Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial.

BACKGROUND AND PURPOSE: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. METHODS: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. RESULTS: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage  among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). CONCLUSIONS: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.

Large-scale in-silico analysis of CSF dynamics within the subarachnoid space of the optic nerve.

BACKGROUND: Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural alterations of the ONSAS, from first principles, with supercomputers. METHODS: Large-scale in-silico investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625 µm/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes. RESULTS: A physiological flow speed of 0.5 mm/s is achieved by imposing a hydrostatic pressure gradient of 0.37-0.67 Pa/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover, ONSAS trabeculae seem key players in mass transfer. CONCLUSIONS: The present analysis suggests that a pressure drop of 0.1-0.2 mmHg over 4 cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome.

Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS.

BACKGROUND AND OBJECTIVES: Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs). Besides, the same relationship was investigated in progressive MS (PMS). Last, we explored the value of cross-sectional brain and spinal cord volumetric measurements in predicting PIRA. METHODS: From an ongoing multicentric cohort study, we selected patients with MS with (1) availability of a susceptibility-based MRI scan and (2) regular clinical and conventional MRI follow-up in the 4 years before the susceptibility-based MRI. Comparisons in spinal cord atrophy rates (explored with linear mixed-effect models) and PRL count (explored with negative binomial regression models) were performed between: (1) relapsing-remitting (RRMS) and PMS phenotypes and (2) patients experiencing PIRA and patients without confirmed disability accumulation (CDA) during follow-up (both considering the entire cohort and the subgroup of patients with RRMS). Associations between baseline MRI volumetric measurements and time to PIRA were explored with multivariable Cox regression analyses. RESULTS: In total, 445 patients with MS (64.9% female; mean [SD] age at baseline 45.0 [11.4] years; 11.2% with PMS) were enrolled. Compared with patients with RRMS, those with PMS had accelerated cervical cord atrophy (mean difference in annual percentage volume change [MD-APC] -1.41; p = 0.004) and higher PRL load (incidence rate ratio [IRR] 1.93; p = 0.005). Increased spinal cord atrophy (MD-APC -1.39; p = 0.0008) and PRL burden (IRR 1.95; p = 0.0008) were measured in patients with PIRA compared with patients without CDA; such differences were also confirmed when restricting the analysis to patients with RRMS. Baseline volumetric measurements of the cervical cord, whole brain, and cerebral cortex significantly predicted time to PIRA (all p ≤ 0.002). DISCUSSION: Our results show that PIRA is associated with both increased spinal cord atrophy and PRL burden, and this association is evident also in patients with RRMS. These findings further point to the need to develop targeted treatment strategies for PIRA to prevent irreversible neuroaxonal loss and optimize long-term outcomes of patients with MS.

Initial Experience with the Solitaire X 3 mm Stent Retriever for the Treatment of Distal Medium Vessel Occlusions.

Endovascular therapy (EVT) is the standard treatment for ischemic stroke caused by a large vessel occlusion (LVO). The effectiveness of EVT for distal medium vessel occlusions (MDVOs) is still uncertain, but newer, smaller devices show potential for EVT in MDVOs. The new Solitaire X 3 mm device offers a treatment option for MDVOs. Our study encompassed consecutive cases of primary and secondary MDVOs treated with the Solitaire X 3 mm stent-retriever as first-line EVT device between January and December 2022 at 12 European stroke centers. The primary endpoint was a first-pass near-complete or complete reperfusion, defined as a modified treatment in cerebral infarction (mTICI) score of 2c/3. Additionally, we examined reperfusion results, National Institutes of Health Stroke Scale (NIHSS) scores at 24 h and discharge, device malfunctions, complications and procedural technical parameters. Sixty-eight patients (38 women, mean age 72 ± 14 years) were included in our study. Median NIHSS at admission was 11 (IQR 6-16). In 53 (78%) cases, a primary combined approach was used as the frontline technique. Among all enrolled patients, first-pass mTICI 2c/3 was achieved in 22 (32%) and final mTICI 2c/3 in 46 (67.6%) patients after a median of 1.5 (IQR 1-2) passes. Final reperfusion mTICI 2b/3 was observed in 89.7% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR 0-4), and no symptomatic intracranial hemorrhages were reported. Based on our analysis, the utilization of the Solitaire X 3 mm device appears to be both effective and safe for performing EVT in cases of MDVO stroke.

