Academic literature on the topic 'Leptomeninges'
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Journal articles on the topic "Leptomeninges"
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Aslan, Sabina, Rahsan Gocmen, Nazire Pınar Acar, Farid Khasiyev, Ekim Gumeler, Figen Soylemezoglu, Aslı Tuncer, Ethem Murat Arsava, Mehmet Akif Topçuoglu, and Isin Unal Cevik. "Two cases of primary leptomeningeal melanomatosis mimicking subacute meningitis." Neuroradiology Journal 31, no. 1 (June 19, 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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Tanaka, Junya, Hisaaki Takahashi, Hajime Yano, and Hiroshi Nakanishi. "Generation of CSF1-Independent Ramified Microglia-Like Cells from Leptomeninges In Vitro." Cells 10, no. 1 (December 25, 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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Zivkovic, Nikola, Dragan Mihailovic, Zaklina Mijovic, and Maja Jovicic-Milentijevic. "Primary leptomeningeal melanocytosis: A case report with an autopsy diagnosis." Vojnosanitetski pregled 69, no. 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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Saad, Ali G., Mayur Jayarao, Lawrence S. Chin, and Ivana Delalle. "Ganglioglioma Associated with Cerebral Cortical Dysplasia: An Unusual Case with Extensive Leptomeningeal Involvement." Pediatric and Developmental Pathology 11, no. 6 (November 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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Funato, H., M. Yoshimura, Y. Ito, R. Okeda, and Y. Ihara. "Proliferating cell nuclear antigen (PCNA) expressed in human leptomeninges." Journal of Histochemistry & Cytochemistry 44, no. 11 (November 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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Leblanc, Richard, Sabah Bekhor, Denis Melanson, and Stirling Carpenter. "Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus papilloma." Journal of Neurosurgery 88, no. 4 (April 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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Kijima, Noriyuki, Takamune Achiha, Tomoyoshi Nakagawa, Ryuichi Hirayama, Manabu Kinoshita, Naoki Kagawa, and Haruhiko Kishima. "CBIO-02. COMPREHENSIVE ANALYSIS OF MECHANISMS AND MOLECULAR TARGETS FOR BREAST CANCER LEPTOMENINGEAL METASTASIS." Neuro-Oncology 22, Supplement_2 (November 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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Ng, Ho-keung, and Wai-sang Poon. "Primary leptomeningeal astrocytoma." Journal of Neurosurgery 88, no. 3 (March 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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Bhan, Arunoday Kuldeep, Khairul I. Ansari, Clara Chen, and Rahul Jandial. "Abstract P1-21-05: GM-CSF is an autocrine driver of HER2+ breast leptomeningeal carcinomatosis." Cancer Research 82, no. 4_Supplement (February 15, 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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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, no. 2 (November 6, 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.
Dissertations / Theses on the topic "Leptomeninges"
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Fowler, Mark Ian. "The role of the human leptomeninges in the inflammatory response to bacterial pathogens." Thesis, University of Southampton, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403755.
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BERSAN, Emanuela. "Characterization of new stem cell niches with neuronal differentiation potential." Doctoral thesis, Università degli Studi di Verona, 2010. http://hdl.handle.net/11562/341480.
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Staminali neuronali adulte (NSC), sono state trovate nelle primcipali aree neurogeniche del cervello, per esempio ippocampo, regione subventricolare (SVZ), bulbi olfattivi, e in alcune regioni non neurogeniche come ad esempio il midollo spinale. Altre regioni del cervello possono ospitare nicchie di NSC e, in particolare, considerando il ruolo delle meningi nel corretto sviluppo della corteccia cerebrale, è nostro interesse esplorare la regione delle leptomeningi che si estende dall’aracnoide fino al primo strato della corteccia cerebrale. Lo scopo di questo progetto è caratterizzare le leptomeningi come potenziale nicchia di cellule staminali neuronali. La regione delle leptomeningi è stata caratterizzata mediante immunoistochimica, in ratti di diversa età, dall’embrione E20, a ratti in età postnatale P0, P15 e nell’adulto. Cellule positive per il marcatore di cellule staminali neuronali nestina, sono state individuate in leptomeninge. Queste cellule sono distribuite fuori dalla membrane basale (positive per il marker Laminina), come una popolazione distinta dagli astrociti (cellule GFAP positive) e dai precursori oligodendrocitari (cellule NG2 positive ), che risiedono nel tessuto circostante. Le cellule nestine positive sono state prelevate dale leptomeningi di ratti P0, P15 e adulti ed espanse in vitro. Le cellule così prelevate sono state espanse in aderenza come una popolazione omogena di cellule nestina positive. Se sottoposto a stimuli differentiativi neuranali, le cellule nestine positive sono in grado di differenziare principalmente in neuroni (positive per MAP2), ma anche in astrociti ed oligodendrociti (positive per O4). Come primo approcio di analisi funzionale delle cellule differenziate in vitro, è stata valutata la loro capacità di rispondere a stimuli depoarizzanti mediante calico imaging, dopo incubazione delle cellule con Fura2. I neuroni ottenuti dal differenziamento in vitro delle cellule nestine positive sono in grado di rispondere all’applicazione dell’agente depolarizzante KCl, suggerendo l’espressione di canali del calico voltaggio dipendenti, come i neuroni funzionali. Il potenziale differenziativo in vivo di queste cellule è stato valutato mediante infusione stereotassica in ippocampo di ratti adulti, di cellule nestine positive estratte dalle leptomeningi di ratti transgenici EGFP. L’ippocampo dei ratti iniettati sono stati analizzati mediante immunofluorescenza a due mesi dall’iniezione delle cellule EGFP. Circa metà delle cellule EGFP identificate in ippocampo esprimevano markers neuronali (DCX, MAP2, NeuN, Neurofilament-160, GAD67). Vista la persistenza di queste cellule nestina positive nelle meningi di ratto durante lo sviluppo fino all’età adulta, dato il loro potenziale proliferativo in vitro ed il loro potenziale differenziativo neuronale sia in vitro che in vivo, queste cellule sono state proposte come nuova entità con il nome di Leptomeningeal stem/progenitor cells (LeSC). Dall’anatomia delle meningi si evince che ricoprono l’intero sistema nervosa centrale, il che comprende anche il midollo spinale. Per questo motivo sono state analizzate anche le leptomeningi che ricoprono il midollo spinale. Come osservato in precedenza per il cervello, cellule positive per il marcatore delle cellule staminali neuronali nestina, sono state individuate in leptomeninge. Queste cellule sono distribuite fuori dalla membrane basale (positive per il marker Laminina), come una popolazione distinta dagli astrociti (cellule GFAP positive) e dai precursori oligodendrocitari (cellule NG2 positive ), che risiedono nel tessuto circostante. Un nuovo studio