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Abstract The gibbon ape leukemia virus (GALV), the amphotropic murine leukemia virus (AMLV) and the human T-cell leukemia virus (HTLV) are retroviruses that specifically bind nutrient transporters with their envelope glycoproteins (Env) when entering host cells. Here, we used tagged ligands derived from GALV, AMLV, and HTLV Env to monitor the distribution of their cognate receptors, the inorganic phosphate transporters PiT1 and PiT2, and the glucose transporter GLUT1, respectively, in basal conditions and after acute energy deficiency. For this purpose, we monitored changes in the distribution of PiT1, PiT2 and GLUT1 in the cerebellum, the frontal cortex, the corpus callosum, the striatum and the substantia nigra (SN) of C57/BL6 mice after administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridinium (MPTP), a mitochondrial complex I inhibitor which induces neuronal degeneration in the striato-nigral network. The PiT1 ligand stained oligodendrocytes in the corpus callosum and showed a reticular pattern in the SN. The PiT2 ligand stained particularly the cerebellar Purkinje cells, while GLUT1 labelling was mainly observed throughout the cortex, basal ganglia and cerebellar gray matter. Interestingly, unlike GLUT1 and PiT2 distributions which did not appear to be modified by MPTP intoxication, PiT1 immunostaining seemed to be more extended in the SN. The plausible reasons for this change following acute energy stress are discussed. These new ligands therefore constitute new metabolic markers which should help to unravel cellular adaptations to a wide variety of normal and pathologic conditions and to determine the role of specific nutrient transporters in tissue homeostasis.

LAMA2-related dystrophies (LAMA2-RD) are rare neuromuscular diseases related to complete or partial merosin deficiency. They represent one of the most common forms of congenital muscular dystrophies worldwide. The clinical manifestations of LAMA2-RD range from severe early-onset to mild later childhood-onset LGMD-like. Presently, there are no approved therapies available for LAMA2-RD. Several promising strategies are currently in pre-clinical development. Due to the variability of the phenotype, it is important to determine the best outcome measure to assess the efficacy of future therapies and the prognostic factors for the disease. We present here a prospective study of the pathophysiology of LAMA2-RD to characterize the disease course by using standardized evaluations. A total of 40 patients with LAMA2-RD, aged from 2 to 15 years, are planned to be enrolled in France and followed for a 2 year period. Visits are performed every 6 months. The assessments are adjusted to age, ambulatory and respiratory status. Evaluations include clinical exam, pulmonary function tests, strength and motor function assessments by using upper limb-specific devices and common scales, timed function tests, and quality of life and burden of care questionnaires. Two consequent muscle MRI are planned at the beginning and the end of the study. Blood and urine samples are collected for biochemical analysis and residual samples are included in biobanks. Samples will also be analyzed in a biomarkers ancillary study (plasmatic analysis by nanoDSF). Data from the patients' usual follow-up care is collected from medical files including psychomotor development, respiratory, cardiac, neurologic and feeding status. The obtained data will help to characterize the course of disease and the spectrum of LAMA2-RD disease at national level and may help to empower future therapeutic studies. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding using in vitro culture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fantou, Lagrue, Laurent, Delbos, Blandin, Jarry, Beriou, Braudeau, Salabert, Marin, Moreau, Podevin, Bourreille, Josien and Martin.)

