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Introduction Le depistage de la carence en vitamine B12 (B12) a longtemps repose sur le seul dosage serique avec un seuil classique de 200 ng/L. Neanmoins, ce seuil apparait peu sensible pour detecter precocement la carence. Les experts ont donc propose un depistage de la carence en B12 a l’aide de 2 marqueurs : acide methylmalonique (MMA) (plasmatique ou urinaire) et homocysteine (plasmatique) (Hcyst). En les utilisant, nous avons observe une prevalence de 23,3 % de carence en B12 chez 490 patients hospitalises en medecine interne dans un travail precedent. Cette methodologie plus sensible permet de depister des carences moins severes, generalement non liees a la maladie de Biermer et dont l’etiologie pose parfois question. Nous avons, dans ce travail, explore l’hypothese d’un lien entre carence en vitamine B12, metformine et inhibiteur de pompes a protons (IPP). Patients et methodes Durant 15 semaines, les patients hospitalises dans le service de medecine interne du CHU d’Angers et subissant un prelevement sanguin ont eu une exploration de la carence en B12, sauf opposition apres information eclairee (protocole MIB12). La carence etait affirmee devant un taux serique de B12 inferieur a 201 ng/L, ou devant un taux entre 201 et 350 ng/L si l’Hcyst etait superieure a 13 μmol/L chez les femmes et 15 μmol/L chez les hommes et/ou si le MMA urinaire etait superieur a 1,5 μmol/mmol de creatininurie. Dans ce travail, seuls les patients beneficiant d’un traitement par metformine ou IPP depuis plus d’un an ont ete inclus. Les patients sous metformine ont ete compares a l’ensemble de la population du protocole MIB12 en analyse univariee (Khi2) et multivariee (regression logistique). Concernant les patients sous IPP, devant de multiples facteurs confondants entre prise d’IPP et etiologies de carences en B12, nous avons compare les patients sous IPP a ceux ne prenant pas d’IPP de meme sexe, de meme âge (±3 ans), apres exclusion des autres causes de carence en B12 et des rares patients sous anti-H2. Resultats Parmi les 490 patients du protocole MIB12, d’âge median de 67,5 ans [50–82], 114 (23,3 %) patients presentaient une carence en B12. Parmi la population totale, 26/490 (5,3 %) patients etaient traites depuis plus d’un an par metformine, dont 13 (50 %) presentent une carence en B12. L’utilisation de metformine seule representait 11,4 % des etiologies de carence en B12. En analyse univariee, l’odd ratio (OR) de carence en B12 sous metformine est de 3,22 [IC95 % : 1,45–7,17] (p = 0,003). En analyse multivariee (variables du modele : âge, sexe, maladie de Biermer, resection ileale, vegetalisme, gastrite a Helicobacter pylori et prise d’IPP), l’OR de carence en B12 sous metformine est de 3,15 [IC95 % : 1,35–7,37] (p = 0,008). Nous avons extrait 84 patients sous IPP, sans autre etiologie potentielle de carence en B12, avec un âge median de 76,5 ans [56,3–88] et les avons apparies a 84 patients ne prenant pas d’IPP, avec un âge median de 76,5 ans [56–87]. Dans le groupe IPP, 19 (22,6 %) patients avaient une carence en B12 contre 8 (9,5 %) dans le groupe sans IPP (p = 0,02) avec un OR de 2,78 [IC95 % : 1,14–6,76]. Discussion Une meta-analyse a estime a 10,7 % la prevalence de la carence en B12 chez des patients diabetiques sous metformine (OR 2,45 [IC95 % : 1,74–3,44]). Neanmoins, les methodologies des etudes selectionnees etaient tres heterogenes [1] . A notre connaissance, une seule etude a evalue les marqueurs MMA et Hcyst chez ces patients, mais ses conclusions sont discordantes avec le reste de la litterature, evoquant un phenomene de transfert de la B12 sous metformine du sang vers les cellules, responsable de « fausses » carences. Cette hypothese est basee sur le constat d’une B12 erythrocytaire elevee sous metformine mais, du fait de l’absence de mitochondries et donc de metabolisme du MMA dans les globules rouges, ces cellules semblent peu representatives du metabolisme intracellulaire global de la B12. Concernant les IPP, les donnees sont plus tenues et les prospectives rares. Une etude retrospective sur 210 155 patients issus du systeme de sante americain met en evidence un OR de carence en B12 sous IPP (> 2 ans) de 1,65 [IC95 % : 1,58–1,73] avec un depistage uniquement base sur le taux serique de B12 [2] . A notre connaissance, une seule autre etude a evalue l’impact des IPP au long cours sur la carence en B12, via l’Hcyst et le MMA, mais sa methodologie ne permet pas de conclure [3] . Conclusion Dans cette etude prospective, nous demontrons qu’un traitement prolonge (> 1 an) par metformine et IPP est associe significativement a la carence en B12, depistee a l’aide des dosages de Hcyst et de MMA, chez des patients hospitalises en medecine interne.

