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Cancer Treatment Reviews Apr 1999Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. This disorder is being diagnosed with increasing frequency as patients live longer and... (Review)
Review
Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. This disorder is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. The most common cancers to involve the leptomeninges are breast cancer, lung cancer, and melanomas. Tumour cells reach the leptominges by hematogenous spread or by direct extension from pre-existing lesions and are then disseminated throughout the neuroaxis by the flow of the cerebrospinal fluid. Patients present with signs and symptoms from injury to nerves that traverse the subarachnoid space, direct tumour invasion into the brain or spinal cord, alterations in blood supply to the nervous system, obstruction of normal cerebrospinal fluid (CSF) flow pathways, or general interference with brain function. The diagnosis is most commonly made by lumbar puncture although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis. Radiologic studies may reveal subarachnoid masses, diffuse contrast enhancement of the meninges, or hydrocephalus without a mass lesion. Without treatment, the median survival of patients with this disorder is 4-6 weeks and death occurs from progressive neurologic dysfunction. Early diagnosis and therapy is critical to preserving neurologic function. Radiation therapy to symptomatic sites and disease visible on neuroimaging studies and intrathecal chemotherapy increases the median survival to 3-6 months. The major favorable prognostic factors include excellent performance status, absence of serious fixed neurologic deficits, normal CSF flow scans, and absent or responsive systemic tumour. Aggressive therapy for this disorder is often accompanied by a necrotizing leukoencephalopathy which becomes symptomatic months after treatment with radiation and intrathecal methotrexate. As currently available therapies are toxic and provide limited benefits, novel approaches are being studied. Further information on the mechanisms of neurotoxicity from antineoplastic agents is critical to providing better outcomes for this increasing common complication of cancer.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Carcinoma; Combined Modality Therapy; Diagnosis, Differential; Diagnostic Imaging; Humans; Meningeal Neoplasms; Meningitis
PubMed: 10395835
DOI: 10.1053/ctrv.1999.0119 -
Nature Communications Jun 2020Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been...
Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.
Topics: Animals; Brain Injuries; Erythrocytes; Lymph Nodes; Lymphangiogenesis; Lymphatic System; Lymphatic Vessels; Male; Meninges; Meningitis; Mice; Mice, Inbred C57BL; Models, Animal; Neck; Subarachnoid Hemorrhage; Vascular Endothelial Growth Factor Receptor-3
PubMed: 32572022
DOI: 10.1038/s41467-020-16851-z -
Current Opinion in Neurobiology Apr 2023The spatial and temporal development of the brain, overlying meninges (fibroblasts, vasculature and immune cells) and calvarium are highly coordinated. In particular,... (Review)
Review
The spatial and temporal development of the brain, overlying meninges (fibroblasts, vasculature and immune cells) and calvarium are highly coordinated. In particular, the timing of meningeal fibroblasts into molecularly distinct pia, arachnoid and dura subtypes coincides with key developmental events in the brain and calvarium. Further, the meninges are positioned to influence development of adjacent structures and do so via depositing basement membrane and producing molecular cues to regulate brain and calvarial development. Here, we review the current knowledge of how meninges development aligns with events in the brain and calvarium and meningeal fibroblast "crosstalk" with these structures. We summarize outstanding questions and how the use of non-mammalian models to study the meninges will substantially advance the field of meninges biology.
Topics: Meninges; Dura Mater; Arachnoid; Brain
PubMed: 36773497
DOI: 10.1016/j.conb.2023.102676 -
Cell Reports Nov 2022The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal...
The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice. Surprisingly, a large subset of afferents was activated during non-noxious conditions such as locomotion. We estimated locomotion-related meningeal deformations and found afferents with distinct dynamics and tuning to various levels of meningeal expansion, compression, shearing, and Z-axis motion. Further, these mechanosensitive afferents were often tuned to distinct directions of meningeal expansion or compression. Thus, in addition to their role in headache-related pain, meningeal sensory neurons track the dynamic mechanical state of the meninges under natural conditions.
Topics: Animals; Mice; Meninges; Neurons, Afferent; Headache; Locomotion
PubMed: 36384109
DOI: 10.1016/j.celrep.2022.111648 -
Chinese Clinical Oncology Jun 2015Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated... (Review)
Review
Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.
Topics: Animals; Combined Modality Therapy; Humans; Meningeal Carcinomatosis; Meningitis; Neuroimaging; Patient Selection; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 26112812
DOI: 10.3978/j.issn.2304-3865.2015.05.02 -
Cancer Control : Journal of the Moffitt... Jan 2017Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia. (Review)
Review
BACKGROUND
Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia.
METHODS
The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of leukemic and lymphomatous meningitis.
RESULTS
Treatment for secondary leukemic and lymphomatous meningitis remains unsatisfactory, and efforts should be made to prevent and treat subclinical disease. Intrathecal and systemic chemotherapy remain the main therapeutic approaches for this disease. Outcomes have improved in patients with primary CNS lymphoma and meningeal involvement.
CONCLUSIONS
Appropriate selection of patients at high risk for leukemic and lymphomatous meningitis is important so that preventive strategies can decrease the incidence of this complication of leukemia and lymphoma. Use of chemotherapy agents that cross the blood-brain barrier and the adoption of high-dose chemotherapy with autologous hematopoietic stem cell transplantation have increased the proportion of patients whose primary disease is cured.
