Early use of high efficacy therapies in pediatric forms of relapsing-remitting multiple sclerosis: A real-life observational study.

Background: Pediatric forms of multiple sclerosis are more active than those in adults. Yet, the effectiveness of different therapeutic approaches is not well studied in this population. Our objective was to compare the effectiveness of the early use of high efficacy therapies (HETs) with the effectiveness of moderate efficacy therapies (METs) in children with MS.

Ocrelizumab versus fingolimod after natalizumab cessation in multiple sclerosis: an observational study.

Background: Exit strategy after natalizumab cessation in multiple sclerosis (MS) is a crucial point because the risk of disease reactivation is high during this period. The objective of this observational study was to compare ocrelizumab to fingolimod after natalizumab cessation in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: All RRMS patients starting fingolimod or ocrelizumab within 6 weeks after natalizumab cessation were included.

CSF interleukin 6 is a useful marker to distinguish pseudotumoral CNS inflammatory diseases from primary CNS lymphoma.

Background: Interleukin 6 (IL-6) is a pleomorphic cytokine that can be found in the cerebrospinal fluid (CSF) in a wide spectrum of inflammatory pathologies of the central nervous system (CNS).

Objective: Our aim was to characterize the diagnostic significance of CSF IL-6 among various CNS inflammatory diseases with pseudotumoral lesions (CNSID) and primary CNS lymphoma (PCNSL).

Methods: We retrospectively analyzed the CSF IL-6 concentrations in 43 consecutive patients with suspected PCNSL.

Optic Nerve Infiltration in Primary Central Nervous System Lymphoma.

Importance: Visual impairment in primary central nervous system lymphoma (PCNSL) is caused mostly by intraocular lymphomatous involvement (vitritis and retinal infiltration), whereas optic nerve infiltration (ONI) is a rare condition.

Objective: To describe the clinical presentation of ONI, its imaging characteristics, and outcome.

Design, Setting And Participants: A total of 752 patients diagnosed with PCNSL were retrospectively identified from the databases of 3 French hospitals from January 1, 1998, through December 31, 2014.

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study.

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated.

Recruitment in pediatric clinical research was influenced by study characteristics and pediatricians' perceptions: a multicenter survey.

Objectives: The aim of this survey was to quantify refusal rates and identify factors of refusal pertaining to studies and recruiting pediatricians in the research recruitment process.

Study Design And Setting: We performed a cross-sectional survey on all clinical studies conducted in six pediatric Clinical Investigation Centers in France over an 18-month period. Data were retrieved using a data collection form for the characteristics of each of the studies included in the survey and a questionnaire addressed to recruiting pediatricians.

Epileptic Amnesic Syndrome revealing Alzheimer's disease.

Objective: To describe the aetiology of a particular form of late-onset temporal lobe epilepsy (TLE) - the Epileptic Amnesic Syndrome (EAS) - that can be responsible for cognitive decline. The syndrome is considered as a reversible cause of memory disturbances, but some patients remain unrelieved despite anticonvulsants.

Design: 4 case-reports and a brief discussion.

Validation of a risk-assessment scale and a risk-adapted monitoring plan for academic clinical research studies--the Pre-Optimon study.

Context: Good Clinical Practice regulates monitoring activities in clinical research. Due to question and design diversity, and limited resources, on-site monitoring is often less intensive in the academic context, and variable. Standardization is needed, and relies on definition and validation of tools accounting for risk.

PHOX2B germline and somatic mutations in late-onset central hypoventilation syndrome.

Rationale: Late-onset central hypoventilation syndrome (LO-CHS) is a rare disorder that may manifest as early as infancy or as late as during adulthood. The potential overlap of LO-CHS with congenital CHS is under debate, even though both disorders can result from heterozygous PHOX2B gene mutations.

Objectives: To characterize the PHOX2B status in a series of 25 patients with LO-CHS referred from 3 months of age to adulthood.

Noninvitation of eligible individuals to participate in pediatric studies: a qualitative study.

Objective: To identify subjective factors that lead investigators not to invite eligible individuals to participate in pediatric studies.

Design: Qualitative study with semistructured interviews.

