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Molecular Immunology May 2023Streptococcus pneumoniae (S. pneumoniae), a clinically important pathogen worldwide, causes serious invasive diseases, such as pneumonia, otitis media, and meningitis.... (Review)
Review
Streptococcus pneumoniae (S. pneumoniae), a clinically important pathogen worldwide, causes serious invasive diseases, such as pneumonia, otitis media, and meningitis. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome, an important component of the innate immune system, plays a key role in defense against pathogen infection; however the specific activation mechanism induced by S. pneumoniae infection is not fully understood. Here, primary mouse macrophages were selected as the in vitro cell model, and the effect of kinases on S. pneumoniae infection-induced NLRP3 inflammasome activation was investigated in vivo and in vitro using the western blot/RT-PCR/Co-IP/immunofluorescence staining/ELISA with or without kinase inhibitor or siRNA pretreatment. In this study, we found that the formation of the NEK7-NLRP3 complex significantly increased during S. pneumoniae infection and that anaplastic lymphoma kinase (ALK) and Jun N-terminal kinase (JNK) were phosphorylated rapidly. ALK and JNK inhibitors significantly reduced the ability of bacterial killing, the gene expression of NLRP3 inflammasome, the formation of apoptosis-associated speck-like protein containing caspase-recruitment domain (ASC) specks and the NEK7-NLRP3 complex, which in turn decreased the activation level of NLRP3 inflammasome-associated molecules and the maturation of interleukin-1β (IL-1β). In addition, ALK regulated the phosphorylation of JNK. Interestingly, the ALK/JNK/NEK7-NLRP3 signaling pathway is also involved in regulating pyroptosis and IL-1β secretion triggered by S. pneumoniae infection. In conclusion, our data suggest, for the first time, that the ALK/JNK/NEK7-NLRP3 signaling pathway may play an important role in NLRP3 inflammasome activation and pyroptosis and consequently regulate the host immune response upon S. pneumoniae infection.
Topics: Animals; Mice; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Anaplastic Lymphoma Kinase; Pyroptosis; Pneumococcal Infections; Streptococcus pneumoniae; Interleukin-1beta; Caspase 1; NIMA-Related Kinases
PubMed: 37001294
DOI: 10.1016/j.molimm.2023.03.016 -
Japanese Journal of Radiology Aug 2023Many types of tumors can develop in the pituitary gland. In the recently revised 5th editions of the World Health Organization (WHO) classifications (2021 WHO... (Review)
Review
Many types of tumors can develop in the pituitary gland. In the recently revised 5th editions of the World Health Organization (WHO) classifications (2021 WHO Classification of Central Nervous System Tumors and the 2022 WHO Classification of Endocrine and Neuroendocrine Tumors), various changes have been made to the tumors other than pituitary neuroendocrine tumor (PitNET)/pituitary adenoma, as well as PitNET. Adamantinomatous craniopharyngioma and papillary craniopharyngioma are now considered separate tumors in the 5th edition of the WHO classification. Tumors positive for thyroid transcription factor 1, a marker of posterior pituitary cells, are now grouped together in the pituicyte tumor family in the 5th edition of the WHO classification of Endocrine and Neuroendocrine Tumors. Poorly differentiated chordoma is newly listed in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. In this paper, we present the latest WHO classification of pituitary tumors (adamantinomatous craniopharyngioma, papillary craniopharyngioma, pituitary blastoma, pituicyte tumor family, tumors of pituitary origin other than those of the pituicyte tumor family, germinoma, meningioma, chordoma, metastatic tumors, lymphoma, and pituitary incidentaloma), review diseases requiring differentiation from tumors (pituitary abscess, hypophysitis, pituitary hyperplasia, Rathke's cleft cyst, arachnoid cyst, and aneurysm), and discuss diagnoses based on imaging findings.
Topics: Humans; Pituitary Neoplasms; Craniopharyngioma; Chordoma; Pituitary Gland; Pituitary Diseases; Adenoma; Neuroendocrine Tumors; Meningeal Neoplasms; World Health Organization
PubMed: 36913010
DOI: 10.1007/s11604-023-01407-0 -
Animals : An Open Access Journal From... Feb 2023The literature about nervous system lymphoma (NSL) in dogs and cats is fragmentary, based on a few case series and case reports with heterogeneous results. The aim of...
