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Background Previously thought to be congenital, AVMs have shown evidence of de-novo formation and continued growth, thus shifting thoughts on their pathophysiology. Pediatric AVM patients have been reported to be more prone to develop AVM recurrence after a seemingly complete cure. Therefore, we assessed the risk of AVM treated in childhood to recur in adulthood after a long-term follow-up in our own cohort. Methods Control DS-angiography was arranged during 2021–2022 as part of a new protocol for all AVM patients who were under 21 years of age at the time of their treatment and in whom the treatment had occurred at least five years earlier. Angiography was offered only to patients under 50 years of age at the time of the new protocol. The complete eradication of AVM after the primary treatment had been originally confirmed with DSA in every patient. Results A total of 42 patients participated in the late DSA control, and 41 of them were included in this analysis after excluding the patient diagnosed with HHT. The median age at the time of admission for AVM treatment was 14.6 (IQR 12–19, range 7–21 years) years. The median age at the time of the late follow-up DSA was 33.8 years (IQR 29.8–38.6, range 19.4–47.9 years). Two recurrent sporadic AVMs and one recurrent AVM in a patient with hereditary hemorrhagic telangiectasia (HHT) were detected. The recurrence rate was 4.9% for sporadic AVMs and 7.1% if HHT-AVM was included. All the recurrent AVMs had originally bled and been treated microsurgically. The patients with sporadic AVM recurrence had been smoking their whole adult lives. Conclusions Pediatric and adolescent patients are prone to develop recurrent AVMs, even after complete AVM obliteration verified by angiography. Therefore, imaging follow-up is recommended.

OBJECTIVE The aim of this study was to reveal the long-term health-related quality of life (HRQOL), educational level, and impact on occupation in 55 patients who experienced ruptured brain arteriovenous malformations (AVMs) that were treated during childhood. METHODS In 2016, questionnaires including the 15D instrument were sent to all living patients older than 18 years (n = 432) in the Helsinki AVM database. The cohort was further specified to include only patients with ruptured AVMs who were younger than 20 years at the time of diagnosis (n = 55). Educational level was compared with the age-matched general population of Finland. The mean 15D scores were calculated for independent variables (Spetzler-Ponce classification, admission age, symptomatic epilepsy, and multiple bleeding episodes) and tested using the independent-samples t-test or ANCOVA. Linear regression was used to create a multivariate model. Bonferroni correction was used with multiple comparisons. RESULTS The mean follow-up time from diagnosis to survey was 24.2 (SD 14.7) years. The difference in the mean 15D scores between Spetzler-Ponce classes did not reach statistical significance. The youngest age group (< 10 years at the time of diagnosis) performed less well on the dimension of usual activities than the older patients. Symptomatic epilepsy significantly reduced the long-term HRQOL. Multiple hemorrhages significantly reduced the scores on three dimensions: mobility, speech, and sexual activity. In the regression model, symptomatic epilepsy was the only significant predictor for a lower 15D score. The educational level of the cohort was for the most part comparable to that of the general population in the same age group. AVM was the reason for early retirement in 11% of the patients, while lowered performance because of the AVM was reported by 37% of the patients. CONCLUSIONS Patients with ruptured AVMs treated in childhood can live an independent and meaningful life, even in the case of the highest-grade lesions. Symptomatic epilepsy significantly reduced the long-term HRQOL, highlighting the need for continuing support for these patients.

Background Spontaneous angiogram-negative subarachnoid hemorrhage (SAH) is considered a benign illness with little of the aneurysmal SAH-related complications. We describe the clinical course, SAH-related complications, and outcome of patients with angiogram-negative SAH. Methods We retrospectively reviewed all adult patients admitted to a neurosurgical intensive care unit during 2004–2018 due to spontaneous angiogram-negative SAH. Our primary outcome was a dichotomized Glasgow Outcome Scale (GOS) at 3 months. We assessed factors that associated with outcome using multivariable logistic regression analysis. Results Of the 108 patients included, 84% had a favorable outcome (GOS 4–5), and mortality was 5% within 1 year. The median age was 58 years, 51% were female, and 93% had a low-grade SAH (World Federation of Neurosurgical Societies grading I–III). The median number of angiograms performed per patient was two. Thirty percent of patients showed radiological signs of acute hydrocephalus, 28% were acutely treated with an external ventricular drain, 13% received active vasospasm treatment and 17% received a permanent shunt. In the multivariable logistic regression model, only acute hydrocephalus associated with unfavorable outcome (odds ratio = 4.05, 95% confidence interval = 1.05–15.73). Two patients had a new bleeding episode. Conclusion SAH-related complications such as hydrocephalus and vasospasm are common after angiogram-negative SAH. Still, most patients had a favorable outcome. Only acute hydrocephalus was associated with unfavorable outcome. The high rate of SAH-related complications highlights the need for neurosurgical care in these patients.

