Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.

Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36).

Variant ataxia telangiectasia identified during evaluation for short stature.

Ataxia telangiectasia (A-T) (OMIM 208900) is an autosomal recessive multisystem disorder characterised by progressive cerebellar ataxia, telangiectasias, immunodeficiency and a predisposition to malignancy. 'Variant' A-T has later onset of neurological symptoms and slower progression compared with the 'classic' form. A woman presented with short stature in late childhood.

This infant is having a stroke: an illustrative case report.

Background: Paediatric stroke is a rare event, and timely intervention is required to minimise long-term disability, reduced quality of life and financial implications. Although reperfusion strategies such as thrombolysis and thrombectomy are now well established in the adult population, and paediatric consensus guidelines allow for reperfusion therapies in children, access is currently limited due to diagnostic delays. This challenge is partly due to the rarity of presentation, infrastructure and public awareness to support early diagnosis as exists in the adult setting.

Response to treatment and outcomes of infantile spasms in Down syndrome.

Aim: To estimate the prevalence, and evaluate presentation, treatment response, treatment side effects, and long-term seizure outcomes in all known cases of children with Down syndrome and infantile spasms on the island of Ireland.

Method: This was a 10-year retrospective multicentre review of clinical records and investigations, focusing on treatment response, side effects, and long-term outcomes.

Results: The prevalence of infantile spasms in Down syndrome was 3.

Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants.

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials.

HK1 haemolytic anaemia in association with a neurological phenotype and co-existing CEP290 Meckel-Gruber in a Romani family.

HK1 deficient Haemolytic Anaemia in association with a Neurological Phenotype & co-existing Meckel-Gruber due to CEP290 in a Romani family.

Multicystic Encephalomalacia: The Neuropathology of Systemic Neonatal Parechovirus Infection.

The Neuropathology of Human Parechovirus (HPeV) is not widely described due to the relatively recent discovery of the virus combined with a limited number of autopsy case reports. We report the case of an infant boy born at 38 weeks who, six days after birth, presented with fever and severe neurological dysfunction. Human Parechovirus Type 3 (HPeV3) RNA was detected in his cerebrospinal fluid (CSF) and blood.

An audit of community-acquired pneumonia antimicrobial compliance using an intervention bundle in an Irish hospital.

Objectives: Hospitalisations with community-acquired pneumonia (CAP) are often not managed in accordance with antimicrobial guidelines. This study aimed to assess whether guideline-driven antimicrobial prescribing for CAP can be improved using an intervention bundle. Secondary measures assessed were hospital length of stay (LOS), mortality, duration of intravenous antibiotics and total antibiotics, improved uptake of appropriate investigations, and documentation of CURB-65 score.

Neuronal antibody prevalence in children with seizures under 3 years: A prospective national cohort.

Objective: To report the prevalence of anti-neuronal antibodies in a prospective whole-nation cohort of children presenting with seizures before their third birthday.

Methods: This was a prospective population-based national cohort study involving all children presenting with new-onset epilepsy or complex febrile seizures before their third birthday over a 3-year period. Patients with previously identified structural, metabolic, or infectious cause for seizures were excluded.

Moyamoya disease and moyamoya syndrome in Ireland: patient demographics, mode of presentation and outcomes of EC-IC bypass surgery.

Background: There are no previously published reports regarding the epidemiology and characteristics of moyamoya disease or syndrome in Ireland.

Aims: To examine patient demographics, mode of presentation and the outcomes of extracranial-intracranial bypass surgery in the treatment of moyamoya disease and syndrome in Ireland.

Methods: All patients with moyamoya disease and syndrome referred to the National Neurosurgical Centre during January 2012-January 2019 were identified through a prospective database.

A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability.

Next generation sequencing provides an important opportunity for improved diagnosis in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the paediatric arena, while the utility of such testing is less well understood in adults with epilepsy. We conducted whole exome sequencing (WES) and copy number variant analyses in an Irish cohort of 101 people with epilepsy and co-morbid intellectual disability to compare the diagnostic yield of genomic testing between adult and paediatric patients.

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.

Progressive intellectual impairment in children with Encephalopathy related to Status Epilepticus during slow Sleep.

We investigated whether Encephalopathy related to Status Epilepticus during slow Sleep (ESES) in childhood was associated with progressive intellectual decline. Participants were identified from the caseload of a single paediatric neurosciences centre and EEG department. A retrospective review of overnight sleep EEG reports (n=2200) over a five-year period identified twenty-two children as having the neurophysiological characteristics of ESES.

Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy.

Sudden unexpected death in epilepsy (SUDEP) represents the most severe degree of the spectrum of epilepsy severity and is the commonest cause of epilepsy-related premature mortality. The precise pathophysiology and the genetic architecture of SUDEP remain elusive. Aiming to elucidate the genetic basis of SUDEP, we analysed rare, protein-changing variants from whole-exome sequences of 18 people who died of SUDEP, 87 living people with epilepsy and 1479 non-epilepsy disease controls.

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders.

De novo point mutations in patients diagnosed with ataxic cerebral palsy.

Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy.

Group problem-solving skills training for self-harm: randomised controlled trial.

Background: Rates of self-harm are high and have recently increased. This trend and the repetitive nature of self-harm pose a significant challenge to mental health services.

Aims: To determine the efficacy of a structured group problem-solving skills training (PST) programme as an intervention approach for self-harm in addition to treatment as usual (TAU) as offered by mental health services.

Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model.

Many neurological conditions are caused by immensely heterogeneous gene mutations. The diagnostic process is often long and complex with most patients undergoing multiple invasive and costly investigations without ever reaching a conclusive molecular diagnosis. The advent of massively parallel, next-generation sequencing promises to revolutionize genetic testing and shorten the 'diagnostic odyssey' for many of these patients.

Development and validation of a measure of the impact of epilepsy on a young person's quality of life: Glasgow epilepsy outcome scale for young persons (GEOS-YP).

Objective: The goal of the work described here was to develop and validate a measure of the impact of epilepsy on an adolescent's quality of life that is based on direct exploration of the adolescent's views.

Methods: Initial scale development was based on data generated through qualitative methods (focus groups) in a previous study [McEwan MJ, Espie CA, Metcalfe J, Brodie MJ, Wilson MT. Seizure 2004;13:15-31].

Memory consolidation and accelerated forgetting in children with idiopathic generalized epilepsy.

Whether children with idiopathic generalized epilepsy exhibit accelerated forgetting of verbal and nonverbal information in comparison to healthy controls matched for age and IQ was explored. Twenty-one children with IGE were compared with 21 healthy controls on measures of verbal and visuospatial memory at delays of 30 minutes and 1 week by use of a minimum-learning criterion controlled for initial learning. For the auditory-verbal memory test, group performance was comparable at 30 minutes, but children with IGE recalled significantly less than controls at 1 week.

Developmental outcome in benign myoclonic epilepsy in infancy and reflex myoclonic epilepsy in infancy: a literature review and six new cases.

Benign myoclonic epilepsy in infancy is a rare syndrome with just over 100 cases reported since the first syndromic description by Dravet and Bureau [Dravet, C., Bureau, M., 1981.

Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports.

In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus representing a spectrum of opinion met in Oxford, sponsored by the Epilepsy Research Foundation (a charitable organization), to discuss and debate the definition, diagnosis and treatment of nonconvulsive status epilepticus. We felt that such a meeting would be useful, as nonconvulsive status epilepticus is a subject that provokes strong reactions, perhaps largely due to the relative lack of evidence and the surfeit of opinion. The meeting was arranged such that there were formal talks followed by a discussion led by one of the attendees.