in collaborazione con la professoressa M. Schwartz group (Weizmann Institute, Rehovot, Israel) è in corso sul potenziale ruolo del sistema immunitario nel regolare le leptomeningi ed in particolare le LeSC (come suggerito da precedenti pubblicazioni del gruppo della prof. Schwartz). Risultati preliminary sul confronto ex vivo della proliferazione delle LeSC in topi SCID e wt, mostrano una significativa diminuzione dl numero di LeSC nestinepositive in topi SCID. Nonostante questa diminuzione di cellule nestine positive, il numero totale di cellule che risiedono in leptomeninge è comparabile in entrambi I topi SCID e wt. E’ in corso una più estensiva caratterizzazione delle leptomeningi dei topi SCID e wt per capire la natura delle cellule nestine negative che risiedono nelle leptomeningi dei topi SCID. L’importanza delle LeSC risiede nella posizione facilmente raggiungibile rispetto alle già note nicchie di staminali neuronali, ed inoltre nell’elevato potenziale differenziativo neuronale. Queste peculiarità apriranno nuovi studi nell’ambito della medicina rigenerativaAdult neural stem cells (NSC), have been found in the main neurogenic regions of brain, i.e. hippocampus, sub ventricular zone (SVZ), olfactory bulb, and in some non-neurogenic regions, i.e. spinal cord. Other brain sites could host NSC niches and, in particular, considering the role of meninges in correct cortex development we were interested in exploring the region residing between arachnoide and the first layers of the cerebral cortex, called Leptomeninges. Aim of this project is characterized the leptomeningeal compartment as potential niche for neural stem cells with ex vivo and in vitro approaches. The leptomeningeal compartment has been characterized by immunohistochemistry at different rat ages, from embryo E20, postnatal day 0 (P0), P15 and adult. We found a(nestin) neuro-epithelial stem cells marker positive cells layer with decreasing thickness from embryo up to adult. Nestin positive cells were distributed outside the basal lamina (marked by laminin), and as a distinct population from astrocytes (stained with GFAP) and oligodendrocytes (stained with NG2). Nestin positive cells were dissected and expanded in vitro from P0, P15 and adult rats leptomeninges. We were able to culture them as homogeneus nestin positive cells population in adherent condition In neuronal differentiating conditions, nestin positive cells mainly differentiate into MAP2 positive cells but also GFAP and O4 (marker for mature oligodendrocyte) positive cells were detected in culture. As a first level of functional evaluation of differentiated cells, their ability to depolarize has been analyzed by calcium imaging assay after Fura-2 loading. In vitro differentiated neurones responded to fast applications of the depolarizing agent KCl suggesting the expression of voltage dependent calcium channels, similar to that of functional neurons. As following step, the in vivo neuronal differentiation potential was assessed by infusion of expanded EGFP LeSC in rat hippocampus. Engrafted LeSC were monitored by immunofluorescence up two months and during this period LeSC were able to survive after injection. About half of EGFP cells engrafted in hippocampus, expressed neuronal markers (DCX, MAP2, NeuN, Neurofilament-160, GAD67) and shown differentiated neuronal morphology. Because of the persistence of these cells up to adulthood, their proliferation capability in vitro, and their differentiation potential into neuronal cells in vitro and in vivo, we suggest to name them leptomeningeal stem/progenitor cells (LeSC) as a new population never described before. Since meninges cover whole brain, also Leptomeninges from rat spinal cord has been analyzed. Nestin positive cells were distributed as previously observed in the brain, outside the basal lamina, and as a distinct population from astrocytes and oligodendrocytes. Cells were dissected and kept in culture as neurosphere and resulted positive for nestin, MAP2, GFAP, O4, and Oct4. A new study In collaboration with professor M. Schwartz group (Weizmann Institute, Rehovot, Israel) is ongoing to understand the potential role of immune system in regulating leptomeninges and LeSC (as suggested by previous publications from Schwartz’s group). Preliminary results Comparison of LeSC proliferation and nestin expression by immunohistochemistry in SCID vs wt mice, revealed a significant decrease of nestin positive LeSC in SCID mice. However total cell number and proliferating cells in leptomeninges were not changed. Further characterizations are ongoing to understand the phenotype of proliferating nestin negative cells in meninges. The importance of Leptomeningeal stem cells reside in the easier reachable localization compared to the already known neural stem cell niches, and in their high neuronal differentiation potential. These characteristics will open novel studies in regenerative medicine.
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Oostenbrugge, Robert Jan van. "Interphase cytogenetics in the cytodiagnosis of leptomeningeal metastases." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=6838.
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Neto, Sara Patrícia Dias. "Clínica de animais de companhia." Master's thesis, Universidade de Évora, 2016. http://hdl.handle.net/10174/19805.
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O presente relatório é resultado do estágio curricular, 11º semestre do Mestrado Integrado em Medicina Veterinária. Este decorreu em duas instituições de referência veterinária em Barcelona (Hospital ARS Veterinária e Hospital Veterinari Montjuïc) e permitiu melhorar e integrar os conhecimentos adquiridos ao longo do curso.
O relatório é composto por três partes: introdução, que situa temporal e espacialmente, relatório de casuística, que abrange todas as atividades realizadas e assistidas, e monografia.
A monografia consiste na descrição de uma afeção neurológica, muito comum em Cavalier king charles spaniel, designada de siringomielia. A monografia inicia-se com uma revisão bibliográfica e termina com o relato de quatro casos clínicos acompanhados no Hospital ARS Veterinário; ABSTRACT:
Small animal practice
This report is the result of the traineeship in the 11th semester of the Integrated Master degree in Veterinary Medicine. It took place in two veterinary reference institutions in Barcelona (hospital ARS veterinary and hospital Veterinari Montjuïc) and contributed to improve and integrate the knowledge acquired throughout the course.
The report consists in three parts: Introduction, which locates temporally and spatially, the sample report covering all activities, and monograph.
The monography is the description of a neurological disorder, very common in Cavalier king charles spaniel, designated syringomyelia. The monography begins with a literature review and ends with the description of four clinical cases followed in ARS veterinary hospital.
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Delisle, Marie-Bernadette. "Les gliomatoses cérébro-méningées : discussion de leur place dans l'histoire des gliomes." Aix-Marseille 2, 1987. http://www.theses.fr/1987AIX21913.
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OTTAVIANI, LICIA. "L’uso della citometria a flusso facilita la diagnosi di meningosi occulta nelle neoplasie ematologiche." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/209620.
