First-Line Aspiration Thrombectomy of M2 Occlusions with a Novel Reperfusion Catheter (REDTM 62): Real-World Experience from Two Tertiary Comprehensive Stroke Centers.

PURPOSE: The direct aspiration first pass technique (ADAPT) is an effective and safe endovascular treatment for distal medium vessel occlusions (DMVOs). We evaluated technical features and initial results of a novel reperfusion catheter (REDTM 62) used for frontline aspiration thrombectomy of M2 occlusions in acute ischemic stroke patients. Appropriate aspiration catheters are crucial for a successful ADAPT maneuver; however, the selection of catheters suitable for smaller-sized vessels is scarce compared to the ones for large vessel occlusions. MATERIALS AND METHODS: All patients treated with ADAPT using REDTM 62 as the frontline treatment approach for acute M2 occlusions between December 2022 and February 2024 were retrospectively enrolled. Demographic data, procedural timings and safety, recanalization rates, and outcome data were recorded. RESULTS: Twenty patients with a median admission National Institutes of Health Stroke Scale (NIHSS) score of 8 were identified. Successful revascularization (DMVO-thrombolysis in cerebral infarction [TICI]≥2b) with REDTM 62 aspiration thrombectomy was obtained in 65.0% (13/20) of cases. The first pass effect was 45.0% (9/20). In 2 cases, the REDTM 62 did not reach the clot due to marked distal vessel tortuosity. Stent retrievers were additionally used in 9 cases and led to an overall DMVO-TICI 2c/3 of 90.0% (18/20). Mean procedural time was 48 minutes. No complications directly related to ADAPT occurred. In-hospital mortality rate was 20.0% (4/20). The median discharge NIHSS score was 2.5. A good functional outcome at discharge (modified Rankin scale 0-2) was achieved in 55.0% (11/20) of cases. CONCLUSION: Our initial experiences with the novel REDTM 62 reperfusion catheter for treatment of M2 occlusions is in line with published data. ADAPT using this catheter may be considered as a safe and effective first-line treatment option. Further studies are warranted to validate the initial results.

Initial Experience with a New Self-Expanding Open-Cell Stent System with Antithrombotic Hydrophilic Polymer Coating (pEGASUS Stent) in the Treatment of Wide-Necked Intracranial Aneurysms.

PURPOSE: We report our initial experience with endovascular embolization of intracranial aneurysms using this new self-expanding open-cell stent system (pEGASUS stent system) with the antithrombogenic hydrophilic polymer coating. MATERIALS AND METHODS: We retrospectively reviewed all patients treated with stent-assisted coiling or the Woven EndoBridge device using the pEGASUS stent system between September 2022 and June 2023. Demographic, clinical, and angiographic data were analyzed as well as short-term follow-up, including procedural complication rates and aneurysmal occlusion rates using the Raymond-Roy occlusion classification (RROC). RESULTS: Twelve patients with 12 wide-necked intracranial aneurysms were treated with the pEGASUS stent system, including 2 acutely ruptured aneurysms embolized in an emergency setting. The treated aneurysms were located at the anterior communicating artery (25.0%), the basilar artery (50.0%), the middle cerebral artery (16.7%), and the internal carotid artery (8.3%). All stents were deployed successfully. Immediate complete aneurysmal occlusion (RROC class I) was achieved in 83.3% (10/12) and near-complete occlusion (RROC II) in 16.7% (2/12). No periprocedural complications occurred in patients treated in the elective setting. A single case of intraoperative in-stent thrombus formation occurred during the treatment of an acutely ruptured basilar aneurysm and was resolved with intravenous Tirofiban. No other periprocedural complications occurred. Eleven out of 12 patients were available for follow up (mean 7.4 months). Complete aneurysmal occlusion without in-stent stenosis (ISS) was seen in 10 patients (90.9%). One patient (9.1%) showed aneurysmal reperfusion (RROC IIIb) with asymptomatic moderate ISS. CONCLUSION: Our initial results demonstrate that the pEGASUS stent system appears to be a safe and effective device for stent assisted embolization of wide-necked intracranial aneurysms. More data is necessary to evaluate long-term follow-up.

Embolization of an Intracranial Vertebral Artery Aneurysm via the Deep Cervical Artery.

Treatment of vertebral artery aneurysms can be challenging due to the unusual vascular anatomy or unfeasibility of traditional endovascular techniques. We describe a novel approach for endovascular treatment of a ruptured intracranial vertebral artery aneurysm with bilateral vertebral artery occlusions and hypoplasia of the posterior communicating arteries. Successful coil embolization was performed using a collateral pathway for microcatheterization via anastomosis between the deep cervical artery and the vertebral artery. This case report highlights a novel alternative endovascular treatment approach for vertebrobasilar aneurysms in case of a poor vascular status with occlusion or lack of traditional endovascular access routes.

Feasibility and safety of ADAPT in acute distal posterior cerebral artery occlusions.

PURPOSE: The direct aspiration first pass technique (ADAPT) is an effective and safe endovascular treatment for distal medium vessel occlusions (DMVO) of the anterior circulation. Clinical experience with ADAPT in the distal posterior circulation, however, is still limited and published data is scarce. In this original work, feasibility, safety and efficacy of ADAPT with distal access catheters (DAC) for treatment of acute distal posterior cerebral artery occlusions (DPCAOs) is evaluated. METHOD: All acute ischemic stroke patients between 2017 and 2022 with primary or secondary DPCAOs in the P2 or P3 segment, that underwent thrombectomy of the DPACO using ADAPT with DACs as frontline therapy, were identified. Demographic data, recanalization rates, procedural safety, and clinical outcome were assessed. RESULTS: Twenty-four patients with primary (n = 6) or secondary (n = 18) DPCAOs (P2: 21/24; P3: 3/24) were included. Median NIHSS score at admission was 14.5 (IQR 9.5). In all cases, the DPCAO could be reached with the DAC. Successful revascularization (DMVO-p-TICI ≥ 2b) with ADAPT was achieved in 79.2% (19/24), including a first pass effect of 62.5% (15/24), leading to complete recanalization (DMVO-p-TICI 3). Median number of passes was 1 (range 1-2). No complications related to distal PCA aspiration thrombectomy occurred. Median NIHSS and mRS scores at discharge were 4 (IQR 8) and 3 (IQR 2), respectively. CONCLUSIONS: ADAPT appears to be feasible, safe and effective for the treatment of acute DPCAOs in the setting of different occlusion patterns. High revascularization rates without procedural complications can be achieved. Further studies are needed to consolidate these results.

Differential Cellular Sensing of Fusion from within and Fusion from without during Virus Infection.

The physical entry of virus particles into cells triggers an innate immune response that is dependent on both calcium and nucleic acid sensors, with particles containing RNA or DNA genomes detected by RNA or DNA sensors, respectively. While membrane fusion in the absence of viral nucleic acid causes an innate immune response that is dependent on calcium, the involvement of nucleic acid sensors is poorly understood. Here, we used lipoplexes containing purified reovirus p14 fusion protein as a model of exogenous or fusion from without and a cell line expressing inducible p14 protein as a model of endogenous or fusion from within to examine cellular membrane fusion sensing events. We show that the cellular response to membrane fusion in both models is dependent on calcium, IRF3 and IFN. The method of sensing fusion, however, differs between fusion from without and fusion from within. Exogenous p14 lipoplexes are detected by RIG-I-like RNA sensors, whereas fusion by endogenous p14 requires both RIG-I and STING to trigger an IFN response. The source of nucleic acid that is sensed appears to be cellular in origin. Future studies will investigate the source of endogenous nucleic acids recognized following membrane fusion events.

Endovascular treatment of distal medium vessel occlusions using microcatheter aspiration thrombectomy.

