A curative approach to central nervous system metastases of neuroblastoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10545-10545 ◽  
Author(s):  
Kim Kramer ◽  
Brian H. Kushner ◽  
Shakeel Modak ◽  
Neeta Pandit-Taskar ◽  
Ursula Tomlinson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Surface Glycoprotein ◽  
Cancer Center ◽  
Salvage Regimen ◽  
Cell Surface Glycoprotein ◽  
Cns Metastasis ◽  
Group 2 ◽  
Group 1

10545 Background: Neuroblastoma metastatic to the central nervous system (CNS NB) is associated with significant mortality (median survival < 6 months, < 10% survival at 36 months). Intraventricular compartmental radioimmunotherapy (cRIT) with radio-iodinated murine IgG1 monoclonal antibody 131I-8H9 targeting tumor cell-surface glycoprotein B7-H3 offers a therapeutic strategy. We analyzed overall survival of patients with CNS NB treated with intraventricular 131I-8H9 cRIT at Memorial Sloan Kettering Cancer Center (MSK) since 2003. Methods: After radiographic and/or pathologic confirmation of CNS NB, and assessment of adequate CSF flow, cRIT eligible patients underwent treatment on an IRB-approved protocol with either temozolomide/irinotecan-based CNS salvage regimen incorporating craniospinal radiation therapy, 131I-8H9 cRIT plus systemic immunotherapy (group 1), or non-regimen therapies with 131I-8H9 cRIT (group 2). cRIT administration involved a 2mCi tracer of 124I- or 131I-8H9 with nuclear imaging and CSF sampling for dosimetry followed by 1 or 2 therapeutic injections up to 70 mCi 131I-8H9. Disease surveillance included serial MR brain/spine, MIBG, CT, and bone marrow evaluation. Data are presented as overall survival after detection of CNS metastasis. Results: 105 patients with CNS NB were evaluated;80 patients (76%) were treated (57 group 1, 23 group 2). Of the 25 patients who were not eligible for cRIT, survival averaged 8.6 months. Of 19 patients with radiographic evidence of disease at the time of cRIT, 7 (36%) demonstrated post cRIT radiographic improvement. At analysis, 45/80 (56%) patients were alive 4.8–152 months (median 58 months) after CNS metastasis, including 36 (45%) at 36 months and 23 (29%) > 60 months. Subgroup analyses of 131I-8H9–treated patients identified age at NB diagnosis (≤18 months), relapse restricted to CNS and group 1 status as factors positively correlated with survival. Conclusions: 76% of patients with CNS NB treated at MSK received 131I-8H9 cRIT, and approximately half completed multimodality CNS salvage regimen with 131I-8H9 cRIT. Despite advanced CNS involvement, over 50% of patients treated with 131I-8H9 cRIT are still alive and nearly 50% have survived at least 36 months. Clinical trial information: NCT00089245.

Tuberculosis of the meninges and central nervous system. Experience of clinical diagnostics in St. Petersburg for 50 years

MedAlliance ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 14-24
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Medical Errors ◽  
Clinical Diagnostics ◽  
Lethal Outcome ◽  
Significant Difference ◽  
Group 2 ◽  
Allergic Vasculitis ◽  
Tuberculosis Meningitis ◽  
Group 1

The clinic and diagnostics of tuberculosis meningitis (TM) in 926 patients treated in St. Petersburg hospitals in 1965–1994 (group 1) and in 1995–2018 (group 2) is presented. The TM clinic is demonstrated to be determined by the form of tuberculosis and its characteristic generalization nature in the presence of repeated waves of bacteremia and allergic vasculitis of greater or lesser severity. There is clinical peculiarity of TM in primary pulmonary tuberculosis and its early large-focal and late miliar generalization, as well as in hematogenous tuberculosis. In patients of the 1st and 2nd groups the TM clinic shows in some respects a noticeable similarity, in others — a significant difference. Despite the typical symptoms, early diagnosis of TM took place in less than 20% of patients. Clinical examples illustrating the unusual development of TM, contrasting with its usual course, are given. A number of objective and subjective factors contributing to the adverse evolution of TM and its lethal outcome are discussed. These include the peculiarity of modern tuberculosis, especially when associated with HIV infection, as well as medical errors associated with ignorance of the pathogenesis of tuberculosis and failure to comply with the minimum examination for tuberculosis.

