nasopharyngeal temperature was 0.11 (95% confidence interval - 0.54 to 0.75) °C and with the bladder temperature - 0.14 (- 0.81 to 0.52) °C. As conclusions, within the reported range of the Bair-Hugger ZHF measurement depth, the anatomical focus of the sensor cannot be determined. Craniotomy did not have a detectable effect on the course of the ZHF temperatures that showed good agreement with the nasopharyngeal and bladder temperatures.

Size of Ruptured Intracranial Aneurysms Is Decreasing: Twenty-Year Long Consecutive Series of Hospitalized Patients.

BACKGROUND AND PURPOSE: Decrease in the incidence of subarachnoid hemorrhage over the past decades has been related to decreased smoking rates, especially among <50-year-old people. We studied whether these epidemiological changes are reflected in changes in the size and location of ruptured intracranial aneurysms (RIAs). METHODS: We identified consecutive patients admitted to a nonprofit academic hospital with saccular RIAs between 1989 and 2008. We averaged and analyzed mean sizes of RIAs in 4-year admission groups. In statistical analysis, we used the χ2 test for categorical variables and the Kruskal-Wallis test to assess differences between continuous and categorical variables. For linear trend assessments, we used the linear-by-linear association and ANOVA tests. RESULTS: Of 2660 consecutive patients (59% women) with RIAs, 1176 (44%) were <50 years on admission. In people <50 years, the averaged annual mean size of RIAs decreased 16% from 9.2 mm in 1989 to 1992 to 7.7 mm in 2005 to 2008 in women and 13% (from 9.3 to 8.1 mm) in men (decreasing linear trend; P=0.001). RIA sizes did not change in 50-year-old or older patients, whereas the proportion of posterior circulation RIAs almost tripled to 13%, also with a linear relationship (P<0.001). CONCLUSIONS: The size of RIAs seems to be decreasing among younger generations of hospital-admitted subarachnoid hemorrhage patients, whereas 50-year-old and older subarachnoid hemorrhage patients have an increasing proportion of posterior circulation RIAs. These epidemiological changes are noteworthy, especially if they are universal and ongoing.

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.

Laitinen's Subgenual Cingulotomy: Anatomical Location and Case Report.

BACKGROUND: The widespread use of deep brain stimulation (DBS) for movement disorders has renewed the interest in DBS for psychiatric disorders. Lauri Laitinen was a pioneer of stereotactic psychosurgery in the 1950s to 1970s, especially by introducing the subgenual cingulotomy. Our aim here was to verify the anatomical target used by Laitinen, to report on a patient who underwent this procedure, and to review the literature. MATERIALS AND METHODS: The records of Helsinki University Hospital were searched for psychosurgical cases performed between 1970 and 1974. Alive consenting patients were interviewed and underwent a brain MRI. RESULTS: We found 1 patient alive who underwent subgenual cingulotomy in 1971 for obsessive thoughts, anxiety, and compulsions, diagnosed at that time as "schizophrenia psychoneurotica." MRI showed bilateral subgenual cingulotomy lesions (254 and 160 mm3, respectively). The coordinates of the center of the lesions in relation to the midcommissural point for the right and left, respectively, were: 7.1 and 7.9 mm lateral; 0.2 mm inferior and 1.4 mm superior, and 33.0 and 33.9 anterior, confirming correct subgenual targeting. The patient reported retrospective satisfactory results. CONCLUSIONS: The lesion in this patient was found to be in the expected location, which gives some verification of the correct placement of Laitinen's subgenus cingulotomy target.

