BACKGROUND Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited. OBJECTIVE To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events. METHODS We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation. RESULTS We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14). CONCLUSION COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected—particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.

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The Notch signaling pathway controls cell fate decision, proliferation, and other biological functions in both vertebrates and invertebrates. Precise regulation of the canonical Notch pathway ensures robustness of the signal throughout development and adult tissue homeostasis. Aberrant Notch signaling results in profound developmental defects and is linked to many human diseases. In this study, we identified the Atrophin family protein RERE (also called Atro2) as a positive regulator of Notch target Hes genes in the developing vertebrate spinal cord. Prior studies have shown that during early embryogenesis in mouse and zebrafish, deficit of RERE causes various patterning defects in multiple organs including the neural tube. Here, we detected the expression of RERE in the developing chick spinal cord, and found that normal RERE activity is needed for proper neural progenitor proliferation and neuronal differentiation possibly by affecting Notch-mediated Hes expression. In mammalian cells, RERE co-immunoprecipitates with CBF1 and Notch intracellular domain (NICD), and is recruited to nuclear foci formed by over-expressed NICD1. RERE is also necessary for NICD to activate the expression of Notch target genes. Our findings suggest that RERE stimulates Notch target gene expression by preventing degradation of NICD protein, thereby facilitating the assembly of a transcriptional activating complex containing NICD, CBF1/RBPjκ in vertebrate, Su(H) in Drosophila melanogaster, Lag1 in C. elegans, and other coactivators.

Background Congenital aortic arch anomalies are commonly encountered during neurointerventional procedures. While some anomalies are identified at an early age, many are incidentally discovered later in adulthood during endovascular evaluations or interventions. Proper understanding of the normal arch anatomy and its variants is pivotal to safely navigate normal aortic arch branches and to negotiate the catheter through anomalies during neurointerventional procedures. This is particularly relevant in the increasingly “transradial first” culture of neurointerventional surgery. Moreover, some of these anomalies have a peculiar predilection for complications including aneurysm formation, dissection, and rupture during the procedure. Therefore, an understanding of these anomalies, their underlying embryological basis and associations, and pattern of circulation will help endovascular neurosurgeons and interventional radiologists navigate with confidence and consider relevant pathologic associations that may inform risk of cerebrovascular disease. Methods Here, we present a brief review of the basic embryology of the common anomalies of the aortic arch along with their neurological significances and discuss, through illustrative cases, the association of aortic arch anomalies with cerebral vascular pathology. Conclusions Understanding the aortic arch anomalies and its embryological basis is essential to safely navigate the cerebral vascular system during neurointerventional surgeries.

OBJECTIVEEngagement in research and scholarship is considered a hallmark of neurosurgical training. However, the participation of neurosurgical trainees in this experience has only recently been analyzed and described in the United States, with little, if any, data available regarding the research environment in neurosurgical training programs across the globe. Here, the authors set out to identify requirements for research involvement and to quantify publication rates in leading neurosurgical journals throughout various nations across the globe.METHODSThe first aim was to identify the research requirements set by relevant program-accrediting and/or board-certifying agencies via query of the literature and published guidelines. For the second part of the study, the authors attempted to determine each country’s neurosurgical research productivity by quantifying publications in the various large international neurosurgical journals—World Neurosurgery, Journal of Neurosurgery, and Neurosurgery—via a structured search of PubMed.RESULTSData on neurosurgical training requirements addressing research were available for 54 (28.1%) of 192 countries. Specific research requirements were identified for 39 countries, partial requirements for 8, and no requirements for 7. Surprisingly, the authors observed a trend of increased average research productivity with the absence of designated research requirements, although this finding is not unprecedented in the literature.CONCLUSIONSA variety of countries of various sizes and neurosurgical workforce densities across the globe have instituted research requirements during training and/or prior to board certification in neurosurgery. These requirements range in intensity from 1 publication or presentation to the completion of a thesis or dissertation and occur at various time points throughout training. While these requirements do not correlate directly to national research productivity, they may provide a foundation for developing countries to establish a culture of excellence in research.

Significance Several signaling pathways have been implicated in regulating blood–brain/spinal cord barrier (BBB) properties in the adult mammalian central nervous system (CNS). However, it has become clear that the role of the Sonic hedgehog pathway has not been accurately defined. The current work addresses this issue by demonstrating that the pathway is required in protoplasmic astrocytes to maintain specific BBB characteristics in select regions of the CNS. In contrast to prior studies, we find that astrocytic, and not endothelial cell, Hedgehog signal transduction is required to maintain BBB properties through an effect on transcytosis but not paracellular diffusion. Our discovery raises the possibility that targeted inhibition of the pathway to achieve transient BBB permeability could be exploited for therapeutic purposes.

<b><i>Introduction:</i></b> Pediatric vein of Galen malformations (VOGMs) are fistulous intracranial malformations arising congenitally within the choroidal fissure that can present with an array of neurological and cardiac sequelae. Associated venous stenosis may result in intracranial venous hypertension and ischemia leading to severe, irreversible cerebral injury. Management of neonatal VOGMs typically involves staged embolization and angioplasty/stenting for relief of venous stenosis. Rarely, jugular foraminal narrowing has been identified as causing jugular bulb stenosis. <b><i>Case Presentation:</i></b> We present the case of a 22-month-old female diagnosed with VOGM prenatally who displayed persistent intracranial venous hypertension despite multiple neuroembolization procedures during the neonatal period. Following initial reduction in arteriovenous shunting, she once again developed venous hypertension secondary to jugular bulb stenosis for which angioplasty was attempted. Failure of angioplasty to relieve the venous hypertension prompted skull base imaging, which revealed jugular foraminal ossification and stenosis. Microsurgical jugular foraminotomy followed by balloon angioplasty and stenting significantly reduced jugular pressure gradients. Restenosis requiring re-stenting developed postoperatively at 9 months, but the patient has remained stable with significant improvement in cortical venous congestion. <b><i>Discussion/Conclusion:</i></b> This case demonstrates the efficacy of microsurgical decompression of the jugular foramen and endovascular angioplasty/stenting as a novel treatment paradigm for the management of intracranial venous hypertension in the setting of VOGM.

<b><i>Background:</i></b> Knobloch syndrome (KS) is a rare autosomal recessive disorder associated with multiple ocular and cranial abnormalities. Occult occipital skull defect or encephalocele should raise suspicion of this disease. It is never reported in neurosurgical literature, possibly due to a lack of clinician familiarity, leading to underdiagnosis and inadequate management. Our patient also had seizures, which is a sporadic presentation of this syndrome. <b><i>Case Description:</i></b> Here, we report a clinico-radiologic finding of a 7-year-old boy who presented with seizures, cataracts, and an occipital bone defect along with bilateral subependymal heterotopias and polymicrogyria. <b><i>Conclusions:</i></b> This case highlights the importance of consideration of this syndrome in children with a midline occipital bone defect with or without encephalocele and seizures. Early recognition of this presentation is critical for obtaining access to appropriate genetic counseling and subsequent monitoring and prevention of complications by surgical intervention.