BACKGROUND AND PURPOSE: Recent studies suggest that endovascular treatment (EVT) in distal medium vessel occlusion (DMVO) stroke is beneficial even beyond middle cerebral artery (MCA) - M2 segment. However, data about aspiration thrombectomy of DMVOs is scarce since common state-of-the-art aspiration catheters are usually too large for small distal intracranial arteries. We report our initial experiences using the microcatheter aspiration thrombectomy (MAT) technique as frontline therapy for acute DMVOs in the MCA territory. METHODS: We retrospectively analyzed all acute ischemic stroke (AIS) patients that underwent MAT of a primary or secondary DMVO in the M3 or M4 segment between January 2019 and October 2021. Recanalization rates, procedural safety and outcome data were recorded. RESULTS: MAT of acute M3 and M4 occlusions was performed in 19 patients with AIS. Six had isolated DMVO strokes, 13 had secondary DMVOs during EVT of a proximal large vessel occlusion. Successful revascularization to DMVO TICI ≥ 2b was achieved in 58% (11/19) with a single pass in all of them. The median National Institutes of Health Strokes Scale (NIHSS) score at admission and discharge was 12 and 3, respectively. 68% (13/19) of the patients had a good clinical outcome at discharge (modified Rankin Scale 0-2). No symptomatic complications related to MAT occurred. CONCLUSIONS: MAT of DMVOs in the MCA territory is technically feasible and effective. Compared to stent retriever-based thrombectomy in DMVOs the hemorrhagic complication rate appears notably lower. Further studies are needed to validate the benefit of mechanical thrombectomy in the distal intracranial vasculature.

Using Drosophila melanogaster to Analyse the Human Paralogs of the ESCRT-III Core Component Shrub/CHMP4/Snf7 and Its Interactions with Members of the LGD/CC2D1 Family.

The evolutionary conserved ESCRT-III complex is a device for membrane remodelling in various cellular processes, such as the formation of intraluminal vesicles (ILVs), cytokinesis, and membrane repair. The common theme of all these processes is the abscission of membrane away from the cytosol. At its heart in Drosophila is Shrub, CHMP4 in humans, which dynamically polymerises into filaments through electrostatic interactions among the protomers. For the full activity, Shrub/CHMP4 requires physical interaction with members of the Lgd protein family. This interaction is mediated by the odd-numbered DM14 domains of Lgd, which bind to the negative interaction surface of Shrub. While only one Lgd and one Shrub exist in the genome of Drosophila, mammals have two Lgd orthologs, LGD1/CC2D1B and LGD2/CC2D1A, as well as three CHMP4s in their genomes, CHMP4A, CHMP4B, and CHMP4C. The rationale for the diversification of the ESCRT components is not understood. We here use Drosophila as a model system to analyse the activity of the human orthologs of Shrub and Lgd at an organismal level. This enabled us to use the plethora of available techniques available for Drosophila. We present evidence that CHMP4B is the true ortholog of Shrub, while CHMP4A and CHMP4C have diverging activities. Nevertheless, CHMP4A and CHMP4C can enhance the activity of CHMP4B, raising the possibility that they can form heteropolymers in vivo. Our structure-function analysis of the LGD1 and LGD2 indicates that the C2 domain of the LGD proteins has a specific function beyond protein stability and subcellular localisation. Moreover, our data specify that CHMP4B interacts more efficiently with LGD1 than with LGD2.

Inhalation Therapy with Nebulized Capsaicin in a Patient with Oropharyngeal Dysphagia Post Stroke: A Clinical Case Report.

Dysphagia and aspiration risk are common sequelae of stroke, leading to increased risk of stroke-associated pneumonia. This is often aggravated by stroke-related impairment of cough, the most immediate mechanical defense mechanism against aspiration. In humans, reflex cough can be repeatedly and safely elicited by inhalation of nebulized capsaicin, a compound contained in chili peppers. Could this cough-eliciting property of capsaicin support the recovery of stroke survivors who present with dysphagia and aspiration risk? We present a clinical case report of a 73-year-old man, admitted to inpatient stroke rehabilitation following a right middle cerebral artery infarct with subsequent dysphagia and hospital-acquired pneumonia. A course of daily inhalation therapy with nebulized capsaicin was initiated, triggering reflex coughs to support secretion clearance and prevent recurrence of pneumonia. Clinical observations in each inhalation therapy session demonstrate good patient response, safety and tolerability of nebulized capsaicin in this mode of application. Repeated Fiberoptic Endoscopic Evaluation of Swallowing (FEES) assessments show concurrent improvement in the patient's swallowing status. Inhalation therapy with nebulized capsaicin may offer a viable treatment to facilitate coughing and clearing of secretions, and to minimize aspiration and risk of aspiration-related pneumonia post stroke. Further investigation in a randomized controlled trial design is warranted.

