Extradural thoracic nerve root hemangioblastoma approached by a combined posterior thoracic spine and video-assisted thoracoscopic surgery: A case report

Background: Hemangioblastomas commonly occur in the posterior fossa and are typically attributed to sporadic or familial Von Hippel–Lindau disease. Spinal hemangioblastomas, found in 7–10% of patients, are usually located within the cord (i.e., intramedullary). Here, a 58-year-old male presented with a purely extradural hemangioblastoma involving a spinal root that was surgically excised. Case Description: A 58-year-old male was admitted with a progressive paraparesis and incomplete sensory deficit. The magnetic resonance imaging documented a solid dumbbell-shaped lesion that extended through the left T3-T4 foramen resulting in nerve root and spinal cord compression. Following arterial embolization and lesion excision by both neurosurgeons and thoracic surgeons, the patient’s deficits improved. The postoperative computed tomography scan documented complete tumor removal, and the neuropathology revealed a hemangioblastoma. Conclusion: Here, we describe a 58-year-old male with a purely extradural thoracic foraminal T3-T4 dumbbell-shaped hemangioblastoma successfully treated by both embolization and surgical excision.

Sporadic Intradural Extramedullary Hemangioblastoma of Cauda Equina with Large Peritumoral Cyst—A Rare Presentation

Cauda equina intradural tumors commonly reported include ependymoma, schwannoma, neurofibroma, meningioma, and drop metastasis. Hemangioblastoma of the neural axis is a rare benign vascular tumor comprising only 1.6 to 6.4% of spinal tumors, and are usually associated with Von-Hippel Lindau disease. Sporadic intradural extramedullary hemangioblastoma involving cauda equina is very rare with only countable reports, and the presence of peritumoral cyst has been reported only once. We report one such case of hemangioblastoma with a large peritumoral cyst, which was diagnosed radiologically and confirmed by histopathology following surgical excision. Pertinent radiological characteristics, diagnostic clues, treatment, and surgical outcomes are discussed.

Retinal Glial Cells in Von Hippel–Lindau Disease: A Novel Approach in the Pathophysiology of Retinal Hemangioblastoma

Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease.

Is there a role for biomarkers in surveillance of pancreatic neuroendocrine neoplasms in Von Hippel-Lindau’s disease?

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of multi-organ neoplasms. Among the manifestations of VHL are pancreatic neuroendocrine neoplasms (panNENs). In order to detect these lesions in a timely manner, patients are enrolled in a surveillance program, in accordance with the several existing VHL guidelines. However, these guidelines remain unclear about the role of biomarkers in diagnosing panNENs, despite the benefits a biomarker may offer regarding early detection of new lesions, thereby possibly limiting radiation exposure, and improving quality of life. The aim is to determine which biomarkers might be available in VHL patients and to assess what their clinical relevance in diagnosing panNENs in VHL patients is. We searched the databases of Pubmed/Medline, Embase and Web of Science to identify relevant articles. Seven studies assessing the diagnostic or prognostic value of biomarkers were included. The results from these studies were conflicting. Since no evident association between VHL-related panNENs and biomarkers was established in studies with larger study populations, currently biomarkers do not play a significant role in early detection or follow-up for panNENs in VHL patients. The absence of evidence underscores the need for specific research to address this unmet need.

Hydroxysafflor Yellow A Blocks HIF-1α Induction of NOX2 and Protects ZO-1 Protein in Cerebral Microvascular Endothelium

Background: Zonula occludens-1 (ZO-1) protein ensures cerebrovascular integrity against brain ischemic injury. Hydroxysafflor yellow A (HSYA) is a major ingredient of safflower (Carthamus tinctorius L.) with anti-oxidative activity. Because conventional ROS scavengers display poor reactivity with endogenous ROS, this study investigated whether HSYA protected ZO-1 by targeting the enzymes responsible for ROS generation.Methords: Photothrombotic stroke model was prepared in mice to evaluate the protective effect of HSYA on cerebrovascular endothelium. The molecular regulation was investigated in cultured cerebral microvascular endothelial cells (bEnd.3 cells).Results: Oral administration of HSYA (50 mg/kg) reduced cerebral vascular leakage with ZO-1 protection in mice after stroke, largely due to suppression of ROS-associated inflammation. In LPS-stimulated bEnd.3 cells, HSYA increased the ratio of NAD+/NADH to restore Sirt1 induction, which bound to Von Hippel-Lindau (VHL) to ensure HIF-1α protein degradation. Although both NOX1 and NOX2 isoforms were inducible in endothelial cells, we identified NOX2 as the driving force of ROS production. Chromatin immunoprecipitation and luciferase report gene assay revealed that HIF-1α transcriptionally regulated p47phox and Nox2 subunits for the assembly of NOX2 complex, which was blocked by HSYA treatment, largely by reducing HIF-1α accumulation. Inflammation-associated lipid peroxidation impaired ZO-1 protein, but HSYA treatment attenuated carbonyl modification and thus prevented ZO-1 protein from 20S proteasome-mediated degradation, eventually protecting endothelial integrity. In microvascular ZO-1 deficient mice, we further confirmed that HSYA protected cerebrovascular integrity and attenuated ischemic injury dependent on ZO-1 protection. Conclusions: HSYA blocked HIF-1α/NOX2 signaling cascades to protect ZO-1 from proteasomal degradation, suggesting that targeting NOX2 in endothelium is a potential therapeutic strategy to protect against ischemic brain injury.