Eyas M. Hattab

To present three new cases of primary intraosseous orbital hemangioma (PIOH), including rare lacrimal bone involvement, and to provide an updated systematic review of previously reported cases. We retrospectively reviewed three patients with orbital PIOH from our institution. Clinical, radiographic, histopathologic, and surgical findings were analyzed. A comprehensive systematic review of 84 previously published PIOH cases was performed to assess demographics, anatomic location, imaging, and treatment outcomes. All three patients had firm, progressively enlarging orbital masses. Imaging showed well-circumscribed, expansile lesions confirmed as PIOH histologically. Case 1 involved the zygomatic and sphenoid bones; Case 2, the maxilla and lacrimal bone; and Case 3, the frontal bone. All underwent orbitotomy with subtotal or complete excision and reconstruction. No recurrence was observed at 1-34 month follow-up. In the systematic review, the zygoma (50%) and frontal bone (44%) were most frequently involved. Common symptoms included swelling, proptosis, pain, and globe displacement. CT was the most used imaging modality. Surgical excision, often with preoperative embolization, remains the preferred treatment. Only one recurrence (1.8%) was reported out of the 56 cases with follow-up data. Orbital PIOH is a rare vascular tumor best managed by tailored surgical excision. Our findings and updated systematic review emphasize individualized planning, particularly in rare sites like the lacrimal bone.

Hydroxychloroquine (HCQ) cardiomyopathy (CM) usually presents with a hypertrophic or restrictive pattern. We present a patient case of dilated HCQ-CM with normal wall thickness in young woman with ...

Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes.

Zika virus (ZIKV) can infect and cause microcephaly and Zika-associated neurological complications in the developing fetal and adult brains. In terms of pathogenesis, a critical question is how ZIKV overcomes the barriers separating the brain from the circulation and gains access to the central nervous system (CNS). Despite the importance of ZIKV pathogenesis, the route ZIKV utilizes to cross CNS barriers remains unclear. Here we show that in mouse models, ZIKV-infected cells initially appeared in the periventricular regions of the brain, including the choroid plexus and the meninges, prior to infection of the cortex. The appearance of ZIKV in cerebrospinal fluid (CSF) preceded infection of the brain parenchyma. Further the brain infection was significantly attenuated by neutralization of the virus in the CSF, indicating that ZIKV in the CSF at the early stage of infection might be responsible for establishing a lethal infection of the brain. We show that cells infected by ZIKV in the choroid plexus were pericytes. Using in vitro systems, we highlight the possibility that ZIKV crosses the blood-CSF barrier by disrupting the choroid plexus epithelial layer. Taken together, our results suggest that ZIKV might exploit the blood-CSF barrier rather than the blood-brain barrier to invade the CNS. Zika virus invades the human brains and causes Zika-associated neurological complications; however, the mechanism(s) by which Zika virus accesses the central nerves system remain unclear. Understanding of the cellular and molecular mechanisms will shed light on development of novel therapeutic and prophylactic targets for Zika virus and other neurotropic viruses. Here we use in vivo and in vitro models to understand how Zika virus enters the brain. In mouse models, we found that Zika virus infects pericytes in the choroid plexus at very early stages of infection and neutralization of Zika virus in the cerebrospinal fluid significantly attenuates the brain infection. Further we show evidence that Zika virus can cross the epithelial cell layers in the choroid plexus from the blood side. Our research highlights that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier.

Massrey C, et al. Anat Cell Biol. 2020 Jan;53:e11. https://doi.org/10.5115/acb.19.051

