Multiple myeloma with central nervous system relapse.
Ontology highlight
ABSTRACT:
SUBMITTER: Egan PA
PROVIDER: S-EPMC7327654 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The optimal management of central nervous system (CNS) relapse of rhabdomyosarcoma (RMS) is unclear. We examined diagnosis, management, and outcomes of patients with RMS developing CNS relapse. Records of 23 patients diagnosed with CNS relapse between 1999 and 2016 were reviewed. Median age at presentation of CNS relapse was 15 years (range, 1-34 years). High-risk features at initial presentation were as follows: 16 alveolar patients, 13 Stage IV, and 13 with primary tumor in parameningeal locations. CNS relapse occurred at a median 12 months (range, 1-23 months) from diagnosis and most common presenting symptoms were headache (n = 9), nausea/vomiting (n = 8), visual difficulty (n = 5), and none (n = 5). Leptomeningeal metastases were detected in 21 patients while only 2 developed parenchymal metastases without leptomeningeal involvement. Fifteen patients received CNS-directed radiation therapy (RT), including craniospinal irradiation to a median 36 Gy (range, 18-36 Gy) and/or whole brain radiotherapy to a median 30 Gy (range, 6-41.4 Gy). Three patients received concurrent chemotherapy. Follow-up magnetic resonance imaging was conducted in 13 patients after RT initiation with 8 demonstrating improvement, 2 with stable disease, and 3 with progression. Twelve patients were tested for reactivity to I-131-labeled monoclonal antibody 8H9, and three tested positive and received at least one intra-Ommaya dose; all three lived >12 months post-CNS relapse. Twenty‐two patients died of CNS disease and one of treatment complications, with metastatic disease at other sites. Median survival post-CNS relapse was 5 months (range, 0.1-49 months). The prognosis for patients with RMS developing CNS relapse remains poor. Treatment including CNS-directed RT should be considered and investigation into preventative therapies is warranted.
| S-EPMC7343338 | biostudies-literature
Project description:The autonomic nervous system (ANS), which consists of antagonistic sympathetic (adrenergic) and parasympathetic (cholinergic) arms, has emerged as an important regulator of neoplastic development, yet little is known about its role in multiple myeloma (MM). Clinical findings that anti-adrenergic β-blocker intake reduces risk of disease-specific death and overall mortality in patients with MM have indicated that adrenergic input may worsen myeloma outcome. However, preclinical studies using β-adrenergic receptor agonists or antagonists produced controversial results as to whether sympathetic pathways promote or inhibit myeloma. Retrospective outcome data demonstrating that high message levels of cholinergic receptor genes predict inferior survival in the Multiple Myeloma Research Foundation CoMMpass trial suggest that parasympathetic input may drive myeloma progression in a subset of patients. Here we review the ill-defined role of the ANS in MM, put myeloma in the context of other cancers, and discuss knowledge gaps that may afford exciting research opportunities going forward.
| S-EPMC7876165 | biostudies-literature
Project description:ObjectiveTo track the clinical outcomes in patients who initially presented with tumefactive demyelinating lesions (TDLs), we summarized the clinical characteristics of various etiologies, and identified possible relapse risk factors for TDLs.MethodsBetween 2001 and 2021, 116 patients initially presented with TDLs in our hospital were retrospectively evaluated. Patients were followed for relapse and clinical outcomes, and grouped according to various etiologies. Demographic information, clinical data, imaging data, and laboratory results of patients were obtained and analyzed. The risk factors of relapse were analyzed by the Log-Rank test and the Cox proportional hazard model in multivariate analysis.ResultDuring a median follow-up period of 72 months, 33 patients were diagnosed with multiple sclerosis (MS), 6 patients with Balo, 6 patients with neuromyelitis optica spectrum disorders (NMOSD), 10 patients with myelin oligodendrocyte glycoprotein antibody-associated demyelination (MOGAD), 1 patient with acute disseminated encephalomyelitis (ADEM), and the remaining 60 patients still have no clear etiology. These individuals with an unknown etiology were categorized independently and placed to the other etiology group. In the other etiology group, 13 patients had recurrent demyelinating phases, while 47 patients did not suffer any more clinical events. Approximately 46.6% of TDLs had relapses which were associated with multiple functional system involvement, first-phase Expanded Disability Status Scale score, lesions morphology, number of lesions, and lesions location (P<0.05). And diffuse infiltrative lesions (P=0.003, HR=6.045, 95%CI:1.860-19.652), multiple lesions (P=0.001, HR=3.262, 95%CI:1.654-6.435) and infratentorial involvement (P=0.006, HR=2.289, 95%CI:1.064-3.853) may be independent risk factors for recurrence. Relapse free survival was assessed to be 36 months.ConclusionsIn clinical practice, around 46.6% of TDLs relapsed, with the MS group showing the highest recurrence rate, and lesions location, diffuse infiltrative lesions, and multiple lesions might be independent risk factors for relapse. Nevertheless, despite extensive diagnostic work and long-term follow-up, the etiology of TDLs in some patients was still unclear. And these patients tend to have monophase course and a low rate of relapse.
