Several research has underlined the multi-system character of COVID-19. Though effects on the Central Nervous System are mainly discussed as disease-specific affections due to the virus' ...neurotropism, no comprehensive disease model of COVID-19 exists on a neurofunctional base by now. We aimed to investigate neuroplastic grey- and white matter changes related to COVID-19 and to link these changes to neurocognitive testings leading towards a multi-dimensional disease model.
Groups of acutely ill COVID-19 patients (n = 16), recovered COVID-19 patients (n = 21) and healthy controls (n = 13) were prospectively included into this study. MR-imaging included T1-weighted sequences for analysis of grey matter using voxel-based morphometry and diffusion-weighted sequences to investigate white matter tracts using probabilistic tractography. Comprehensive neurocognitive testing for verbal and non-verbal domains was performed.
Alterations strongly focused on grey matter of the frontal-basal ganglia-thalamus network and temporal areas, as well as fiber tracts connecting these areas. In acute COVID-19 patients, a decline of grey matter volume was found with an accompanying diminution of white matter tracts. A decline in executive function and especially verbal fluency was found in acute patients, partially persisting in recovered.
Changes in gray matter volume and white matter tracts included mainly areas involved in networks of executive control and language. Deeper understanding of these alterations is necessary especially with respect to long-term impairments, often referred to as 'Post-COVID'.
The aim of our study was to systematically compare two-point Dixon fat suppression (FS) and spectral FS techniques in contrast enhanced imaging of the head and neck region.
Three independent readers ...analysed coronal T
weighted images recorded after contrast medium injection with Dixon and spectral FS techniques with regard to FS homogeneity, motion artefacts, lesion contrast, image sharpness and overall image quality.
85 patients were prospectively enrolled in the study. Images generated with Dixon-FS technique were of higher overall image quality and had a more homogenous FS over the whole field of view compared with the standard spectral fat-suppressed images (p < 0.001). Concerning motion artefacts, flow artefacts, lesion contrast and image sharpness no statistically significant difference was observed.
The Dixon-FS technique is superior to the spectral technique due to improved homogeneity of FS and overall image quality while maintaining lesion contrast. Advances in knowledge: T
with Dixon FS technique offers, compared to spectral FS, significantly improved FS homogeneity and over all image quality in imaging of the head and neck region.
To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on ...hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients’ FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage.
Patients with unresectable metastasized osteosarcoma have a poor prognosis. Current treatment options do not offer a chance to cure the disease in this situation. Despite the fact that immunotherapy ...has expanded its indications continuously over previous years, its use is not yet established in osteosarcoma. There is a lack of randomized controlled studies that could show a significant benefit in this rare tumor entity. So far, efficacy of immunotherapy is only reported in individual cases as well as in mouse models. To predict a response to immunotherapy, testing for programmed death-ligand 1 (PD-L1) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) can be useful, but status is not yet clear for most cancer entities.
Single case study and review of the literature.
This report presents the case of a 37-year-old patient with metastatic advanced osteosarcoma, who had no more established options for tumor treatment left. PD-L1 expression in the most recent tumor sample was high (tumor proportion score (TPS) 90%, combined positive score (CPS) 92%) but no MSI could be detected. In an individual therapy attempt, an ongoing and profound remission of all tumor manifestations due to four cycles of immunotherapy with ipilimumab and nivolumab was reached. Despite discontinuation of immunotherapy for 3 months due to therapy-related pneumonitis, remission of all tumor manifestations was ongoing, and no detectable relapse in restaging before onset of Nivolumab-maintenance could be observed.
The present case constitutes the first report of an adult patient with metastasized advanced osteosarcoma who reached a deep remission of disease by immunotherapy with ipilimumab and nivolumab, which continued even though immunotherapy had to be interrupted. To verify whether the high expression of PD-L1, as seen in this patient, is a predictive marker for response to immunotherapy in osteosarcoma, requires further investigation.
Objective:
Flow diverter (FD) stents have become one of the most common tools for treating intracranial aneurysms; however, their role in treating posterior circulation aneurysms is still discussed ...with controversy. In this study, we evaluated the safety and effectiveness of p64 FD for the treatment of saccular, unruptured aneurysms in the posterior circulation over a long-term follow-up period in a single center.
