Autoregulated splicing of β programs T cell fate in response to antigen-receptor stimulation.

T cell receptor (TCR) sensitivity to peptide-major histocompatibility complex (MHC) dictates T cell fate. Canonical models of TCR sensitivity cannot be fully explained by transcriptional regulation. In this work, we identify a posttranscriptional regulatory mechanism of TCR sensitivity that guides alternative splicing of TCR signaling transcripts through an evolutionarily ultraconserved poison exon (PE) in the RNA-binding protein (RBP) TRA2β in mouse and human.

Dorsal arachnoid web of the thoracic spine associated with an arachnoid cyst and a presyrinx state as an unexplained cause of thoracic myelopathy: illustrative case.

Background: Dorsal thoracic arachnoid web is a rare diagnosis and is not commonly seen in neurosurgical practice. Patients can present with symptoms and signs of thoracic myelopathy in the setting of an arachnoid cyst and a presyrinx state.

Observations: A 57-year-old male with a 10-year history of worsening bilateral leg weakness and chronic back pain re-presented to the neurosurgery clinic after being seen by neurology and orthopedic spine surgery.

Healthcare transition in pediatric neurosurgery: lessons learned from a pilot program for patients with hydrocephalus and spina bifida.

Objective: The pediatric neurosurgical community has increasingly recognized the importance of healthcare transition, the process of moving a patient from a pediatric to an adult model of care. However, surveys of pediatric neurosurgeons have revealed that few institutions have formal transition programs. Here, the authors share their preliminary experience with the development of a formal transition pilot program for patients with spina bifida and/or hydrocephalus.

Reconstitution of the alternative pathway of the complement system enables rapid delineation of the mechanism of action of novel inhibitors.

The complement system plays a critical role in the innate immune response, acting as a first line of defense against invading pathogens. However, dysregulation of the complement system is implicated in the pathogenesis of numerous diseases, ranging from Alzheimer's to age-related macular degeneration and rare blood disorders. As such, complement inhibitors have enormous potential to alleviate disease burden.

Loss of Endothelial TDP-43 Leads to Blood Brain Barrier Defects in Mouse Models of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

Loss of nuclear TDP-43 occurs in a wide range of neurodegenerative diseases, and specific mutations in the gene that encodes the protein are linked to familial Frontal Temporal Lobar Dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS). Although the focus has been on neuronal cell dysfunction caused by TDP-43 variants, mRNA transcripts are expressed at similar levels in brain endothelial cells (ECs). Since increased permeability across the blood brain barrier (BBB) precedes cognitive decline, we postulated that altered functions of TDP-43 in ECs contributes to BBB dysfunction in neurodegenerative disease.

Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case.

Background: Esthesioneuroblastoma (ENB) is a rare neoplasm of the sinonasal tract. Currently, the optimal treatment includes maximal resection combined with radiotherapy and/or chemotherapy. Although ENBs often recur and have an aggressive clinical course, spinal metastases are extremely rare and the underlying molecular mechanisms are poorly understood.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

Objective: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema.

Natural history of mild trigonocephalic deformities.

Objective: Ridging along the metopic suture line can be a common cause of concern for parents and has been theorized to represent a mild form of trigonocephaly, a cranial deformity associated with risks of negative cosmetic outcomes, if not surgically corrected. Yet the literature contains sparse reports of long-term cosmetic results or expectations for infants with isolated metopic ridging compared with those with severe trigonocephaly, or even what objective metrics discriminate isolated metopic ridging from severe trigonocephaly. Therefore, the authors' goals for this study were to 1) quantify the degree of frontal deformity among patients with metopic ridge, metopic craniosynostosis, and normocephalic head shapes; and 2) document the natural history of frontal deformities in isolated metopic ridge patients in the 1st year of life.

Recruitment into Academic Neurosurgery Using a Model for Successful Cross-Campus Research Collaboration: A Premedical Student Survey.

Objective: Recruitment of diverse and talented students to the field of neurosurgery is key to its continued growth and scientific advancement. Barriers, including poor perceptions and lack of early exposure, can impact recruitment and have been compounded by the ongoing COVID-19 pandemic. This study examines the impact of an inaugural Neurosurgery Research Consortium meeting on premedical students, assessing whether this exposure generated interest and improved perceptions of a career in neurosurgery.

Incorporation of a biparietal narrowing metric to improve the ability of machine learning models to detect sagittal craniosynostosis with 2D photographs.

Objective: Sagittal craniosynostosis is the most common form of craniosynostosis and typically results in scaphocephaly, which is characterized by biparietal narrowing, compensatory frontal bossing, and an occipital prominence. The cephalic index (CI) is a simple metric for quantifying the degree of cranial narrowing and is often used to diagnose sagittal craniosynostosis. However, patients with variant forms of sagittal craniosynostosis may present with a "normal" CI, depending on the part of the suture that is closed.

