Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis:A case report

BACKGROUND Brain metastases(BM)are very rare in gastric adenocarcinoma(GaC),and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness.However,its pathogenesis remains unclear.Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor(MET)amplification.Therefore,treatment with savolitinib,a small molecule inhibitor of c-Met,was selected.CASE SUMMARY A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain.Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy.The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department.Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification.After discussing treatment options with the patient,savolitinib tablets were administered.After a month of treatment,the intracranial lesions shrank considerably.CONCLUSION BM is very rare in advanced GaC,especially in meningeal cancer,that is characterized by rapid disease deterioration.There are very few effective treatment options available;however,technological breakthroughs in genomics have provided a basis for personalized treatment.Furthermore,MET amplification may be a key driver of BM in gastric cancer;however,this conclusion requires further investigation.

Ischemic Stroke Complicating Neuromeningeal and Pulmonary Tuberculosis in Children: About a Case in Senegal

Tuberculosis is a major public health problem, especially in developing countries. Neuro-meningeal involvement is rare but represents one of the most severe forms with high morbidity and mortality. We report the case of an ischemic stroke complicating neuromeningeal and pulmonary tuberculosis in a four-month-old infant at the National Hospital Center of children Albert Royer (Senegal). The case was a four-month-old, male infant with no history. His vaccination was up to date according to Senegal’s expanded vaccination program. There was no notion of tuberculosis contagion. He was seen for a prolonged fever for more than a month and chronic cough. He had moderate malnutrition. Neurological examination revealed coma, meningeal syndrome, generalized tonic convulsions and hypertonia. The pupils were in bilateral miosis. Osteotendinous reflexes were abolished with a bilateral Babinski sign. He also had severe respiratory distress, bilateral pulmonary condensation syndrome. Brain computed tomography was in favor of an ischemic stroke. The test GeneXpert MTB/RIF was positive on cerebrospinal fluid and gastric tubing fluid. The curative treatment was based on a quadruple therapy based on rifampicin, isoniazid, pirazinamide and ethambutol. The evolution was unfavorable with the death of the patient.

Neurocutaneous melanosis with an intracranial cystic-solid meningeal melanoma in an adult:A case report and review of literature

BACKGROUND Neurocutaneous melanosis(NCM)is a rare congenital,nonhereditary neurocutaneous syndrome that mainly occurs in children;adult NCM is very rare.Due to its rarity,the clinical features and treatment strategies for NCM remain unclear.The purpose of this study was to explore the clinical features,diagnosis,treatment and prognosis of NCM in adults.Most intracranial meningeal melanomas are solid masses,and cystic-solid malignant melanomas are very rare.Due to the lack of data,the cause of cystic changes and the effect on prognosis are unknown.CASE SUMMARY A 41-year-old woman was admitted to the hospital with intermittent headache for 1 mo.Magnetic resonance imaging(MRI)showed a 4.7 cm×3.6 cm cystic-solid mass in the left temporal lobe with peritumoral edema.The entire mass was removed,and postoperative pathology indicated malignant melanoma.CONCLUSION MRI is the first-choice imaging approach for diagnosing central nervous system diseases in NCM patients,although cerebrospinal fluid may also be used.At present,there is no optimal treatment plan;gross total resection combined with BRAF inhibitors and MEK inhibitors might be the most beneficial treatment.

Leptomeningeal carcinomatosis as the initial manifestation of gastric adenocarcinoma:A case report

Leptomeningeal involvement is usually reported as a secondary event in advanced gastric carcinoma.Leptomeningeal carcinomatosis(LMC),as the initial manifestation of asymptomatic gastric cancer,is exceedingly rare with only a few cases reported in recent years.The presenting neurologic symptoms include headache,vomiting and seizures and are usually clinically atypical.The diagnosis of LMC is made via identification of malignant cells that originate from epithelial cells in the cerebrospinal fluid by cytological examination and provides cues to track the primary tumor.Endoscopic examinations are crucial to confirm the presence of gastric cancer,and imaging studies,especially gadolinium-enhanced magnetic resonance imaging of the brain,are sometimes helpful in diagnosis.Thus far,there is no standard therapy for LMC,and despite all measures,the prognosis of the condition is extremely poor.Here,we report on the clinical features and diagnostic procedures for a patient with occult gastric cancer with Bormann typeⅠmacroscopic appearance and poor differentiation in pathology,who presented with LMC-induced neurological symptoms as the initial clinical manifestation.Additionally,we review the similar cases reported over the past years,making comparison among cases in order to provide more information for the future diagnosis.

