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Zusammenfassung. Intrakranielle atherosklerotische Stenosen sind die häufigste Ursache von ischämischen Hirnschlägen weltweit. Drei Behandlungsverfahren stehen heutzutage für Patienten mit intrakraniellen atherosklerotischen Stenosen zur Verfügung: Das beste konservative Management (bestehend aus Medikamenten, einer optimalen Einstellung vaskulärer Risikofaktoren und einem gesunden Lebensstil), die endovaskuläre Therapie und die chirurgische Therapie. Bei asymptomatischen intrakraniellen atherosklerotischen Stenosen wird aktuell ein bestes konservatives Management empfohlen, ebenso in der Regel bei Patienten mit symptomatischen intrakraniellen atherosklerotischen Stenosen. Ausgewählte Patienten können aber von einer zusätzlichen endovaskulären Therapie profitieren, bspw. wenn sie trotz bestem konservativen Management wiederholte Hirninfarkte im Gefässterritorium der Stenose zeigen. In seltenen Fällen kann auch ein chirurgisches Vorgehen in Frage kommen. Bei Patienten mit symptomatischer extrakranieller atherosklerotischer Karotisstenose konnte wiederholt gezeigt werden, dass die Behandlung mittels Karotisendarterektomie (CEA) ein tieferes Sterblichkeits- und Hirnschlagrisiko aufweist als die Behandlung mittels endovaskulärer Therapie (CAS). Insbesondere bei Patienten im Alter von über 70 Jahren sollte aktuell in der Regel eine CEA dem CAS vorgezogen werden, da das Risiko innerhalb von 30 Tagen nach Behandlung zu versterben oder einen Hirnschlag zu erleiden bei Patienten, welche mit einem CAS behandelt werden praktisch doppelt so hoch liegt, wie bei Patienten, die mittels CEA behandelt werden. Die Studienergebnisse, welche modernisierte Techniken und Devices verwenden, bleiben abzuwarten. Aktuell bleibt es unklar, ob Patienten mit asymptomatischer extrakranieller atherosklerotischer Karotisstenose unter bester konservativer Therapie überhaupt von einer invasiven Therapie im Sinne einer CEA oder eines CAS profitieren.

Background and purpose Little is known about the angiographic presentation of Moyamoya angiopathy (MMA) in non-Asian patients. Methods Conventional cerebral angiograms from 155 Caucasian patients diagnosed as MMA were analyzed with respect to extracranial champagne bottle neck sign, Suzuki stages, collateral status, as well as presence of aneurysms and posterior cerebral artery stenosis. Results In 84 of 155 angiograms, the extracranial carotid artery was visualized, in 65 of them (77.4%), a champagne bottle neck sign was noted. Of the 278 analyzable hemispheres, 13.7%,11.2%, 37.8%, 27.3%, 8.6%, and 1.4% were classified as Suzuki stage I, stage II, stage III, stage IV, stage V, and stage VI, respectively. Among 280 hemispheres, in 53 hemispheres (18.9%) isolated basal collaterals (pathway I) and in 104 hemispheres (37.1%) choroidal and pericallosal collaterals (including basal collaterals, pathway II) were found. In 74 hemispheres (26.4%) ethmoidal collaterals (pathways III), and in 17 hemispheres (6.1%) vault collaterals were visualized. Patients with higher Suzuki stages IV–VI (p = 0.008) and ethmoidal collaterals (p p Conclusions This is so far the largest observational study about angiography in Caucasian European MMA patients. A comparison with Asian data indicates similarity of disease in Caucasian and Asian patients.

BackgroundSubstantial clinical evidence supporting the benefit of mechanical thrombectomy (MT) for distal occlusions within the posterior circulation is still missing. This study aims to investigate the procedural feasibility and safety of MT for isolated occlusions of the posterior cerebral artery.MethodsWe retrospectively reviewed patients from three stroke centers with acute ischemic stroke attributed to isolated posterior cerebral artery occlusion (IPCAOs) who underwent MT between January 2014 and December 2019. Procedural and safety assessment included successful recanalization rates (defined as Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b), number of MT attempts and first-pass effect (TICI 3), intracranial hemorrhage (ICH), mortality, and intervention-related serious adverse events. Treatment effects were evaluated by the rate of early neurological improvement (ENI) and early functional outcome was assessed with the modified Rankin Scale (mRS) at discharge. A systematic literature review was conducted to identify and summarize previous reports on MT for IPCAOs.ResultsForty-three patients with IPCAOs located in the P1 (55.8%, 24/43), P2 (37.2%, 16/43), and P3 segment (7%, 3/43) were analyzed. The overall rate of successful recanalization (TICI ≥2b) was 86% (37/43), including a first pass-effect of 48.8% (21/43) leading to TICI 3. sICH occurred in 7% (3/43) and there were two cases with iatrogenic vessel dissection and one perforation. ENI was observed in 59% (23/39) and excellent functional outcome (mRS ≤1) in 46.2% (18/39) of patients who were discharged. The in-hospital mortality rate was 9.3% (4/43).ConclusionOur study suggests the technical feasibility and safety of thrombectomy for IPCAOs. Further studies are needed to investigate safety and long-term functional outcomes with posterior circulation stroke-adjusted outcome assessment.