Temporal changes in outcome following intensive care unit treatment after traumatic brain injury: a 17-year experience in a large academic neurosurgical centre.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of morbidity and mortality. However, it remains undetermined whether long-term outcomes after TBI have improved over the past two decades. METHODS: We conducted a retrospective analysis of consecutive TBI patients admitted to an academic neurosurgical ICU during 1999-2015. Primary outcomes of interest were 6-month all-cause mortality (available for all patients) and 6-month Glasgow Outcome Scale (GOS, available from 2005 onwards). GOS was dichotomized to favourable and unfavourable functional outcome. Temporal changes in outcome were assessed using multivariate logistic regression analysis, adjusting for age, sex, GCS motor score, pupillary light responsiveness, Marshall CT classification and major extracranial injury. RESULTS: Altogether, 3193 patients were included. During the study period, patient age and admission Glasgow Coma Scale score increased, while the overall TBI severity did not change. Overall unadjusted 6-month mortality was 25% and overall unadjusted unfavourable outcome (2005-2015) was 44%. There was no reduction in the adjusted odds of 6-month mortality (OR 0.98; 95% CI 0.96-1.00), but the adjusted odds of favourable functional outcome significantly increased (OR 1.08; 95% CI 1.04-1.11). Subgroup analysis showed outcome improvements only in specific subgroups (conservatively treated patients, moderate-to-severe TBI patients, middle-aged patients). CONCLUSIONS: During the past two decades, mortality after significant TBI has remained largely unchanged, but the odds of favourable functional outcome have increased significantly in specific subgroups, implying an improvement in quality of care. These developments have been paralleled by notable changes in patient characteristics, emphasizing the importance of continuous epidemiological monitoring.

Natural History of Ruptured but Untreated Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Knowledge on a natural history of untreated ruptured intracranial aneurysms is based on a small historical cohort from 1960s. We calculated mortality rates for patients with untreated ruptured intracranial aneurysms using a more recent and relatively large hospital cohort. METHODS: Patients admitted to the study hospital between 1968 and 2007 with saccular but untreated ruptured intracranial aneurysms were identified from the hospital aneurysm registry of 6850 patients. The study cohort included only patients who were followed up until death and for whom the date of symptom onset and the date of hospital admission were available. RESULTS: For 510 patients identified, the median survival time from symptom onset to death was 20 days. The 1-year mortality rate was 65%, but varied substantially by admission delays and clinical status on admission, being lowest (13%) for patients admitted later than a month after symptom onset and highest (89%) for poor-grade patients. The 1-year mortality rate was 75% for good-grade patients admitted within a week. CONCLUSIONS: Mortality rates for patients with untreated ruptured intracranial aneurysms are even worse than presented in the historical study. When discussing with subarachnoid hemorrhage patients and their relatives about treatment options, the presented natural history figures are of use.

Evaluation of novel computerized tomography scoring systems in human traumatic brain injury: An observational, multicenter study.

BACKGROUND: Traumatic brain injury (TBI) is a major contributor to morbidity and mortality. Computerized tomography (CT) scanning of the brain is essential for diagnostic screening of intracranial injuries in need of neurosurgical intervention, but may also provide information concerning patient prognosis and enable baseline risk stratification in clinical trials. Novel CT scoring systems have been developed to improve current prognostic models, including the Stockholm and Helsinki CT scores, but so far have not been extensively validated. The primary aim of this study was to evaluate the Stockholm and Helsinki CT scores for predicting functional outcome, in comparison with the Rotterdam CT score and Marshall CT classification. The secondary aims were to assess which individual components of the CT scores best predict outcome and what additional prognostic value the CT scoring systems contribute to a clinical prognostic model. METHODS AND FINDINGS: TBI patients requiring neuro-intensive care and not included in the initial creation of the Stockholm and Helsinki CT scoring systems were retrospectively included from prospectively collected data at the Karolinska University Hospital (n = 720 from 1 January 2005 to 31 December 2014) and Helsinki University Hospital (n = 395 from 1 January 2013 to 31 December 2014), totaling 1,115 patients. The Marshall CT classification and the Rotterdam, Stockholm, and Helsinki CT scores were assessed using the admission CT scans. Known outcome predictors at admission were acquired (age, pupil responsiveness, admission Glasgow Coma Scale, glucose level, and hemoglobin level) and used in univariate, and multivariable, regression models to predict long-term functional outcome (dichotomizations of the Glasgow Outcome Scale [GOS]). In total, 478 patients (43%) had an unfavorable outcome (GOS 1-3). In the combined cohort, overall prognostic performance was more accurate for the Stockholm CT score (Nagelkerke's pseudo-R2 range 0.24-0.28) and the Helsinki CT score (0.18-0.22) than for the Rotterdam CT score (0.13-0.15) and Marshall CT classification (0.03-0.05). Moreover, the Stockholm and Helsinki CT scores added the most independent prognostic value in the presence of other known clinical outcome predictors in TBI (6% and 4%, respectively). The aggregate traumatic subarachnoid hemorrhage (tSAH) component of the Stockholm CT score was the strongest predictor of unfavorable outcome. The main limitations were the retrospective nature of the study, missing patient information, and the varying follow-up time between the centers. CONCLUSIONS: The Stockholm and Helsinki CT scores provide more information on the damage sustained, and give a more accurate outcome prediction, than earlier classification systems. The strong independent predictive value of tSAH may reflect an underrated component of TBI pathophysiology. A change to these newer CT scoring systems may be warranted.