Muscular dystrophies due to heterozygous pathogenic variants in LMNA gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. The natural history of these conditions is not well defined, particularly in patients with congenital or early onset who arguably present with the highest disease burden. Thus the definition of natural history endpoints along with clinically revelant outcome measures is essential to establishing both clinical care planning and clinical trial readiness for this patient group. We designed a large international cross-sectional retrospective natural history study of patients with genetically proven muscle laminopathy who presented with symptoms before two years of age intending to identify and characterize an optimal clinical trial cohort with pertinent motor, cardiac and respiratory endpoints. Quantitative statistics were used to evaluate associations between LMNA variants and distinct clinical events. The study included 151 patients (median age at symptom onset 0.9   years, range: 0.0-2.0). Age of onset and age of death were significantly lower in patients who never acquired independent ambulation compared to patients who achieved independent ambulation. Most of the patients acquired independent ambulation (n = 101, 66.9%), and subsequently lost this ability (n = 86; 85%). The age of ambulation acquisition (median: 1.2 years, range: 0.8-4.0) and age of ambulation loss (median: 7 years, range: 1.2-38.0) were significantly associated with the age of the first respiratory interventions and the first cardiac symptoms. Respiratory and gastrointestinal interventions occurred during first decade while cardiac interventions occurred later. Genotype-phenotype analysis showed that the most common mutation, p.Arg249Trp (20%), was significantly associated with a more severe disease course. This retrospective natural history study of early onset LMNA -related muscular dystrophy confirms the progressive nature of the disorder, initially involving motor symptoms prior to onset of other symptoms (respiratory, orthopaedic, cardiac and gastrointestinal). The study also identifies subgroups of patients with a range of long-term outcomes. Ambulatory status was an important mean of stratification along with the presence or absence of the p.Arg249Trp mutation. These categorizations will be important for future clinical trial cohorts. Finally, this study furthers our understanding of the progression of early onset LMNA -related muscular dystrophy and provides important insights into the anticipatory care needs of LMNA -related respiratory and cardiac manifestations., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Ventilating a young patient via a tracheostomy remains an invasive method to tackle the respiratory compromise often observed in several neuromuscular disorders. This approach significantly impacts the schooling of these children. The authors have surveyed professionals dealing with education, care, or social support nationwide. Regional discrepancies in practices of schooling in such situations are noted. Tracheostomy seems a major factor of exclusion out of the ordinary schooling system., (© 2020 médecine/sciences – Inserm.)

Objective: To clarify the prevalence, long-term natural history, and severity determinants of SEPN1 -related myopathy (SEPN1-RM), we analyzed a large international case series., Methods: Retrospective clinical, histologic, and genetic analysis of 132 pediatric and adult patients (2-58 years) followed up for several decades., Results: The clinical phenotype was marked by severe axial muscle weakness, spinal rigidity, and scoliosis (86.1%, from 8.9 ± 4 years), with relatively preserved limb strength and previously unreported ophthalmoparesis in severe cases. All patients developed respiratory failure (from 10.1±6 years), 81.7% requiring ventilation while ambulant. Histopathologically, 79 muscle biopsies showed large variability, partly determined by site of biopsy and age. Multi-minicores were the most common lesion (59.5%), often associated with mild dystrophic features and occasionally with eosinophilic inclusions. Identification of 65 SEPN1 mutations, including 32 novel ones and the first pathogenic copy number variation, unveiled exon 1 as the main mutational hotspot and revealed the first genotype-phenotype correlations, bi-allelic null mutations being significantly associated with disease severity ( p = 0.017). SEPN1-RM was more severe and progressive than previously thought, leading to loss of ambulation in 10% of cases, systematic functional decline from the end of the third decade, and reduced lifespan even in mild cases. The main prognosis determinants were scoliosis/respiratory management, SEPN1 mutations, and body mass abnormalities, which correlated with disease severity. We propose a set of severity criteria, provide quantitative data for outcome identification, and establish a need for age stratification., Conclusion: Our results inform clinical practice, improving diagnosis and management, and represent a major breakthrough for clinical trial readiness in this not so rare disease., (© 2020 American Academy of Neurology.)