Setting: Four pediatric teaching hospitals in Paris.

Transgenic models to study disorders of respiratory control in newborn mice.

Recent studies described the in vivo respiratory phenotype of mutant newborn mice with targeted deletions of genes involved in respiratory control development. Whole-body flow barometric plethysmography is the noninvasive method of choice for studying unrestrained newborn mice. The main characteristics of the early postnatal development of respiratory control in mice are reviewed, including available data on breathing patterns and on hypoxic and hypercapnic ventilatory responses.

Development of respiratory control: evolving concepts and perspectives.

The mechanisms underlying respiratory system immaturity in newborns have been investigated, both in vivo and in vitro, in humans and in animals. Immaturity affects breathing rhythmicity and its modulation by suprapontine influences and by afferents from central and peripheral chemoreceptors. Recent research has moved from bedside tools to sophisticated technologies, bringing new insights into the plasticity and genetics of respiratory control development.

Pediatric disorders with autonomic dysfunction: what role for PHOX2B?

Hirschsprung disease, neuroblastomas, and congenital central hypoventilation syndrome can occur in combination, and familial cases have been reported in all three conditions. This suggests variable expression of a single genetic abnormality as the common cause to these neural crest disorders. Because the PHOX2B gene is pivotal in the development of most relays of the autonomic nervous system, including all autonomic neural crest derivatives, it was considered a candidate gene for the above conditions.

Sleep-disordered breathing in newborn mice heterozygous for the transcription factor Phox2b.

Rationale: Central congenital hypoventilation syndrome (CCHS) is a rare autosomal dominant syndrome present from birth, and characterized by depressed ventilation during sleep. Heterozygous mutations of the homeobox gene Phox2b were recently found in a very high proportion of patients.

Objectives: To determine whether newborn mice with heterozygous targeted deletion of the transcription factor Phox2b would display sleep-disordered breathing.

PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome.

The Phox2b gene is necessary for autonomic nervous-system development. Phox2b-/- mice die in utero with absent autonomic nervous system circuits, since autonomic nervous system neurons either fail to form or degenerate. We first identified the Phox2b human ortholog, PHOX2B, as the gene underlying congenital central hypoventilation syndrome (CCHS, or Ondine curse), with an autosomal dominant mode of inheritance and de novo mutation at the first generation.

The French Congenital Central Hypoventilation Syndrome Registry: general data, phenotype, and genotype.

Objective: To analyze the main clinical features, genetic mutations, and outcomes of patients of the French Congenital Central Hypoventilation Syndrome (CCHS) Registry.

Design: A country-wide cohort established throughout a long-term multicenter effort.

Patients: Seventy French patients with CCHS (29 male patients and 41 female patients).

PHOX2B gene mutation in a patient with late-onset central hypoventilation.

Congenital central hypoventilation syndrome, which is related to abnormal autonomic control of breathing and typically manifests at birth, was recently associated with PHOX2B gene mutations. In contrast, central hypoventilation with later onset constitutes a poorly defined group of unknown etiology. Here, we report on the identification of a de novo heterozygous PHOX2B mutation in a patient with central hypoventilation manifesting in childhood.

Genes and genetics in respiratory control.

The genetic approach to respiratory control is opening up new paths for research into developmental respiratory control disorders. Despite the identification of numerous genes involved in respiratory control, none of the genetically engineered mice developed to date fully replicate the human respiratory phenotype of human developmental respiratory disorders. However, combining studies in humans and studies in mouse models has proved useful in identifying candidate genes for human developmental respiratory control disorders and providing pathogenic information.

Effects of warm and cool thermal conditions on ventilatory responses to hyperoxic test in neonates.

Body temperature interacts with respiratory control, but it is unclear what sites or mechanisms mediate those interactions. We hypothesized that warm and cool thermal conditions affect the decrease in ventilation (VE) seen during the hyperoxic test (HT), a breathing response believed to reflect the strength of the peripheral chemoreceptor drive. A breath-by-breath analysis during a 30 s HT was performed in eight premature neonates (postconceptional age: 36 +/- 1 weeks) under neutral, warm, and cool thermal conditions.