Phenotypic and genetic spectrum of ATP6V1A encephalopathy: a disorder of lysosomal homeostasis.

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.

Gain-of-function and loss-of-function GABRB3 variants lead to distinct clinical phenotypes in patients with developmental and epileptic encephalopathies.

Many patients with developmental and epileptic encephalopathies present with variants in genes coding for GABA receptors. These variants are presumed to cause loss-of-function receptors leading to reduced neuronal GABAergic activity. Yet, patients with GABA receptor variants have diverse clinical phenotypes and many are refractory to treatment despite the availability of drugs that enhance GABAergic activity.

Simple and Robust Detection of Gene Deletions and Duplications Using as Reference.

Genotyping of the gene is the most commonly applied pharmacogenetic test globally. Significant economic interests have led to the development of a plurality of assays, available for almost any genotyping platform or DNA detection chemistry. Of all the genetic variants, copy number variations are particular difficult to detect by polymerase chain reaction.

Accurate identification of EEG recordings with interictal epileptiform discharges using a hybrid approach: Artificial intelligence supervised by human experts.

Objective: To evaluate the diagnostic performance of artificial intelligence (AI)-based algorithms for identifying the presence of interictal epileptiform discharges (IEDs) in routine (20-min) electroencephalography (EEG) recordings.

Methods: We evaluated two approaches: a fully automated one and a hybrid approach, where three human raters applied an operational IED definition to assess the automated detections grouped into clusters by the algorithms. We used three previously developed AI algorithms: Encevis, SpikeNet, and Persyst.

Automated detection of absence seizures using a wearable electroencephalographic device: a phase 3 validation study and feasibility of automated behavioral testing.

Objective: Our primary goal was to measure the accuracy of fully automated absence seizure detection, using a wearable electroencephalographic (EEG) device. As a secondary goal, we also tested the feasibility of automated behavioral testing triggered by the automated detection.

Methods: We conducted a phase 3 clinical trial (NCT04615442), with a prospective, multicenter, blinded study design.

Minimum standards for inpatient long-term video-EEG monitoring: A clinical practice guideline of the international league against epilepsy and international federation of clinical neurophysiology.

The objective of this clinical practice guideline is to provide recommendations on the indications and minimum standards for inpatient long-term video-electroencephalographic monitoring (LTVEM). The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology develop guidelines aligned with the Epilepsy Guidelines Task Force. We reviewed published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement.

Structural mapping of GABRB3 variants reveals genotype-phenotype correlations.

Purpose: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations.

Methods: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases.

Accelerated long-term forgetting in adult patients with genetic generalized epilepsy.

Objective: Accelerated long-term forgetting (ALF) has been demonstrated among children but not adults with genetic generalized epilepsy (GGE). We investigated (1) how forgetting patterns of verbal and visuospatial material differ between patients with GGE and healthy controls (HCs) and (2) whether ALF is associated with ictal or interictal epileptic activity.

Methods: Forty-two patients with GGE (39, 92.

Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum.

Background And Objectives: Purine-rich element-binding protein A () gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of syndrome by collecting data, including EEG, from a large cohort of affected patients.

Expert Opinion: Managing sleep disturbances in people with epilepsy.

Poor sleep and daytime sleepiness are common in people with epilepsy. Sleep disorders can disrupt seizure control and in turn sleep and vigilance problems can be exacerbated by seizures and by antiepileptic treatments. Nevertheless, these aspects are frequently overlooked in clinical practice and a clear agreement on the evidence-based guidelines for managing common sleep disorders in people with epilepsy is lacking.

The Angelman Syndrome Online Registry - A multilingual approach to support global research.

In collaboration with the German Angelman syndrome (AS) community, we developed a web-based AS Online Registry to congregate existing as well as future information and scientifically quantify observations made by parents, families and medical professionals. With its user-friendly design as well as its concise and multilingual questionnaire, the registry aims at families who had so far refrained from being recruited by other, more comprehensive and/or English-only, registries. Data can be entered by both parents/families and medical professionals.

4-Aminopyridine is a promising treatment option for patients with gain-of-function -encephalopathy.

Developmental and epileptic encephalopathies are devastating disorders characterized by epilepsy, intellectual disability, and other neuropsychiatric symptoms, for which available treatments are largely ineffective. Following a precision medicine approach, we show for -encephalopathy that the K channel blocker 4-aminopyridine can antagonize gain-of-function defects caused by variants in the K1.2 subunit in vitro, by reducing current amplitudes and negative shifts of steady-state activation and increasing the firing rate of transfected neurons.

The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study.

Objective: To compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF.

Methods: This was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA.

Self-control and coping responses are mediating factors between child behavior difficulties and parental stress and family impact in caregivers of children with severe epilepsy.

