Immunothrombosis and vascular heterogeneity in cerebral cavernous malformation.

Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA sequencing to investigate the transcriptome of mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). We found that Ccm3-deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared with wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. We created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3 expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model, this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCMs. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM.

Frailty indices predict mortality, complications and functional improvements in supratentorial meningioma patients over 80 years of age.

PURPOSE: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years. METHODS: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery. RESULTS: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2)). CONCLUSION: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement.

Digital exoscope versus surgical microscope in spinal dural arteriovenous fistula surgery: a comparative series.

OBJECTIVE: Surgical treatment of spinal dural arteriovenous fistulas (DAVFs) has been reported to be superior to endovascular treatment in terms of occlusion of the fistula. Despite the increased availability of digital 3D exoscopes, the potential benefits of using an exoscope in spinal DAVF surgery have not been studied. The purpose of this study was to report and compare the results of exoscope- and microscope-assisted surgery for spinal DAVFs. METHODS: All consecutive adult patients (≥ 18 years of age) treated surgically for spinal DAVFs from January 2016 to January 2023 in a tertiary neurosurgical referral center were included. All patients were operated on by one neurosurgeon. Their pre- and postoperative clinical findings, imaging studies, and intra- and postoperative events were evaluated and surgical videos from the operations were analyzed. RESULTS: Altogether, 14 patients received an operation for spinal DAVF during the study period, 10 (71%) with an exoscope and 4 (29%) with a microscope. The DAVFs were most commonly located in the lower parts of the thoracic spine in both groups. The duration of exoscopic surgeries was shorter (141 vs 151 minutes) and there was less blood loss (60 vs 100 ml) than with microscopic surgeries. No major surgical complications were observed in either group. Of the 14 patients, 10 had gait improvement postoperatively: 7 (78%) patients in the exoscope group and 3 (75%) in the microscope group. None of the patients experienced deterioration following surgery. CONCLUSIONS: Exoscope-assisted surgery for spinal DAVFs is comparable in safety and effectiveness to traditional microscopic surgery. With practice, experienced neurosurgeons can adapt to using the exoscope without major additional risks to the patient.

Long-term treatment outcomes and natural course of low-grade intracranial dural arteriovenous fistulas.

OBJECTIVE: In contrast to high-grade dural arteriovenous fistula (dAVF), low-grade dAVF is mainly associated with tinnitus and carries a low risk of morbidity and mortality. It remains unclear whether the benefits of active interventions outweigh the associated risk of complications in low-grade dAVF. METHODS: The authors conducted a retrospective single-center study that included all consecutive patients diagnosed with an intracranial low-grade dAVF (Cognard type I and IIa) during 2012-2022 with DSA. The authors analyzed symptom relief, symptomatic angiographic cure, treatment-related complications, risk for intracerebral hemorrhage (ICH), and mortality. All patients were followed up until the end of 2022. RESULTS: A total of 81 patients were diagnosed with a low-grade dAVF. Of these, 48 patients (59%) underwent treatment (all primary endovascular treatments), and 33 patients (41%) did not undergo treatment. Nine patients (19%) underwent retreatments. Angiographic follow-up was performed after median (IQR) 7.7 (6.1-24.1) months by means of DSA (mean 15.0, median 6.4 months, range 4.5-83.4 months) or MRA (mean 29.3, median 24.7 months, range 5.9-62.1 months). Symptom control was achieved in 98% of treated patients after final treatment. On final angiographic follow-up, 73% of patients had a completely occluded dAVF. There were 2 treatment-related complications resulting in 1 transient (2%) and 1 permanent (2%) neurological complication. One patient showed recurrence and progression of a completely occluded low-grade dAVF to an asymptomatic high-grade dAVF. No cases of ICH- or dAVF-related mortality were found in either treated patients (median [IQR] follow-up 5.1 [2.0-6.8] years) or untreated patients (median [IQR] follow-up 5.7 [3.2-9.0] years). CONCLUSIONS: Treatment of low-grade dAVF provides a high rate of symptom relief with small risks for complications with neurological sequela. The risks of ICH and mortality in patients with untreated low-grade dAVF are minimal. Symptoms may not reveal high-grade recurrence, and radiological follow-up may be warranted in selected patients with treated low-grade dAVF. An optimal radiographic follow-up regimen should be developed by a future prospective multicenter registry.