Methods:
From our prospectively maintained database, we retrospectively identified patients who underwent treatment of an intracranial saccular aneurysm arising from the posterior circulation with ≥1 p64 FD implanted or attempted between October 2012 and December 2019. Aneurysms could have been treated with prior or concomitant saccular treatment (e.g., coiling, intra-aneurysmal flow diversion). Aneurysms with parent vessel implants other than p64, fusiform aneurysms, and dissections were excluded. Peri- and postprocedural complications, clinical outcome, and clinical and angiographic follow-up results were evaluated.
Results:
In total, 54 patients (45 female, 9 male; mean age 55.1 years) with 54 intracranial aneurysms met the inclusion criteria. In 51 cases (94.4%), one p64 was implanted; in 2 cases (3.7 %), two p64s were implanted; in one case, deployment of the p64 was not feasible. Procedural complications occurred in 3.7% and postprocedural complications in 9.3 %, respectively. Hemorrhagic complications occurred in 2/54 patients (3.7%), thereof one fatal parenchymal hemorrhage. Ischemic complications were observed in 5/54 patients (9.3%). Early, mid-term, and long-term angiographic follow-up examinations showed complete or near-complete aneurysm occlusion, defined according to the O'Kelly –Marotta (OKM) scale as OKM C + D in 56, 75.6, and 82.9 %, respectively. Asymptomatic side vessel occlusions occurred in 3.8%, each during the first follow-up.
Conclusions:
The implantation of a p64 FD is a safe and effective device for endovascular treatment of posterior circulation saccular aneurysms with a high success rate and low morbi-mortality.
A 40-year-old Caucasian man presented with sudden onset of left-sided hemiparesis associated with dysphonia, dysphagia, and right-sided weakness on shoulder elevation and head rotation. The clinical ...examination revealed deviation of the tongue to the right, absence of right-sided gag reflex, right-sided palatal and vocal cord paresis, and weakness of the right trapezius and sternocleidomastoid muscles; all were in addition to left-sided brachiocephalic-accentuated hemiparesis. The diagnostic examination revealed dissection of the right carotid artery with occlusion of the middle cerebral artery and infarction in the lenticular-striatal artery territory. Mechanical thrombectomy with stent angioplasty of the right internal carotid artery was performed. The paresis of the left side of the body completely regressed within a week after symptom onset, but the dysphonia, weakness of the right trapezius and sternocleidomastoid muscles, and especially dysphagia persisted and regressed slowly but gradually. The patient required percutaneous gastric tube feeding for the next 12 weeks, possibly because of involvement of subcortical white matter tracts. The constellation of symptoms and clinical findings were consistent with Collet-Sicard syndrome, an extremely rare disorder caused by direct compression of the caudal cranial nerves at the base of the skull.
Available 4- and 5-year updates for progression-free and for overall survival demonstrate a lasting clinical benefit for melanoma patients receiving anti-PD-directed immune checkpoint inhibitor ...therapy. However, at least one-half of the patients either do not respond to therapy or relapse early or late following the initial response to therapy. Little is known about the reasons for primary and/or secondary resistance to immunotherapy and the patterns of relapse. This review, prepared by an interdisciplinary expert panel, describes the assessment of the response and classification of resistance to PD-1 therapy, briefly summarizes the potential mechanisms of resistance, and analyzes the medical needs of and therapeutic options for melanoma patients resistant to immune checkpoint inhibitors. We appraised clinical data from trials in the metastatic, adjuvant and neo-adjuvant settings to tabulate frequencies of resistance. For these three settings, the role of predictive biomarkers for resistance is critically discussed, as well as are multimodal therapeutic options or novel immunotherapeutic approaches which may help patients overcome resistance to immune checkpoint therapy. The lack of suitable biomarkers and the currently modest outcomes of novel therapeutic regimens for overcoming resistance, most of them with a PD-1 backbone, support our recommendation to include as many patients as possible in novel or ongoing clinical trials.
