Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Impact of Stereotactic Ventriculocisternostomy on Delayed Cerebral Infarction and Outcome After Subarachnoid Hemorrhage.

Background and Purpose- Delayed cerebral infarction (DCI) is an important cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage is a new method for DCI prevention. Here, we assess the effects of implementing STX-VCS in an unselected aSAH patient population of a tertiary referral center. Methods- Retrospective cohort study of all consecutive aSAH patients admitted to a neurosurgical referral center during a 7-year period (April 2012 to April 2019). Midterm STX-VCS was introduced and offered to patients at high risk for DCI. We compared the incidence and burden of DCI, neurological outcome, and the use of induced hypertension and endovascular rescue therapy in this consecutive aSAH population 3.5 years before versus 3.5 years after STX-VCS became available. Results- Four hundred thirty-six consecutive patients were included: 222 BEFORE and 214 AFTER. Fifty-seven of 214 (27%) patients received STX-VCS. Stereotactic procedures resulted in one (2%) subdural hematoma. Favorable neurological outcome at 6 months occurred in 118 (53%) patients BEFORE and 139 (65%) patients AFTER (relative risk, 0.79 [95% CI, 0.66-0.95]). DCI occurred in 40 (18.0%) patients BEFORE and 17 (7.9%) patients AFTER (relative risk, 0.68 [95% CI, 0.57-0.86]), and total DCI volumes were 8933 (100%) and 3329 mL (36%), respectively. Induced hypertension was used in 97 (44%) and 30 (15%) patients, respectively (relative risk, 0.55 [95% CI, 0.46-0.65]). Thirty (13.5%) patients BEFORE versus 5 (2.3%) patients AFTER underwent endovascular rescue therapies (relative risk, 0.17 [95% CI, 0.07-0.42]). Conclusions- Selecting high-risk patients for STX-VCS reduced the DCI incidence, burden, and related mortality in a consecutive aSAH patient population. This was associated with an improved neurological outcome.

Emergency Free-Hand Bedside Catheter Evacuation of Large Intracerebral Hematomas Following Thrombolysis for Ischemic Stroke: A Case Series.

INTRODUCTION: Symptomatic intracerebral hemorrhage (sICH) following systemic thrombolysis for ischemic stroke is often devastating, and open surgical evacuation is considered dangerous due to the increased risk of perioperative bleeding, and stereotactic placement of a catheter is too time-consuming. We therefore evaluated the feasibility of a free-hand bedside catheter technique for emergency hematoma evacuation. METHODS: Patients who had a supratentorial sICH after thrombolysis, a hematoma volume > 30 ml, and an ensuing reduction in vigilance were consecutively treated with acute minimally invasive catheter hematoma evacuation. Catheter insertion and trajectory were planned via 3D-reconstructed computed tomography (CT) scan, and free-hand insertion of an external ventricular catheter into the core of the hematoma was performed bedside, followed by careful blood aspiration. Cranial CT was used to verify catheter position and residual hematoma volume. In cases, where the residual volume exceeded 15 ml, urokinase (5000 IE) was administered into the clot every 6 h until the volume decreased to < 15 ml. RESULTS: In all six patients, catheter aspiration immediately reduced hematoma volume by 77%, from 73 ± 20 ml to 17 ± 16 ml (p = 0.028). In four patients, the hematoma was almost completely removed (< 10 ml) by singular aspiration. In the remaining two patients with a residual hematoma size > 15 ml, consecutive urokinase application resulted in a further reduction to 1 ml and 15 ml, respectively, after 30 h. The median National Institues of Health Stroke Scale/Score after sICH was 19.5 points, rapidly decreasing to 11 after catheter aspiration (p = 0.027), and further improving to 4 at discharge. No procedure-related complications were observed. CONCLUSIONS: Emergency free-hand bedside catheter aspiration is a reasonable option for hematoma evacuation in large thrombolysis-associated sICH when performed by experienced neurosurgeons. Larger studies would help in determining the generalizability of our findings to other centers and assessing their impact on functional outcome.

Development of a Standardized Cranial Phantom for Training and Optimization of Functional Stereotactic Operations.

