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1

Aslan, Sabina, Rahsan Gocmen, Nazire Pınar Acar, Farid Khasiyev, Ekim Gumeler, Figen Soylemezoglu, Aslı Tuncer, Ethem Murat Arsava, Mehmet Akif Topçuoglu y Isin Unal Cevik. "Two cases of primary leptomeningeal melanomatosis mimicking subacute meningitis". Neuroradiology Journal 31, n.º 1 (19 de junio de 2017): 42–46. http://dx.doi.org/10.1177/1971400917708581.

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Primary involvement of leptomeninges with melanocytic tumours is rarely seen and its diagnosis is challenging. Here we summarise two cases of primary leptomeningeal melanomatosis presenting as subacute meningitis. Both cases have pleocytosis and high protein on cerebrospinal fluid analysis, and demonstrated atypical cells on cytology. On magnetic resonance imaging, there is diffuse leptomeningal thickening and avid enhancement of intracranial and intraspinal leptomeninges. One of them demonstrates T1 shortening due to magnetic effects of melanin, the other case is amelanotic and shows hypointensity on precontrast T1-weighted images. Both cases can be diagnosed with biopsy. In conclusion, these cases highlight the importance of the correct interpretation of cytological and magnetic resonance imaging findings in patients with atypical findings.
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2

Tanaka, Junya, Hisaaki Takahashi, Hajime Yano y Hiroshi Nakanishi. "Generation of CSF1-Independent Ramified Microglia-Like Cells from Leptomeninges In Vitro". Cells 10, n.º 1 (25 de diciembre de 2020): 24. http://dx.doi.org/10.3390/cells10010024.

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Although del Río-Hortega originally reported that leptomeningeal cells are the source of ramified microglia in the developing brain, recent views do not seem to pay much attention to this notion. In this study, in vitro experiments were conducted to determine whether leptomeninges generate ramified microglia. The leptomeninges of neonatal rats containing Iba1+ macrophages were peeled off the brain surface. Leptomeningeal macrophages strongly expressed CD68 and CD163, but microglia in the brain parenchyma did not. Leptomeningeal macrophages expressed epidermal growth factor receptor (EGFR) as revealed by RT-PCR and immunohistochemical staining. Cells obtained from the peeled-off leptomeninges were cultured in a serum-free medium containing EGF, resulting in the formation of large cell aggregates in which many proliferating macrophages were present. In contrast, colony-stimulating factor 1 (CSF1) did not enhance the generation of Iba1+ cells from the leptomeningeal culture. The cell aggregates generated ramified Iba1+ cells in the presence of serum, which express CD68 and CD163 at much lower levels than primary microglia isolated from a mixed glial culture. Therefore, the leptomeningeal-derived cells resembled parenchymal microglia better than primary microglia. This study suggests that microglial progenitors expressing EGFR reside in the leptomeninges and that there is a population of microglia-like cells that grow independently of CSF1.
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3

Zivkovic, Nikola, Dragan Mihailovic, Zaklina Mijovic y Maja Jovicic-Milentijevic. "Primary leptomeningeal melanocytosis: A case report with an autopsy diagnosis". Vojnosanitetski pregled 69, n.º 7 (2012): 631–34. http://dx.doi.org/10.2298/vsp1207631z.

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Introduction. Primary melanocytosis of the leptomeninges is a rare tumor, most likely originating from the melanocytes in the leptomeninges. The average survival is only about 5 months. Case report. A 61- years-old woman presented with headache, amaurosis and hallucinations lasted for two months, and she had been treated at the Clinic for Psychiatry and Clinic for Infectious Diseases. The cerebrospinal fluid analysis showed a lower level of glucose and a higher level of proteins. Small shaded areas of basal leptomeninges and hydrocephalus were found by computed tomography and magnetic resonance imaging. The autopsy showed a dark brown mass on basal leptomeninges with blurred boundaries. No pigmented skin lesions were found. Histopathological analysis revealed a primary leptomeningeal melanocytosis. Conclusion. Primary leptomeningeal melanocytosis is a rare tumor, difficult to diagnose. This case is being presented for its specificity, since this diagnosis is not frequently seen in practice.
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4

Saad, Ali G., Mayur Jayarao, Lawrence S. Chin y Ivana Delalle. "Ganglioglioma Associated with Cerebral Cortical Dysplasia: An Unusual Case with Extensive Leptomeningeal Involvement". Pediatric and Developmental Pathology 11, n.º 6 (noviembre de 2008): 474–78. http://dx.doi.org/10.2350/07-10-0360.1.

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Ganglioglioma is a tumor occurring in children and young adults and characterized by a superficial cortical location and biphasic histologic differentiation encompassing neuronal and glial elements. Ganglioglioma may arise anywhere throughout the neuraxis, including the optic nerve, brain stem, pineal gland, cerebellum, cerebrum, and spinal cord; however, the majority of glioneuronal neoplasms involve the temporal lobe. Gangliogliomas may show focal leptomeningeal involvement, but predominant leptomeningeal involvement by gangliogliomas is extremely rare; only 2 cases of ganglioglioma extensively involving the leptomeninges have been reported. In this report, we present an unusual case of a ganglioglioma predominantly present within the leptomeninges of a 15-year-old boy with a history of seizures. Furthermore, the cerebral cortex beneath the tumor showed dysplastic changes. We report a very unusual case of ganglioglioma involving predominantly the cerebral leptomeninges and associated with adjacent cerebral cortical dysplasia. Histologic characteristics and diagnostic pitfalls are discussed.
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5

Funato, H., M. Yoshimura, Y. Ito, R. Okeda y Y. Ihara. "Proliferating cell nuclear antigen (PCNA) expressed in human leptomeninges." Journal of Histochemistry & Cytochemistry 44, n.º 11 (noviembre de 1996): 1261–65. http://dx.doi.org/10.1177/44.11.8918901.

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Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.
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6

Leblanc, Richard, Sabah Bekhor, Denis Melanson y Stirling Carpenter. "Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus papilloma". Journal of Neurosurgery 88, n.º 4 (abril de 1998): 757–60. http://dx.doi.org/10.3171/jns.1998.88.4.0757.

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✓ Choroid plexus papillomas can metastasize to the subarachnoid space, but extensive metastasis has only been reported when the tumors are malignant. The authors report a case of diffuse, extensive metastasis to the craniospinal leptomeninges from a benign fourth ventricular choroid plexus papilloma in an adult. This 19-year-old woman presented with a 2-year history of headache, blurred vision, diplopia, and ataxia. Magnetic resonance imaging of the brain and spinal cord revealed obstructive hydrocephalus caused by a 4-cm, partially calcified, inhomogeneously enhancing tumor of the fourth ventricle that was displacing the pons, medulla oblongata, and cerebellum. Innumerable cystic lesions of varying size were also seen in the cranial and spinal leptomeninges. Histological examination of the resected fourth ventricular tumor and of a few of the leptomeningeal lesions revealed a benign choroid plexus papilloma and leptomeningeal choroid plexus cysts. This singular case of diffuse and extensive metastasis to the craniospinal leptomeninges from a histologically benign fourth ventricular papilloma adds to the available information about the biological potential of these tumors and expands the differential diagnosis of posterior fossa lesions with subarachnoid metastasis.
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7

Kijima, Noriyuki, Takamune Achiha, Tomoyoshi Nakagawa, Ryuichi Hirayama, Manabu Kinoshita, Naoki Kagawa y Haruhiko Kishima. "CBIO-02. COMPREHENSIVE ANALYSIS OF MECHANISMS AND MOLECULAR TARGETS FOR BREAST CANCER LEPTOMENINGEAL METASTASIS". Neuro-Oncology 22, Supplement_2 (noviembre de 2020): ii16. http://dx.doi.org/10.1093/neuonc/noaa215.062.