The authors systematically treated 94 patients with West syndrome using the same protocol of sodium valproate and steroids, starting with hydrocortisone (HC) orally for two weeks. If seizures stopped, HC was withdrawn; if they persisted, tetracosactrin (TA; synthetic ACTH) was administered for another two weeks then HC was slowly withdrawn. 90 per cent of the symptomatic cases were controlled by HC, the remainder by TA. 65 per cent of symptomatic cases were controlled by HC; this rose to 78 per cent if patients treated by HC then TA were included. At 31 months follow-up, the percentage of favourable results was 72 per cent for cryptogenic and 60 per cent for symptomatic cases. For the latter, best results were obtained in patients with periventricular leukomalacia, postnatal distress and porencephaly. Patients suffering from sequelae of full-term distress or encephalopathy of unknown aetiology were the most resistant.

Introduction Selon le critere classique avec un seuil serique de vitamine B12 (B12) de 200 ng/L, la prevalence de sa carence est estimee a 1 a 2 % de la population generale, jusqu’a 10 % chez les plus de 65 ans. Neanmoins, ce seuil apparait insuffisamment sensible pour detecter precocement la carence. Les experts ont donc propose un depistage de la carence en B12 a l’aide de 2 marqueurs : l’acide methylmalonique et l’homocysteine [1] . De cette facon, nous avons observe une frequence de 22,4 % de carence en B12 chez 492 patients hospitalises en medecine interne dans un travail precedent. Pour 43,6 % des patients carences, aucune etiologie usuelle de carence n’avait ete decelee. La frequence des connectivites en medecine interne interroge donc sur leur lien potentiel avec la carence en B12. En 2005, Andres et al. proposaient d’inclure la sclerodermie systemique et le syndrome de Sjogren primaire parmi les etiologies du syndrome de non-dissociation de la B12, mais peu de donnees sont disponibles en ce sens [2] . Nous nous sommes donc interroges sur le lien entre syndrome de Sjogren, sclerodermie systemique et carence en vitamine B12. Patients et methodes Tous les patients hospitalises sur une periode de 15 semaines dans le service de medecine interne du CHU d’Angers et devant subir un prelevement sanguin ont eu un dosage de B12, sauf opposition apres information eclairee. La carence etait affirmee devant une concentration serique de B12 inferieure a 201 ng/L, ou devant une concentration entre 201 et 350 ng/L si la concentration d’homocysteine etait superieure a 13 μmol/L chez les femmes et 15 μmol/L chez les hommes et/ou si la concentration d’acide methylmalonique urinaire etait superieure a 1,5 μmol/mmol de creatininurie. Nous avons retenu comme populations d’interet les patients atteints d’un syndrome de Sjogren primaire, repondant aux criteres de 2002, et d’une sclerodermie systemique sans syndrome de Sjogren associe, repondant aux criteres de 2013. En raison des caracteristiques demographiques particulieres des connectivites, nous avions prevu une comparaison des patients atteints de syndrome de Sjogren et de sclerodermie systemique a des temoins apparies, en 1 pour 5, sur l’âge (± 3 ans) et le sexe, par tirage au sort. La population temoin etait issue des 403 patients restant parmi 492 de notre precedente etude, apres exclusion des patients porteurs d’un syndrome de Sjogren, d’une sclerodermie systemique, d’une maladie de Biermer ou presentant une hypervitaminose B12. Resultats Parmi les 492 patients, 20 etaient atteints d’un syndrome de Sjogren primaire (4,1 %), d’âge median 72,5 ans [50,5–78], dont 18 femmes (90 %). La population appariee de 100 temoins avaient un âge median de 72,5 ans [51,25–78,75]. La carence en B12 etait plus frequente dans le groupe avec syndrome de Sjogren avec 45 % contre 20 % chez les temoins apparies ( p = 0,018) avec risque relatif (RR) de 2,25, [IC95 % ; 1,21–4,20]. Vingt patients au sein des 492 avaient une sclerodermie systemique sans syndrome de Sjogren associe (4,1 %), l’âge median etait 54 ans [49,25–66,75], avec 70 % de femmes. La population appariee de 100 temoins avaient un âge median de 54,5 ans [44–66]. Sept patients avaient une carence en B12 dans le groupe sclerodermie systemique (35 %), significativement superieure aux 13 % de la population temoin appariee ( p = 0,016) avec un RR de 2,69 [IC95 % ; 1,23–5,90]. Parmi les patients carences, le recours aux inhibiteurs de pompe a protons, frequent dans le traitement de la sclerodermie systemique, ne differait pas entre les groupes, 57,1 % pour le groupe avec sclerodermie systemique (4 sur 7) contre 38,5 % (5 sur 13) pour les temoins ( p = 0,64). Discussion A l’aide d’un depistage de la carence en B12 base sur le dosage de l’homocysteine et de l’acide methylmalonique, nous avons pu mettre en evidence une frequence augmentee des carences chez les patients atteints de syndrome de Sjogren (45 %) et de sclerodermie systemique (35 %) en comparaison a des populations de temoins apparies. Pour le syndrome de Sjogren, l’association est soutenue par des hypotheses physiopathologiques : destruction des glandes salivaires avec deficit secondaire en haptocorrine, infiltration lymphocytaire gastrique, insuffisance pancreatique exocrine a minima. Mais seules quelques etudes non prospectives avaient pu evoquer ce lien [3] . La question de la carence en B12 en cas de sclerodermie systemique interroge sur le lien avec l’atteinte digestive, et notamment gastrique de la maladie. Nos effectifs faibles ne permettent pas de repondre a cette question. Pour la sclerodermie systemique, l’imputabilite des inhibiteurs de pompe a protons n’est pas confirmee dans cette etude. Neanmoins, les effectifs faibles peuvent masquer cet effet. Conclusion Les donnees issues de ce travail prospectif montrent un risque relatif de carence en B12 de 2,25 [IC95 % ; 1,21–4,20] en cas de syndrome de Sjogren primaire et de 2,69 [IC95 % ; 1,23–5,90] en cas de sclerodermie systemique sans syndrome de Sjogren associe en comparaison a des populations appariees sur le sexe et l’âge, hospitalisees dans un service de medecine interne. Ces resultats plaident en faveur d’un depistage plus systematique de la carence en B12 dans la prise en charge du syndrome de Sjogren et de la sclerodermie systemique.