BACKGROUND: In recent years, simulations based on phantom models have become increasingly popular in the medical field. In the field of functional and stereotactic neurosurgery, a cranial phantom would be useful to train operative techniques, such as stereo-electroencephalography (SEEG), to establish new methods as well as to develop and modify radiological techniques. In this study, we describe the construction of a cranial phantom and show examples for it in stereotactic and functional neurosurgery and its applicability with different radiological modalities. METHODS: We prepared a plaster skull filled with agar. A complete operation for deep brain stimulation (DBS) was simulated using directional leads. Moreover, a complete SEEG operation including planning, implantation of the electrodes, and intraoperative and postoperative imaging was simulated. RESULTS: An optimally customized cranial phantom is filled with 10% agar. At 7°C, it can be stored for approximately 4 months. A DBS and an SEEG procedure could be realistically simulated. Lead artifacts can be studied in CT, X-ray, rotational fluoroscopy, and MRI. CONCLUSIONS: This cranial phantom is a simple and effective model to simulate functional and stereotactic neurosurgical operations. This might be useful for teaching and training of neurosurgeons, establishing operations in a new center and for optimization of radiological examinations.

Early Vasospasm after Aneurysmal Subarachnoid Hemorrhage Predicts the Occurrence and Severity of Symptomatic Vasospasm and Delayed Cerebral Ischemia.

BACKGROUND: Cerebral vasospasm usually develops several days after subarachnoid hemorrhage (SAH) and is generally acknowledged as a strong outcome predictor. In contrast, much less is known about the nature and eventual consequences of early angiographic vasospasm (EAVS) seen on admission digital subtraction angiography (DSA). Therefore, we aimed at identifying the risk factors and clinical impact of EAVS after SAH. METHODS: Five hundred and thirty-one SAH patients with admission DSA performed within 72 h after the bleeding event were selected from a comprehensive database containing all consecutive SAH patients treated at our institution between January 2005 and December 2012. Predictors of EAVS, as well as associations between EAVS and delayed vasospasm-related complications, and unfavorable outcome (defined as modified Rankin scale >3) were evaluated in univariate and multivariate analyses. RESULTS: EAVS was seen on 60 DSAs (11.3%) and was independently correlated with delayed symptomatic vasospasm requiring intra-arterial spasmolysis (OR 5.24, p < 0.0001), angioplasty (OR 2.56, p = 0.015) and repetitive endovascular treatment (OR 4.71, p < 0.0001). EAVS also increased the risk for multiple versus single territorial infarction on the follow-up CT scan(s) (OR 2.04, p = 0.047) and independently predicted unfavorable outcome (OR 2.93, p = 0.008). The presence of radiographic signs suspicious for fibromuscular dysplasia were independently associated with the occurrence of EAVS (OR 2.98, p = 0.026) and the need for repetitive endovascular vasospasm treatment (OR 3.95, p = 0.019). CONCLUSIONS: In view of the strong correlation with delayed symptomatic vasospasm and its ischemic complications, EAVS can be considered an alerting signal for severe symptomatic vasospasm. Therefore, more attention should be paid to the presence of EAVS on admission DSA.

Decompressive hemicraniectomy in the management of acute stroke in children with Moyamoya disease: the difficult balance between the spontaneous postoperative revascularization process and the need for cranial reconstruction.

BACKGROUND AND IMPORTANCE: The decompressive hemicraniectomy (DCH) after malignant middle cerebral artery infarction in children is a rare procedure, and the indication is discussed as being controversial. Etiological Moyamoya disease has some additional challenges concerning the therapeutic strategy that have not mentioned in the recent literature, as it is dependent on special pathophysiology. CLINICAL PRESENTATION: We report a case of a four-year-old patient with a decompressive hemicraniectomy after malignant middle cerebral artery infarction on the right hemisphere based on a Moyamoya syndrome with proximal MCA occlusions on both sides. After the decompression there was a good restitution of the hemiparesis, aphasia, and consciousness loss on admission. The bone flap replacement is usually done after three month in our department to ensure brain swelling has subsided. In this patient the cranioplasty was not arranged because of the development of collateral vessels to the right motor region through the craniotomy defect, to protect the supply of the eloquent cortex. CONCLUSION: We conclude that the indication of DCH and postoperative treatment should be discussed individually, especially when neovascularisation developments can occur like in Moyamoya disease. An important point is the right timing for bone flap replacement, which should be directly after cerebral edema has subsided prior to the evolution of collaterals through the craniotomy defect. Additionally, leaving the opportunity for neovascularization through smaller defects has to be taken into account.

