Developmental and physiological responses of Brachypodium distachyon to fluctuating nitrogen availability.

The Nitrogen Use Efficiency (NUE) of grain cereals depends on nitrate (NO3-) uptake from the soil, translocation to the aerial parts, nitrogen (N) assimilation and remobilization to the grains. Brachypodium distachyon has been proposed as a model species to identify the molecular players and mechanisms that affects these processes, for the improvement of temperate C3 cereals. We report on the developmental, physiological and grain-characteristic responses of the Bd21-3 accession of Brachypodium to variations in NO3- availability. As previously described in wheat and barley, we show that vegetative growth, shoot/root ratio, tiller formation, spike development, tissue NO3- and N contents, grain number per plant, grain yield and grain N content are sensitive to pre- and/or post-anthesis NO3- supply. We subsequently described constitutive and NO3--inducible components of both High and Low Affinity Transport Systems (HATS and LATS) for root NO3- uptake, and BdNRT2/3 candidate genes potentially involved in the HATS. Taken together, our data validate Brachypodium Bd21-3 as a model to decipher cereal N nutrition. Apparent specificities such as high grain N content, strong post-anthesis NO3- uptake and efficient constitutive HATS, further identify Brachypodium as a direct source of knowledge for crop improvement.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

Spatiotemporal source analysis in scalp EEG vs. intracerebral EEG and SPECT: a case study in a 2-year-old child.

OBJECTIVE: This case study aims to demonstrate that spatiotemporal spike discrimination and source analysis are effective to monitor the development of sources of epileptic activity in time and space. Therefore, they can provide clinically useful information allowing a better understanding of the pathophysiology of individual seizures with time- and space-resolved characteristics of successive epileptic states, including interictal, preictal, postictal, and ictal states. METHODS: High spatial resolution scalp EEGs (HR-EEG) were acquired from a 2-year-old girl with refractory central epilepsy and single-focus seizures as confirmed by intracerebral EEG recordings and ictal single-photon emission computed tomography (SPECT). Evaluation of HR-EEG consists of the following three global steps: (1) creation of the initial head model, (2) automatic spike and seizure detection, and finally (3) source localization. During the source localization phase, epileptic states are determined to allow state-based spike detection and localization of underlying sources for each spike. In a final cluster analysis, localization results are integrated to determine the possible sources of epileptic activity. The results were compared with the cerebral locations identified by intracerebral EEG recordings and SPECT. RESULTS: The results obtained with this approach were concordant with those of MRI, SPECT and distribution of intracerebral potentials. Dipole cluster centres found for spikes in interictal, preictal, ictal and postictal states were situated an average of 6.3mm from the intracerebral contacts with the highest voltage. Both amplitude and shape of spikes change between states. Dispersion of the dipoles was higher in the preictal state than in the postictal state. Two clusters of spikes were identified. The centres of these clusters changed position periodically during the various epileptic states. CONCLUSION: High-resolution surface EEG evaluated by an advanced algorithmic approach can be used to investigate the spatiotemporal characteristics of sources located in the epileptic focus. The results were validated by standard methods, ensuring good spatial resolution by MRI and SPECT and optimal temporal resolution by intracerebral EEG. Surface EEG can be used to identify different spike clusters and sources of the successive epileptic states. The method that was used in this study will provide physicians with a better understanding of the pathophysiological characteristics of epileptic activities. In particular, this method may be useful for more effective positioning of implantable intracerebral electrodes.

[Experience with levetiracetam in the treatment of childhood refractory epilepsy]. / Utilisation du lévétiracétam (LEV) dans le traitement des épilepsies réfractaires de l'enfant : expérience du service de neuropédiatrie du CHU d'Amiens en France.

INTRODUCTION: In young children presenting drug-resistant epilepsy, the number of approved antiepileptic drugs is limited. Levetiracetam (LEV) is one of the most recent antiepileptic drugs (AED) introduced on the market and data on its effectiveness and tolerance in children are scarce. PATIENTS AND METHODS: The objective of this retrospective study was to report our experience with the use of levetiracetam as an adjuvant therapy in a population of 42 children presenting a drug-resistant epilepsy. The study was conducted over a 5-year-period (from 1 January 2004 to 30 June 2007). RESULTS: The patients' mean age was 10.8 years (range, 2.1-19 years). The mean duration of epilepsy was 6.6 years (range, 1.5-19 years). After the administration of LEV, 10 patients (23.8%) became seizure-free and 16 (38.1%) had more than 50% seizure reduction. A reduction of less than 50% was observed in 13 patients (31%). Three patients (7.1%) presented an increase in seizure frequency. The effectiveness of LEV was similar in partial and generalized epilepsy. LEV was well tolerated by these patients. The main adverse effects were anorexia, asthenia, and behavioral disorders, and drowsiness was encountered in 17% of the patients. All persistent adverse events were noted. In children under 4 years of age, LEV was particularly well tolerated. CONCLUSION: This study confirms the effectiveness and tolerance of LEV used as an adjuvant therapy in children presenting drug-resistant epilepsy, particularly in the very young ones.

