Endovascular Treatment and Peri-interventional Management of Ruptured Cerebrovascular Lesions During Pregnancy : Case Series and Case-based Systematic Review.

PURPOSE: Hemorrhagic stroke, particularly occurring from ruptured cerebrovascular malformations, is responsible for 5-12% of all maternal deaths during pregnancy and the puerperium. Whether endovascular treatment is feasible and safe for both the mother and the fetus, is still a matter of debate. The main objective of this case series and systematic review was to share our multi-institutional experience and to assess the feasibility and safety of endovascular treatment during pregnancy, as well as the corresponding maternal and fetal outcomes based on currently available evidence. METHODS: We report a case series of 12 pregnant women presenting with hemorrhagic stroke from ruptured cerebrovascular arteriovenous malformations or aneurysms who underwent endovascular treatment prior to delivery. A systematic literature review of pregnant patients with endovascular treated cerebrovascular malformations, published between 1995 and 2022, was performed. Clinical patient information, detailed treatment strategies, maternal and fetal outcomes as well as information on the delivery were collected and assessed. RESULTS: In most patients the course was uneventful and an excellent outcome without significant neurological deficits (mRS ≤ 1) was achieved. Furthermore, the maternal outcome was not worse compared to the general population who underwent endovascular treatment of ruptured vascular brain lesions. Also, in most cases a healthy fetus was born. CONCLUSION: Endovascular treatment of ruptured cerebrovascular malformations during pregnancy is safe and feasible regarding both aspects, the maternal and fetal outcomes. Still, a stronger knowledge base is needed to correctly approach future cases of intracranial hemorrhage in the pregnant population.

Brain cortical alterations in COVID-19 patients with neurological symptoms.

Background: Growing evidence suggests that the central nervous system is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since infected patients suffer from acute and long-term neurological sequelae. Nevertheless, it is currently unknown whether the virus affects the brain cortex. The purpose of this study was to assess the cortical gray matter volume, the cortical thickness, and the cortical surface area in a group of SARS-CoV-2 infected patients with neurological symptoms compared to healthy control subjects. Additionally, we analyzed the cortical features and the association with inflammatory biomarkers in the cerebrospinal fluid (CSF) and plasma. Materials and methods: Thirty-three patients were selected from a prospective cross-sectional study cohort during the ongoing pandemic (August 2020-April 2021) at the university hospitals of Basel and Zurich (Switzerland). The group included patients with different neurological symptom severity (Class I: nearly asymptomatic/mild symptoms, II: moderate symptoms, III: severe symptoms). Thirty-three healthy age and sex-matched subjects that underwent the same MRI protocol served as controls. For each anatomical T1w MPRAGE image, regional cortical gray matter volume, thickness, and surface area were computed with FreeSurfer. Using a linear regression model, cortical measures were compared between groups (patients vs. controls; Class I vs. II-III), with age, sex, MRI magnetic field strength, and total intracranial volume/mean thickness/total surface area as covariates. In a subgroup of patients, the association between cortical features and clinical parameters was assessed using partial correlation adjusting for the same covariates. P-values were corrected using a false discovery rate (FDR). Results: Our findings revealed a lower cortical volume in COVID-19 patients' orbitofrontal, frontal, and cingulate regions than in controls (p < 0.05). Regional gray matter volume and thickness decreases were negatively associated with CSF total protein levels, the CSF/blood-albumin ratio, and CSF EN-RAGE levels. Conclusion: Our data suggest that viral-triggered inflammation leads to neurotoxic damage in some cortical areas during the acute phase of a COVID-19 infection in patients with neurological symptoms.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Immunotherapy of glioblastoma explants induces interferon-γ responses and spatial immune cell rearrangements in tumor center, but not periphery.