The literature about nervous system lymphoma (NSL) in dogs and cats is fragmentary, based on a few case series and case reports with heterogeneous results. The aim of our study was to retrospectively analyze 45 cases of canine and 47 cases of feline NSL and compare our results with previously reported data, also providing an extensive literature review. Breed, age, gender, clinical signs, type, and neurolocalization were recorded for each case. The pathological patterns and phenotype were assessed by histopathology and immunohistochemistry. The occurrence of central and peripheral NSL was similar between the two species in both primary and secondary types. NSL occurred with a slightly higher prevalence in Labrador Retrievers, and spinal cord lymphoma (SCL) was associated with young age in cats. The most frequent locations were the forebrain in dogs and the thoracolumbar segment in cats. Primary central nervous system lymphoma (CNSL) in cats most frequently involved the forebrain meninges, particularly as a B-cell phenotype. Peripheral NSL mostly affected the sciatic nerve in dogs and had no preferred location in cats. Nine different pathological patterns were identified, with extradural as the most prevalent SCL pattern in both species. Finally, lymphomatosis cerebri was described for the first time in a dog.
PubMed: 36899719
DOI: 10.3390/ani13050862 -
Cancer May 2023Management of brain tumors has been challenging given the limited therapeutic options and disabling morbidities associated with central nervous system (CNS) dysfunction.... (Review)
Review
Management of brain tumors has been challenging given the limited therapeutic options and disabling morbidities associated with central nervous system (CNS) dysfunction. This review focuses on recent developments in the field, with an emphasis on clinical management. The growing clinical trials landscape reflects advanced insights into cancer immunology and genomics and the need to address molecular and clinical heterogeneity. Recent phase 3 trials investigating anti-PD-1 immunotherapies, particularly nivolumab, have failed to demonstrate improved survival in glioblastoma, underscoring the need to better understand the complexity of CNS immunologic surveillance. Conversely, targeted therapies have accounted for several US Food and Drug Administration approvals extended to brain tumors, particularly therapies directed to BRAF V600E mutations and TRAK fusions, underscoring a need to routinely screen patients for these rare molecular abnormalities. In primary CNS lymphoma, attention has turned to long-term outcomes of consolidation therapies, and recent studies have highlighted the excellent disease control afforded by high-dose chemotherapy and stem cell transplantation. Meningiomas remain a focus of investigations, with preliminary promising results observed with octreotide combined with mTOR inhibition, and immunotherapy with single-agent pembrolizumab. Finally, proton radiotherapy has emerged as a novel alternative for leptomeningeal metastases from solid tumors, which can now be treated more safely with craniospinal irradiation and monitored by the enumeration of circulating tumor cells in the cerebrospinal fluid as a biomarker. Taken together, these incremental advances have improved outcomes in select brain tumor patient populations, whereas ongoing clinical trials hold the promise of meaningful advances and breakthroughs for larger proportions of patients with brain tumors.
Topics: Humans; Brain Neoplasms; Glioblastoma; Meningioma; Meningeal Neoplasms
PubMed: 36825454
DOI: 10.1002/cncr.34711 -
Therapeutic Advances in Neurological... 2022A middle-aged, previously healthy male patient presented with high fever, headache, and aching limbs for 3 days. Laboratory results showed signs of acute kidney...
A middle-aged, previously healthy male patient presented with high fever, headache, and aching limbs for 3 days. Laboratory results showed signs of acute kidney injury, elevated procalcitonin, and mild thrombocytopenia. On neurological examination, he had no focal neurological deficits, especially no meningism or visual disturbances. Cerebrospinal fluid (CSF) examination showed mild lymphocytic pleocytosis, and magnetic resonance imaging (MRI) revealed a lesion of the splenium corporis callosum. The patient received anti-infective treatment with acyclovir and ceftriaxone until laboratory results returned positive hantavirus IgM and IgG antibodies in the serum indicating an active hantavirus infection. The renal retention parameters and thrombocytopenia receded following treatment with intravenous fluids, analgesic, and antipyretic agents. MRI follow-up 10 days later showed a residual small FLAIR-positive lesion without any persistent callosal diffusion abnormality. The patient was discharged symptom-free after 8 days and had recovered fully 2 months later. The source of infection in this patient remained unclear. Cytotoxic lesions of the corpus callosum (CLCC) are secondary lesions usually with a good prognosis but require further investigation regarding their underlying etiology and should not be confounded with primary callosal lesions, such as ischemia or lymphoma.
