Incidence and phenotypes of childhood-onset genetic epilepsies:a prospective population-based national cohort

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy

Headache and Psychological Comorbidities: An Appraisal of the Evidence

Background: It has been observed that there is a higher-than-expected risk of anxiety and depression in children with chronic headache and also an increased risk for the persistence of headache in patients with anxiety and depression. Objectives: This review aims to identify and assess the relationships between primary headache disorders and comorbid emotional and psychological disorders. Methods: A targeted review of the literature was carried out. Results: The associations between the disorders are more pronounced in clinic patients, who may represent the severe end of the headache spectrum, but less clear in patients who were identified in population-based studies and who may represent the “average” child with headache or the “average” child with psychological disorders. Conclusions: Understanding this bidirectional association of comorbid disorders is of great importance to offering a holistic biopsychosocial approach to the management of headache disorders in children and adolescents and in addressing the risks for and the co-existence of psychological comorbidities

The resistance of Palestinians in Jerusalem to the Israeli occupation between 1987 and 2015.

The aim of this study is to search the Palestinian’s resistance of the Israeli occupation in Jerusalem timed of (1987-2015), and surveying the chronology of the current intifada and the previous intifadas without focusing on any partial or daily circumstances or parts. The core of this study concentrates on the means and methods that the Palestinians used in Jerusalem in order to resist the Israeli occupation in (1987-2015), and the Palestinians progression in the reduction of the occupation here and far targets achievements. It is also measure the positive achievements of the Palestinians resistance related to the city future in the final negotiations. In order to achieve the goals of the study, the researcher adopted the (analytical description) as a main method, partially he utilized the quantity method. This study passed the preparation phase, developed the research methodology, improved the research styles and methods, in addition to data analysis and insertion. The researcher also relied on inductive reasoning in processing the data, classifying and listing resistance operations in Jerusalem. The study presents the forms of resistance displayed between 1987 and 2015, and discusses the motives behind the determination of Palestinian to resist, particularly in light of the Oslo Peace Accords; that maintained the status quo in Jerusalem and postponed discussing issues pertaining to it until the final negotiations. The years following the Oslo Peace Accords, however, have witnessed a growing escalation in Israeli oppressive policies towards Palestinians. The study finds that Israel has ceaselessly imposed military, security, political and legislative measures aimed at extending its hegemony over all spheres of Palestinian life in Jerusalem including geography, demography and religion. Yet, Palestinians in Jerusalem have not given up on resisting the occupation as much as they could and through the means available at their disposal Peaceful popular resistance, also referred to as “nonviolent resistance,” has been the dominant form of resistance employed by Jerusalem’s Palestinians over the past few decades. Even though Israel did manage to achieve many of its initial goals in Jerusalem, this study shows that Palestinian’s resistance and defiance were the primary obstacles of the absolute Judaization of the holy city. They also maintained the belonging soul among Arab and Muslim peoples towards Jerusalem and it’s holy sites. The researcher presents main conclusions, that the study has arrived, where the Palestinian’s resistance evolves in accordance with Israel’s security developments in the city. Additionally, this resistance is transgenerational and does not fade. The perseverance of Palestinians in Jerusalem is attributed to their willingness to sacrifice and their profound feeling of belonging both to the city and its holy sites. Meanwhile, the main reason for the frustration of Palestinians in Jerusalem is the lack of political will among Palestinian and Arab leaders to provide them with genuine support and assistance. This led the researcher to raise the following question: What is the future of Palestinian resistance to the Israeli occupation in Jerusalem, particularly in light of the latest regional and international unrest that indicates to the possibility of Israel assuming sweeping ascendancy in the conflict over Jerusalem? Thus, the study has reached several recommendations, the most important of which is the necessity to exert more efforts that could lead to the establishment of a centralized Palestinian reference point capable of working on the field in route to “unifying the national effort”. Furthermore, there is a need to create independent research centers specializing in issues concerning Jerusalem in order to document the acts of resistance in the city, separate from other research sectors. The study also recommends the circulation of Arab and Islamic culture among Palestinian as it constitutes core of the authentic Palestinian narrative in the face of Israeli falsehoods. In addition to, the centrality of Al Aqsa Mosque in the conflict should be emphasized as should the unity of national identity in defense of the city and its residenc

Experts' opinion about the pediatric secondary headaches diagnostic criteria of the ICHD-3 beta

Background: The 2013 International Classification of Headache Disorders-3 was published in a beta version to allow clinicians to confirm the validity of the criteria or suggest improvements based on field studies. The aim of this work was to review the Secondary Headache Disorders and Cranial Neuralgias and Other Headache Disorders sections of ICHD-3 beta data on children and adolescents (age 0-18 years) and to suggest changes, additions, and amendments

Experts’ opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents

Background The 2013 International Classification of Headache Disorders-3 (ICHD-3) was published in a beta version to allow the clinicians to confirm the validity of the criteria or to suggest improvements based on field studies. The aim of this work was to review the Primary Headache Disorders Section of ICHD-3 beta data on children and adolescents (age 0-18 years), and to suggest changes, additions, and amendments. Methods Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the literature available on pediatric headache, they made observations and proposed suggestions for the primary headache disorders section of ICHD-3 beta data on children and adolescents. Results Some headache disorders in children have specific features which are different from those seen in adults and which should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psycho-social basis in children and adolescents making primary headache disorders in children distinct from those in adults. Conclusions Several recommendations are presented in order to make ICHD-3 more appropriate for use with children

Experts’ opinion about the pediatric secondary headaches diagnostic criteria of the ICHD-3 beta

Background: The 2013 International Classification of Headache Disorders-3 was published in a beta version to allow clinicians to confirm the validity of the criteria or suggest improvements based on field studies. The aim of this work was to review the Secondary Headache Disorders and Cranial Neuralgias and Other Headache Disorders sections of ICHD-3 beta data on children and adolescents (age 0–18\ua0years) and to suggest changes, additions, and amendments. Methods: Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the available literature on pediatric headache, they made observations and proposed suggestions for the mentioned headache disorders on children and adolescents. Results: Some headache disorders in children have specific features, which are different from adults that should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psychosocial basis in children and adolescents making primary headache disorders in children distinct from those in adults. Conclusions: Several recommendations are presented in order to make ICHD-3 more appropriate for use in children