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Scopo del lavoro. L’analisi citomorfologica (CM) del liquor cefalorachidiano (LCR) fallisce nell’evidenziare la presenza di cellule maligne in circa il 45% dei casi, mentre l’analisi citofluorimetrica (CFM) sembra essere più sensibile nella rilevazione di cellule neoplastiche nel liquor. L’obbiettivo del nostro studio è stato quello di valutare la superiorità della CFM rispetto alla CM nella diagnosi di localizzazione meningea nelle patologie ematologiche, e di valutare, inoltre, l’impatto clinico della positività dell’ esame citofluorimetrico in assenza di cellule blastiche morfologicamente riconoscibili.
Materiali e metodi. Sono stati pertanto analizzati 81 campioni di LCR di pazienti affetti da neoplasie ematologiche: 39 pazienti con Leucemia Mieloide Acuta (LMA), 13 Leucemia Linfatica Acuta-B (LLA-B), 2 Leucemia/Linfoma linfoblastico T (LL-T), 2 Linfoma di Burkitt (LB), 1 Leucemia Plasmacellulare (LP), e 17 Linfoma non-Hodgkin diffuso a grandi cellule B (LNH-GC). I campioni sono stati studiati mediante: esame chimico, conta cellulare, CM e CMF.
Risultati. Ventisei campioni sono risultati essere CFM positivi, di questi 9 (35%) risultavano essere anche CM positivi (CFMpos/CMpos), invece 17 (65%) erano CM negativi (CFMpos/CMneg). Dei 17 pazienti (CFMpos/CMneg) 7 erano affetti da disordini linfoproliferativi aggressivi e 10 da Leucemia Mieloide Acuta (LMA), 5 (71%) dei 7 pazienti affetti da disordini linfoproliferativi hanno sviluppato recidiva meningea manifesta nonostante la somministrazione profilattica di farmaci per via intratecale, e solo 1 (10%) dei 10 pazienti affetti da LMA, è andato incontro a recidiva al SNC, sebbene non sia stata effettuata nessuna profilassi in questo gruppo di pazienti. Nessuno tra i pazienti CFM negativi ha sviluppato recidiva meningea (p<0.0001). Abbiamo inoltre osservato una differenza statisticamente significativa nella sopravvivenza globale (SG) con una più lunga SG nei pazienti doppi negativi e una più breve SG in quelli doppi positivi. I pz (CFMpos/CMneg) mostravano una SG intermedia (p=0.02)
Discussione e conclusioni. Il nostro studio conferma la maggiore sensibilità della CFM rispetto alla CM nell’analisi del LCR. In particolare, nelle patologie linfoproliferative la citofluorometria sembra incrementare la diagnosi di localizzazioni leptomeningee occulte e predire lo sviluppo di meningosi conclamate. Di contro, il significato della sola positività della CFM nelle LMA non sembra avere lo stesso impatto clinico e questo potrebbe
dipendere dalle caratteristiche biologiche della malattia stessa e dai regimi terapeutici basati sull’uso della Citarabina ad alte dosi o in infusione continua nelle LMA.Cytomorphology (CM) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45% of patients in whom leptomeningeal disease is present. Flow cytometry (FC) is considered more sensitive than CM, but clinical implications of FC positivity/CM negativity are not established. CSF samples from 81 patients with haematologic malignancies were examined by CM and FC. Overall, 26 (32%) of 81 cases were FC positive; of these 26, 9 (35%) were also CM positive(FCpos/CMpos) while 17 (65%) were CM negative (FCpos/CMneg) (p=0.00002). Of 17 FCpos/CMneg patients, 7 were affected with various forms of aggressive lymphoproliferative disorders and 10 with acute myeloid leukaemia (AML). Five patients (71%) of 7 with lymphoproliferative diseases developed overt central nervous system (CNS) disease whereas only 1 (10%) of 10 patients with AML experienced overt leukaemic meningitis. None of FCneg/CMneg patients experienced overt CNS disease (p<0.0001). FCpos/CMneg patients showed a significantly shorter overall survival (OS) as compared to FCneg/CMneg cases (p=0.02). In conclusion our data suggest that in lymphoid malignancies, FC significantly improves detection of leptomeningeal occult localization and predict overt disease, conversely in AML, FC positivity does not appear to have clinical significance, likely due to the use of ARAC based regimens and biology of disease.
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Tu, Qian. "Application de la technique CellSearch® Veridex pour la détection de cellules tumorales dans les liquides biologiques chez les patients atteints de cancers." Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0066/document.
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L’apparition de la technique CellSearch® a permis d’obtenir la sensibilité et la spécificité suffisantes et de détecter les CTCs en ciblant les marqueurs spécifiques dans le sang périphérique. Elle permet la numération et l’étude morphologique des CTCs qui est largement utilisée et validée. Nous décrivons une adaptation de la méthode CellSearch® pour détecter les cellules tumorale chez les LM (métastases leptoméningées) patients atteints de cancers du sein, du poumon et mélanomes, qui semble atteindre une sensibilité améliorée en comparaison avec la cytologie conventionnelle. Nous présentons également un cas clinique pour la détection de cellules tumorales dans l’ascite et du sang chez un patient avec le cancer de l’oesophage métastatique. De plus, la détection des cellules tumorales dans le redon chez les patients subis une chirurgie de la tête et du cou a été également réalisée. En utilisant cette méthode, les résultats sont non seulement quatitatifs, mais aussi quantitatifs avec des images numériques de chaque cellule, et des résultats séquentiels ont été étudiés chez certains patients atteints de cancer du sein, de cancer du poumon et de mélanome. Les données ont montré des changements dynamiques des nombres de cellules tumorales détectées dans le LCR, mais leurs corrélations avec la réponse au traitement ou la progression de la maladie ont besoin des études supplémentaires plus contrôlées avec une grande cohorte de patients. La mise en évidence de cette application serait importante en clinique pour le diagnostic, le pronostic et le traitement des patients atteints de cancer avec des métastases aux niveaux du SNC, du péritoineThe introduction of CellSearch® technology allows to give sufficient sensitivity and specificity and to detect CTCs targeting specific markers in peripheral blood. The enumeration and morphological study of CTCs are widely used and validated. We described an adaptation of the CellSearch® method to detect tumor cells in LM (leptomeningeal metastases) patients with breast cancer, lung cancer and melanoma, which appeared to achieve an improved sensitivity in comparison with conventional cytology. We also presented a case report for the detection of tumor cells in the ascites and blood of a patient with metastatic oesophageal cancer. Furthermore, the detection of tumor cells in aspirative drains after neck dissectionin from the patients undergoing surgery for head and neck cancer was also performed. Using this method, the results were not only quatitative but also quantitative with digital images of each cell, and sequential results were studied in some patients with breast cancer, lung cancer and melanoma. The data showed dynamic changes of the numbers of tumor cells detected in CSF, but their correlation with the response to treatment or disease progression need additional more controlled studies with a large cohort of patients. The application would be important for the clinical diagnosis, prognosis and treatment of cancer patients with CNS metastases and peritoneal metastases
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Wu, Xianglei. "Évaluation concomitante des signatures fonctionnelles des réponses lymphocytaires T spécifiques des Antigènes Associés aux Tumeurs et des Cellules Tumorales Circulantes : Impact sur le pronostic des patients atteints de carcinome épidermoïde des voies aéro-digestives supérieures." Thesis, Université de Lorraine, 2017. http://www.theses.fr/2017LORR0037/document.
