Targeting coagulation factor XII as a novel therapeutic option in brain trauma.

Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use.

No correlation between NF1 mutation position and risk of optic pathway glioma in 77 unrelated NF1 patients.

Neurofibromatosis type 1 (NF1) is a common monogenic disorder whereby affected individuals are predisposed to developing CNS tumors, including optic pathway gliomas (OPGs, occurring in ~15 to 20 % of cases). So far, no definite genotype-phenotype correlation determining NF1 patients at risk for tumor formation has been described, although enrichment for mutations in the 5' region of the NF1 gene in OPG patients has been suggested. We used whole exome sequencing, targeted sequencing, and copy number analysis to screen 77 unrelated NF1 patients with (n = 41) or without (n = 36; age ≥10 years) optic pathway glioma for germline NF1 alterations.

Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke.

Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation.

Beneficial impact of high-field intraoperative magnetic resonance imaging on the efficacy of pediatric low-grade glioma surgery.

Objective: Intraoperative MRI (iMRI) is assumed to safely improve the extent of resection (EOR) in patients with gliomas. This study focuses on advantages of this imaging technology in elective low-grade glioma (LGG) surgery in pediatric patients.

Methods: The surgical results of conventional and 1.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features.

Neuroendoscopic Trans-Third Ventricular Approach for Surgical Management of Ecchordosis Physaliphora.

Background: We sought to report the successful surgical management of a case of ecchordosis physaliphora (EP) using a neuro-endoscopic trans-third ventricular approach (ETTVA) and to provide a current review of literature on EP.

Case Description: A 57-year-old man presenting with a 2-year history of diplopia due to right abducens nerve palsy and paresthesia of the left body underwent magnetic resonance imaging, which revealed a retroclival intracisternal lesion. The cystic lesion was considered to be most likely EP according to neuroradiologic features.

Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice.

Background: Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A).

Long-Term, Continuous Intra-Arterial Nimodipine Treatment of Severe Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Background: Secondary vasospasm and disturbances in cerebrovascular autoregulation are associated with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. An intra-arterial application of nimodipine has been shown to increase the vessel diameter, although this effect is transient. The feasibility of long-term, continuous, intra-arterial nimodipine treatment and its effects on macrovasospasm, autoregulation parameters, and outcome were evaluated in patients with refractory severe macrovasospasm.

Fingolimod (FTY720-P) Does Not Stabilize the Blood-Brain Barrier under Inflammatory Conditions in an in Vitro Model.

Breakdown of the blood-brain barrier (BBB) is an early hallmark of multiple sclerosis (MS), a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P), a signaling protein, via S1P receptors (S1P₁). Fingolimod phosphate (FTY720-P) a functional S1P₁ antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes.

Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study.

Immune cells (IC) play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA), chronic cerebrovascular disease (CCD) and healthy volunteers (HV).

Endoscopic bronchial valve treatment: patient selection and special considerations.

As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe emphysema and significant hyperinflation. Lung function parameters and comorbidities of the patient, as well as the extent and distribution of the emphysema are factors to be considered when choosing the patient and the intervention. Endoscopic bronchial valve placement with complete occlusion of one lobe in patients with heterogeneous emphysema is the preferred technique because of its reversibility.

Pretreatment with rivaroxaban attenuates stroke severity in rats by a dual antithrombotic and anti-inflammatory mechanism.

Stroke outcome is more favourable in patients receiving oral anticoagulants compared with non-anticoagulated patients. The reasons for this "stroke-attenuating" property of oral anticoagulants are largely unknown. This study examined whether prestroke anticoagulation with rivaroxaban, a novel direct factor Xa inhibitor, influences stroke severity, thrombin-mediated intracerebral thrombus formation and pro-inflammatory processes in a rat model of brain ischaemia/reperfusion injury.

Efficacy and Safety of Platelet Glycoprotein Receptor Blockade in Aged and Comorbid Mice With Acute Experimental Stroke.

Background And Purpose: Despite the medical and socioeconomic effect of ischemic stroke and extensive preclinical research, treatment options for ischemic stroke are limited. We recently identified and characterized essential steps of thrombus formation in stroke and demonstrated that inhibition of the platelet glycoprotein (GP) receptors Ib and VI, but not IIb/IIIa, protects young and healthy mice from ischemic neurodegeneration. Whether these findings translate to the clinic remains unclear.

Bevacizumab treatment for symptomatic spinal ependymomas in neurofibromatosis type 2.

Background: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome associated with vestibular schwannomas, meningiomas, and spinal ependymomas. There have been anecdotal reports of radiographic response of spinal ependymomas in NF2 patients being treated for progressive vestibular schwannomas with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF).

