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ABSTRACT: Pediatric multiple sclerosis (MS) accounts for up to 5% of all MS cases. Work conducted over the past 5 years has provided new information about the treatment, pathogenesis, demographics, and natural history of this disorder. Genetic and environmental factors seem to exert critical influences on its development. Clinical, MRI and laboratory data from prepubertal and postpubertal children suggest differences between the immune response and/or CNS environment in younger compared with older children and adults with MS. Randomized, controlled treatment trials for pediatric MS have not yet been performed, but therapies used in adult MS have been evaluated in this population, and their use seems to be safe. This article provides a comprehensive review of current knowledge regarding pediatric MS, highlighting new advances in the field.
Nature Reviews Neurology 10/2009; 5(11):621-31. · 12.46 Impact Factor
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ABSTRACT: Distinguishing between a first episode of multiple sclerosis and acute disseminated encephalomyelitis in children who present with an initial demyelinating event can be a clinical challenge. New brain MRI criteria that aim to differentiate these clinical presentations, and revised McDonald MRI criteria specific for the pediatric population, are both worthy of note.
Nature Reviews Neurology 05/2009; 5(4):186-8. · 12.46 Impact Factor
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ABSTRACT: To evaluate eating behavior and energy balance as a cause of increased body mass index (BMI) in narcolepsy.
Case controlled pilot study.
University hospital.
13 patients with narcolepsy (7 "typical" patients, with HLA DQB1*0602 and clear cut cataplexy, with suspected hypocretin deficiency; and 6 "atypical" narcoleptics, i.e., HLA negative or without cataplexy), and 9 healthy controls matched for age, gender, and ethnicity.
Energy balance was evaluated by measuring BMI, rest energy expenditure with calorimetry, daily food and water intake, and plasma hormone levels. Eating behavior was evaluated using psychometric tests (EAT-40, EDI2, CIDI-2, MADRS).
Patients with narcolepsy (whether typical or not) tended to be overweight and to have a lower basal metabolism than controls. Only patients with typical narcolepsy tended to eat less than controls. Narcoleptic patients who were overweight ate half as much as others, indicating caloric restriction. Plasma glucose, cortisol, thyroid, and sex hormones levels did not differ between groups, while prolactin levels were twice as high in patients with narcolepsy as in controls. Narcoleptic patients had higher EAT-40 scores and more frequent features of bulimia nervosa (independent of depressive mood) than controls, suggesting a mild eating disorder, classified as "Eating Disorder Not Other Specified."
Both lower basal metabolism and subtle changes in eating behavior (rather than in calorie intake) could explain the positive energy balance leading to overweight in narcolepsy. Eating behavior changes may be a strategy to control weight or to avoid daytime sleepiness.
Sleep 11/2007; 30(10):1267-73. · 5.05 Impact Factor
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ABSTRACT: To identify the neural structures and pathways underlying cataplexy during status cataplecticus in a narcoleptic patient, using brain perfusion single photon emission computed tomography (SPECT).
A 68-year-old woman with hypocretin-deficient narcolepsy-cataplexy suffered status cataplecticus after having stopped clomipramine. She underwent a 99mTc-ethylcysteinate dimer brain SPECT during an episode of cataplexy; this image was compared with her brain SPECT during an intervening asymptomatic period. Subtraction SPECT coregistered to magnetic resonance imaging (MRI)(SISCOM)-determined anatomic areas differentially perfused during cataplexy and basal wakefulness state.
The areas hyperactivated during cataplexy corresponded on brain MRI with the cingular area, the left and right orbitofrontal cortex, the right temporal cortex, and the right putamen. No significant hypoperfused region was observed during the cataplectic episode.
Cataplexy during status cataplecticus partially resembles normal rapid eye movement sleep (with high cingular, orbitofrontal, and putamen activity) but without the other imaging characteristics of this state (no hyperactivation of the pons, amygdale, or occipital cortex).
Sleep 03/2007; 30(2):153-6. · 5.05 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) occurs at all ages of the pediatric population. Childhood MS may represent up to 10% of all MS cases. Establishing the diagnosis of MS in a child is complicated by the limited diagnostic criteria and the possibility of significant clinical and magnetic resonance imaging (MRI) overlap with acute disseminated encephalomyelitis and other pediatric diseases. Although the clinical profile of MS appears similar to that seen in adults, several features may differ and specific issues arise in children. Sex ratios are different between young children with MS and adolescents--implicating a role for sex hormones in disease pathogenesis and/or modification of disease expression. Younger patients with MS are more likely to have seizures, brainstem, and cerebellar symptoms than adults. Children with MS may have fewer T2 hyperintense areas on MRI scans, therefore not meeting MRI criteria established for adults. It is possible that the pediatric MS course is more indolent than in adult patients but the disease may lead to significant disability at a younger age, e.g., while patients are students, young professionals, or want to start a family. There has been no controlled clinical trial in children with disease modifying therapies approved for adult MS due to the limited number of patients under the age of 18 years compared with the adult contingent. As a result, children are receiving adult therapies in an arbitrary manner and our understanding of pediatric treatment effect and tolerability is limited. Available data on tolerability of approved drugs for adults is reviewed.
NeuroRx 05/2006; 3(2):264-75.
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Dorothée Chabas
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ABSTRACT: Osteopontin (OPN) was initially isolated from bovine bone cortex, as a complex syalilated phospho-glyco-protein of around 60 kDa, with many postranslational modifications. It has been long considered a structural bone protein linking bone cells to the bone extracellular matrix (osteo : bone, pontin : bridge). It has been cloned for the first time in 1986. Since then, it was established that it is part of a protein family called SIBLINGs, which genes share common expression in bone and tooth, and encode among others a RGD motif. OPN is an intracellular as well as secreted protein, which binds to multiple organic or mineral ligands, like the integrin receptor alphaVbeta3, CD44, factor H and hydroxyapatite, depending on its final configuration (phosphorylation state). Pleiotropic functions of osteopontin have been demonstrated, and the osteopontin knock out phenotype in mice gave some new insight on the implication of the molecule in vivo. Osteopontin inhibits mineralization in bone and urine. Besides, it is a strong chemoattractive and proinflammatory molecule, implicated in tumors, like breast or prostate cancers, and in the defense against various infectious agents like tuberculosis, listeria or herpes. More recently, its key implication in TH1 mediated autoimmune diseases like multiple sclerosis and its animal model experimental autoimmune encephalomyelitis has been demonstrated. Osteopontin is a valuable therapeutic target in the animal model, and a biological tool correlating with clinical disease activity in humans. Structural, functional and pathological aspects of osteopontin are reviewed, as well as the osteopontin deficient phenotype in mouse.
Medecine sciences: M/S 11/2005; 21(10):832-8. · 0.64 Impact Factor
