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pediatric neuroinflammatory

Evangeline Wassmer, Tanuja Chitnis, Daniela Pohl, Maria Pia Amato, Brenda Banwell, Angelo Ghezzi, Rogier Q Hintzen, Lauren B Krupp, Naila Makhani, Kevin Rostásy, Marc Tardieu, Silvia Tenembaum, Amy Waldman, Emmanuelle Waubant, Andrew J Kornberg
The International Pediatric Multiple Sclerosis Study Group held its inaugural educational program, "The World of Pediatric MS: A Global Update," in September 2014 to discuss advances and challenges in the diagnosis and management of pediatric multiple sclerosis (MS) and other neuroinflammatory CNS disorders. Highlights included a discussion on the revised diagnostic criteria, which enable the differentiation of MS, acute disseminated encephalomyelitis, neuromyelitis optica, and other neuroinflammatory disorders...
August 30, 2016: Neurology
Nathalie Strazielle, Jean-François Ghersi-Egea
The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation...
July 26, 2016: Current Pharmaceutical Design
Geoffrey C Owens, Julia W Chang, My N Huynh, Thabiso Chirwa, Harry V Vinters, Gary W Mathern
Rasmussen encephalitis (RE) is a rare pediatric neuroinflammatory disease of unknown etiology characterized by intractable seizures, and progressive atrophy usually confined to one cerebral hemisphere. Surgical removal or disconnection of the affected cerebral hemisphere is currently the only intervention that effectively stops the seizures. Histopathological evaluation of resected brain tissue has shown that activated brain resident macrophages (microglia) and infiltrating T cells are involved in the inflammatory reaction...
2016: Frontiers in Immunology
Philippe Horellou, Min Wang, Vixra Keo, Pascale Chrétien, Ché Serguera, Patrick Waters, Kumaran Deiva
Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MOG)...
December 15, 2015: Journal of Neuroimmunology
George P Liao, Matthew T Harting, Robert A Hetz, Peter A Walker, Shinil K Shah, Christopher J Corkins, Travis G Hughes, Fernando Jimenez, Steven C Kosmach, Mary-Clare Day, KuoJen Tsao, Dean A Lee, Laura L Worth, James E Baumgartner, Charles S Cox
OBJECTIVES: The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post-traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow-derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow-derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls...
March 2015: Pediatric Critical Care Medicine
Ajay Kumar, Mitchel T Williams, Harry T Chugani
We applied PET scanning with (11)C-[R]-PK11195 (PK) to evaluate neuroinflammatory changes in basal ganglia and thalamus in children with clinically diagnosed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and Tourette syndrome. Seventeen children with PANDAS (mean age: 11.4 ± 2.6 years; 13 males), 12 with Tourette syndrome (mean age: 11.0 ± 3.0 years; 10 males), and 15 normal adults (mean age: 28.7 ± 7.9 years; 8 males) underwent dynamic PK PET imaging and binding potential, a measure of ligand-TSPO receptor (expressed by activated microglia) binding, was calculated for basal ganglia and thalamus...
May 2015: Journal of Child Neurology
Mehdi Ghasemi, Ali Fatemi
It is well established that glial cells have critical roles in the inflammatory processes in the central nervous system (CNS). These cells can be activated by a variety of endogenous and exogenous stimuli (i.e. gliosis) and can produce high levels of bioactive compounds that are noxious for neuronal cell function. One of the most important molecules released by activated glial cells is the bioactive free radical nitric oxide (NO). Although NO physiologically acts as both neuromodulator and neurotransmitter in the brain, excess production of NO by glial cells has diverse harmful effects on neuronal function, causing neuronal cell injury/death...
September 2014: Neuroscience and Biobehavioral Reviews
Russell C Dale, Fabienne Brilot, Lisa V Duffy, Marinka Twilt, Amy T Waldman, Sona Narula, Eyal Muscal, Kumaran Deiva, Erik Andersen, Michael R Eyre, Despina Eleftheriou, Paul A Brogan, Rachel Kneen, Gulay Alper, Banu Anlar, Evangeline Wassmer, Kirsten Heineman, Cheryl Hemingway, Catherine J Riney, Andrew Kornberg, Marc Tardieu, Amber Stocco, Brenda Banwell, Mark P Gorman, Susanne M Benseler, Ming Lim
OBJECTIVE: To assess the utility and safety of rituximab in pediatric autoimmune and inflammatory disorders of the CNS. METHODS: Multicenter retrospective study. RESULTS: A total of 144 children and adolescents (median age 8 years, range 0.7-17; 103 female) with NMDA receptor (NMDAR) encephalitis (n = 39), opsoclonus myoclonus ataxia syndrome (n = 32), neuromyelitis optica spectrum disorders (n = 20), neuropsychiatric systemic lupus erythematosus (n = 18), and other neuroinflammatory disorders (n = 35) were studied...