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Nous avons abordé dans l’ensemble de nos travaux deux paramètres importants pour l’immunomonitoring des patients atteints d’un cancer : les cellules tumorales circulantes (CTC) comme un indicateur de la « charge antigénique tumorale » et la réponse immune lymphocytaire T spécifique d’antigènes associés aux tumeurs (AAT). Nous avons évalué d’abord la valeur diagnostique et pronostique des CTC dans les cancers des voies aérodigestives supérieures (« HNSCC » en anglais) par une revue systématique et meta-analyse de la littérature. Les preuves actuelles identifient le test de détection de CTC comme un test extrêmement spécifique, mais de faible sensibilité dans les HNSCC. En outre, la présence de CTC indique une DFS (« disease free survival ») inférieure. Nous rapportons également pour la première fois un cas rare d’énumération extrêmement élevée de CTC détectées par le système CellSearch® chez un patient présentant un carcinome épidermoïde de la cavité buccale en utilisant. Le nombre absolu de CTC pourrait donc prédire une phase particulière de développement du cancer ainsi qu'une mauvaise survie, contribuant potentiellement à une prise en charge médicale personnalisée. De plus, nous décrivons une adaptation de la méthode CellSearch® qui nous avons développée pour détecter les cellules tumorales dans le liquide céphalo-rachidien de patients atteints de méningites carcinomateuses. Cette nouvelle approche permet une sensibilité nettement améliorée en comparaison avec la cytologie conventionnelle. La technologie CellSearch®, appliquée à des volumes limités des échantillons et permettant une augmentation du temps pré-analytique, pourrait ainsi avoir un grand intérêt dans le diagnostic de métastases leptoméningées chez les patients atteints d’un cancer d’origine épithéliale. Par une évaluation concomitante des CTC et des réponses lymphocytaires spécifiques aux AAT chez 24 patients avec HNSCC, nous avons trouvé que les CTC pourraient être un indicateur indépendant de la charge tumorale immunogène. L'absence de CTC, la présence de lymphocytes T spécifiques aux AAT, ou la combinaison de ceux-ci, étaient tous des paramètres montrant une tendance pour une meilleure survie globale ou une survie sans maladie. L’amplitude et les signatures fonctionnelles des lymphocytes T spécifiques aux AAT chez les patients atteints de HNSCC étaient associées à la présence de CTC. Ces résultats suggèrent qu’une évaluation concomitante de ces deux paramètres pourrait être plus informative sur le pronostic et potentiellement sur l’impact des traitements (notamment dans la perspective d’un traitement par des « immune checkpoints »)We have evaluated herein two important parameters in the immunomonitoring of cancer patients: circulating tumor cells (CTC) as an indicator of “tumoral antigenic load” and tumor-associated antigens (TAA) specific T-cells. We firstly evaluated the diagnostic and prognostic value of CTC in Head and Neck Squamous Cell Carcinoma (HNSCC) by a systematic review and meta-analysis. We came to the conclusion that current evidence identifies the CTC detection test as an extremely specific but low sensitive test in HNSCC. In addition, the presence of CTC indicates a worse disease-free disease (DFS). Also, we report for the first time a rare case of extremely high enumeration of circulating tumor cells detected in a patient with squamous cell carcinoma of the oral cavity using the CellSearch® system. The absolute number of CTC could therefore predict a particular phase of cancer development as well as a poor survival, potentially contributing to personalized health. In addition, we describe an adaptation of the CellSearch® method that we have developed for detecting tumor cells in the cerebrospinal fluid of patients with carcinomatous meningitis. This new approach reaches a significantly improved sensitivity compared to conventional cytology. CellSearch® technology, applied to limited sample volumes and allowing an increased pre-analytical time, may be of great interest in the diagnosis of leptomeningeal metastases in patients with epithelial cancer. By a concomitant evaluation of CTC and TAA-specific lymphocyte responses in 24 HNSCC patients, we describe that CTC could be an independent indicator of immunogenic tumor burden. The absence of CTC, the presence of TAA-specific T-cells, or the combination of these, were all parameters showing a trend for a better overall survival or DFS. The amplitude and functional signatures of TAA-specific T-lymphocytes in patients with HNSCC were associated with the presence of CTC. These results suggest that a concomitant evaluation of these two parameters may be more pertinent for prognosis assessment as well as for treatment impact, especially in “checkpoint-inhibitors” new immunotherapies
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Touat, Mahdi. "Mécanismes et implications thérapeutiques de l'hypermutation dans les gliomes Mechanisms and Therapeutic Implications of Hypermutation in Gliomas Mismatch Repair Deficiency in High-Grade Meningioma: A Rare but Recurrent Event Associated With Dramatic Immune Activation and Clinical Response to PD-1 Blockade Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial Hyman DM. BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study Glioblastoma Targeted Therapy: Updated Approaches From Recent Biology Successful Targeting of an ATG7-RAF1 Gene Fusion in Anaplastic Pleomorphic Xanthoastrocytoma With Leptomeningeal Dissemination Ivosidenib in IDH1-Mutated Advanced Glioma." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL071.