Innovative and Highly Sensitive Detection of Clostridium perfringens Enterotoxin Based on Receptor Interaction and Monoclonal Antibodies.

Clostridium perfringens enterotoxin (CPE) regularly causes food poisoning and antibiotic-associated diarrhea; therefore, reliable toxin detection is crucial. To this aim, we explored stationary and mobile strategies to detect CPE either exclusively by monoclonal antibodies (mAbs) or, alternatively, by toxin-enrichment via the cellular receptor of CPE, claudin-4, and mAb detection. Among the newly generated mAbs, we identified nine CPE-specific mAbs targeting five distinct epitopes, among them mAbs recognizing CPE bound to claudin-4 or neutralizing CPE activity in vitro. In surface plasmon resonance experiments, all mAbs and claudin-4 revealed excellent affinities towards CPE, ranging from 0.05 to 2.3 nM. Integrated into sandwich enzyme-linked immunosorbent assays (ELISAs), the most sensitive mAb/mAb and claudin-4/mAb combinations achieved similar detection limits of 0.3 pg/mL and 1.0 pg/mL, respectively, specifically detecting recombinant CPE from spiked feces and native CPE from 30 different C. perfringens culture supernatants. The implementation of mAb- and receptor-based ELISAs into a mobile detection platform enabled the fast detection of CPE, which will be helpful in clinical laboratories to diagnose diarrhea of assumed bacterial origin. In conclusion, we successfully employed an endogenous receptor and novel high affinity mAbs for highly sensitive and specific CPE-detection. These tools will be useful for both basic and applied research.

Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection.

Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.

Abstract art paintings, global image properties, and verbal descriptions: An empirical and computational investigation.

While global image properties (GIPs) relate to preference ratings in many categories of visual stimuli, this relationship is typically not seen for abstract art paintings. Using computational network science and empirical methods, we further investigated GIPs and subjective preferences. First, we replicated the earlier observation that GIPs do not relate to preferences for abstract art. Next, we estimated the network structure of abstract art paintings using two approaches: the first was based on verbal descriptions and the second on GIPs. We examined the extent to which network measures computed from these two networks (1) related to preference for abstract art paintings and (2) determined affiliation of images to specific art styles. Only semantic-based network predicted the subjective preference ratings and art style. Finally, preference and GIPs differed for sub-groups of abstract art paintings. Our results demonstrate the importance of verbal descriptors in evaluating abstract art, and that it is not useful in empirical aesthetics to treat abstract art paintings as a single category.

An Electrochemical Fiveplex Biochip Assay Based on Anti-Idiotypic Antibodies for Fast On-Site Detection of Bioterrorism Relevant Low Molecular Weight Toxins.

Modern threats of bioterrorism force the need for multiple detection of biothreat agents to determine the presence or absence of such agents in suspicious samples. Here, we present a rapid electrochemical fiveplex biochip screening assay for detection of the bioterrorism relevant low molecular weight toxins saxitoxin, microcystin-LR, T-2 toxin, roridin A and aflatoxin B1 relying on anti-idiotypic antibodies as epitope-mimicking reagents. The proposed method avoids the use of potentially harmful toxin-protein conjugates usually mandatory for competitive immunoassays. The biochip is processed and analyzed on the automated and portable detection platform pBDi within 13.4 min. The fiveplex biochip assay revealed toxin group specificity to multiple congeners. Limits of detection were 1.2 ng/mL, 1.5 ng/mL, 0.4 ng/mL, 0.5 ng/mL and 0.6 ng/mL for saxitoxin, microcystin-LR, T-2 toxin, roridin A or aflatoxin B1, respectively. The robustness of the fiveplex biochip for real samples was demonstrated by detecting saxitoxin, microcystin-LR, HT-2 toxin, roridin A and aflatoxin B1 in contaminated human blood serum without elaborate sample preparation. Recovery rates were between 52-115% covering a wide concentration range. Thus, the developed robust fiveplex biochip assay can be used on-site to quickly detect one or multiple low molecular weight toxins in a single run.

Upregulation of SPDEF is associated with poor prognosis in prostate cancer.