Diabetes insipidus with impaired vision caused by germinoma and perioptic meningeal seeding:A case report

BACKGROUND Germinoma is a type of germ cell tumor that most frequently arises in the midline axis of the brain.Impaired vision is a clinical manifestation of germinnoma.Although rare,intracranial germinoma seeding to the perioptic arachnoid space is one cause of visual acuity decrease.CASE SUMMARY An 11yearold girl who presented with polyuria and polydipsia and subsequently developed diminution of vision.Imaging showed bilateral heterogeneous enhancement of the optic nerve sheaths and atrophy of the optic nerve,and transsphenoidal biopsy revealed a germinoma.The patient experienced poor visual recovery following chemotherapy and radiotherapy.Germinomas are rare and they are mostly identified in children and adolescents.The manifestations include diabetes insipidus,pituitary dysfunction,visual complaints,etc.The mechanisms that lead to visual loss include intracranial hypertension,compression of optic chiasma,and tumor invasion.A literature review was performed to summarize the cases with a tumor infiltrating the optic nerve.Most of the reported patients were adolescents and presented with anterior pituitary hormone deficiency.Enhancement of optic nerve sheaths and optic disc pallor could be identified in most of the cases.The purpose of this report is to provide awareness that in cases where a germinoma is associated with visual loss,though rare,perioptic meningeal seeding should be taken into consideration.CONCLUSION The case report suggests that children with diabetes insipidus need a complete differential diagnosis.

Meningeal melanocytoma in the cerebellopontine angle:A rare case report and review of the literature

Primary meningeal melanocytoma(MM)in the cerebellopontine angle(CPA)region is an extremely rare neoplasm that originates from the melanocytes in the leptomeninges.These lesions are usually misdiagnosed as they mimic other common CPA lesions through their nonspecific presenting symptoms,signs,and radiological characteristics.Here,we report a 47-year-old Chinese female patient who presented with a 1-month history of the right-sided tongue numbness and 1-week history of the right-sided face numbness that had been worsening for 2 days.The tumor,in the right CPA region,showed a slight isointensity on T1-weighted image and mixed signal intensity on T2-weighted image.The clinical presentation,surgical treatment,and pathologic characteristics were determined.The tumor was microsurgically resected and gross-total resection was achieved.The tumor revealed a solid,capsulated,brown-black lesion.Immunohistochemistry showed that the tumor cells were positive for human melanoma black-45(HMB-45),melanoma antigen(MelanA),S100,SOX10,and BRAF,confirming the final diagnosis of meningeal melanocytoma.Ultimately,no signs of radiological local recurrence were observed during the two-year follow-up.Collectively,meningeal melanocytoma is difficult to distinguish from common tumors in the CPA region before operation due to the lack of specificity in imaging and symptoms.Complete surgical resection is the best therapeutic option for this tumor.Although the tumor is commonly considered as a benign lesion,recurrence and metastasis are common,and pathogenesis remains unclear.

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and HIV Infection at a Local Hospital in Lima, Peru

Objective: To determine the associated factors for in-hospital mortality in patients with meningeal cryptococcosis and HIV infection at a local hospital in Lima, Perú. Materials and methods: We carried out a case-control study by reviewing the medical histories available at a local hospital in Lima, Peru. We determined the factors associated with mortality using a logistic regression model. Results: The information of 90 patients was analyzed, 37 dead and 53 alive. In the multivariate analysis we found two variables associated with mortality: Glasgow at admission (OR = 4.55 (1.61 – 12.20), p = 0.01) and serum antigen titer greater than 1024 (OR = 20.48 (1.6 – 261.04, p = 0.02). The protective factor found was a longer hospitalization stay (OR = 0.80 (0.69 – 0.93, p = 0.005).Conclusions: A low Glasgow score and serum antigen titer greater than 1024 are associated factors with mortality, whereas hospitalization length is a protective factor.

Rupture of a True Aneurysm of the Posterior Meningeal Artery at Its Anomalous Origin from the Internal Carotid Artery: Case Report

The posterior meningeal artery (PMA) usually originates from the third segment of the vertebral artery. Many variations in its origin and course have been observed;however, as far as we know, the association of true aneurysm of the PMA and its anomalous origin from the internal carotid artery has not been reported previously. We reported the case of a 59-year-old woman who suddenly presented a loss of consciousness without head trauma, computed tomography (CT) revelated intracerebellous hematoma associated with a subarachnoid hemorrhage of the posterior cerebral fossa. Cerebral angiography demonstrated a true aneurysm of the PMA which originated from the internal carotid artery.

