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BackgroundUsing a surgical aneurysm model, this study assessed the performance of a new flow diverter (FD), the DiVeRt, and evaluated the angiographic and histologic features at different periods after stent deployment.MethodsFifteen New Zealand White rabbits were treated 3 days prior to intervention and until euthanization with dual antiplatelets. DiVeRt was implanted in bilateral carotid aneurysms (n=30) as well as in the aorta (n=15). The rate of technical success, assessment of aneurysm occlusion (measured by the O'Kelly–Marotta grading (OKM) scale), and stent patency were examined using angiography and histologic examinations in three groups at 1, 3, and 6 months follow-up (FU). In each FU group one control animal was included and treated with the XCalibur stent (n=3).ResultsOverall, DiVeRt placement was successful and without apparent intraprocedural complications. In total, four stents in the carotid artery were occluded and in-stent stenosis was registered in two carotid (7%) and one aortic (6%) vessels. Complete or near complete aneurysm occlusion (OKM scale D1 and C3) was seen in 100% in the 1-month FU group, 70% in the 2-month FU group, and 100% in the 3-month FU group. Histology showed loose, organizing fibrous tissue matrix within the sac and adequate neck endothelialization in all vessels. All branches covered by the DiVeRt remained patent.ConclusionsThe DiVeRt system appears to be feasible and effective for the treatment of aneurysms with high rates of complete aneurysm occlusion, excellent vessel patency, and evidence of high biocompatibility. Occurrences of parent artery occlusion at follow-up did not result in clinical consequences.

IntroductionUpon completion of the workup for stroke, etiology cannot be identified in approximately one-third of the patients, with an embolic stroke of undetermined source (ESUS) accounting for around 50% of these cryptogenic etiologies. Whether management of complex long-term monitoring in order to detect suspected atrial fibrillation (AFib) could be initiated and managed through a neurologist is not sufficiently investigated.Patients and MethodsWe recruited all consecutive patients with ESUS who received implantation after neurological adjudication of Reveal LINQ® loop recorder between January 2016 and July 2020. We collected demographic, clinical, heart- and neuroimaging, laboratory, and electrocardiographic data assessed on prolonged baseline ECG monitoring, number of supraventricular (SVEs) and ventricular (VEs) extrasystolic complexes, and from preimplantation ECG–PQ interval. AFib detection was manually supervised and determined positive when the duration was over 120 s.ResultsWe followed a total of 131 patients for a median of 504 days. There were 45 (34%) manually verified AFib diagnoses. In univariate analysis, earlier implantation after ESUS was associated with AFib detection (13 vs. 31 days, p = 0.011). In multivariate analysis, increased rate of AFib was associated with a more prolonged PQ interval (per 50-ms increase) (HR 1.99, 95% CI 1.39–2.85) and number of SVEs (HR 1.29, 95% CI 1.05–1.57) measured on pre-implantation ECG.ConclusionWe observed similar predictors for Afib after ESUS, albeit with higher frequency than previously reported. This study suggests that the neurologist-led decision, management, and evaluation of ILR after ESUS is feasible.

BACKGROUND With an aging population, acquisition of a better understanding of prognostic factors in elderly patients with Glioblastoma multiforme (GBM) is of utmost importance. Epileptic seizures have been found to correlate with improved overall survival (OS) in low-grade gliomas; however, the impact of epilepsy in GBM patients on outcome parameters is poorly defined. This study aims at specifically evaluating the impact of epilepsy in elderly GBM patients. Material & METHODS Two Austrian academic neurosurgical centers retrospectively analyzed all elderly (≥ 65 years) GBM patients with de-novo tumors, who underwent surgery between 09/2006 and 07/2021. Epidemiological, histopathological and survival data were gained from patients’ electronic charts and screened for presence of epilepsy preoperatively or during follow-up. Tumor volume was assessed using standardized software. RESULTS 391 patients (55% males, 45% females) with a median age at surgery of 73 years (IqR 68.5-77.5) were analyzed. The mean predicted OS was 12.4 months (CI95% 10.9-14.0). Mean follow-up was 10.4 months (CI95% 9.1-11.6) in our cohort. Median tumor volume amounted to 26.47 cm3 (IqR 12.65-43.49). 95 patients (24%) suffered from preoperative epilepsy. 17 (18%) patients showed epilepsy after tumor resection. Four patients (1.0%) showed a worsening of already preoperatively diagnosed seizures. Patients with lower tumor volumes experienced significantly more often seizures compared to patients with larger tumors, p< 0.001. Survival did not correlate with preoperative epilepsy (p > 0.05). However, Cox-regression revealed that multifocal tumor location (HR=1.777, p=0.025) and thalamic involvement (HR=11.121, p=0.030) influenced OS. Surgery-associated complications shortened OS significantly (HR=1.945 [CI95% 1,296-2,916], p=0.025). CONCLUSION Even though epilepsy was not found to directly impact survival in elderly GBM patients, we found that surgery led to epilepsy freedom in a significant proportion of our patient cohort, thereby potentially leading to improved QoL. Greatest focus should be set on avoiding any surgery-associated deficits, since these severely influence the OS.

