Analysis of clinical characteristics of leptomeningeal metastasis with band-like high signal in the brainstem

Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.

Is it a normal phenomenon for pediatric patients to have brain leptomeningeal contrast enhancement on 3-tesla magnetic resonance imaging?

Determining whether sevoflurane sedation in children leads to“pseudo”prominent leptomeningeal contrast enhancement(pLMCE)on 3 Tesla magnetic resonance imaging will help reduce overdiagnosis by radiologists and clarify the pathophysiological changes of pLMCE.

Does sevoflurane sedation in pediatric patients lead to“pseudo”leptomeningeal enhancement in the brain on 3 Tesla magnetic resonance imaging?

BACKGROUND Prominent leptomeningeal contrast enhancement(LMCE)in the brain is observed in some pediatric patients during sedation for imaging.However,based on clinical history and cerebrospinal fluid analysis,the patients are not acutely ill and do not exhibit meningeal signs.Our study determined whether sevoflurane inhalation in pediatric patients led to this pattern of‘pseudo’LMCE(pLMCE)on 3 Tesla magnetic resonance imaging(MRI).AIM To highlight the significance of pLMCE in pediatric patients undergoing enhanced brain MRI under sedation to avoid misinterpretation in reports.METHODS A retrospective cross-sectional evaluation of pediatric patients between 0-8 years of age was conducted.The patients underwent enhanced brain MRI under inhaled sevoflurane.The LMCE grade was determined by two radiologists,and interobserver variability of the grade was calculated using Cohen’s kappa.The LMCE grade was correlated with duration of sedation,age and weight using the Spearman rho rank correlation.RESULTS A total of 63 patients were included.Fourteen(22.2%)cases showed mild LMCE,48(76.1%)cases showed moderate LMCE,and 1 case(1.6%)showed severe LMCE.We found substantial agreement between the two radiologists in detection of pLMCE on post-contrast T1 imaging(kappa value=0.61;P<0.001).Additionally,we found statistically significant inverse and moderate correlations between patient weight and age.There was no correlation between duration of sedation and pLMCE.CONCLUSION pLMCE is relatively common on post-contrast spin echo T1-weighted MRI of pediatric patients sedated by sevoflurane due to their fragile and immature vasculature.It should not be misinterpreted for meningeal pathology.Knowing pertinent clinical history of the child is an essential prerequisite to avoid radiological overcalling and the subsequent burden of additional investigations.

Targeted therapy for leptomeningeal metastases in non-small cell lung cancer-Changing treatment paradigms

Leptomeningeal metastasis is an uncommon but serious complication in patients with advanced cancers. Leptomeningeal metastasis is diagnosed in approximately 5% of the patients, most commonly among patients with cancers of breast and lung, melanoma, and gastrointestinal malignancies. Treatment goal is to improve survival and quality of the patients. Use of targeted therapies and immunotherapy has led to improved survival of patients with non-small cell lung cancer （NSCLC）. In this article, we review emerging data on use of mutation-specific agents and immunotherapy in the treatment of leptomeningeal metastasis among patients with NSCLC.

Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination:A retrospective analysis

BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer:A case report

BACKGROUND Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal(LM)metastasis than other types of lung cancers and have a poor prognosis.Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis.CASE SUMMARY A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital.She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance.epidermal growth factor receptor(EGFR)mutation was detected by genomic examination,so she was first treated with gefitinib for 10 months before acquiring resistance.Cell-free cerebrospinal fluid(CSF)circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation,while biopsy and cytology from the patient’s CSF and the first enhanced cranial magnetic resonance imaging(MRI)showed no positive findings.A month later,the enhanced MRI showed linear leptomeningeal enhancement,and the cytology and biochemical examination in CSF remained negative.Therefore,osimertinib(80 mg/d)was initiated as a second-line treatment,resulting in a good response within a month.CONCLUSION This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy.Moreover,the routine screening of chest CT with the novel coronavirus may provide unexpected benefits。

A Novel Combined Approach for Metastatic Breast Cancer with Dural and Leptomeningeal Disease with an Impressive Clinical Outcome: A Case Study

Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with leptomeningeal disease. Patient underwent multi targeted epigenetic therapies applied in a protocol called MTET. She continued to respond to the interval treatment, which consisted only of the nutraceutical agents. Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.

Leptomeningeal metastases originated from esophagogastric junction/gastric cancer:A brief report of two cases

Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present two patients; one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer, who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment. Furthermore, a thorough and short review of the literature is carried out.

Unusual magnetic resonance imaging findings of brain and leptomeningeal metastasis in lung adenocarcinoma:A case report

BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor mutations.However,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.CASE SUMMARY We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance imaging.Surgical and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local leptomeninges.CONCLUSION This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with LM.Radiologists should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.

Leptomeningeal Carcinomatosis Presenting Early in Non-Small Cell Lung Cancer

Purpose: We present the case of a patient presenting with altered mental status on post-operative day seven after a diagnostic lung biopsy. The diagnosis of carcinomatous letomeningeal metastasis was confirmed. Methods: We discuss meningeal carcinomatosis in lung cancer, and describe challenges to diagnosis, therapy, and prognosis. Results: A review of the literature describing the clinical and oncologic principles of letomeningeal carcinomatosis in lung cancer is performed. Discussion: Leptomeningeal carcinomatosis (LC) occurs in approximately 5% of patients with non-small cell lung cancer and incurs a bleak prognosis. Presenting neurologic symptoms can be varied and diagnosis is confirmed via lumbar puncture and cerebrospinal fluid cytology. Few data exist regarding optimal treatment, although intrathecal chemotherapy has been shown to provide a modest improvement in median survival.