Melanin-concentrating hormone (MCH) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to exhibit mostly functionally antagonistic, but in some cases agonistic activities, e.g., in pigment cells and in the brain. Neuropeptide E-I (NEI) displays functional MCH-antagonist and MSH-agonist activity in different behavioral paradigms; the role of neuropeptide G-E (NGE) is not known. This study addressed the question of possible molecular interactions between alpha-MSH, MCH and the MCH-precursor-derived peptides NEI and NGE at the level of the pigment cell MCH receptor subtype (MCH-Rpc) and the different melanocortin (MC) receptors. Radioreceptor assays using [125I]MCH, [125l]alpha-MSH and [125I]NEI as radioligands and bioassays were performed with MCI-R-positive and MC1-R-negative mouse B16 melanoma cells and with COS cells expressing the different MC receptors. The IC50s of alpha-MSH and NEI or NGE for [125I]MCH displacement from mouse MCH-Rpc were 80-fold and, respectively,300-fold higher than that of MCH, and the IC50s for MCH and NEI or NGE for [125I]alpha-MSH displacement from mouse MC1-R were 50,000-fold and200,000-fold higher than that of alpha-MSH. No high-affinity binding sites for NEI were detected on B16 melanoma cells and there was no significant displacement of [1251]alpha-MSH by MCH, NEI or NGE with MC3-R, MC4-R and MC5-R expressed in COS cells. At concentrations of 100 nM to 10 microM, however, MCH, NEI and NGE induced cAMP formation and melanin synthesis which could be blocked by agouti protein or inhibitors of adenylate cyclase or protein kinase A. This shows that mammalian MCH-precursor-derived peptides may mimic MSH signalling via MC1-R activation at relatively high, but physiologically still relevant concentrations, as e.g. found in autocrine/paracrine signalling mechanisms.

