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pediatric neuroinflammatory

Federica Zibordi, Zorzi Giovanna, Carecchio Miryam, Nardocci Nardo
The terms Pediatric Autoimmune Neuropsychiatric disorders associated with streptococcal infections (PANDAS), Pediatric acute-onset neuropsychiatric Syndrome (PANS), and Childhood Acute Neuropsychiatric Symptoms (CANS) have been used to describe certain acute onset neuropsychiatric pediatric disorders. This clinical characteristic was unusually abrupt onset of obsessive compulsive symptoms and/or severe eating restrictions and concomitant cognitive, behavioral or neurological symptoms. Because the CANS/PANS criteria define a broad spectrum of neuropsychiatric conditions, the syndrome is presumed to result from a variety of disease mechanisms and to have multiple etiologies, ranging from postinfectious autoimmune and neuroinflammatory disorders to toxic, endocrine or metabolic disorders...
February 1, 2018: European Journal of Paediatric Neurology: EJPN
Rinze Neuteboom, Colin Wilbur, Danielle Van Pelt, Moses Rodriguez, Ann Yeh
Acquired demyelinating syndromes in childhood comprise a spectrum of monophasic and recurrent inflammatory conditions of the central nervous system. Examples of monophasic conditions include, clinically isolated syndromes such as optic neuritis and transverse myelitis, as well as acute disseminated encephalomyelitis, whereas recurrent disorders include entities such as multiple sclerosis and neuromyelitis optica spectrum disorder. Knowledge about these disorders has expanded due to rigorously evaluated diagnostic criteria, magnetic resonance imaging features, outcomes, and serum biomarkers in these disorders...
August 2017: Seminars in Pediatric Neurology
Shayne Mason, Carolus J Reinecke, Regan Solomons
Background: In Africa, tuberculosis is generally regarded as persisting as one of the most devastating infectious diseases. The pediatric population is particularly vulnerable, with infection of the brain in the form of tuberculous meningitis (TBM) being the most severe manifestation. TBM is often difficult to diagnose in its early stages because of its non-specific clinical presentation. Of particular concern is that late diagnosis, and subsequent delayed treatment, leads to high risk of long-term neurological sequelae, and even death...
2017: Frontiers in Neuroscience
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee
OBJECTIVE: To assess the role of microglia and macrophages in neuroinflammatory disorders in children via biomarkers, and establish control reference ranges. METHODS: In an IRB-approved case-control study of 98 children, the concentrations of CSF/serum CHI3L1, sCD14, and sCD163 were measured by ELISA. Groups were controls (non-inflammatory neurological disorders, NIND, n=37), opsoclonus-myoclonus syndrome (OMS, n=37), and other inflammatory neurological disorders (OIND, n=24)...
October 15, 2017: Journal of the Neurological Sciences
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee
Pediatric-onset opsoclonus-myoclonus syndrome (OMS) is a devastating neuroinflammatory, often paraneoplastic, disorder. The objective was to characterize demographic, clinical, and immunologic aspects in the largest cohort reported to date. Cross-sectional data were collected on 389 children in an IRB-approved, observational study at the National Pediatric Myoclonus Center. Non-parametric statistical analysis was used. OMS manifested in major racial/ethnic groups, paralleling US population densities. Median onset age was 1...
2017: Frontiers in Neurology
Mark Borchert, Grant T Liu, Stacy Pineles, Amy T Waldman
Few diseases blur the margins between their childhood and adult-onset varieties as much as optic neuritis. This report will review our state of knowledge of pediatric optic neuritis, as well as its relationship to the latest consensus definitions of neuroinflammatory disease. Current diagnostic and treatment options will be explored, as well as our potential to uncover an understanding of pediatric optic neuritis through systematic prospective studies. The risk of evolving multiple sclerosis is probably less than in adults, but pediatric optic neuritis is more likely to be an initial manifestation of acute disseminated encephalomyelitis...
September 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
Sathya Vadivelu, Sudhakar Vadivelu, Maureen Mealy, Smurti Patel, Libby Kosnik-Infinger, Daniel Becker
PURPOSE: Transverse myelitis (TM) is an acute inflammatory spinal cord injury. Asymptomatic Chiari I malformation (CMI) management is highly controversial, particularly when associated with a spinal syrinx. Here, we assess the occurrence of CMI in the pediatric TM population and management outcomes. METHODS: We performed a retrospective cohort study based on 61 consecutively identified pediatric TM cases over an -8-year period. We reviewed demographic characteristics, radiographic findings, presenting symptoms, and long-term outcomes...
May 24, 2017: Developmental Neurorehabilitation
Yimeng Xia, Heng Xu, Chenfei Jia, Xiaodong Hu, Yu Kang, Xiaoxuan Yang, Qingsheng Xue, Guorong Tao, Buwei Yu
BACKGROUND: Sevoflurane is the most widely used inhalational anesthetic in pediatric medicine. Despite this, sevoflurane has been reported to exert potentially neurotoxic effects on the developing brain. Clinical interventions and treatments for these effects are limited. Tanshinone IIA (Tan IIA), extracted from Salvia miltiorrhiza (Danshen), has been documented to alleviate cognitive decline in traditional applications. Therefore, we hypothesized that preadministration of Tan IIA may attenuate sevoflurane-induced neurotoxicity, suggesting that Tan IIA is a new and promising drug capable of counteracting the effects of cognitive dysfunction produced by general anesthetics...
April 2017: Anesthesia and Analgesia
X Zhang, F Liu, W Slikker, C Wang, M G Paule
The association of general anesthesia with developmental neurotoxicity, while nearly impossible to study in pediatric populations, is clearly demonstrable in a variety of animal models from rodents to nonhuman primates. Nearly all general anesthetics tested have been shown to cause abnormal brain cell death in animals when administered during periods of rapid brain growth. The ability to repeatedly assess in the same subjects adverse effects induced by general anesthetics provides significant power to address the time course of important events associated with exposures...
March 2017: Neurotoxicology and Teratology
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 bloodbrain 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 addedvalue 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...
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
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