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Background: Congenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide and is a major cause of neurodevelopmental impairment in children. At this point there are insufficient data on neurodevelopmental outcome of children with cCMV, both symptomatic and asymptomatic. Aim: This study aimed to describe the neurodevelopmental outcome in a large prospective cohort of children with cCMV.Methods: All children with cCMV, included in the Flemish cCMV register, were eligible for this study. Data on neurodevelopmental outcome was available in 753 children. Data on neuromotor, cognitive, behavioral, audi-ological and ophthalmological outcome were analyzed.Results: Neurodevelopmental outcome was normal in 530/753 (70,4 %) at any age of last follow-up. Mild, moderate and severe neurodevelopmental impairment was found in 128/753 (16,9 %), 56/753 (7,4 %) and 39/ 753 (5,2 %), respectively. Adverse outcome is found both in the symptomatic and asymptomatic children (53,5 % versus 17,8 %). Autism spectrum disorder (ASD) was diagnosed more often than in the general population in Flanders (2,5 % versus 0,7 %). Speech and language impairment was found in 2 %, even in absence of hearing loss.Conclusion: Both symptomatic and asymptomatic cCMV children are at risk of sequelae, with higher risk in case of first trimester infection. During follow-up of this population, special attention should be given to the audio-logical follow-up, the presence of hypotonia at young age, the possible higher risk of ASD and the risk of speech and language impairment even in absence of hearing loss. Our results emphasize the need for multidisciplinary neurodevelopmental follow-up of all cCMV infected children.

We present an instrument for dark-field x-ray microscopy installed on beamlineID06 of the ESRF — the first of its kind. Dark-field x-ray microscopy uses full field illumination of the sample and provides three-dimensional (3D) mapping of micro-structure and lattice strain in crystalline matter. It is analogous to dark-field electron microscopy in that an objective lens magnifies diffracting features of the sample. The use of high-energy synchrotron x-rays, however, means that these features can be large and deeply embedded. 3D movies can be acquired with a time resolution of seconds to minutes. The field of view and spatial resolution can be adapted by simple reconfiguration of the x-ray objective lens, reaching spatial and angular resolution of 30-100 nm and 0.001°, respectively. The instrument furthermore allows pre-characterization of samples at larger length scales using 3DXRD or DCT, such that a region of interest (e.g. a singlegrain) can be selected for high-resolution studies without the need to dismount the sample. As examples of applications we show work on mapping the subgrains in plastically deformed iron and aluminum alloys, mapping domains and strain fields in ferroelectric crystals, and studies of biominerals. This ability to directly characterize complex, multi-scale phenomena in-situ is a key step towards formulating and validating multi-scale models that account for the entire heterogeneity of materials. As an outlook, we discuss future prospects for such multi-scale characterization by combining DFXM with 3DXRD/DCT, and coherent x-ray methods for coarser and finer length-scales, respectively.

One of the peak moments of the debate on the European refugee crisis was caused by the circulation of images of Alan Kurdi, a three-year-old Syrian boy who drowned in the Aegean Sea on September 2, 2015. The images triggered worldwide reactions from politicians, nongovernmental organizations, and citizens. This article analyzes these reactions through a qualitative study of 961 tweets from Turkey and Flanders (Belgium), contextualizing them into the framing and representation of refugees before and after the images were released. Our study finds that, despite their iconic qualities and potential to mobilize Twitter users around refugee issues, the images did not cause a major shift in common discourses and representations. Instead, references to Kurdi were incorporated into preexisting discourses on and representations of refugees, thus offering different actors in the public debate on refugees with new symbols and motifs to construct meaning.

Summary Purpose Neurexins are neuronal adhesion molecules located in the presynaptic terminal, where they interact with postsynaptic neuroligins to form a transsynaptic complex required for efficient neurotransmission in the brain. Recently, deletions and point mutations of the neurexin 1 (NRXN1) gene have been associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if NRXN1 deletions also increase the risk of idiopathic generalized epilepsies (IGEs). Methods We screened for deletions involving the NRXN1 gene in 1,569 patients with IGE and 6,201 controls using high-density oligonucleotide microarrays. Key Findings We identified exon-disrupting deletions of NRXN1 in 5 of 1,569 patients with IGE and 2 of 6,201 control individuals (p = 0.0049; odds ratio (OR) 9.91, 95% confidence interval (CI) 1.92–51.12). A complex familial segregation pattern in the IGE families was observed, suggesting that heterozygous NRXN1 deletions are susceptibility variants. Intriguingly, we identified a second large copy number variant in three of five index patients, supporting an involvement of heterogeneous susceptibility alleles in the etiology of IGE. Significance We conclude that exon-disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.

Background:In Belgium, evidence-based practice guidelines on the field of adolescent substance misuse are currently being developed, using the ADAPTE methodology. Guideline appraisal with the AGREE II instrument is one of its important steps. Context: Research preceding the launch of AGREE II confirmed[for full text, please go to the a.m. URL], G-I-N Conference 2012

Background: Evidence-based practice guidelines for substance misuse in adolescents in Belgium will be developed using the ADAPTE methodology. Objectives: To get a comprehensive overview of relevant evidence-based practice guidelines on the prevention, screening, detection and treatment of alcohol[for full text, please go to the a.m. URL], G-I-N Conference 2012

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3\% and account for 20-30\% of all epilepsies. Despite their high heritability of 80\%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.