Radiofrequency thermocoagulation as a treatment for hemifacial spasm: long-term follow-up and management of recurrences.

BACKGROUND: Radiofrequency thermocoagulation (RFT) is a treatment used to relieve symptoms of cranial nerve disorders. The current study is the first to describe the results of hemifacial spasm (HFS) patients with a history of repeated RFT in the second-largest consecutive single-center patient series with long-term follow-up. METHOD: This retrospective study was conducted in the largest hospital district in Finland (Helsinki and Uusimaa). Consecutive HFS patients who had an RFT to treat HFS in the Hospital District of Helsinki and Uusimaa between 2009-2020 were included. RESULTS: Eighteen patients with 53 RFTs were identified from the medical records. 11 (61 %) patients had repeated RFTs, and the mean number of RFTs per patient was 3.33 (3.29 SD). The mean follow-up was 5.54 years (7.5 SD). 12 (67 %) patients had had microvascular decompression (MVD) before RFT. Patients were satisfied with the results after 87 % of RFTs. Relief of the twitching of the face lasted 11.27 months (11.94 SD). All patients had postoperatively transient facial paresis. Postoperative paresis lasted a mean of 6.47 months (6.80 SD). The depth of paresis was postoperatively typically moderate (36.54 %, House Brackmann III). 23.08 % had mild paresis (House-Brackmann II), 23.08 % had moderately severe dysfunction (House-Brackmann IV), 9.62 % had severe dysfunction, and 7.69 % had total paralysis of the facial muscles (House-Brackmann VI). Duration of relief in the face twitching (p 0.002) and temperature at the final coagulation point (p 0.004) were statistically significant predictors of satisfaction with the RFT results. CONCLUSIONS: RFT can be used to treat recurrences of HFS repeatedly. It provides symptom relief for around 11 months, lasting four times longer than with botulinum toxin injections. Patients are satisfied, although an RFT produces transient, sometimes even severe, facial paresis.

3D exoscopic versus microscopic superficial temporal artery to middle cerebral artery bypass surgery for moyamoya disease - a comparative series.

PURPOSE: Superficial temporal artery to middle cerebral artery (STA-MCA) direct bypass surgery is the most common surgical procedure to treat moyamoya disease (MMD). Here, we aim to compare the performance of the 3D exoscope in bypass surgery with the gold standard operative microscope. METHODS: All direct STA-MCA bypass procedures performed at a single university hospital for MMD between 2015 and 2023 were considered for inclusion. Data were retrospectively collected from patient files and surgical video material. From 2020 onwards, bypass procedures were exclusively performed using a digital three-dimensional exoscope as visualization device. Results were compared with a microsurgical bypass control group (2015-2019). The primary endpoint was defined as total duration of surgery, duration of completing the vascular anastomosis (ischemia time), bypass patency, number of stiches to perform the anastomosis, added stiches after leakage testing of the anastomosis and the Glasgow outcome scale (GOS) at last follow-up as secondary outcome parameter. RESULTS: A total of 16 consecutive moyamoya patients underwent 21 STA-MCA bypass procedures. Thereof, six patients were operated using a microscope and ten patients using an exoscope (ORBEYE® n = 1; AEOS® n = 9). Total duration of surgery was comparable between devices (microscope: 313 min. ± 116 vs. exoscope: 279 min. ± 42; p = 0.647). Ischemia time also proved similar between groups (microscope: 43 min. ± 19 vs. exoscope: 41 min. ± 7; p = 0.701). No differences were noted in bypass patency rates. The number of stiches per anastomosis was similar between visualization devices (microscope: 17 ± 4 vs. exoscope: 17 ± 2; p = 0.887). In contrast, more additional stiches were needed in microscopic anastomoses after leakage testing the bypass (p = 0.035). CONCLUSION: Taking into account the small sample size, end-to-side bypass surgery for moyamoya disease using a foot switch-operated 3D exoscope was not associated with more complications and led to comparable clinical and radiological results as microscopic bypass surgery.

Flow diversion of ruptured intracranial aneurysms: a single-center study with a standardized antithrombotic treatment protocol.

