An International, Multicenter Feasibility Study on Active and Continuous Irrigation With Cerebrospinal Fluid Exchange for Improving Outcomes in Cerebral Ventriculitis.

BACKGROUND AND OBJECTIVES: Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRAflow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis. METHODS: We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRAflow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths. RESULTS: Four centers contributed data for a total of 21 patients who had IRRAflow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRAflow placement. Antibiotics were administered through the IRRAflow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths. CONCLUSION: The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis.

Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage: Location, Distribution Patterns, Infarct Load, and Effect on Outcome.

BACKGROUND AND OBJECTIVES: Delayed cerebral ischemia (DCI) is one of the main contributing factors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Unsuccessful treatment can cause irreversible brain injury in the form of DCI-related infarction. We aimed to assess the association between the location, distribution, and size of DCI-related infarction in relation to clinical outcome. METHODS: Consecutive patients with SAH treated at 2 university hospitals between 2014 and 2019 (Helsinki, Finland) and between 2006 and 2020 (Aachen, Germany) were included. Size of DCI-related infarction was quantitatively measured as absolute volume (in milliliters). In a semiquantitative fashion, infarction in 14 regions of interest (ROIs) according to a modified Alberta Stroke Program Early CT Score (ASPECTS) was noted. The association of infarction in these ROIs along predefined regions of eloquent brain, with clinical outcome, was assessed. For this purpose, 1-year outcome was measured by the Glasgow Outcome Scale (GOS) and dichotomized into favorable (GOS 4-5) and unfavorable (GOS 1-3). RESULTS: Of 1,190 consecutive patients with SAH, 155 (13%) developed DCI-related infarction. One-year outcome data were available for 148 (96%) patients. A median overall infarct volume of 103 mL (interquartile range 31-237) was measured. DCI-related infarction was significantly associated with 1-year unfavorable outcome (odds ratio [OR] 4.89, 95% CI 3.36-7.34, p < 0.001). In patients with 1-year unfavorable outcome, vascular territories more frequently affected were left middle cerebral artery (affected in 49% of patients with unfavorable outcome vs in 30% of patients with favorable outcome; p = 0.029), as well as left (44% vs 18%; p = 0.003) and right (52% vs 14%; p < 0.001) anterior cerebral artery supply areas. According to the ASPECTS model, the right M3 (OR 8.52, 95% CI 1.41-51.34, p = 0.013) and right A2 (OR 7.84, 95% CI 1.97-31.15, p = 0.003) regions were independently associated with unfavorable outcome. DISCUSSION: DCI-related infarction was associated with a 5-fold increase in the odds of unfavorable outcome, after 1 year. Ischemic lesions in specific anatomical regions are more likely to contribute to unfavorable outcome. TRIAL REGISTRATION INFORMATION: Data collection in Aachen was registered in the German Clinical Trial Register (DRKS00030505); on January 3, 2023.

Description of the local hemodynamic environment in intracranial aneurysm wall subdivisions.

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient-specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier-Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low-shear environments can contribute to aneurysm pathology through distinct mechanisms.

Distribution of rupture sites and blebs on intracranial aneurysm walls suggests distinct rupture patterns in ACom and MCA aneurysms.

The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient-specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient-specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high-flow in ACom with thin blebs at impingement sites and low-flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure-high-flow and low-flow conditions-highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient-specific characteristics impact these processes, which need further investigation.

Long-term risk of hemorrhage and mortality after treatment of high-grade intracranial dural arteriovenous fistulas.

BACKGROUND: Despite recent multi-institutional efforts, long-term data on clinical and radiological outcomes after treatment of high-grade dural arteriovenous fistulas (dAVFs) remain scarce. This study aimed to evaluate the long-term risk of hemorrhage and fistula-related mortality after treatment. METHODS: Retrospective analysis of all consecutive patients primarily diagnosed with a high-grade dAVF (Cognard grade 2b, 2a+b, 3, 4) between January 2012 and September 2022 at a large neurovascular center. Primary endpoints were intracranial hemorrhage (ICH) and all-cause mortality after treatment; secondary endpoints were angiographic occlusion, complication rate and neurological deficits. RESULTS: A total of 121 patients underwent 141 treatments (122 endovascular therapy (EVT), 5 radiotherapy, 14 surgery) of which 12 patients (10%) underwent retreatment. Follow-up was available in all patients for a median of 4.2 (IQR 2.5 to 6.6) years. Eleven patients (9%) died during the follow-up period, of which three deaths (2%) occurred after hemorrhagic presentation, one of them attributable to treatment. One death (0.8%) was due to delayed hemorrhage after partial occlusion from EVT. No other post-treatment bleedings occurred. Angiographic follow-up after multimodality treatment was available in 93% of patients after a median of 6 months; the overall occlusion rate was 90%. The overall rate of complications was 25% after EVT and 14% after surgery. The rates of new transient and permanent neurological deficits after EVT were 9% and 3%, respectively. CONCLUSIONS: The long-term rate of re-bleeding or dAVF-related mortality was low when high rates of angiographic occlusion were achieved. The risk for treatment-related complications leading to neurological sequela was low.