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Une élévation majeure de la charge mutationnelle (hypermutation) est observée dans certains gliomes. Néanmoins, les mécanismes de ce phénomène et ses implications thérapeutiques notamment concernant la réponse à la chimiothérapie ou à l'immunothérapie sont encore mal connus. Sur le plan du mécanisme, une association entre hypermutation et mutations des gènes de la voie de réparation des mésappariements de l'ADN (MMR) a été rapportée dans les gliomes, cependant la plupart des mutations MMR observées dans ce contexte n'étaient pas fonctionnellement caractérisées, et leur rôle dans le développement d’hypermutation restait de ce fait incertain. De plus, l'impact de l'hypermutation sur l'immunogénicité des cellules gliales et sur leur sensibilité au blocage des points de contrôles immunitaires (par exemple par traitement anti-PD-1) n’est pas connu. Dans cette étude, nous analysons de manière exhaustive les déterminants cliniques et moléculaires de la charge et des signatures mutationnelle dans 10 294 gliomes, dont 558 (5,4%) tumeurs hypermutées. Nous identifions deux principales voies responsables d'hypermutation dans les gliomes : une voie "de novo" associée à des déficits constitutionnels du système MMR et de la polymérase epsilon (POLE), ainsi qu'une voie "post-traitement", plus fréquente, associée à l'acquisition de déficits MMR et de résistance secondaire dans les gliomes récidivant après chimiothérapie par temozolomide. Expérimentalement, la signature mutationnelle des gliomes hypermutés post-traitement (signature COSMIC 11) était reproduite par les dommages induits par le témozolomide dans les cellules MMR déficientes. Alors que le déficit MMR s'associe à l'acquisition de résistance au témozolomide, des données cliniques et expérimentales suggèrent que les cellules MMR déficientes conservent une sensibilité à la nitrosourée lomustine. De façon inattendue, les gliomes MMR déficients présentaient des caractéristiques uniques, notamment l'absence d'infiltrats lymphocytaires T marqués, une hétérogénéité intratumorale importante, une survie diminuée ainsi qu’un faible taux de réponse aux traitements anti-PD-1. De plus, alors que l'instabilité des microsatellites n'etait pas détectée par des analyses en bulk dans les gliomes MMR déficients, le séquençage du génome entier à l'échelle de la cellule unique de gliome hypermuté post-traitement permettait de démontrer la presence de mutations des microsatellites. Collectivement, ces résultats supportent un modèle dans lequel des spécificités dans le profil mutationnel des gliomes hypermutés pourraient expliquer l’absence de reconnaissance par le système immunitaire ainsi que l’absence de réponse aux traitements par anti-PD-1 dans les gliomes MMR déficients. Nos données suggèrent un changement de pratique selon lequel la recherche d’hypermutation par séquençage tumoral lors de la récidive après traitement pourrait informer le pronostic et guider la prise en charge thérapeutique des patientsHigh tumor mutational burden (hypermutation) is observed in some gliomas; however, the mechanisms by which hypermutation develops and whether it predicts chemotherapy or immunotherapy response are poorly understood. Mechanistically, an association between hypermutation and mutations in the DNA mismatch-repair (MMR) genes has been reported in gliomas, but most MMR mutations observed in this context were not functionally characterized, and their role in causing hypermutation remains unclear. Furthermore, whether hypermutation enhances tumor immunogenicity and renders gliomas responsive to immune checkpoint blockade (e.g. PD-1 blockade) is not known. Here, we comprehensively analyze the clinical and molecular determinants of mutational burden and signatures in 10,294 gliomas, including 558 (5.4%) hypermutated tumors. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and MMR genes, and a more common, post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas recurring after temozolomide. Experimentally, the mutational signature of post-treatment hypermutated gliomas (COSMIC signature 11) was recapitulated by temozolomide-induced damage in MMR-deficient cells. While MMR deficiency was associated with acquired temozolomide resistance in glioma models, clinical and experimental evidence suggest that MMR-deficient cells retain sensitivity to the chloroethylating nitrosourea lomustine. MMR-deficient gliomas exhibited unique features including the lack of prominent T-cell infiltrates, extensive intratumoral heterogeneity, poor survival and low response rate to PD-1 blockade. Moreover, while microsatellite instability in MMR-deficient gliomas was not detected by bulk analyses, single-cell whole-genome sequencing of post-treatment hypermutated glioma cells demonstrated microsatellite mutations. Collectively, these results support a model where differences in the mutation landscape and antigen clonality of MMR-deficient gliomas relative to other MMR-deficient cancers may explain the lack of both immune recognition and response to PD-1 blockade in gliomas. Our data suggest a change in practice whereby tumor re-sequencing at relapse to identify progression and hypermutation could inform prognosis and guide therapeutic management
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PRETTO, Silvia. "The meningeal stem cell niche in health and disease." Doctoral thesis, 2012. http://hdl.handle.net/11562/441538.
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Il nostro gruppo ha dimostrato per la prima volta che una nuova nicchia di cellule precursori/staminali con potenziale di differenziamento neuronale risiede nelle meningi cerebrali di ratti in età postnatale. Grazie alla loro locazione superficiale, le meningi possono rappresentare una un nuovo ed accessibile tessuto ospitante cellule neuronali precursori/staminali nel Sistema Nervoso Centrale (SNC). Questo rappresenta un importante aspetto che può aprire nuove prospettive per la possibile estrazione e collezione di Cellule Staminali Neuronali (CSN) per la medicina rigenerativa e il trapianto autologo. Inoltre, ogni vaso nel SNC è circondato dallo Spazio Perivascolare (spazio di Virchow-Robin) formato da estroflessioni delle meningi e riempito da liquido cerebrospinale. Ciò suggerisce che le cellule precursori/staminali possono essere ampiamente distribuite anche nel parenchima del SNC. Per questo, noi ipotizziamo che le cellule neuronali precursori/staminali residenti nelle meningi possono contribuire alla omeostasi del SNC in situazioni normali e di malattia. La verifica di questa ipotesi può offrire nuove prospettive per la generazione di nuovi approcci farmacologici per il trattamento di malattie neurodegenerative.
Basandosi sugli ottimi potenziali e sulla rilevanza delle nostre precedenti scoperte, durante il mio PhD, ho indirizzato i miei studi nelle seguenti principali domande:
Come si distribuiscono le cellule meningee precursori/staminali nel cervello e nel midollo spinale di adulto?
La nicchia meningea di cellule precursori/staminali è modificata da condizioni patologiche?
Il piano sperimentale di questi due anni di PhD è stato focalizzato nello studio delle cellule meningee precursori/staminali e nella nicchia staminale meningea di organismi modello (ratti e topi). Al fine di analizzare la nicchia meningea a livello cellulare e molecolare, abbiamo usato la combinazione di diverse tecniche come la microscopia confocale ad immunofluorescenza, la real time PCR, il western blot e la coltura di cellule in vitro.
Per descrivere le caratteristiche cellulari e molecolari della nicchia staminale meningea, abbiamo analizzato l’espressione e la distribuzione di markers per le cellule progenitrici/staminali (nestina, dcx, cxcr4), per la proliferazione (ki67), l’auto-rinnovamento (oct4, BrdU) e per la matrice extracellulare (laminina, fibronectina). Abbiamo trovato che cellule precursori/staminali con capacità di auto-rinnovamento sono presenti nelle meningi del cervello adulto. Inoltre, abbiamo dimostrato che la presenza di una popolazione di cellule immature nestina positive è una caratteristica conservata tra le speci, compresa quella umana.
Il complesso equilibrio presente nel CNS adulto include anche la partecipazione di nicchie NSC funzionali. per studiare l'influenza del SNC in condizioni di malattia nella nicchia staminale meningea, abbiamo analizzato le meningi del cervello di topi affetti da una severa immunodeficienza (SCID) e le meningi del midollo spinale di ratti lesionati (SCI).