Drug-coated balloons (DCB) are an established tool in the prevention and treatment of coronary and peripheral artery restenosis. The underlying effects of restenosis resemble those in the ...neurovascular field, yet data on the use of DCB in cervical and intracranial arteries is rare.BackgroundDrug-coated balloons (DCB) are an established tool in the prevention and treatment of coronary and peripheral artery restenosis. The underlying effects of restenosis resemble those in the neurovascular field, yet data on the use of DCB in cervical and intracranial arteries is rare.Medline, and international and major national guidelines and recommendations were systematically searched for data addressing the use of DCB in the neurovascular setting.MethodsMedline, and international and major national guidelines and recommendations were systematically searched for data addressing the use of DCB in the neurovascular setting.Of the 1448 relevant records found in Medline, 166 publications were considered for this review.ResultsOf the 1448 relevant records found in Medline, 166 publications were considered for this review.Data on the use of DCB in the neurovascular setting show a possible benefit over preceding alternatives, such as self-expanding stents, and balloon-mounted or drug-eluting stents. Nonetheless, the role of DCB remains under-researched, and publications remain lacking.ConclusionsData on the use of DCB in the neurovascular setting show a possible benefit over preceding alternatives, such as self-expanding stents, and balloon-mounted or drug-eluting stents. Nonetheless, the role of DCB remains under-researched, and publications remain lacking.
Purpose In elective carotid artery stenting (CAS), antiplatelet therapy (APT) is crucial. Several international societies have provided guidelines for loading time and dosage in endovascular ...treatment; however, no recommendations have been made for urgent, nonthrombectomy-associated CAS without adequate loading time. Here, we investigated the short-term outcomes for APT-naïve patients receiving "crash loading" (CL) on the day of intervention, compared with those for patients wi APT onset 3-5 days (semi-CL) or more than 5 days before CAS (EL). Methods Outcomes of patients 30 days after CAS were evaluated in terms of the rates of in-stent thrombus, re-stenosis, stroke, hemorrhagic and thrombotic events, other periprocedural occurrences, in-hospital death and CAS-associated death. Patients' biological, pathological and hemostatic factors were recorded and compared. Results A total of 1158 patients who received CAS at the authors' neuroradiology institution were analyzed: 275 EL, 846 semi-CL, and 37 CL. The patients receiving CL had the lowest rate of stroke, but the highest rates of CAS-associated and in-hospital deaths, although the deaths were not necessarily associated with APT. In-stent thrombosis was the highest in the semi-CL group. The rates and types of periprocedural occurrences favored the CL group. Conclusion With the medical regimen used in this study, urgent CAS with CL APT did not produce more ischemic, thrombotic and hemorrhagic complications than longer loading times. However, careful patient selection might be crucial and adequate loading times should remain the standard of care.
Mobile brain perfusion ultrasound (BPU) is a novel non-imaging technique creating only hemispheric perfusion curves following ultrasound contrast injection and has been specifically designed for ...early prehospital large vessel occlusion (LVO) stroke identification. We report on the first patient investigated with the SONAS® system, a portable point-of-care ultrasound system for BPU. This patient was admitted into our stroke unit about 12 h following onset of a fluctuating motor aphasia, dysarthria and facial weakness resulting in an NIHSS of 3 to 8. Occlusion of the left middle cerebral artery occlusion was diagnosed by computed tomography angiography. BPU was performed in conjunction with injection of echo-contrast agent to generate hemispheric perfusion curves and in parallel, conventional color-coded sonography (TCCS) assessing MCAO. Both assessments confirmed the results of angiography. Emergency mechanical thrombectomy (MT) achieved complete recanalization (TICI 3) and post-interventional NIHSS of 2 the next day. Telephone follow-up after 2 years found the patient fully active in professional life. Point-of-care BPU is a non-invasive technique especially suitable for prehospital stroke diagnosis for LVO. BPU in conjunction with prehospital stroke scales may enable goal-directed stroke patient placement, i.e., directly to comprehensive stroke centers aiming for MT. Further results of the ongoing phase II study are needed to confirm this finding.