Hemangioblastomas (HBs) are rare, benign, hypervascularized tumors. Fluorescent imaging with indocyanine green (ICG) can visualize tumor angioarchitecture. The authors report a case of multiple HBs involving two radiologically silent lesions only detected intraoperatively by ICG fluorescence. A 26-year-old woman presented with a cystic cerebellar mass on the tentorial surface of the left cerebellar hemisphere on MRI. A left paramedian suboccipital approach was performed to remove the mural nodule with the aid of ICG injection. The first injection, applied just prior to removing the nodule, highlighted the tumor and vessels. After resection, two new lesions, invisible on the preoperative MRI, surprisingly enhanced on fluorescent imaging 35 minutes after the ICG bolus. Both silent lesions were removed. Histological analysis of all three lesions revealed they were positive for HB. The main goal of this report is to hypothesize possible explanations about the mechanism that led to the behavior of the two silent lesions. Intraoperative ICG videoangiography was useful to understand the 3D angioarchitecture and HB flow patterns to perform a safe and complete resection in this case. Understanding the HB ultrastructure and pathophysiological mechanisms, in conjunction with the properties of ICG, may expand potential applications for their diagnosis and future treatments.

Background We wanted to understand how patients with different modified Rankin Scale (mRS) grades differ regarding their health-related quality of life (HRQoL) and how this affects the interpretation and dichotomization of the grade. Methods In 2016, all adult patients in our brain arteriovenous malformation (AVM) database (n = 432) were asked to fill in mailed letters including a questionnaire about self-sufficiency and lifestyle and the 15D HRQoL questionnaire. The follow-up mRS was defined in 2016 using the electronic patient registry and the questionnaire data. The 15D profiles of each mRS grade were compared to those of the general population and to each other, using ANCOVA with age and sex standardization. Results Patients in mRS 0 (mean 15D score = 0.954 ± 0.060) had significantly better HRQoL than the general population (mean = 0.927 ± 0.028), p p Conclusions Using 15D, we were able to find significant differences in the HRQoL between mRS 0 and mRS 1 AVM patients, against the recent findings on stroke patients using EQ-5D in their analyses. Although the dichotomization cut point is commonly set between mRS 1 and 2, patients in these grades had a similar HRQoL and a decreased ability to continue their premorbid lifestyle, in contrast to patients in mRS 0.

BACKGROUND: The use of a digital three-dimensional (3D) exoscope system in neurosurgery is increasing as an alternative to the operative microscope. The objective of this study was to compare a digital 3D exoscope system with a standard operating microscope as a neurosurgical visualization tool in a highly challenging experimental setting. METHODS: End-to-side bypass procedures, each at a depth of 9 cm, were performed in a simulation setting. The quality of the task and the depth effect, visualization, magnification, illumination, and ergonomics were evaluated. RESULTS: No major differences were noted between the microscope and the 3D exoscope in terms of the quality of the work. Working with the 3D exoscope was more time-consuming than working with the microscope. Changing the depth and focus was faster using the operative microscope. The 3D exoscope enabled higher magnification and offered better ergonomic features. CONCLUSIONS: In a highly challenging experimental setting, comparable procedural quality was found for the microscope and the 3D exoscope. Each visualization tool had advantages and disadvantages. Over time and with technologic advances, the digital 3D exoscope may become the main operative visualization system in microneurosurgery.

Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for the first time the formation of neutrophil extracellular traps (NETs) in rodents and humans with CCM. Through RNA-seq analysis of cerebellum endothelial cells from wild-type mice and mice with an endothelial cell-specific ablation of the Ccm3 gene (Ccm3iECKO), we show that endothelial cells from Ccm3iECKO mice have an increased expression of inflammation-related genes. These genes encode proinflammatory cytokines and chemokines, as well as adhesion molecules, which promote recruitment of inflammatory and immune cells. Similarly, immunoassays showed elevated levels of these cytokines and chemokines in the cerebellum of the Ccm3iECKO mice. Consistently, both flow cytometry and immunofluorescence analysis showed infiltration of different subsets of leukocytes into the CCM lesions. Neutrophils, which are known to fight against infection through different strategies, including the formation of NETs, represented the leukocyte subset within the most pronounced increase in CCM. Here, we detected elevated levels of NETs in the blood and the deposition of NETs in the cerebral cavernomas of Ccm3iECKO mice. Degradation of NETs by DNase I treatment improved the vascular barrier. The deposition of NETs in the cavernomas of patients with CCM confirms the clinical relevance of NETs in CCM.

Background Research on the prevalence of smokers in patients with brain arteriovenous malformation (AVM) remains nonexistent, even though smoking is a well-known risk factor for intracranial aneurysms. Objective To examine the prevalence and smoking habits of AVM patients. Methods Data on smoking habits were collected with a quality-of-life questionnaire mailed in 2016 to all patients in our large AVM database. These smoking data were supplemented with registry data derived from medical records. The prevalence of smokers was compared to that of the general population, derived from statistics of National Institute for Health and Welfare. Logit transformation of proportions and Students t distribution were used to calculate the 95% CIs for prevalence estimates. Results Of the 384 patients aged over 18 yr on admission, 277 (72.1%) returned the questionnaires in 2016. When compared to age, sex, and admission year matched general population, the proportion of smokers in AVM patients was 48% (CI = 41%-55%) and 19% (CI = 16%-21%) in the general population. The difference increased in older age groups; in those aged 65 to 77 yr, the percentage of smokers reached 73% (CI = 46%-90%), while the corresponding percentage in the general population was 7% (CI = 5%-9%). Conclusion We observed considerably higher rates of smoking among AVM patients when compared to age, sex, and admission year matched general population. Our results suggest that in the development of AVMs, the role played by nicotine and other substances in tobacco smoke should be examined. Cigarette smoking could potentially be a common cerebrovascular risk factor.