Objectives: To gain a better understanding of parental support needs by assessing parental individual psychological factors as mediating factors between child behavior difficulties and parental perceived stress and family impact of severe childhood epilepsy.

Methods: One-hundred and sixty two parents of children with severe epilepsy were enrolled in the survey during the hospitalization of their child at the Danish Epilepsy Center. Questionnaires targeted the impact on the family, coping style responses, sense of control, and the level of parental perceived stress.

Post-traumatic stress disorder (PTSD) symptoms in children with severe epilepsy.

Objectives: To assess symptoms of post-traumatic stress disorder (PTSD) in children with severe epilepsy and the associations of trauma symptoms across age, comorbid symptoms, epilepsy-specific factors, parental resources, and psychopathology.

Methods: Fifty children with severe epilepsy across three different age groups (0-5 yrs., 6-12 yrs.

Importance of access to epilepsy monitoring units during the COVID-19 pandemic: Consensus statement of the International League against epilepsy and the International Federation of Clinical Neurophysiology.

Restructuring of healthcare services during the COVID-19 pandemic has led to lockdown of Epilepsy Monitoring Units (EMUs) in many hospitals. The ad-hoc taskforce of the International League Against Epilepsy (ILAE) and the International Federation of Clinical Neurophysiology (IFCN) highlights the detrimental effect of postponing video-EEG monitoring of patients with epilepsy and other paroxysmal events. The taskforce calls for action to continue functioning of Epilepsy Monitoring Units during emergency situations, such as the COVID-19 pandemic.

'Everything is as before, but nothing is as it was'-A phenomenological-hermeneutic study of meaningfulness in adult patients with refractory epilepsy after interdisciplinary epilepsy rehabilitation.

Background: Interdisciplinary Rehabilitation aimed at adults with refractory epilepsy (RE) establishes scientific evidence of higher health-related QoL, including improved self-worth and increased self-awareness as outcomes. Yet, there is very little research-based knowledge of how life transforms itself after the rehabilitation program from patients' perspectives.

Aim: The aim of this study was to identify and describe how - from the patient perspectives - life transforms itself after rehabilitation among adults with RE, focusing on the meaningfulness of interdisciplinary rehabilitation.

Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1.

Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1.

PRICKLE2 revisited-further evidence implicating PRICKLE2 in neurodevelopmental disorders.

PRICKLE2 encodes a member of a highly conserved family of proteins that are involved in the non-canonical Wnt and planar cell polarity signaling pathway. Prickle2 localizes to the post-synaptic density, and interacts with post-synaptic density protein 95 and the NMDA receptor. Loss-of-function variants in prickle2 orthologs cause seizures in flies and mice but evidence for the role of PRICKLE2 in human disease is conflicting.

The influence of the abundance and morphology of epileptiform discharges on diagnostic accuracy: How many spikes you need to spot in an EEG.

Objective: The operational definition of interictal epileptiform discharges (IEDs) of the International Federation of Clinical Neurophysiology (IFCN) described six morphological criteria. Our objective was to assess the impact of pattern-repetition in the EEG-recording, on the diagnostic accuracy of using the IFCN criteria. For clinical implementation, specificity over 95% was set as target.

Expansion of the CCDC22 associated Ritscher-Schinzel/3C syndrome and review of the literature: Should the minimal diagnostic criteria be revised?

The Ritscher-Schinzel syndrome (RTSCS) is a rare condition with craniofacial, cardiac and fossa posterior abnormalities. RTSCS is subdivided into Ritscher-Schinzel syndrome 1 (RTSCS1) caused by pathogenic variants in coiled-coil domain-containing protein 22 (CCDC22), and Ritscher-Schinzel syndrome 2 (RTSCS2) caused by pathogenic variants in WASH complex subunit 5 (WASHC5). CCDC22 is inherited in an X-linked recessive manner while WASHC5 is inherited in an autosomal recessive manner.

Automated ictal EEG source imaging: A retrospective, blinded clinical validation study.

Objective: EEG source imaging (ESI) is a validated tool in the multimodal workup of patients with drug resistant focal epilepsy. However, it requires special expertise and it is underutilized. To circumvent this, automated analysis pipelines have been developed and validated for the interictal discharges.

Validation of ICD-11 PTSD and DSO using the International Trauma Questionnaire in five clinical samples recruited in Denmark.

: The 11 version of the International Classification of Diseases (ICD-11) revised the diagnosis of Posttraumatic Stress Disorder (PTSD) and introduced Complex PTSD as a sibling disorder to PTSD. As the Danish Health Authorities will implement the ICD-11 in 2022, it is more relevant than ever to introduce a measure that enables the identification of ICD-11 PTSD and CPTSD. : The primary aim of the present study was to test the construct validity of the ICD-11 conceptualization of PTSD and DSO in five clinical samples using translated versions of the International Trauma Questionnaire (ITQ).

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.

Objective: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.