Copy number variation in a hospital-based cohort of children with epilepsy

Objective: To evaluate the diagnostic yield of microarray analysis in a hospital-based cohort of children with seizures and to identify novel candidate genes and susceptibility loci for epilepsy. Methods: Of all children who presented with their first seizure in the University Medical Center Groningen (January 2000 through May 2013) (n = 1,368), we included 226 (17%) children who underwent microarray analysis before June 2014. All 226 children had a definite diagnosis of epilepsy. All their copy number variants (CNVs) on chromosomes 1-22 and X that contain protein-coding genes and have a prevalence of <1% in healthy controls were evaluated for their pathogenicity. Results: Children selected for microarray analysis more often had developmental problems (82% vs. 25%, p < 0.001), facial dysmorphisms (49% vs. 8%, p < 0.001), or behavioral problems (41% vs. 13%, p < 0.001) than children who were not selected. We found known clinically relevant CNVs for epilepsy in 24 of the 226 children (11%). Seventeen of these 24 children had been diagnosed with symptomatic focal epilepsy not otherwise specified (71%) and five with West syndrome (21%). Of these 24 children, many had developmental problems (100%), behavioral problems (54%) or facial dysmorphisms (46%). We further identified five novel CNVs comprising four potential candidate genes for epilepsy:MYT1L, UNC5D, SCN4B,andNRXN3. Significance: The 11% yield in our hospital-based cohort underscores the importance of microarray analysis in diagnostic evaluation of children with epilepsy

Topography-Mediated Myotube and Endothelial Alignment, Differentiation, and Extracellular Matrix Organization for Skeletal Muscle Engineering

Understanding the response of endothelial cells to aligned myotubes is important to create an appropriate environment for tissue-engineered vascularized skeletal muscle. Part of the native tissue environment is the extracellular matrix (ECM). The ECM is a supportive scaffold for cells and allows cellular processes such as proliferation, differentiation, and migration. Interstitial matrix and basal membrane both comprise proteinaceous and polysaccharide components for strength, architecture, and volume retention. Virtually all cells are anchored to their basal lamina. One of the physical factors that affects cell behavior is topography, which plays an important role on cell alignment. We tested the hypothesis that topography-driven aligned human myotubes promote and support vascular network formation as a prelude to in vitro engineered vascularized skeletal muscle. Therefore, we used a PDMS-based topography substrate to investigate the influence of pre-aligned myotubes on the network formation of microvascular endothelial cells. The aligned myotubes produced a network of collagen fibers and laminin. This network supported early stages of endothelial network formation.</p

Cervical high-intensity intramedullary lesions in achondroplasia:Aetiology, prevalence and clinical relevance

In achondroplastic patients with slight complaints of medullary compression the cervical spinal cord regularly exhibits an intramedullary (CHII) lesion just below the craniocervical junction with no signs of focal compression on the cord. Currently, the prevalence of the lesion in the general achondroplastic population is studied and its origin is explored. Eighteen achondroplastic volunteers with merely no clinical signs of medullary compression were subjected to dynamic magnetic resonance imaging (MRI). The presence of a CHII lesion and craniocervical medullary compression in flexed and retroflexed craniocervical positions was explored. Several morphological characteristics of the craniocervical junction, possibly related to compression on the cord, were assessed. A CHII lesion was observed in 39% of the subjects and in only one of these was compression at the craniocervical junction present. Consequently, no correlation between the CHII lesion and compression could be established. None of the morphological characteristics demonstrated a correlation with the CHII lesion, except thinning of the cord at the site of the CHII lesion. CHII lesions are a frequent finding in achondroplasia, and are generally unaccompanied by clinical symptoms or compression on the cord. Further research focusing on the origin of CHII lesions and their clinical implications is warranted. aEuro cent MRI now reveals exquisite detail of the cervical spinal cord. aEuro cent Cervical cord lesions are observed in one third of the achondroplastic population. aEuro cent These lesions yield high signal intensity on T2 weighted MRI. aEuro cent They are generally unaccompanied by clinical symptoms or cord compression. aEuro cent Their aetiology is unclear and seems to be unrelated to mechanical causes

Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; design of a prospective randomized controlled trial

Background. The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser Disc Decompression (PLDD). This treatment can be carried out in an outpatient setting and swift recovery and return to daily routine are suggested. Thus far, no randomized trial into cost-effectiveness of PLDD versus standard surgical procedure has been performed. We present the design of a randomized controlled trial, studying the cost-effectiveness of PLDD versus conventional open discectomy in patients with sciatica from lumbar disc herniation. Methods/design. The study is a randomized prospective multi-center trial, in which two treatment strategies are compared in a parallel group design. Patients (age 18-70 years) visiting the neurosurgery department of the participating hospitals, are considered for inclusion in the trial when sciatica due to lumbar disc herniation has lasted more than 8 weeks. Patients with disc herniation smaller than 1/3 of the spinal canal diameter, without concomitant lateral recess stenosis or sequestration, are eligible for participation, and are randomized into one of two treatment arms; either Percutaneous Laser Disc Decompression or conventional discectomy. The functional outcome of the patient, as assessed by the Roland Disability Questionnaire for Sciatica at 8 weeks and 1 year after treatment, is the primary outcome measure. The secondary outcome parameters are recovery as perceived by the patient, leg and back pain, incidence of re-intervention, complications, quality of life, medical consumption, absence of work and secondary costs. Discussion. Open discectomy is still considered to be the golden standard in the surgical treatment of lumbar disc herniation. Whether Percutaneous Laser Disc Decompression has at least as much efficacy as the standard surgical procedure, and is more cost-effective, will be determined by this trial. Trial registration. Current Controlled Trials ISRCTN25884790