Objective: To evaluate whether somatic mutations have role in saccular intracranial aneurysm pathogenesis Approach and Results: We performed whole exome sequencing of DNA derived from 20 saccular cerebral aneurysms followed by somatic variant calling. Eleven (55%) of the 20 patients had detectable nonsynonymous somatic mutations and in total, 48 mutations were detected in the aneurysm samples. The mutations were highly enriched in cancer-related genes and 37 were predictably deleterious. A p.Tyr562Asp somatic mutation was detected in the PDGFRB gene; somatic mutations at the same codon have been reported in fusiform cerebral aneurysms. Conclusions: These results widen the concept on the role of somatic mutations in cerebral aneurysms, indicating their possible role in the more common saccular aneurysm, similarly to the rarer fusiform aneurysm.

Aki Laakso tutkimusryhmän jäsenenä. Currently available simulators are supposed to allow young neurosurgeons to hone their technical skills in a safe environment, without causing any unnecessary harm to their patients caused by their inexperience. For this training method to be largely accepted in neurosurgery, it is necessary to prove simulation efficacy by means of large-scale clinical validation studies. We correlated and analysed the performance at a simulator and the actual operative skills of different neurosurgeons (construct validity). We conducted a study involving 92 residents and attending neurosurgeons from different European Centres; each participant had to perform a virtual task, namely the placement of an external ventricular drain (EVD) at a neurosurgical simulator (ImmersiveTouch). The number of attempts needed to reach the ventricles and the accuracy in positioning the catheter were assessed. Data suggests a positive correlation between subjects who placed more EVDs in the previous year and those who get better scores at the simulator (p = .008) (fewer attempts and better surgical accuracy). The number of attempts to reach the ventricle was also analysed; senior residents needed fewer attempts (mean = 2.26; SD = 1.11) than junior residents (mean = 3.12; SD = 1.05) (p = .007) and staff neurosurgeons (mean = 2.89, SD = 1.23). Scoring results were compared by using the Fisher's test, for the analysis of the variances, and the Student's T test. Surprisingly, having a wider surgical experience overall does not correlate with the best performance at the simulator. The performance of an EVD placement on a simulator correlates with the density of the neurosurgical experience for that specific task performed in the OR, suggesting that simulators are able to differentiate neurosurgeons according to their surgical ability. Namely this suggests that the simulation performance reflects the surgeons' consistency in placing EVDs in the last year.

BACKGROUND: A supplementary grading scale (Supplemented Spetzler-Martin grade, Supp-SM) was introduced in 2010 as a refinement of the SM system to improve preoperative risk prediction of brain arteriovenous malformations (AVMs). OBJECTIVE: To determine the ability to predict surgical outcomes using the Supp-SM grading scale. METHODS: This retrospective study was conducted on 200 patients admitted to the Helsinki University Hospital between 2000 and 2014. The validity of the Supp-SM and SM grading systems was compared using the area under the receiver operating characteristic (AUROC) curves, with respect to the change between preoperative and early (3-4 mo) as well as final postoperative modified Rankin Scale (mRS) scores. RESULTS: The performance of the Supp-SM was superior to that of the SM grading scale in the early follow-up (3-4 mo): AUROC = 0.57 (95% confidence interval [CI]: 0.49-0.65) for SM and AUROC = 0.67 (95% CI: 0.60-0.75) for Supp-SM. The Supp-SM performance continued improving over SM at the late follow-up: AUROC = 0.63 (95% CI: 0.55-0.71) for SM and AUROC = 0.70 (95% CI: 0.62-0.77) for Supp-SM. The perforating artery supply, which is not part of either grading system, plays an important role in the early follow-up outcome (P = .008; odds ratio: 2.95; 95% CI: 1.32-6.55) and in the late follow-up outcome (P

INTRODUCTION Navigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value. METHODS The nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications. RESULTS nTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here. CONCLUSION At present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.

Background Despite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics-driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application. Results From ten patients undergoing surgery for recGBM, we established individual cell cultures and characterized the GSCs by functional assays. 7/10 GSC cultures could be serially expanded. The individual GSCs displayed intertumoral differences in their proliferative capacity, expression of stem cell markers and variation in their in vitro and in vivo morphology. We defined a time frame of 10 weeks from surgery to complete the entire pre-clinical work-up; establish individualized GSC cultures, evaluate drug sensitivity patterns of 525 anticancer drugs, and identify options for individualized treatment. Within the time frame for clinical translation 5/7 cultures reached sufficient cell yield for complete drug screening. The DSRT revealed significant intertumoral heterogeneity to anticancer drugs (p

Recently, the use of digital exoscopes has been increasingly promoted as an alternative to microscopes. The aim of this study is to compare experimental bypass quality in both visualization methods.This study used two hundred 1-mm chicken wing vessels, which were used for either exoscopic or microscopic (100 samples each) bypass procedures. All procedures were recorded between July 2018 and September 2018. The bypass quality was evaluated according to our published practical scale (time, stitch distribution, intima-intima attachment, and orifice size).Both methods are effective in doing bypass suturing (practical scale score was good, 86% vs. 85%; P = 0.84). There were no significant differences regarding intima-intima attachment (P = 0.26) and orifice size (P = 0.25). However, suturing time (P0.001) was less using the microscope, whereas stitch distribution (P = 0.001) was better using the exoscope. Different suturing techniques (interrupted vs. continuous) had overall comparable results (P = 0.55).Both methods produced equally satisfactory results in experimental bypass procedures. The exoscope has the potential for better 3-dimensional visualization and sharing the surgeon's view with others for teaching purposes.