Telemedicine Utilization in an Outpatient Pediatric Neurosurgical Clinic: A Prospective Survey of Patient and Family Preferences.

Objective: After becoming widespread during the COVID-19 pandemic, telemedicine continues to play an important role in outpatient neurosurgical care. Nevertheless, the factors that influence individual decisions to choose telemedicine versus in-person appointments remain understudied. Here, we performed a prospective survey of pediatric neurosurgical patients and caregivers presenting for telemedicine or in-person outpatient visits, to identify factors associated with appointment choice.

Clinical metrics and tools for provider assessment and tracking of trigonocephaly.

Objective: Quantitative measurements of trigonocephaly can be used to characterize and track this phenotype, which is associated with metopic craniosynostosis. Traditionally, trigonocephaly metrics were extracted from CT scans; however, this method exposes patients to ionizing radiation. Three-dimensional optical scans are another option but are not routinely available in most outpatient settings.

DNA methylation provides diagnostic value for meningioma recurrence in clinical practice.

Background: Meningiomas are the most common intracranial tumors. Recent advancements in the genetic profiling of tumors have allowed information including DNA copy number analysis, mutational analysis, and RNA sequencing to be more frequently reported, in turn allowing better characterization of meningiomas. In recent years, analysis of tumor methylomes that reflects both cell-origin methylation signatures and somatically acquired DNA methylation changes has been utilized to better classify meningiomas with great success.

T2-weighted Imaging Hyperintensity and Transcranial Motor-evoked Potentials During Cervical Spine Surgery: Effects of Sevoflurane in 150 Consecutive Cases.

Background: There is debate on the impact of inhalational esthetic agents on transcranial motor evoked potentials (TcMEPs) during intraoperative neuromonitoring. Current guidelines advise their avoidance, which contrasts with common clinical practice.

Methods: This retrospective cohort study of 150 consecutive cervical spine surgeries at a single institution compared stimulation voltages and TcMEP amplitudes in patients who did and did not receive sevoflurane as part of a balanced anesthetic technique.

Spinal Lymphoma Presenting as an Epidural and Retropleural Mass With Concomitant Pathologic Compression Fracture: A Case Report.

Lymphoma has traditionally earned the nickname "the great mimicker". Its presentation as a primary spinal tumor is rare, and therefore seldom included in the differential diagnosis. However, its mimicking nature and diverse presentation make it very difficult to exclude entirely.

Early experience with targeted therapy as a first-line adjuvant treatment for pediatric low-grade glioma.

Objective: Pediatric low-grade gliomas (pLGGs) frequently exhibit dysregulation of the mitogen-activated protein kinase (MAPK) pathway. Targeted therapies, including mutant BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib), have shown promise in patients in whom conventional chemotherapy has failed. However, few studies have investigated the use of targeted therapy as a first-line treatment for pLGG.

MYC regulates a pan-cancer network of co-expressed oncogenic splicing factors.

MYC is dysregulated in >50% of cancers, but direct targeting of MYC has been clinically unsuccessful. Targeting downstream MYC effector pathways represents an attractive alternative. MYC regulates alternative mRNA splicing, but the mechanistic links between MYC and the splicing machinery in cancer remain underexplored.

Pilocytic Astrocytoma Arising from the Conus Medullaris in an Adult: A Case Report.

Low-grade, sporadic, pilocytic astrocytomas (PAs) are rare spinal cord tumors diagnosed in adult patients. Their localization to the conus medullaris is exceedingly rare, having only been described in a limited number of case reports. Here, we describe a case of a 22-year-old female presenting with back pain, lower extremity weakness, hypoesthesia, and urinary incontinence.

Family-acquired photographs for the evaluation of pediatric head shape via telemedicine: an analysis of photograph quality.

Objective: Telemedicine can be an effective tool for the evaluation of the pediatric patient with a cranial deformity, but it increases the reliance of neurosurgical providers on data provided by patients and families. Family-acquired photographs, in particular, can be used to augment the evaluation of pediatric head shape abnormalities via telemedicine, but photographs of sufficient quality are necessary. Here, the authors systematically reviewed the quality and utility of family-acquired photographs for patients referred to their pediatric neurosurgery clinic for telemedicine-based head shape evaluations.

Landscape of genetic variants in sporadic meningiomas captured with clinical genomics.

Background: Meningiomas are the most common primary central nervous system tumor. Previous studies have characterized recurrent genetic alterations that can predict patient prognosis and potentially provide new avenues for therapeutic intervention. Continued efforts to characterize the genomic changes in meningioma samples can aid in the discovery of therapeutic targets and appropriate patient stratification.