[Familial and non-familial benign infantile seizures: A homogeneous entity?]. / Convulsions infantiles bénignes familiales et non familiales : une entité homogène ?

Among the epileptic syndromes occurring during infancy, which are mostly non-idiopathic and associated with a poor prognosis, benign infantile convulsions are characterized by a favourable evolution. This work aims to analyse and compare the clinical, EEG and outcome characteristics of familial benign infantile convulsions (FBIC) and non-familial benign infantile convulsions (NFBIC). This is a retrospective study, conducted between 1988 and 2008, in 40 infants who presented benign infantile seizures during the two first years of life. All of them had no personal history, normal psychomotor development, normal neurological examinations, no abnormalities on biological and radiological investigations and a favourable outcome. In 14 cases, there was a familial history of familial benign infantile convulsions. However, among the 26 cases with non-familial benign infantile convulsions, 11 children had a familial history of other epileptic syndrome. That may suggest a genetic familial susceptibility. In the two groups, the clinical features and the electroencephalography were similar. The seizures had short duration and occurred most often in clusters. Twenty-nine children had secondarily generalized partial seizures and 11 infants had generalized seizures but a focal onset cannot be excluded. The antiepileptic drugs allowed rapid resolution of seizures. One child necessitated a prolonged antiepileptic treatment. In the other cases, seizures cured in the first year without recurrence of seizures after treatment discontinuation. The evolution was characterised in five children by a later occurrence of dystonia. This subgroup was described as infantile convulsion and choreoathetosis syndrome (ICCA). Benign infantile convulsions are probably an underestimated epileptic syndrome. The diagnosis is relatively easy in the familial forms with dominant autosomal transmission. In contrast, in sporadic forms, the diagnosis can be confirmed only by the evolution. The good prognosis must be tempered by the subsequent onset of dystonia consisted in the ICCA syndrome and justifies a prolonged follow-up.

[Infratentorial ischemic stroke in children: Three case reports]. / Accidents vasculaires cérébraux de la fosse postérieure chez l'enfant : à propos de trois cas.

Ischemic stroke is rare in children, most of which occur in the supratentorial brain, and infratentorial infarcts are very rare. Some clinical manifestations may be similar but others such as ataxia and cranial nerve palsy are more specific. Vertebral artery dissection is the most frequent cause of stroke in the vertebrobasilar territory, but the cause most often remains unknown in children. We report three cases of infratentorial stroke in children. The first observation concerns a 4-year-old boy brought to medical attention because left hemicorporal motor deficit associated with ataxia following a minor cranial traumatism. While computed tomography (CT) of the brain was normal, magnetic resonance imaging (MRI) revealed an area of signal alteration on the diffusion-weighted image within the right protuberance. The second observation is a 15-year-old girl who developed sudden-onset ataxia. The CT scan and MRI of the brain revealed an acute bilateral cerebellar stroke. MRI angiography showed an anatomical variant of the left vertebral artery that did not participate in the Willis polygon. In these two observations, no other abnormalities were detected except they were homozygotous for MTHFR mutation in the first observation and minor alpha-thalassemia for the second one. The outcome in these two children was good without sequelae after a 6-month follow-up. The third observation is a 6-year-old girl who suddenly exhibited cephalalgia, ataxia, and left visual impairment. The brain MRI revealed left occipital and cerebellar strokes due to vertebral artery dissection. The authors recommend the systematic search for vertebral artery dissection in cases of infratentorial stroke.

Maturation of response time and attentional control in ADHD: evidence from an attentional capture paradigm.