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.

CTA analysis and assessment of morphological factors related to rupture in 413 posterior communicating artery aneurysms.

Posterior communicating artery (PcomA) aneurysms are frequently encountered, but there are few publications on their morphology. A growing number of aneurysms are incidental findings, which makes evaluation of rupture risk important. Our goal was to identify morphological features and anatomical variants associated with PComA aneurysms and to assess parameters related to rupture. We studied CT angiographies of 391 consecutive patients treated between 2000 and 2014 at a single institution. We determined clinically important morphological parameters and performed univariate and multivariate analysis. There were a total of 413 PComA aneurysms: 258 (62%) were ruptured and 155 (38%) unruptured. Ruptured PComA aneurysms had the potential to cause severe bleeding with IVH and/or temporal ICH (n = 170, 66% of ruptured). The main types of PComA origin were classified as follows: (1) separate (32%), (2) side by side (21%) and (3) a joint neck with the aneurysm (6%). After the multivariate logistic regression, the morphological parameters related to PComA aneurysm rupture were an irregular aneurysm dome, neck diameter, and aspect ratio >1.5. The most marked morphological features of the PComA aneurysms were: saccular nature (99%), infero-posterior dome orientation (42%), infrequency of large or giant aneurysms (4%), narrow neck compared to the aneurysm size, PComA originating directly from the aneurysm neck or the dome (28%), and fetal or dominant PComA on the side of the aneurysm (35%). There were location-related parameters that were more strongly associated with PComA aneurysm rupture than aneurysm size: an irregular aneurysm dome, larger diameter of the aneurysm neck and aspect ratio >1.5.

Long-Term Excess Mortality After Aneurysmal Subarachnoid Hemorrhage: Patients With Multiple Aneurysms at Risk.

BACKGROUND AND PURPOSE: There is high case-fatality rate and loss of productive life-years related to aneurysmal subarachnoid hemorrhage (aSAH) but data on long-term survival of patients with aSAH are scarce. We aim to evaluate long-term excess mortality and related risk factors after an aSAH event. METHODS: Survivors (n=3078) of aSAH who had survived for ≥1 year were reviewed for this retrospective follow-up study, which was conducted in the Department of Neurosurgery in Helsinki between 1980 and 2007. Follow-up started 1 year after the aSAH and continued until death or the end of 2012 (48 918 patient-years). Mortality and relative survival ratios were derived using a matched general population. RESULTS: Survivors of aSAH after 20 years showed 17% excess mortality compared with the general population. Even young patients and patients with good recovery showed excess mortality. The highest excess mortality was among patients with multiple aneurysms, old age, poor preoperative clinical condition, conservative aneurysm treatment, and unfavorable clinical outcome at 1 year. CONCLUSIONS: Even after initially favorable recovery from an aSAH, survivors experience excess mortality in the long run in comparison to a matched general population. Cardiovascular disease at younger age and cerebrovascular events were overrepresented as causes of death, which indicates the importance of treatment of vascular risk factors. Young patients and patients with multiple aneurysms who are recovering from an aSAH should be followed-up and treated most actively.

Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

BACKGROUND: Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. OBJECTIVE: To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. MATERIALS AND METHODS: We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. RESULTS: Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. CONCLUSION: Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-µSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.

