Understanding the Pathogenesis of Lateral Supratentorial Neurenteric Cysts in Close Proximity to Other Vascular Pathologies: A Case Report and Review of Embryology.

Several theories have been postulated to explain the embryogenesis of central nervous system (CNS) neurenteric cysts (NCs), but the exact mechanism remains poorly understood. Of those, the neurenteric canal migration hypothesis suggesting endodermal cell migration through the neurenteric canal and settling among ectodermal cells prior to neural tube closure might be the most robust as it explains, in contrast to other hypotheses, the existence of lateral supratentorial lesions, which are extremely rare, compared to their infratentorial counterparts. This mechanism might be supported by past medical history or the coexistence of CNS epidermoid cysts, which are thought to arise due to improper neural tube closure potentially increasing the probability of endodermal migration and subsequent NC development, yet there are no reported cases in the literature. We present a case of a patient with a history of a previously resected intracranial epidermoid cyst, representing three simultaneous pathologies including a laterally based right frontal NC along with a right corona radiata cavernous malformation lesion, and right middle cerebral artery bifurcation aneurysm. The three lesions were treated microsurgically in one operative session without complications. We discuss the case and review the relevant pathoembryology of laterally based supratentorial NC.

Neurologically Devastating Intraparenchymal Hemorrhage in COVID-19 Patients on Extracorporeal Membrane Oxygenation: A Case Series.

BACKGROUND AND IMPORTANCE: Extracorporeal membrane oxygenation (ECMO) represents a life-saving therapy in cases of refractory hypoxia and has been utilized in patients suffering from the most severe forms of coronavirus disease 2019 (COVID-19). A strikingly high mortality rate of 94% was described in early reports of patients with COVID-19 transitioned to ECMO. Later case reports and series demonstrating successful recovery from COVID-19 after ECMO have revived interest in this therapeutic modality, including the recent approval of ECMO for COVID-19 patients by the Food and Drug Administration (FDA). Here, we present the first reports of devastating intracranial hemorrhage as a complication of veno-venous (VV) ECMO in two COVID-19 patients. CLINICAL PRESENTATION: We performed a retrospective analysis of 2 cases of devastating intracranial hemorrhage in patients on VV-ECMO for the treatment of COVID-19. Collected data included clinical history, laboratory results, treatment, and review of all available imaging. Both patients demonstrated activated partial thromboplastin times (aPTT) within an appropriate therapeutic range. No risk factors that clearly predicted likelihood of this complication were identified. CONCLUSION: Understanding the complications of ECMO in this cohort and developing therapeutic algorithms to aid in optimal patient selection will be critical in the limited resource setting experienced as a result of global pandemic. We propose the use of head computed tomography (CT) to identify devastating neurological complications as early as possible, aiding in the resource allocation of ECMO machines to the most appropriately selected patients.

Cost-Effectiveness of Biomarker Screening for Traumatic Brain Injury.

Intracranial hemorrhage after traumatic brain injury (TBI) can be life threatening and requires prompt diagnosis. Computed tomography (CT) scans are a rapid and accurate way to evaluate for hemorrhage. In patients with mild and moderate TBI, however, in whom the incidence of intracranial pathology is low, scanning every patient with CT can be costly. The Food and Drug Administration recently approved a novel biomarker screen, the Banyan Trauma Indicator (BTI), to help streamline the decision for CT scanning in mild to moderate TBI. The BTI screen diagnoses intracranial lesions with a sensitivity and specificity of 97.5% and 99.6%, respectively. We performed cost analyses of the BTI screen to determine the threshold of cost-effectiveness, compared with application of clinical decision rules or routine CT scans, for cases of mild or moderate TBI. With a 0.104 probability of an intracranial lesion in mild TBI, the biomarker screen is cost-effective if the cost is $308.96 or below per test. In moderate TBI, because of the greater prevalence of intracranial lesions at 0.663, there is a lower need for screening, and BTI becomes cost-effective up to $73.41 per test.

Endovascular therapies for malignant gliomas: Challenges and the future.

Malignant gliomas are very difficult tumors to treat, with few effective therapies, early progression and high rates of recurrence. Here we review the literature on malignant gliomas treated with endovascular therapy. Endovascular therapy for malignant gliomas falls into one of three categories: (1) neoadjuvant embolization and devascularization; (2) direct intra-arterial drug delivery; and (3) disruption of the blood-brain barrier for improved intra-arterial drug delivery. There is a range of therapeutic benefits based on the endovascular intervention used. Challenges remain for those who aim to treat malignant gliomas with an endovascular approach. Specifically, embolization is difficult to accomplish in the small vessels that feed into malignant gliomas, and intra-arterial chemotherapy has yet to prove itself better than traditional intravenous chemotherapy. However, there exists promise in the therapeutic potential of intra-arterial chemotherapy paired with disruption of the blood-brain barrier at tumor-specific sites, and as such, continued research to optimize this approach is expected to yield benefit for patients with malignant gliomas.

Neuropilin-2 contributes to tumorigenicity in a mouse model of Hedgehog pathway medulloblastoma.

The Hedgehog (Hh) signaling pathway has been implicated in the most common childhood brain tumor, medulloblastoma (MB). Given the toxicity of post-surgical treatments for MB, continued need exists for new, targeted therapies. Based upon our finding that Neuropilin (Nrp) transmembrane proteins are required for Hh signal transduction, we investigated the role of Nrp in MB cells. Cultured cells derived from a mouse Ptch (+/-) ;LacZ MB (Med1-MB), effectively modeled the Hh pathway-related subcategory of human MBs in vitro. Med1-MB cells maintained constitutively active Hh target gene transcription, and consistently formed tumors within one month after injection into mouse cerebella. The proliferation rate of Med1-MBs in culture was dependent upon Nrp2, while reducing Nrp1 function had little effect. Knockdown of Nrp2 prior to cell implantation significantly increased mouse survival, compared to transfection with a non-targeting siRNA. Knocking down Nrp2 specifically in MB cells avoided any direct effect on tumor vascularization. Nrp2 should be further investigated as a potential target for adjuvant therapy in patients with MB.

FARP1 promotes the dendritic growth of spinal motor neuron subtypes through transmembrane Semaphorin6A and PlexinA4 signaling.

The dendritic morphology of neurons dictates their abilities to process and transmit information; however, the signaling pathways that regulate dendritic growth and complexity are poorly understood. Here, we show that retinoids induce the expression of the FERM Rho-GEF protein FARP1 in the developing spinal cord. FARP1 is expressed in subsets of motor neurons and is enriched in dendrites of lateral motor column (LMC) neurons that innervate the limb. FARP1 is necessary and sufficient to promote LMC dendritic growth but does not affect dendrite number or axonal morphology. We show that FARP1 serves as a specific effector of transmembrane Semaphorin6A and PlexinA4 signals to regulate LMC dendritic growth, and that its Rho-GEF domain is necessary for this function. These findings reveal that retinoid and Sema6A/PlexA4 signaling pathways intersect through FARP1 to control dendritic growth, and uncover the existence of subtype-specific signaling networks that control dendritic developmental programs in spinal motor neurons.