Traumatic Middle Meningeal Artery Pseudoaneurysms Presenting with Intractable Epistaxis: A Rare Case Report and Review of Literature

Middle meningeal artery (MMA) pseudoaneurysms are very rare and are most often traumatic. They may present as an epidural or intraparenchymal hematoma. This study reports a rare case in which a patient suffered from intractable epistaxis because of a pseudoaneurysm in middle meningeal artery and skull base fracture after craniocerebra trauma. Pseudoaneurysm and the feeding artery were embolized by using Onyx-18 liquid embolic system. Complete cessation of bleeding was achieved in this case immediately after the endovascular therapies. In this study, clinical manifestation, diagnostic imaging and endovascular treatment are described. Formation mechanisms and the treatment of traumatic pseudoaneurysm of middle meningeal artery are discussed.

Philadelphie chromosome—Positive <i>de novo</i>acute myeloid leukemia. Isolated meningeal relapse in a patient treated with imatinib mesylate

Acute myeloid leukemia philadelphie positive (Ph+ AML) is a rare aggressive acute leukemia with poor prognosis. We report a patient with ph positive AML (FAB5), the transcript bcr/abl was not performed at diagnosis. She achieved complete remission after conventional induction chemotherapy. The consolidation therapy was based on Imatinib only due to infectious complications. She was in complete hematologic and cytogenetic remission for 19 months, and after she exhibited an isolated meningeal relapse. A second remission was achieved with intrathecal chemotherapy and cranial irradiation. Imatinib was switched to second generation Tyrosine kinase Inhibitor which had better diffusion into cerebrospinal fluid. She is in complete hematologic, cytogenetic and meningeal remission after 14 months of treatment. Imatinib monotherapy affords insufficient protection from CNS relapse. Second generation Tyrosine kinase Inhibitor seems to have better efficiency. Ph+ AML with monoblastic differentiation should be considered, like Ph+ ALL, at high risk of meningeal leukemia and should receive central nervous system prophylaxis.

Characteristic analysis of diffuse leptomeningeal glioneuronal tumor misdiagnosed as cryptococcal meningitis in adolescent female

Diffuse leptomeningeal glioneuronal tumor(DLGNT)in adolescent female is rare and easy to be misdiagnosed due to its nonspecificity.This article described the characteristics of an adolescent female DLGNT patient with no history of tumor whose first symptoms are headache and vision loss,and analyzed the causes why DLGNT is easy to be misdiagnosed as cryptococcal meningitis.Treatment remedies:the adolescent female presented with progressive exacerbations of headache,vomiting and vision loss after general treatment.Dynamic monitoring of routine biochemical changes in cerebrospinal fluid(CSF)found abnormal high CSF pressure and protein,repeated examination of antibodies and acid-fast bacilli were negative,and high-throughput pathogen gene examination excluded viral meningitis,tuberculous meningitis and other diseases.To save the optic nerve,the Ommaya capsule was implanted to reduce the intracranial pressure.After diagnostic antifungal treatment,the patient’s condition did not improve.To identify the etiology,extensive meningeal enhancement was eventually detected by enhanced magnetic resonance imaging(MRI),and highly atypical tumor cells were identified by repeated examination of fresh CSF cytology.Post treatment evaluating:for DLGNT,consult oncology.Meningeal biopsy and PET-CT(positron emission tomographycomputed tomography)examination were recommended,and intrathecal chemotherapy and whole-brain radiotherapy were performed according to the examination results.But the patient’s family refused to have a meningeal biopsy and asked to be released from the hospital.Conclusions:the adolescent female without a history of tumor can not rule out the disease,and cryptococcal meningitis also has meningeal enhancement.The gold standard for the diagnosis of DLGNT is to find cancer cells.There is no effective cure for DLGNT,the timely placement of Ommaya sac can significantly improve the quality of the patient’s life,and the active adoption of targeted therapy is expected to extend the patient’s survival.

Meningeal Hemangiopericytoma: A Rare Intracranial Tumor—About a Case

Introduction: Hemangiopericytoma is a very rare vascular tumor, difficult to diagnose, often confused with a meningioma. Imaging is not very specific and the diagnostic certainty remains histological. Observation: We report a case of meningeal hemangiopericytoma in a 48-year-old patient with a history of active smoking and whose sister died of glioblastoma. He was brought to the emergency room for a fall, confusion, and tonic-clonic seizures. The diagnosis was suspected on imaging (CT and MRI, in front of a syndrome of right temporal intraventricular mass measured at 37 mm in diameter, centered on the choroid plexus, with perilesional vasogenic edema and posterior white commissure. There was homogeneous enhancement of the lesion after gadolinium injection. The diagnosis was confirmed by immunohistochemical study, which showed diffuse expression of STAT6 and partial labeling for CD34, without significant expression of SSTR2. Expression of neurofilament protein was also found in the brain parenchyma. Conclusion: Hemangiopericytoma is a rare tumor, characterized by its malignant potential, its high rate of recurrence and distant metastasis. The management is based on a total microsurgical resection followed by radiotherapy.

