Antecedents of epilepsy and seizures among children born at extremely low gestational age

ObjectiveTo identify specific risk factors for epilepsy for individuals born extremely preterm.Study DesignIn a prospective cohort study, at 10-year follow-up, children were classified as having epilepsy or seizures not associated with epilepsy. We evaluated for association of perinatal factors using time-oriented, multinomial logistic regression models.ResultsOf the 888 children included in the study, 66 had epilepsy and 39 had seizures not associated with epilepsy. Epilepsy was associated with an indicator of low socioeconomic status, maternal gestational fever, early physiologic instability, postnatal exposure to hydrocortisone, cerebral white matter disease and severe bronchopulmonary dysplasia. Seizure without epilepsy was associated with indicators of placental infection and inflammation, and hypoxemia during the first 24 postnatal hours.ConclusionsIn children born extremely preterm, epilepsy and seizures not associated with epilepsy have different risk profiles. Though both profiles included indicators of infection and inflammation, the profile of risk factors for epilepsy included multiple indicators of endogenous vulnerability

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)

BACKGROUND Deficiency of adenosine deaminase 2 (DADA2) is a syndrome with pleiotropic manifestations including vasculitis and hematologic compromise. A systematic definition of the relationship between ADA2 mutations and clinical phenotype remains unavailable. OBJECTIVE We tested whether the impact of ADA2 mutations on enzyme function correlates with clinical presentation. METHODS DADA2 patients with severe hematologic manifestations were compared with vasculitis-predominant patients. Enzymatic activity was assessed using expression constructs reflecting all 53 missense, nonsense, insertion and deletion genotypes from 152 patients across the DADA2 spectrum. RESULTS We identified DADA2 patients presenting with pure red cell aplasia (PRCA, n = 5) or bone marrow failure syndrome (BMF, n = 10). Most patients did not exhibit features of vasculitis. Recurrent infection, hepatosplenomegaly and gingivitis were common in patients with BMF, of whom half died from infection. Unlike DADA2 patients with vasculitis, patients with PRCA and BMF proved largely refractory to tumor necrosis factor inhibitors. ADA2 variants associated with vasculitis predominantly reflected missense mutations with at least 3% residual enzymatic activity. By contrast, PRCA and BMF were associated with missense mutations with minimal residual enzyme activity, nonsense variants, and insertions / deletions resulting in complete loss of function. CONCLUSION Functional interrogation of ADA2 mutations reveals an association of subtotal function loss with vasculitis, typically responsive to TNF blockade, whereas more extensive loss is observed in hematologic disease which may be refractory to treatment. These findings establish a genotype-phenotype spectrum in DADA2

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141801/1/epi13937_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141801/2/epi13937.pd

Alteration of inhibitory circuits in the somatosensory cortex of Ts65Dn mice, a model for Down's syndrome

Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4¿5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients

An empirical approach to selecting community-based alcohol interventions:combining research evidence, rural community views and professional opinion

<p>Abstract</p> <p>Background</p> <p>Given limited research evidence for community-based alcohol interventions, this study examines the intervention preferences of rural communities and alcohol professionals, and factors that influence their choices.</p> <p>Method</p> <p>Community preferences were identified by a survey of randomly selected individuals across 20 regional Australian communities. The preferences of alcohol professionals were identified by a survey of randomly selected members of the Australasian Professional Society on Alcohol and Other Drugs. To identify preferred interventions and the extent of support for them, a budget allocation exercise was embedded in both surveys, asking respondents to allocate a given budget to different interventions. Tobit regression models were estimated to identify the characteristics that explain differences in intervention preferences.</p> <p>Results</p> <p>Community respondents selected school programs most often (88.0%) and allocated it the largest proportion of funds, followed by promotion of safer drinking (71.3%), community programs (61.4%) and police enforcement of alcohol laws (60.4%). Professionals selected GP training most often (61.0%) and allocated it the largest proportion of funds, followed by school programs (36.6%), community programs (33.8%) and promotion of safer drinking (31.7%). Community views were susceptible to response bias. There were no significant predictors of professionals' preferences.</p> <p>Conclusions</p> <p>In the absence of sufficient research evidence for effective community-based alcohol interventions, rural communities and professionals both strongly support school programs, promotion of safer drinking and community programs. Rural communities also supported police enforcement of alcohol laws and professionals supported GP training. The impact of a combination of these strategies needs to be rigorously evaluated.</p

UV-induced electrical and optical changes in PVC blends

2-Chloro-polyaniline (2-Cl-PANI) in its non-conducting (emeraldine base, EB) form, prepared by a chemical route, was dissolved together with poly-(vinylchloride) (PVC) in THF for casting into thin (10-50 μm) films. Upon exposure to UV radiation, the electrical conductivity of these films increased by more than 4 orders of magnitude (from 10-6 to 10-2 S/cm). This is attributed to the dehydrochlorination of PVC by exposure to energetic photons and subsequent doping of 2-Cl-PANI (i.e. conversion to emeraldine salt, ES) by in situ created HCl. The doped films could be returned to their undoped form by exposure to NH3 vapours. The UV-induced doping/NH3 undoping cycles could be repeated several times. Various spectroscopic techniques were employed to follow the changes in the films upon exposure to UV radiation. The same photo-dehydrochlorination process has also been utilized for optical and/or lithographic purposes by preparing PVC blends containing methyl violet, and acid-base indicator dye. The photo-dehydrochlorination can be effectively sensitized by incorporating hydroquinone into the PVC blends containing methyl violet

Overview of diagnosis and management of paediatric headache. Part I: diagnosis

Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)