Purpose: KCNQ2 and KCNQ3 mutations are known to be responsible for Benign Familial Neonatal Seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether patients present with a particular phenotype. Method: We analyzed 80 patients with unexplained neonatal or earlyinfantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail. Results: We found seven different heterozygous KCNQ2 mutations in eight patients (8/80; 10%); six mutations were proven de novo. One parent with a milder phenotype was mosaic for the mutation. The eight patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had severe-profound intellectual disability with motor impairment. EEG at onset showed a burst suppression pattern or multifocal epileptic activity. Early MRI of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved. Conclusion: KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a very distinct electro-clinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin.

Mitochondrial disorders of oxidative phosphorylation (OXPHOS disorders) affect ~1/5000 individuals in the general population and present with a surprisingly wide range of multisystemic and neuromuscular phenotypes. The m.14487T>C mutation is a known pathogenic mtDNA mutation resulting in an amino acid substitution (p.M63V) in NADH dehydrogenase 6 (ND6), a complex I subunit of the mitochondrial respiratory chain, and has thus far been found in isolated cases with infantile Leigh syndrome and progressive dystonia. We report here adult and late-onset phenotypes as it was seen in a 5-generation Belgian family with 12 affected family members. Clinical and mutation load data were available for 9 family members, while biochemical analysis of the respiratory chain was performed in 3 muscle biopsies. Heteroplasmic m.14487T>C levels (36-52 % in leukocytes, 97-99 % in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100 % in leukocytes, 100 % in muscle). We found lower mutation loads (between 8 and 35 % in blood) in adult patients with clinical features including migraine with aura, Leber Hereditary Optic Neuropathy (LHON), sensorineural hearing loss and Diabetes Mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. Conclusions: The m.14487T>C mutation resulted in a broad spectrum of phenotypes in our family. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Mitochondrial disorders of the oxidative phosphorylation (OXPHOS) system affect ~1/5000 individuals in the general population and present with a surprisingly wide range of multisystemic and neuromuscular phenotypes. The m.14487T>C mutation is a known pathogenic mtDNA mutation resulting in an amino acid substitution (p.M63V) in NADH dehydrogenase 6 (MT ND6), a complex I subunit of the mitochondrial respiratory chain. Thus far it has been found in isolated cases with infantile Leigh syndrome and progressive dystonia. We report here adult and late-onset phenotypes as it was seen in a 5-generation Belgian family with 12 affected family members. Clinical and mutation load data were available for 9 family members, while biochemical analysis of the respiratory chain was performed in 3 muscle biopsies. Heteroplasmic m.14487T>C levels (36-52 % in leukocytes, 97-99 % in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100 % in leukocytes, 100 % in muscle). We found lower mutation loads (8-35 % in blood) in adult patients with clinical features including migraine with aura, Leber Hereditary Optic Neuropathy (LHON), sensorineural hearing loss and Diabetes Mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue of these patients. Conclusions: The m.14487T>C mutation resulted in a broad spectrum of phenotypes in our family. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Opsoclonus-myoclonus syndrome (OMS), a movement disorder characterised by chaotic eye movements and myoclonus, is a rare clinical entity. We present two cases of opsoclonus-myoclonus syndrome of paraneoplastic origin. In the first patient the syndrome was associated with a breast carcinoma and in the second patient with a non small cell lung carcinoma. However none of the commonly associated antibodies were found in these cases. From the neuropathological findings from the first patient we find arguments that support the current hypothesis on the pathophysiology of OMS namely a dysfunction in brainstem and cerebellum. We conclude that in adults with OMS one has to be very suspicious of a possible neoplastic origin of the syndrome. The antibodies associated with some cases of OMS are thought to play a role in the pathophysiology of the syndrome although the exact immunologic mechanism remains unknown. Research into the neuropathological substrate of OMS yields a broad range of abnormalities in brain stem and cerebellum. However none of these findings seem to be pathognomonic. As for the possible therapy of OMS, several immunomodulating strategies can be used with varying success. At present there is no established standard therapy.

In 2008, a group of Belgian epilepsy experts published recommendations for antiepileptic drug (AED) treatment of epilepsies in adults and children. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence for efficacy, common daily practice and the personal views and experiences of the authors. In November 2011 the validity of these recommendations was reviewed by the same group of Belgian epilepsy experts who contributed to the preparation of the original paper. The recommendations made in 2008 for initial monotherapy in paediatric patients were still considered to be valid, except for the first choice treatment for childhood absence epilepsy. This update therefore focuses on the treatment recommendations for initial monotherapy and add-on treatment in adult patients. Several other relevant aspects of treatment with AEDs are addressed, including considerations for optimal combination of AEDs (rational polytherapy), pharmacokinetic properties, pharmacodynamic and pharmacokinetic interaction profile, adverse effects, comorbidity, treatment of elderly patients, AED treatment during pregnancy, and generic substitution of AEDs.

After decades in which party competition was fought in the centre ground, the 2017 UK General Election witnessed a return to more conflictual politics. This article assesses public support for the electoral strategies of the main parties and examines the extent to which the issues the parties campaigned on resonated with their own supporters, as well as with the wider public. Drawing on the issue-yield framework, the article shows that the Conservative campaign – generally considered to be badly run – did not focus on issues that would fully exploit the opportunities for expanding support that were open to the party. Labour, by contrast, played a much better hand. While taking a clear left-wing stance on many policies that were popular with its constituency, the party also skilfully emphasised valence issues that Labour is often seen as more credible on, such as healthcare and education.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65,046 European population controls (5/393 cases versus 32/65,046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.