July 8, 2014: Neurology
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee, Steven J Verhulst
Using a panel of seven brain cell-specific biomarkers in cerebrospinal fluid (CSF), pediatric opsoclonus-myoclonus syndrome (OMS) (n=234) was compared to pediatric non-inflammatory neurological controls (n=84) and other inflammatory neurological disorders (OIND) (n=44). Only CSF NFL was elevated in untreated OMS versus controls (+83%). It was 87% higher in OIND than in OMS. On combination treatment with front-loaded ACTH, IVIg, rituximab, median CSF NFL decreased by 60% to control levels. These biochemical data suggest neuronal/axonal injury in some children with OMS without indicators of astrogliosis, and reduction on sufficient immunotherapy...
January 15, 2014: Journal of Neuroimmunology
Wojciech Wiszniewski, Jill V Hunter, Neil A Hanchard, Jason R Willer, Chad Shaw, Qi Tian, Anna Illner, Xueqing Wang, Sau W Cheung, Ankita Patel, Ian M Campbell, Violet Gelowani, Patricia Hixson, Audrey R Ester, Mahshid S Azamian, Lorraine Potocki, Gladys Zapata, Patricia P Hernandez, Melissa B Ramocki, Regie L P Santos-Cortez, Gao Wang, Michele K York, Monica J Justice, Zili D Chu, Patricia I Bader, Lisa Omo-Griffith, Nirupama S Madduri, Gunter Scharer, Heather P Crawford, Pattamawadee Yanatatsaneejit, Anna Eifert, Jeffery Kerr, Carlos A Bacino, Adiaha I A Franklin, Robin P Goin-Kochel, Gayle Simpson, Ladonna Immken, Muhammad E Haque, Marija Stosic, Misti D Williams, Thomas M Morgan, Sumit Pruthi, Reed Omary, Simeon A Boyadjiev, Kay K Win, Aye Thida, Matthew Hurles, Martin Lloyd Hibberd, Chiea Chuen Khor, Nguyen Van Vinh Chau, Thomas E Gallagher, Apiwat Mutirangura, Pawel Stankiewicz, Arthur L Beaudet, Mirjana Maletic-Savatic, Jill A Rosenfeld, Lisa G Shaffer, Erica E Davis, John W Belmont, Sarah Dunstan, Cameron P Simmons, Penelope E Bonnen, Suzanne M Leal, Nicholas Katsanis, James R Lupski, Seema R Lalani
White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ~70% of young carrier parents who underwent brain MRI...
August 8, 2013: American Journal of Human Genetics
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee, Jerry A Colliver
OBJECTIVE: To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). METHODS: Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND))...
March 15, 2013: Journal of the Neurological Sciences
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee, Anna L Travelstead, Jerry A Colliver, Jayne M Ness, Richard M Ransohoff
BACKGROUND: B-cell dysregulation has been implicated but not fully characterized in pediatric opsoclonus-myoclonus syndrome (OMS), a neuroblastoma-associated neuroinflammatory disorder. OBJECTIVE: To assess the role of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two critical B cell-modulating cytokines, as potential biomarkers of disease activity and treatment biomarkers in OMS. METHODS: Soluble BAFF and APRIL were measured in cerebrospinal fluid (CSF) and serum by ELISA in 433 children (296 OMS, 109 controls, 28 other inflammatory neurological disorders (OIND))...
2013: Journal of Neuroinflammation
E Muscal, R L Brey
The most common neurological manifestations of antiphospholipid syndrome (APS) in all age-groups include stroke and transient ischemic attacks due to arterial thromboses and cerebral ischemia. Antiphospholipid antibodies may cause additional non-criteria neurological impairments through vascular, neuroinflammatory and direct neuronal effects. Anti-aggregant or anticoagulant therapies are indicated for APS-related ischemic strokes. Treatment regimens for asymptomatic antibody-positive patients and those with refractory or recurrent disease remain controversial...
April 2010: Lupus
Ubaid Hameed Shah, Veena Kalra
Migraine is the most common cause of acute recurrent headaches in children. The pathophysiological concepts have evolved from a purely vascular etiology to a neuroinflammatory process. Clinical evaluation is the mainstay of diagnosis and should also include family history. Investigations help to rule out secondary causes. The role of new drugs in treatment of migraine is discussed and trials are quoted from literature. Indications for starting prophylaxis should be evaluated based on frequency of attacks and influence on quality of life...
2009: International Journal of Pediatrics
Lynnae Schwartz, Eugene O Major
The human immunodeficiency virus type 1 (HIV-1) is a neurotrophic lentivirus that enters and infects the central nervous system (CNS) of adults and children, giving rise to the clinical syndromes of AIDS-dementia complex (ADC) in adults and HIV-1-associated progressive encephalopathy (PE) in pediatric patients. The clinical presentation and progression of neuroAIDS in the developing brain of children is distinct from that seen in adult patients. Neuroimaging, and upon autopsy, neuropathological findings corresponding to clinical disease in pediatric patients include impaired brain growth, reactive gliosis, myelin pallor, calcifications of the basal ganglia, cortical and cerebral atrophy with neuronal loss and ventricular enlargement, and abnormalities of cerebral vasculature...
July 2006: Current HIV Research
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