A Case Report of Rare Acute Ischemic Stroke Due to Meningeal Irritation

Stroke is a rapidly developing symptom or sign of loss of cerebral function secondary to interruption of the blood supply due to a thrombus or hemorrhage. These diseased vessels are usually affected by well-recognized risk factors, but in some cases other rare conditions may be related to stroke development. Herein, we introduce one of these rare stroke conditions in a 37-year-old previously healthy male who presented to the emergency department with misleading symptoms and signs of reduced level of consciousness, isolated medical 3rd nerve palsy and possible drug overdose. A thorough neurological examination and investigation demonstrated a case of acute ischemic stroke as a consequence of meningeal irritation with an underlying inflammatory response. The patient was treated simultaneously for both conditions and responded dramatically with full recovery upon discharge. Thus, consideration of acute stroke in patients with no previous known risk factors is highly recommended especially with unusual neurological findings.

Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases

The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.

Advancements in diagnosis and treatment of meningeal carcinomatosis in solid cancer

Meningeal carcinomatosis (MC) is a disease that malignant tumor cells cultivate in the cerebrospinal fluid or meninges. With the development of therapy methods and new techniques, survival time of patients with tumor is prolonged, and the incidence of MC is increasing. Diagnosis is based on the evaluation of clinical manifestations, cerebrospinal fluid and neuroimaging findings. Furthermore, in recent years, the diagnostic value of the tumor-derived cell-free DNA in the cerebrospinal fluid (CSF) is promising and may improve the diagnostic yield of CSF analysis. Traditional treatments of MC include surgery, radiation therapy, systemic therapy, and intrathecal therapy. Recently, molecular targeted therapy and immunotherapy have received more and more attention. The authors review the epidemiology, pathogenesis, clinical manifestation, diagnosis and treatment of MC in solid cancer, and discuss the diagnosis and treatment options currently available as well as those under investigation.

Human herpesvirus 7 meningitis in an adolescent with normal immune function:A case report

BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.

Meningoencephalitis due to Listeria monocytogenes in a Young Immunocompetent Patient: Case Report with Literature Review

Meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompetent individuals. We present the case of a young adult patient without immunocompromise, who developed meningoencephalitis due to L. monocytogenes;This case is exceptional, since it occurred in an individual outside the classic age group, in addition to not having risk factors, which is why it should be considered an atypical causal agent.

Early Nursing Intervention in Children with Viral Meningitis

Aim: To explore the effect of a WeChat peer education program in children with severe viral meningitis combined with respiratory failure. Design: Retrospective cohort study. Methods: Patients who had severe viral meningitis combined with respiratory failure, were admitted to the hospital from March 2017 to June 2018, and who received the WeChat-based nursing intervention were included. Patients who received routine nursing were used as controls. The family’s emotional state, self-care ability, and rehabilitation were analyzed. Results: There were 37 patients in the WeChat group (19 boys (51.3%) and 18 girls (48.7%);mean of 5.1 ± 2.4 years of age) and 37 controls (20 boys (54.1%) and 17 girls (45.9%);mean of 5.9 ± 2.4 years of age) (all P > 0.05). After nursing, improvements in the self-assessed anxiety score and self-assessed depression score were better in the WeChat group (anxiety: -29.2% vs. -20.3%, P = 0.015;depression: -25.2% vs. -15.4%, P = 0.009). After nursing, the improvements in the condition management ability scale and condition management difficulty scale scores were better in the WeChat group (ability: +80.5% vs. +44.4%. P = 0.001;difficulty: +58.4% vs. +37.8%, P = 0.003). After nursing, the improvement in the Fugl-Meyer score was better in the WeChat group (+138.0% vs. +53.0%, P Conclusion: Early nursing intervention combined with WeChat peer education can improve the emotional state of children with severe viral meningitis combined with respiratory failure and their caregivers. Impact: Viral meningitis is associated with a good prognosis, but central nervous system complications can be observed. Early intervention is the key to a good prognosis. Internet-based nursing and coaching can improve self-efficacy and care ability in patients with various conditions, as well as improve the emotional state of the children and their caregivers. The research might have an impact on any children’s hospital that deals with viral meningitis.