Revised French guidelines for the diagnosis and management of migraine in adults and children.

International audience: N/A

Defining the Structural Parameters That Confer Anticonvulsant Activity by the Site-by-Site Modification of ( R )- N ′-Benzyl 2-Amino-3-methylbutanamide

Primary Amino Acid Derivatives (PAADs) (N′-benzyl 2-substituted 2-amino acetamides) are structurally related to Functionalized Amino Acids (FAAs) (N′-benzyl 2- substituted 2-acetamido acetamides) but differ by the absence of the terminal N-acetyl group. Both classes exhibit potent anticonvulsant activities in the maximal electroshock seizure animal model and the reported structure-activity relationships (SARs) of PAADs and FAAs differ in significant ways. Recently, we documented that PAAD efficacy was associated with a hydrocarbon moiety at the C(2)-carbon, while in the FAAs, a substituted heteroatom one atom removed from the C(2)-center was optimal. Previously in this issue, we showed that PAAD activity was dependent upon the electronic properties of the 4′-N′-benzylamide substituent, while FAA activity was insensitive to electronic changes at this site. In this study, we prepared analogs of (R)-N′-benzyl 2-amino-3-methylbutanamide to identify the structural components for maximal anticonvulsant activity. We demonstrated that the SAR of PAADs and FAAs diverged at the terminal amide site and that PAADs had considerably more structural latitude in the types of units that could be incorporated at this position, suggesting that these compounds function according to different mechanism(s)

Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus

ObjectiveDisturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).MethodsPrepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.ResultsUrine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.ConclusionsOur findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning

Hypersensitivity Reaction to Midazolam

International audienceThe incidence of hypersensitivity due to anesthesia in children is 1/7741. Hypersensitivity reactions are a result of either an immunologic mechanism (allergic or anaphylactic reaction) generally mediated by immunoglobulines E (IgE) or immunoglobulines G (IgG) antibodies or a non immunologic mechanism (pseudo-allergic or anaphylactoid reaction) related to different phenomenon such as non specific histamine liberation. In children, latex is the principal cause of anaphylaxis during anesthesia (41%) followed by non depolarizing muscle relaxants (19%) and antibiotics (9%); anaphylaxis due to hypnotics is rare (2,43%) and midazolam is responsible in only 0,5% of the cases. Anaphylaxis during anesthesia is mediated by immunoglobulines E antibodies in 42% of the cases in children. We describe here a case of a six year old child who presented a hypersensitivity skin reaction to midazolam thirty minutes after intrarectal midazolam administration. It was a generalized rash of the whole body without pruritis. The prick tests realized six weeks after the reaction were negative and the intradermoreaction was positive to midazolam confirming the hypersensitivity reaction to midazolam. A hypersensitivity identification card to midazolam was delivered to the patient

Emotional Status, Perceived Control of Pain, and Pain Coping Strategies in Episodic and Chronic Cluster Headache

Cluster headache (CH) is a chronic syndrome characterized by excruciatingly painful attacks occurring with circadian and circannual periodicity. The objectives of the present study were, in CH patients, to determine by principal component analysis the factor structure of two instruments commonly used in clinics to evaluate pain locus of control (Cancer Locus of Control Scale–CLCS) and coping strategies (Coping Strategies Questionnaire–CSQ), to examine the relationship between internal pain controllability and emotional distress, and to compare psychosocial distress and coping strategies between two subsets of patients with episodic or chronic CH. Results indicate, for CLCS, a 3-factor structure (internal controllability, medical controllability, religious controllability) noticeably different in CH patients from the structure reported in patients with other painful pathologies and, for CSQ, a 5-factor structure of CSQ which did not markedly diverge from the classical structure. Perceived internal controllability of pain was strongly correlated with study measures of depression (HAD depression/anhedonia subscale, Beck Depression Inventory). Comparison between subsets of patients with episodic or chronic CH of emotional status, pain locus of control, perceived social support and coping strategies did not reveal significant differences apart for the Reinterpreting pain sensations strategy which was more often used by episodic CH patients. Observed tendencies for increased anxiety and perceived social support in patients with episodic CH, and for increased depression and more frequent use of the Ignoring pain sensations strategy in patients with chronic CH, warrant confirmation in larger groups of patients

Evaluation of a new [18F] labeled tracer targeting synaptic vesicle protein 2C by ex vivo autoradiography and in vivo PET study in rat brain.

Introduction The synaptic vesicle protein 2 (SV2) family is a group of integral membrane glycoproteins homologous to the major facilitator superfamily and could be involved in several neuronal diseasesa. The binding of the novel, no-carrier-added, [18F] labeled compound [18F]UCB-F to the SV2C isoform was evaluated in rat brain. Methods Radiochemistry No-carrier added [18F]UCB-F was obtained following the method shown in Fig. 1. The identity and purity of the tracer were evaluated by radioUPLC and chiral radioHPLC. Autoradiography Sprague Dawley rat brain sections were incubated at RT with buffered [18F]UCB-F solutions and exposed on film. Matching sections were stained with cresyl violet for structural identification. PET studies PET studies (Siemens Concorde Focus 120 µPET) were performed under isoflurane anesthesia. The tracer was injected as a bolus via the tail vein. After a 10-min transmission scan to correct for attenuation, dynamic emission data was recorded for a total of 60 min. The impact of P-glycoprotein (P-gp) activity on tracer uptake in the brain was evaluated using cyclosporine (50 mg/kg SC). Metabolite analysis During PET studies, arterial blood samples were taken for the measurement of tracer metabolites. Plasma was separated by centrifugation and proteins were acid-precipitated. Metabolites were detected using HPLC and confirmed by gamma counting. Results The tracer was obtained with a decay corrected yield of ±10%. Specific activity ranged from 10 GBq/µmol to 40 GBq/µmol. Ex vivo autoradiography showed that the binding of [18F]UCB-F to SV2C closely matched the expected distribution b (Fig.2). In vivo PET studies revealed that [18F]UCB-F briefly entered the brain, but exhibited extremely rapid washout. A large accumulation in the liver and intestines was observed. Metabolite analysis in the plasma revealed high protein binding and rapid metabolism. Inhibition of P-gp transport with cyclosporin had no clear effect on the rapid washout from the brain. Conclusions Despite a close match between [18F]UCB-F SV2C binding and the expected brain distribution, the pharmacokinetics in rat brain appear unfavorable for the use of this tracer to quantify SV2C in vivo. Acknowledgement / References a Lynch & al (2004) Proc. Natl. Acad. Sci. USA 101:9861 b Janz & Sudhof (1999) Neuroscience 94:1279 c The authors thank the Walloon Region and the FRNS Belgium for financial support