| S-EPMC9752826 | biostudies-literature
Project description:Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease where cells in the central nervous system play a critical role. To our knowledge, alemtuzumab, fumarates (dimethyl, diroximel, and monomethyl), glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and teriflunomide are either limited to the periphery or insufficiently studied to confirm direct central nervous system effects in participants with multiple sclerosis. In contrast, cladribine and sphingosine 1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are central nervous system-penetrant and could have beneficial direct central nervous system properties.
| S-EPMC10755740 | biostudies-literature
Project description:Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases.
| S-EPMC6631306 | biostudies-literature
Project description:The brown ghost knifefish (Apteronotus leptorhynchus) is a weakly electric teleost fish of particular interest as a model organism for a variety of research areas in neuroscience, including neurophysiology, neuroethology, and neurobiology. This versatile model system has been more recently used in the study of central nervous system development and regeneration during adulthood, as well as in the study of vertebrate aging and senescence. Despite substantial scientific interest in this species, no genomic resources are currently available. After evaluating several trimming and transcript reconstruction strategies, de novo assembly using Trinity uncovered at least 11,847 unique components (“genes”) containing full or near-full length protein sequences based on alignment to a reference set of known Actinopterygii protein sequences, with as many as 42,459 components containing at least a partial protein-coding sequence, providing broad coverage of the proteome. Shotgun proteomics confirmed translation of open reading frames from over 2,000 transcripts, including alternative splice variants. Assignment of tandem mass spectra obtained was shown to be greatly improved with the assembly compared with using databases of sequences from closely related organisms.
2015-07-16 | PXD001285 | Pride
Project description:Purpose of reviewCentral nervous system (CNS) tuberculosis is the most devastating form of tuberculosis (TB), with mortality and or neurological sequelae in over half of individuals. We reviewed original research and systematic reviews published since 1 January 2019 for new developments in CNS TB pathophysiology, diagnosis, management and prognosis.Recent findingsInsight in the pathophysiology is increasing steadily since the landmark studies in 1933, focussing on granuloma type classification, the relevance of the M. tuberculosis bacterial burden and the wide range of immunological responses. Although Xpert/RIF has been recommended by the WHO for extrapulmonary TB diagnosis, culture is still needed to increase the sensitivity of TB meningitis diagnosis. Sequential MRIs can improve understanding of neurological deficits at baseline and during treatment. Pharmacokinetic/pharmacodynamic modelling suggests that higher doses of rifampicin and isoniazid in TB meningitis could improve survival.SummaryRecent studies in the field of CNS-TB have largely focussed on TB meningitis. The outcome may improve by optimizing treatment dosing. This needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses. This could improve understanding of the biology of this disease and improve patient outlook by enabling individualised host-directed therapy.
| S-EPMC8283909 | biostudies-literature
Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode. A light-weight membrane fraction enriched for myelin was purified from mouse brains as described previously (Jahn et al., Neuromethods, 2013). For RNA-Seq, RNA was isolated from myelin of mice from indicated ages.
2016-06-24 | E-GEOD-78151 | biostudies-arrayexpress
Project description:The central nervous system (CNS) of patients with multiple sclerosis (MS) is the site where disease pathology is evident. Damaged CNS tissue is commonly associated with immune cell infiltration. This infiltrate often includes B cells that are found in multiple locations throughout the CNS, including the cerebrospinal fluid (CSF), parenchyma, and the meninges, frequently forming tertiary lymphoid structures in the latter. Several groups, including our own, have shown that B cells from distinct locations within the MS CNS are clonally related and display the characteristics of an antigen-driven response. However, the antigen(s) driving this response have yet to be conclusively defined. To explore the antigen specificity of the MS B cell response, we produced recombinant human immunoglobulin (rIgG) from a series of expanded B cell clones that we isolated from the CNS tissue of six MS brains. The specificity of these MS-derived rIgG and control rIgG derived from non-MS tissues was then examined using multiple methodologies that included testing individual candidate antigens, screening with high-throughput antigen arrays and evaluating binding to CNS-derived cell lines. We report that while several MS-derived rIgG recognized particular antigens, including neurofilament light and a protocadherin isoform, none were unique to MS, as non-MS-derived rIgG used as controls invariably displayed similar binding specificities. We conclude that while MS CNS resident B cells display the characteristics of an antigen-driven B cell response, the antigen(s) driving this response remain at large.
| S-EPMC4663633 | biostudies-literature
Project description:BackgroundPeople with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.ObjectiveThe objective is to measure the prevalence of CNS-active polypharmacy in pwMS.MethodsThis serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.ResultsThe number of subjects included at each time point ranged from 23,917 subjects in 2008 to 55,797 subjects in 2021. In 2021, subjects with CNS-active polypharmacy were more likely to be 46-65 years of age and have CNS-related comorbidities compared to those without CNS-active polypharmacy. From 2008 to 2021, the age-adjusted prevalence of CNS-active polypharmacy among female subjects increased from 19.8% (95% confidence interval (CI) = 19.1-20.4) to 26.4% (95% CI = 25.9-26.8) versus 15.9% (95% CI = 14.8-17.0) to 18.6% (95% CI = 17.9-19.2) in male subjects.ConclusionThe prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex.
| S-EPMC11363472 | biostudies-literature