Topographic distribution of inflammation factors in a healing aneurysm.

BACKGROUND: Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing. METHODS: Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall. RESULTS: Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing. CONCLUSION: The presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

Anatomical distribution and clinical significance of middle cerebral artery M2 segment vessel occlusions and its cortical branches in acute ischaemic stroke patients.

Background: Characterisation of anatomical distribution and the clinical impact of middle cerebral artery M2 (MCA-M2) segment occlusion and its subsequent cortical branches (CBs) in acute ischaemic stroke patients (AIS). Methods: Retrospective, monocentric study analysing radiological and clinical data of AIS patients with MCA-M2 segment occlusion with regard to the anatomic distribution of MCA-M2 occlusion and its subsequent CB. Results: A total of 203 patients (median age 77 (IQR 66-83) years, 112 women) were included. There was an equal distribution of right-sided versus left-sided MCA-M2 vessel occlusions (right: n=97; left: n=106), as well as with a median number of affected MCA-M2 CBs of 4 (IQR, 3-6) and a median National Institute of Health Stroke Scale score (NIHSS) on admission of 9 (3-15). For both hemispheres, CBs of the inferior trunks were significantly more affected than the superior trunks. Endovascular treatment (EVT, n=94) was associated with a significant better outcome compared with patients with medical management alone (p=0.027). Conclusion: In acute MCA-M2 segment occlusions, inferior trunks are significantly more affected compared with the superior trunks. The subsequent CBs of the paracentral region of both hemispheres are more commonly involved. In eloquent vascular territories, EVT was more often performed.

A Diagnostic Biomarker for Cervical Myelopathy Based on Dynamic Magnetic Resonance Imaging.

STUDY DESIGN: Multicenter prospective observational study. OBJECTIVE: Diffusion tensor imaging in flexion extension improves the diagnosis of degenerative cervical myelopathy (DCM). We aimed to provide an imaging biomarker for the detection of DCM. SUMMARY OF BACKGROUND DATA: DCM is the most common form of spinal cord dysfunction in adults; however, imaging surveillance for myelopathy remains poorly characterized. PATIENTS AND METHODS: Symptomatic DCM patients were examined in maximum neck flexion-extension and neutral positions in a 3T-magnetic resonance imaging scanner and allocated to 2 groups: (1) Patients with visible intramedullary hyperintensity (IHIS) on T2-weighted imaging (IHIS+, n = 10); and (2) Patients without IHIS (IHIS-, n = 11). Range of motion, space available for the spinal cord, apparent diffusion coefficient (ADC), axial diffusivity (AD), radial diffusivity, and fractional anisotropy were measured and compared between the neck positions and between the groups as well as between control (C2/3) and pathologic segments. RESULTS: Significant differences between the control level (C2/3) and pathologic segments were appreciated for the IHIS+ group at neutral neck position in AD; at flexion in ADC and AD; and at neck extension in ADC, AD, and fractional anisotropy values. For the IHIS- group, significant differences between the control level (C2/3) and pathologic segments were found only for ADC values in neck extension. When comparing diffusion parameters between groups, radial diffusivity was significantly different in all 3 neck positions. CONCLUSION: Significant increases in ADC values between the control and pathologic segments were found for both groups in neck extension only. This may serve as a diagnostic tool to identify early changes in the spinal cord related to myelopathy to indicate potentially reversible spinal cord injury and support the indication for surgery in select circumstances.

Large-scale morphometry of the subarachnoid space of the optic nerve.