BACKGROUND: Differences in the postgraduate training programs of neurosurgical residents are suspected throughout Europe. The influence of working hour restrictions by the European Working Time Directive (WTD) 2003/88/EC on the number of surgical procedures remains unclear. We designed a survey to collect information on the number of surgical procedures, performed by European neurosurgical trainees during residency. This article reports preliminary data. METHODS: An electronic survey was distributed among the European Association of Neurosurgical Societies (EANS) member countries by national delegates of the training committee, as well as by members of the Young Neurosurgeons' committee. The EANS mailing list of individual members was also used for distribution. All responses received between 04/2018 and 12/2018 were considered. RESULTS: From n = 180 responses received, 42 were omitted as responders were still in residency and for 58 relevant information was missing. The final sample was n = 80, with a mean responder's age of 43.0 years (SD 8.6) and 88.8% being male. Responses came from 16 European countries; board certification was received between the years of 1976-2018. The numbers of surgical procedures performed independently were 511 (mean, 95% confidence interval (CI) 413-610), supervised were 514 (95%CI 360-668) and assisted were 752 (95%CI 485-1019) throughout residency. More detailed numbers for specific procedure types are reported in the article. Independently performed cranial procedures outnumbered spinal procedures (p < 0.006), and adult procedures outnumbered pediatric procedures (p < 0.001). There was a strong decrease in caseload between 1976 and 2018, with trainees performing on average 65 cases less throughout residency for each calendar year increase in board certification (95% CI - 116 to - 15, p = 0.012). Trainees graduating residency before introduction of the European WTD 2003/88/EC participated in more procedures than those graduating afterwards (mean 2797 vs. 1418, p = 0.005). CONCLUSIONS: The preliminary analysis of the first 80 responses now provides a first reference frame for caseload that can be used by current and future European residents to critically compare their own operative numbers to. There was a strong decline in surgical cases over time, and trainees graduating after introduction of the European WTD 2003/88/EC had less surgical exposure. The survey remains open, and we invite further European neurosurgeons to provide their data in order to get even more robust estimates.

Introduction: Accurately balancing risks of interventional treatment and intracranial hemorrhage (ICH) in the untreated course of unruptured brain arteriovenous malformation (uBAVM) patients is critical for optimal management. Observational studies of uBAVM afford an opportunity to address important gaps and previous criticisms of randomized data to help guide treatment decisions and assess long-term risk/benefit ratio. We previously published an individual patient data meta-analysis (IPDMA) in 4 MARS cohorts and identified ICH presentation and increasing age as significant predictors of ICH during follow-up, but was not powered to detect predictors in those with uBAVM. Thus, the goals of this project are to identify risk factors for ICH in uBAVMs, to estimate the risk with precision, and to create personalized, risk-prediction models. Methods: MARS is an international, multi-center study of 11 cohorts with target enrollment of 4,500 uBAVM patients ascertained through population-based or referral-based studies. We are harmonizing both retrospective and prospective data, including clinical, lifestyle, imaging, and angiographic factors. Treatments, complications, and functional outcomes (physician and patient-reported) will be updated annually between 2018-2022. We propose to: 1) identify predictors of outcome in uBAVMs using IPDMA; 2) test whether long-term outcomes differ by treatment using statistical approaches for causal inference and unbiased estimates; 3) compare treatment outcomes in randomized and non-randomized data to address generalizability; and 4) validate models and provide a novel tool for calculating individualized risks. Eligible sites have: a) prior BAVM publications; b) data from a minimum of 100 uBAVM patients; c) agree to random outcome adjudication; and d) agree to MARS data sharing policy. Discussion: The NIH-funded MARS consortium will provide important and comprehensive characterization of the untreated and treated course of uBAVMs, using large observational datasets and sophisticated epidemiological approaches. The data and models generated will be a useful resource for decision-making. We welcome participation from eligible sites with longitudinal data on uBAVM patients

Background A major barrier to effective treatment of glioblastoma (GBM) is the large intertumoral heterogeneity at the genetic and cellular level. In early phase clinical trials, patient heterogeneity in response to therapy is commonly observed; however, how tumor heterogeneity is reflected in individual drug sensitivities in the treatment-naïve glioblastoma stem cells (GSC) is unclear. Methods We cultured 12 patient-derived primary GBMs as tumorspheres and validated tumor stem cell properties by functional assays. Using automated high-throughput screening (HTS), we evaluated sensitivity to 461 anticancer drugs in a collection covering most FDA-approved anticancer drugs and investigational compounds with a broad range of molecular targets. Statistical analyses were performed using one-way ANOVA and Spearman correlation. Results Although tumor stem cell properties were confirmed in GSC cultures, their in vitro and in vivo morphology and behavior displayed considerable tumor-to-tumor variability. Drug screening revealed significant differences in the sensitivity to anticancer drugs (p