PubMed: 36601083
DOI: 10.1177/17562864221144808 -
Medicine Dec 2022Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and isolated meningeal PCNSL, without evidence of parenchymal involvement, is... (Review)
Review
RATIONALE
Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and isolated meningeal PCNSL, without evidence of parenchymal involvement, is even less common, occurring in only 10% to 15% of cases.
PATIENT CONCERNS
A 65-years-old female presented to our hospital with progressive lower extremity motor dysfunction and blurred vision. The initial neurological examination revealed decreased muscle strength in both lower extremities and sensory dysfunction of lower extremities, saddle area, and buttocks. Brain magnetic resonance imaging showed no abnormalities. Lumbar enhanced magnetic resonance imaging showed T11 to L3 horizontal meningeal enhancement. Cerebrospinal fluid (CSF) cytology revealed lymphoma cells. Immunohistochemistry and flow cytometry of the CSF were performed as auxiliary methods to establish the diagnosis of lymphoma.
DIAGNOSES
The patient was diagnosed primary meningeal central nervous system lymphoma.
INTERVENTIONS
During hospitalization, the patient was treated with 2 courses of high-dose intrathecal methotrexate and rituximab combined with intrathecal chemotherapy and supportive treatment.
OUTCOMES
After 2 years of follow-up, the patient was able to walk and take care of herself.
LESSONS
Cases of PCNSL involving only the meninges are rare. Multimodal analysis of the CSF comprises an important component of the diagnostic work-up for patients with primary meningeal central nervous system lymphoma.
Topics: Humans; Female; Aged; Central Nervous System Neoplasms; Lymphoma; Meninges; Rituximab; Brain
PubMed: 36596043
DOI: 10.1097/MD.0000000000032567 -
Brain Sciences Dec 2022This paper reports the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity.
OBJECTIVE
This paper reports the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity.
METHODS
From June 2016 to December 2019, patients suspected to have neurological autoimmune disease after having their serum and cerebrospinal fluid (CSF) tested for conventional neural antibodies were scanned for additional autoantibodies by immunohistochemistry. Samples that showed a characteristic immunoreactive pattern reminiscent of the GFAP of astrocytes were selected and confirmed by cell-based assay using cells-expressing human GFAPα.
RESULTS
A total of 15 patients (eight male and seven female) with a median age at onset of 53 years (range 28-72) were identified as GFAP-IgG-positive. Fourteen cases had GFAP-IgG detected in the CSF, while serum GFAP-IgG was detected in 11 cases. Eleven of the fifteen patients (73.3%) presented with an acute monophasic course, of which 10 (90.9%) had antecedent flu-like symptoms. The predominant phenotype was meningoencephalitis (46.7%), followed by meningoencephalomyelitis in 40% of the cases. The most common clinical features included long tract signs, brainstem symptoms, tremors, headaches, and psychiatric symptoms. Magnetic resonance imaging (MRI) revealed the enhancement of the meninges, the surface of the brainstem, the cerebellum, and the spinal cord as predominant. Inflammatory CSF showed mild lymphocyte-predominant pleocytosis with a median of 51/μL and elevated protein with a median of 87.5 mg/dL. Five patients had coexisting antibodies, including NMDAR-IgG in three patients and Yo and MOG-IgG in one patient each. One patient underwent a stereotactic brain biopsy, and the neuropathology diagnosis was diffuse large B-cell lymphoma. One patient had ovarian teratoma. Eleven of the fifteen (73.3%) patients received both intravenous immunoglobulin and steroids. Among them, three patients also received immunosuppressive agents later. During a two-year follow-up, 9 of the 15 (60%) patients achieved complete clinical remission.
CONCLUSIONS
The clinical presentation of GFAP astrocytopathy is heterogeneous. It can be characterized by an acute monophasic course and a chronic relapsing course. Tremors are a prominent clinical manifestation in patients with an acute monophasic course with GFAP-IgG antibodies only. Most patients responded well to immunotherapy. In patients with GFAP autoimmunity, presenting with a chronic relapsing course, one should actively search for immunogenic factors and the culprit antibodies. In the case of primary central nervous system lymphoma, GFAP autoimmunity does not always equate to autoimmune GFAP astrocytopathy.