scholarly journals OTHR-04. Gynecological Malignancies With Metastasis To The Central Nervous System: A Case Series and Systematic Review of the Literature

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii15-iii15
Author(s):  
Azeem Sajjad ◽  
Adeleso Adesina ◽  
Penelope Halkiadakis ◽  
Kelsey Murphy ◽  
Kathleen Mulligan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Literature Review ◽  
Metastatic Disease ◽  
Case Series ◽  
Progression Free Survival ◽  
Gynecologic Malignancies ◽  
Free Survival ◽  
Cns Metastasis

Abstract Introduction Gynecologic malignancies are an increasingly common proportion of central nervous system metastatic disease. As genetic sequencing technology improves and becomes more accessible, mutations associated with CNS metastasis are easier to elucidate. The aims of this case series and systematic literature review are to describe the patient population with CNS metastatic disease from a gynecologic primary, and to investigate why the proportion of CNS metastasis from gynecologic malignancies is increasing. Ultimately, we hope to improve understanding of this subset of metastatic CNS malignancies and improve management strategies. Methods A literature review of articles describing patients from 1990–2020 who were diagnosed with CNS metastasis from a known gynecologic primary malignancy was performed. Demographics, cancer type, mutation characteristics, management for metastatic disease, progression free survival, number of CNS metastases, and location of metastatic disease were assessed. Inclusion criteria were age&gt;18 years, diagnosis of primary ovarian, uterine, or cervical cancer with confirmed metastatic disease to the CNS, including brain parenchyma, leptomeninges, or intradural spinal cord or dural metastases. Exclusion criteria included pediatric population and bony metastases (e.g., bony spine metastases without evidence of meningeal/parenchymal invasion). Results Our review showed that patients with gynecological metastasis to the CNS generally have worse outcomes regarding overall survival, progression free survival, and quality of life than patients without CNS metastasis. Discussion Our results infer that the reported increase in incidence of CNS metastasis from gynecologic malignancies is a reflection of improvement of detection given advances in technology, improved patient follow up, and increased overall survival of patients with gynecologic malignancies. Further characterization of mutations from gynecologic malignancies associated with brain metastasis could result in development of more treatment options for patients in the future and help determine factors that contribute to developing metastasis to the CNS of various degrees, thus, potentially inform treatment strategies.

scholarly journals Central nervous system metastases from breast carcinoma: a clinical and laboratorial study in 47 patients

1998 ◽  
Vol 56 (2) ◽  
pp. 188-192 ◽  
Author(s):  
ALUÍZIO B.B. MACHADO ◽  
ALEXANDRE A.C. MACHADO ◽  
JOSÉ ALEXANDRE M. BARBUTO ◽  
RICARDO M. DE OLIVEIRA
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Diagnostic Methods ◽  
Motor Deficits ◽  
Time Interval ◽  
Central Nervous System Metastases ◽  
Group 2 ◽  
Magnetic Resonance Imaging Mri ◽  
Csf Examination ◽  
Group 1

In this retrospective study, 47 patients with clinical diagnosis of central nervous system metastases of breast cancer were evaluated by computerized tomography (CT), magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination. The patients were divided in 2 groups: 1, without leptomeningeal neoplasm and 2, with leptomeningeal neoplasm. In the group 2, the time interval between the primary disease and the central nervous system metastasis as well as the survival time were shorter than in group 1 (40 and 4.3 months in group 2 versus 57 and 10 months respectively, in group 1). In both groups the most common neurological symptoms and signs were intracranial hypertension and motor deficits. The most sensitive diagnostic methods were CT and MRI in group 1, and the CSF examination in group 2. The use of the tumor markers CEA and CA-15.3 in the routine examination of CSF showed promising results, mainly in leptomeningeal forms.