La nicchia staminale meningea nei topi SCID era profondamente cambiata. Il numero di cellule precursori/staminali era statisticamente diminuita e ciò era associato ad un drammatico aumento delle componenti della matrice cellulare ed extracellulare (fibroblasti, fibronectina e collagene). Oltre a questo, le cellule precorsori/staminali delle meningi di topi SCID hanno dimostrato una velocità proliferativa diminuita in vitro. Questi risultati indicano che la mancanza del sistema immunitario adattativo porta ad una diminuzione delle proprietà staminali della nicchia staminale meningea.
Nei ratti SCI abbiamo invece trovato che la nicchia di cellule precursori/staminali aumenta in spessore, e queste cellule aumentano la loro capacità proliferativa e il loro numero. Inoltre, la lesione induce un globale aumento della staminalità legata al profilo di espressione genica. Questa osservazione suggerisce che la SCI induce nelle meningi del midollo spinale un'amplificazione delle proprietà di staminalità della nicchia.
In conclusione, i principali risultati di questo lavoro sono:
1) Una popolazione di cellule Precursori/staminali è presente nelle meningi adulte ed è conservata tra le specie.
2) La nicchia meningea, compresa la popolazione di cellule nestina positive del cervello di topo adulto risulta perturbata in modelli di immunodeficienza;
3) La nicchia meningea del midollo spinale di ratto adulto è attivata da un trauma di natura contusiva: le cellule precursori/staminali proliferano ed aumentano in numero.
Tutti assieme questi risultati suggeriscono un nuovo ruolo delle meningi come una potenziale nicchia di cellule precorsori/staminali endogene che possono essere modificate in condizione di malattia.
Sarà necessaria un ulteriore valutazioni dei meccanismi molecolari coinvolti in condizioni fisiopatologiche delle cellule precursori/staminali delle meningi. Altri risultati potranno aprire interessanti prospettive nella ricerca di nuovi trattamenti farmacologici e nella medicina rigenerativa applicata alle malattie del SNC.Our group have demonstrated for the first time that a new niche for stem/precursor cells with neural differentiation potential resides in brain meninges (arachnoid and pia mater) of postnatal rats. Meningeal stem/progenitor cells express the neural stem progenitor marker nestin and can be extracted and expanded in vitro as neurospheres. Moreover, they can be induced to differentiate into neurons both in vitro and in vivo (Bifari et al., 2009). Thanks to their superficial location, meninges might represent a new easy accessible tissue hosting neural stem/progenitor cell in the Central Nervous system (CNS). This represents an important aspect that may open new perspective for the possible collection of Neural Stem Cells (NSCs) for regenerative medicine and autologous transplantation. Moreover, every parenchymal vessels inside the CNS are surrounded by a perivascular space (Virchow–Robin space) formed by the extroflexions of meninges filled with cerebrospinal fluid suggesting that meningeal stem/progenitor cells might be widely distributed also in CNS parenchyma. Thus, we hypothesized that meningeal stem/progenitor cells may contribute to CNS homeostasis in health and disease. Verifying this hypothesis could offer new insights for the generation of novel pharmacological approaches to treat neurodegenerative diseases. Based on the great potential and the relevance of our previous finding, during my PhD period, I addressed the following main questions: How is the distribution of the meningeal stem/progenitor cell niche in adult brain and spinal cord? Is the meningeal stem/progenitor cell niche modified by pathological conditions? The experimental plan of these two years of PhD has been focused on the study of the meningeal stem/progenitor cells and the meningeal stem cell niche in healthy and disease animal models (rat and mice). To analyze the meningeal niche at the cellular and molecular levels, we used the combinations of different technical approaches such as immunofluorescence confocal microcopy, real time PCR, western blot and in vitro cell culture. To describe the molecular and cellular features of the meningeal stem/progenitor cells and the organization of the meningeal stem cell niche in adult animals, we analyzed the expression and 4 distribution of markers of stem/progenitor cells (nestin/dcx/cxcr4), proliferation (ki67), self renewal (oct4, BrdU) and extracellular matrix components (laminin, fibronectin, condroitin sulphate, collagen 1a). We found that stem/progenitor cells with self-renewal and proliferative properties are present in adult brain and spinal cord meninges. Moreover, we have shown that the presence of immature nestin/positive cells population is a conserved feature across species including human. The complex dynamic equilibrium present in healthy adult CNS also involves the participation of functional NSC niches. In CNS, various pathogenic events acting by different mechanisms may cause neural cell loss and chronic inflammation. Several agents and mediators sustaining these mechanisms also act on niche homeostasis and it is therefore expected that these conditions may have a deep impact on NSC biology and NSC niche properties. To investigate the influence of CNS disease conditions on the meningeal stem cell niche, we have analyzed meninges of severe combined immunodeficient (SCID) mice and spinal cord injured (SCI) rats. Meningeal stem cell niche in SCID mice was deeply changed. The number of the stem/progenitor cells was statistically significantly decreased associated with a dramatically increase in the cellular and extracellular matrix components related to fibrosis (i.e. fibroblasts, fibronectin and collagene). Furthermore, stem/progenitor cells of meninges have shown a lower proliferation rate in vitro. These data indicate that the lack of the adaptive immune system decreases the stemness properties of the meningeal stem cell niche. In SCI mice model we found that meningeal stem/progenitor cell niche is activated. Following the contusion the meningeal niche increase in thickens, stem/progenitor cells largely increase their proliferation and number. Moreover, we found that SCI induced a global increase in the stemness related gene expression profile. This observation suggests that SCI induces in spinal cord meninges an amplification of the stemness properties of the niche. In conclusion the main results of this work are: I) A stem/precursor cell population, is present in adult meninges and is conserved across species; II) The meningeal niche, including the immature nestin positive cell population, of adult mice brain result perturbed in immunodeficient animal model; 5 III) Meningeal niche is activated by contusive spinal cord injury: meningeal stem/precursor cells proliferate and increase in number. All together our data suggest a novel role for meninges as a potential niche harboring endogenous stem/precursor cells that can be functionally modulated in disease conditions. Depending on specific disease-related stimuli, the meningeal stem cell niche can react both by increasing or decreasing its stem cell properties. This differential response to specific conditions, suggests a potential role and contribution of the meningeal stem/progenitor cells in the physiopathological events occurring in CNS diseases. Further evaluation of the molecular mechanisms involved in the meningeal stem/progenitor cells contribution to the physiopathology of different diseases, will open new prospective for the research on pharmacological treatments and regenerative medicine applied to CNS disease.
Books on the topic "Leptomeninges"
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Abrey, Lauren E., Marc C. Chamberlain, and Herbert H. Engelhard, eds. Leptomeningeal Metastases. New York: Springer-Verlag, 2005. http://dx.doi.org/10.1007/b104814.
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E, Abrey Lauren, Chamberlain Marc C, and Engelhard Herbert H, eds. Leptomeningeal metastases. New York: Springer, 2005.