SAM pointed domain-containing Ets transcription factor (SPDEF), a member of the ETS transcription factor family, has been associated with prostate cancer development; however, its role in tumour development and progression is controversial. In the present study, SPDEF expression was analysed on a tissue microarray with >12,000 prostate cancer samples. SPDEF expression levels were higher in most prostate cancer samples than in normal prostate epithelium, suggesting SPDEF was upregulated in cancer. Nuclear SPDEF expression was identified in 80% of prostate cancer samples, and considered weak in 26.4%, moderate in 40.1% and strong in 13.5% of cases. SPDEF positivity was significantly associated with tumour stage, Gleason grade, lymph node metastasis and PSA recurrence (all P<0.0001). SPDEF overexpression was more common in ERG positive (94%) than in ERG negative cancer (69%; P<0.0001). Elevated SPDEF expression predicted poor prognosis independent from established prognostic parameters, including Gleason grade, pT, pN, serum PSA level and nodal status (P<0.01). In summary, SPDEF overexpression was associated with aggressive behaviour, particularly in ERG negative prostate cancer, and may have potential for clinical application.

[Reviewing the psychological and physical health effects of forests]. / Les effets de la forêt sur la santé physique et mentale. Une revue de la littérature scientifique.

Civilization illnesses today impact, and will impact in the future, everyday life of people, particularly in high-income countries. Consequences are loss in life expectancy, reduction of quality of life as well as rising economic loads. The positive effects of stays and visits in natural environments on human well-being are known for a long time. Particularly, there are many indications that forest stays have health-promoting effects. This narrative review of the literature presents the current state of the research on health-promoting effects of forest exposure. Forest exposure has positive health effects on the cardiovascular system, the immune system and on mood. Especially in the context of stress reduction, forest exposure seems to have positive influences. However, little can be concluded about the extent of these positive effects, as most studies work without control environment or control groups. Moreover forest exposure is often associated with physical activity which is also known to have health benefits. Against the background of the positive health promoting trend further research should be carried out.

Electrochemical Biochip Assays Based on Anti-idiotypic Antibodies for Rapid and Automated On-Site Detection of Low Molecular Weight Toxins.

Phycotoxins and mycotoxins, such as paralytic shellfish poisoning toxins, type A trichothecenes, and aflatoxins are among the most toxic low molecular weight toxins associated with human poisoning incidents through the consumption of naturally contaminated food. Therefore, there is an utmost need for rapid and sensitive on-site detection systems. Herein, an electrochemical biochip for fast detection of saxitoxin, T-2 toxin as well as aflatoxin M1 and their corresponding congeners, respectively, using a portable and fully automated detection platform (pBDi, portable BioDetector integrated) was developed. Toxin analysis is facilitated upon the biochip via an indirect competitive immunoassay using toxin-specific antibodies combined with anti-idiotypic antibodies. The developed biochips enable detection in the low ng/mL-range within 17 min. Moreover, the assays cover a wide linear working range of 2-3 orders of magnitude above the limit of detection with an inter-chip coefficient of variation lower than 15%. The broad specificity of the employed antibodies which react with a large number of congeners within the respective toxin group allows efficient screening of contaminated samples for the presence of these low molecular weight toxins. With respect to the analysis of human urine samples, we focused here on the detection of saxitoxin, HT-2 toxin, and aflatoxin M1, all known as biomarkers of acute toxin exposure. Overall, it was proved that the developed biochip assays can be used to rapidly and reliably identify severe intoxications caused by these low molecular weight toxins.

Face Attractiveness versus Artistic Beauty in Art Portraits: A Behavioral Study.

From art portraits, the observer may derive at least two different hedonic values: The attractiveness of the depicted person and the artistic beauty of the image that relates to the way of presentation. We argue that attractiveness is a property that is predominantly driven by perceptual processes, while the perception of artistic beauty is based predominantly on cognitive processing. To test this hypothesis, we conducted two behavioral experiments. In a gist study (Experiment 1), we showed that ratings on attractiveness were higher after short-term presentation (50 ms) than after long-term presentation (3000 ms), while the opposite pattern was found for artistic beauty. In an experiment on perceptual contrast (Experiment 2), we showed that the perceptual contrast effect was stronger for attractiveness than for artistic beauty. These results are compatible with our hypothesis that appreciation of artistic beauty is cognitively modulated at least in part, while processing of attractiveness is predominantly driven perceptually. This dichotomy between cognitive and perceptual processing of different kinds of beauty suggests the participation of different neuronal mechanisms.