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Abstract Leptomeningeal metastasis from solid cancer is a devastating state for cancer patients. Leptomeningeal metastasis is diagnosed either by cerebrospinal fluid cytology and/or magnetic resonance imaging (MRI). However, it remains unclear as to whether tumor cells attached to leptomeninges are the same from floating tumor cells in cerebrospinal fluid (CSF). In this study, we aim to analyze the differences between tumor cells attached to leptomeninges and floating cells in CSF by xenograft models. We used breast cancer cell line, MDA-MB-231, labelled with green fluorescent protein (GFP) and luciferase. We injected those cells into right lateral ventricle of NOD/Shi-scid IL2Rγ KO mice. When the mice got any signs of tumor, we dissected spinal cord and got CSF from mice. We sorted tumor cells by flow cytometry and extracted RNA from the sorted tumor cells from spinal cord and CSF, respectively. We analyzed transcriptome differences between tumor cells from spinal cord and CSF by RNA sequencing. We found that extracellular matrix related proteins were highly upregulated while cell growth related proteins were downregulated in tumor cells from spinal cord compared with those from CSF. These results suggest that tumor cells attached to leptomeninges have different transcriptome profiles from floating tumor cells in CSF and extracellular matrix related proteins could be therapeutic targets for breast cancer leptomeningeal metastasis.
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8

Ng, Ho-keung y Wai-sang Poon. "Primary leptomeningeal astrocytoma". Journal of Neurosurgery 88, n.º 3 (marzo de 1998): 586–89. http://dx.doi.org/10.3171/jns.1998.88.3.0586.

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✓ Gliomas very rarely arise from the leptomeninges. They can be both solitary and diffuse, and histological examination reveals mostly astrocytic tumors. The authors report a case (the 12th reported in the literature) of a solitary primary glioma of the leptomeninges in a 79-year-old man who presented with repeated seizures. A magnetic resonance image revealed an ill-defined enhancing lesion in the cerebral meninges. Autopsy examination showed a poorly demarcated astrocytoma in the sylvian fissure infiltrating the adjacent subarachnoid space. The literature concerning primary leptomeningeal glioma is reviewed.
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9

Bhan, Arunoday Kuldeep, Khairul I. Ansari, Clara Chen y Rahul Jandial. "Abstract P1-21-05: GM-CSF is an autocrine driver of HER2+ breast leptomeningeal carcinomatosis". Cancer Research 82, n.º 4_Supplement (15 de febrero de 2022): P1–21–05—P1–21–05. http://dx.doi.org/10.1158/1538-7445.sabcs21-p1-21-05.

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Abstract Leptomeningeal carcinomatosis (LC) occurs when tumor cells spread to the cerebrospinal fluid containing leptomeninges surrounding the brain and spinal cord. LC is an ominous complication of cancer with a dire prognosis. Although any malignancy can spread to the leptomeninges, breast cancer, particularly the HER2+ subtype, is its most common origin. HER2+ breast LC (HER2+ LC) remains incurable, with few treatment options, and the molecular mechanisms underlying proliferation of HER2+ breast cancer cells in the acellular, protein, and cytokine-poor leptomeningeal environment remain elusive. Therefore, we sought to characterize signaling pathways that drive HER2+ LC development as well as those that restrict its growth to leptomeninges. Primary HER2+ LC patient-derived ("Lepto") cell lines in co-culture with various central nervous system (CNS) cell types revealed that oligodendrocyte progenitor cells (OPC), the largest population of dividing cells in the CNS, inhibited HER2+ LC growth in vitro and in vivo, thereby limiting the spread of HER2+ LC beyond the leptomeninges. Cytokine array-based analyses identified Lepto cell-secreted granulocyte-macrophage colony-stimulating factor (GM-CSF) as an oncogenic autocrine driver of HER2+ LC growth. Liquid chromatography-tandem mass spectrometry-based analyses revealed that the OPC-derived protein TPP1 proteolytically degrades GM-CSF, decreasing GM-CSF signaling and leading to suppression of HER2+ LC growth and limiting its spread. Lastly, intrathecal delivery of neutralizing anti-GM-CSF antibodies and a pan-Aurora kinase inhibitor (CCT137690) synergistically inhibited GM-CSF and suppressed activity of GM-CSF effectors, reducing HER2+ LC growth in vivo. Thus, OPC suppress GM-CSF-driven growth of HER2+ LC in the leptomeningeal environment, providing a potential targetable axis. Citation Format: Arunoday Kuldeep Bhan, Khairul I Ansari, Clara Chen, Rahul Jandial. GM-CSF is an autocrine driver of HER2+ breast leptomeningeal carcinomatosis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-05.
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10

Shibata-Germanos, Shannon, James R. Goodman, Alan Grieg, Chintan A. Trivedi, Bridget C. Benson, Sandrine C. Foti, Ana Faro et al. "Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges". Acta Neuropathologica 139, n.º 2 (6 de noviembre de 2019): 383–401. http://dx.doi.org/10.1007/s00401-019-02091-z.

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Abstract The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer’s disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.
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11

Dankner, Matthew, Stephanie Lam, Theresa Degenhard, Livia Garzia, Marie-Christine Guiot, Kevin Petrecca y Peter M. Siegel. "The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers". Cancers 13, n.º 4 (10 de febrero de 2021): 732. http://dx.doi.org/10.3390/cancers13040732.

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Metastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachnoid space surrounding the brain and spinal cord to form tumors called leptomeningeal metastases. Leptomeningeal metastasis involves cancer cells that reach the subarachnoid space and proliferate in the cerebrospinal fluid compartment within the leptomeninges, a sequela associated with a myriad of symptoms and poor prognosis. Cancer cells exposed to cerebrospinal fluid in the leptomeninges must contend with a unique microenvironment from those that establish within the brain or other organs. Leptomeningeal lesions provide a formidable clinical challenge due to their often-diffuse infiltration within the subarachnoid space. The molecular mechanisms that promote the establishment of leptomeningeal metastases have begun to be elucidated, demonstrating that it is a biological entity distinct from parenchymal brain metastases and is associated with specific molecular drivers. In this review, we outline the current state of knowledge pertaining to the diagnosis, treatment, and molecular underpinnings of leptomeningeal metastasis.
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12

Huang, Wanyi, Fan Zeng, Yebo Gu, Muzhou Jiang, Xinwen Zhang, Xu Yan, Tomoko Kadowaki et al. "Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1β Production in Leptomeningeal Cells". Journal of Alzheimer's Disease 83, n.º 2 (14 de septiembre de 2021): 665–81. http://dx.doi.org/10.3233/jad-210031.