Aims: The aim of this study was to review the clinical effects of bevacizumab treatment for symptomatic, NF2-associated ependymomas

Methods: We conducted a retrospective review of all patients with NF2 treated with bevacizumab for symptomatic ependymoma at three NF2 specialty centers.

Congenital left temporal large arachnoid cyst causing intraorbital optic nerve damage in the second decade of life.

Aim: Intracranial sylvian arachnoid cysts are often asymptomatic lesions. We present a 16-year-old female patient with progressive loss of vision together with an unusual visual field defect on the left eye accompanied by headache.

Method: A left frontotemporal sylvian arachnoid cyst was known since she was 9 months old, but observed ever since in the asymptomatic patient.

Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms.

Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis.

PROSAIKA: a prospective multicenter registry with the first programmable gravitational device for hydrocephalus shunting.

Objective: Cerebrospinal fluid (CSF) overdrainage is a major problem in shunt therapy for hydrocephalus. The adjustable gravitational valve proSA allows for the first time a targeted compensation for overdrainage in the upright position without interfering with the differential pressure valve. To evaluate benefit, safety and reliability, the multicenter prospective registry PROSAIKA was conducted in 10 German neurosurgical centers.

Animal models of ischemic stroke and their application in clinical research.

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke.

Analysis of IDH1-R132 mutation, BRAF V600 mutation and KIAA1549-BRAF fusion transcript status in central nervous system tumors supports pediatric tumor classification.

Objective: Gliomas are the leading cause of cancer-related morbidity in children and comprise a clinical, histological and molecular heterogenous group of CNS tumors. Appropriate treatment of these tumors relies on correct classification into tumor types and malignancy grades.

Methods: We examined 170 (0-18 years) pediatric and 131 (19-35 years) young adult brain tumors including pilocytic astrocytomas (PAs), pilomyxoid astrocytomas (PMAs), diffuse astrocytomas (DAs), gangliogliomas, dysembryoplastic neuroepithelial tumors (DNTs) and pleomorphic xanthoastrocytomas (PXAs) for IDH1 and BRAF mutation/BRAF fusion gene status.

Visualizing the pressure and time burden of intracranial hypertension in adult and paediatric traumatic brain injury.

Purpose: To assess the impact of the duration and intensity of episodes of increased intracranial pressure on 6-month neurological outcome in adult and paediatric traumatic brain injury.

Methods: Analysis of prospectively collected minute-by-minute intracranial pressure and mean arterial blood pressure data of 261 adult and 99 paediatric traumatic brain injury patients from multiple European centres. The relationship of episodes of elevated intracranial pressure (defined as a pressure above a certain threshold during a certain time) with 6-month Glasgow Outcome Scale was visualized in a colour-coded plot.

Computed tomography predictors of response to endobronchial valve lung reduction treatment. Comparison with Chartis.

Rationale: Chartis Pulmonary Assessment System (Pulmonx Inc., Redwood, CA) is an invasive procedure used to assess collateral ventilation and select candidates for valve-based lung volume reduction (LVR) therapy. Quantitative computed tomography (QCT) is a potential alternative to Chartis and today consists primarily of assessing fissure integrity (FI).

Blocking of plasma kallikrein ameliorates stroke by reducing thromboinflammation.

Objective: Recent evidence suggests that ischemic stroke is a thromboinflammatory disease. Plasma kallikrein (PK) cleaves high-molecular-weight kininogen to release bradykinin (BK) and is a key constituent of the proinflammatory contact-kinin system. In addition, PK can activate coagulation factor XII, the origin of the intrinsic coagulation cascade.

Comparison of different tractography algorithms and validation by intraoperative stimulation in a child with a brain tumor.

Background: Advanced modalities such as functional magnetic resonance imaging (MRI) and diffusion MR tractography offer in vivo information about brain networks and are therefore increasingly used for neurosurgical planning in children also.

Aim: This study aims to study the application of routine and advanced tractography algorithms and its comparison with intraoperative subcortical electrical stimulation.

Method: Presurgical functional MRI and MR diffusion tractography were performed on a 6-year-old patient presenting with seizures, but no motor symptoms, due to a neuroectodermal tumor in the left central region.

Transient but not permanent benefit of neuronal progenitor cell therapy after traumatic brain injury: potential causes and translational consequences.

Background: Numerous studies have reported a beneficial impact of neural progenitor cell transplantation on functional outcome after traumatic brain injury (TBI) during short and medium follow-up periods. However, our knowledge regarding long-term functional effects is fragmentary while a direct comparison between local and systemic transplantation is missing so far.

Objectives: This study investigated the long-term (12 week) impact of human fetal neuronal progenitor cell (hNPC) transplantation 24 h after severe TBI in rats.

CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke.

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion.