Non-ischemic cerebral enhancing (NICE) lesions after flow diversion for intracranial aneurysms: a multicenter study.

BACKGROUND: Non-ischemic cerebral enhancing (NICE) lesions have been reported as a rare complication of various neuroendovascular procedures, but information on their incidence after flow diversion is scant. It is unclear if specific devices or novel coating technologies may impact their occurrence. METHODS: We conducted a multicenter study on the incidence of NICE lesions after flow diverter (FD) implantation for cerebral aneurysm treatment. RESULTS: Eight centers identified 15 patients and provided detailed data. The clinical presentation ranged from asymptomatic to hemiplegia and cognitive impairment. The mean time to diagnosis after treatment was 65.1±101.5 days. Five centers disclosed information on all of their 1201 FD procedures during the inclusion period (2015-2022), during which 12 patients were diagnosed with NICE lesions in these institutions-that is, an incidence of 1%. FD coatings did not increase the incidence (6/591 patients (1%) treated with surface-modified FD vs 6/610 patients (1%) treated with bare FD; P=1.00). Significantly increased rates of 3.7% (6 cases in 161 procedures; P<0.01) and 3.3% (5 cases in 153 procedures; P<0.01) were found with stents of two specific product lines. The use of one product line was associated with a significantly lower incidence (0 cases in 499 procedures (0%); P<0.01). CONCLUSIONS: Novel stent coatings are not associated with an increased incidence of NICE lesions. The incidence rate of 1% suggests that these lesions may occur more often after flow diversion than after other endovascular treatments. We found a concerning accumulation of NICE lesion cases when FDs from two product families were used.

Reference Values of Cerebral Artery Diameters of the Anterior Circulation by Digital Subtraction Angiography: A Retrospective Study.

A threshold-based classification of cerebral vasospasm needs reference values for intracranial vessel diameters on digital subtraction angiography (DSA). We aimed to generate adjusted reference values for this purpose by retrospectively analyzing angiograms and potential influencing factors on vessel diameters. Angiograms of the anterior circulation were evaluated in 278 patients aged 18−81 years. The vessel diameters of 453 angiograms (175 bilateral) were gathered from nine defined measuring sites. The effect sizes of physical characteristics (i.e., body weight and height, body mass index, gender, age, and cranial side) and anatomical variations were calculated with MANOVA. Segments bearing aneurysms were excluded for the calculation of reference values. Adjusted vessel diameters were calculated via linear regression analysis of the vessel diameter data. Vessel diameters increased with age and body height. Male and right-sided vessels were larger in diameter. Of the anatomical variations, only the hypoplastic/aplastic A1 segment had a significant influence (p < 0.05) on values of the anterior cerebral artery and the internal carotid artery with a small effect size (|ω2| > 0.01) being excluded from the reference values. We provide gender-, age-, and side-adjusted reference values and nomograms of arterial vessel diameters in the anterior circulation.

The Supratrochlear Artery Sign-A New Piece in the Puzzle of Cerebral Vasospasm.

BACKGROUND: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) has been extensively investigated, but the impact of collateralization remains unclear. We investigated the predictive value of collateral activation for delayed cerebral ischemia (DCI)-related infarctions and functional outcome. METHODS: Data from 43 patients with CVS (January 2014 to August 2021) were evaluated for the angiographic presence of leptomeningeal and ophthalmic collaterals (anterior falcine artery (AFA), supratrochlear artery (STA), dorsal nasal artery (DNA)) on internal carotid artery angiograms. Vasospasm-related infarction and the modified Rankin Scale (mRS) score after six months were chosen as the endpoints. RESULTS: 77% of the patients suffered from DCI-related infarctions. In 233 angiograms (at hospitalization, before spasmolysis, after six months), positive vessel signs were observed in 31 patients for STA, 35 for DNA, and 31 for AFA. The STA sign had the highest positive (84.6%) and negative (85.7%) predictive value for unfavorable outcome (mRS 4-6) in patients aged ≥50 years. DNA and AFA signs were not meaningful predictors for either endpoint. Leptomeningeal collaterals showed a positive Pearson's correlation with the STA sign in 87.5% (p = 0.038) without providing any prediction for either endpoint. CONCLUSIONS: The STA sign is associated with clinical outcome in patients with CVS after SAH aged ≥50 years, and was correlated with the occurrence of leptomeningeal collaterals.