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Background: Studies have reported that synaptic failure occurs before the Alzheimer’s disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1β in response to systemic inflammation. Objective: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Methods: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1β production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). Results: Systemic P. gingivalis infection increased the expression of IL-1β in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1β secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. Conclusion: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB/NLRP3 inflammasome-mediated IL-1β production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.
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13

Tsitouridis, J., S. Stamos, J. Demertzis y P. Nikolopoulos. "Cerebral Leptomeningeal Angiomatosis CT and MRI evaluation". Rivista di Neuroradiologia 11, n.º 4 (agosto de 1998): 463–70. http://dx.doi.org/10.1177/197140099801100405.

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Leptomeningeal angiomatosis is an uncommon benign hamartomatous lesion usually involving the leptomeninges with or without cerebral cortex involvement. Three middle-aged patients with seizures from adulthood had undergone CT and MRI examinations and craniotomies which revealed leptomeningeal angiomatosis. Another two young patients with Sturge-Weber syndrome and leptomeningeal angiomatosis were also evaluated. MRI is clearly helpful in establishing the topography and vascular malformative nature of the lesion, while CT is more accurate in detecting vascular calcifications.
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14

Johnson, Mahlon. "Metastases to Meningiomas: A Comprehensive Literature Review Including Mediating Proteins". Cancers 14, n.º 23 (29 de noviembre de 2022): 5877. http://dx.doi.org/10.3390/cancers14235877.

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Approximately 5–15% of solid tumors metastasizing to the central nervous system metastasize to the leptomeninges. Less common, is metastasis to leptomeningeal meningiomas. These are primarily carcinomas of the breast and lung. Awareness of this phenomenon is critical to the evaluation of meningiomas, especially since the metastases may be the first indication of an occult tumor elsewhere in the body. Lack of clear demarcation between the metastasis and meningioma parenchyma, as well as histological features similar to the meningioma, may hinder recognition. The mechanisms underlying metastases anchoring and spread along the leptomeninges are not established. However, several cell adhesion molecules are thought to contribute to this phenomenon. E cadherin is a cell adhesion molecule present in meningioma cells. Binding to endothelium by adhesion molecules such as ICAM, B1 integrin, P-selectin, PECAM-1, CXCL12 and SDF-1 have also been proposed as part of the mechanisms underlying breast carcinoma metastases. In addition, the leptomeninges and meningiomas express mesothelin that acts as an anchoring protein coupling with mucin-16. Consequently, metastatic tumor cell mucin and mesothelin may also facilitate the anchoring of metastases to meningiomas.
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Ezzeddine, Rima, Matthew Dankner, Paul Savage, Steven Hebert, William Brothers, Matthew G. Annis, Sarah M. Maritan et al. "Abstract 2436: CIRBP is a functional mediator of leptomeningeal metastasis". Cancer Research 82, n.º 12_Supplement (15 de junio de 2022): 2436. http://dx.doi.org/10.1158/1538-7445.am2022-2436.

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Abstract Background: Cold-Inducible RNA Binding Protein (CIRBP) has been implicated in cancer initiation. Moreover, we have previously identified an association of CIRBP with the invasive growth of parenchymal brain metastases. Using a patient-derived xenograft (PDX) model, in which cells implanted in the mouse mammary fat pad spontaneously metastasize to the leptomeninges, we identified CIRBP as being elevated in leptomeningeal metastases (LM) compared to matched primary mammary tumors. LM grow in the subarachnoid space that harbors the cerebral spinal fluid (CSF). The leptomeninges represent an inhospitable environment for disseminated cancer cells since the CSF is mitogen and nutrient poor. To investigate the importance of CIRBP for metastatic breast cancer cells in the leptomeninges, we stably reduced CIRBP expression in MDA-MB-231 cells and performed mammary fat pad and cranial injections. CIRBP knockdown had no influence on primary tumor growth, but diminished growth within the brain. Hypothesis: We hypothesize that CIRBP functions as a stress response protein enabling cancer cells to grow in the harsh environment of the CSF. Results: In response to various cellular stressors, such as hypothermia, hypoxia or UV irradiation, CIRBP can translocate from the nucleus to the cytoplasm. We show that culturing MDA-MB-231 cells in artificial CSF (aCSF) also causes CIRBP relocation from nucleus to cytoplasm. Using RNA-IP approaches, we have identified mRNAs bound by CIRBP in breast cancer cells treated with aCSF. Ultimately, we will determine whether any of the identified CIRBP-regulated targets contribute to the formation of LM. Finally, we have generated CIRBP variants that are confined either to the nucleus or the cytoplasm. We are currently assessing the ability of these compartment-restricted CIRBP proteins to promote the formation of central nervous system metastases. Conclusions: We have identified CIRBP as a promoter of leptomeningeal metastasis. Our results have begun to reveal the mechanisms through which CIRBP mediates this process. Citation Format: Rima Ezzeddine, Matthew Dankner, Paul Savage, Steven Hebert, William Brothers, Matthew G. Annis, Sarah M. Maritan, Marc R. Fabian, Claudia Kleinman, Morag Park, Peter M. Siegel. CIRBP is a functional mediator of leptomeningeal metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2436.
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16

Koutsouras, George W., Annelle Amsellem, Timothy Richardson y Harish Babu. "Multifocal spinal glioblastoma and leptomeningeal carcinomatosis in an elderly male with hydrocephalus and myelopathy". Surgical Neurology International 12 (8 de diciembre de 2021): 595. http://dx.doi.org/10.25259/sni_985_2021.

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Background: Primary spinal glioblastoma multiforme with multifocal leptomeningeal enhancement is rarely diagnosed or documented. We describe a rare case of multifocal spinal isocitrate dehydrogenase (IDH) wild type glioblastoma with leptomeningeal carcinomatosis in an elderly male presenting with a chronic subdural hematoma, progressive myelopathy, and communicating hydrocephalus. Case Description: A 77-year-old male with a medical history of an acoustic schwannoma, anterior cranial fossa meningioma, and immune thrombocytopenic purpura presented with right-sided weakness after repeated falls. Magnetic resonance imaging of the brain and spine demonstrated a left-sided subdural hematoma, leptomeningeal enhancement of the brain and skull base, ventricles, and the cranial nerves, and along with florid enhancement of the leptomeninges from the cervicomedullary junction to the cauda equina. Most pertinent was focal thickening of the leptomeninges at T1 and T6 with mass effect on the spinal cord. A T6 laminectomy with excisional biopsy of the lesion was planned and completed. Findings were significant for glioblastoma the World Health Organization Grade IV IDH 1 wild type of the thoracic spinal cord. Subsequently, his mental status declined, and he developed progressive hydrocephalus which required cerebrospinal fluid diversion. Unfortunately, the patient had minimal improvement in his neurological exam and unfortunately died 2 months later. Conclusion: In a review of the limited literature describing similar cases of primary spinal glioblastoma, the prognosis of this aggressive tumor remains unfavorable, despite aggressive treatment options. The purpose of this report is to increase awareness of this rare condition as a potential differential diagnosis in patients presenting with multifocal invasive spinal lesions.
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17

Remsik, Jan, Xinran Tong, Min Jun Li, Ugur Sener, Jessica Wilcox, Kiana Chabot, Russell Kunes et al. "LMD-16. Choroid plexus orchestrates anti-cancer immunity in leptomeninges". Neuro-Oncology Advances 3, Supplement_3 (1 de agosto de 2021): iii10—iii11. http://dx.doi.org/10.1093/noajnl/vdab071.041.