Clinical utility and cost-effectiveness of CT-angiography in the diagnosis of nontraumatic subarachnoid hemorrhage.

INTRODUCTION: CT-angiography gains an increasing role in the initial diagnosis of patients with nontraumatic subarachnoid hemorrhage (SAH). However, the implementation of CT-angiography does not always exclude the necessity of conventional angiography. Our objective was to determine the practical utility and cost-effectiveness of CT-angiography. METHODS: All patients with nontraumatic subarachnoid hemorrhage admitted to our university hospital after implementation of CT-angiography between June 1, 2011 and June 30, 2012 were retrospectively analyzed in regard to factors of treatment flow, radiation exposure, harms of contrast medium loading, and diagnostic costs. A control group of the same size was assembled from previously admitted SAH patients, who did not undergo pretreatment CT-angiography. Furthermore, cost-effectiveness analysis was performed. RESULTS: The final analysis consisted of 93 patients in each group. Of 93 patients with pretreatment CT-angiography, 74 had to undergo conventional angiography for diagnostic and/or therapeutic purposes. CT-angiography had significant impact on the reduction of collective effective radiation dose by 4.419 mSv per person (p = 0.0002) and was not associated with additional harms. Despite the significantly earlier detection of aneurysms with CT-angiography (p < 0.0001), there were no significant differences in the timing of aneurysm repair and duration of ICU and general hospital stay. There was an increase of diagnostic costs-the cost-effectiveness analysis showed, however, that benefits of CT-angiography in respect to radiation exposure and risk of conventional angiography-related complications justify the additional costs of CT-angiography. CONCLUSIONS: Although the implementation of CT-angiography in SAH diagnosis cannot completely replace conventional angiography, it can be approved in regard to radiation hygiene and cost-effectiveness.

Cerebral aneurysms: Germany-wide real-world outcome data of endovascular or neurosurgical treatment from 2007 to 2019.

BACKGROUND: Evidence on clinical outcome after endovascular treatment (EVT) vs neurosurgical clipping of intracranial aneurysms (IAs) is based on one randomized and one pseudo-randomized trial for ruptured aneurysms. Herein, we analyze nationwide real-world hospital outcomes after EVT vs clipping of ruptured and unruptured IAs. METHODS: This cohort study analyzed all EVT and clipping procedures for IAs in Germany between 2007 and 2019. The data basis was the billing-data of all German hospitals from the German Federal Statistical Office. EVT and clipping interventions, comorbidities, and in-hospital outcomes were identified using International Classification of Diseases (ICD) and Operation and Procedure (OPS) codes. Discharge type was used as a surrogate marker for functional independence. Poor clinical outcome at discharge was additionally defined by the dichotomous US National Inpatient Sample-Subarachnoid hemorrhage Outcome Measure score (NIH-SOM). Secondary outcomes included length of hospital stay, prolonged mechanical ventilation (>48 hour), and hospital reimbursement. RESULTS: We analyzed 90 039 procedures (62.6% EVT, 35.52% clipping, 1.8% combined) for the treatment of IAs. After adjustment in-hospital mortality was equal after EVT compared with clipping, in ruptured IAs (adjusted OR (aOR) 0.98, p=0.707) and unruptured IAs (aOR 0.92, p=0.482). Functional independence was more likely after EVT for ruptured (aOR 0.81, p<0.001) and unruptured IAs (aOR 0.4, p<0.001). Poor clinical outcome was more likely after clipping for ruptured (aOR 0.67, p<0.001) and unruptured IAs (aOR 0.56, p<0.001). CONCLUSIONS: In German clinical practice, we observed higher rates of functional independence and lower rates of poor outcomes at discharge with equal mortality for EVT.

Reliability of High-resolution Gadolinium-enhanced MR Cisternography and Gasket-seal Technique for Management of Anterior Skull Base Defects.