Nimodipine vs. Milrinone - Equal or Complementary Use? A Retrospective Analysis.

Background: Cerebral vasospasm (CVS) continues to account for high morbidity and mortality in patients surviving the initial aneurysmal subarachnoid hemorrhage (SAH). Nimodipine is the only drug known to reduce delayed cerebral ischemia (DCI), but it is believed not to affect large vessel CVS. Milrinone has emerged as a promising option. Our retrospective study focused on the effectiveness of the intra-arterial application of both drugs in monotherapy and combined therapy. Methods: We searched for patients with aneurysmal SAH, angiographically confirmed CVS, and at least one intra-arterial pharmacological angioplasty. Ten defined vessel sections on angiograms were assessed before and after vasodilator infusion. The improvement in vessel diameters was compared to the frequency of DCI-related cerebral infarction before hospital discharge and functional outcome reported as the modified Rankin Scale (mRS) score after 6 months. Results: Between 2014 and 2021, 132 intra-arterial interventions (144 vascular territories, 12 bilaterally) in 30 patients were analyzed for this study. The vasodilating effect of nimodipine was superior to milrinone in all intradural segments. There was no significant intergroup difference concerning outcome in mRS (p = 0.217). Only nimodipine or the combined approach could prevent DCI-related infarction (both 57.1%), not milrinone alone (87.5%). Both drugs induced a doubled vasopressor demand due to blood pressure decrease, but milrinone alone induced tachycardia. Conclusions: The monotherapy with intra-arterial nimodipine was superior to milrinone. Nimodipine and milrinone may be used complementary in an escalation scheme with the administration of nimodipine first, complemented by milrinone in cases of severe CVS. Milrinone monotherapy is not recommended.

Standardized Classification of Cerebral Vasospasm after Subarachnoid Hemorrhage by Digital Subtraction Angiography.

BACKGROUND: During the last decade, cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) was a current research focus without a standardized classification in digital subtraction angiography (DSA). This study was performed to investigate a device-independent visual cerebral vasospasm classification for endovascular treatment. METHODS: The analyses are DSA based rather than multimodal. Ten defined points of intracranial arteries were measured in 45 patients suffering from cerebral vasospasm after SAH at three time points (hospitalization, before spasmolysis, control after six months). Mathematical clustering of vessel diameters was performed to generate four objective grades for comparison. Six interventional neuroradiologists in two groups scored 237 DSAs after a new visual classification (grade 0-3) developed on a segmental pattern of vessel contraction. For the second group, a threshold-based criterion was amended. RESULTS: The raters had a reproducibility of 68.4% in the first group and 75.2% in the second group. The complementary threshold-based criterion increased the reproducibility by about 6.8%, while the rating deviated more from the mathematical clustering in all grades. CONCLUSIONS: The proposed visual classification scheme of cerebral vasospasm is suitable as a standard grading procedure for endovascular treatment. There is no advantage of a threshold-based criterion that compensates for the effort involved. Automated vessel analysis is superior to compare inter-group results in research settings.

Endovascular Treatment of Intracranial Aneurysms in Small Peripheral Vessel Segments-Efficacy and Intermediate Follow-Up Results of Flow Diversion With the Silk Vista Baby Low-Profile Flow Diverter.