BACKGROUND: The meninges, formed by dura, arachnoid and pia mater, cover the central nervous system and provide important barrier functions. Located between arachnoid and pia mater, the cerebrospinal fluid (CSF)-filled subarachnoid space (SAS) features a variety of trabeculae, septae and pillars. Like the arachnoid and the pia mater, these structures are covered with leptomeningeal or meningothelial cells (MECs) that form a barrier between CSF and the parenchyma of the optic nerve (ON). MECs contribute to the CSF proteome through extensive protein secretion. In vitro, they were shown to phagocytose potentially toxic proteins, such as α-synuclein and amyloid beta, as well as apoptotic cell bodies. They therefore may contribute to CSF homeostasis in the SAS as a functional exchange surface. Determining the total area of the SAS covered by these cells that are in direct contact with CSF is thus important for estimating their potential contribution to CSF homeostasis. METHODS: Using synchrotron radiation-based micro-computed tomography (SRµCT), two 0.75 mm-thick sections of a human optic nerve were acquired at a resolution of 0.325 µm/pixel, producing images of multiple terabytes capturing the geometrical details of the CSF space. Special-purpose supercomputing techniques were employed to obtain a pixel-accurate morphometric description of the trabeculae and estimate internal volume and surface area of the ON SAS. RESULTS: In the bulbar segment, the ON SAS microstructure is shown to amplify the MECs surface area up to 4.85-fold compared to an "empty" ON SAS, while just occupying 35% of the volume. In the intraorbital segment, the microstructure occupies 35% of the volume and amplifies the ON SAS area 3.24-fold. CONCLUSIONS: We provided for the first time an estimation of the interface area between CSF and MECs. This area is of importance for estimating a potential contribution of MECs on CSF homeostasis.

Case report: Experience with the Cube Navigation System in complex access routes during CT-guided lumbosacral infiltration therapy.

Purpose: Computed tomography (CT)-guided infiltrations are a mainstay in the treatment of lower back pain. Needle placement is usually performed using the free-hand method, where the translation from the planned needle angle to the actual needle insertion angle is estimated. However, the free-hand method is especially challenging in cases where a double-oblique access route (out-of-plane) rather than an in-plane route is necessary. In this case series, we report our experience with the patient-mounted Cube Navigation System to guide needle placement for complex access routes in lumbar pain therapy. Research design and methods: We retrospectively analyzed the cases of five patients in whom a double-oblique access route was necessary for CT-guided lumbar infiltration pain treatment. Each of those procedures was done using the Cube Navigation System to provide navigational guidance. The mean patient age was 69 ± 13 years (range 58-82 years; all females). Technical success, procedure time, and number of control scans were determined retrospectively. Results: Technical success (i.e., positioning and accuracy) was obtained in all cases. Mean procedure time was 15 ± 7 min (10-22 min); on average, 2 ± 1 CT control scans were performed. There were no complications or material failures reported in the present study. Conclusion: Double-oblique punctures with the Cube Navigation System in this initial case series of complex access routes at the lumbar spine were accurate and the procedure was time efficient. In the authors' view, the Cube Navigation System has the potential to improve needle guidance for complex access routes, especially considering the ease of use of the device.

A Multicenter Longitudinal MRI Study Assessing LeMan-PV Software Accuracy in the Detection of White Matter Lesions in Multiple Sclerosis Patients.

BACKGROUND: Detecting new and enlarged lesions in multiple sclerosis (MS) patients is needed to determine their disease activity. LeMan-PV is a software embedded in the scanner reconstruction system of one vendor, which automatically assesses new and enlarged white matter lesions (NELs) in the follow-up of MS patients; however, multicenter validation studies are lacking. PURPOSE: To assess the accuracy of LeMan-PV for the longitudinal detection NEL white-matter MS lesions in a multicenter clinical setting. STUDY TYPE: Retrospective, longitudinal. SUBJECTS: A total of 206 patients with a definitive MS diagnosis and at least two follow-up MRI studies from five centers participating in the Swiss Multiple Sclerosis Cohort study. Mean age at first follow-up = 45.2 years (range: 36.9-52.8 years); 70 males. FIELD STRENGTH/SEQUENCE: Fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetization prepared rapid gradient echo (T1-MPRAGE) sequences at 1.5 T and 3 T. ASSESSMENT: The study included 313 MRI pairs of datasets. Data were analyzed with LeMan-PV and compared with a manual "reference standard" provided by a neuroradiologist. A second rater (neurologist) performed the same analysis in a subset of MRI pairs to evaluate the rating-accuracy. The Sensitivity (Se), Specificity (Sp), Accuracy (Acc), F1-score, lesion-wise False-Positive-Rate (aFPR), and other measures were used to assess LeMan-PV performance for the detection of NEL at 1.5 T and 3 T. The performance was also evaluated in the subgroup of 123 MRI pairs at 3 T. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) and Cohen's kappa (CK) were used to evaluate the agreement between readers. RESULTS: The interreader agreement was high for detecting new lesions (ICC = 0.97, Pvalue < 10-20 , CK = 0.82, P value = 0) and good (ICC = 0.75, P value < 10-12 , CK = 0.68, P value = 0) for detecting enlarged lesions. Across all centers, scanner field strengths (1.5 T, 3 T), and for NEL, LeMan-PV achieved: Acc = 61%, Se = 65%, Sp = 60%, F1-score = 0.44, aFPR = 1.31. When both follow-ups were acquired at 3 T, LeMan-PV accuracy was higher (Acc = 66%, Se = 66%, Sp = 66%, F1-score = 0.28, aFPR = 3.03). DATA CONCLUSION: In this multicenter study using clinical data settings acquired at 1.5 T and 3 T, and variations in MRI protocols, LeMan-PV showed similar sensitivity in detecting NEL with respect to other recent 3 T multicentric studies based on neural networks. While LeMan-PV performance is not optimal, its main advantage is that it provides automated clinical decision support integrated into the radiological-routine flow. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Risk of intracranial aneurysm recurrence after microsurgical clipping based on 3D digital subtraction angiography.