PURPOSE: Precise preoperative localization of anterior skull base defects is important to plan surgical access, increase the success rate and reduce complications. A stable closure of the defect is vital to prevent recurrence of cerebrospinal fluid (CSF) rhinorrhea. The purpose of this retrospective case series was to evaluate the reliability of a new high-resolution gadolinium-enhanced compressed-sensing SPACE technique (CS T1 SPACE) for magnetic resonance (MR) cisternography to detect cerebrospinal fluid leaks of the anterior skull base and to assess the long-term success rate of the gasket-seal technique for closure of skull base defects. METHOD: All patients with spontaneous or postoperative cerebrospinal fluid rhinorrhea and defects of the anterior skull base presenting to the Departments of Otorhinolaryngology and Neurosurgery between 2019 and 2020, receiving a computed tomography (CT) cisternography and MR cisternography (on a 3T whole-body MR scanner using a 64-channel head and neck coil) with CS T1 SPACE sequence and closure of the defect with the gasket-seal technique, were enrolled in the study. For the cisternography, iodinated contrast agent (15 ml Solutrast 250 M®), saline (4 mL) mixed with a 0.5 mL of gadoteridol was injected into the lumbar subarachnoid space. RESULTS: A total of four patients were included in the study and MR cisternography with CS T1 SPACE sequence was able to precisely localize CSF leaks in all patients. The imaging results correlated with intraoperative findings. All defects could be successfully closed with the gasket-seal technique. The mean follow-up was 35.25 months (range 33-37 months). CONCLUSION: MR cisternography with CS T1 SPACE sequence could be a promising technique for precise localization of CSF leaks and the gasket-seal technique resulted in good closure of the CSF fistula in this case series.

Don't delay, but don't despair: symptom duration, comorbidity and outcome after closure of spinal cerebrospinal fluid leaks.

OBJECTIVE: Microsurgical sealing of spinal cerebrospinal fluid (CSF) leaks is a viable treatment option in spontaneous intracranial hypotension (SIH). Several factors may influence the outcome, with symptom duration probably the most modifiable variable. METHODS: Patients with closure of spinal CSF leaks between September 2020 and March 2023 and a follow-up period of 6 months were included in this retrospective single-center study. Pre- and postoperative scores for impact of headaches (Headache Impact Test, HIT-6) and quality of life (QoL, EQ-5D-5L) were systematically collected. Multiple regression modelling and subgroup analyses for different symptom durations and comorbidities were performed for these outcomes. RESULTS: One hundred patients (61% female, median age 43.5 years) were included. Six months postoperatively, there was significant improvement in headache impact (HIT-6: 66 (IQR 62-69) to 52 (IQR 40-61, p < 0.001) and QoL (EQ-5D-5L VAS: 40 (IQR 30-60) to 79 (IQR 60-90); EQ-5D-5L Index: 0.67 (IQR 0.35-0.8) to 0.91 (IQR 0.8-0.94, p < 0.001, respectively). Subgroup analysis for a symptom duration above (74%) and below 90 days (26%) and comorbidity, as well as multiple regression analysis, revealed a trend in favor of early treatment and lower comorbidity. However, even after a prolonged symptom duration, improvements were significant. CONCLUSION: As patients with shorter symptom duration show a trend for a better outcome, our results promote a timely diagnosis and treatment in SIH patients. However, a significant postoperative improvement can still be expected even after a prolonged symptom duration.

Non-invasive biomarkers for spontaneous intracranial hypotension (SIH) through phase-contrast MRI.

BACKGROUND AND OBJECTIVE: Spontaneous intracranial hypotension (SIH) is an underdiagnosed disease. To depict the accurate diagnosis can be demanding; especially the detection of CSF-venous fistulas poses many challenges. Potential dynamic biomarkers have been identified through non-invasive phase-contrast MRI in a limited subset of SIH patients with evidence of spinal longitudinal extradural collection. This study aimed to explore these biomarkers related to spinal cord motion and CSF velocities in a broader SIH cohort. METHODS: A retrospective, monocentric pooled-data analysis was conducted of patients suspected to suffer from SIH who underwent phase-contrast MRI for spinal cord and CSF velocity measurements at segment C2/C3 referred to a tertiary center between February 2022 and June 2023. Velocity ranges (mm/s), total displacement (mm), and further derivatives were assessed and compared to data from the database of 70 healthy controls. RESULTS: In 117 patients, a leak was located (54% ventral leak, 20% lateral leak, 20% CSF-venous fistulas, 6% sacral leaks). SIH patients showed larger spinal cord and CSF velocities than healthy controls: e.g., velocity range 7.6 ± 3 mm/s vs. 5.6 ± 1.4 mm/s, 56 ± 21 mm/s vs. 42 ± 10 mm/s, p < 0.001, respectively. Patients with lateral leaks and CSF-venous fistulas exhibited an exceptionally heightened level of spinal cord motion (e.g., velocity range 8.4 ± 3.3 mm/s; 8.2 ± 3.1 mm/s vs. 5.6 ± 1.4 mm/s, p < 0.001, respectively). CONCLUSION: Phase-contrast MRI might become a valuable tool for SIH diagnosis, especially in patients with CSF-venous fistulas without evidence of spinal extradural fluid collection.