Background and Purpose: Low-profile flow diverter stents (FDS) quite recently amended peripheral segments as targets for hemodynamic aneurysm treatment; however, reports on outcomes, especially later than 3 months, are scarce. This study therefore reports our experience with the novel silk vista baby (SVB) FDS and respective outcomes after 8 and 11 months with special respect to specific adverse events. Materials and Methods: Forty-four patients (mean age, 53 years) harboring 47 aneurysms treated with the SVB between June 2018 and December 2019 were included in our study. Clinical, procedural, and angiographic data were collected. Follow-ups were performed on average after 3, 8, and 11 months, respectively. Treatment effect was assessed using the O'Kelly Marotta (OKM) grading system. Results: Overall, angiographic follow-ups were available for 41 patients/45 aneurysms. Occlusion or significant reduction in aneurysmal perfusion (OKM: D1, B1-B3 and A2-A3) was observed in 98% of all aneurysms after 8 months. Only 2% of the treated aneurysms remained morphologically unaltered and without an apparent change in perfusion (OKM A1). Adverse events in the early post-interventional course occurred in seven patients; out of them, mRS-relevant morbidity at 90 days related to FDS treatment was observable in two patients. One death occurred in the context of severe SAH related to an acutely ruptured dissecting aneurysm of the vertebral artery. Conclusion: The SVB achieves sufficient occlusion rates of intracranial aneurysms originating from peripheral segments, which are comparable to prior established conventional FDS with acceptably low complication rates. However, alteration of a hemodynamic equilibrium in distal localizations requires special attention to prevent ischemic events.

Evaluation of the interrater and intermethod agreement of the German multiparametric ultrasound criteria for the grading of internal carotid artery stenosis.

PURPOSE: The interdisciplinary German guidelines for the diagnosis and treatment of internal carotid artery stenosis (ICAS) recommend a multiparametric approach for the sonographic grading of extracranial ICAS. The aim of this study is to evaluate the interrater and intermethod agreement of this elaborated sonographic approach with different angiographic modalities. METHODS: Patients with extracranial ICAS were examined twice with colour-coded duplex sonography (CDS) by two experienced vascular neurologists. Each of the ten criteria and the resulting stenotic value were assessed. Grading of ICAS based on the multiparametric ultrasound criteria was compared with different angiography modalities (magnetic resonance angiography (MRA), computed tomography angiography (CTA), digital subtraction angiography (DSA)). RESULTS: Seventy-four consecutive patients with 91 extracranial ICAS were recruited from our stroke unit and neurovascular outpatient clinic. Interrater agreement for each single ultrasound criterion ranged from moderate to excellent (for the peak systolic velocity). Concerning the absolute stenotic value of ICAS, an excellent agreement between both ultrasound examiners with an ICC of 0.91 (range 0.87-0.94; p < 0.001) was found. In 96% of ICAS, the difference between the stenotic values was ≤ 10%. Intermethod agreements between CDS and DSA, CTA, and MRA were also good for both sonographers. CONCLUSION: Strictly adhering to the multiparametric "DEGUM ultrasound criteria", we found an excellent interrater agreement and a good intermethod agreement compared with angiography for the sonographic grading of extracranial ICAS. Thus, multiparametric CDS is in particular suitable for the follow up of extracranial ICAS even when examinations are done by different sonographers.

Single-Center Experience With the Bare p48MW Low-Profile Flow Diverter and Its Hydrophilically Covered Version for Treatment of Bifurcation Aneurysms in Distal Segments of the Anterior and Posterior Circulation.

Background and Purpose: Flow diversion has profoundly changed the way aneurysms are treated. However, it conventionally requires dual antiplatelet medication and has yet been considered off-label use in the posterior circulation or within peripheral vessels of the anterior circulation. Here, we report our experience with the p48MW/p48MW hydrophilic coating (HPC) in the anterior and posterior circulation. This novel low-profile flow diverter is specifically designed for treatment of small peripheral vessels, and the p48MW HPC has an anti-thrombotic polymer coating, which allows application of a single antiplatelet function medication in conditions that expectably require further surgery. Materials and Methods: Thirty-two patients were prospectively included. Twenty-six treatments were performed with one flow diverter, four required two overlapping flow diverters, one case demanded three overlapping flow diverters, and in one case, extensive dissecting aneurysm telescoping with eight flow diverters was necessary. Twenty-two complex bifurcation aneurysms were treated. Three months' follow-up was available for 14 patients. Results: Deployment was uneventful in all cases. In four cases, undersizing was unavoidable and resulted in significant shortening of the flow diverter, which demanded implantation of further flow diverters to sufficiently treat the target aneurysm. Three flow diverters required balloon angioplasty for optimal wall approximation. All parent vessels remained patent. Available 3-month follow-up studies showed decreased influx or delayed washout in all aneurysms; none was occluded completely. There were no device-related clinical complications. Conclusions: Implantation of the p48MW/p48MW HPC is safe and effective for treatment of distally located cerebral aneurysms. Considering the reported rates of ischemic complications associated with flow diversion of complex bifurcation aneurysms, the p48MW/p48MW HPC potentially provides increased safety for complex bifurcation aneurysms in the anterior and posterior circulation.