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Abstract Choroid plexus (CP) forms an anatomically functional barrier between the blood and cerebrospinal fluid (CSF) that dictates the cellular and humoral composition of the CSF. The immunological response of CP to inflammatory stimuli, such as cancer, remains unclear. Here, we find that CP orchestrates the immune composition of CSF in the steady state as well as in the presence of metastatic cancer. We show that the circulation-derived leptomeningeal monocyte-macrophages entering the CSF through CP promote the growth of leptomeningeal metastasis (LM) by perturbing the environment with a storm of dozens of pro- and anti-inflammatory cytokines. Functional manipulation of Type II Interferon pathway specifically within inflamed leptomeninges revealed that IFN-γ can serve as a dominant signal, further recruiting peripheral myeloid cells and activating their protective anti-tumoral response. This preclinical strategy was sufficient to controll the growth of syngeneic LM cancer cells and delay the onset of lethal LM.
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18

Kauer, Ronja V., Stefano Bagatella y Anna Oevermann. "Diffuse Leptomeningeal Oligodendrogliomatosis in a Cow". Veterinary Pathology 57, n.º 2 (17 de diciembre de 2019): 253–57. http://dx.doi.org/10.1177/0300985819887534.

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A 4.5-year-old cow showing neurological signs consistent with predictors of bovine spongiform encephalopathy (BSE) was investigated as a potential BSE-suspect case and proved to be negative. Macroscopic analysis revealed a tan neoplastic mass growing along the leptomeninges of the caudal brain and extending into the third (III) ventricle without significantly involving the neuroparenchyma. Pathological features (uniform round hyperchromatic neoplastic cells embedded in abundant myxoid matrix, microcysts, microvascular proliferation) and diffuse Olig2 expression were most consistent with diffuse high-grade leptomeningeal oligodendrogliomatosis. In line with former reports of extensive leptomeningeal involvement in bovine oligodendroglioma, this report suggests that bovine oligodendroglial tumors have a strong propensity to grow within the leptomeningeal space. In addition, it indicates that Olig2 is a useful marker to confirm glial lineage in formalin-fixed, paraffin-embedded bovine tissue.
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19

Ishizaka, Mami, Kinuko Shibata, Tomoko Senbongi y Koichi Ishikawa. "Neurotrophic properties of leptomeninges". Biomedical Reviews 10 (31 de diciembre de 1999): 31. http://dx.doi.org/10.14748/bmr.v10.5.

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20

Ahmad, Ehtasham, Mohamed Mohamed y Apostolos Vrettos. "Primary Diffuse Leptomeningeal Gliomatosis: Radiological/Pathological Features". Case Reports in Neurological Medicine 2016 (2016): 1–4. http://dx.doi.org/10.1155/2016/5016840.

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We present the case of a 43-year-old lady who presented with headaches, visual impairment, and seizures, progressing rapidly over the course of a few weeks. Extensive workup excluded an inflammatory or infectious cause. Imaging studies revealed diffuse thickening of the leptomeninges and serial CSF analysis showed raised opening pressures and increased protein levels. A diagnostic biopsy of the lower thoracic dura confirmed the diagnosis of primary diffuse leptomeningeal gliomatosis (PDGL). She was managed supportively for her symptoms and unfortunately she passed away a few weeks later.
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21

Chen, Robert, David R. Macdonald y David A. Ramsay. "Primary diffuse leptomeningeal oligodendroglioma". Journal of Neurosurgery 83, n.º 4 (octubre de 1995): 724–28. http://dx.doi.org/10.3171/jns.1995.83.4.0724.

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✓ The authors describe a case of a diffuse primary leptomeningeal oligodendroglioma in a 17-year-old girl who presented with raised intracranial pressure and hydrocephalus. She underwent imaging studies and a left frontotemporal craniotomy that revealed a cystic oligodendroglioma in the suprasellar cistern and spread of neoplastic cells to the spinal leptomeninges. The tumor showed little response to maximum radiotherapy and chemotherapy, and the patient died from complications of high-dose chemotherapy 2 years after diagnosis. Postmortem examination of the brain and spinal cord revealed diffuse meningeal infiltration by neoplastic cells and no evidence of an intraparenchymal origin. Glial heterotopias were noted at several sites along the brain base, adding circumstantial support to the theory that leptomeningeal gliomas are derived from ectopic glial tissue in the subarachnoid space.
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22

Thibodeau, Lee L., Aurelio Ariza y Joseph M. Piepmeier. "Primary leptomeningeal sarcomatosis". Journal of Neurosurgery 68, n.º 5 (mayo de 1988): 802–5. http://dx.doi.org/10.3171/jns.1988.68.5.0802.

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✓ This report describes a case of primary leptomeningeal sarcomatosis in a 50-year-old man who presented with progressive deficits involving multiple cranial nerves and spinal roots. Despite the clinical evidence supporting a diffuse process involving the leptomeninges, radiological, serological, and cerebrospinal fluid examinations failed to reveal the cause of the disorder. Consequently, surgical exploration and biopsy were required to obtain a pathological diagnosis. This case report illustrates the difficulty in diagnosing this disease and supports the use of open biopsy in patients with chronic meningeal disease when the diagnosis cannot be established by less invasive methods.
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23

Khosla, Atulya Aman, Shreya Saxena, Ahmad Ozair, Vyshak Alva Venur, David M. Peereboom y Manmeet S. Ahluwalia. "Novel Therapeutic Approaches in Neoplastic Meningitis". Cancers 15, n.º 1 (25 de diciembre de 2022): 119. http://dx.doi.org/10.3390/cancers15010119.

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Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges, or the dura. Neoplastic meningitis (NM), also known by different terms, including leptomeningeal carcinomatosis and carcinomatous meningitis, occurs due to solid tumors and hematologic malignancies and is associated with a poor prognosis. The current management paradigm entails a multimodal approach focused on palliation with surgery, radiation, and chemotherapy, which may be administered systemically or directly into the cerebrospinal fluid (CSF). This review focuses on novel therapeutic approaches, including targeted and immunotherapeutic agents under investigation, that have shown promise in NM arising from solid tumors.
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24

Fults, Daniel W., Michael D. Taylor y Livia Garzia. "Leptomeningeal dissemination: a sinister pattern of medulloblastoma growth". Journal of Neurosurgery: Pediatrics 23, n.º 5 (mayo de 2019): 613–21. http://dx.doi.org/10.3171/2018.11.peds18506.