Controlling the Photocorrosion of Zinc Sulfide Nanoparticles in Water by Doping with Chloride and Cobalt Ions.

Photodegradation under UV light irradiation is a major drawback in photocatalytic applications of sulfide semiconductors. ZnS nanoparticles were doped with very low amounts of chloride or cobalt ions in the ppm range and codoped with chloride and cobalt ions during their synthesis by precipitation in aqueous solution followed by calcination. The high-temperature wurtzite phase annealed at 800 °C had a high susceptibility to UV irradiation in water, while the low-temperature zincblende phase annealed at 400 °C was found to be stable. Chlorine doping increased the rate of photocorrosion in water, whereas cobalt doping led to a stabilization of the ZnS nanoparticles. Based on photochemical and spectroscopic investigations applying UV/vis, X-ray photoelectron, and photoluminescence spectroscopy, the increased susceptibility of Cl-doped ZnS is ascribed to a higher number of surface point defects, whereas the stabilization by Co2+ is caused by additional recombination pathways for the charge carriers in the bulk, thus avoiding photocorrosion processes at the surface. Additional doping of Cl-doped ZnS with cobalt ions was found to counteract the detrimental effect of the chloride ions efficiently.

Viral Evasion Strategies in Type I IFN Signaling - A Summary of Recent Developments.

The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.

Nuclear Egress of Herpesviruses: The Prototypic Vesicular Nucleocytoplasmic Transport.

Herpesvirus particles mature in two different cellular compartments. While capsid assembly and packaging of the genomic linear double-stranded DNA occur in the nucleus, virion formation takes place in the cytoplasm by the addition of numerous tegument proteins as well as acquisition of the viral envelope by budding into cellular vesicles derived from the trans-Golgi network containing virally encoded glycoproteins. To gain access to the final maturation compartment, herpesvirus nucleocapsids have to cross a formidable barrier, the nuclear envelope (NE). Since the ca. 120 nm diameter capsids are unable to traverse via nuclear pores, herpesviruses employ a vesicular transport through both leaflets of the NE. This process involves proteins which support local dissolution of the nuclear lamina to allow access of capsids to the inner nuclear membrane (INM), drive vesicle formation from the INM and mediate inclusion of the capsid as well as scission of the capsid-containing vesicle (also designated as "primary virion"). Fusion of the vesicle membrane (i.e., the "primary envelope") with the outer nuclear membrane subsequently results in release of the nucleocapsid into the cytoplasm for continuing virion morphogenesis. While this process has long been thought to be unique for herpesviruses, a similar pathway for nuclear egress of macromolecular complexes has recently been observed in Drosophila. Thus, herpesviruses may have coopted a hitherto unrecognized cellular mechanism of vesicle-mediated nucleocytoplasmic transport. This could have far reaching consequences for our understanding of cellular functions as again unraveled by the study of viruses.

Herpesvirus nuclear egress: Pseudorabies Virus can simultaneously induce nuclear envelope breakdown and exit the nucleus via the envelopment-deenvelopment-pathway.

Herpesvirus replication takes place in the nucleus and in the cytosol. After entering the cell, nucleocapsids are transported to nuclear pores where viral DNA is released into the nucleus. After gene expression and DNA replication new nucleocapsids are assembled which have to exit the nucleus for virion formation in the cytosol. Since nuclear pores are not wide enough to allow passage of the nucleocapsid, nuclear egress occurs by vesicle-mediated transport through the nuclear envelope. To this end, nucleocapsids bud at the inner nuclear membrane (INM) recruiting a primary envelope which then fuses with the outer nuclear membrane (ONM). In the absence of this regulated nuclear egress, mutants of the alphaherpesvirus pseudorabies virus have been described that escape from the nucleus after virus-induced nuclear envelope breakdown. Here we review these exit pathways and demonstrate that both can occur simultaneously under appropriate conditions.