Multiomic spatial landscape of innate immune cells at human central nervous system borders.

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.

Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy.

PURPOSE: To analyze the safety profile of subdural and depth electrode implantation in a large monocentric cohort of patients of all ages undergoing intracranial EEG exploration because of drug resistant focal epilepsy diagnosed and implanted by a constant team of epileptologists and neurosurgeons. METHODS: We retrospectively analyzed data from 452 implantations in 420 patients undergoing invasive presurgical evaluation at the Freiburg Epilepsy Center from 1999 to 2019 (n = 160 subdural electrodes, n = 156 depth electrodes and n = 136 combination of both approaches). Complications were classified as hemorrhage with or without clinical manifestations, infection-associated and other complications. Furthermore, possible risk factors (age, duration of invasive monitoring, number of electrode contacts used) and changes in complication rates during the study period were analyzed. RESULTS: The most frequent complications in both implantation groups were hemorrhages. Subdural electrode explorations caused significantly more symptomatic hemorrhages and required more operative interventions (SDE 9.9%, DE 0.3%, p < 0.05). Hemorrhage risk was higher for grids with 64 contacts than for smaller grids (p < 0.05). The infection rate was very low (0,2%). A transient neurological deficit occurred in 8.8% of all implantations and persisted for at least 3 months in 1.3%. Transient, but not persistent neurological deficits were more common in patients with implanted subdural electrodes than in the depth electrode group. CONCLUSION: The use of subdural electrodes was associated with a higher risk of hemorrhage and transient neurological symptoms. However persistent deficits were rare with either approach, demonstrating that intracranial investigations using either subdural electrodes or depth electrodes carry acceptable risks in patients with drug-resistant focal epilepsy.

Epilepsy surgery in early infancy: A retrospective, multicenter study.

Although epilepsy surgery is the only curative therapeutic approach for lesional drug-resistant epilepsy (DRE), there is reluctance to operate on infants due to a fear of complications. A recent meta-analysis showed that epilepsy surgery in the first 6 months of life can achieve seizure control in about two thirds of children. However, robust data on surgical complications and postoperative cognitive development are lacking. We performed a retrospective multicenter study of infants who underwent epilepsy surgery in the first 6 months of life. 15 infants underwent epilepsy surgery at a median age of 134 days (IQR: 58) at four centers. The most common cause was malformation of cortical development, and 13 patients underwent a hemispherotomy. Two thirds required intraoperative red blood transfusions. Severe intraoperative complications occurred in two patients including death in one infant due to cardiovascular insufficiency. At a median follow-up of 1.5 years (IQR: 1.8), 57% of patients were seizure-free. Three patients where reoperated at a later age, resulting in 79% seizure freedom. Anti-seizure medication could be reduced in two thirds, and all patients improved in their development. Our findings suggest that early epilepsy surgery can result in good seizure control and developmental improvement. However, given the perioperative risks, it should be performed only in specialized centers.

Pilot study on high-resolution radiological methods for the analysis of cerebrospinal fluid (CSF) shunt valves.