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Leptomeningeal dissemination (LMD) is the defining pattern of metastasis for medulloblastoma. Although LMD is responsible for virtually 100% of medulloblastoma deaths, it remains the least well-understood part of medulloblastoma pathogenesis. The fact that medulloblastomas rarely metastasize outside the CNS but rather spread almost exclusively to the spinal and intracranial leptomeninges has fostered the long-held belief that medulloblastoma cells spread directly through the CSF, not the bloodstream. In this paper the authors discuss selected molecules for which experimental evidence explains how the effects of each molecule on cell physiology contribute mechanistically to LMD. A model of medulloblastoma LMD is described, analogous to the invasion–metastasis cascade of hematogenous metastasis of carcinomas. The LMD cascade is based on the molecular themes that 1) transcription factors launch cell programs that mediate cell motility and invasiveness and maintain tumor cells in a stem-like state; 2) disseminating medulloblastoma cells escape multiple death threats by subverting apoptosis; and 3) inflammatory chemokine signaling promotes LMD by creating an oncogenic microenvironment. The authors also review recent experimental evidence that challenges the belief that CSF spread is the sole mechanism of LMD and reveal an alternative scheme in which medulloblastoma cells can enter the bloodstream and subsequently home to the leptomeninges.
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25

Thomas, Jean E., Evelyn Falls, Manuel E. Velasco y Aiman Zaher. "Diagnostic Value of Immunocytochemistry in Leptomeningeal Tumor Dissemination". Archives of Pathology & Laboratory Medicine 124, n.º 5 (1 de mayo de 2000): 759–61. http://dx.doi.org/10.5858/2000-124-0759-dvoiil.

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Abstract Differentiating chronic aseptic meningitis from leptomeningeal carcinomatosis or gliomatosis can be difficult, particularly when the differentiation is based solely on routine cytologic examination. The diagnosis of cerebrospinal fluid tumor dissemination in at-risk patients requires cytologic examination of cerebrospinal fluid and radiography of the leptomeninges. Routine cytologic examination alone has proven less than desirable, in most instances providing confirmation in as little as 50% of cases in the first lumbar puncture. This percentage increases to 85% to 90% after multiple lumbar punctures. We retrospectively reviewed 2 cases of leptomeningeal dissemination (one gliomatosis, the other carcinomatosis) with initial false-negative test results. However, after further examination of the cerebrospinal fluid by selected battery of immunocytochemical stains, both cases were identified as positive for malignancy (ie, false negatives). Immunocytochemistry can be useful in distinguishing chronic aseptic meningitis from leptomeningeal carcinomatosis or gliomatosis in patients at risk or when abnormal cells are seen on routine cerebrospinal fluid cytologic examination.
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26

Ohlsson, R., F. Hedborg, L. Holmgren, C. Walsh y T. J. Ekstrom. "Overlapping patterns of IGF2 and H19 expression during human development: biallelic IGF2 expression correlates with a lack of H19 expression". Development 120, n.º 2 (1 de febrero de 1994): 361–68. http://dx.doi.org/10.1242/dev.120.2.361.

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The spatial patterns of IGF2 and H19 gene expression are strikingly similar during parts of human embryonic/fetal and early postnatal development. Notable exceptions were found with the ciliary anlage of the embryonic retina and the choroid plexus/leptomeninges, where transcripts from the IGF2 but not the H19 locus could be detected. Moreover, in contrast to the other tissue samples examined, the choroid plexus/leptomeninges expressed both parental IGF2 alleles. Whilst RNase protection analysis revealed a weak activity of the P1 promoter in the choroid plexus/leptomeninges, the P2, P3 and P4 promoters were all active wherever IGF2 was expressed. We discuss these observations with respect to a hypothesized coordinated control of the reciprocally imprinted and closely linked IGF2 and H19 loci.
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27

Severson, Gregory S., Douglas S. Harrington, Dennis D. Weisenburger, Rodney D. McComb, John H. Casey, Benjamin R. Gelber, B. Varet, R. Abelanet y Henry H. Rappaport. "Castleman's disease of the leptomeninges". Journal of Neurosurgery 69, n.º 2 (agosto de 1988): 283–86. http://dx.doi.org/10.3171/jns.1988.69.2.0283.

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✓ Castleman's disease is a rare, benign lymphoproliferative disorder that usually arises in lymph nodes, most commonly in the mediastinum. The authors report the clinical and pathological features of three patients with localized Castleman's disease of the leptomeninges. There were two women, aged 63 and 82 years, and one 25-year-old man. Two patients had progressive focal motor seizures of 3 and 24 months' duration, and the third patient presented acutely with generalized seizures. The clinical diagnosis was meningioma in each case, based on computerized tomography scans, cerebral arteriography, and the operative findings. All three lesions arose in the leptomeninges, compressed the underlying cerebral cortex, and infiltrated the overlying dura to a variable extent. Surgical excision of the tumor resulted in marked clinical improvement in all three patients. Histologically, two cases were classified as the hyaline-vascular type and one as the plasma cell type. Immunohistochemical stains of the latter case revealed a monoclonal population of mature plasma cells. Only a few scattered polyclonal plasma cells were seen in the other two cases. The authors conclude that Castleman's disease involving the leptomeninges is a rare disorder that may mimic meningioma clinically and radiographically.
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28

Liu, Yicong, Zhou Wu, Xinwen Zhang, Junjun Ni, Weixian Yu, Yanmin Zhou y Hiroshi Nakanishi. "Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse toPorphyromonas gingivalisLPS". Mediators of Inflammation 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/407562.

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We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response toPorphyromonas gingivalis (P.g.)LPS. The expression of Toll-like receptor 2 (TLR2), TLR4, TNF-α, and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. Inin vitrostudies,P.g.LPS induced the secretion of TNF-αand IL-1βfrom THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF-αand IL-1βin leptomeningeal cells after treatment with the conditioned medium fromP.g.LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment withP.g.LPS alone. Furthermore, the mean mRNA levels of TNF-αand IL-1βin microglia after treatment with the conditioned medium fromP.g.LPS-stimulated leptomeningeal cells were significantly higher than those afterP.g.LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced theP.g.LPS-induced TNF-αand IL-1βproduction by leptomeningeal cells through inhibiting the nuclear factor-κB signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis.
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29

Pawłowska, Ewa, Anna Romanowska y Jacek Jassem. "Radiotherapy for Leptomeningeal Carcinomatosis in Breast Cancer Patients: A Narrative Review". Cancers 14, n.º 16 (12 de agosto de 2022): 3899. http://dx.doi.org/10.3390/cancers14163899.

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Leptomeningeal carcinomatosis (LC), defined as the infiltration of the leptomeninges by cancer cells, is a rare oncological event with the most common etiology being breast cancer (BC), lung cancer, and melanoma. Despite innovations in radiotherapy (RT), firm evidence of its impact on survival is lacking, and concerns are related to its possible neurotoxicity. Owing to a paucity of data, the optimal treatment strategy for LC remains unknown. This review discusses current approaches, indications, and contraindications for various forms of RT for LC in BC. A separate section is dedicated to new RT techniques, such as proton therapy. We also summarize ongoing clinical trials evaluating the role of RT in patients with LC.
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30

Moly, Kazi Nilufar, S. M. Abu Ahsan y Md Shafiqul Lslam. "Sturge Weber Syndrome". Bangabandhu Sheikh Mujib Medical University Journal 8, n.º 1 (26 de julio de 2016): 68. http://dx.doi.org/10.3329/bsmmuj.v8i1.28924.