L'angiome plan trigemine est une malformation vasculaire de la face, presente des la naissance, dont la particularite est d'etre parfois associe a une localisation intracrânienne, realisant alors le syndrome de Sturge-Weber (SSW). Evaluer le risque de cette association permet une meilleure prise en charge de l'enfant atteint.

To describe the contribution made by consultations for learning disorders through their specific aims.The prognosis of children with specific learning difficulties, suffering from dysphasia, dyslexia, dyscalculia, dyspraxia, dysexecutive or dysattentional syndrome, partly depends on whether the methods and materials required for their re-educational and pedagogical adaptation are financed, made available and explained to the child's family in the cases that have been classed as the severest. This is the goal of the 37 reference centres that have been set up in France in the last five years. This work describes the objectives of this consultation, as well as specific ways in which useful information about the child can be shared.Consultation for learning difficulties involves an interdisciplinary assessment that allows the case of a child with learning disorders to be placed within a new set of dynamics.

Coordinating professionals for the initial assessment and treatment of children with learning difficulties is a complicated task.Initial contact with the sources of information, the history and physical examination, a fast neuropsychological evaluation and requesting suitable tests allow the professional to reach an evaluation that will lead to a proposal for re-education. Evaluating the results of the re-education, coordination among the re-educators and the school, and explanations for the family are essential conditions for favourable progress to be made.In a visit for learning disorders, the role of the neuropaediatrician is crucial, especially to optimise the performance of the team as regards time and efficiency, and to improve the quality of the service offered to the child.

The development and multiplication of information about learning disorders leads to the need to systematise the knowledge available and to base it on the clinical data.Apart from trouble-free diagnoses, non-verbal learning disorders are characterised by their high comorbidity rate. They are associated to attention deficit with or without hyperactivity, motor coordination disorder, dyscalculia, problems with social development and also, to a certain extent, oral and written language disorders. Depending on countries, a child with a good fundamental intellectual capacity and good development of language, but motor clumsiness and low visuospatial skills with or without relational difficulties can be diagnosed in different ways. In this study, after briefly reviewing the literature on comorbidity and the contexts of the work, we propose a set of guidelines for basic examination that can be used in visits due to learning disorders, including suggestive history, areas that require detailed questioning, and central tests.Partly because of the comorbidity, following the introductory visit, only a multidisciplinary team can study a child with non-verbal learning disorder properly, using specific tests to pinpoint the profile of their difficulties; their strong points should also be stressed.

Melanin-concentrating hormone (MCH) is a neuropeptide occurring in all vertebrates and some invertebrates and is now known to stimulate pigment aggregation in teleost melanophores and food-intake in mammals. Whereas the two MCH receptor subtypes hitherto cloned, MCH-R1 and MCH-R2, are thought to mediate mainly the central effects of MCH, the MCH-R on pigment cells has not yet been identified, although in some studies MCH-R1 was reported to be expressed by human melanocytes and melanoma cells. Here we present data of a structure-activity study in which 12 MCH peptides were tested on rat MCH-R1 and mouse B16 melanoma cell MCH-R, by comparing receptor binding affinities and biological activities. For receptor binding analysis with HEK-293 cells expressing rat MCH-R1 (SLC-1), the radioligand was [125I]-[Tyr13]-MCH with the natural sequence. For B16 cells (F1 and G4F sublines) expressing B16 MCH-R, the analog [125I]-[D-Phe13, Tyr19]-MCH served as radioligand. The bioassay used for MCH-R1 was intracellular Ca2+ mobilization quantified with the FLIPR instrument, whereas for B16 MCH-R the signal determined was MAP kinase activation. Our data show that some of the peptides displayed a similar relative increase or decrease of potency in both cell types tested. For example, linear MCH with Ser residues at positions 7 and 16 was almost inactive whereas a slight increase in side-chain hydrophilicity at residues 4 and 8, or truncation of MCH at the N-terminus by two residues hardly changed binding affinity or bioactivity. On the other hand, salmonic MCH which also lacks the first two residues of the mammalian sequence but in addition has different residues at positions 4, 5, 9, and 18 exhibited a 5- to 10-fold lower binding activity than MCH in both cell systems. A striking difference in ligand recognition between MCH-R1 and B16 MCH-R was however observed with modifications at position 13 of MCH: whereas L-Phe13 in [Phe13, Tyr19]-MCH was well tolerated by both MCH-R1 and B16 MCH-R, change of configuration to D-Phe13 in [D-Phe13, Tyr19]-MCH or [D-Phe13]-MCH led to a complete loss of biological activity and to a 5- to 10-fold lower binding activity with MCH-R1. By contrast, the D-Phe13 residue increased the affinity of [D-Phe13, Tyr19]-MCH to B16 MCH-R about 10-fold and elicited MAP kinase activation as observed with [Phe13, Tyr19]-MCH or MCH. These data demonstrate that ligand recognition by B16 MCH-R differs from that of MCH-R1 in several respects, indicating that the B16 MCH-R represents an MCH-R subtype different from MCH-R1.