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination-Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age., Results: Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking., Conclusion: Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation., Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]., Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach., Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

Objective: To genotypically and phenotypically characterize a large pediatric myotonic dystrophy type 1 (DM1) cohort to provide a solid frame of data for future evidence-based health management., Methods: Among the 2,697 patients with genetically confirmed DM1 included in the French DM-Scope registry, children were enrolled between January 2010 and February 2016 from 24 centers. Comprehensive cross-sectional analysis of most relevant qualitative and quantitative variables was performed., Results: We studied 314 children (52% females, with 55% congenital, 31% infantile, 14% juvenile form). The age at inclusion was inversely correlated with the CTG repeat length. The paternal transmission rate was higher than expected, especially in the congenital form (13%). A continuum of highly prevalent neurodevelopmental alterations was observed, including cognitive slowing (83%), attention deficit (64%), written language (64%), and spoken language (63%) disorders. Five percent exhibited autism spectrum disorders. Overall, musculoskeletal impairment was mild. Despite low prevalence, cardiorespiratory impairment could be life-threatening, and frequently occurred early in the first decade (25.9%). Gastrointestinal symptoms (27%) and cataracts (7%) were more frequent than expected, while endocrine or metabolic disorders were scarce., Conclusions: The pedDM-Scope study details the main genotype and phenotype characteristics of the 3 DM1 pediatric subgroups. It highlights striking profiles that could be useful in health care management (including transition into adulthood) and health policy planning., (© 2019 American Academy of Neurology.)

Objectives Autism spectrum disorders and intellectual disability present a challenge for therapeutic and dietary management. We performed a re-analysis of plasma amino acid chromatography of children with autism spectrum disorders ( n = 22) or intellectual disability ( n = 29) to search for a metabolic signature that can distinguish individuals with these disorders from controls ( n = 30). Methods We performed univariate and multivariate analyses using different machine learning strategies, from the raw data of the amino acid chromatography. Finally, we analysed the metabolic pathways associated with discriminant biomarkers. Results Multivariate analysis revealed models to discriminate patients with autism spectrum disorders or intellectual disability and controls from plasma amino acid profiles ( P < 0.0003). Univariate analysis showed that autism spectrum disorder and intellectual disability patients shared similar differences relative to controls, including lower glutamate ( P < 0.0001 and P = 0.0002, respectively) and serine ( P = 0.002 for both) concentrations. The multivariate model ( P < 6.12.10 -7 ) to discriminate between autism spectrum disorders and intellectual disability revealed the involvement of urea, 3-methyl-histidine and histidine metabolism. Biosigner analysis and univariate analysis confirmed the role of 3-methylhistidine ( P = 0.004), histidine ( P = 0.003), urea ( P = 0.0006) and lysine ( P = 0.002). Conclusions We revealed discriminant metabolic patterns between autism spectrum disorders, intellectual disability and controls. Amino acids known to play a role in neurotransmission were discriminant in the models comparing autism spectrum disorders or intellectual disability to controls, and histidine and b-alanine metabolism was specifically highlighted in the model.

Objective: Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2-deficient mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with RTT., Methods: The trial was a 6-month, multicenter, randomized, double-blind, placebo-controlled study registered with ClinicalTrials.gov, number NCT00990691. Girls diagnosed according to clinical examination and confirmed by genotyping were randomly assigned in a 1:1:1 ratio to receive 2-3 mg/kg Desipramine per day (high Desipramine), 1-2 mg/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome was the change of apnea hypopnea index (AHI), defined by the number of apnea and hypopnea events per hour, assessed at 6 months from baseline. Intention-to-treat analysis was applied., Results: The median change in AHI from baseline to 6 months was -31 (IQR: -37 to -11) for the high Desipramine, -17.5 (IQR: -31 to 13) for the low Desipramine, and -13 (IQR:-31 to 0) for the placebo group. We did not find any significant difference in these changes between the groups ( P  = 0.781). A significant inverse correlation between Desipramine plasma concentration and AHI ( r  = -0.44; P  = 0.0002) was underlined., Interpretation: This first clinical trial of desipramine did not show clinical efficacy. Although required further studies, the significant correlation between Desipramine concentrations and improvement of AHI provided additional and relevant reasons to test the noradrenergic pathway in RTT.