OBJECTIVES: Despite their life-saving capabilities, cerebrospinal fluid (CSF) shunts exhibit high failure rates, with a large fraction of failures attributed to the regulating valve. Due to a lack of methods for the detailed analysis of valve malfunctions, failure mechanisms are not well understood, and valves often have to be surgically explanted on the mere suspicion of malfunction. The presented pilot study aims to demonstrate radiological methods for comprehensive analysis of CSF shunt valves, considering both the potential for failure analysis in design optimization, and for future clinical in-vivo application to reduce the number of required shunt revision surgeries. The proposed method could also be utilized to develop and support in situ repair methods (e.g. by lysis or ultrasound) of malfunctioning CSF shunt valves. MATERIALS AND METHODS: The primary methods described are contrast-enhanced radiographic time series of CSF shunt valves, taken in a favorable projection geometry at low radiation dose, and the machine-learning-based diagnosis of CSF shunt valve obstructions. Complimentarily, we investigate CT-based methods capable of providing accurate ground truth for the training of such diagnostic tools. Using simulated test and training data, the performance of the machine-learning diagnostics in identifying and localizing obstructions within a shunt valve is evaluated regarding per-pixel sensitivity and specificity, the Dice similarity coefficient, and the false positive rate in the case of obstruction free test samples. RESULTS: Contrast enhanced subtraction radiography allows high-resolution, time-resolved, low-dose analysis of fluid transport in CSF shunt valves. Complementarily, photon-counting micro-CT allows to investigate valve obstruction mechanisms in detail, and to generate valid ground truth for machine learning-based diagnostics. Machine-learning-based detection of valve obstructions in simulated radiographies shows promising results, with a per-pixel sensitivity >70%, per-pixel specificity >90%, a median Dice coefficient >0.8 and <10% false positives at a detection threshold of 0.5. CONCLUSIONS: This ex-vivo study demonstrates obstruction detection in cerebro-spinal fluid shunt valves, combining radiological methods with machine learning under conditions compatible to future in-vivo application. Results indicate that high-resolution contrast-enhanced subtraction radiography, possibly including time-series data, combined with machine-learning image analysis, has the potential to strongly improve the diagnostics of CSF shunt valve failures. The presented method is in principle suitable for in-vivo application, considering both measurement geometry and radiological dose. Further research is needed to validate these results on real-world data and to refine the employed methods. In combination, the presented methods enable comprehensive analysis of valve failure mechanisms, paving the way for improved product development and clinical diagnostics of CSF shunt valves.

Quality of Life After Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor disability outcome. Data on quality of life (QoL) among survivors are scarce because patients with poor-grade aSAH are underrepresented in clinical studies reporting on QoL after aSAH. OBJECTIVE: To provide prospective QoL data on survivors of poor-grade aSAH to aid clinical decision making and counseling of relatives. METHODS: The herniation World Federation of Neurosurgical Societies scale study was a prospective observational multicenter study in patients with poor-grade (World Federation of Neurosurgical Societies grades 4 & 5) aSAH. We collected data during a structured telephone interview 6 and 12 months after ictus. QoL was measured using the EuroQoL - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, with 0 representing a health state equivalent to death and 1 to perfect health. Disability outcome for favorable and unfavorable outcomes was measured with the modified Rankin Scale. RESULTS: Two hundred-fifty patients were enrolled, of whom 237 were included in the analysis after 6 months and 223 after 12 months. After 6 months, 118 (49.8%) patients were alive, and after 12 months, 104 (46.6%) patients were alive. Of those, 95 (80.5%) and 89 (85.6%) reached a favorable outcome with mean EQ-5D-3L index values of 0.85 (±0.18) and 0.86 (±0.18). After 6 and 12 months, 23 (19.5%) and 15 (14.4%) of those alive had an unfavorable outcome with mean EQ-5D-3L index values of 0.27 (±0.25) and 0.19 (±0.14). CONCLUSION: Despite high initial mortality, the proportion of poor-grade aSAH survivors with good QoL is reasonably large. Only a minority of survivors reports poor QoL and requires permanent care.

Hydrocephalus Shunting in Supratentorial Glioblastoma: Functional Outcomes and Management.