PubMed: 36552122
DOI: 10.3390/brainsci12121662 -
European Journal of Case Reports in... 2022Uveo-meningeal syndromes are any disorder characterized by the involvement of the uvea and the meninges. They can have multiple causes, including infectious, autoimmune...
UNLABELLED
Uveo-meningeal syndromes are any disorder characterized by the involvement of the uvea and the meninges. They can have multiple causes, including infectious, autoimmune and malignant diseases. We report the case of a patient with a 10-year-old diagnosis of myelodysplastic syndrome that had been stable. He presented with new onset uveitis, ataxia, diplopia and fluctuating consciousness level, without any obvious cause revealed by brain imaging or blood chemistries. An extensive aetiological search showed no obvious cause. Initially, the patient improved spontaneously and was discharged. However, 2 months later, he deteriorated once again, this time with disperse adenomegalies that were not present previously. The bone marrow biopsy showed a high number of blasts, which affirmed the progression of the previously known myelodysplastic syndrome. The lymph nodes were not biopsied due to very low life expectancy, making the procedure futile. A presumptive diagnosis of uveo-meningitis caused by paraneoplastic syndrome was made. The patient died a few months later.
LEARNING POINTS
Uveo-meningeal syndrome (UMS) is a rare entity usually of infectious or inflammatory aetiology.UMS may be caused by some neoplastic disorders, mainly lymphoma and metastasis of solid tumours; myelodysplastic syndrome (MDS) has not been previously implicated.Diagnosis should include lumbar puncture and a thorough search for the aetiology; treatment is directed towards the aetiology.
PubMed: 36415835
DOI: 10.12890/2022_003633 -
Annals of Oncology : Official Journal... Feb 2023Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to...
BACKGROUND
Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity.
PATIENTS AND METHODS
To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data.
RESULTS
Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue.
CONCLUSIONS
The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.
Topics: Humans; Phosphatidylinositol 3-Kinases; Lymphoma, Large B-Cell, Diffuse; Mutation; Polycomb Repressive Complex 2; Central Nervous System; Central Nervous System Neoplasms
PubMed: 36402300
DOI: 10.1016/j.annonc.2022.11.002 -
Scientific Reports Nov 2022To explore the clinical advantages of 3D Slicer combined with Sina/MosoCam multimodal system in preoperative planning of brain lesions surgery. By collecting the data of...
To explore the clinical advantages of 3D Slicer combined with Sina/MosoCam multimodal system in preoperative planning of brain lesions surgery. By collecting the data of brain lesions patients undergoing craniotomy under the preoperative positioning of 3D Slicer combined Sina/MosoCam multimodal system in the people's Hospital of Wuhan University from January 2021 to October 2021, the preoperative planning of patients was introduced, and the size of surgical bone window, operation time, preoperative and postoperative neurological dysfunction were counted. We collected the case data of 35 patients who were reconstructed by 3D Slicer and located by Sina/MosoCam projection. There were 14 cases of malignant tumors (7 cases of glioma, 2 cases of diffuse large B-cell lymphoma, 5 cases of metastatic cancer) and 21 cases of benign tumors (17 cases of meningioma, 1 case of central neurocytoma, 2 cases of cavernous hemangioma and 1 case of arachnoid cyst). All 35 patients were located accurately before operation, the lesions were found quickly during operation, and the postoperative imaging data confirmed that the lesions were removed completely, of which 28 cases (80%) had significantly improved neurological symptoms one month after operation. 3D Slicer combined with Sina/MosoCam multimodal system has many advantages, such as simple and easy to learn, convenient operation, accurate positioning and free. It is considered to be a new technology that is practical, reliable, convenient for diagnosis and preoperative planning. It is suitable for popularization and use in neurosurgery and other operating rooms of all medical institutions.
Topics: Humans; Meningioma; Glioma; Neurosurgical Procedures; Meningeal Neoplasms; Brain; Imaging, Three-Dimensional; Retrospective Studies
PubMed: 36357434
DOI: 10.1038/s41598-022-22549-7