ObjectiveTo discover the health-related quality of life (HRQOL) of patients with treated arteriovenous malformation (AVM), we used the self-applicable HRQOL instrument, the 15D, and analyzed the scores in both in the whole study population and specified cohorts.MethodsThe 15D questionnaires were mailed to adult patients with AVM alive in 2016 (n = 432) in our database. Patients with completely eradicated AVM (n = 262) were included in a subsequent analysis. The results were compared with those of the general population standardized for age and sex. Subgroup analyses were conducted for epilepsy, number of bleeding episodes, location of the lesion, modified Rankin Scale score, and Spetzler-Ponce classification (SPC) using independent-samples t test or analysis of covariance. Tobit regression was used to explain the variance in the 15D score.ResultsPatients had impaired HRQOL compared to the reference population (p < 0.0001). Deep location, multiple bleeding episodes, and refractory epilepsy were associated with impaired HRQOL. Patients in SPC A and B had similar posttreatment 15D scores, whereas those in class C had an impaired HRQOL. Significant explanatory variables in the regression model were age, sex, number of bleeding episodes, refractory epilepsy, and SPC.ConclusionsWith careful patient selection, patients in SPC B can reach as favorable HRQOL as those in SPC A provided the operation is successful. Multiple bleeding episodes should be prevented with effective treatment aiming at complete AVM obliteration. The postoperative treatment of patients with AVM should focus on preventing depressive symptoms, anxiety, and epileptic seizures. We encourage other research groups to use HRQOL instruments to fully understand the consequences of neurologic and neurosurgical diseases on patients' HRQOL.

Prior to the routine use of vertebral angiography, posterior fossa AVMs were usually found unexpectedly during the evacuation of posterior fossa hematomas [1]. In 1932 (May 5th), Olivecrona had reported their first successful radical removal of a left cerebellar AVM in a 37-year-old male who was misdiagnosed of having a posterior fossa tumor. After an 8-h-long marathon surgery under local anesthesia and with a blood transfusion of 2000 ml, the AVM was removed. The postoperative course was uneventful and the patient left the hospital 3 months later [2]. As vertebral angiography became more widely used, the preoperative diagnosis of posterior fossa AVMs became possible. Even so, at that time, neurosurgeons thought that it was possible to operate on small-to-moderate-sized AVMs in silent areas of the brain but were reluctant to touch AVMs in nonsilent areas [2], including the more demanding posterior fossa. Neurosurgeons were, however, disappointed that only very few AVMs could be removed entirely without great risk, which led to the development of other, ineffectual techniques, such as vertebral artery or feeder ligation [1].

BACKGROUND: Arteriovenous malformations (AVMs) of the posterior fossa are demanding lesions that often present with rupture. Studies including outcome analyses in surgically operated patients with ruptured infratentorial AVMs are scarce. Certain anatomic and demographic features have shown associations with postoperative outcomes. METHODS: Eighty-six patients with infratentorial AVM were collected from our AVM database. Fifty-four patients were admitted from 1990 onward, and their demographic, lesion, and treatment characteristics were analyzed. The cohort was further refined to 38 consecutive patients with surgically treated ruptured infratentorial AVM admitted to our center between 1990 and 2014, and statistical analyses of factors influencing outcomes were conducted. RESULTS: Twenty-seven patients (69%) had a favorable outcome at early follow-up and 24 (67%) had a favorable outcome at final follow-up. Factors associated with poor outcome in early recovery on univariate analyses were deep venous drainage of the lesion (odds ratio (OR 5.3; P = 0.037) and high Hunt & Hess score (P = 0.003). In the multivariate model, independent predictors for poor outcome were deep venous drainage (OR, 14.5; P = 0.010) and older age at admission (OR, 1.06; P = 0.028). The sole independent predictor for poor outcome at last follow-up was deep venous drainage (OR, 5.00; P = 0.046). The total follow-up time was 370 person-years. CONCLUSIONS: AVMs of the posterior fossa usually present with rupture and thus require prompt clinical treatment. The majority of surgically treated patients recover favorably. Our data show that venous drainage patterns have the greatest influence on the patient's postoperative condition. Other influencing factors include the severity of hemorrhage and patient age at admission.

Objective To assess prospectively neuro-ophthalmic findings associated with unruptured intracranial aneurysms and treatment morbidity and to identify factors predicting these findings. Methods Patients admitted to Helsinki University Central Hospital and treated surgically or endovascularly during 2011 underwent a neuro-ophthalmic examination, including formal visual field testing, before operation, at discharge, and 2–4 months and ≥6 months postoperatively. Univariate and multivariate analysis was used to identify factors predicting eye movement disorders. Results Study participants included 142 patients with 184 treated aneurysms: 7 (5%) had a third, fourth, or sixth nerve palsy or skew deviation preoperatively, and 16 (11%) had a third, fourth, or sixth nerve palsy or skew deviation postoperatively; the frequency was 8 (6%) at the last follow-up evaluation. Other findings included compressive optic neuropathy (n = 4), ischemic optic neuropathy (n = 1), Weber syndrome (n = 3), Benedikt syndrome (n = 1), and Wallenberg syndrome (n = 1). Of the 140 survivors at 6 months, 7 (5%) presented with visual field defects resulting from the aneurysm or its treatment. In the best bivariate model, factors independently predicting postoperative eye movement disorders were aneurysm location in the posterior circulation with an odds ratio of 142.02 (95% confidence interval = 20.13–1002.22) and aneurysm size (odds ratio = 1.28 for each 1-mm increase in diameter, 95% confidence interval = 1.12–1.47). Conclusions Management of unruptured intracranial aneurysms is fairly safe from a neuro-ophthalmic perspective, with some treatment-related morbidity being transient and minor. Although rare, an irreversible deficit is possible and should be taken into account when considering preventive treatment.