OBJECTIVE: Current knowledge of recurrence rates after intracranial aneurysm (IA) surgery relies on 2D digital subtraction angiography (DSA), which fails to detect more than 75% of small aneurysm remnants. Accordingly, the discrimination between recurrence and growth of a remnant remains challenging, and actual assessment of recurrence risk of clipped IAs could be inaccurate. The authors report, for the first time, 3D-DSA-based long-term durability and risk factor data of IA recurrence and remnant growth after microsurgical clipping. METHODS: Prospectively collected data for 305 patients, with a total of 329 clipped IAs that underwent baseline 3D-DSA, were evaluated. The incidence of recurrent IA was described by Kaplan-Meier curves. Risk factors for IA recurrence were analyzed by multivariable Cox proportional hazards and logistic regression models. RESULTS: The overall observed proportion of IA recurrence after clipping was 2.7% (9 of 329 IAs) at a mean follow-up of 46 months (0.7% per year). While completely obliterated IAs did not recur during follow-up, incompletely clipped aneurysms (76 of 329) demonstrated remnant growth in 11.8% (3.4% per year). Young age and large initial IA size significantly increased the risk of IA recurrence. CONCLUSIONS: The findings support those in previous studies that hypothesized that completely clipped IAs have an extremely low risk of recurrence. Conversely, the results highlight the significant risk posed by incompletely clipped IAs. Young patients with initial large IAs and incomplete obliteration have an especially high risk for IA recurrence and therefore should be monitored more closely.

Impact of Very Small Aneurysm Size and Anterior Communicating Segment Location on Outcome after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Very small anterior communicating artery aneurysms (vsACoA) of <5 mm in size are detected in a considerable number of patients with aneurysmal subarachnoid hemorrhage (aSAH). Single-center studies report that vsACoA harbor particular risks when treated. OBJECTIVE: To assess the clinical and radiological outcome(s) of patients with aSAH diagnosed with vsACoA after aneurysm treatment and at discharge. METHODS: Information on n = 1868 patients was collected in the Swiss Subarachnoid Hemorrhage Outcome Study registry between 2009 and 2014. The presence of a new focal neurological deficit at discharge, functional status (modified Rankin scale), mortality rates, and procedural complications (in-hospital rebleeding and presence of a new stroke on computed tomography) was assessed for vsACoA and compared with the results observed for aneurysms in other locations and with diameters of 5 to 25 mm. RESULTS: This study analyzed n = 1258 patients with aSAH, n = 439 of which had a documented ruptured ACoA. ACoA location was found in 38% (n = 144/384) of all very small ruptured aneurysms. A higher in-hospital bleeding rate was found in vsACoA compared with non-ACoA locations (2.8 vs 2.1%), especially when endovascularly treated (2.1% vs 0.5%). In multivariate analysis, aneurysm size of 5 to 25 mm, and not ACoA location, was an independent risk factor for a new focal neurological deficit and a higher modified Rankin scale at discharge. Neither very small aneurysm size nor ACoA location was associated with higher mortality rates at discharge or the occurrence of a peri-interventional stroke. CONCLUSION: Very small ruptured ACoA have a higher in-hospital rebleeding rate but are not associated with worse morbidity or mortality.