Purpose While there is class I evidence for mechanical thrombectomy (MT) for anterior circulation large vessel occlusion (LVO) stroke, no high-class evidence exists for the posterior circulation. Here, we sought to compare clinical features of anterior vs. posterior LVO as well as predictors of posterior LVO MT outcome. Methods Acute ischemic stroke patients who underwent mechanical thrombectomy for anterior and posterior large vessel occlusion (LVO) stroke between 02/2016 and 08/2020 from two comprehensive stroke centers were reviewed. Anterior and posterior LVO strokes were compared. Additionally, predictors for a favorable outcome (mRS 0–3), death (mRS 6), as well as futile revascularization (mRS 4–6 despite TICI 2b/3 revascularization) for posterior LVO were analyzed. Results Collectively, 813 LVO thrombectomy cases were analyzed, and 77/813 (9.5%) were located in the posterior circulation. While favorable 90-day functional outcome rates did not differ between anterior and posterior LVO (p=0.093), death was significantly more frequent among posterior LVO cases (p=0.013). In the posterior LVO subgroup, a primary aspiration technique and successful revascularization TICI 2b/3 irrespective of time to the intervention was independently associated with achieving a favorable outcome. Primary aspiration was identified to inversely associate with futile revascularization. Conclusion Anterior and posterior circulation MT patients have distinct clinical profiles. The use of primary aspiration appears fundamental for beneficial outcomes in posterior circulation MT.

Pooled data of randomized controlled trials investigating mechanical thrombectomy (MT) to treat anterior circulation large vessel occlusion have demonstrated safety and effectiveness across all age groups, including ≥ 80 years of age; however, only a few nonagenarians were in the ≥ 80 years subgroup. Therefore, the benefit of MT in nonagenarians is mostly unknown. Two comprehensive stroke centers retrospectively reviewed all acute ischemic stroke patients who underwent MT for anterior circulation large vessel occlusion (LVO) stroke between February 2016 and August 2020. Revascularization TICI2b/3, symptomatic intracranial hemorrhage (ICH), and functional outcome using modified Rankin scale (mRS) were assessed for cases aged

BACKGROUND AND PURPOSE: Reports investigating the relationship between in-procedure blood pressure (BP) and outcomes in patients undergoing endovascular thrombectomy (EVT) due to anterior circulation stroke are sparse and contradictory. ----- METHODS: Consecutive EVT-treated adults (modern stent retrievers, BP managed in line with the recommendations, general anesthesia, invasive BP measurements) were evaluated for associations of the rate of in-procedure systolic BP (SBP) and mean arterial pressure (MAP) excursions to >120%/120% was independently associated with lower ILV, while higher in-procedure mean SBP/MAP was associated with lower odds of hemorrhages. mRS 0-2 was achieved in 75/155 (48.4%) evaluated patients (nine had missing mRS data). Higher rate of SBP/MAP excursions to >120% and higher reference SBP/MAP were independently associated with higher odds of mRS 0-2, while higher ILV was associated with lower odds of mRS 0-2. Rate of SBP/MAP excursions to

Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity.