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. Thein vitrocharacteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implantsin vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant.

There are conflicting opinions regarding the optimal waiting time to perform surgery after rupture of supratentorial arteriovenous malformations (AVMs) to achieve the best possible outcome. To analyze factors influencing outcomes for ruptured supratentorial AVMs after surgery, paying particular attention to the timing of the surgery. We retrospectively investigated 59 patients admitted to our center between 2000 and 2014 for surgical treatment of ruptured supratentorial AVMs. We evaluated the effect of timing of surgery and other variables on the outcome at 2-4 months (early outcome), at 12 months (intermediate outcome) after surgery, and at final follow-up at the end of 2016 (late outcome). Age over 40 years (OR 18.4; 95% CI 1.9-172.1; p = 0.011), high Hunt and Hess grade (4 or 5) before surgery (OR 13.5; 95% CI 2.1-89.2; p = 0.007), hydrocephalus on admission (OR 12.9; 95% CI 1.8-94.4; p = 0.011), and over 400 cm(3) bleeding during surgery (OR 11.5; 95% CI 1.5-86.6; p = 0.017) were associated with an unfavorable early outcome. Age over 40 years (OR 62.8; 95% CI 2.6-1524.9; p = 0.011), associated aneurysms (OR 34.7; 95% CI 1.4-829.9; p = 0.029), high Hunt and Hess grade before surgery (OR 29.2; 95% CI 2.6-332.6; p = 0.007), and over 400 cm(3) bleeding during surgery (OR 35.3; 95% CI 1.7-748.7; p = 0.022) were associated with an unfavorable intermediate outcome. Associated aneurysms (OR 8.2; 95% CI 1.2-55.7; p = 0.031), high Hunt and Hess grade before surgery (OR 5.7; 95% CI 1.3-24.3; p = 0.019), and over 400 cm(3) bleeding during surgery (OR 5.8; 95% CI 1.2-27.3; p = 0.027) were associated with an unfavorable outcome at last follow-up. Elapsed time between rupture and surgery did not affect early or final outcome. Early surgery in patients with ruptured supratentorial arteriovenous malformation is feasible strategy, with late results comparable to those achieved with delayed surgery. Many other factors than timing of surgery play significant roles in long-term outcomes for surgically treated ruptured supratentorial AVMs.

Objectives: To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. Methods: We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. Results: At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. Conclusions: STN-DBS improves motor function and enables the reduction in anti-parkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted.

Background Population-based long-term data on pediatric patients with cerebral arteriovenous malformations (AVMs) are limited. Objective To clarify the characteristics and long-term outcome of pediatric patients with AVM. Methods A retrospective analysis was performed on 805 consecutive brain AVM patients admitted to a single center between 1942 and 2014. The patients were defined as children if they were under 18 yr at admission. Children were compared to an adult cohort. Changing patterns of presentation were also analyzed by decades of admission. Results The patients comprised 127 children with a mean age of 12 yr. The mean follow-up time was 21 yr (range 0-62). Children presented more often with intracerebral hemorrhage (ICH) but less often with epilepsy than adults. Basal ganglia, cerebellar, and posterior paracallosal AVMs were more common in pediatric than in adult patients. Frontal and temporal AVMs, in contrast, were more common in adult than in pediatric patients. As the number of incidentally and epilepsy-diagnosed AVMs increased, ICH rates dropped in both cohorts. In total, 22 (82%) pediatric and 108 (39%) adult deaths were assessed as AVM related. After multivariate analysis, small AVM size and surgical treatment correlated with a favorable long-term outcome. Conclusion Hemorrhagic presentation was more common in children than in adults. This was also reflected as lower prevalence of epileptic presentation in the pediatric cohort. Lobar and cortical AVM locations were less frequent, whereas deep and cerebellar AVMs were more common in children. Hemorrhagic presentation correlated negatively with incidentally and epilepsy-diagnosed AVMs. In children, AVM was a major cause of death, but in adults, other factors contributed more commonly to mortality.

The method nTMS has proven useful for the preoperative workup of brain tumor and epilepsy surgery in localization of the motor cortical areas. We have developed a videoed nrTMS setup combined with object naming to localize language-related cortical areas in preoperative planning. The method has high sensitivity and predicts well the cortical areas not involved in language in comparison with the results of DES during object naming in patients going through awake craniotomy. Nevertheless, the optimal stimulus parameters to achieve the most precise preoperative information are still searched for. The method may also have potential for plastic cortical change follow-up due to tumor growth or after tumor removal. No harmful side effects have occurred in the control or patient studies. Though the first reports using only nrTMS language mapping to localize the cortical language representations are favorable, DES during awake craniotomy is still the gold standard of cortical language-related areas’ functional localization.