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.

Intracranial Arteriovenous Malformations During Pregnancy and Puerperium-A Retrospective Nationwide Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: The knowledge about the management of patients with brain arteriovenous malformations (AVM) during pregnancy is limited, owing partly to insufficient evidence about the outcomes of newborns. This study aims to explore symptomatic AVMs and their outcomes during pregnancy, delivery, and the postpartum period. METHODS: We conducted a retrospective analysis by combining patients with symptomatic AVM from a nationwide population-based cohort of all women with a pregnancy resulting in delivery during 1987 to 2016 (n = 1 773 728 deliveries) and our AVM database (n = 805, 1942-2014). Cerebrovascular events during pregnancy were identified through International Classification of Diseases-9, International Classification of Diseases-10, or surgical procedure codes from the Hospital Discharge and Medical Birth Registers. Our analysis focused on treatment characteristics and outcomes of patients with AVM hemorrhage or symptomatic AVM during pregnancy, delivery, or puerperium. RESULTS: A total of 28 women with symptomatic AVMs during pregnancy, delivery, or postpartum period were followed for an average of 12.8 years (SD = 15.5) after admission. Among them, 21 (75%) experienced AVM hemorrhages during pregnancy, puerperium, or delivery. The mean age of patients was 28.9 years (SD = 5.5). Hemorrhages occurred predominantly during the second (n = 9, 43% of all ruptures) or the third trimester (n = 5, 24%). Two AVM ruptures occurred during labor. Treatment for AVM took place during pregnancy (n = 7, 25%) or puerperium (n = 3, 14%) in 10 patients (35.7%). Only 5 mothers (17.8%) had not been previously pregnant. There was no significant difference in mean Apgar scores between those with AVM hemorrhage (8.3) and those without (8.4). CONCLUSION: Most mothers in the study had prior pregnancies, suggesting a potentially weaker association between AVM rupture and pregnancy compared to previous reports. Notably, 2 AVM ruptures occurred during spontaneous vaginal deliveries. Outcomes were generally favorable in both mothers and infants. More research is needed to refine our understanding of the optimal timing for invasive treatment during pregnancy.

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.

Endoscopic transsphenoidal resection of parasellar abducens nerve schwannoma: A video demonstration.

Background: The abducens nerve schwannoma (ANS) in the sellar and parasellar region are extremely rare. Only around two dozen of ANS have been described in the world literature. These cases were, however, operated through the transcranial approach. We demonstrate, with the help of an edited video, that ANS located in the sellar and parasellar region can be safely and effectively operated through a transsphenoidal approach under endoscopic visualization. Case Description: Here, we present a case of a 30-year-old male who presented with a nine-month history of diplopia, weight gain, and loss of sexual functions. On neuro-opthalmological examination, a mild abducens palsy on the left side. Other cranial nerves were intact. On endocrinological testing, mild hypopituitarism on gonadal and thyroid axes. Magnetic resonance imaging (MRI) scan showed a contrast-enhanced cystic lesion in the sellar and parasellar region extending into the left temporal fossa. The patient underwent endonasal transsphenoidal endoscopic resection. A binostril standard approach was used, the left middle concha resected, and the nasoseptal flap was raised [Video 1]. The tumor was relatively soft and avascular yet invasive and could be removed with straight and curved suctions and gentle curettage. Subcapsular dissection was the key to saving the sixth nerve. Only minimal remnant posterior to the left internal carotid artery was assumed to be left behind. No cerebrospinal fluid (CSF) leakage was noted during the surgery. The skull base defect was reconstructed with the left-sided nasoseptal flap [Video 1]. Postoperatively, no new cranial nerve deficits. Diplopia is preoperative. Endocrine functions were unchanged. No CSF leak was observed. Postoperative MRI scan showed a near total resection. There was no operation-relevant complication. Diplopia resolved completely in a follow-up period of 6 months. Conclusion: The endoscopic transsphenoidal route is safe and effective for the resection of parasellar ANS. Subcapsular dissection is key to keep the sixth nerve intact.

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.

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.

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.

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.

Proteomics on human cerebral cavernous malformations reveals novel biomarkers in neurovascular dysfunction for the disease pathology.

