Cerebellar Degeneration as Presenting Symptom of Recurrent Endometrial Stromal Sarcoma with Sex-Cord Elements

We report a 66-year-old woman with slowly progressive ataxia due to cerebellar atrophy. Imaging studies revealed multiple lesions in both the lungs and dorsal subpleural space. A biopsy identified the lesions as metastases of a low-grade endometrial stromal sarcoma containing sex-cord elements. The histological appearance was identical to a uterine tumor the patient was treated for with hysterectomy 16 years before. The metastases were removed surgically, and after 3 months ataxia had regressed. We conclude that the presenting cerebellar degeneration in this patient resulted from the metastatic recurrence of the endometrial tumor

A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage

Stroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been shown to compensate for myelin loss and prevent axonal loss through the replacement of lost oligodendrocytes, an inefficient process leaving axons chronically demyelinated. Phenotypic screening approaches in demyelinating paradigms revealed substances that promote myelin repair. We established an ex vivo adult organotypic coronal slice culture (OCSC) system to study repair after stroke in a resource-efficient way. Post-photothrombotic OCSCs can be manipulated for 8 d by exposure to pharmacologically active substances testing remyelination activity. OCSCs were isolated from a NG2-CreERT2-td-Tomato knock-in transgenic mouse line to analyze oligodendroglial fate/differentiation and kinetics. Parbendazole boosted differentiation of NG2+ cells and stabilized oligodendroglial fate reflected by altered expression of associated markers PDGFR-α, CC1, BCAS1 and Sox10 and GFAP. In vitro scratch assay and chemical ischemia confirmed the observed effects upon parbendazole treatment. Adult OCSCs represent a fast, reproducible, and quantifiable model to study OPC differentiation competence after stroke. Pharmacological stimulation by means of parbendazole promoted OPC differentiation

OSIRIS – The scientific camera system onboard Rosetta

The Optical, Spectroscopic, and Infrared Remote Imaging System OSIRIS is the scientific camera system onboard the Rosetta spacecraft (Figure 1). The advanced high performance imaging system will be pivotal for the success of the Rosetta mission. OSIRIS will detect 67P/Churyumov-Gerasimenko from a distance of more than 106 km, characterise the comet shape and volume, its rotational state and find a suitable landing spot for Philae, the Rosetta lander. OSIRIS will observe the nucleus, its activity and surroundings down to a scale of ~2 cm px−1. The observations will begin well before the onset of cometary activity and will extend over months until the comet reaches perihelion. During the rendezvous episode of the Rosetta mission, OSIRIS will provide key information about the nature of cometary nuclei and reveal the physics of cometary activity that leads to the gas and dust coma. OSIRIS comprises a high resolution Narrow Angle Camera (NAC) unit and a Wide Angle Camera (WAC) unit accompanied by three electronics boxes. The NAC is designed to obtain high resolution images of the surface of comet 7P/Churyumov-Gerasimenko through 12 discrete filters over the wavelength range 250–1000 nm at an angular resolution of 18.6 μrad px−1. The WAC is optimised to provide images of the near-nucleus environment in 14 discrete filters at an angular resolution of 101 μrad px−1. The two units use identical shutter, filter wheel, front door, and detector systems. They are operated by a common Data Processing Unit. The OSIRIS instrument has a total mass of 35 kg and is provided by institutes from six European countrie

Case report: First case of neuromelioidosis in Europe: CNS infection caused by Burkholderia pseudomallei

Neuromelioidosis is a rare CNS infection caused by Burkholderia pseudomallei and is characterized by high morbidity and mortality. Our report presents the diagnostic and therapeutic approach of the first case of neuromelioidosis confirmed in Europe. A 47-year-old man with a medical history of recurrent otitis with otorrhea and fever after tympanoplasty and radical cavity revision operation on the left ear was admitted with headache, decreased level of consciousness, dysarthria, left-sided hemiparesis, and urinary incontinence. After extensive investigations including MRI, microbiological, serological, and CSF analyses, and, ultimately, brain biopsy, a diagnosis of neuromelioidosis was established. Despite antibiotic treatment, the patient showed no clinical improvement and remained in a severely compromised neurological state under mandatory mechanical ventilation. Neuromelioidosis can pose a diagnostic challenge requiring an extensive diagnostic evaluation because of its uncommon clinical and radiological presentations

IFNβ secreted by microglia mediates clearance of myelin debris in CNS autoimmunity

INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS) leading to progressive neurological disability. Interferon β (IFNβ) represents a standard treatment for relapsing-remitting MS and exogenous administration of IFNβ exhibits protective effects in experimentally induced CNS autoimmunity. Also, genetic deletion of IFNβ in mice leads to an aggravation of disease symptoms in the MS model of experimental autoimmune encephalomyelitis (EAE). However, neither the underlying mechanisms mediating the beneficial effects nor the cellular source of IFNβ have been fully elucidated. RESULTS: In this report, a subpopulation of activated microglia was identified as the major producers of IFNβ in the CNS at the peak of EAE using an IFNβ-fluorescence reporter mouse model. These IFNβ expressing microglia specifically localized to active CNS lesions and were associated with myelin debris in demyelinated cerebellar organotypic slice cultures (OSCs). In response to IFNβ microglia showed an enhanced capacity to phagocytose myelin in vitro and up-regulated the expression of phagocytosis-associated genes. IFNβ treatment was further sufficient to stimulate association of microglia with myelin debris in OSCs. Moreover, IFNβ-producing microglia mediated an enhanced removal of myelin debris when co-transplanted onto demyelinated OSCs as compared to IFNβ non-producing microglia. CONCLUSIONS: These data identify activated microglia as the major producers of protective IFNβ at the peak of EAE and as orchestrators of IFNβ-induced clearance of myelin debris. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0192-4) contains supplementary material, which is available to authorized users

Stroke aftercare in Germany: findings from an online survey in the outpatient setting of a neurovascular network

The evidence-based acute treatment of stroke patients in Germany is carried out according to standardized algorithms in more than 300 certified stroke units, and its quality is repeatedly assured by the German Stroke Society (DSG) and others. However, nationally structured and uniform stroke aftercare programs are missing, despite evidence that they contribute to the success of rehabilitation and improvement of everyday life. We used a 27-item online questionnaire, which was mailed to 4,195 outpatient physicians in the catchment area of the neurovascular network Neurovascular Network North Rhine plus (NEVANO+) located in the western part of Germany to assess actual structures of stroke aftercare, identify barriers, and possible solutions. Based on 152 completed anonymous answers to the questionnaire, a descriptive evaluation revealed that general practitioners and neurologists are seen to be responsible for stroke aftercare. Important improvement aspects, among others, were identified in intersectoral cooperation, the use of a post-stroke checklist, and connections to local self-help organizations. Stroke units could play a key role in stroke aftercare by providing these checklists, connecting self-help organizations, and offering education and coaching for supportive coordinating staff. Furthermore, existing neurovascular networks can be expanded to include rehabilitation clinics, geriatric clinics, and outpatient physicians to improve intersectoral communication, collaboration, and post-stroke care. Further studies should investigate whether intersectoral cooperation, checklists, and cooperation with self-help organizations within an extended neurovascular network have a positive impact on stroke aftercare and patients’ quality of life

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Neutrophils extracellular traps myeloperoxidase and elastase predict cerebral vasospasms after aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is a highly fatal and morbid disease. Despite successful coiling or clipping of a ruptured aneurysm, the patients suffer post-aSAH complications, including early brain injury, cerebral vasospasm (CVS), delayed cerebral ischemia (DCI), and systemic infections that mainly determine the clinical outcomes. Diagnostic biomarkers to predict accurately post-aSAH complications are needed. In this prospective exploratory study, we investigated the predictive value of neutrophil extracellular traps (NETs) components for CVS after aSAH. In the study, 62 patients with aSAH, 17 patients with unruptured cerebral aneurysms, and 12 healthy controls were included. The serum levels of myeloperoxidase (MPO), elastase (ELA), and citrullinated histone H3 (cH3) on day 1 and day 4 of hospital admission were measured with ELISA. Data were scaled using the Yeo-Johnson transformation. Values in two groups were compared using a t-test and in multiple groups using ANOVA. Logistic regression was used to model the outcome probability, including CVS, as the function of ELISA values. Among the patients with aneurysms, those who suffered aSAH had significantly higher levels of MPO (113.9 ± 294.4 vs. 422.3 ± 319.0 ng/ml, p < 0.05), ELA (84.8 ± 221.0 vs. 199.2 ± 218.9 ng/ml, p < 0.05), and cH3 (0.0 ± 0.0 vs. 2.8 ± 1.5, ng/ml, p < 0.05) on day one after aSAH, suggesting the involvement of NETs components in pathophysiology of aSAH and the events following aSAH. Individually, MPO and ELA levels taken on day 1 after SAH did not differ between patients with CVS and patients without CVS. However, when taken together into a logistic model, they allowed for predicting CVS with high sensitivity (91 %) and specificity (79 %). MPO and ELA, along with other clinical parameters, can be used as early predictors of CVS in aSAH patients and can serve as guidance during treatment decisions in the management of aSAH