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<p>Sturge weber syndrome is a rare sporadic condition of mesodermal phacomatosis, also called encephalotrigeminal angio­matosis (synonyms : fourth phacomatosis or mother spot), is a neurocutaneous disorder with angiomas that involve the leptomeninges (leptomeningeal angiomas) and the skin of the face (purple colored flat cutaneous haemangiomas ), typically in the ophthalmic (V1) and maxillary (V2) distributions of the trigeminal nerve. The hallmark of sturge weber syndrome is a facial cutaneous venous dilation, also referred to as a nevus flammeus or port wine stain (PWS). Because of the rarity, we report here a one &amp; half year old male child who presented with features of the Sturge Weber Syndrome on both side of face.</p>
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31

Cao, C., K. Matsumura, K. Yamagata y Y. Watanabe. "Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 272, n.º 6 (1 de junio de 1997): R1712—R1725. http://dx.doi.org/10.1152/ajpregu.1997.272.6.r1712.

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We previously showed that a febrile dose of lipopolysaccharide (LPS) in rats resulted in induction of cyclooxygenase-2 (COX-2) mRNA in brain blood vessels/leptomeninges and telencephalic neurons. To elucidate the causal link between fever and LPS-induced COX-2 mRNA, we experimentally modified one or the other of these parameters and examined their relation. 1) LPS-induced fever was suppressed by pretreatment with a COX-2-specific inhibitor. 2) Levels of COX-2 mRNA in the neurons and blood vessels 2.5 h after LPS administration were even higher in the inhibitor-pretreated rats (afebrile) than in vehicle-pretreated ones (febrile). 3) After repeated administration of LPS, rats became tolerant to LPS, in which state LPS induced neither fever nor COX-2 mRNA in blood vessels/leptomeninges. When rats had not completely established LPS tolerance, they showed various degrees of fever that were closely correlated with the level of COX-2 mRNA in blood vessels but not with that in neurons. 4) Urethan anesthesia reduced basal as well as LPS-induced COX-2 mRNA in telencephalic neurons, but the rats still responded to LPS with fever and induction of COX-2 mRNA in the blood vessels/leptomeninges. These results suggest that COX-2 induced in brain blood vessels/leptomeninges is involved in the molecular mechanism of LPS-induced fever.
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32

Fujii, M., T. Orita, T. Nishizaki, H. Aoki y K. Tanaka. "Primitive neuroectodermal tumor of the leptomeninges". Neuroradiology 33, n.º 3 (1991): 260–63. http://dx.doi.org/10.1007/bf00588232.

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33

de Vries, J., R. Scheremet, M. Altmannsberger, R. Michilli, A. Lindemann y W. Hinkelbein. "Primary leiomyosarcoma of the spinal leptomeninges". Journal of Neuro-Oncology 18, n.º 1 (febrero de 1994): 25–31. http://dx.doi.org/10.1007/bf01324600.

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34

Schyns, Marc, Dominiek Maes, Wikke Kuller y Erik Weerts. "Microscopical Evaluation of Smears of the Leptomeninges to Predict Meningitis in Piglets". Veterinary Sciences 9, n.º 7 (5 de julio de 2022): 341. http://dx.doi.org/10.3390/vetsci9070341.

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Meningitis, caused by bacterial infections such as Streptococcus spp., is a frequently observed cause of death in pigs. In order to implement effective treatment and avoid further losses, it is important to establish this diagnosis quickly. However, this is often difficult because macroscopic lesions may not be visible, and additional laboratory testing may take several days. The present study investigated whether microscopical examination of impression smears of the leptomeninges taken during necropsy can help in establishing a presumptive diagnosis of meningitis in pigs more quickly. In total, 54 pigs suffering from neurological signs and/or (acute) mortality were examined. They were 3 to 10 weeks old and originated from 16 farms. From each pig, bacterial culture was performed on one half of the brain using a swab from the leptomeninges. From the other half, paired cytological impression smears of the leptomeninges were stained with a commercial quick stain dye (Hemacolor®) and Gram stain and microscopically evaluated for the abundance of neutrophils and the presence of short-chain coccoid bacteria. Bacterial culture of the leptomeninges was positive in 36/54 cases, in 28 of which Streptococcus spp. were found. The numbers of smears with low, moderate, or high abundance of neutrophils were 19, 17, and 18, respectively. Short-chain coccoid bacteria were detected successfully in 12 pigs in the Gram-stained smear. The positive predictive value of smears with moderate or high abundance of neutrophils for bacterial presence and, therefore, likely meningitis was 89%, whereas the negative predictive value of smears with low abundance of neutrophils was 74%. The positive predictive value of smears with short chains of coccoid bacteria for diagnosis of Streptococcus spp. was 100%, whereas the negative predictive value was 62%. In conclusion, microscopical examination of impression smears of the leptomeninges of piglets with neurological signs and/or (acute) mortality is a feasible procedure that can help swine practitioners in establishing a tentative diagnosis of meningitis more quickly, especially if neutrophils are abundant, and short chains of coccoid bacteria are present.
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35

Balakrishnan, Rajesh, Rokeya Porag, Dewan Shamsul Asif, A. M. Rejaus Satter, Md Taufiq y Samson S. K. Gaddam. "Primary Intracranial Melanoma with Early Leptomeningeal Spread: A Case Report and Treatment Options Available". Case Reports in Oncological Medicine 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/293802.

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Primary CNS melanomas are rare and they constitute about 1% of all cases of melanomas and 0.07% of all brain tumors. These tumors are aggressive in nature and may metastasise to other organs. Till date less than 25 cases have been reported in the literature. The primary treatment for local intraparenchymal tumours is complete resection and/or radiotherapy and it is associated with good survival. However once there is disease spread to leptomeninges the overall median survival is around 10 weeks. In this case report we describe a primary intracranial melanoma without any dural attachment in 16-year-old boy who had radical excision of the tumor followed by radiotherapy who eventually had rapidly developed leptomeningeal disease and review the literature with a focus on the clinic pathological, radiological, and treatment options.
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36

Criswell, Theodore P., Matthew MacGregor Sharp, Howard Dobson, Ciara Finucane, Roy O. Weller, Ajay Verma y Roxana O. Carare. "The structure of the perivascular compartment in the old canine brain: a case study". Clinical Science 131, n.º 22 (13 de noviembre de 2017): 2737–44. http://dx.doi.org/10.1042/cs20171278.