Brain AVMs are rare and complex vascular lesions of unknown etiology, with the incidence rate of newly diagnosed cases of approximately 1–1.5 in 100,000 person years. Prevalence of AVMs in the population is unknown, but may be as high as 0.2%, even though the prevalence of confirmed AVM diagnosis is only 0.02%. AVMs seem to be slightly more common in males. Although the incidence of unruptured and asymptomatic AVMs is probably gradually increasing with the availability of noninvasive imaging, the most common and dangerous form of presentation of an AVM is still hemorrhagic stroke. Epileptic seizures, headache and focal neurological deficits are other forms of presenting symptoms. Although intracranial hemorrhage caused by an AVM may be somewhat less harmful than hemorrhagic strokes by other causes, AVM hemorrhage typically affects younger populations, and untreated AVMs are associated with significant long-term excess mortality. Average annual risk of rupture of an all untreated AVMs combined is between 2% and 4%, but the risk is highly variable and depends on the individual characteristics of the lesion. Factors associated with increased risk of hemorrhage include previous rupture, deep and infratentorial location, deep venous drainage, associated aneurysms and possibly large size.

Aneurysms at the junction of the vertebral artery (VA) and posterior inferior cerebellar artery (PICA) are relatively rare. Their treatment is challenged by the diverse anatomy of the VA and PICA, close involvement of the PICA in the aneurysm neck, and scant space deep in the posterior fossa next to the cranial nerves, brain stem, and obstructing structures of the skull base. Computed tomography angiography (CTA) visualizes bony structures in addition to the vasculature, and being noninvasive and easily available, it can serve for planning microsurgical treatment. We analyzed the anatomy of PICA aneurysms imaged by CTA to promote planning the treatment.We examined the CTA images of 70 consecutive patients with a saccular PICA aneurysm who were all treated in the Department of Neurosurgery, Helsinki, Finland, 2001 to 2011.Each of the 70 patients had 1 aneurysm at the VA-PICA junction. The proportion of small aneurysms (7 mm) was high, 67%. The dome-to-neck ratio was1.2 in 24 (34%) of the aneurysms. In the coronal view, 58 (83%) aneurysms projected cranially, and only 2 (3%) caudally. The aneurysms were located from 1 mm below the foramen magnum to 31 mm above it, most arising at the level of the jugular tubercle. The median distance to the aneurysm from the midline was 6 mm, ranging from 7.5 mm contralateral to the origin of the parent artery to 14 mm ipsilateral. Compared with the right VA, the left VA was larger, it harbored the most aneurysms, and its aneurysms were more often ruptured.Relation of PICA aneurysms to skull base structures is highly variable; the aneurysms can also be extracranial, or lie on the site of the skull contralateral to the origin of the parent artery. These anatomical variations demand meticulous study of the angiography in each individual case, especially before surgical treatment of the aneurysm.

Object Terson's syndrome (TS) is a vitreous hemorrhage in association with subarachnoid hemorrhage (SAH). Its diagnosis is often delayed, which may result in vision loss secondary to treatable conditions. Methods to hasten early diagnosis and consequent ophthalmic referral are desirable. The aims of this study were 1) to assess the specificity and sensitivity of conventional head CT for diagnosing TS in patients with aneurysmal SAH (aSAH); and 2) to determine the incidence of TS and its association with age, sex, aSAH severity, and overall mortality. Methods Patients admitted to Helsinki University Central Hospital who underwent surgery or endovascular treatment for a ruptured intracranial aneurysm during 2011 were participants in this prospective study. They underwent serial dilated fundoscopic examinations during a 6-month period. Two radiologists independently reviewed ocular findings suggestive of TS on conventional CT head scans obtained in all patients as a routine diagnostic procedure. Associations between TS and relevant clinical, radiological, and demographic data were analyzed with uni- and multivariate logistic regression. Results Of 121 participants, 13 (11%) presented with TS, and another 22 (18%) with intraretinal hemorrhages. For reviewing CT head scans, the overall observed agreement between the 2 raters was 96% (116 of 121 cases), with a substantial κ of 0.69 (95% CI 0.56–0.82). The sensitivity of the CT findings for TS was 42%, and the specificity was 97%. Associations of the World Federation of Neurosurgical Societies (WFNS) and Hunt and Hess grades on admission, the presence of intracerebral hemorrhage, female sex, and aneurysm length with TS were all statistically significant. Logistic regression demonstrated that sex and WFNS grade were independently associated with TS and provided the best fit to the data. Conclusions Routinely looking for TS findings in CT head scans may prove valuable in clinical practice. Terson's syndrome is associated with female sex and poor clinical condition on admission.

Backgound/Objective: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [18F]flutemetamol and the level of amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site. Methods: Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [18F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain. Results: Four of the 17 patients (23.5%) had amyloid-ß pathology based on the overall pathology read and also showed increased [18F]flutemetamol uptake. [18F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-ß levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-ß level and uptake of [18F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [18F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%. Conclusions: [18F]Flutemetamol detects brain amyloid-ß in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.