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.

Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation

Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully elucidated.Moreover,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited.Here,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation.He was urgently hospitalized due to leptomeningeal metastasis.We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status.The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.

Leptomeningeal carcinomatosis:an unusual cause of headache in bronchial carcinoma

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Leptomeningeal metastases from non-small cell lung cancer:state of the art and recent advances

Patients with leptomeningeal metastases(LM)from non-small cell lung cancer(NSCLC)have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy.In the past,some randomized clinical trials have been conducted with heterogeneous inclusion criteria,diagnostic parameters,response evaluation and primary endpoints.Efforts to develop a standardized magnetic resonance imaging(MRI)assessment and liquid biopsy techniques to monitor disease evolution in plasma or cerebrospinal fluid(CSF)are underway.This review aims to cover the main clinical and diagnostic challenges of LM from NSCLC,in particular the role of MRI,CSF cytology and liquid biopsy for the diagnosis and monitoring of the disease,as well as the most recent clinical trials on targeted therapies.Targeted therapy,such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase rearranged inhibitors,represent a feasible treatment with encouraging results in terms of disease control and survival.For ineligible patients,immune checkpoint inhibitors could represent a therapeutic option with acceptable tolerance,although clinical trials focused on LM from NSCLC are lacking and represent a research focus for the future.

Leptomeningeal metastases in prostate cancer:A review of the current literature

Leptomeningeal metastasis/leptomeningeal carcinomatosis(LMC;terms used interchangeably)is an inflammatory complication of primary tumors that involves the spread of the disease to the meninges(specifically the arachnoid and pia maters)and spinal cord.In the United States,approximately 110,000 new cases are diagnosed each year,and the prognosis is usually poor.Complications of LMC include cognitive impairment,cranial nerve dysfunction,ischemic stroke,and mortality.The survival times of untreated and treated LMC are approximately 4–6 weeks and 2–4 months,respectively.Leptomeningeal carcinomatoses are usually metastatic cancers that spread to the central nervous system.Although lung and breast cancers have a clearly defined relationship with LMC,it remains unclear whether prostate cancer(PC)is also directly associated with LMC.To determine whether such association exists,we conducted a PubMed review of the literature on patients with PC with coexisting LMCs.Our search yielded 23 case reports of patients with preexisting PC who developed LMC.In addition,2 retrospective cohort studies were examined.Various findings were identified in the revised cases and studies.The first 3 findings were related to the progression of the disease:patients presenting with neurological disease symptoms were in remission from PC for 7 years on average,LMCs tended to occur after other cancer diagnoses,and the disease had already rapidly progressed by the time the symptoms were present.Regarding diagnosis,the major finding was that most LMCs were detected by magnetic resonance imaging(which does not detect early dissemination),and it was suggested that single-photon emission computed tomography or positron emission tomography imaging could be used for earlier detection.Finally,in terms of treatment,the main finding was that treatment was palliative rather than curative and that prognosis remained poor despite treatment.On the basis of these results,we recommend for individuals with risk factors,such as high-grade PC and hormonal PC,to be evaluated on a case-by-case basis for increased surveillance of LMC development.

The role of Epstein-Barr virus in multiple sclerosis:from molecular pathophysiology to in vivo imaging

Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus(EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.

Acute development of collateral circulation and therapeutic prospects in ischemic stroke

In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without hemorrhagic transformation.We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome,and it disappears promptly once the effective recanalization is achieved.Contrary to the belief that collateral vessels develop over time in chronic stenotic condition,there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress,which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries.We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1,which is a known shear-stress mechanosensing protein.

Intracranial Intermediate-Grade Melanocytic Neoplasm: Case Report Associated with Nevus of Ota

Melanocytic lesions of the CNS are rare tumours originating from melanocytes that are present in the leptomeninges. They consist of a spectrum of pigmented tumours ranging from melanocytoma to melanoma. A small group of these tumours have histopathological features between those of a benign melanocytoma and a malignant melanoma;these present as intermediate grade melanocytic neoplasms. Naevus of Ota is a blue hyperpigmented dermal lesion characterized by increased number of melanocytes in the distribution of ophthalmic and maxillary divisions of the trigeminal nerve. The association of an intracranial intermediate-grade melanocytic neoplasm with a nevus of Ota is extremely rare, with only 2 cases reported in the literature to date. As a result, their behavior and progression are still poorly understood. We present the first case of a familial naevus of Ota associated with intermediate-grade melanocytic neoplasm.

Intracranial malignant meningioma with cerebrospinal fluid dissemination： a case report

Malignant meningiomas are uncommon intracranial tumors. The metastasis of malignant meningiomas to distant extracranial sites are well known. However, dissemination of the tumours in the cerebrospinal fluid （CSF） is rare and few cases have been reported. We present a case of histologically proven malignant meningioma with CSF dissemination at the remote intracranial area and into the spinal canal detected with maqnetic resonance imaging.

Single-cell transcriptomic profiling of the hypothalamic median eminence during aging

Aging is a slow and progressive natural process that compromises the normal functions of cells,tissues,organs,and systems.The aging of the hypothalamic median eminence(ME),a structural gate linking neural and endocrine systems,may impair hormone release,energy homeostasis,and central sensing of circulating molecules,leading to systemic and reproductive aging.However,the molecular and cellular features of ME aging remain largely unknown.Here,we describe the transcriptional landscape of young and middleaged mouse ME at single-cell resolution,revealing the common and cell type-specific transcriptional changes with age.The transcriptional changes in cell-intrinsic programs,cell-cell crosstalk,and cellextrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular,signaling,and molecular levels.Importantly,our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome.Together,our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process,which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.