Topics: Disease Management; Humans; Leukemia; Lymphoma; Meningitis; Prognosis
PubMed: 28178710
DOI: 10.1177/107327481702400105 -
Neuroscience Dec 2016Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic... (Review)
Review
Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic physiology and underlying mechanisms contributing to the development of migraine are still poorly understood and development of new therapeutic targets is long overdue. Until recently, the major contributing pathophysiological event thought to initiate migraine was cerebral and meningeal arterial vasodilation. However, the role of vasodilation in migraine is unclear and recent findings challenge its necessity. While vasodilation itself may not contribute to migraine, it remains possible that vessels play a role in migraine pathophysiology in the absence of vasodilation. Blood vessels consist of a variety of cell types that both release and respond to numerous mediators including growth factors, cytokines, adenosine triphosphate (ATP), and nitric oxide (NO). Many of these mediators have actions on neurons that can contribute to migraine. Conversely, neurons release factors such as norepinephrine and calcitonin gene-related peptide (CGRP) that act on cells native to blood vessels. Both normal and pathological events occurring within and between vascular cells could thus mediate bi-directional communication between vessels and the nervous system, without the need for changes in vascular tone. This review will discuss the potential contribution of the vasculature, specifically endothelial cells, to current neuronal mechanisms hypothesized to play a role in migraine. Hypothalamic activity, cortical spreading depression (CSD), and dural afferent input from the cranial meninges will be reviewed with a focus on how these mechanisms can influence or be impacted by blood vessels. Together, the data discussed will provide a framework by which vessels can be viewed as important potential contributors to migraine pathophysiology, even in light of the current uncertainty over the role of vasodilation in this disorder.
Topics: Animals; Brain; Cortical Spreading Depression; Humans; Meninges; Migraine Disorders; Vasodilation
PubMed: 27312704
DOI: 10.1016/j.neuroscience.2016.06.012 -
Neurology India 2022Hypertrophic pachymeningitis (HPM) is a unique disorder characterized by thickening and fibrosis of the dura mater. Clinically it presents with headache, cranial nerve... (Observational Study)
Observational Study
BACKGROUND
Hypertrophic pachymeningitis (HPM) is a unique disorder characterized by thickening and fibrosis of the dura mater. Clinically it presents with headache, cranial nerve palsies, and other focal neurological deficits. Two forms exist, one is primary, where all other causes have been excluded and the other is secondary where an identifiable cause exists. It is important to recognize these secondary causes as treatment depends on the etiology.
OBJECTIVE
To elucidate the various characteristics of HPM. To delineate clinical-radiological features that help differentiate secondary from primary causes and to understand treatment response and disease outcomes of HPM.
METHODS
This retrospective observational study included 33 patients who presented with radiological diagnosis of HPM from January 2014 to July 2019. Spontaneous intracranial hypotension patients were excluded. All patients were extensively evaluated for secondary causes and treatment outcomes were analyzed on follow-up.
RESULTS AND CONCLUSIONS
Secondary causes of HPM were present in 48% cases. The clue for primary causes is an associated Tolosa-Hunt syndrome. Secondary causes in our series are immunological, infection, and malignancy. Clues to differentiate primary from these secondary causes are clinical like myelopathy, seizures, poor response to immunosuppression; radiological like hypertrophic cranial nerves, infarcts, bony erosion, and leptomeningeal involvement. There are case reports in literature but large Indian studies are lacking. This manuscript presents a large cohort of cases with HPM, which helps differentiate primary from secondary causes, as management and prognosis depend on etiology. An algorithm depicting the approach to the management of HPM has been presented.
Topics: Humans; Magnetic Resonance Imaging; Meningitis; Cranial Nerve Diseases; Headache; Treatment Outcome; Hypertrophy; Dura Mater
PubMed: 36537427
DOI: 10.4103/0028-3886.364052 -
Cellular and Molecular Life Sciences :... Oct 2023Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune... (Review)
Review
Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune trafficking. Although these vessels were overlooked for centuries, they have now been characterized in humans, non-human primates, and rodents. Recent studies in mice have explored the stereotyped growth and expansion of MLVs in dura mater, the various transcriptional, signaling, and environmental factors regulating their development and long-term maintenance, and the pathological changes these vessels undergo in injury, disease, or with aging. Key insights gained from these studies have also been leveraged to develop therapeutic approaches that help augment or restore MLV functions to improve brain health and cognition. Here, we review fundamental processes that control the development of peripheral lymphatic networks and how these might apply to the growth and expansion of MLVs in their unique meningeal environment. We also emphasize key findings in injury and disease models that may reveal additional insights into the plasticity of these vessels throughout the lifespan. Finally, we highlight unanswered questions and future areas of study that can further reveal the exciting therapeutic potential of meningeal lymphatics.
Topics: Mice; Animals; Lymphatic Vessels; Meninges; Central Nervous System; Lymphatic System; Models, Animal
PubMed: 37872442
DOI: 10.1007/s00018-023-04984-5 -
Annals of Medicine Dec 2023Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges... (Review)
Review
Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges and brain parenchyma, as well as the spinal cord and meninges; Disability and mortality rates are high. In recent years, due to the increase of drug-resistant tuberculosis patients, population mobility and the prevalence of acquired immune deficiency syndrome, the incidence rate of tuberculosis has increased significantly, and tuberculous meningitis has also increased. At present, tuberculosis is still a worldwide infectious disease that seriously threatens human health, especially in underdeveloped and developing countries. China is the largest developing country in the world with a large population. The situation of tuberculosis prevention and control is grim. Its disability rate is the highest in tuberculosis infection. In addition to the common non-specific manifestations, tuberculous meningoencephalitis may also have rare manifestations of stroke, hearing loss and visual loss. Understanding and timely improvement of corresponding examinations and targeted treatment will help improve the prognosis of patients.
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Brain; Meningoencephalitis; China
PubMed: 36598144
DOI: 10.1080/07853890.2022.2164348