Bryan Lynch

Children's University Hospital, Temple Street | CUH · Neurology

Therapeutic plasma exchange (TPE) is utilised in the management of a limited number of paediatric renal conditions. Despite its widespread acceptance and advancements in the practice of apheresis, there remains a paucity of data pertaining to paediatrics. We present a large retrospective review of our cohort of paediatric patients undergoing TPE fo...

Background: Typical absence seizures (TAS) are seen in idiopathic generalized epilepsy. Electroencephalography (EEG) contributes to syndrome characterization and counseling in an area where genetics does not currently play a significant role. Prominent interictal EEG findings are seen in juvenile absence epilepsy (JAE) and are thus thought to be a...

Our objective was to establish the rate of neurological involvement in Shiga toxin-producing Escherichia coli –hemolytic uremic syndrome (STEC-HUS) and describe the clinical presentation, management and outcome. A retrospective chart review of children aged ≤ 16 years with STEC-HUS in Children’s Health Ireland from 2005 to 2018 was conducted. Labor...

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 tre...

Objectives To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). Methods In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021....

Pathogenic variants in the voltage-gated sodium channel gene (SCN1A) are amongst the most common genetic causes of childhood epilepsies. There is considerable heterogeneity in both the types of causative variants and associated phenotypes; a recent expansion of the phenotypic spectrum of SCN1A associated epilepsies now includes an early onset sever...

Our objective was to establish the rate of neurological involvement in STEC-HUS and describe the clinical presentation, management and outcome. A retrospective chart review of children aged ≤16 years with STEC-HUS in Children’s Health Ireland from 2005 to 2018 was conducted. Laboratory confirmation of STEC infection was required for inclusion. Neur...

Objective To explore the phenotypic spectrum of RHOBTB2 -related disorders, and specifically to determine whether patients fulfil criteria for alternating hemiplegia of childhood (AHC), we report the clinical features of 11 affected individuals. Methods Individuals with RHOBTB2 -related disorders were identified through a movement disorder clinic...

Since 1972, eighteen patients (10 females/8 males) have been detected by newborn bloodspot screening (NBS) with neonatal‐onset Maple Syrup Urine Disease (MSUD) in Ireland. Patients were stratified into three clusters according to clinical outcome at the time of data collection, including developmental, clinical and IQ data. A fourth cluster compris...

Abstract STUDY OBJECTIVES:We aimed to describe the clinical features of narcolepsy in patients referred to our sleep center between 2009 and 2016, and to compare these features across age groups and between sporadic versus AS03-adjuvanted H1N1 influenza vaccine-related cases. METHODS:This is a retrospective, consecutive study of adult and pediatri...

Aim To describe the population of young people in Ireland diagnosed with narcolepsy with regards to vaccine exposure, symptomatology, investigation results and experience of medical treatment. Method Retrospective review of medical records at the single tertiary referral centre for young people with narcolepsy in Ireland. Results Sixty-seven pati...

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

X-linked infantile spinal muscular atrophy (SMAX2), OMIM 301830, is a rare, severe form of spinal muscular atrophy, caused by variants in the Ubiquitin like modifier-activating enzyme 1 (UBA1) gene. Clinical features reported to date include marked hypotonia, areflexia, arthrogryposis, contractures, myopathic facies and tongue fibrillations. Previo...

Objective: Pathogenic variants in KCNB1, encoding the voltage-gated potassium channel KV 2.1, are associated with developmental and epileptic encephalopathy (DEE). Previous functional studies on a limited number of KCNB1 variants indicated a range of molecular mechanisms by which variants affect channel function, including loss of voltage sensitiv...

Introduction: The severe epilepsies of infancy and childhood are a heterogeneous group of severe epilepsies characterised by several seizure types, where the epileptic activity in addition to the seizures contributes to cognitive impairment or regression. They account for a significant proportion of the refractory epilepsies and are usually associa...

A 16 month old toddler presented with global developmental delay, truncal hypotonia and microcephaly. Her background history was significant for bilateral developmental dysplasia of the hip, recurrent upper respiratory tract infections, conductive hearing loss and a scalp haemangioma. Development had been apparently normal up until 6 months of age....

Despite early diagnosis through Newborn Bloodspot Screening and strict dietary treatment, there are long-term complications of Classical Galactosaemia, including female infertility, osteopenia, and, in some cases, learning disabilities or neurological symptoms such as tremor or ataxia. Therefore, neurological symptoms may easily be attributed to an...

Aims We report the case of a male infant who presented following a normal pregnancy with typical symptoms of X-linked infantile spinal muscular atrophy including hypotonia, weakness, areflexia and respiratory insufficiency, however contractures were absent. X-linked infantile spinal muscular atrophy (SMAX2), OMIM 301830, is a rare, severe form of s...