Background: Severe leukoaraiosis (LA) is an established risk factor for poor outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke. There is uncertainty whether this association also applies to successfully recanalized patients with M1 segment middle cerebral artery (MCA) occlusions. Methods: A retrospective single-centre study of patients with successful reperfusion (thrombolysis in cerebral infarction, TICI 2b or 3) after MT for an M1 MCA occlusion was performed over a 7-year period. LA score (LAS) was assessed using the age-related white matter change scale on pre-interventional brain imaging. Results: A total of 209 patients (median age 75.0 years) were included. LAS was assessed on pre-interventional imaging by computed tomography in 177 (84.7%) patients and magnetic resonance imaging in 32 (15.3%) patients. The median LAS was 1 (IQR 0–8), and severe LA consisted of the top 25 percentile, ranging from 9 to 24. Multivariable analysis demonstrated an association of severe LA (OR 0.32, 95% CI 0.12–0.88, p = 0.023), higher NIHSS on admission (OR 0.89, 95% CI 0.84–0.94, p < 0.001), advanced age (OR 0.97, 95% CI 0.95–1.00, p = 0.039), good leptomeningeal collaterals (OR 3.65, 95% CI 1.46–8.15, p = 0.001), and TICI 3 score (OR 3.26, 95% CI 10.52–7.01) with good clinical outcome after 3 months as measured with the modified Rankin scale. Conclusion: Severe LA is associated with poor clinical outcome at 3 months in acute stroke patients undergoing MT due to emergent M1 MCA occlusion.

Background Clinical outcome after large vessel occlusion (LVO) stroke depends on collateral integrity. We aimed to evaluate whether the completeness of the circle of Willis (CoW) and anterior temporal artery (ATA) determines the status of leptomeningeal collaterals (LC) in patients with acute LVO (internal carotid artery (ICA) and middle cerebral artery M1 (MCA) occlusion) treated with endovascular thrombectomy. Patients and methods LC, cross-flow through the anterior communicating artery (ACoA), presence of the ipsilateral posterior communicating artery (IpsiPCoA) and presence of the ATA were evaluated using CT angiography. LC was graded as good when ≥50% collateral filling was noted compared to the unaffected hemisphere. Results We included 159 patients with a median age of 75 years (IQR 63–82), MCA M1 occlusion in 96 (60%) and good outcome in 68 (45.6%). The LC were good in 129 (81.1%) patients. Complete IpsiPCoA and incomplete ACoA status was inversely associated with good LC in LVO (OR 0.51 (95% CI 0.02–0.07)). A complete CoW was associated with good LC in ICA occlusions, OR 8.4 (p = .025). Good outcome (modified Rankin scale 0–2 at 3 months) was associated with good LC (OR 5.63 (95% CI 1.11–28.4)), small ischemic lesion volume (OR 0.94 (95% CI 0.97–0.98)) and absence of the ACoA and IpsiPCoA (OR 4.47 (95% CI 1.09–18.3)). Conclusions ATA presence was associated with good leptomeningeal collaterals in LVO (OR 8.13 (95% CI 1.69–39.0)) and in MCA M1 patients (OR 7.9 (95% CI 1.7–36.4)). The effect of ATA was most pronounced in MCA M1 occlusions, and that of ACoA was most pronounced in ICA occlusions.

Identifying major support mechanisms in the neural microenvironment could have significant impact against growth and invasion of malignant gliomas. The NFkB pathway is a major signaling hub that drives tumor progression and at the same time regulates the inflammatory responses of normal tissues. Here we show that animals with a stunted NFkB response exhibit reduced reactivity against intracranial gliomas, which surprisingly reduces tumor growth and invasion. NFkB-deficient mice (RelA + /- TNFR1-/-) were injected intracranially with mouse GL261 glioblastoma cells to analyze tumor phenotype. Histological and MRI analyses showed significantly smaller tumors in RelA + /- mice compared to control littermates. Interestingly, immunohistochemical studies indicated that tumors in RelA + /- mice had vascularization and infiltration of microglia/macrophages comparable to controls, but significant reduction of M2 microglia/macrophage polarization and GFAP-positive astroglia. The lower reactivity of RelA + /- astroglia was also evident following intracranial implantation of highly invasive mouse glioblastoma cells (Mut4; GFAP-Cre:Nf1loxP/+ Trp53-/+ PTENloxP/+), suggesting that the astrocyte compartment played a major role in tumor growth or invasion. To test this hypothesis we prepared cultures of brain slices, where astrocytes and their secreted ECM are the major components challenging glioma cells. Interestingly, glioblastoma cells were significantly less invasive in brain slices from NFkB-deficient mice compared to wild-type tissue. Further analysis of RelA-/–astrocytes demonstrated reduced migration towards glioblastoma cells, increased expression of neural chondroitin sulfate proteoglycans and reduced expression of the metalloproteases that cleave these inhibitory ECM proteins, lending support to the reduced tumor progression observed in vivo. Taken together, these results strongly suggest that activation of NFkB in the neural microenvironment underlies the reactive glial response that promotes tumor growth and invasion. In particular, our results highlight astroglial NFkB signaling as a driver of glioma malignancy that should be considered for long-term targeted strategies.