Inattention and hyperactivity/impulsivity are the core symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). Slowness, although less known, has been also recently reported in children with ADHD and may contribute to their learning difficulties. Slow response time and greater response time variability have been highlighted by several computerized tasks. The goal of the present work was to evaluate the age-related response time in ADHD children and in a group of matched control children during an attentional capture paradigm. The study population included 75 children with ADHD (aged between 6 and 13) and 75 age- and gender-matched typical developing children (Control group). The children with ADHD made more errors than children on the control group. The response times and the response time variability decreased with age in both groups and were significantly greater in ADHD than in controls. The distractor effect was similar in both groups. The maturation of response times and response time variability with age is quite similar in children with ADHD and typical developing children but whatever the age-class, children with ADHD were slower and exhibited greater response time variability than control children that could explain the variation during day-time of attention capacities in ADHD.

Visual sensory processing deficit in the occipital region in children with attention-deficit / hyperactivity disorder as revealed by event-related potentials during cued continuous performance test.

AIMS OF THE STUDY: Recent studies described several changes of attention-related components of late frontal event-related potentials (ERPs) during Go/NoGo paradigm in children with attention-deficit/hyperactivity disorder (ADHD). We aimed to determine whether ERP components corresponding to earlier encoding of visual incoming information are also modulated by attentional disorders. METHODS: We recorded high-resolution EEG in 15 children meeting DSM-IV criteria for ADHD, comprising 15 age-matched control groups during an equiprobable Go/NoGo task in a cued continuous performance test (CPT-AX) paradigm. Both P100 and N200 ERP components were measured in response to both Go and NoGo stimuli. We analyzed both components with SwLORETA in order to localize their brain sources. RESULTS: A low rate of Go correct response and high rate of omission errors were observed in ADHD children. When compared to controls, these displayed delayed P100 and N200 latency, and lower P100-NoGo amplitude. In addition, the P100 latency was delayed for NoGo compared to Go condition. The source of P100 was located in occipital area. A sizable decrease in early electrical activity was found in ADHD, especially in the NoGo condition. CONCLUSION: Our results suggest an early deficit in visual sensory integration within the occipital cortex in children with ADHD.

Brain functional modeling, what do we measure with fMRI data?

The description of specific circuits in networks should allow a more realistic definition of dynamic functioning of the central nervous system which underlies various brain functions. After introducing the programmed and acquired networks and recalling the concepts of functional and effective connectivity, we presented biophysical and physiological aspects of the BOLD signal. Then, we briefly presented a few data-driven and hypothesis-driven methods; in particular we described structural equation modeling (SEM), a hypothesis-driven approach used to explore circuits within networks and model spatially and anatomically interconnected regions. We compared the SEM method with an alternative hypothesis-driven method, dynamic causal modeling (DCM). Finally, we presented independent components analysis (ICA), an exploratory data-driven approach which could be used to complete the directed brain interactivity studies. ICA combined with SEM/DCM may allow extension of the statistical and explanatory power of fMRI data.

Differences in effective connectivity between dyslexic children and normal readers during a pseudoword reading task: an fMRI study.

PURPOSE: This fMRI study investigated phonological and lexicosemantic processing in dyslexic and in chronological age- and reading level-matched children in a pseudoword reading task. MATERIALS AND METHODS: The effective connectivity network was compared between the three groups using a structural model including the supramarginal cortex (BA 40; BA: Brodmann area), fusiform cortex (BA 37) and inferior frontal cortex (BA 44/45) areas of the left hemisphere. RESULTS: The results revealed differences in connectivity patterns. In dyslexic patients, in contrast with chronological age- and reading level-matched groups, no causal relationship was demonstrated between BA 40 and BA 44/45. However, a significant causal relationship was demonstrated between BA 37 and BA 44/45 both in dyslexic children and in the reading level-matched group. CONCLUSIONS: These findings were interpreted as evidence for a phonological deficit in developmental dyslexia.

Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic studies of boys with attention-deficit/hyperactivity disorder (ADHD) have detected decreased volumes in total and frontal brain, basal ganglia, and cerebellar vermis. We tested these findings in a sample of girls with ADHD. METHODS: Anatomic brain magnetic resonance images from 50 girls with ADHD, of severity comparable with that in previously studied boys, and 50 healthy female control subjects, aged 5 to 15 years, were obtained with a 1.5-T scanner with contiguous 2-mm coronal slices and 1.5-mm axial slices. We measured volumes of total cerebrum, frontal lobes, caudate nucleus, globus pallidus, cerebellum, and cerebellar vermis. Behavioral measures included structured psychiatric interviews, parent and teacher ratings, and the Wechsler vocabulary and block design subtests. RESULTS: Total brain volume was smaller in girls with ADHD than in control subjects (effect size, 0.40; P =.05). As in our previous study in boys with ADHD, girls with ADHD had significantly smaller volumes in the posterior-inferior cerebellar vermis (lobules VIII-X; effect size, 0.54; P =.04), even when adjusted for total cerebral volume and vocabulary score. Patients and controls did not differ in asymmetry in any region. Morphometric differences correlated significantly with several ratings of ADHD severity and were not predicted by past or present stimulant drug exposure. CONCLUSIONS: These results confirm previous findings for boys in the posterior-inferior lobules of the cerebellar vermis. The influence of the cerebellar vermis on prefrontal and striatal circuitry should be explored.