CSF Surfactant Protein Changes in Preterm Infants After Intraventricular Hemorrhage.

Introduction: Surfactant proteins (SP) have been shown to be inherent proteins of the human CNS and are altered during acute and chronic disturbances of CSF circulation. Aim of the study was to examine the changes of surfactant protein concentrations in CSF of preterm babies suffering from intraventricular hemorrhage. Patients and Methods: Consecutive CSF samples of 21 preterm infants with intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were collected at primary intervention, after 5-10 days and at time of shunt insertion ~50 days after hemorrhage. Samples were analyzed for surfactant proteins A, B, C, and G by ELISA assays and the results were compared to 35 hydrocephalus patients (HC) without hemorrhage and 6 newborn control patients. Results and Discussion: Premature patients with IVH showed a significant elevation of surfactant proteins SP-A, C, and G compared to HC and control groups: mean values for the respective groups were SP-A 4.19 vs. 1.08 vs. 0.38 ng/ml. Mean SP-C 3.63 vs. 1.47 vs. 0.48 ng/ml. Mean SP-G 3.86 vs. 0.17 vs. 0.2 ng/ml. SP-A and G concentrations were slowly falling over time without reaching normal values. SP-C levels declined faster following neurosurgical interventions and reached levels comparable to those of hydrocephalus patients without hemorrhage. Conclusion: Intraventricular hemorrhages of premature infants cause posthemorrhagic CSF flow disturbance and are associated with highly significant elevations of surfactant proteins A, C, and G independent of total CSF protein concentrations.

Basilar artery origin of an orbital artery - A rare variant and review of the embryology of the orbital arterial supply.

We present a patient with separation of the arterial supply to the globe and the extra-ocular muscles. The ophthalmic artery originates from the typical adult location and supplies only the globe. Arising from the basilar artery was a branch that supplies the extra-ocular muscles. There was no apparent connection between these vessels around the optic nerve and no evidence of supply from the external carotid artery. We discuss the embryology of the ophthalmic artery from the point of view of Padget and Lasjaunias and offer our opinion on the on-going controversy. We believe this is the first case to highlight the trigeminal-primitive maxillary-stapedial anastamotic pathway.

Flow diversion in challenging vascular anatomies: the use of low profile stent retrievers for safe and accurate positioning of the microcatheter.

BACKGROUND: Hemodynamic therapy with Flow-Diverters has become a fundamental option for treatment of cerebral aneurysms. A major obstacle of Flow-Diverters is the comparatively stiff microcatheter required for implantation. Consequentially, maneuverability is limited and primary catheterization of peripheral targets may be difficult or even futile in challenging vascular anatomies. To overcome this, a highly navigable microcatheter must be used to attain the desired vascular segment, followed by a hardly controllable exchange-maneuver via a long microwire, involving a high risk for wire-perforation. Our study aimed to investigate the value of low-profile stent-retrievers as a railway for introduction of the required microcatheter, which allows to maintain a stable endovascular position and reduce the risk for procedural vessel injury. METHODS: 14cases (8females, mean-age 59y) of Flow-Diverter-Implantation requiring the use of a low-profile stent-retriever were reviewed. All cases featured a challenging vascular anatomy. After micro-catheterization of the desired segment, the stent-retriever was carefully deployed as an anchor in a secure, distal location. In all cases a pREset/LITE-stent-retriever was used for introduction of the equipment required for implantation. RESULTS: In all cases the anchoring-maneuver was performed without technical complications. The stent-retrievers maintained a stable position after deployment in all situations. No potential traumatic sudden movements of the microcatheter occurred. No procedure-related perforations, dissections or vasospasms were observable during the interventions or their aftermath. CONCLUSIONS: In our experience the stent-retriever-anchoring-maneuver represents a potentially essential and safe amendment for flow diverter treatment in technically challenging situations.

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm.

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment.

Flow diversion beyond the circle of Willis: endovascular aneurysm treatment in peripheral cerebral arteries employing a novel low-profile flow diverting stent.