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Dilatation of periarteriolar spaces in MRI of the ageing human brains occurs in white matter (WM), basal ganglia and midbrain but not in cerebral cortex. Perivenous collagenous occurs in periventricular but not in subcortical WM. Here we test the hypotheses that (a) the capacity for dilatation of periarteriolar spaces correlates with the anatomical distribution of leptomeningeal cells coating intracerebral arteries and (b) the regional development of perivenous collagenous in the WM correlates with the population of intramural cells in the walls of veins. The anatomical distribution of leptomeningeal and intramural cells related to cerebral blood vessels is best documented by electron microscopy, requiring perfusion-fixed tissue not available in human material. We therefore analysed perfusion-fixed brain from a 12-year-old Beagle dog as the canine brain represents the anatomical arrangement in the human brain. Results showed regional variation in the arrangement of leptomeningeal cells around blood vessels. Arterioles are enveloped by one complete layer of leptomeninges often with a second incomplete layer in the WM. Venules showed incomplete layers of leptomeningeal cells. Intramural cell expression was higher in the post-capillary venules of the subcortical WM when compared with periventricular WM, suggesting that periventricular collagenosis around venules may be due to a lower resistance in the venular walls. It appears that the regional variation in the capacity for dilatation of arteriolar perivascular spaces in the white WM may be related to the number of perivascular leptomeningeal cells surrounding vessels in different areas of the brain.
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37

Lee, Jung koo, Hak-cheol Ko, Jin-gyu Choi, Youn Soo Lee y Byung-chul Son. "A Case of Diffuse Leptomeningeal Glioneuronal Tumor Misdiagnosed as Chronic Tuberculous Meningitis without Brain Biopsy". Case Reports in Neurological Medicine 2018 (2 de julio de 2018): 1–7. http://dx.doi.org/10.1155/2018/1391943.

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Here we report a rare case of diffuse leptomeningeal glioneuronal tumor (DLGNT) in a 62-year-old male patient misdiagnosed as having tuberculous meningitis. Due to its rarity and radiologic findings of leptomeningeal enhancement in the basal cisterns on magnetic resonance imaging (MRI) similar to tuberculous meningitis, DLGNT in this patient was initially diagnosed as communicating hydrocephalus from tuberculous meningitis despite absence of laboratory findings of tuberculosis. The patient’s symptoms and signs promptly improved after a ventriculoperitoneal shunting surgery followed by empirical treatment against tuberculosis. Five years later, mental confusion and ataxic gait developed in this patient again despite well-functioning ventriculoperitoneal shunt. Aggravation of leptomeningeal enhancement in the basal cisterns was noted in MRI. An additional course of antituberculosis medication with steroid was started without biopsy of the brain. Laboratory examinations for tuberculosis were negative again. After four months of improvement, his mental confusion, memory impairment, dysphasia, and ataxia gradually worsened. A repeated MRI of the brain showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain surface and leptomeninges revealed a very rare occurrence of DLGNT. His delayed diagnosis of DLGNT might be due to prevalence of tuberculosis in our country, similarity in MRI finding of prominent leptomeningeal enhancement in the basal cisterns, and extreme rarity of DLGNT in the elderly. DLGLT should be considered in differential diagnosis of medical conditions presenting as communicating hydrocephalus with prominent leptomeningeal enhancement. A timely histologic diagnosis through a leptomeningeal biopsy of the brain and spinal cord in case of unusual leptomeningeal enhancement with uncertain laboratory findings is essential because cytologic examination of the cerebrospinal fluid in DLGNT is known to be negative.
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38

Wang, Yao, Yajun Gao, Xue Li, Xiaolin Sun, Zhanqi Wang, Hanchi Wang, Ran Nie, Weixian Yu y Yanmin Zhou. "Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling". BioMed Research International 2020 (15 de septiembre de 2020): 1–12. http://dx.doi.org/10.1155/2020/4616308.

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Background. The brain is in many ways an immunologically and pharmacologically privileged site because of the blood-brain barrier (BBB). But for chronic peripheral inflammation, inflammatory signals can be transmitted from the peripheral system into the central nervous system (CNS) through multiple channels and result in neuroinflammation. Leptomeningeal cells that form the BBB can trigger one signaling pathway by releasing cytokines to transmit inflammatory signals. Besides, the Janus kinase (JAK) family may have a certain function in the activation of leptomeninges. In the present study, we try to use coniferyl aldehyde (CA), a natural anti-inflammatory phenolic compound, to inhibit this inflammatory process and elucidate the underlying molecular mechanisms. Results. Secretion of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) significantly increased after incubation with P. gingivalis. Moreover, TNF-α, IL-1β, and IL-6 levels were upregulated, and the JAK2 signaling was enhanced in leptomeningeal cells in a conditioned medium from activated macrophages, which leads to the immune response in microglia. However, this inflammatory effect of leptomeningeal cells was reversed by CA administration, accompanied by the decreased immune response in microglia. The western blot assay revealed that JAK2 phosphorylation was suppressed in leptomeningeal cells treated with CA. Conclusions. This study demonstrates that activated macrophages by P. gingivalis markedly induce the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) from leptomeningeal cells, thereby activating the JAK2 signaling pathway and subsequently enhancing immune responses in microglia in the CNS. CA effectively inhibits the inflammatory effect of leptomeningeal cells via suppressing the JAK2 signaling pathway.
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39

Chi, Yudan, Jan Remsik, Vaidotas Kiseliovas, Camille Derderian, Ugur Sener, Majdi Alghader, Fadi Saadeh et al. "ETMM-03. CANCER CELLS DEPLOY LIPOCALIN- 2 TO COLLECT LIMITING IRON IN LEPTOMENINGEAL METASTASIS". Neuro-Oncology Advances 3, Supplement_1 (1 de marzo de 2021): i14. http://dx.doi.org/10.1093/noajnl/vdab024.059.

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Abstract The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)-filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. A Phase Ia/1b clinical trial focused on this novel treatment approach is underway.
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40

Chi, Yudan, Jan Remsik, Vaidotas Kiseliovas, Camille Derderian, Ugur Sener, Majdi Alghader, Fadi Saadeh et al. "Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis". Science 369, n.º 6501 (16 de julio de 2020): 276–82. http://dx.doi.org/10.1126/science.aaz2193.

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The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)–filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. Thus, cancer cells appear to survive in the CSF by outcompeting macrophages for iron.
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41

Gomez, Caitlin, Jeffrey Wu, Whitney Pope, Harry Vinters, Antonio DeSalles y Michael Selch. "Pineocytoma with diffuse dissemination to the leptomeninges". Rare Tumors 3, n.º 4 (1 de noviembre de 2011): 163–65. http://dx.doi.org/10.4081/rt.2011.e53.

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Pineal parenchymal tumors are rare. Of the three types of pineal parenchymal tumors, pineocytomas are the least aggressive and are not known to diffusely disseminate. In this paper, we report the successful treatment of a case of pineocytoma with diffuse leptomeningeal relapse following initial stereotactic radiotherapy. A 39-year-old female presented with headaches, balance impairment, urinary incontinence, and blunted affect. A pineal mass was discovered on magnetic resonance imaging (MRI). A diagnosis of pineocytoma was established with an endoscopic pineal gland biopsy, and the patient received stereotactic radiotherapy. Ten years later, she developed diffuse leptomeningeal dissemination. The patient was then successfully treated with craniospinal radiation therapy. Leptomeningeal spread may develop as late as 10 years after initial presentation of pineocytoma. Our case demonstrates the importance of long-term follow-up of patients with pineal parenchymal tumors following radiation therapy, and the efficacy of craniospinal radiation in the treatment of leptomeningeal dissemination.
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42

Johnson, Mahlon D., Fran Vito y Mary J. O'Connell. "Mesothelin Expression in the Leptomeninges and Meningiomas". Journal of Histochemistry & Cytochemistry 56, n.º 6 (17 de marzo de 2008): 579–85. http://dx.doi.org/10.1369/jhc.2008.950477.