Melanin-concentrating hormone (MCH) is a potent orexigenic neuropeptide and a physiological antagonist of alpha-melanocyte-stimulating hormone (alpha-MSH) in the brain as well as at peripheral sites, including the pigmentary systems of specific vertebrates. Two receptor subtypes for MCH, MCH-R1 and MCH-R2, have been cloned, but other receptor subtypes are likely to exist. Based on our own data and the current literature, we have compared the expression of different receptors for MCH in various mammalian cell lines and tissues. Summarizing all data currently available, we conclude that the two cloned MCH receptors, MCH-R1 and MCH-R2, exhibit differences in their expression pattern, although MCH-R1 is generally colocalized in all tissues where MCH-R2 expression is found. It appears that MCH-R1 is more abundant and has a wider distribution pattern than MCH-R2. Other hypothetical MCH-R subtypes may be expressed in specific tissues, e.g., in the pigment cell system.

Melanin-concentrating hormone (MCH), a cyclic nonadecapeptide, is predominantly expressed in mammalian neurons located in the zona incerta and lateral hypothalamus. Current interest in MCH relates to its role in the control of feeding behaviour. Two receptors for MCH were recently found: MCH-R(1) and MCH-R(2). We show here by RT-PCR analysis and immunofluorescence studies that the human neuroblastoma cell line Kelly expresses MCH and MCH-R(1) but not MCH-R(2). In competition assays using 125I-labelled MCH an inhibitory concentration 50% (IC(50)) of 76nM was determined for MCH, indicating a high affinity of Kelly cells for MCH. MCH induces mitogen-activated protein kinase (MAPK) phosphorylation in Kelly cells but no increase in the intracellular free Ca(2+) concentration. This suggests that MCH signals via Galpha(i)/Galpha(0) in these cells. The presence and functionality of MCH-R(1) renders this neuronal cell a very useful model for future structure-activity studies in a physiological environment mimicking the human brain for the evaluation of potential appetite-regulating drugs.

To know the frequency of Todd s paralysis during the video EEG monitoring studies, to investigate in its pathophysiology, and to confirm its value to localise the epileptic focus.We reviewed 114 monitoring studies, in 102 patients.Sixty patients had epileptic seizures. An obvious paresis was noted in four seizures of two patients (3 and 1, respectively). Both patients had frontal epilepsy. During the paralysis, in the first patient the EEG showed ictal discharges on the contralateral centrotemporal area. In the second patient, the EEG demonstrated slow waves in the contralateral frontal region. The ictal onset was contralateral to the paresis in all cases. No patient with pseudoseizures had paralysis.Postconvulsive paralysis are not frequent in video EEG monitoring studies. However, if present it points out to a contralateral seizure onset. In our series it happened in patients with frontal seizures. The EEG may help to clarify if it correspond to a true postictal phenomenon or to a ictal paralysis.

LTG is a new antiepileptic drug that is nowadays very often used in epileptic patients.To determine efficacy and safety of Lamotrigine (LTG) in the first five years after its marketing in patients at a third level university hospital, as well as its impact on the management of classic antiepileptic drugs (AED).We reviewed retrospectively our Epilepsy Unit Database. One hundred patients were treated with LTG in a 5-year period. Efficacy was evaluated comparing seizure frequency in a 6-month period before and after LTG. The type of epilepsy, side effects, blood levels and concomitant treatments were considered in the analysis.LTG was effective in all groups of epileptic patients studied. Eighteen percent of patients became seizure-free. Seventeen percent of patients improved more than 50%. Fifty-seven percent of patients remained treated with LTG after four years of follow-up. Side effects were mild, but frequent; only four patients discontinued LTG because of adverse effects. Serum levels were usually high, but showed no relation with clinical efficacy. The mean number of AED taken per patient increased.LTG is a safe an effective drug in epilepsy. It has a clear impact in the management of the epileptic patients.