BACKGROUND: The use of antithrombotic medication following acute flow diversion for a ruptured intracranial aneurysm (IA) is challenging with no current guidelines. We investigated the incidence of treatment-related complications and patient outcomes after flow diversion for a ruptured IA before and after the implementation of a standardized antithrombotic medication protocol. METHODS: We conducted a single-center retrospective study including consecutive patients treated for acutely ruptured IAs with flow diversion during 2015-2023. We divided the patients into two groups: those treated before the implementation of the protocol (pre-protocol) and those treated after the implementation of the protocol (post-protocol). The primary outcomes were hemorrhagic and ischemic complications. A secondary outcome was clinical outcome using the modified Ranking Scale (mRS). RESULTS: Totally 39 patients with 40 ruptured IAs were treated with flow diversion (69% pre-protocol, 31% post-protocol). The patient mean age was 55 years, 62% were female, 63% of aneurysms were in the posterior circulation, 92% of aneurysms were non-saccular, and 44% were in poor grade on admission. Treatment differences included the use of glycoprotein IIb/IIIa inhibitors (pre-group 48% vs. post-group 100%), and the use of early dual antiplatelets (pre-group 44% vs. 92% post-group). The incidence of ischemic complications was 37% and 42% and the incidence of hemorrhagic complications was 30% and 33% in the pre- and post-groups, respectively, with no between-group differences. There were three (11%) aneurysm re-ruptures in the pre-group and none in the post-group. There were no differences in mortality or mRS 0-2 between the groups at 6 months. CONCLUSION: We found no major differences in the incidence of ischemic or hemorrhagic complications after the implementation of a standardized antithrombotic protocol for acute flow diversion for ruptured IAs. There is an urgent need for more evidence-based guidelines to optimize antithrombotic treatment after flow diversion in the setting of subarachnoid hemorrhage.

Changes in treatment of intracranial aneurysms during the last decade in a large European neurovascular center.

OBJECTIVE: Treatment modality for ruptured and unruptured intracranial aneurysms has shifted during the last two decades from microsurgical treatment towards endovascular treatment. We present how this transition happened in a large European neurovascular center. METHODS: We conducted a retrospective observational study consecutive patients treated for an unruptured or ruptured intracranial aneurysm at Helsinki University Hospital during 2012-2022. We used Poisson regression analysis to report age-adjusted treatment trends by aneurysm location and rupture status. RESULTS: A total of 2491 patients with intracranial aneurysms were treated (44% ruptured, 56% unruptured): 1421 (57%) surgically and 1070 (43%) endovascularly. A general trend towards fewer treated aneurysms was noted. The proportion of patients treated surgically decreased from 90% in 2012 to 20% in 2022. The age-adjusted decrease of surgical versus endovascular treatment was 6.9%/year for all aneurysms, 6.8% for ruptured aneurysms, and 6.8% for unruptured aneurysms. The decrease of surgical treatment was most evident in unruptured vertebrobasilar aneurysms (10.8%/year), unruptured communicating artery aneurysms (10.1%/year), ruptured communicating artery aneurysms (10.0%/year), and ruptured internal carotid aneurysms (9.0%/year). There was no change in treatment modality for middle cerebral artery aneurysms, of which 85% were still surgically treated in 2022. A trend towards an increasing size for treated ruptured aneurysms was found (p = 0.033). CONCLUSION: A significant shift of the treatment modality from surgical to endovascular treatment occurred for all aneurysm locations except for middle cerebral artery aneurysms. Whether this shift has affected long-term safety and patient outcomes should be assessed in the future.

Even short-term training improves the skills of novice exoscope users: a prospective laboratory experiment.