ADAM23 is a cell-surface glycoprotein expressed by central nervous system neurons

2004 ◽  
Vol 78 (5) ◽  
pp. 647-658 ◽  
Author(s):  
Alexander P. Goldsmith ◽  
Samuel J. Gossage ◽  
Charles ffrench-Constant
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Surface ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
A Cell

Effect of Antagonism at Central Nervous System M3 Muscarinic Receptors on Laryngeal Chemoresponse

1997 ◽  
Vol 106 (11) ◽  
pp. 920-926 ◽  
Author(s):  
Brent E. Richardson ◽  
Kerri J. Pernell ◽  
George S. Goding
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Messenger Rna ◽  
Sudden Infant ◽  
Respiratory Drive ◽  
Age Related ◽  
M3 Receptors ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The laryngeal chemoresponse (LCR), comprising laryngeal adductor spasm, central apnea, and subsequent cardiovascular instability, is thought to be a factor in sudden infant death syndrome. A muscarinic subtype receptor, M3, appears to be involved in central respiratory drive and control. Both the duration of the LCR apnea and levels of M3 receptor messenger RNA in the brain stem change according to postnatal age. This study examined the effect of central nervous system antagonism at M3 receptors on the LCR with respect to animal age and dose of antagonist. Ten piglets in each of three age groups (group 1, 5 to 8 days; group 2, 18 to 21 days; and group 3, 40 to 43 days) received a series of four increasing doses of an M3 antagonist ( p-fluoro-hexahydro-siladiphenidol) by intracerebral ventricle injection. The LCR was evoked at baseline and after each dose of antagonist. An effect on susceptible animals (groups 1 and 2) was evident by the second antagonist dose, and persisted for the remainder of the experiment (2 hours). At completion of the experiment, mean apnea duration had decreased in group 1 (61%, p < .05), and group 2 (57%, p < .05), but was unchanged in group 3 (<10%, p not significant). Length of mean baseline apneas correlated directly with degree of apnea shortening. The reduction is not attributable to changes in arterial Po2 or Pco2 or baseline respiratory rate. These results support an age-related influence on the LCR by M3 receptors in younger animals that decreases with maturation.

scholarly journals Incidence and risk factors for seizures in central nervous system infections in childhood

2009 ◽  
Vol 15 (2) ◽  
pp. 83-88
Author(s):  
Paulo Breno Noronha Liberalesso ◽  
Izabella Celidônio Bertoldo da Silva ◽  
Karlin Fabianne Klagenberg ◽  
Ari Leon Jurkiewicz ◽  
Bianca Simone Zeigelboim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Nervous System ◽  
Viral Encephalitis ◽  
Viral Meningitis ◽  
Central Nervous System Infections ◽  
Stiff Neck ◽  
The Central Nervous System ◽  
Group 2 ◽  
Group 1

INTRODUCTION: The infections of the central nervous system remain as a public health problem in several countries and there is a direct relation between poverty and underdevelopment with high mortality and morbidity rates. Seizures represents a complication related to infections of the central nervous system, are considered a clinical emergency and requiring neurological investigation. OBJECTIVE: In this article, we propose to describe the incidence and risk factors for seizures in central nervous system infections in childhood. METHODS: a retrospective study was performed between October 2007 and October 2008 and all patients who were hospitalized with the diagnosis of infections of the central nervous system were analyzed. Newborns were excluded. The patients were divided into GROUP 1 (without seizures) and GROUP 2 (with seizures). RESULTS: 731 patients were included, 47.75% males, with average age of 15.7 years. GROUP 1 - with fever (652/92.35%), headache (580/82.15%), vomits (550/77.9%), and viral meningitis predominance (652/93.06%). GROUP 2 - with fever (25/100%), vomits (12/48), headache (6/24%), and viral encephalitis predominance (14/56%). Ten (40%) patients from the GROUP 2 presented EEG alterations. The incidence of seizures was 3.42% and a significant statistical difference was noticed related to mean age (p<0.000069), presence of headache (p<0.0000), vomits (p<0.0005), stiff neck (p<0.0105) and drowsiness (p<0.0265). CONCLUSIONS: the occurrence of seizures during the hospitalization is significantly more frequent in cases of viral encephalitis and bacterial meningitis compared to viral meningitis. The risk of seizures increases in early ages. Headache, vomits, stiff neck and drowsiness are more frequent symptoms in children with infection of the central nervous system who presented seizures during the hospitalization.

scholarly journals Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Muhammad Hassan ◽  
Muhammad Sohail Halim ◽  
Rubbia Afridi ◽  
Nam V. Nguyen ◽  
Quan Dong Nguyen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Optical Coherence Tomography ◽  
Nervous System ◽  
Ocular Disease ◽  
Ocular Involvement ◽  
Optical Coherence ◽  
Ellipsoid Zone ◽  
Intraretinal Fluid ◽  
Group 2 ◽  
Group 1