The cell nucleus is highly organized into distinct domains that spatially separate physiological processes. One of these domains, the Sp100-promyelocytic leukemia protein nuclear body (NB), is implicated in pathological processes, such as cancer and viral infection, yet its functions remain poorly understood. We show here that Sp100 interacts physically and functionally with ETS-1 and that NB morphology is affected by ETS-1. ETS-1 is a member of the ets family of transcription factors, which are key mediators of physiological and pathological processes. We have found that Sp100 interacts with two regions of ETS-1 (domains A+B and D+E+F). ETS-1 alters NBs while remaining localized throughout the nucleus, apparently by recruitment of the core component Sp100 away from the NBs. Sp100 strongly increases ETS-1 activation of natural and ets-focused promoters, through a mechanism involving the activation (C) domain of ETS-1 in addition to the interaction domains. Sp100 acts as a novel coactivator that potentiates the activator function of ETS-1. Our results provide an important new connection between nuclear structures and an important regulator of gene expression.

The vagal nerve stimulation is a new technique for the treatment of drug resistant epilepsies. DEVELOPMENT: In 1997, it was approved in United States by the FDA to be used in adults with refractory focal epilepsies not candidates for epilepsy surgery. Its mechanism of action is unknown. The results in the controlled studies indicated a decrease of 30 50% in the seizure frequency in around 50% of the patients. Although more experience is needed to corroborate these results, it seems reasonable as a treatment for patients with difficult epilepsies, especially when the response to the antiepileptic drugs is poor or they are producing secondary effects, and the resection of the focus is not possible.

Approximately 20% of all epileptic patients are not satisfactorily controlled by the available antiepileptic drugs. Some of these patients have epileptic syndromes which could potentially be treated by surgery.The technological advances applied to diagnostic and therapeutic methods have improved the identification of epileptic patients who may benefit from surgery. Up to 80% of the patients with focal epilepsies symptomatic of well defined lesions may become free of seizures after excision of the lesion or epileptogenic focus. Other forms of epilepsy, such as the so-called catastrophic infantile forms, may improve temporarily when techniques such as hemispherectomy or callosotomy are used. The morbidity and mortality of these surgical procedures are minimal. The results depend on correct selection of the patients. A strict protocol for rigorous evaluation of the patients should be used, with the collaboration of neurologists, epileptologist neuropaediatricians, neuropsychologists, neurophysiologists, neuroimaging specialists, psychiatrists and neurosurgeons. There should first be clear answers to three key questions: 1. Who is a good candidate? 2. How should the selection be made? and 3. When is the best time for evaluation?At present it seems clear that the surgery of epilepsy is used less than it could be. It is therefore necessary to encourage the development of specialist units to select patients and treat them, and to develop the means whereby patients can obtain this highly specialized attention.

Studies of twins, familial aggregates and particular phenotypic conditions have shown an inherited basis for some dysphasias or specific developmental language impairments (SLI). This predisposition is usually multifactorial but the analysis of some families allows to postulate an autosomal dominant transmission of deficits in specific modular aspects of linguistic competences. Moreover, neuroimaging studies have shown modifications of normal volumetric interhemispheric asymmetries, and in group of SLI with receptive prominent disorder coexist epileptiform activity in wakefulness and non-REM sleep EEG; in some of these cases, antiepileptic drugs, specially steroids, can significantly ameliorate the language processing. As many patients with SLI have a difficulty for discrimination of subtle temporal indices, a hypothesis can also be made of a dysfunction in various subcortical structures (thalamus, basal ganglia, cerebellum) modulating the cerebral cortex in phonological processing.