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Wong, Franklin C. L., ed. Radiopharmaceuticals in the Management of Leptomeningeal Metastasis. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-14291-8.
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Chamberlain, Marc C., Stephanie E. Combs, and Soichiro Shibui. Neoplastic meningitis: metastases to the leptomeninges and cerebrospinal fluid. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199651870.003.0021.
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Carcinomatous meningitis or meningeal carcinomatosis is a term that defines leptomeningeal metastases arising as a result of metastases from systemic solid cancers. Similarly, lymphomatous and leukaemic meningitis result from cerebrospinal fluid dissemination of lymphoma or leukaemia. All three entities are commonly referred to as neoplastic meningitis or leptomeningeal metastases due to involvement of both the cerebrospinal fluid compartment as well as the leptomeninges comprised of the pia and arachnoid. Treatment options are limited for these neurological complications and outcomes are generally poor. New therapeutic strategies are desperately needed as more cancer patients survive longer and are at increased risk for neoplastic meningitis.
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Abrey, Lauren E., Marc Chamberlain, and Herbert Engelhard. Leptomeningeal Metastases. Springer, 2014.
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Wong, Franklin C. L. Intrathecal Radionuclides in the Management of Leptomeningeal Metastasis. Springer International Publishing AG, 2022.
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Leptomeningeal Metastases (Cancer Treatment and Research Book 125). Springer, 2006.
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Fisch, Adam. Arterial Supply. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199845712.003.0251.
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Chapter 19 discusses arterial supply, including the Circle of Willis, leptomeningeal cerebral arteries, deep cerebral arteries, arterial border zones, and arteries of the brainstem, cerebellum, spinal cord, and thalamus.
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Quain, Angela, and Anne M. Comi. Sturge-Weber Syndrome and Related Cerebrovascular Malformation Syndromes. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0112.
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Sturge-Weber syndrome is a rare disorder presenting with a capillary malformation, better known as a port-wine birthmark, on the upper face, glaucoma, and a leptomeningeal angioma. Most children develop seizures and strokes, with variable degrees of neurodevelopmental impairments including hemiparesis, visual field deficits, cognitive deficits, epilepsy, and migraines. In 2013, a somatic activating mutation in GNAQ was identified in the capillary malformations and leptomeningeal angiomas of Sturge-Weber patients. In the diagnosis of Sturge-Weber syndrome, contrast-enhanced imaging is essential to the diagnosis of brain involvement. Functional imaging has demonstrated impaired venous drainage and a role for seizures in exacerbating perfusion deficits. Aggressive seizure management is fundamental to treatment. Some data supports the use of low-dose aspirin to reduce the occurrence of strokelike episodes and seizures.
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Cruz, Andrea T., and Jeffrey R. Starke. Central Nervous System Tuberculosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0154.
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Mycobacterium tuberculosis is a common cause of bacterial meningitis in areas with high HIV prevalence and its diagnosis often is delayed in industrialized nations. Children (particularly infants) and immunocompromised persons are at higher risk of developing TB meningitis. Lymphocytic meningitis, high CSF protein, and (in children) frequently an abnormal chest radiograph should raise clinician index of suspicion for TB meningitis. Neuroimaging may show hydrocephalus, basilar leptomeningeal enhancement, ischemia, and/or tuberculomas. Prompt recognition and initiation of antituberculous antibiotics and corticosteroids can decrease morbidity and mortality.
Book chapters on the topic "Leptomeninges"
1
Gerstner, Elizabeth R., and Tracy T. Batchelor. "Leptomeningeal Metastases." In International Neurology, 543–45. Oxford, UK: Wiley-Blackwell, 2010. http://dx.doi.org/10.1002/9781444317008.ch139.
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Brastianos, Priscilla K., Charilaos H. Brastianos, and April F. Eichler. "Leptomeningeal Metastasis." In Central Nervous System Metastasis, the Biological Basis and Clinical Considerations, 187–200. Dordrecht: Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-94-007-5291-7_10.
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Grimm, Sean, and Marc Chamberlain. "Leptomeningeal Metastases." In Neuro-oncology, 200–212. Oxford, UK: Blackwell Publishing Ltd., 2012. http://dx.doi.org/10.1002/9781118321478.ch19.
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Wagner, Sabine, and Martin Benesch. "Leptomeningeal Dissemination." In Encyclopedia of Cancer, 1–5. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-27841-9_3313-2.
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Rhun, Emilie Le, Sophie Taillibert, and Marc C. Chamberlain. "Leptomeningeal metastases." In International Neurology, 593–95. Chichester, UK: John Wiley & Sons, Ltd, 2016. http://dx.doi.org/10.1002/9781118777329.ch145.
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Mason, Warren P. "Leptomeningeal Metastases." In Cancer Neurology in Clinical Practice, 107–19. Totowa, NJ: Humana Press, 2003. http://dx.doi.org/10.1007/978-1-59259-317-0_10.
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Camoriano, Gerardo D., Anitha Raghunath, and Jade S. Schiffman. "Leptomeningeal Disease." In Ophthalmic Oncology, 395–406. Boston, MA: Springer US, 2010. http://dx.doi.org/10.1007/978-1-4419-0374-7_32.
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Wagner, Sabine, and Martin Benesch. "Leptomeningeal Dissemination." In Encyclopedia of Cancer, 2469–73. Berlin, Heidelberg: Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/978-3-662-46875-3_3313.
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Wagner, Sabine, and Martin Benesch. "Leptomeningeal Dissemination." In Encyclopedia of Cancer, 2001–4. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_3313.
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Špero, Martina. "Leptomeningeal Surprise." In Neuroradiology - Expect the Unexpected, 181–88. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-73482-8_27.
Full textConference papers on the topic "Leptomeninges"
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Mantovani, Gabriel Paulo, Rodrigo Fellipe Rodrigues, and Wyllians Vendramini Borelli. "Primary central nervous system angeitis (APSNC) is a vasculitis." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.697.
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Context: Primary central nervous system angeitis (APSNC) is a vasculitis confined to the central nervous system (CNS). Its incidence rate is 2.4 cases per 1,000,000 person-years. It affects predominantly small and medium sized arteries of the cerebral parenchyma, spinal cord and leptomeninges. The most common manifestations are headache, cognitive impairment, stroke and transient ischemic attack. The fact that it results in multifocal inflammation of the arteries and veins can lead to ischemic or hemorrhagic infarctions in multiple vascular territories, more common in the subcortical white matter. Case report: A woman with a past of epilepsy and headache present to us with acute intraparenchymal hemorrhagic stroke, after extensive investigation, arrived at the presumed diagnosis of APSNC. Conclusion:Tests such as MRI and arteriography have low sensitivity and specificity for APSNC and brain biopsy is still the gold standard method for diagnosis, but in practice it is performed in less than half of the cases in clinical practice, this is due to several factors. Next, it is important to note that the biopsy efficiency is around 53-74% in unselected areas, reaching 80% if the site is selected affected by non-invasive exams. The literature specifies brain biopsy as a procedure with relatively low morbidity and mortality, however, it was not performed in more than a half of cases.