BACKGROUND: Flow diversion (FD) has emerged as superior minimally invasive therapy for cerebral aneurysms. However, aneurysms of small peripheral vessel segments have not yet been adequately treatable. More specifically, currently established devices necessitate large microcatheters which impede atraumatic maneuvering. The Silk Vista Baby (SVB), a novel flow diverter, offers the as yet unique feature of deliverability via a 0.017 inch microcatheter. This study reports our first experience with the SVB in challenging intracranial vessels employing a vessel-specific tailored microcatheter strategy. MATERIALS AND METHODS: 25 patients (27 aneurysms) were prospectively included. A total of 30 SVBs were employed, predominantly targeting demanding aneurysms of the anterior communicating artery complex. The efficacy of the FD was assessed using two-dimensional vector-based perfusion and conventional digital subtraction angiography (DSA) after implantation and at the first follow-up at 3 months. The first follow-up was available in 22 patients. RESULTS: All devices were implanted without technical or clinical complications. Eleven treatments were performed using the recommended Headway 17. In 14 interventions the even more maneuverable Excelsior SL10 was used, which was previously tried and tested for safety 'in vitro' as an alternative delivery system. Aneurysmal influx was strongly reduced after implantation. All parent vessels remained patent. 17/27 aneurysms were completely occluded at first follow-up (∼2.7 months), 6/27 aneurysms showed decreased influx or delayed washout and one remained unchanged. In three cases follow-up DSAs are remaining. CONCLUSIONS: SVB provides enhanced controllability in vulnerable segments beyond the circle of Willis. Smaller variants (2.25 mm and 2.75 mm) can safely be implanted via the superiorly navigable Excelsior SL10. Hence, the SVB represents the next evolutionary step in minimally invasive treatment of cerebral aneurysms.

Rheologically Essential Surfactant Proteins of the CSF Interacting with Periventricular White Matter Changes in Hydrocephalus Patients - Implications for CSF Dynamics and the Glymphatic System.

