Contribution of fetal brain MRI in management of severe fetal anemia.

INTRODUCTION: Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. MATERIAL AND METHODS: Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. RESULTS: 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. CONCLUSION: MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia.

[Pain in children with neurological impairment: A review from the French Pediatric Neurology Society]. / La douleur chez l'enfant en situation de handicap neurologique : mise au point de la Commission « déficience intellectuelle et handicap ¼ de la Société française de neurologie pédiatrique.

Management of pain is one of the major expectations of children with neurological impairment and their families. The medical literature is poor on this topic accounting for approximately 0.15 % of the publications on pain in general. The objective of the French Pediatric Neurology Society was to review the current knowledge on this topic. Bibliographic research was conducted with PubMed and RefDoc for publications between 1994 and 2014 in French or English. A total of 925 articles were retrieved and 92 were selected for review. Pain is common in this population: a 2-week survey indicated that pain occurs in 50-75 % of children. Pain negatively impacts the quality of life of children and their parents. Children with neurological impairment express their pain with pain expression patterns and specific patterns common to children (change of tone, abnormal movements, spasticity, paradoxical reactions, such as laughter, self-injury or vasomotor dysfunction). Some children with neurological impairment are able to use self-report pain scales. If not, observational measures should be used. Behavioral rating scales specifically designed for this population are more sensitive than others. Scales must be selected according to children's communication skills, type of pain, and the context. Sometimes behavioral changes are the only expression of pain: any change in sleep, tone, feeding, or mood must suggest pain in this population. Management of pain remains difficult. There are no specific guidelines. Procedural pain management guidelines and the usual analgesic drugs can be used in children with neurological impairment with specific concerns regarding tolerance and side effects. These children are particularly at risk for neuropathic pain. A multidisciplinary approach is helpful, involving physicians, nurses, physiotherapists, psychologists and parents.

[Organization of collaborative deliberation for limiting or withholding treatments in children]. / Comment organiser la délibération collégiale pour limiter ou arrêter les traitements en pédiatrie?

In 2005, the French law on patients' rights at the end of life required that decisions to withdraw or withhold life-sustaining treatments be made and carried out by the physician in charge of the patient, after obtaining advice from an independent consulting colleague and the caregiving team. The purpose of this study was to identify theoretical and practical obstacles to this collaborative deliberation and to propose practical guidelines to organize it.

[Ten practical issues concerning acute poisoning with carbon monoxide in pregnant women]. / Dix questions pratiques concernant l'intoxication aiguë au monoxyde de carbone chez la femme enceinte.

BACKGROUND: The poisoning of carbon monoxide (CO) is the leading cause of death by poisoning in France. Its consequences are potentially serious to the fetus. Literature is ancient and little known. PURPOSE AND METHOD: Make an inventory of knowledge about carbon monoxide poisoning during pregnancy. RESULT: The CO causes maternal then fetal tissue hypoxia primarily by binding to hemoglobin with which it has a high affinity. Its transplacental passage may cause fetal harm, predominantly in the brain. Severity seems correlated with maternal symptoms during exposure. In the absence of maternal symptoms, however, the available data are reassuring. Hyperbaric oxygen therapy may reduce the risk to the fetus. DISCUSSION: Oxygen therapy should be offered in all cases of CO poisoning, especially if there are maternal symptoms during exposure. In addition, a fetal echography directed on the cephalic pole - even a fetal magnetic resonance imaging three weeks after exposure - should also be proposed.

[Prenatal analysis of primary sulci by ultrasonography and MRI]. / Analyse anténatale des sillons primaires en échographie et en IRM.

Gyration abnormalities often reflect severe neurological diseases. Their diagnosis is impeded by our limited knowledge about normal sulci anatomy throughout fetal brain development. Primary sulci appears in a specific chronology which is unchanged among all fetuses. We think it is interesting to remind of sulci anatomy and then to depict sulci MRI and ultrasonography appearance at 22, 27 and 32 weeks of gestation. We pay particular attention to the lateral sulcus, also called Sylvian fissure.

[The consulting physician for withdrawal of life-sustaining treatments in children]. / Le médecin consultant pour les limitations et les arrêts de traitement en pédiatrie.

In 2005, the French law on patients' rights at the end of life ratified that decisions to withdraw or withhold life-sustaining treatments must be made and carried out by the physician in charge of the patient, after obtaining the advice of an independent consulting colleague. The purpose of this text is to put forward the perspective of a pediatric multidisciplinary workshop regarding the role of the consulting physician and to propose guidelines to help choose this consultant.

[Characteristics of tuberous sclerosis in children]. / Spécificités de la sclérose tubéreuse de Bourneville chez l'enfant.