Studies of twins, familial aggregates and particular phenotypic conditions have shown an inherited basis for some dysphasias or specific developmental language impairments (SLI). This predisposition is usually multifactorial but the analysis of some families allows to postulate an autosomal dominant transmission of deficits in specific modular aspects of linguistic competences. Moreover, neuroimaging studies have shown modifications of normal volumetric interhemispheric asymmetries, and in group of SLI with receptive prominent disorder coexist epileptiform activity in wakefulness and non-REM sleep EEG; in some of these cases, antiepileptic drugs, specially steroids, can significantly ameliorate the language processing. As many patients with SLI have a difficulty for discrimination of subtle temporal indices, a hypothesis can also be made of a dysfunction in various subcortical structures (thalamus, basal ganglia, cerebellum) modulating the cerebral cortex in phonological processing.

Summary: One hundred twenty children aged 10 months to 16 years 9 months were included in three studies with lamotrigine (LTG): a single-blind study (n = 60), a pharmacokinetic study (n = 23), and a compassionate group (n = 37). At 3 months, 11 patients had become seizure-free and 34 had >50% decrease in seizure frequency. The best results involved absence epilepsy, Lennox-Gastaut syndrome (LGS), and other symptomatic generalized epilepsy. Forty-two patients were followed > 1 year, 22 for a mean of 2.2 years, and there was no significant increase in seizure frequency as compared with 3-month follow-up. Fourteen patients became seizure-free for >6 months; all except 1 had generalized epilepsy. For 12 patients, treatment could be reduced to monotherapy, but for those with valproate (VPA) comedication LTG dosage had to be increased; 25% of patients with VPA monotherapy exhibited skin rash, appearing 3–18 days after starting LTG. For 4 patients, LTG could be reintroduced after VPA was withdrawn. Ten patients had ataxia and/or drowsiness and 2 had vomiting. For all other patients, tolerance was excellent.

Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae.

Objective. To know the frequency of Todd 's paralysis during the video-EEG monitoring studies, to investigate in its pathophysiology, and to confirm its value to localise the epileptic focus. Patients and methods. We reviewed 114 monitoring studies, in 102 patients. Results. Sixty patients had epileptic seizures. An obvious paresis was noted in four seizures of two patients (3 and 1, respectively). Both patients had frontal epilepsy. During the paralysis, in the first patient the EEG showed ictal discharges on the contralateral centrotemporal area. In the second patient, the EEG demonstrated slow waves in the contralateral frontal region. The ictal onset was contralateral to the paresis in all cases. No patient with pseudoseizures had paralysis. Conclusions. Postconvulsive paralysis are not frequent in video-EEG monitoring studies. However, if present it points out to a contralateral seizure onset. In our series it happened in patients with frontal seizures. The EEG may help to clarify if it correspond to a true postictal phenomenon or to a ictal paralysis.

The emergence of low-cost carriers (LCCs) has been a key catalyst for the development of the aviation industry in the last decade. Indeed, extensive research has been undertaken to analyze the business model and impact on the aviation sector and beyond. Despite recent developments in the LCC markets in Asia and Latin America, much of the research has been focused on developed countries. Therefore, the purpose of this book is to identify the premises and prerequisites of the LCC model, and assess whether this business model could be successful in other less-developed countries, in particular the countries of Sub-Saharan Africa. This book identifies various definitions that have been applied to describe the LCC business model. In essence the majority of researchers define LCCs as carriers which, through a variety of operational processes, have achieved a cost advantage over full-service carriers (FSCs). This cost advantage is, in most cases, translated to the consumers by a lower fare offering. Although many carriers are defined as LCCs, the LCC model has developed into many different variations since the original Southwest Airlines model, the first U.S. LCC, which began operations in the 1960s.

For the purposes of this book, "open skies" refers to a bilateral or multilateral air service agreement that liberalizes the rules for international aviation markets and minimizes government intervention. It can apply to passenger or cargo services or both, for both scheduled and charter air services. This book evaluates Africa's progress toward liberalizing air services. It specifically examines what the term implementation means in the context of applying the principles of one of the major pan-African multilateral agreements, the Yamoussoukro decision. It also highlights the shortcomings of the 20-year-old effort toward liberalizing air services in Africa by analyzing pending or completed implementation steps both on a pan-Africa level and within various regions. The book focuses on the challenges posed by the poor aviation safety and security standards in most African countries. Finally the sector work measures the impact of certain policy steps of the decision and evaluates the economic significance of air transportation and its full liberalization in Africa. It concludes with policy recommendations that aim at completing implementation to fully liberalize Africa's air services.