A patient-tailored, ex vivo drug response platform for glioblastoma (GBM) would facilitate therapy planning, provide insights into treatment-induced mechanisms in the immune tumor microenvironment (iTME), and enable the discovery of biomarkers of response. We cultured regionally annotated GBM explants in perfusion bioreactors to assess iTME responses to immunotherapy. Explants were treated with anti-CD47, anti-PD-1, or their combination, and analyzed by multiplexed microscopy [CO-Detection by indEXing (CODEX)], enabling the spatially resolved identification of >850,000 single cells, accompanied by explant secretome interrogation. Center and periphery explants differed in their cell type and soluble factor composition, and responses to immunotherapy. A subset of explants displayed increased interferon-γ levels, which correlated with shifts in immune cell composition within specified tissue compartments. Our study demonstrates that ex vivo immunotherapy of GBM explants enables an active antitumoral immune response within the tumor center and provides a framework for multidimensional personalized assessment of tumor response to immunotherapy.

COVID-19 and Preexisting Comorbidities: Risks, Synergies, and Clinical Outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated symptoms, named coronavirus disease 2019 (COVID-19), have rapidly spread worldwide, resulting in the declaration of a pandemic. When several countries began enacting quarantine and lockdown policies, the pandemic as it is now known truly began. While most patients have minimal symptoms, approximately 20% of verified subjects are suffering from serious medical consequences. Co-existing diseases, such as cardiovascular disease, cancer, diabetes, and others, have been shown to make patients more vulnerable to severe outcomes from COVID-19 by modulating host-viral interactions and immune responses, causing severe infection and mortality. In this review, we outline the putative signaling pathways at the interface of COVID-19 and several diseases, emphasizing the clinical and molecular implications of concurring diseases in COVID-19 clinical outcomes. As evidence is limited on co-existing diseases and COVID-19, most findings are preliminary, and further research is required for optimal management of patients with comorbidities.

Initial Experience With the Trevo NXT Stent Retriever.

Background: The application of a new coating to the delivery wire of the Trevo retriever has the potential to improve its handling. We therefore report our initial experience with this new stent retriever for mechanical thrombectomy of large and medium vessel occlusions. Methods: We pooled data of four high-volume European stroke centers over the time period from October 2020 to February 2021. Patients were included in our study if the Trevo NXT stent retriever was used as a first-line device. Primary endpoints were first-pass near-complete or complete reperfusion, defined as mTICI score of ≥2c. Secondary endpoints were final reperfusion, National Institutes of Health Stroke Scale (NIHSS) at 24 h and discharge, device malfunctions, complications during the procedure, and subjective ratings of the interventionalists regarding device functionality. Results: Eighty patients (39 women, mean age 74 ± 14 years) were eligible for our study. Median NIHSS at admission was 15 (IQR, 8-19), and median Alberta Stroke Program Early CT Score at baseline was 9 (IQR, 8-10). In 74 (93%) patients a primary combined approach was used as first-line technique. First-pass near-complete reperfusion was achieved in 43 (54%) and first-pass complete reperfusion in 34 (43%) patients. Final near-complete reperfusion was achieved in 66 (83%) patients after a median of 1.5 (1-3) passes, while final successful reperfusion was observed in 96% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR, 0-5), and 3 patients (4%) suffered a symptomatic intracranial hemorrhage. Conclusions: Based on our initial data, we conclude that the Trevo NXT is an effective and safe tool for mechanical thrombectomy especially when used for combined approaches.

Treatment and Postinterventional Management of a Fusiform Intracranial Aneurysm in a Professional Soccer Player: A Case Report.

INTRODUCTION: While intracranial aneurysms are common lesions affecting between 1 and 5% of the general population, the prevalence in professional athletes remains unknown. The result is uncertainty and lack of guidelines on appropriate treatment of these patients. CASE PRESENTATION: A 29-year-old professional soccer player presented in our hospital with an incidentally found intracranial aneurysm. After detailed depiction of the aneurysm and interdisciplinary discussion, endovascular treatment using a flow diverter was chosen to be the best treatment modality. Postinterventional medication consisted of dual antiplatelet therapy with aspirin and clopidogrel. The main challenge in managing the case of our patient was the combination of the dual antiplatelet treatment regime with his professional career in a contact sport. CONCLUSION: Due to lack of literature or similar reports regarding the management of professional athletes with intracranial aneurysms, the optimal treatment strategy remains unclear. Even though decisions should be made dynamically and case-adapted to each situation, developing a registry could help provide guidance and new ideas for similar cases in the future.