Treatment of iatrogenic vertebral artery injury during C1-C2 arthrodesis with a covered stent.

Iatrogenic vertebral artery injury (VAI) has been described in the context of both anterior and posterior approaches to the cervical spine.1 2 Endovascular treatment of VAI primarily entails vessel sacrifice or vascular reconstruction. The latter option offers the advantage of achieving hemostasis while maintaining parent vessel patency.

Transradial versus transfemoral access for mechanical thrombectomy: A single institution experience.

Background: There has been debate in the literature regarding the adoption of a "radial-first" approach for mechanical thrombectomy (MT) in acute ischemic stroke (AIS). Conflicting reports suggest that transradial access (TRA) may allow for shorter times to reperfusion while others conclude that long-term functional outcomes may favor transfemoral access (TFA). Here, we report a single-institution experience with the adoption of TRA as the primary route for acute stroke intervention.

Vertebral Artery to Middle Cerebral Artery Bypass for Flow Augmentation.

Background And Importance: Extracranial-intracranial bypass remains an enduring procedure for a select group of patients suffering from steno-occlusive cerebrovascular disease. Although the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass is most familiar among neurosurgeons, particular circumstances preclude the use of an STA donor. In such cases, alternative revascularization strategies must be pursued.

Hemodynamic outcomes of stenting for vertebrobasilar insufficiency in patients with a low flow state.

Introduction: The Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study determined patients with low flow in their vertebrobasilar (VB) system are at increased risk of recurrent stroke. Endovascular interventions such as angioplasty and stenting are reserved for patients with refractory symptoms; however, few series to date have demonstrated either hemodynamic or clinical outcomes in this high-risk patient group. We present our combined institutional series of patients with symptomatic VB atherosclerotic disease and low-flow state who underwent angioplasty and stenting.

Transradial flow diversion with an aberrant right subclavian artery.

Transradial access for diagnostic and therapeutic neurointerventional procedures has gained popularity due to a decreased incidence of access site complications and improved patient comfort compared with transfemoral access.1-4 An aberrant right subclavian artery is an aortic arch variant characterized by a right subclavian artery that arises directly from the arch as the most distal great vessel. Transradial access with an aberrant right subclavian artery is anatomically challenging due to the predilection of the catheter system to collapse into the descending aorta.

A persistent trigeminal artery demonstrates cerebrovascular embryologic development.

Background: Cerebrovascular embryologic development is characterized by the presence of four well-described carotid-vertebrobasilar (VB) anastomoses. As the fetal hindbrain matures and the VB system develops, these connections involute, yet some may persist into adulthood. The persistent primitive trigeminal artery (PPTA) is the most common of these anastomoses.

Accelerated Aging in Cyclophilin B-Deficient Mice Downstream of p21-Cip1/Waf1.

Loss of bone mass and strength is a common problem of advanced age in humans. Defective bone is also a primary finding in osteogenesis imperfecta (OI), a genetic condition most commonly caused by autosomal dominant mutations in the type I collagen genes. Although altered collagen has been proposed to correlate with cellular processes that underlie aging, the causal relationships between them in vivo have not yet been completely explored.

Phase I trial of sargramostim/pelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors.

Background: Brain tumors are the leading cause of cancer death for pediatric patients. Pelareorep, an immunomodulatory oncolytic reovirus, has intravenous efficacy in preclinical glioma models when preconditioned with GM-CSF (sargramostim). We report a phase I trial with the primary goal of evaluating the safety of sargramostim/pelareorep in pediatric patients with recurrent or refractory high-grade brain tumors and a secondary goal of characterizing immunologic responses.

Early expression of mature αβ TCR in CD4CD8 T cell progenitors enables MHC to drive development of T-ALL bearing NOTCH mutations.

During normal T cell development in mouse and human, a low-frequency population of immature CD4CD8 double-negative (DN) thymocytes expresses early, mature αβ T cell antigen receptor (TCR). We report that these early αβ TCR+ DN (EADN) cells are DN3b-DN4 stage and require CD3δ but not major histocompatibility complex (MHC) for their generation/detection. When MHC - is present, however, EADN cells can respond to it, displaying a degree of coreceptor-independent MHC reactivity not typical of mature, conventional αβ T cells.

Microsurgical Clipping of a Ruptured Basilar-P1 Junction Aneurysm.

In current neurosurgical practice, treatment paradigms for posterior circulation aneurysms have shifted away from microsurgical clip ligation toward endovascular therapy. This is largely due to the results of the International Subarachnoid Aneurysm Trial and International Study of Unruptured Intracranial Aneurysms, which, in part, showed that outcomes in patients with ruptured aneurysms were better with coiling and that a location in the posterior circulation was an independent risk factor for poor outcome, respectively. Nevertheless, there exist certain anatomic features that highlight the importance of a microsurgical approach.