Congenital myasthenia syndromes (CMS) are a group of genetic disorders responsible for neuromuscular junction dysfunction. Usually beginning before 2 years of age, they are revealed by fatigability and muscle weakness, especially after stress, and often prevent the child's normal development. Over recent years, major advances in therapeutic strategies have been made following the discovery of numerous mutations responsible for CMS and the understanding of their pathogenic role. Here we report a pediatric CMS case caused by a mutation of the ɛ subunit of the acetylcholine receptor. The initial treatment with acetylcholinesterase inhibitor rapidly showed its limits in terms of both effectiveness and tolerance. The association with 3.4 diaminopyridine (DAP), a new drug available to treat such conditions, has transformed the motor outcome of our patient and allowed psychomotor development. In addition to 3.4 DAP, other molecules adapted to other types of CMS are now available. Three major groups of CMS can be distinguished depending on whether the deficit is at the presynaptic, synaptic, or postsynaptic level of the neuromuscular junction. Depending on the type of CMS, therapeutic management may include acetylcholinesterase inhibitors, 3.4 DAP, fluoxetine, quinidine sulfate, or ephedrine. With the case report, we provide a recent review of the literature on such new therapeutic options, their indications and restrictions, their mechanism of action, and prescription modalities. Knowing the precise CMS type and the appropriate therapeutic options available is essential for the proper management of such chronic and severe but relatively treatable childhood disorders., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Primary lymphedema in children, especially generalized disease with facial involvement, is rare., Objective: We sought to report 3 childhood cases of lymphedema with associated neurologic findings and to provide a pathophysiologic explanation for this association., Methods: Clinical observations, electroencephalography, and neuroimaging studies were evaluated. Microcomparative genomic hybridization was performed in 1 case., Results: The 3 children had primary lymphedema of all 4 limbs and the face. This was confirmed by lymphoscintigraphy, which showed hypoplasia of vessels and hypofixation of lymph nodes. They had nonspecific neurologic disorders and electroencephalography abnormalities, without intellectual deficit. Neuroimaging revealed normal findings. Microcomparative genomic hybridization in 1 patient revealed no cytogenetic anomaly. The outcome was fatal in 1 case with development of visceral lymphedema and coma., Limitations: Genetic studies were performed in only 1 case., Conclusion: These observations suggest that neurologic assessment and electroencephalography are indicated for patients with lymphedema of the limbs and face to identify this syndrome., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Synaptic function is central to brain function. Understanding the synapse is aided by studies of patients lacking individual synaptic proteins. Common neurological diseases are genetically complex. Their understanding is likewise simplified by studies of less common monogenic forms. We detail the disease caused by absence of the synaptic protein CNKSR2 in 8 patients ranging from 6 to 62 years old. The disease is characterized by intellectual disability, attention problems, and abrupt lifelong language loss following a brief early childhood epilepsy with continuous spike-waves in sleep. This study describes the phenotype of CNKSR2 deficiency and its involvement in systems underlying common neurological disorders., (© 2014 American Neurological Association.)