BACKGROUND AND PURPOSE: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. METHODS: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. RESULTS: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). CONCLUSIONS: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.

Predicting six-month mortality of patients with traumatic brain injury: usefulness of common intensive care severity scores.

INTRODUCTION: The aim of this study was to evaluate the usefulness of the APACHE II (Acute Physiology and Chronic Health Evaluation II), SAPS II (Simplified Acute Physiology Score II) and SOFA (Sequential Organ Failure Assessment) scores compared to simpler models based on age and Glasgow Coma Scale (GCS) in predicting long-term outcome of patients with moderate-to-severe traumatic brain injury (TBI) treated in the intensive care unit (ICU). METHODS: A national ICU database was screened for eligible TBI patients (age over 15 years, GCS 3-13) admitted in 2003-2012. Logistic regression was used for customization of APACHE II, SAPS II and SOFA score-based models for six-month mortality prediction. These models were compared to an adjusted SOFA-based model (including age) and a reference model (age and GCS). Internal validation was performed by a randomized split-sample technique. Prognostic performance was determined by assessing discrimination, calibration and precision. RESULTS: In total, 1,625 patients were included. The overall six-month mortality was 33%. The APACHE II and SAPS II-based models showed good discrimination (area under the curve (AUC) 0.79, 95% confidence interval (CI) 0.75 to 0.82; and 0.80, 95% CI 0.77 to 0.83, respectively), calibration (P > 0.05) and precision (Brier score 0.166 to 0.167). The SOFA-based model showed poor discrimination (AUC 0.68, 95% CI 0.64 to 0.72) and precision (Brier score 0.201) but good calibration (P > 0.05). The AUC of the SOFA-based model was significantly improved after the insertion of age and GCS (∆AUC +0.11, P < 0.001). The performance of the reference model was comparable to the APACHE II and SAPS II in terms of discrimination (AUC 0.77; compared to APACHE II, ΔAUC -0.02, P = 0.425; compared to SAPS II, ΔAUC -0.03, P = 0.218), calibration (P > 0.05) and precision (Brier score 0.181). CONCLUSIONS: A simple prognostic model, based only on age and GCS, displayed a fairly good prognostic performance in predicting six-month mortality of ICU-treated patients with TBI. The use of the more complex scoring systems APACHE II, SAPS II and SOFA added little to the prognostic performance.

Visual field findings after a ruptured intracranial aneurysm.

BACKGROUND: Visual field defects (VFDs) negatively affect activities of daily living and rehabilitation following aneurysmal subarachnoid haemorrhage (aSAH). The aim here was to assess VFDs in patients with aSAH and their associations with age, gender, aSAH severity, and clinical outcome. METHODS: Patients admitted to Helsinki University Central Hospital and treated during 2011 were participants in this prospective study. Findings obtained with the Octopus 900 perimeter (Haag-Streit Inc, Koenic, Switzerland), the Goldmann perimeter (Haag-Streit Inc, Bern, Switzerland), or the confrontation visual field test on admission and 3 days, 14 days, 2 to 4 months, and 6 months postoperatively were assigned to 16 classes. Associations between post-chiasmal VFDs and relevant clinical, radiological, and demographic data were analysed with uni- and multivariate logistic regression. RESULTS: Of 105 survivors at 6 months, 20 (19 %) had VFDs occurring for aneurysm- or operation-related reasons; homonymous hemianopias or quadrantanopias were the most common finding, occurring in 16 patients (15 %). Posterior ischaemic optic neuropathy presented in two patients (2 %). Ten survivors (10 %) no longer fulfilled visual field requirements for driving licences. Significant associations emerged between VFDs at 6 months and the Hunt and Hess (H&H), World Federation of Neurosurgical Societies (WFNS), and Fisher grades on admission, presence of intracerebral haemorrhage (ICH), hydrocephalus, or postoperative infarction, and higher modified Rankin Scale scores at 6 months. Multivariate logistic regression showed the H&H grade and presence of ICH to independently predict VFDs. CONCLUSIONS: Assessing VFDs is advisable, especially among patients with poor-grade aSAH (H&H grade IV or V) and ICH.