Zika virus (ZIKV) can infect and cause microcephaly and Zika-associated neurological complications in the developing fetal and adult brains. In terms of pathogenesis, a critical question is how ZIKV overcomes the barriers separating the brain from the circulation and gains access to the central nervous system (CNS). Despite the importance of ZIKV pathogenesis, the route ZIKV utilizes to cross CNS barriers remains unclear. Here we show that in mouse models, ZIKV-infected cells initially appeared in the periventricular regions of the brain, including the choroid plexus and the meninges, prior to infection of the cortex. The appearance of ZIKV in cerebrospinal fluid (CSF) preceded infection of the brain parenchyma. We show that ZIKV infects pericytes in the choroid plexus, and that ZIKV infection of pericytes is dependent on AXL receptor tyrosine kinase. Using an in vitro Transwell system, we highlight the possibility of ZIKV to move from the blood side to CSF side, across the choroid plexus epithelial layers, via a nondestructive pathway (e.g., transcytosis). Finally, we demonstrate that brain infection is significantly attenuated by neutralization of the virus in the CSF, indicating that ZIKV in the CSF at the early stage of infection might be responsible for establishing a lethal infection of the brain. Taken together, our results suggest that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier. AUTHOR SUMMARY: Zika virus invades the human brains and causes Zika-associated neurological complications; however, the mechanism(s) by which Zika virus accesses the central nerves system remain unclear. Understanding of the cellular and molecular mechanisms will shed light on development of novel therapeutic and prophylactic targets for Zika virus and other neurotropic viruses. Here we use in vivo and in vitro models to understand how Zika virus enters the brain. In mouse models, we found that Zika virus infects pericytes in the choroid plexus at very early stages of infection and neutralization of Zika virus in the cerebrospinal fluid significantly attenuate the brain infection. Further we show evidence that Zika virus can cross the epithelial cell layers in the choroid plexus from the blood side. Our research highlights that ZIKV invades the host brain by exploiting the blood-CSF barrier rather than the blood-brain barrier.

Pilocytic astrocytoma is a low-grade central nervous system tumor most commonly seen in children. Dissemination from a primary intracranial tumor along the neuroaxis has been described at both presentation and disease progression. However, the development of an intradural extramedullary pilocytic astrocytoma independent of a primary intraparenchymal tumor in an adult patient with no history of pilocytic astrocytoma has rarely been reported. A 69-year-old woman presented with progressive myelopathic symptoms and thoracic radicular pain. MRI imaging of the whole spine showed an enhancing intradural extramedullary lesion extending from the cervical cord to T11 causing cord compression. Laminectomies were performed for surgical decompression and histopathology was consistent with pilocytic astrocytoma. Complete staging was done that included imaging of the brain and cerebrospinal fluid cytology. No other tumor was found by these methods. Postoperatively the patient was treated with large field spinal radiation and concurrent chemotherapy followed by adjuvant chemotherapy. She has thus far been clinically and radiographically stable. This is a rare case of an adult with multiple spinal pilocytic astrocytomas in an intradural extramedullary location, typically the result of cerebrospinal fluid dissemination of neoplastic cells from a primary intracranial tumor site (i.e. drop metastasis). No conventional primary tumor was identified in this patient, suggesting these tumors may arise from heterotopic gliomas.

Examination of tissue sections using desorption electrospray ionization (DESI)-MS revealed phospholipid-derived signals that differ between gray matter, white matter, gliomas, meningiomas, and pituitary tumors, allowing their ready discrimination by multivariate statistics. A set of lower mass signals, some corresponding to oncometabolites, including 2-hydroxyglutaric acid and N-acetyl-aspartic acid, was also observed in the DESI mass spectra, and these data further assisted in discrimination between brain parenchyma and gliomas. The combined information from the lipid and metabolite MS profiles recorded by DESI-MS and explored using multivariate statistics allowed successful differentiation of gray matter (n = 223), white matter (n = 66), gliomas (n = 158), meningiomas (n = 111), and pituitary tumors (n = 154) from 58 patients. A linear discriminant model used to distinguish brain parenchyma and gliomas yielded an overall sensitivity of 97.4% and a specificity of 98.5%. Furthermore, a discriminant model was created for tumor types (i.e., glioma, meningioma, and pituitary), which were discriminated with an overall sensitivity of 99.4% and a specificity of 99.7%. Unsupervised multivariate statistics were used to explore the chemical differences between anatomical regions of brain parenchyma and secondary infiltration. Infiltration of gliomas into normal tissue can be detected by DESI-MS. One hurdle to implementation of DESI-MS intraoperatively is the need for tissue freezing and sectioning, which we address by analyzing smeared biopsy tissue. Tissue smears are shown to give the same chemical information as tissue sections, eliminating the need for sectioning before MS analysis. These results lay the foundation for implementation of intraoperative DESI-MS evaluation of tissue smears for rapid diagnosis. Significance Brain tumors can lead to a significant source of morbidity and mortality. The primary treatment is microsurgical resection, and the extent of resection is associated with length of survival. Unfortunately, reliable intraoperative tools for diagnosis and safe maximal resection of the tumor mass are lacking. Mass spectra (lipid and metabolite profiles) can be used to distinguish between healthy and diseased tissues by comparison of patterns of peak intensities using multivariate statistics. This experiment can be done on a timescale amenable to intraoperative analysis using tissue smears. These data can provide surgeons with near real-time pathologic information and guide the intraoperative resection of the tumor at the difficult to detect peritumoral borders.