BACKGROUND: Glioblastoma is the most common and the most challenging to treat adult primary central nervous system tumor. Although modern management strategies modestly improved the overall survival, the prognosis remains dismal associated with poor life quality and the clinical course often dotted by treatment side effects and cognitive decline. Functional deterioration might be caused by obstructive or communicating hydrocephalus but due to poor overall prognosis surgical treatment options are often limited and its optimal management strategies remain elusive. We aimed to investigate risk factors, treatment options and outcomes for tumor-associated hydrocephalus in a contemporary 10 years cohort of glioblastoma patients. METHODS: We reviewed electronic health records of 1800 glioblastoma patients operated at the Department of Neurosurgery, Medical Center - University of Freiburg from 2009 to 2019. Demographics, clinical characteristics and radiological features were analyzed. Univariate analysis for nominal variables was performed either by Fisher's exact test or Chi-square test, as appropriate. RESULTS: We identified 39 glioblastoma patients with symptomatic communicating hydrocephalus treated by ventricular shunting (incidence 2.1%). Opening of the ventricular system during a previous tumor resection was associated with symptomatic hydrocephalus (p<0.05). There was also a trend toward location (frontal and temporal) and larger tumor volume. Number of craniotomies before shunting was not considered as a risk factor. Shunting improved hydrocephalus symptoms in 95% of the patients and Karnofsky Performance Score (KPS) could be restored after shunting. Of note, 75% of the patients had a post-shunting oncological treatment such as radiotherapy or chemotherapy, most prevalently chemotherapy. Infection (7.7%) and over- or under drainage (17.9%) were the most common complications requiring shunt revision in ten patients (25.6%), No peritoneal metastasis was found. The median overall survival (OS) was 385 days and the median post shunting survival was 135 days. CONCLUSION: Ventricular system opening was identified as a risk factor for communicating hydrocephalus in glioblastoma patients. Although glioblastoma treatment remains challenging, shunting improved hydrocephalus-related functional status and may be considered even in a palliative setting for symptom relief.

Patterns of intracerebral hemorrhage that result in unfavorable outcomes in patients with subarachnoid hemorrhage.

OBJECTIVE(S): Intracerebral hemorrhage (ICH) contributes considerably to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH). Specific patterns of aSAH-associated ICH that are not compatible with favorable outcome remain unknown. The main objective of this study is to report patterns of aSAH-associated ICH that result in unfavorable outcomes. METHODS: This is a retrospective analysis of 1036 consecutive aSAH patients admitted to an academic neurosurgical center in a 15-year period (01/2005-12/2019). Admission imaging was investigated for presence, location and size of intracerebral hemorrhage. The rates of favorable outcome at 6 months (modified Rankin Scale) relative to ICH location and volume were analyzed to identify patterns of ICH which were incompatible with favorable outcome. RESULTS: 284 of 1036 patients (27.4%) suffered from aSAH-related ICH. The median ICH volume was 14.0 ml. Outcome of patients with ICH < 10 ml was comparable to patients without ICH. ICH volumes > 10 ml were associated with worse outcomes. We identified the fronto-basal brain to tolerate even larger ICH without compromise of neurological outcomes. ICH located in the frontal, fronto-insular, temporo-insular and temporal regions were associated with intermediate prognoses as outcome declined with larger ICH volumes. ICH located in the basal ganglia, cerebellum, corpus callosum and bifrontal ICH were associated with particularly poor outcomes irrespective of ICH volumes. CONCLUSION: aSAH-associated ICH of the basal ganglia, cerebellum, corpus callosum and bifrontal brain are associated with exceptionally poor outcomes. ICH volume alone is insufficient for prognostic considerations.

Facilitation of drug-resistant epilepsy and catastrophic status epilepticus in children with combined pituitary hormone deficiency.

PURPOSE: Clinicians and researchers often focus on the primary cause of seizures and epilepsy, but outcomes in individual patients also depend on multiple other variables, which might be easy to adjust. Previous studies suggest mutual interactions between endocrine disorders and epilepsy. We therefore hypothesized that combined pituitary hormone deficiency (CPHD) facilitates seizures and epilepsy. METHODS: This is a retrospective study from a pediatric center. We determined the proportion of CPHD patients with epilepsy and examined basic clinical features in this group. Patients with super-refractory status epilepticus (SRSE) were reviewed to identify subjects with co-morbid CPHD. Those cases were analyzed in detail. RESULTS: 12 of 73 CPHD patients (16%) also had epilepsy. Various etiologies of CPHD were represented, though five subjects had a cranial tumor or cortical malformation. Epilepsy was drug resistant in all but one patient. Among 12 identified patients with SRSE, 4 were unexpected new-onset cases. Three of these subjects also had CPHD with ACTH deficiency and a febrile infection prior to SRSE. Another common feature was the devastating clinical course: In all three patients, initial MRI already suggested severe neuronal damage, SRSE persisted for at least one week with ongoing need for anesthetic coma, and outcome was poor (two patients survived with major sequelae, one child deceased during the episode). CONCLUSION: Our findings indicate that CPHD may predispose for drug-resistant epilepsy and refractory seizures with catastrophic outcome. We suggest that in children with new-onset SRSE, screening for CPHD should be considered.

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.