Postnatal changes in Fos-like immunoreactivity evoked by hypoxia in the rat brainstem and hypothalamus.

We have recently used Fos expression in adult rats to map neuronal populations activated in the brainstem and hypothalamus during the acute ventilatory response to moderate hypoxia (O(2) 11%). Although present at birth, this response evolves postnatally. The present investigation aimed at a better understanding of these maturational processes by delineating structures that might functionally develop after birth. The developmental pattern Fos expression evoked by hypoxia was analysed in rats aged from 0 to 26 postnatal days. The numbers of Fos positive neurons markedly increased with the age in the medullary areas related to respiratory control during the 2 first postnatal weeks. Thereafter, the response plateaued in the nucleus tractus solitarius and attenuated in the ventral medulla. In the upper brainstem (parabrachial area, central grey) and the hypothalamus (posterior and dorsomedial nuclei, ventral zone), Fos response to hypoxia was absent or weak at birth and increased until late development. The significance of the development of evoked Fos expression in these rostral sites is discussed together with their possible contribution to the maturation of O(2)-sensitive chemoreflex pathways.

Brainstem and hypothalamic areas involved in respiratory chemoreflexes: a Fos study in adult rats.

The adaptation to hypoxia and hypercapnia requires the activation of several anatomical structures along the neuraxis. In this study, using Fos immunoreactivity, we sought to map neuronal populations involved in chemoreflex networks activated during the responses to moderate hypoxia (O(2) 11%), and hypercapnia (CO(2) 5%) in the brainstem and the hypothalamus of the rat. In the medulla, hypoxia elicited marked and significant staining in the nucleus of the solitary tract (NTS), and in parapyramidal neurons located near the ventral surface, whereas hypercapnia evoked significantly c-fos only near the ventral surface in paraolivar neurons. In contrast, within pontine and suprapontine structures, both hypoxia and hypercapnia evoked similarly Fos immunoreactivity in the lateral parabrachialis area, the central grey, the caudal hypothalamus (dorsomedial and posterior hypothalamic nuclei), and in a ventro-lateral hypothalamic area, extending from the rostral limit of the mammillary nuclei to the retrochiasmatic area. More rostrally, labelling was observed in the paraventricular nucleus of the hypothalamus in response to hypercapnia, and in the supraoptic nucleus in response to hypoxia. These results support the hypothesis that chemoreflexes pathways are not only restricted to medulla and pons but also involved mesencephalic and hypothalamic regions. The parabrachialis area and the central grey may be key relays between caudal and ventral hypothalamic neurons, and medullary neurons involved in the response to hypoxia and hypercapnia.

Cerebral white matter disease in children may be caused by mitochondrial respiratory chain deficiency.

Several mitochondrial diseases are known to occasionally involve the cerebral white matter, namely Leigh syndrome, Kearns-Sayre syndrome, and MELAS syndrome, but in these cases the major finding is alteration in the basal ganglia and brainstem. Here we report on severe diffuse white matter involvement and respiratory chain enzyme deficiency or mitochondrial DNA rearrangement in 5 unrelated families. It is interesting that white matter lesions were the only abnormal neuroradiologic feature in 3 of the 5 families, and multiple small cyst-like white matter lesions were found in 2 of 5 probands. Respiratory chain deficiency should be considered in the diagnosis of severe white matter involvement in childhood.

[Benign infantile convulsions. French collaborative study]. / Convulsions bénignes du nourrisson. Etude collaboratrice française.