BACKGROUND: Cerebral cavernous malformation (CCM) is a disease associated with an elevated risk of focal neurological deficits, seizures, and hemorrhagic stroke. The disease has an inflammatory profile and improved knowledge of CCM pathology mechanisms and exploration of candidate biomarkers will enable new non-invasive treatments. METHODS: We analyzed protein signatures in human CCM tissue samples by using a highly specific and sensitive multiplexing technique, proximity extension assay. FINDINGS: Data analysis revealed CCM specific proteins involved in endothelial dysfunction/inflammation/activation, leukocyte infiltration/chemotaxis, hemostasis, extracellular matrix dysfunction, astrocyte and microglial cell activation. Biomarker expression profiles matched bleeding status, especially with higher levels of inflammatory markers and activated astrocytes in ruptured than non-ruptured samples, some of these biomarkers are secreted into blood or urine. Furthermore, analysis was also done in a spatially resolving manner by separating the lesion area from the surrounding brain tissue. Our spatial studies revealed that although appearing histologically normal, the CCM border areas were pathological when compared to control brain tissues. Moreover, the functional relevance of CD93, ICAM-1 and MMP9, markers related to endothelial cell activation and extracellular matrix was validated by a murine pre-clinical CCM model. INTERPRETATION: Here we present a novel strategy for proteomics analysis on human CCMs, offering a possibility for high-throughput protein screening acquiring data on the local environment in the brain. Our data presented here describe CCM relevant brain proteins and specifically those which are secreted can serve the need of circulating CCM biomarkers to predict cavernoma's risk of bleeding.

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.

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.

Digital 3D Exoscope is Safe and Effective in Surgery for Intradural Extramedullary Tumors: A Comparative Series.

BACKGROUND: Digital 3D exoscopes have been shown to be comparably safe and effective as surgical microscopes in complex microneurosurgical procedures. However, the results of exoscopic spinal tumor surgeries are scarce. The purpose of this study is to compare results of a transition from microscope to exoscope in surgeries for spinal intradural extramedullary tumors. METHODS: We included all consecutive patients with intradural extramedullary spinal tumors operated on by the senior author during January 2016 to October 2023. The 3D exoscope was used in the latter half of the series from November 2020. We evaluated pre- and postoperative clinical findings, imaging studies, intra- and postoperative events, and analyzed surgical videos from the operations retrospectively. RESULTS: We operated 35 patients (exoscope n = 19, microscope n = 16) for intradural extramedullary tumors (meningioma n = 18, schwannoma n = 12, other n = 5). Tumors in the cervical and thoracic spine were more common than in the lumbar region. The duration of surgery was slightly longer (median 220 vs. 185 minutes) in the exoscope group. However, the rate of gross total resection of the tumor was higher (81% vs. 67%) and the tumors more often located anteriorly to the spinal cord (42% vs. 13%) in the exoscope group. No major complications (i.e., permanent motor deficit or postoperative hematoma) occurred in either group. We saw postoperative gait improvement in 81% and 85% of the patients with preoperative deterioration of gait after exoscopic and microscopic surgeries, respectively. CONCLUSIONS: This study demonstrates that exoscope-assisted surgery for spinal intradural extramedullary tumors is comparable in safety and effectiveness to traditional microscopic surgery.

Hemangioblastoma and arteriovenous malformation in the same patient: a not random association or two isolated entities? Systematic review starting from a unique case.

BACKGROUND: The association between intracranial hemangioblastomas and arteriovenous malformations has been documented in very few cases in literature since 1965 and might present in three modalities: "intermixed, adjacent and separated (spatially and temporally)". Often, the pattern of presentation is "intermixed". According to our systematic review, we propose an adjustment of the previous classification, specifically for these entities. We describe the first case of a truly "spatially separated" association between these two lesions. METHODS: Our study encompassed all adult patients diagnosed with both intracranial hemangioblastoma and AVM who were evaluated in the last 20-year period, from 2003 to 2023 at Helsinki University Hospital. Cases of this coexistence were retrospectively identified and collected from clinical records. For the systematic review, studies reporting the coexistence of hemangioblastoma and AVM in adult patients (>18 years old) were selected. Given the rarity of this pattern, case reports were also included. RESULTS: The combined analysis of our systematic review and institutional retrospective study revealed a total of only seven identified cases. We applied the classification of neoplasms and AVM by Yano, modifying and adapting it into our screened patient series. We systematically reclassified "adjacent" and genuinely "spatially separated" patterns based on the vascular axis supplying both lesions. CONCLUSIONS: Hemangioblastomas and AVMs rarely coexist in the same patient. Our study reports the first instance of a truly "spatially separated" sporadic association between these vascular lesions. The rarity of such coexistence underscores the need for a nuanced and systematic classification to guide the management of these infrequent cases.

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.