Abstract Background To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. Methods This study was a cross-sectional study and patients with a confirmed diagnosis of PCNSL with or without ocular involvement were included. Patient cohort finder tool was used to identify patients with lymphoma using ICD-10 codes (C82–C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who had underdone OCT imaging at ophthalmology clinic. Clinic charts of 460 patients with lymphoma and available OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). OCT scans of patients in both study groups were analyzed for the presence of (1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer and inner retina; (2) RPE thickening; (3) Vitreous debris; (4) Intraretinal fluid; (5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference between the groups. Results Twenty-two eyes (11 patients) with PCNSL were included this study (Group 1: 6 eyes and Group 2: 16 eyes). Mean age of subjects was 65 years. Five patients (45.45%) were female. There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and presence of RPE thickening, intraretinal fluid, and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p = 0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). Conclusions OCT finding of hyperreflective deposits present in eyes with lymphoma secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. However, the vitreous deposits are more commonly found in eyes with ocular disease. These hyperreflective deposits can serve as biomarkers for early detection of ocular involvement by PCNSL.

scholarly journals Clinical Features and Outcome of Patients with Acute Myeloid Leukaemia (AML) and Central Nervous System Involvement at the Time of Diagnosis and during the Course of AML - Retrospective, Multicentre Study of the Polish Adult Leukemia Group (PALG)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1321-1321
Author(s):  
Elzbieta Patkowska ◽  
Joanna Gora Tybor ◽  
Ewa Lech Maranda ◽  
Maciej Kazmierczak ◽  
Marta Baranska ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Characteristics ◽  
Central Nervous System Involvement ◽  
Chromosome 8 ◽  
Group 2 ◽  
Adult Leukemia ◽  
Leukemia Group ◽  
Acute Myeloid ◽  
Group 1

Abstract Introduction: Central nervous system involvement (CNSi) in acute myeloid leukemia (AML) can be found both at the time of diagnosis and during the AML course, with an incidence of 5-15%. However, there is lack of precise clinical characteristics and commonly recommended therapies for AML patients with the CNSi. Such patients demonstrate worse prognosis and reduced survival compared to those without CNSi, therefore allocation them to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) regardless of their cytogenetic risk seems to be the best treatment option. Aims: The aim of the study was to assessed clinical characteristics and treatment outcome of patients with AML and the CNSi who were treated between 2004 and 2014 in 8 hematology departments of the Polish Adult Leukemia Group (PALG). Results: The analysis comprised 65 patients (62% males and 38% females) with the median age of 45 years (range 20-81 years). The CNSi was observed in 33 (51%) patients at the time of AML diagnosis (group 1) and in 32 (49%) subjects during the course of AML (group 2). The most common neurological symptoms were headaches (47% vs 48%, p= 0.99) and altered mental status (21% vs 30%, p= 0.32) observed in the group 1 and 2, respectively. Higher rates of paraparesis (39% vs 9%, p= 0.002) and motor deficits (33% vs 9%, p= 0.011) were noted in the group 2 compared to the group 1. The CNSi was the most frequently found in the AML not otherwise specified (AML NOS) subtype (61% in the group 1 and 50% in the group 2; p= 0.39). The AML subtype with recurrent cytogenetic abnormalities was diagnosed in 30% of patients form the group 1 and 28% of subjects from the group 2 (p= 0.85). The therapy and dysplasia related AML subtype was diagnosed in 6% of patients from the group 1 compared to the 16% of patients from the group 2 (p= 0.21). Using the FAB classification of AML, the CNSi in the group 1 occurred more often among patients with the M4 (42%) and the M5 (30%) subtype, whilst in the group 2 it was found in the M2 (25%) and the M5 (22%) subtype. The cytogenetic risk distribution according to the SWOG (ie. favorable, intermediate and poor) were 13%, 28% and 16% in the group 1 and 18%, 15% and 21 % in the group 2, respectively (p=0,39). The group 1 was more likely to have abnormal cytogenetics involving the chromosome 8 or 16 compared to the group 2 (62% vs 27%, p= 0.012). After the diagnosis of the CNSi, systemic chemotherapy was administered to 100% of patients from the group 1 and to 80% of patients from the group 2. Intrathecal chemotherapy was administered to 94% patients in both groups, whereas 19% of patients were subjected to subsequent brain radiation therapy. The cytarabine with methotrexate with corticosteroid was given intrathecally to 83% of patients, whilst the cytarabine monotherapy, the methotrexate with or without corticosteroid and liposomal cytarabine were given intrathecally to 1.5%, 9.1% and 18.2% patients, respectively. The CNS remission rate was higher in the group 1 compared to the group 2 (72% vs 39%, p= 0,003). Allo-HSCT in the first complete remission (CR1) as well as allo-HSCT after the AML relapse were performed with similar frequency in the both groups (21% vs 25%; p= 0.72 and 12% vs. 16%; p=0.73, respectively). The probability of a 1-year overall survival (OS) between the group 1 and 2 was not significantly different (52% vs 58% , p= 0.8). However, the OS rate was significantly higher in patients who underwent allo-HSCT in their CR1 compared to that in the patients without allo-HSCT (94% vs 39%; p<0.001). It is worth noting that the OS rate was also higher when more consolidation courses were given before allo-HSCT (17% vs 67% vs 83% ; p<0.001 for 0-1 vs 2-3 vs 4 courses, respectively). Conclusions: The cytogenetic profile seems to be a key difference in patients' characteristics with the CNSi at the time of diagnosis or during the course of AML, with the chromosome 8 or 16 aberrations observed more often in the former group. The survival of AML patients with CNSi was short with the 1-year OS rate below 60%. However, the OS rate was significantly improved in those patients who underwent allo-HSCT in their CR1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Increased central cholinergic drive contributes to the apneas of serotonin-deficient rat pups during active sleep