Changes in empowerment and anxiety of patients and parents during genetic counselling for epilepsy

Genetic testing and counselling are increasingly important in epilepsy care, aiming at finding a diagnosis, understanding aetiology and improving treatment and outcome. The psychological impact of genetic counselling from patients' or parents & rsquo; perspectives is, however, unknown. We studied the counseleereported outcome of genetic counselling before and after genetic testing for epilepsy by evaluating empowerment - a key outcome goal of counselling reflecting cognitive, decisional and behavioural control, emotional regulation and hope - and anxiety. We asked patients or their parents (for those (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods

A recent workshop entitled The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods was held in Paris in December 2010, sponsored by the French National Centre for Scientific Research (CNRS) and by the journal Human Biology. This workshop was intended to foster a debate on questions related to the family names and to compare different multidisciplinary approaches involving geneticists, historians, geographers, sociologists and social anthropologists. This collective paper presents a collection of selected communications

The use of 4D-CTA in the diagnostic work-up of brain arteriovenous malformations

Neuro Imaging Researc

In search of Coulson’s lost theorem

In Hückel theory, the bond number is the sum of the orders of the π bonds incident on a given carbon center. From the work of Coulson and his school, it has been believed for over 70 years that the bond number has a maximum of 3⎯⎯√ and that this bound is realized by exactly one conjugated framework, that of the trimethylenemethane radical. Search of published literature and archived correspondence failed to find any formal proof of these two statements. Here, we provide a new formula for bond number that leads to an easily checked proof of both. The bond number of graphene is 1.574 597… (90.9% of the mathematical limit), and this value appears to act as a separator for the classes of metallic and semiconducting single-walled nanotubes, as defined within Hückel theory

COVID-19 and Neurointerventional Service Worldwide: A Survey of the European Society of Minimally Invasive Neurological Therapy (ESMINT), the Society of NeuroInterventional Surgery (SNIS), the Sociedad Iberolatinoamericana De Neuroradiologia Diagnostica Y Terapeutica (SILAN), the Society of Vascular and Interventional Neurology (SVIN), and the World Federation of Interventional and Therapeutic Neuroradiology (WFITN)

BACKGROUND This survey was focused on the provision of neurointerventional services, the current practices of managing patients under COVID-19 conditions, and the expectations for the future. METHODS Invitations for this survey were sent out as a collaborative effort of the European Society of Minimally Invasive Neurological Therapy (ESMINT), the Society of NeuroInterventional Surgery (SNIS), the Sociedad Iberolatinoamericana de Neuroradiologia Diagnostica y Terapeutica (SILAN), the Society of Vascular and Interventional Neurology (SVIN), and the World Federation of Interventional and Therapeutic Neuroradiology (WFITN). RESULTS Overall, 475 participants from 61 countries responded (six from Africa (1%), 81 from Asia (17%), 156 from Europe (33%), 53 from Latin America (11%), and 172 from North America (11%)). The majority of participants (96%) reported being able to provide emergency services, though 26% of these reported limited resources. A decrease in emergency procedures was reported by 69% of participants (52% in ischemic and hemorrhagic stroke, 11% ischemic, and 6% hemorrhagic stroke alone). Only 4% reported an increase in emergency cases. The emerging need for social distancing and the rapid adoption of remote communication was reflected in the interest in establishing case discussion forums (43%), general online forums (37%), and access to angio video streaming for live mentoring and support (33%). CONCLUSION Neurointerventional emergency services are available in almost all centers, while the number of emergency patients is markedly decreased. Half of the participants have abandoned neurointerventions in non-emergent situations. There are considerable variations in the management of neurointerventions and in the expectations for the future

Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers

The c.40_42delAGA variant in the phospholamban gene (PLN) has been associated with dilated and arrhythmogenic cardiomyopathy, with up to 70% of carriers experiencing a major cardiac event by age 70. However, there are carriers who remain asymptomatic at older ages. To understand the mechanisms behind this incomplete penetrance, we evaluated potential phenotypic and genetic modifiers in 74 PLN:c.40_42delAGA carriers identified in 36,339 participants of the Lifelines population cohort. Asymptomatic carriers (N = 48) showed shorter QRS duration (− 5.73 ms, q value = 0.001) compared to asymptomatic non-carriers, an effect we could replicate in two different independent cohorts. Furthermore, symptomatic carriers showed a higher correlation (rPearson = 0.17) between polygenic predisposition to higher QRS (PGSQRS) and QRS (p value = 1.98 × 10–8), suggesting that the effect of the genetic variation on cardiac rhythm might be increased in symptomatic carriers. Our results allow for improved clinical interpretation for asymptomatic carriers, while our approach could guide future studies on genetic diseases with incomplete penetrance.</p