Tuberous sclerosis complex is a genetic multisystem disease characterized by hamartic development of many organs, most notably the brain, heart, kidneys, lungs, and skin. This autosomic dominant disorder results from mutations in one of two genes, TSC1 and TSC2, coding for hamartin and tuberin, respectively. The hamartin-tuberin complex inhibits the mammalian target of rapamycin pathway, which controls cell growth and proliferation. The clinical presentation is highly variable and most features of tuberous sclerosis become evident only in childhood after the child is several years of age, limiting their usefulness for early diagnosis. The aim of this article is to define the pediatric clinical manifestations of tuberous sclerosis in correlation with patient age. Sometimes, a prenatal diagnosis can be made based on fetal ultrasound and MRI, which show cardiac and brain lesions. However, newborns are most often asymptomatic. In the 1st year, seizures are the most common symptoms, with a high incidence of infantile spasms. In children between 2 and 10 years of age, neurological symptoms are the most frequent with epilepsy, mental retardation, and autism, but extraneurological manifestations can be diagnosed. In adolescents, most features of tuberous sclerosis become evident and renal and pulmonary manifestations must be sought. The knowledge of age-dependent clinical features of tuberous sclerosis can provide an earlier diagnosis and improve the management of these patients with a special role for multidisciplinary consultation.

MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations.

BACKGROUND: Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. METHOD: Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. RESULTS: 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. CONCLUSION: Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.

Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations.

OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we searched for additional mutations in a cohort of 100 patients with lissencephaly spectrum for whom no mutation was identified in DCX, LIS1 and ARX genes and compared these data to five previously described patients with TUBA1A mutations. RESULTS: We detected de novo TUBA1A mutations in six patients and highlight the existence of a prominent form of TUBA1A related lissencephaly. In four patients, the mutations identified, c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T (p.G436R), have not been reported before and in two others, the mutation corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a hot spot of mutation. All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia. When compared with a large series of lissencephaly of other origins (ILS17, ILSX or unknown origin), these features appear to be specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients share a common clinical phenotype that consists of congenital microcephaly, mental retardation and diplegia/tetraplegia. CONCLUSIONS: Our data highlight the presence of consistent and specific abnormalities that should allow the differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX and ARX genes.

[Neuropediatric approach to autism]. / Approche neuropédiatrique de l'autisme.

Autism is defined by 3 main criteria: disturbance of reciprocal social interaction, disturbance of communication (including language comprehension and spoken language) and disturbance of normal variation in behaviour and imaginative activities; an onset before age 36 months is also required. The neuropediatric contribution to autism is dominated by the search for an underlying organic etiology, especially if there are arguments for an associated encephalopathy: ante- or perinatal medical history, dysmorphic signs, skin spots, neurological abnormalities, somatic abnormalities compatible with a neurometabolic disorder. The main associated conditions with autism are: chromosome anomalies, monogenic syndrome (including fragile X syndrome), neurocutaneous syndromes, epileptic encephalopathies, neurometabolic diseases, and dystrophinopathies. The identification of an associated medical condition to autism is primordial in prospect of genetic counselling, and by the change induced in familial perception of autism.

[Pharmacologic treatment of acute migraine attack in children]. / Traitement médicamenteux de l'accès migraineux chez l'enfant.

Migraine, according to the criteria of the International Headache Society, occurs in about 5 to 10% of children. Management of acute headache is only one of the parts of the treatment, along with identification of migraine precipitants, adjustments in lifestyle, and when necessary the use of preventive therapy, which can include non pharmacologic (relaxation or biofeedback) or pharmacologic treatment. In the acute migraine attack, a single dose of either ibuprofen 10 mg/kg or paracetamol 15 mg/kg has been shown to be effective, with only a few adverse effects. In severe migraine attacks, dihydroergotamine mesylate administered orally (20 to 40 microg/kg) or intravenously (maximum 1 mg/day) may be helpful, but there have been no large placebo-controlled trials of this treatment. Among the different triptans, it is the sumatriptan nasal spray whose efficacy has been best demonstrated. The most frequent adverse event is transitory unpleasant taste.

[Drug treatment of migraine in children: state of the art]. / Traitement de fond de la migraine de l'enfant: état des connaissances du traitement pharmacologique.

Migraine, according to the criteria of the International Headache Society, occurs in about 5-10% of children. Preventive therapy includes identification of migraine precipitants, possible adjustments in lifestyle, appropriate management of acute headache, and when necessary the use of pharmacologic agents. It should be started if migraine attacks are severe or frequent. Non-pharmacologic prophylactic treatment is the modality of choice, based on relaxation or biofeedback. Despite its high incidence, only a few controlled trials have investigated the prophylactic treatment of migraine in children. Only flunarizine (5 mg/day) has been shown to be effective in two double-blind, placebo-controlled trials. Some evidence also exists that propranolol (60 mg/day) and pizotifen (0.5-1.5 mg/day) are effective. For all other drugs studied in migraine prophylaxis, the results remain vague (e.g. amitriptyline), or suggest inefficacy (e.g. clonidine, tryptophane). Most of the drugs used in the treatment of migraine in children are well tolerated. The most common adverse effects are drowsiness and bodyweight gain.

The Richieri-Costa and Pereira form of acrofacial dysostosis: first case in a non-Brazilian infant.

We report on a French boy with cleft mandible, pre/postaxial hand anomalies, and clubfoot born to consanguineous parents. These findings are comparable to those of previous cases of the autosomal recessive Richieri-Costa and Pereira syndrome of short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and clubfoot. This is the first case in a non-Brazilian infant.