BackgroundFlat detector computed tomography (FDCT) is widely used for periprocedural imaging in the angiography suite. Sine Spin FDCT (SFDCT) is the latest generation of cone beam CT using a double oblique trajectory for image acquisition to reduce artefacts and improve soft tissue brain imaging. This study compared the effective dose, image quality and diagnostic performance of the latest generation of SFDCT with multidetector CT (MDCT).MethodsAn anthropomorphic phantom equipped with MOSFET detectors was used to measure the effective dose of the new 7sDCT Sine Spin protocol on a latest generation biplane angiographic C-arm system. Diagnostic performance was evaluated on periprocedurally acquired SFDCT for depiction of anatomical details, detection of hemorrhage, and ischemia and was compared with preprocedurally acquired MDCT. Inter- and intra-rater correlation as well as sensitivity and specificity were calculated.ResultsBoth modalities showed equal diagnostic performance in the supratentorial ventricular system. SFDCT provided inferior image quality in grey-white matter differentiation and infratentorial structures. Intraventricular, subarachnoid and parenchymal hemorrhages were diagnosed with a sensitivity of 83.3%, 84.2% and 75% and a specificity of 97.3%, 80.0% and 100%, respectively; early ischemic lesions with a sensitivity of 73.3% and specificity 94.7%. The effective dose measured for the 7sDCT Sine Spin protocol was 2 mSv.ConclusionsOur findings confirm the high diagnostic sensitivity and specificity of SFDCT in detecting intracranial hemorrhage and early ischemic lesions. The delineation of grey-white matter differentiation and infratentorial structures remains a limiting factor. In comparison to previous studies, the new 7sDCT Sine Spin protocol showed a lower effective dose.

Endovascular mechanical thrombectomy (EVT) is widely accepted as the first-line treatment for acute ischemic stroke in patients with large vessel occlusion. Being an invasive treatment, this method is associated with various preoperative, perioperative, and postoperative complications. These complications may influence peri-interventional morbidity and mortality and therefore treatment efficacy and clinical outcome. The aim of this review is to discuss the most common types of complications associated with EVT, the probable mechanisms of injury, and effective methods to manage and prevent complications.

Atherosclerosis of the intracranial arteries and of the extracranial carotid artery.

BackgroundThe degree of reperfusion is the most important modifiable predictor of 3 month functional outcome and mortality in ischemic stroke patients treated with mechanical thrombectomy. Whether the beneficial effect of reperfusion also leads to a reduction in long term mortality is unknown.MethodsPatients undergoing mechanical thrombectomy between January 2010 and December 2018 were included. The post-thrombectomy degree of reperfusion and emboli in new territories were core laboratory adjudicated. Reperfusion was evaluated according to the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Vital status was obtained from the Swiss population register. Adjusted hazard ratios (aHRs) using time split Cox regression models were calculated. Subgroup analyses were performed in patients with borderline indications.ResultsOur study included 1264 patients (median follow-up per patient 2.5 years). Patients with successful reperfusion had longer survival times, attributable to a lower hazard of death within 0–90 days and for >90 days to 2 years (aHR 0.34, 95% CI 0.26 to 0.46; aHR 0.37, 95% CI 0.22 to 0.62). This association was homogeneous across all predefined subgroups (p for interaction >0.05). Among patients with successful reperfusion, a significant difference in the hazard of death was observed between eTICI2b50 and eTICI3 (aHR 0.51, 95% CI 0.33 to 0.79). Emboli in new territories were present in 5% of patients, and were associated with increased mortality (aHR 2.3, 95% CI 1.11 to 4.86).ConclusionSuccessful, and ideally complete, reperfusion without emboli in new territories is associated with a reduction in long term mortality in patients treated with mechanical thrombectomy, and this was evident across several subgroups.

Background Progressive multifocal leukoencephalopathy (PML) is a rare complication of patients treated with fingolimod. Case presentation Routine MRI eventually led to diagnosis of asymptomatic early PML that remained stable after discontinuation of fingolimod. As blood lymphocyte counts normalized, signs of immune reconstitution inflammatory syndrome (IRIS) and renewed MS activity developed. Both, advanced laboratory and ultrahigh field MRI findings elucidated differences between PML and MS. Conclusions In our case, early discontinuation of fingolimod yielded a good outcome, lymphocyte counts reflected immune system activity, and paraclinical findings helped to differentiate between PML-IRIS and MS.