Object The aim of this study was to assess the early and long-term excess mortality in patients with intracranial dural arteriovenous fistula (DAVF) compared with a matched general Finnish population in an unselected, population-based series. Methods The authors identified 227 patients with DAVFs admitted to 2 of the 5 Departments of Neurosurgery in Finland—Helsinki and Kuopio University Hospitals—between 1944 and 2006. All patients were followed until death or the end of 2009. Long-term excess mortality was estimated using the relative survival ratio compared with the general Finnish population matched by age, sex, and calendar year. Results The median follow-up period was 10 years (range 0–44 years). Two-thirds (67%) of the DAVFs were located in the region of transverse and sigmoid sinuses. Cortical venous drainage (CVD) was present in 28% of the DAVFs (18% transverse and sigmoid sinus, 42% others). Of the 61 deaths counted, 11 (18%) were during the first 12 months and were mainly caused by treatment complications (5 of 11, 45%). The 1-year survivors presenting with hemorrhage experienced excess mortality until 7 years from admission. However, DAVFs with CVD were associated with significant, continuous excess mortality. There were more cerebrovascular and cardiovascular deaths in this group of patients than expected in the general Finnish population. Location other than transverse and sigmoid sinuses was also associated with excess mortality. Conclusions In the patients with DAVF there was excess mortality during the first 12 months, mainly due to treatment complications. Thereafter, their overall long-term survival became similar to that of the matched general population. However, DAVFs with CVD and those located in regions other than transverse and sigmoid sinuses were associated with marked long-term excess mortality after the first 12 months.

Background and Purpose— Long-term angiographic follow-up studies on pediatric aneurysm patients are scarce. Methods— We gathered long-term clinical and angiographic follow-up data on all pediatric aneurysm patients (≤18 years at diagnosis) treated at the Department of Neurosurgery, Helsinki University Central Hospital, between 1937 and 2009. Results— Fifty-nine patients with cerebral aneurysms in childhood had long-term clinical and radiological follow-up (median, 34 years; range, 4–56 years). Twenty-four patients (41%) were diagnosed with altogether 25 de novo and 11 recurrent aneurysms, with 9 (25%) of the aneurysms being symptomatic. New subarachnoid hemorrhage occurred in 7 patients; 4 of these patients died. Eight patients (33%) had multiple new aneurysms. The annual rate of hemorrhage was 0.4%, and the annual rate for the development of de novo or recurrent aneurysm was 1.9%. There were no de novo aneurysms in 7 patients with previously unruptured aneurysms. However, 1 recurrent aneurysm was diagnosed. Current and previous smoking (risk ratio, 2.44; 95% confidence interval, 1.07–5.55) was the only statistically significant risk factor for de novo and recurrent aneurysm formation in patients with previous subarachnoid hemorrhage, whereas hypertension, sex, or age at onset had no statistically significant effect. Smoking was also a statistically significant risk factor for new subarachnoid hemorrhage. Conclusions— Patients with ruptured intracranial aneurysms in childhood have a high risk for new aneurysms and new subarachnoid hemorrhage, especially if they start to smoke as adults. Life-long angiographic follow-up is mandatory.

When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca's with Wernicke's area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case-and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.

Background Various surgical approaches for the removal of tuberculum sellae meningiomas (TSMs) have previously been described. Objective To assess the reliability and safety of the lateral supraorbital (LSO) approach to remove TSMs. Methods We identified all TSM patients operated on at the Department of Neurosurgery at Helsinki University Central Hospital, Finland, by the senior author (J.H.) using the LSO approach between September 1997 and August 2010. We retrospectively analyzed the clinical data, radiological findings, surgical treatment, histology, and outcome of patients and discuss the operative technique. Results Apparent complete tumor removal was achieved in 45 patients (87%). Of 42 patients, preexisting visual deficit improved in 22, remained the same in 13, and worsened in 7, and de novo visual deficit occurred in 1 patient. At 3 months post-discharge, 47 patients (90%) had a good recovery, 4 (8%) were moderately disabled, and 1 (2%) died 40 days after surgery of unexplained cardiac arrest. Seven patients (13%) had minimal residual tumors, 2 of which required reoperation. During the median follow-up of 59 months (range, 1-133 months), tumor recurred in 1 of the patients who had undergone a second operation. Conclusion TSMs of all sizes can be removed via the LSO approach with minimal morbidity and mortality. Low-power or no coagulation is recommended near the optic nerves and the optic chiasm to preserve their vascular support from the internal carotid artery perforators. Our results are comparable to those obtained using more extensive and time-consuming approaches. We recommend the LSO approach to remove TSMs.

Saccular intracranial aneurysms (sIA) are pouch-like pathological dilatations of intracranial arteries that develop when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. Some sIAs remain stable over time, but in others mural cells die, the matrix degenerates, and eventually the wall ruptures, causing life-threatening hemorrhage. The wall of unruptured sIAs is characterized by myointimal hyperplasia and organizing thrombus, whereas that of ruptured sIAs is characterized by a decellularized, degenerated matrix and a poorly organized luminal thrombus. Cell-mediated and humoral inflammatory reaction is seen in both, but inflammation is clearly associated with degenerated and ruptured walls. Inflammation, however, seems to be a reaction to the ongoing degenerative processes, rather than the cause. Current data suggest that the loss of mural cells and wall degeneration are related to impaired endothelial function and high oxidative stress, caused in part by luminal thrombosis. The aberrant flow conditions caused by sIA geometry are the likely cause of the endothelial dysfunction, which results in accumulation of cytotoxic and pro-inflammatory substances into the sIA wall, as well as thrombus formation. This may start the processes that eventually can lead to the decellularized and degenerated sIA wall that is prone to rupture.