Introduction: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology., Case Report: We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool., Discussion: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The gibbon ape leukemia virus (GALV), the amphotropic murine leukemia virus (AMLV) and the human T-cell leukemia virus (HTLV) are retroviruses that specifically bind nutrient transporters with their envelope glycoproteins (Env) when entering host cells. Here, we used tagged ligands derived from GALV, AMLV, and HTLV Env to monitor the distribution of their cognate receptors, the inorganic phosphate transporters PiT1 and PiT2, and the glucose transporter GLUT1, respectively, in basal conditions and after acute energy deficiency. For this purpose, we monitored changes in the distribution of PiT1, PiT2 and GLUT1 in the cerebellum, the frontal cortex, the corpus callosum, the striatum and the substantia nigra (SN) of C57/BL6 mice after administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridinium (MPTP), a mitochondrial complex I inhibitor which induces neuronal degeneration in the striato-nigral network.The PiT1 ligand stained oligodendrocytes in the corpus callosum and showed a reticular pattern in the SN. The PiT2 ligand stained particularly the cerebellar Purkinje cells, while GLUT1 labelling was mainly observed throughout the cortex, basal ganglia and cerebellar gray matter. Interestingly, unlike GLUT1 and PiT2 distributions which did not appear to be modified by MPTP intoxication, PiT1 immunostaining seemed to be more extended in the SN. The plausible reasons for this change following acute energy stress are discussed.These new ligands therefore constitute new metabolic markers which should help to unravel cellular adaptations to a wide variety of normal and pathologic conditions and to determine the role of specific nutrient transporters in tissue homeostasis.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the mitochondrial complex I of the respiratory chain. This results in ATP and ion homeostasis disturbances, which lead to selective death of the substantia nigra dopaminergic neurons. Well known as a Parkinson's disease model, the MPTP animal model also provides a potential paradigm of the energy deficiencies found in childhood. In these conditions, anticonvulsants may provide neuroprotection by limiting cellular energy consumption. We tested valproate, topiramate and lamotrigine in the MPTP mouse model. Dopamine transporter (DAT) density was assessed by quantitative autoradiography, tyrosine hydroxylase (TH) was evaluated by immunohistochemistry and dopamine (DA) levels by HPLC-ED whereas neuronal apoptosis was monitored through active caspase-3. Expectedly, the DAT density, TH immunoreactive neurons and DA content in the MPTP group were respectively reduced to 51%, 40% and 26% versus control animals. Unlike valproate and topiramate, lamotrigine provided a significant neuroprotection against MPTP in maintaining these levels at 99%, 74% and 58% respectively and reducing the induced apoptosis. Altogether, the data indicate that lamotrigine limits dopaminergic neuronal death in the substantia nigra and promotes striatal dendrites sprouting. Lamotrigine, a widely used and well-tolerated molecule in young patients, could represent a valuable adjuvant therapy in various energy deficiency conditions during childhood.

Unlabelled: Recruitment, work load and morbidity linked to newborn asphyxia during delivery at term: a study from Pediatric Mobile Intensive Care Units., Objective: In a population of term neonates transported by the mobile intensive care units (MICU), we aimed to determine the incidence of neonates with anoxic-ischemic encephalopathy related to asphyxia, to analyze in this population the difficulties of management, and to try to identify which of these newborns require new therapeutic strategies., Methods: This retrospective study was performed over a 2-year period (2000 and 2001) in 3 paediatric MICU from the Ile de France area. During this period, 7,648 infants were transported including 3,301 newborns of more than 36 weeks of gestational age and less than 72 hours of life. These neonates came from 73 different hospitals. Among these 3,301 infants, 237 neonates (124 boys and 113 girls) with anoxic-ischemic encephalopathy related to asphyxia were selected in the present study. Inclusion criteria were association of one obligatory criterion of fetal distress during delivery and at least one criterion of neonatal asphyxia or one criterion of anoxic-ischemic encephalopathy. Data were compiled and analyzed with Epidata package and Epi info package, respectively., Results: These 237 neonates with anoxic-ischemic represented 12% of MICU activity at the same gestational and postnatal ages. The mean gestational age was 39.5 + 1.5 weeks. The mean birth weight was 3,188 + 559 g. More than 50% of these neonates were born in level I maternities. Fifty-three percent of the infants were born by caesarean section. Eighty-three percent of the neonates had an Apgar score at 1 minute <3. Eighty-eight percent of the neonates received resuscitation care at 5 minutes of life and 34% of these had an Apgar score at 10 minutes <5. In 50% of the cases, the MICUs arrived at the maternity of delivery within 1 h 45 min of life and transportation of the neonates was completed after 3 hours of life. The neonates were transported to an intensive care unit in 88% of the cases (half to a polyvalent intensive care unit and half to a neonatal intensive care unit). Forty-four percent of transported neonates had no encephalopathy, 30% had a severe encephalopathy or seizures, 27% had multiple organ failure. Mortality reached 28% and encephalopathy accounted for two thirds of these deaths. Neonates who arrived in pediatric care units after 3 hours of life had more severe morbidity than neonates who arrived before 3 hours of life., Conclusion: Pediatric MICUs transport the most severely affected neonates. The initial clinical state is critical, and systemic and neurological complications are frequent and severe. Calls to the MICU should be made earlier in order to enable a better impact of new neuroprotective strategies.