Surfactant proteins (SP) are multi-systemic proteins playing crucial roles in the regulation of rheological properties of physiological fluids, host defense, and the clearance of potentially harmful metabolites. Hydrocephalus patients suffer from disturbed central nervous system (CNS) fluid homeostasis and exhibit remarkably altered SP concentrations within the cerebrospinal fluid (CSF). A connection between CSF-SPs, CSF flow, and ventricular dilatation, a morphological hallmark of hydrocephalus, has been reported previously. However, currently there are no studies investigating the link between rheologically active SPs and periventricular white matter changes caused by impaired CSF microcirculation in hydrocephalic conditions. Thus, the aim of this study was to assess their possible relationships. The present study included 47 individuals (27 healthy subjects and 20 hydrocephalus patients). CSF specimens were analyzed for concentrations of SP-A, SP-C, and SP-D by using enzyme-linked immunosorbent assays (ELISAs). Axial T2w turbo inversion recovery magnitude (TIRM) magnetic resonance imaging was employed in all cases. Using a custom-made MATLAB-based tool for quantification of magnetic resonance signal intensities in the brain, parameters related to disturbed deep white matter CSF microcirculation were estimated (TIRM signal intensity (SI)-mean, minimum, maximum, median, mode, standard deviation, and percentiles, p10th, p25th, p75th, p90th, as well as kurtosis, skewness, and entropy of the SI distribution). Subsequently, statistical analysis was performed (IBM SPSS 24™) to identify differences between hydrocephalic patients and healthy individuals and to further investigate the connections between CSF-SP changes and deep white matter signal intensities. SP-A (0.38 ± 0.23 vs. 0.76 ± 0.49 ng/ml) and SP-C (0.54 ± 0.28 vs. 1.27 ± 1.09 ng/ml) differed between healthy controls and hydrocephalus patients in a statistically significant manner. Also, corresponding quantification of white matter signal intensities revealed statistically significant differences between hydrocephalus patients and healthy individuals: SImean (370.41 ± 188.15 vs. 222.27 ± 99.86, p = 0.001), SImax (1115.30 ± 700.12 vs. 617.00 ± 459.34, p = 0.005), SImedian (321.40 ± 153.17 vs. 209.52 ± 84.86, p = 0.001), SImode (276.55 ± 125.63 vs. 197.26 ± 78.51, p = 0.011), SIstd (157.09 ± 110.07 vs. 81.71 ± 64.94, p = 0.005), SIp10 (229.10 ± 104.22 vs. 140.00 ± 63.12, p = 0.001), SIp25 (266.95 ± 122.62 vs. 175.63 ± 71.42, p = 0.002), SIp75 (428.80 ± 226.88 vs. 252.19 ± 110.91, p = 0.001), SIp90 (596.47 ± 345.61 vs. 322.06 ± 176.00, p = 0.001), skewness (1.19 ± 0.68 vs. 0.43 ± 1.19, p = 0.014), and entropy (5.36 ± 0.37 vs. 4.92 ± 0.51, p = 0.002). There were no differences regarding SP-D levels in hydrocephalus patients vs. healthy controls. In the acute hydrocephalic subgroup, correlations were as follows: SP-A showed a statistically significant correlation with SImax (r = 0.670, p = 0.024), SIstd (r = 0.697, p = 0.017), SIp90 (r = 0.621, p = 0.041), and inverse correlation with entropy (r = - 0.700, p = 0.016). SP-C correlated inversely with entropy (r = - 0.686, p = 0.020). For the chronic hydrocephalus subgroup, the following correlations were identified: SP-A correlated with kurtosis of the TIRM histogram (r = - 0.746, p = 0.021). SP-C correlated with SImean (r = - 0.688, p = 0.041), SImax (r = - 0.741, p = 0.022), SImedian (r = - 0.716, p = 0.030), SImode (r = - 0.765, p = 0.016), SIstd (r = - 0.671, p = 0.048), SIp25 (r = - 0.740, p = 0.023), SIp75 (r = - 0.672, p = 0.048), and SIp90 (r = - 0.667, p = 0.050). SP-D apparently does not play a major role in CSF fluid physiology. SP-A and SP-C are involved in different aspects of CNS fluid physiology. SP-A appears to play an essential compensatory role in acute hydrocephalus and seems less involved in chronic hydrocephalus. In contrary, SP-C profile and white matter changes are remarkably connected in CSF of chronic hydrocephalus patients. Considering the association between CSF flow phenomena, white matter changes, and SP-C profiles, the latter may especially contribute to the regulation of paravascular glymphatic physiology.

Segment Occlusion vs. Reconstruction-A Single Center Experience With Endovascular Strategies for Ruptured Vertebrobasilar Dissecting Aneurysms.

Objective: Ruptured dissecting aneurysms of the intracranial vertebral arteries exhibit an extraordinarily high risk for morbidity and mortality and are prone to re-rupture. Therefore, early treatment is mandatory to induce stagnation of the critical dynamic mural process. Appropriate endovascular approaches are segment sacrifice and reconstruction, however, both carry specific risks and benefits. To date most studies discuss only one of these approaches and focus on one specific device or technique. Therefore, our study aimed to present our experiences with both techniques, providing a considered approach on when to perform endovascular reconstruction or sacrifice. Materials and Methods: We retrospectively reviewed patients with subarachnoid hemorrhage in our database, suffering from dissecting aneurysms of the intradural vertebral arteries and treated endovascularly in the acute setting. A total of 16 cases were included. Clinical history, radiologic findings and outcomes were analyzed. Results: In 7 patients a reconstructive approach was chosen with 4 of them receiving stent-assisted coiling as primary strategy. One of the 7 patients suffered early re-bleeding due to progression of the dissection and therefore treatment was augmented with implantation of 2 flow diverters. The remaining 2 patients were primarily treated with flow diverters in telescoping technique. In 9 patients a deconstructive approach was followed: 6 patients were treated with proximal coil-occlusion of the V4 segment, 3 patients received distal coiling of the V4 segment. Two patients died (GOS 1) in the subacute stage due to sequelae of recurrent episodes of raised intracranial pressure and parenchymal hemorrhage. Two patients kept severe disability (GOS 3), six patients had moderate disability (GOS 4) and seven patients showed full recovery (GOS 5). None of the patients suffered from a procedural or postprocedural ischemic stroke. Conclusions: In patients with good collateral vascularization, proximal, or distal partial segment sacrifice via with endovascular coil occlusion seems to yield the best risk-benefit ratio for treatment of ruptured dissecting V4 aneurysms, especially since no continued anticoagulation is required and possibly essential surgery remains feasible in this scenario. If possible, PICA occlusion should be avoided-although even proximal PICA occlusion can become necessary, when weighing against the risk of an otherwise untreated ruptured V4 dissecting aneurysm. Contrarily, if the dominant V4 segment is affected, the hemodynamic asymmetry prohibits occlusion and necessitates reconstruction of the respective segment. For this, implants with high metal coverage treating the entire affected segment appear to be the most promising approach.