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Caliari, Vitória de Ataide, Herika Negri, Claudio vidal, Bruno lobo, Dhyego lacerda, and Débora de Moura Muniz. "Primary Central Nervous System Lymphoma of the Posterior Fossa in Immunocompetent Patient: A Case Report and Review of Literature." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.025.
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Context: Primary central nervous system lymphomas (PCNSL) are a rare but very aggressive subtype of extranodal non-Hodgkin lymphomas. They represent only 4% of primary central nervous system lesions and are more common in patients with aggressive non-Hodgkin lymphomas, who are HIV positive. Moreover, PCNSL, usually presents as intraparenchymal supratentorial expansive lesions, while secondary CNS lymphomas tend to present as metastases in the leptomeninges. Although they are more common in immunocompromised patients, their incidence has increased with advancing age. Due to its uniqueness in findings, rarity, and severity of the case, we present an immunocompetent elderly patient with a primary lesion of the posterior fossa. Case report: A 85-year-old female was admitted to the emergency room with incoercible vomiting for 48 hours. Initial clinical examination showed dysmetry, and dysbasia. There was no clinical history compatible with immunosuppression. The initial magnetic resonance imaging revealed two non-enhancing contrast lesions in T1 and hyperintense in T2/Flair in the left caudate nucleus, and at the right cerebellar hemisphere near the fourth ventricle and a third parafalcine lesion with homogenous contrast-enhancing on T1 compatible with an incidental meningioma. PET scan, thyroid and breast ultrasonography, and abdominal MRI were done to rule out metastasis, and all results were negative. The histopathological analysis after a stereotactic biopsy performed on the caudate nucleus lesion confirmed the presence of primary central nervous system lymphoma. Conclusions: The pattern of PCNSL is changing due to aging. Knowing this is indispensable for the correct diagnosis and management.
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Soares, Izadora Fonseca Zaiden, João Nicoli Ferreira dos Santos, and Lis Gomes Silva. "Dramatic cognitive improvement with acetylcholinesterase inhibitor in cerebral amyloid angiopathyrelated inflammation." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.578.
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Context: Cerebral amyloid angiopathy (CAA) is characterized by progressive deposition of amyloid-ß fibrils in the walls of small arterioles and capillaries of the leptomeninges and cerebral cortex. A rare subtype of CAA is CAA-related inflammation (CAA-RI), which exhibits marked perivascular or transmural inflammatory infiltration in brain tissue. The major clinical features of CAA-RI are rapidly progressive dementia, behavioral changes, headache, seizures, or stroke-like signs. Conclusive diagnosis requires histopathological confirmation, but validated clinicoradiological criteria for the diagnosis of probable CAA-RI have good sensitivity (82%) and specificity (97%). Treatment with high dose corticosteroids with or without other immunosuppressive therapy is recommended. We report a case of probable CAA-RI that did not respond to corticosteroid therapy but had a surprising improvement with acetylcholinesterase inhibitor. Case report: A 77-year-old illiterate woman presented with a history of subacute onset of seizures and behavioral changes. Her medical history was positive for a hearing loss due to a toxic exposure in childhood, and a cured breast cancer. The neurological examination showed attention impairment, disorientation, and incoherent speech. CSF showed a mildly elevated protein count. Brain MRI met criteria for probable CAA-RI. She had a poor response with high doses of corticosteroids, but after a trial with Donepezil she showed important cognitive and functional improvement. Conclusion: This result attracts attention to the importance of the cholinergic pathway in the etiology and pathological mechanisms of CAA. Randomized Controlled Trials would be required to confirm our hypothesis and to find new therapeutic options for CAA.
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Amjad, M. A., N. Sharma, D. C. Kazmierski, P. O. Ochieng, and Z. Hamid. "Small Cell Lung Carcinoma Presenting with Leptomeningeal Carcinomatosis." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4877.
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Gubeladze, T., H. Hofmann, A. Krvavac, and A. K. Agrawal. "Persistent Headache and Leptomeningeal Enhancing Lesions - Initial Manifestation of Sarcoidosis." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a3290.
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Remsik, Jan, Xinran Tong, Ugur Sener, Min Jun Li, Jessica Wilcox, Danielle Isakov, Camille Derderian, Kiana Chabot, Andrea Schietinger, and Adrienne Boire. "Abstract 1751: Decoding the immune system response to leptomeningeal metastasis." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1751.
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Chi, Yudan. "Abstract 1120: Proinflammatory milieu promotes leptomeningeal metastasis by activation of LCN2." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-1120.
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Smalley, Inna, Brittany Evernden, Vincent Law, Rajappa Kenchappa, John Puskas, Elena Ryzhova, Nam Tran, et al. "Abstract 2108: Detection and molecular profiling of leptomeningeal disease in melanoma." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2108.
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Chi, Yudan. "Abstract 1120: Proinflammatory milieu promotes leptomeningeal metastasis by activation of LCN2." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-1120.
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Hyder, S., N. V. Gadela, E. Wasserman, and N. Perosevic. "Who Turned the Lights On? A Curious Case of Leptomeningeal Enhancement." In American Thoracic Society 2021 International Conference, May 14-19, 2021 - San Diego, CA. American Thoracic Society, 2021. http://dx.doi.org/10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a2343.
Full textReports on the topic "Leptomeninges"
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Marenco-Hillembrand, Lina, Michael A. Bamimore, Julio Rosado-Philippi, Blake Perdikis, David N. Abarbanel, Alfredo Quinones-Hinojosa, Kaisorn L. Chaichana, and Wendy J. Sherman. The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, December 2022. http://dx.doi.org/10.37766/inplasy2022.12.0112.
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Review question / Objective: Among adult patients with leptomeningeal carcinomatosis from solid tumors (population) treated with chemotherapy, targeted therapy, or immunotherapy (intervention and comparator) what are the differences in overall survival (OS) and progression-free survival (PFS) and treatment response based on clinical trial outcomes? Eligibility criteria: Included articles reported 1) human subjects ≥ 18 years 2) diagnosis of leptomeningeal carcinomatosis from solid tumors confirmed by imaging or cerebrospinal fluid (CSF) cytology and clinical or neurological symptoms 3) clinical trials 4) with either PFS or MOS outcomes listed. Book chapters, case reports, review articles, observational studies, ed-itorials, and publications of leptomeningeal cancer from hematological tumors and studies consisting solely of pediatric patients were excluded from the analysis.