Durch die Analyse autoptischer, histologischer, operativer und angiografischer Befunde wurde eine Terminologie der intrazerebralen Gefasmalformationen erarbeitet. Die unterschiedlichen Gefasmalformationen werden in diesem Kapitel dargestellt.

Treatment of a symptomatic stenosis is known to be most beneficial within 14 days after the presenting event but this can frequently not be achieved in daily practice. The aim of this study was the assessment of factors responsible for this time delay to treatment. A retrospective analysis of a prospective two-center CAS database was carried out to investigate the potential factors that influence a delayed CAS treatment. Of 374 patients with a symptomatic carotid stenosis, 59.1% were treated beyond ≥14 days. A retinal TIA event (OR = 3.59, 95% CI 1.47-8.74, p < 0.01) was found to be a predictor for a delayed treatment, whereas the year of the intervention (OR = 0.32, 95% CI 0.20-0.50, p < 0.01) and a contralateral carotid occlusion (OR = 0.42, 95% CI 0.21-0.86, p = 0.02) were predictive of an early treatment. Similarly, within the subgroup of patients with transient symptoms, the year of the intervention (OR = 0.28, 95% CI 0.14-0.59, p < 0.01) was associated with an early treatment, whereas a retinal TIA as the qualifying event (OR = 6.96, 95% CI 2.37-20.47, p < 0.01) was associated with a delayed treatment. Treatment delay was most pronounced in patients with an amaurosis fugax, whereas a contralateral carotid occlusion led to an early intervention. Although CAS is increasingly performed faster in the last years, there is still scope for an even more accelerated treatment strategy, which might prevent future recurrent strokes prior to treatment. peerReviewed

PurposeCarotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA) for patients with significant carotid stenosis. However, diffusion-weighted imaging (DWI) has indicated that CAS is associated with a significantly higher burden of microemboli. This study evaluated the potential effect on intellectual functions of new DWI lesions after CEA or CAS.MethodsThis prospective study analyzed the neuropsychologic outcomes after revascularization in 24 CAS and 31 CEA patients with severe carotid stenosis compared with a control group of 27 healthy individuals. All patients underwent clinical examinations, magnetic resonance imaging scans, and a neuropsychologic test battery that assessed six major cognitive domains performed immediately before CEA or CAS, ≤72 hours after, and at 3 months.ResultsNew DWI lesions were detected among 15 of 21 (71%) of the CAS patients immediately after treatment but in only 1 of the 28 CEA patients (4%; P < .01). As a group, patients with new DWI lesions showed a decline in their performance in the cognitive domains, attention, and visuoconstructive functions within 72 hours of carotid revascularization. Individually, however, in none of the cognitive domains did the decreases reach a clinically relevant threshold of z < −1.5. Moreover, the cognitive performance was not significantly different between patients with and without new DWI lesions 3 months after treatment. The cognitive performance was similar between CEA and CAS patients at all points.ConclusionsThe findings support the assumption that new brain lesions, as detected with DWI after CAS or CEA, do not affect cognitive performance in a manner that is long-lasting or clinically relevant. Despite the higher embolic load detected by DWI, CAS is not associated with a greater cognitive decline than CEA.

Introduction Carotid artery stenting (CAS) requires adequate follow-up imaging to assess complications such as in-stent stenosis or occlusion. Options include digital subtraction angiography, CT angiography, ultrasound, and MR angiography (MRA), which may offer a non-invasive option for CAS follow-up imaging. The aim of this study was to assess contrast-enhanced MRA (CE-MRA) and three-dimensional time-of-flight MRA (3D-TOF) for visualization of the in-stent lumen in different carotid stents. Methods In this study, we compared CE-MRA and 3D-TOF of five different carotid stents (Guidant Acculink®, Cordis Precise®, Boston Wallstent®, Abbot Vascular Xact®, Cook Zilver®) in three diameters (4, 6, and 8 mm) using a vascular flow model at 3.0 T with the help of a recently developed carotid surface coil. Stent-related artifacts were objectively assessed by calculating artificial lumen narrowing (ALN) and relative in-stent signal (RIS). Results RIS and ALN depended heavily on stent type, stent diameter, and the employed MR sequence. ALN and RIS were relatively favorable for Acculink®, Precise®, and Zilver® stents with both CE-MRA and 3D-TOF. CE-MRA provided better results for the Wallstent, while the Xact stent was difficult to visualize with both MRA protocols. Conclusion Both CE-MRA and 3D-TOF are viable options for depicting the in-stent lumen in carotid stents. For specific stents, 3D-TOF provided image quality comparable to CE-MRA and may thus be suitable for in vivo assessment. Development of stent-specific pathways for follow-up imaging seems advisable to address stent-related differences in image quality.