BACKGROUND: The surgical 3D exoscopes have recently been introduced as an alternative to the surgical microscopes in microneurosurgery. Since the exoscope availability is still limited, it is relevant to know whether even a short-term exoscope training develops the skills needed for performing exoscope-assisted surgeries. METHODS: Ten participants (six consultants, four residents) performed two laboratory bypass test tasks with a 3D exoscope (Aesculap Aeos®). Six training sessions (6 h) were performed in between (interval of 2-5 weeks) on artificial models. The participants were divided into two groups: test group (n = 6) trained with the exoscope and control group (n = 4) with a surgical microscope. The test task was an artificial end-to-side microsurgical anastomosis model, using 12 interrupted 9-0 sutures and recorded on video. We compared the individual as well as group performance among the test subjects based on suturing time, anastomosis quality, and manual dexterity. RESULTS: Altogether, 20 bypass tasks were performed (baseline n = 10, follow-up n = 10). The median duration decreased by 28 min and 44% in the exoscope training group. The decrease was steeper (29 min, 45%) among the participants with less than 6 years of microneurosurgery experience compared to the more experienced participants (13 min, 24%). After training, the participants with at least 1-year experience of using the exoscope did not improve their task duration. The training with the exoscope led to a greater time reduction than the training with the microscope (44% vs 17%). CONCLUSIONS: Even short-term training with the exoscope led to marked improvements in exoscope-assisted bypass suturing among novice microneurosurgeons. For the more experienced participants, a plateau in the initial learning curve was reached quickly. A much longer-term effort might be needed to witness further improvement in this user group.

Temporal Changes in CSF Cell Parameters After SAH: Comparison of Ventricular and Spinal Drain Samples.

BACKGROUND: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)-derived and lumbar spinal drain-derived samples. METHODS: We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain-derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling. RESULTS: We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4-5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64-618 × 106). The cell ratio and index peaked at 8-9 days (0.90% [IQR 0.35-1.98%] and 2.71 [IQR 1.25-6.73], respectively). In spinal drain-derived samples, the leucocyte count peaked at days 6-7, reaching a median of 238 × 106 (IQR 60-396 × 106). The cell ratio and index peaked at 14-15 days (4.12% [IQR 0.63-10.61%]) and 12-13 days after aSAH (8.84 [IQR 3.73-18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain-derived samples at days 6-17, and the cell ratio as well as the cell index was significantly higher in spinal drain-derived samples compared to EVD samples at days 10-15. CONCLUSIONS: CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.

Child- and parent-related determinants for out-of-home care in a nationwide population with neurodevelopmental disorders: a register-based Finnish birth cohort 1997 study.

Neurodevelopmental disorders (NDDs) are among the most common health issues in childhood and adolescence. Psychiatric disorders are known to be overrepresented among children using child welfare services and placed in out-of-home care (OHC). Child- and parent-related determinants for OHC among a national population with NDDs were evaluated utilising longitudinal register data from the national Finnish Birth Cohort 1997 (n = 58,802) from birth to 18 years (1997-2015). The cohort members with NDDs (n = 5,143, 9% of total cohort) formed our study population. Based on their history of OHC, cohort members with NDD were categorised to OHC (n = 903) and non-OHC groups (n = 4,240). Of all cohort members with NDDs, 17.6% had a history of OHC. Within NDDs, a significant excess of ADHD diagnosis was observed in the OHC group compared to the non-OHC group (49% vs. 26%). The OHC group with NDDs was significantly characterised by having comorbid psychiatric diagnosis for conduct and oppositional disorders (adj. RR 2.21), substance use disorders (adj. RR 1.61) and depression and anxiety disorders (adj. RR 1.60). Of all parent-related determinants, the most prevailing in the OHC group compared to the non-OHC group, was social assistance received by parent (88% vs. 44.5%). The longer the period (in years) for received social assistance, the greater the likelihood for OHC (adj. RRs range from 2.41 for one year to 5.24 for over 4 years). Further, significantly associating determinants for OHC were parental psychiatric disorders (adj. RR 1.42) and parental death (adj. RR 1.23). Our findings from the population-based cohort of children and adolescents with NDDs highlight the importance of screening and assessment of family situation. Also, effective prevention and treating of comorbid psychiatric disorders, especially conduct and oppositional disorders is essential.

The Finnish Adoptive Family Study of Schizophrenia: differences in somatic diseases and conditions between adoptees with high or low genetic risk for schizophrenia spectrum disorders.