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43

Mendel, Richard C., Michael Pollay, Gary B. Bobele, Richard W. Leech y Roger A. Brumback. "Primary Primitive Neuroectodermal Tumor of the Leptomeninges". Journal of Child Neurology 11, n.º 5 (septiembre de 1996): 404–7. http://dx.doi.org/10.1177/088307389601100513.

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44

Mansouri, Bobbak, Daniel P. Barboriak y Ramsey K. Kilani. "Gliosarcoma Metastatic to the Leptomeninges and Dura". Journal of Neuroimaging 23, n.º 2 (1 de septiembre de 2011): 245–47. http://dx.doi.org/10.1111/j.1552-6569.2011.00641.x.

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45

Cabrera villegas, A., J. C. Martín urreta y J. P. Ciria santos. "Metástasis en leptomeninges descubiertas con PET-FDG". Revista Española de Medicina Nuclear 20, n.º 4 (enero de 2001): 309–10. http://dx.doi.org/10.1016/s0212-6982(01)71964-7.

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46

Johnson, Mahlon D., Jay E. Reeder y Mary O'Connell. "APOBEC3B expression in human leptomeninges and meningiomas". Oncology Letters 12, n.º 6 (10 de noviembre de 2016): 5344–48. http://dx.doi.org/10.3892/ol.2016.5377.

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Qian, Min, Haitao Ren, Tao Qu, Zhaohui Lu, Yueli Zou, Junying He, Yanhuan Zhao, Lin Chen y Hongzhi Guan. "Spectrum of Clinical, Neuroimaging, and Cerebrospinal Fluid Features of Adult Neurocutaneous Melanocytosis". European Neurology 80, n.º 1-2 (2018): 1–6. http://dx.doi.org/10.1159/000488687.

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Background: Neurocutaneous melanocytosis (NCM) is a poorly understood disease due to its rarity. This study aimed to summarize the characteristics of adult NCM and improve the awareness of this disease. Methods: The clinical data of 13 adult patients with NCM were retrospectively reviewed, including neuroimages, cerebrospinal fluid (CSF), and histological features. Results: There were 9 males and 4 females. The mean age at symptom onset was 36.5 years. The initial symptoms included intracranial hypertension in 8 patients and seizure in 4 patients. Ten patients had large and/or multiple congenital melanocytic nevi. MRI revealed hydrocephalus and diffuse thickening of the leptomeninges with T1 shortening in all patients. Post-contrast T1-weighted images showed diffuse linear enhancement of the leptomeninges. Lumbar punctures showed increased open pressure, and elevated protein levels and decreased glucose concentrations in CSF. Cells with intracytoplasmic coarse black granules were found in the CSF and were positive for S100, HMB45, and vimentin. Histopathology of the cutaneous lesions and meninges showed melanocytes but no evidence of malignant melanoma. Conclusion: Adult NCM patients present a diversity of clinical manifestations. Brain MRI showing diffuse thickening of the leptomeninges with T1 shortening is useful in diagnosing NCM. Heterocellular melanin may be of great value for early diagnosis of NCM in challenging cases.
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Le Zuo, Michelle Xiao, Naomi M. Fettig, Lisa C. Osborne, Jennifer L. Gommerman y Valeria Ramaglia. "Age-related susceptibility to grey matter demyelination and neurodegeneration is associated with meningeal neutrophil accumulation in an animal model of MS". Journal of Immunology 208, n.º 1_Supplement (1 de mayo de 2022): 104.10. http://dx.doi.org/10.4049/jimmunol.208.supp.104.10.

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Abstract People living with multiple sclerosis (MS) experience episodic central nervous system (CNS) white matter lesions instigated by autoreactive T cells. With age, MS patients show evidence of grey matter demyelination and experience devastating non-remitting symptomology. What drives progression is unclear and has been hampered by the lack of suitable animal models. Here we show that passive experimental autoimmune encephalomyelitis (EAE) induced by an adoptive transfer of young Th17 cells induces a non-remitting clinical phenotype that is associated with persistent leptomeningeal inflammation and cortical pathology in old, but not young SJL/J mice. While the quantity and quality of T cells did not differ in the brains of old vs young EAE mice, an increase in neutrophils and a decrease in B cells was observed in the brains of old mice. Neutrophils were also found in the leptomeninges of a subset of progressive MS patient brains that showed evidence of leptomeningeal inflammation and subpial cortical demyelination. Taken together, our data show that while Th17 cells initiate CNS inflammation, subsequent clinical symptoms and grey matter pathology are dictated by age and associated with other immune cells such as neutrophils.
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49

Juanes-Velasco, Pablo, Norma Galicia, Elisa Pin, Ricardo Jara-Acevedo, Javier Carabias-Sánchez, Rodrigo García-Valiente, Quentin Lecrevisse et al. "Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid". Cancers 14, n.º 2 (17 de enero de 2022): 449. http://dx.doi.org/10.3390/cancers14020449.

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In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.
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50

Guerra-Garcia, Maria, Henriette Balinda, Ande Bao, Michael Garcia, Andrea Gilbert, William Phillips, John Floyd y Andrew Brenner. "LMD-14. Preclinical safety and activity of intraventricular Rhenium-186 Nanoliposome (186RNL) for leptomeningeal metastases". Neuro-Oncology Advances 3, Supplement_3 (1 de agosto de 2021): iii10. http://dx.doi.org/10.1093/noajnl/vdab071.039.

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Abstract Introduction Leptomeningeal metastases (LM) is a clinical complication that occurs when cancer cells invade the leptomeninges and cerebrospinal fluid of patients with malignant tumors. Once diagnosed, limited treatment options exist, and survival is poor. Rhenium-186 Nanoliposome (186RNL) is a liposomal encapsulated beta emitter with a short path length of 1.8 mm, thereby allowing high specific activity brachytherapy with limited exposure to surrounding tissues. Methods To establish the maximum tolerated dose (MTD) of 186RNL by intraventricular (IT) injection, eight cohorts of Wistar rats (n=3 each) were injected IT with increasing activity of 186RNL at doses of 0 (control), 0.480, 0.800, 1.000, 1.150, and 1.340 mCi. Toxicity was assessed by daily food and water intake, daily weights, and observing for neurological deficits. To assess efficacy, C6-Luc glioma cells were injected IT and 15 days post inoculation the animals were treated with 0.69 mCi of 186RNL. Absorbed doses were assessed with gamma camera imaging at 0h, 24h, and 48h post-treatment. Tumor growth was assessed by luciferase bioluminescence. Results No evidence of adverse 186RNL-related effects was observed in rats through 3 months following administration of up to 1.34 mCi with an absorbed dose of up to 1075 Gy. Hence, the MTD exceeded the doses evaluated in this study. A significant difference in survival between the control and treatment groups (n=8 each) was observed at 2 weeks post treatment, with 50% survival in the control group and 100% survival in the treatment group (p=0.0087). The only significant treatment-related histologic finding among treated rats was slight focal thickening of the leptomeninges, suggesting a mild reactive hypertrophy. Conclusion Intraventricular delivery of 186RNL is well tolerated and improves animal survival at 2 weeks in a rat model of LM.
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