αCaMKIIT286A mutant mice lack long-term potentiation (LTP) in the hippocampal CA1 region and are impaired in spatial learning. In situ hybridization confirms that the mutant mice show the same developmental expression of αCaMKII as their wild-type littermates. A simple hypothesis would suggest that if LTP is a substrate for learning, then enriching the environment should cause learning-dependent changes in wild-type mice that have LTP. Such changes would not be seen in LTP-deficient αCaMKIIT286A mutants. Excitatory synaptic currents in CA1 neurons, recorded with patch clamp in brain slices, revealed that enrichment induces an increase in glutamate release probability and a decreased miniature current amplitude. Confocal microscopy also showed dendritic spine density to be reduced. However, contrary to the hypothesis above, these enrichment-induced changes occur only in the mutant mice and are not detectable in wild-type littermates. We suggest that enrichment induces αCaMKII-independent changes in both wild-type and mutant mice. Such changes may be subsequently reversed in wild-type animals via αCaMKII-dependent mechanisms, such as LTP. Reversal of plasticity has long been hypothesized to be essential for the hippocampus to maintain its role in memory processing. The inability to reverse plasticity in αCaMKIIT286A mutant mice would then result in impairment of spatial learning.

Autosomal recessive hereditary spastic paraplegia with thin corpus callosum (ARHSP-TCC) is one of the most prevalent forms of complex ARHSP. Mutations in the SPG11 gene are the most common cause for ARHSP-TCC and accounts for up to 70% of all cases. The mutational spectrum of SPG11 gene is broad as all types of DNA alterations are detected in the gene and most mutations lead to a premature truncation of the protein, suggesting “loss of function” as the likely pathogenic mechanism. In the current study, we report a consanguineous Turkish family with ARHSP inheritance manifesting white matter abnormalities including TCC with relatively late age of onset. Sequencing of SPG11 gene revealed a homozygous insertion of 15 nucleotides at position 6886 in exon 38 (c.6886_6900Dup15) leading to an in-frame insertion of five amino acids at codon 2296 (p.K2296_L2300Dup5), which resides within a predicted, highly conserved, intradiol ring-cleavage dioxygenase domain (2104 -2381 residues). In silico structural prediction of intradiol domain of the mutated Spatacsin protein revealed that the duplication of five amino acids leads to an extra turn in α-helix and a slightly longer loop region. Our structural analysis suggests that it is unlikely that insertion mutation (c.6886_6900Dup15) causes dysfunctional protein rather the minor conformation changes may elicit a “gain of function”, which may be detrimental to endogenous function of Spatacsin thus cause HSP.

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (

For prosthetic heart valves the risk of infection is much higher than for native heart valves. During the course of infective endocarditis 20-40% of all patients suffer from cerebrovascular complications such as ischaemic stroke or intracerebral haemorrhage. We present the case of a 57-year-old woman who had undergone surgery to mechanically replace an aortic heart valve 11 months ago and suffered from repeated ischaemic strokes with secondary haemorrhage. The initial antibiotic regimen was ineffective in treating the later diagnosed Staphylococcus aureus infection of the prosthetic valve. Escalation of the antibiotic treatment was not able to halt the clinical course that finally led to the patient's death. The case report emphasizes the importance of early identification of the aetiology of infection in patients with mechanical heart valve replacement. Without rapid and adequate treatment there is a considerable risk for the development of severe neurological sequelae and cardiac failure that can ultimately result in a fatal course of this clinical picture. peerReviewed

The superior olivary complex (SOC) is an auditory brainstem region that represents a favourable system to study rapid neurotransmission and the maturation of neuronal circuits. Here we performed serial analysis of gene expression (SAGE) on the SOC in 60-day-old Sprague-Dawley rats to identify genes specifically important for its function and to create a transcriptome reference for the subsequent identification of age-related or disease-related changes. Sequencing of 31 035 tags identified 10 473 different transcripts. Fifty-seven per cent of the unique tags with a count greater than four were statistically more highly represented in the SOC than in the hippocampus. Among them were genes encoding proteins involved in energy supply, the glutamate/glutamine shuttle, and myelination. Approximately 80 plasma membrane transporters, receptors, channels, and vesicular transporters were identified, and 25% of them displayed a significantly higher expression level in the SOC than in the hippocampus. Some of the plasma membrane proteins were not previously characterized in the SOC, e.g. the purinergic receptor subunit P2X(6) and the metabotropic GABA receptor Gpr51. Differential gene expression between SOC and hippocampus was confirmed using RNA in situ hybridization or immunohistochemistry. The extensive gene inventory presented here will alleviate the dissection of the molecular mechanisms underlying specific SOC functions and the comparison with other SAGE libraries from brain will ease the identification of promoters to generate region-specific transgenic animals. The analysis will be part of the publicly available database ID-GRAB.