BACKGROUND AND AIMS: There is some evidence that offspring of patients with schizophrenia have higher somatic morbidity, which is thought to be partially due to genetic links between somatic disorders and schizophrenia. This study explored differences in somatic diseases and conditions of adoptees with high genetic risk (HR) or low genetic risk (LR) for schizophrenia spectrum disorders. MATERIAL AND METHODS: The study is part of the Finnish Adoptive Family Study of Schizophrenia. The adoptive research design used made it possible to examine how the somatic health of adoptees raised in similar adoptive families, is affected by their genetic susceptibility to schizophrenia. The study sample consisted of 373 adoptees, of whom 190 had HR and 183 had LR for schizophrenia spectrum disorders. Data on somatic morbidity were gathered from the hospital records and from the national registers of the Care Register of Health Care and the Social Insurance Institution. RESULTS: The only statistically significant difference found was in genitourinary diseases, the likelihood being twofold higher in HR adoptees compared to LR adoptees (16.8% vs. 8.2%; adj. OR = 2.13, 95% CI 1.06-4.25, p = .033). Adoptees who were female and aged over 40 had a higher prevalence of genitourinary illnesses than non-adoptees. CONCLUSION: The significant prevalence of genitourinary diseases in adoptees at risk for schizophrenia spectrum disorders suggests that some specific somatic diseases and schizophrenia may have a shared hereditary etiology. More research is required for specific somatic diseases in study populations that can differentiate between the effects of genetic and environmental factors.

Herpesviruses, polyomaviruses, parvoviruses, papillomaviruses, and anelloviruses in vestibular schwannoma.

Etiology of vestibular schwannoma (VS) is unknown. Viruses can infect and reside in neural tissues for decades, and new viruses with unknown tumorigenic potential have been discovered. The presence of herpesvirus, polyomavirus, parvovirus, and anellovirus DNA was analyzed by quantitative PCR in 46 formalin-fixed paraffin-embedded VS samples. Five samples were analyzed by targeted next-generation sequencing. Viral DNA was detected altogether in 24/46 (52%) tumor samples, mostly representing anelloviruses (46%). Our findings show frequent persistence of anelloviruses, considered normal virome, in VS. None of the other viruses showed an extensive presence, thereby suggesting insignificant role in VS.

Surgeon experience in glioblastoma surgery of the elderly-a multicenter, retrospective cohort study.

PURPOSE: To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. METHODS: GBM patients aged ≥ 65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). RESULTS: 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0-12.0); median EOR was 89.4%. Surgery-related morbidity affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P < .001); patients with surgery-related morbidity were less likely to receive adjuvant treatment (P = .002). In multivariable testing, adjuvant therapy (P < .001; HR = 0.064, 95%CI 0.028-0.144) remained the only significant predictor for improved OS. CONCLUSION: Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial for generating a treatment benefit for this cohort.

Inflammation and neutrophil extracellular traps in cerebral cavernous malformation.

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.

How I do it-Helsinki style mini-pterional craniotomy for clipping of middle cerebral artery bifurcation aneurysms.

BACKGROUND: Different versions of the mini-pterional (MPT) approach have been described often with the idea the smaller the better. Attempts to reduce incision and craniotomy size for better cosmetic results should not be performed at the expense of safety. METHOD: We present our take on the MPT as a balance between size and safety which can be adopted by vascular neurosurgeons in training. The craniotomy stays within the confines of the superior temporal line and is completely covered by temporal muscle after closure. CONCLUSION: This approach is cosmetically superior while still offering anatomical familiarity and sufficient instrument maneuverability.

Taming the exoscope: a one-year prospective laboratory training study.

PURPOSE: Digital 3D exoscopes have been recently introduced as an alternative to a surgical microscope in microneurosurgery. We designed a laboratory training program to facilitate and measure the transition from microscope to exoscope. Our aim was to observe the effect of a one-year active training on microsurgical skills with the exoscope by repeating a standardized test task at several time points during the training program. METHODS: Two board-certified neurosurgeons with no previous exoscope experience performed the same test tasks in February, July, and November during a 12-month period. In between the test tasks, both participants worked with the exoscope in the laboratory and assisted during clinical surgeries on daily basis. Each of the test segments consisted of repeating the same task 10 times during one week. Altogether, 60 test tasks were performed, 30 each. The test task consisted of dissecting and harvesting the ulnar and radial arteries of the second segment of a chicken wing using an exoscope (Aesculap AEOS). Each dissection was recorded on video and analyzed by two independent evaluators. We measured the time required to complete the task as well as several metrics for evaluating the manual skills of the dissection and handling of the exoscope system. RESULT: There was a clear reduction in dissection time between the first and the last session, mean 34 min (SD 5.96) vs. 26 min (SD 8.69), respectively. At the end of the training, both neurosurgeons used the exoscope more efficiently utilizing more available options of the device. There was correlation between the dissection time and several of the factors we used for evaluating the work flow: staying in focus, zoom control, reduction of unnecessary movements or repetitive manual motions, manipulation technique of the vessel under dissection, handling of the instruments, and using them for multiple dissection purposes (stretching, cutting, and splitting). CONCLUSION: Continuous, dedicated long-term training program is effective for microsurgical skill development when switching from a microscope to an exoscope. With practice, the micromotor movements become more efficient and the use of microinstruments more versatile.