Delayed intracerebral hemorrhage from a traumatic carotid-cavernous fistula associated with an enucleated orbit.

Spontaneous intracerebral hemorrhage (ICH) from a traumatic carotid-cavernous fistula (CCF) is a rare occurrence with few cases reported in the literature. Patients classically present shortly after the inciting trauma with symptoms of ocular venous hypertension. We report a case of an ICH due to delayed rupture of a venous aneurysm from a CCF in a patient with decades-old history of enucleation of the left globe secondary to trauma with no sentinel symptoms.

TNFRSF13B genotypes control immune-mediated pathology by regulating the functions of innate B cells.

Host genes define the severity of inflammation and immunity but specific loci doing so are unknown. Here we show that TNF receptor superfamily member 13B (TNFRSF13B) variants, which enhance defense against certain pathogens, also control immune-mediated injury of transplants, by regulating innate B cells' functions. Analysis of TNFRSF13B in human kidney transplant recipients revealed that 33% of those with antibody-mediated rejection (AMR) but fewer than 6% of those with stable graft function had TNFRSF13B missense mutations.

TNFRSF13B polymorphisms counter microbial adaptation to enteric IgA.

TNFRSF13B encodes the transmembrane activator and CAML interactor (TACI) receptor, which drives plasma cell differentiation. Although TNFRSF13B supports host defense, dominant-negative TNFRSF13B alleles are common in humans and other species and only rarely associate with disease. We reasoned that the high frequency of disruptive TNFRSF13B alleles reflects balancing selection, the loss of function conferring advantage in some settings.

Intervention for symptomatic vertebrobasilar disease.

Disease of the vertebral (VA) and basilar arteries (BA) can lead to stroke of the posterior circulation and may warrant management strategies which differ from the anterior circulation. The mechanism and location of the disease determine its natural history and therefore affect the relative risks and benefits of the possible treatment options. Vertebrobasilar (VB) atherosclerotic disease is a source of both hemodynamic and embolic posterior circulation stroke.

Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype.

Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial-mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase (PPIase) activity of cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here we demonstrate that in cultured TECs, CypA silencing triggers loss of epithelial features and enhances transforming growth factor β (TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail.

Chemotherapy-induced cellular senescence suppresses progression of Notch-driven T-ALL.

T cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy that occurs in children and young adults. Current therapies include intensive chemotherapy and ionizing radiation that preferentially kill malignant cells. Unfortunately, they are frequently accompanied by unintended negative impacts, including the induction of cellular senescence and long-term toxicities in normal host tissues.

Immunotherapy in pediatric B-cell acute lymphoblastic leukemia.

Advances in multi-agent chemotherapy and supportive care have dramatically improved survival of children with B-cell acute lymphoblastic leukemia (B-ALL); however, patients with relapsed and refractory disease continue to represent a therapeutic challenge. Hematopoietic stem cell transplant was the first immunotherapeutic approach to be used in the treatment of patients with relapsed or refractory disease. However, novel therapies such as bispecific antibodies that engage T-cells and chimeric antigen receptor T-cells (CAR-T) therapy have emerged as novel FDA-approved options that have the potential to become the new standard of care for these difficult-to-treat leukemias.

Non-syndromic single-suture craniosynostosis in triplets.

Introduction: Craniosynostosis is the premature fusion of one or more cranial sutures. The cause of non-syndromic craniosynostosis has been attributed to a complex interaction among genetic, epigenetic, and environmental factors. Increased concordance rates in monozygotic twins support a genetic etiology while a concordance rate less than 100% suggests environmental and/or epigenetic influences.

Protein synthesis inhibition enhances paraptotic death induced by inhibition of cyclophilins in glioblastoma cells.

Treatment of cancer is frequently unsuccessful related to the loss of apoptotic signaling in malignant cells. This is a particular problem for high-grade gliomas, such as Glioblastoma Multiforme (GBM), which are almost universally fatal within a year or so of diagnosis. Novel therapies that capitalize on non-apoptotic cell death pathways may yield more effective outcomes, if their underlying mechanisms can be more completely deciphered.

Atypical Presentation of a Pediatric Cerebellar Ganglioglioma.

Background/aims: Gangliogliomas (GGs) are rare central nervous system tumors occurring primarily in the supratentorial compartment with infratentorial instances most often involving the brain stem. Infratentorial GGs typically present with signs and symptoms of increased intracranial pressure (ICP), cranial nerve deficits, or focal cerebellar findings; rarely, these tumors have been associated with focal seizures.

Methods: In this report, we describe an atypical presentation of a cerebellar GG in a 20-month-old male who initially presented with syncope and emesis in the absence of electrographic evidence of seizures, radiographic evidence of hydrocephalus, or elevated ICP.