Localization, Occurrence, and CSF Changes of SP-G, a New Surface Active Protein with Assumable Immunoregulatory Functions in the CNS.

Conventional surfactant proteins (A, B, C, and D) are important players of the innate immunity in the central nervous system and serve as effective regulators of cerebrospinal fluid rheology, probably being involved in clearance of detrimental metabolites like beta-amyloid and phospho-tau. Recently, a novel surfactant protein, SP-G, was described in kidneys and peripheral endocrine and exocrine glands. So far, its presence and possible functions in the central nervous system are unknown. Therefore, our study aimed to elucidate the presence of SP-G in the brain and its concentration in normal and pathologic samples of cerebrospinal fluid in order to gain first insight into its regulation and possible functions. A total of 121 samples of human cerebrospinal fluid (30 controls, 60 hydrocephalus patients, 7 central nervous system infections, and 24 brain hemorrhage patients) and 21 rat brains were included in our study. CSF samples were quantified using a commercially available ELISA system. Results were analyzed statistically using SPSS 22, performing Spearman Rho correlation and ANOVA with Dunnett's post hoc analysis. Rat brains were investigated via immunofluorescence to determine SP-G presence and colocalization with common markers like aquaporin-4, glial fibrillary acidic protein, platelet endothelial adhesion molecule 1, and neuronal nuclear antigen. SP-G occurs associated with brain vessels, comparable to other conventional SPs, and is present in a set of cortical neurons. SP-G is furthermore actively produced by ependymal and choroid plexus epithelium and secreted into the cerebrospinal fluid. Its concentrations are low in control subjects and patients suffering from aqueductal stenosis, higher in normal pressure hydrocephalus (p < 0.01), and highest in infections of the central nervous system and brain hemorrhage (p < 0.001). Interestingly, SP-G did correlate with total CSF protein in patients with CNS infections and hemorrhage, but not with cell count. Based on the changes in CSF levels of SP-G in hydrocephalus, brain hemorrhage, and CNS infections as well as its abundance at CSF flow-related anatomical structures closely associated with immunological barrier systems, importance for CSF rheology, brain waste clearance, and host defense is assumable. Thus, SP-G is a potential new CSF biomarker, possibly not only reflecting aspects of CNS innate immune responses, but also rheo-dynamically relevant changes of CSF composition, associated with CSF malabsorbtion. However, further studies are warranted to validate our findings and increase insight into the physiological importance of SP-G in the CNS.

Histogram Profiling of Postcontrast T1-Weighted MRI Gives Valuable Insights into Tumor Biology and Enables Prediction of Growth Kinetics and Prognosis in Meningiomas.

BACKGROUND: Meningiomas are the most frequently diagnosed intracranial masses, oftentimes requiring surgery. Especially procedure-related morbidity can be substantial, particularly in elderly patients. Hence, reliable imaging modalities enabling pretherapeutic prediction of tumor grade, growth kinetic, realistic prognosis, and-as a consequence-necessity of surgery are of great value. In this context, a promising diagnostic approach is advanced analysis of magnetic resonance imaging data. Therefore, our study investigated whether histogram profiling of routinely acquired postcontrast T1-weighted images is capable of separating low-grade from high-grade lesions and whether histogram parameters reflect Ki-67 expression in meningiomas. MATERIAL AND METHODS: Pretreatment T1-weighted postcontrast volumes of 44 meningioma patients were used for signal intensity histogram profiling. WHO grade, tumor volume, and Ki-67 expression were evaluated. Comparative and correlative statistics investigating the association between histogram profile parameters and neuropathology were performed. RESULTS: None of the investigated histogram parameters revealed significant differences between low-grade and high-grade meningiomas. However, significant correlations were identified between Ki-67 and the histogram parameters skewness and entropy as well as between entropy and tumor volume. CONCLUSIONS: Contrary to previously reported findings, pretherapeutic postcontrast T1-weighted images can be used to predict growth kinetics in meningiomas if whole tumor histogram analysis is employed. However, no differences between distinct WHO grades were identifiable in out cohort. As a consequence, histogram analysis of postcontrast T1-weighted images is a promising approach to obtain quantitative in vivo biomarkers reflecting the proliferative potential in meningiomas.

Histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging can predict histopathological findings including proliferation potential, cellularity, and nucleic areas in head and neck squamous cell carcinoma.

Our purpose was to analyze possible associations between histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging DCE MRI and histopathological findings like proliferation index, cell count and nucleic areas in head and neck squamous cell carcinoma (HNSCC). 30 patients (mean age 57.0 years) with primary HNSCC were included in the study. In every case, histogram analysis parameters of Ktrans, Ve, and Kep were estimated using a mathlab based software. Tumor proliferation index, cell count, and nucleic areas were estimated on Ki 67 antigen stained specimens. Spearman's non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. KI 67 correlated with Ktrans min (p = -0.386, P = 0.043) and s Ktrans skewness (p = 0.382, P = 0.045), Ve min (p = -0.473, P = 0.011), Ve entropy (p = 0.424, P = 0.025), and Kep entropy (p = 0.464, P = 0.013). Cell count correlated with Ktrans kurtosis (p = 0.40, P = 0.034), Ve entropy (p = 0.475, P = 0.011). Total nucleic area correlated with Ve max (p = 0.386, P = 0.042) and Ve entropy (p = 0.411, P = 0.030). In G1/2 tumors, only Ktrans entropy correlated well with total (P =0.78, P =0.013) and average nucleic areas (p = 0.655, P = 0.006). In G3 tumors, KI 67 correlated with Ve min (p = -0.552, P = 0.022) and Ve entropy (p = 0.524, P = 0.031). Ve max correlated with total nucleic area (p = 0.483, P = 0.049). Kep max correlated with total area (p = -0.51, P = 0.037), and Kep entropy with KI 67 (p = 0.567, P = 0.018). We concluded that histogram-based parameters skewness, kurtosis and entropy of Ktrans, Ve, and Kep can be used as markers for proliferation activity, cellularity and nucleic content in HNSCC. Tumor grading influences significantly associations between perfusion and histopathological parameters.

Histogram analysis parameters of apparent diffusion coefficient reflect tumor cellularity and proliferation activity in head and neck squamous cell carcinoma.

Our purpose was to analyze associations between apparent diffusion coefficient (ADC) histogram analysis parameters and histopathologicalfeatures in head and neck squamous cell carcinoma (HNSCC). The study involved 32 patients with primary HNSCC. For every tumor, the following histogram analysis parameters were calculated: ADCmean, ADCmax, ADCmin, ADCmedian, ADCmode, P10, P25, P75, P90, kurtosis, skewness, and entropy. Furthermore, proliferation index KI 67, cell count, total and average nucleic areas were estimated. Spearman's correlation coefficient (p) was used to analyze associations between investigated parameters. In overall sample, all ADC values showed moderate inverse correlations with KI 67. All ADC values except ADCmax correlated inversely with tumor cellularity. Slightly correlations were identified between total/average nucleic area and ADCmean, ADCmin, ADCmedian, and P25. In G1/2 tumors, only ADCmode correlated well with Ki67. No statistically significant correlations between ADC parameters and cellularity were found. In G3 tumors, Ki 67 correlated with all ADC parameters except ADCmode. Cell count correlated well with all ADC parameters except ADCmax. Total nucleic area correlated inversely with ADCmean, ADCmin, ADCmedian, P25, and P90. ADC histogram parameters reflect proliferation potential and cellularity in HNSCC. The associations between histopathology and imaging depend on tumor grading.