Immunoliposomes for detection of rupture-prone intracranial aneurysms.

BACKGROUND: It is estimated that significant (3.2%) of population carries intracranial aneurysm (IA). An increasing number of imaging studies have caused that the chance of finding an incidental aneurysm is becoming more common. Since IA rupture causes subarachnoidal hemorrhage (SAH) and have significant mortality and morbidity prophylactic treatment should be considered when IA is detected. The benefit and risk of treatment of IA is based on epidemiological estimate which takes account patient and aneurysm characteristics. However we know that aneurysm rupture is biological process where inflammation of aneurysm wall is actively leading to degeneration of aneurysm wall and finally weakens it until it bursts. Until now, there have not been imaging method to detect inflammatory process of aneurysm wall METHODS: We created targeting immunoliposome for use in the imaging of aneurysm. Immunoliposome comprises antibodies against at least one vascular inflammatory marker associated with aneurysm inflammation and a label and/or a contrast agent. RESULTS: Histological analysis of IAs where immunoliposome comprises antibodies against vascular inflammation with a label shows promising results for selectively detecting aneurysms inflammation. In magnetic resonance imaging (MRI) we were able to detect immunoliposomes carrying gadolinium. CONCLUSION: Our work opens a new avenue for using contrast labeled immunoliposomes for detecting rupture-prone aneurysms. Immunoliposomes can cary gadolinium and selectively bind to inflammatory section of aneurysm that can be detected with MRI. Further research is needed to develop immunoliposomes to be used with MRI in humans to target treatment to those patients who benefit from it the most.

Small amount of alcohol did not deteriorate microsurgical dexterity: a prospective laboratory study.

BACKGROUND: Alcohol consumption has been reported to deteriorate surgical performance both immediately after consumption as well as on the next day. We studied the early effects of alcohol consumption on microsurgical manual dexterity in a laboratory setting. METHOD: Six neurosurgeons or neurosurgical residents (all male) performed micro- and macro suturing tasks after consuming variable amounts of alcohol. Each participant drank 0-4 doses of alcohol (14 g ethanol). After a delay of 60-157 min, he performed a macrosurgical and microsurgical task (with a surgical microscope). The tasks consisted of cutting and re-attaching a circular latex flap (diameter: 50 mm macrosuturing, 4 mm microsuturing) with eight interrupted sutures (4-0 multifilament macrosutures, 9-0 monofilament microsutures). We measured the time required to complete the sutures, and the amplitude and the frequency of physiological tremor during the suturing. In addition, we used a four-point ordinal scale to rank the quality of the sutures for each task. Each participant repeated the tasks several times on separate days varying the pre-task alcohol consumption (including one sober task at the end of the data collection). RESULTS: A total of 93 surgical tasks (47 macrosurgical, 46 microsurgical) were performed. The fastest microsurgical suturing (median 11 min 49 s, [interquartile range (IQR) 654 to 761 s]) was recorded after three doses of alcohol (median blood alcohol level 0.32‰). The slowest microsurgical suturing (median 15 min 19 s, [IQR 666 to 1121 s]) was observed after one dose (median blood alcohol level 0‰). The quality of sutures was the worst (mean 0.70 [standard deviation (SD) 0.48] quality points lost) after three doses of alcohol and the best (mean 0.33 [SD 0.52] quality points lost) after four doses (median blood alcohol level 0.44‰). CONCLUSIONS: Consuming small amount of alcohol did not deteriorate microsurgical performance in our study. An observed reduction in physiological tremor may partially explain this.

Recurrence of brain arteriovenous malformations in pediatric patients: a long-term follow-up study.

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.