Incidence and Outcome of Peri-interventional Vasospasm During Endovascular or Microsurgical Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Peri-interventional vasospasm (PIVS) is associated with high risk of delayed cerebral vasospasm (DCVS), delayed cerebral ischemia, and poor outcome after aneurysmal subarachnoid hemorrhage. However, the incidence rate associated with treatment of unruptured intracranial aneurysm (UIA) remains unclear. OBJECTIVE: To define the incidence and clinical significance of PIVS in UIA repair based on intraoperative/peri-interventional digital subtraction angiography. METHODS: A consecutive series of 205 patients who underwent UIA treatment by means of microsurgical clipping (n = 109) or endovascular coil embolization (n = 96) was assessed for the occurrence of PIVS. In all cases, PIVS was detected, measured, and classified using intraoperative/peri-interventional digital subtraction angiography. Severity of PIVS, association of PIVS with the development of DCVS, and neurological outcome were analyzed. RESULTS: Intraoperative PIVS was present in n = 14/109 (13%) patients with microsurgical clipping. Of these, caliber irregularities were mild (n = 10), moderate (n = 3), and severe (n = 1). In endovascularly treated patients, 6/96 (6%) developed PIVS, which were either mild (n = 3) or moderate (n = 3). Management in all cases included immediate intensive blood pressure management and application of topical papaverine or intra-arterial nimodipine immediately on detection of PIVS. No patient developed DCVS or lasting neurological deficits attributable to PIVS. CONCLUSION: This series revealed a relatively high overall incidence of PIVS (10%). However, no association of PIVS with the development of DCVS or poor outcome was found. In contrast to ruptured intracranial aneurysms, PIVS in unruptured intracranial aneurysms-if immediately and adequately addressed-seems to be benign and without sequelae for patient's functional outcome.

Elevated perioptic lipocalin-type prostaglandin D synthase concentration in patients with idiopathic intracranial hypertension.

The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l; P < 0.0001, Mann-Whitney U-test). These measurements demonstrate a change and imbalance in the biochemical environment of the optic nerve. Its possible effect is discussed.

Testing the applicability and performance of Auto ML for potential applications in diagnostic neuroradiology.

To investigate the applicability and performance of automated machine learning (AutoML) for potential applications in diagnostic neuroradiology. In the medical sector, there is a rapidly growing demand for machine learning methods, but only a limited number of corresponding experts. The comparatively simple handling of AutoML should enable even non-experts to develop adequate machine learning models with manageable effort. We aim to investigate the feasibility as well as the advantages and disadvantages of developing AutoML models compared to developing conventional machine learning models. We discuss the results in relation to a concrete example of a medical prediction application. In this retrospective IRB-approved study, a cohort of 107 patients who underwent gross total meningioma resection and a second cohort of 31 patients who underwent subtotal resection were included. Image segmentation of the contrast enhancing parts of the tumor was performed semi-automatically using the open-source software platform 3D Slicer. A total of 107 radiomic features were extracted by hand-delineated regions of interest from the pre-treatment MRI images of each patient. Within the AutoML approach, 20 different machine learning algorithms were trained and tested simultaneously. For comparison, a neural network and different conventional machine learning algorithms were trained and tested. With respect to the exemplary medical prediction application used in this study to evaluate the performance of Auto ML, namely the pre-treatment prediction of the achievable resection status of meningioma, AutoML achieved remarkable performance nearly equivalent to that of a feed-forward neural network with a single hidden layer. However, in the clinical case study considered here, logistic regression outperformed the AutoML algorithm. Using independent test data, we observed the following classification results (AutoML/neural network/logistic regression): mean area under the curve = 0.849/0.879/0.900, mean accuracy = 0.821/0.839/0.881, mean kappa = 0.465/0.491/0.644, mean sensitivity = 0.578/0.577/0.692 and mean specificity = 0.891/0.914/0.936. The results obtained with AutoML are therefore very promising. However, the AutoML models in our study did not yet show the corresponding performance of the best models obtained with conventional machine learning methods. While AutoML may facilitate and simplify the task of training and testing machine learning algorithms as applied in the field of neuroradiology and medical imaging, a considerable amount of expert knowledge may still be needed to develop models with the highest possible discriminatory power for diagnostic neuroradiology.

Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis.

Importance: The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood. Objective: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss. Design, Setting, and Participants: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021. Exposures: According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability. Main Outcomes and Measures: Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models. Results: Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, -0.36; 95% CI, -0.60 to -0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, -0.18; 95% CI, -0.34 to -0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity. Conclusions and Relevance: Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.

Case Report: Cerebrospinal Fluid Dynamics in the Optic Nerve Subarachnoid Space and the Brain Applying Diffusion Weighted MRI in Patients With Idiopathic Intracranial Hypertension-A Pilot Study.

Purpose: The aim of this study was to examine the cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) and the brain in patients with idiopathic intracranial hypertension (IIH) and papilledema (PE) compared to healthy controls by applying non-invasive diffusion-weighted MRI. Methods: A retrospective analysis of diffusion-weighted MR images of 5 patients with IIH (10 ONs), mean age: 31 ± 10 years (5 women), and 11 healthy controls (22 ONs, mean age: 60 ± 13 years, 5 women) was performed. The flow velocity flow-range ratio (FRR) between the intracranial cavity and the SAS of the ON was calculated in both groups and then compared. Results: The mean FRR was 0.55 ± 0.08 in patients with IIH and 0.63 ± 0.05 in healthy controls. The difference between patients with IIH and healthy controls was statistically significant (p < 0.05). Conclusions: The CSF flow velocity was decreased in patients with IIH with PE compared to healthy controls. The reduced CSF flow dynamics might be involved in the pathophysiology of PE in IIH and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON. Summary: Idiopathic intracranial hypertension is a neurological disease, where vision loss is the most feared complication of this disorder. The pathophysiology of IIH is not fully understood but is strongly linked to a reduced uptake of CSF into the central dural sinus veins. In this study, we examined the CSF flow rates in the SAS ON and the brain in patients with IIH and PE compared to healthy controls by applying non-invasive diffusion-weighted MRI. Knowing about the flow ratio of CSF may be of clinical relevance for the treatment decisions of IIH. If medical treatment fails, surgical options for lowering the ICP pressure need to be taken into consideration. As the primary goal of treatment is to prevent the loss of vision and visual field, it is important to know whether the communication of CSF between the intracranial CSF and the CSF in the perioptic space is intact. We showed that the CSF flow velocity was decreased in IIH patients with PE compared to healthy controls. The reduced CSF flow might be involved in the pathophysiology of PE in IIH, and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON.

Interrater and intrarater agreement superior for three-dimensional digital subtraction angiography (3D-DSA) over 2D-DSA classification for detecting remnants after intracranial aneurysm clipping, a GRRAS Reliability and Agreement Study.

BACKGROUND: Growing evidence suggests that three-dimensional digital subtraction angiography (3D-DSA) is superior to 2D-DSA in detection of intracranial aneurysm (IA) remnants after clipping. With a simple, practical quantitative scale proposed to measure maximal remnant dimension on 3D-DSA, this study provides a rigorous interrater and intrarater reliability and agreement study comparing this newly established scale with a commonly used (Sindou) 2D-DSA scale. METHOD: Records of 43 patients with clipped IAs harboring various sized remnants who underwent 2D- and 3D-DSA between 2012 and 2018 were evaluated. Using the 2D and 3D scales, six raters scored these remnants and repeated the scoring task 8 weeks later. Interrater and intrarater agreement for both grading schemes were calculated using kappa (κ) statistics. RESULTS: Interrater agreement was highly significant, yielding κ-values at 95% CI (p = 0.000) of 0.225 for the first [0.185; 0.265] and 0.368 s [0.328; 0.408] time points for 2D-DSA and values of 0.700 for the first [0.654; 0.745] and 0.776 s [0.729; 0.822] time points for 3D-DSA. Intrarater agreement demonstrated κ-values between 0.139 and 0.512 for 2D-DSA and between 0.487 and 0.813 for 3D-DSA scores. CONCLUSION: Interrater and intrarater agreement was minimal or weak for 2D-DSA scores, but strong for 3D-DSA scores. We propose that baseline 3D-DSA characterization may prove more reliable when categorizing clipped IA remnants for purposes of risk stratification and lifelong follow-up.