BACKGROUND: Benign infantile non febrile seizures are not well known, leading us to study their clinical and EEG characteristics. METHODS: Between 1981 and 1994, we assembled 34 patients with the following inclusion criteria: non febrile seizures between 1 month and 2 years of age, normal personal history, no abnormality on clinical, biological and radiological investigations, normal developmental outcome with at least 1 year follow-up. RESULTS: These 34 patients were recognized as 14 familial cases (identical seizures affecting parents) and 11 non familial cases. The other nine cases had different or undefined epilepsy in the family. The clinical and EEG characteristics were the same: at the mean age of 6 months, brief partial seizures (often secondarily or apparently generalized) occurring in a cluster of two to 12 episodes a day for a mean duration of 2.5 days, with ictal EEG showing focal discharge, often slow waves or focal spikes on post-ictal tracing and normal interictal EEG. CONCLUSION: The clinical and EEG characteristics are important in order to recognize this type of infantile convulsions (familial or not familial), which have a good prognosis and need no aggressive treatment.

[Symptomatic and cryptogenic epilepsies in the child]. / Epilepsies symptomatiques et cryptogénétiques de l'enfant.

Symptomatic and cryptogenic epilepsies are related to detected or suspected cerebral lesions. Early identification of defined epileptic syndromes and etiology is helpful to adapt treatment. Generalized epilepsies are severe, often refractory and generally associated with cognitive dysfunction or regression. Partial symptomatic or cryptogenic epilepsies represent about 40% of all epilepsies in childhood and diagnosis as well as therapeutic strategy can be difficult. Semiology of partial seizures is related to epileptogenic focus and discharge propagation. Causes are numerous and are to be always extensively searched.

[Use of the admission service and pediatric emergency service of a university hospital center by adolescents (12-19 years): utilization and messages]. / Passage des adolescents (12-19 ans) au service d'accueil et d'urgences pédiatriques d'un Centre Hospitalier Universitaire: usage et messages.

A retrospective survey concerning all patients ages 12-19 who had registered themselves at the admitting service of the paediatric emergency unit in the university hospital centre of Amiens was carried out in 1995. 2812 adolescents were received (18% of total admissions). The male/female sex-ratio was 1 to 3. The average age was 13.2 years old. Hospitalisations were more frequent in the spring and were predominantly on Mondays (17%). More than 2/3 of the adolescents were accompanied by their parents and 20% were referred by their doctors or by the SAMU (mobile emergency medical service). Two percent arrive alone. Traumatic pathology is the main reason for admission (1960 patients). Organic pathologies represent 24% of admissions and are essentially digestive pathologies (40%). "Suffering" adolescents (defined as those requiring an intervention with a psychotherapist as a matter of priority) only represent 6% of visits to the emergency unit, of which 2/3 correspond to suicide attempts. 24% of adolescents are hospitalised at the university hospital centre of Amiens within the paediatric services or specialised services (ENT, stomatology, etc.).

Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study.

Clinical, neuroanatomic, neurobehavioral, and functional brain-imaging studies suggest a role for the cerebellum in cognitive functions, including attention. However, the cerebellum has not been systematically studied in attention-deficit hyperactivity disorder (ADHD). We quantified the cerebellar and vermal volumes, and the midsagittal areas of three vermal regions, from MRIs of 46 right-handed boys with ADHD and 47 matched healthy controls. Vermal volume was significantly less in the boys with ADHD. This reduction involved mainly the posterior inferior lobe (lobules VIII to X) but not the posterior superior lobe (lobules VI to VII). These results remained significant even after adjustment for brain volume and IQ. A cerebello-thalamo-prefrontal circuit dysfunction may subserve the motor control, inhibition, and executive function deficits encountered in ADHD.

Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia.

OBJECTIVE: Studies have suggested that the maldeveloped neural circuitry producing schizophrenic symptoms may include the cerebellum. The authors found further support for this hypothesis by examining cerebellar morphology in severely ill children and adolescents with childhood-onset schizophrenia. METHOD: Anatomic brain scans were acquired with a 1.5-T magnetic resonance imaging scanner for 24 patients (mean age = 14.1 years, SD = 2.2) with onset of schizophrenia by age 12 (mean age at onset = 10.0 years, SD = 1.9) and 52 healthy children. Volumes of the vermis, inferior posterior lobe, fourth ventricle, and total cerebellum and the midsagittal area of the vermis were measured manually. RESULTS: After adjustment for total cerebral volume, the volume of the vermis and the midsagittal area and volume of the inferior posterior lobe remained significantly smaller in the schizophrenic patients. There was no group difference in total cerebellar or fourth ventricle volume. CONCLUSIONS: These findings are consistent with observations of small vermal size in adult schizophrenia and provide further support for abnormal cerebellar function in childhood- and adult-onset schizophrenia.