Symptoms Of Central Nervous System Disease Research Articles

Study of clinicodemographic profile of acute central nervous system infection in children and its correlation with neuroimaging

Background: Infection of central nervous system (CNS) is most common cause of fever associated with signs and symptoms of CNS disease in children. Viral infections of CNS are more common than other infections. Radiology and pathology go together in understanding etiology causing CNS infections which have similar clinical manifestations making specific diagnosis difficult. The present study aims to study the utility of different neuroimaging patterns in diagnosis of acute CNS infection. Aims include: to study utility and pattern of neuroimaging in CNS infection in paediatric age group, and to study socio-demographic and clinical profile of CNS infection in children.Methods: Prospective observational study in children 1 month-12 years who presented with CNS infection.Results: Total 58 cases were suspected to have CNS infection, which was more prevalent in 1 month-1 year (27.58%), followed by 5-8 year (24.13%), 1-3 year (22.41), >8 year (20.68%) and 3-5 year (5.17%). Neuroimaging was done in all suspected case (58) of CNS infection in which 30 (51.7%) had abnormal neuroimaging where 3(10%) showed pyogenic meningitis, 7 (23.23%) tubercular meningitis (TBM), 4 (13.13%) tuberculoma, 3 (10%) TBM and tuberculoma, 4 (13.3%) viral meningitis, 1 (3.3%) herpes simplex encephalitis (HSE), 1 (3.3%) COVID encephalitis, 4 (13.3%) acute disseminated encephalomyelitis (ADEM) while 2 (6.66%) brain abscess. Correlation between final diagnosis and neuroimaging was 100% in ADEM, brain abscess, tuberculoma, TB spine, HSV followed by TBM (77.77%), pyogenic meningitis (27.27%) and viral encephalitis (26.66%). Clinically diagnosed acute CNS infection was confirmed in 51.72% and wrong in 48.27%.Conclusions: CNS infections were more common in less than 5 years age. Approximately 50% patients had abnormal neuroimaging finding. It was found that neuroimaging was more accurate in early diagnosis, categorization of CNS infection and detection of complications with high sensitivity.

Safety and Efficacy of Emapalumab in Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis

Abstract Introduction: Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare, genetic life-threatening syndrome characterized by hyper-inflammation that is mainly driven by high production of interferon (IFN)-𝛾, leading to the development of fever, splenomegaly, cytopenias and coagulopathy. There are currently no approved treatments for HLH, and recent attempts to improve the dexamethasone/etoposide-based regimen (HLH-94) did not show a significant improvement in overall probability of survival. Emapalumab (NI-0501) is a fully human, anti-IFN-𝛾 monoclonal antibody that binds to and neutralizes IFN-𝛾 and is in development for treatment of HLH. Methods: This open-label pivotal study (NCT01818492) includes patients ≤18 years with a diagnosis of pHLH based on genetic confirmation, family history, or the presence of ≥5 of the 8 HLH-2004 diagnostic criteria. Patients were either treatment-naïve or had failed previous conventional HLH therapy prior to study entry. The emapalumab initial dose was 1 mg/kg given intravenously every 3-4 days. Subsequent doses could be increased up to 10 mg/kg based on the evolution of clinical and laboratory response parameters. Emapalumab was administered concomitantly with 5 to10 mg/m2/day of dexamethasone which could be tapered during the study. Treatment duration was 8 weeks (with possible shortening to a minimum of 4 weeks). Treatment could be extended up to allogeneic hematopoietic stem cell transplantation (HSCT) whenever needed. The primary efficacy endpoint of the study was overall response at end of treatment assessed by pre-defined objective parameters. Overall Response Rate (ORR) was assessed as normalization or at least 50% improvement from baseline of fever, splenomegaly, cytopenias, hyperferritinemia, fibrogen and/or D-Dimer levels, central nervous system (CNS) abnormalities, with no sustained worsening of sCD25 serum levels. The primary analysis used an exact binomial test to evaluate the null hypothesis that ORR be at most 40% at a one-sided 0.025 significance level. Data presented are from 34 patients of whom 27 entered the study after failing conventional HLH therapy. Following completion of the main study patients entered into an extension phase (NCT02069899). The data cut-off applied is July 20 2017. Results: Patient characteristics are summarized in Table 1. Disease presentation at study entry was consistent with the broad spectrum of pHLH abnormalities, both in terms of HLH-2004 diagnostic criteria and other known HLH features; over 30% of patients had signs and/or symptoms of CNS disease. Efficacy results are summarized in Table 2. ORR was significantly higher than the pre-specified null hypothesis of 40%; thus the primary endpoint was met. The response rate based on investigator's clinical judgement was 70.6% and 70.4% in the two groups. Emapalumab infusions were in general well tolerated, with mild to moderate infusion-related reactions reported in 27% of patients. The observed safety events pre-HSCT conditioning mostly included HLH manifestations, infections or toxicities due to other administered drugs. Infections caused by pathogens potentially favored by IFN-𝛾 neutralization occurred in 1 patient during emapalumab treatment (Disseminated histoplasmosis), and resolved with appropriate treatment. No off-target effects were observed. Conclusions: This is the first prospective HLH study that reports response rates based on pre-defined objective criteria. Our results indicate that emapalumab should be considered as a new therapeutic option in pHLH thanks to its targeted mode of action. Treatment with emapalumab was able to control HLH activity with a favorable safety and tolerability profile in a very fragile population. The majority of patients proceeded to HSCT with favorable outcome. Disclosures Jordan: Novimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allen:Novimmune: Membership on an entity's Board of Directors or advisory committees. Sevilla:Rocket Pharmaceuticals Inc: Honoraria, Patents & Royalties; Novimmune: Other: currently participating in and have participated in Novimmune-sponsored clinical trials within the past two years . Grom:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AB2Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; NovImmune: Consultancy, Membership on an entity's Board of Directors or advisory committees. De Benedetti:Novartis: Consultancy, Research Funding; SOBI: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; UCB: Consultancy; Eli-Lylli: Consultancy; Abbvie: Research Funding; Novimmune: Research Funding; Pfizer: Research Funding. Ferlin:Novimmune: Employment, Equity Ownership, Patents & Royalties. Ballabio:Novimmune: Employment, Equity Ownership. De Min:Novimmune: Employment, Equity Ownership.

Cancer of the tonsil presenting as central nervous system metastasis: A case report

Metastases from tonsilar cancers are uncommon, usually found in the lung and less commonly in the bone, liver, and mediastinal sites. Only approximately 20% of patients die from distant metastasis. Central nervous system (CNS) metastases usually appear later in the course of the disease, with only 1% to 2% of patients developing metastasis involving the CNS in the course of their disease. Patients seen with symptomatic CNS lesions are rare. A case report is presented of a patient seen with signs and symptoms of CNS disease from an isolated CNS metastasis. The primary site was ultimately determined to be of tonsilar origin. The patient's treatment and outcome are discussed. Tonsilar cancers seen with signs and symptoms of CNS disease is a rare event. The benefit of aggressive treatment of isolated CNS metastasis from head and neck cancers will likely be gained from case reports because the incidence is quite low.