2019 ◽  
Vol 126 (5) ◽  
pp. 1175-1183 ◽  
Author(s):  
Marina R. Davis ◽  
Jennifer L. Magnusson ◽  
Kevin J. Cummings
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tryptophan Hydroxylase ◽  
Respiratory Pattern ◽  
Whole Body ◽  
Active Sleep ◽  
Tryptophan Hydroxylase 2 ◽  
Rat Pups ◽  
Group 2 ◽  
Group 1

Infant rat pups lacking central nervous system (CNS) serotonin (5-hydroxytryptamine; 5-HT) have unstable breathing during prolonged periods of active sleep. Given that cholinergic neurons are drivers of active sleep and project to respiratory patterning regions in the brainstem, we hypothesized that 5-HT preserves respiratory stability in active sleep by dampening central cholinergic drive. We used whole-body plethysmography coupled with nuchal electromyography to monitor the breathing pattern of 2-wk-old tryptophan hydroxylase 2 ( TPH2)+/+ and TPH2-deficient ( TPH2−/−) pups in active sleep, before and after muscarinic blockade. For the group 1 experiment we injected methylatropine (Ap-M), a CNS-impermeant form of atropine, followed ~30 min later by an injection of atropine sulfate (Ap-S), the CNS-permeant form (both 1 mg/kg, 10 μl bolus iv); both injections occurred within an active sleep episode. We analyzed the effect of each drug on the coefficient of variation of the respiratory period (CV-P) during active sleep. For the group 2 experiment rats were cycled through several episodes of active and quiet sleep before administration of Ap-S (1 mg/kg, 200 μl ip) or vehicle. We assessed the effect of Ap-S on the apnea indices of both genotypes during quiet and active sleep. In group 1 Ap-S significantly reduced the CV-P of TPH2−/− pups ( P = 0.03), an effect not observed in TPH2+/+ pups or following Ap-M. In group 2 the apnea index of TPH2−/− pups was significantly reduced following Ap-S injection ( P = 0.04), whereas the apnea index of TPH2+/+ littermates was unaffected ( P = 0.58). These findings suggest that central 5-HT reduces apnea and stabilizes breathing by reducing cholinergic signaling through muscarinic receptors. NEW & NOTEWORTHY Serotonin in the central nervous system (CNS) is necessary for maintaining the stability of breathing in the early postnatal period, particularly during active sleep. Here we show that the administration of atropine to the CNS selectively stabilizes the respiratory pattern of tryptophan hydroxylase 2-deficient rat pups and reduces their apneas. This suggests that CNS serotonin stabilizes breathing at least in part by reducing central cholinergic drive.

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