Introduction Rett syndrome (RS) is an X-linked dominant neurodevelopmental disorder affecting girls, most commonly caused by MECP2 loss-of-function mutations. The typical phenotype of RS is characterised by a period of developmental stagnation in late infancy, followed by progressive dementia, developmental regression, stereotyped hand-movements, m...

Background Narcolepsy is a rare and under-recognised disease characterised by excessive daytime sleepiness, disturbed nocturnal sleep, hallucinations, and cataplexy, with a major impact on quality of life. Diagnosis can be challenging. We present a series of recent children presenting to a district general hospital over a 2.5 year period with chron...

Pathogenic variants in KCNB1 , encoding the voltage-gated potassium channel Kv2.1, are associated with developmental and epileptic encephalopathies (DEE). Previous functional studies on a limited number of KCNB1 variants indicated a range of molecular mechanisms by which variants affect channel function, including loss of voltage sensitivity, loss...

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Objectives To describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease. Methods We identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmi...

Movement disorders are increasingly identified in infantile encephalopathies due to single gene disorders (e.g. SCN2A, CDKL5, ARX). The associated movement disorder can be challenging to recognise and treat. We report a 2 year-old boy with a background history of Ohtahara syndrome due to a missense variant in ARX (the aristaless-related homeobox ge...

Aims Post-malaria neurological syndrome (PMNS) is described as a rare post-infectious encephalopathy occurring within two months of resolved malaria infection and with an aparasitaemia. PMNS encompasses three separate neurological syndromes: A delayed cerebellar syndrome, an acute demyelinating polyneuropathy (GBS) and an acute disseminated encepha...

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A humanised anti-C5 monoclonal antibody (eculizumab) is available for the treatment of aHUS. We present the first description of atypical HUS in a child with a coexistent diagnosis of a POL-III leukodystrophy. On standard eculizumab dosing regime, there w...

Objective: The aim and objective of this study was to assess the knowledge and views of parents on transitional and adolescent care in young adults with epilepsy, and to develop a transitional and adolescent program for epilepsy. Methods: Data were collected from questionnaires completed by parents during focus groups exploring transitional care...

Neuronal intranuclear (hyaline) inclusion disease (NIID) is a rare neurodegenerative disorder with a variable clinical presentation and multiple subtypes. We present the clinicopathologic details of a patient with juvenile-onset NIID and discuss the pathogenesis. We also discuss the utility of antemortem skin biopsy which was negative in our case.

We report three affected members, a mother and her two children, of a non-consanguineous Irish family who presented with a suspected autosomal dominant spinocerebellar ataxia characterized by early motor delay, poor coordination, gait ataxia, and dysarthria. Whole exome sequencing identified a novel missense variant (c.106C>T; p.[Arg36Cys]) in the...

Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptoma...

MELAS is a rare mitochondrial disorder. We report two cases in Irish males where the characteristics were evident,but the diagnosis not made for a considerable period of time. In one of the cases the symptoms were presumed secondary to prematurity. In the other the symptoms were presumed secondary to epilepsy and he had three respiratory arrests se...

SLC1A4 deficiency is a recently described neurodevelopmental disorder associated with microcephaly, global developmental delay, abnormal myelination, thin corpus callosum and seizures. It has been mainly reported in the Ashkenazi-Jewish population with affected individuals homozygous for the p.Glu256Lys variant. Exome sequencing performed in an Iri...

Despite the advent of antiviral therapy, herpes simplex encephalitis (HSE) remains a devastating condition with significant morbidity and mortality. Neurologic relapse after initial improvement is generally attributed to herpes simplex virus reactivation. In 2013, inflammation caused by anti-N-methyl-d-aspartate receptor antibodies was reported in...

Acute Flaccid Paralysis (AFP) surveillance, including case investigation and specimen collection is a gold standard method for poliomyelitis surveillance. The expected annual non-polio AFP rate <15 years of age in Ireland is = 1/100 000 population. This study reviewed all cases of AFP reported to the Irish Paediatric Surveillance Unit and the Healt...

Early onset epileptic encephalopathies (EOEEs) represent a significant diagnostic challenge. Newer genomic approaches have begun to elucidate an increasing number of responsible single genes as well as emerging diagnostic strategies. In this single-center study, we aimed to investigate a cohort of children with unexplained EOEE. We performed whole-...

Movement disorders such as ataxia are a recognized complication of classical galactosaemia, even in diet-compliant patients. Here, we report the coexistence of classical galactosaemia and Friedreich ataxia (FRDA) in nine children from seven Irish Traveller families. These two autosomal recessive disorders, the loci for which are located on either s...

To examine a cohort of paediatric multiple sclerosis (MS) patients in an Irish tertiary paediatric neurology referral centre with emphasis on presentation, investigations and management, comparing to other described cohorts. Methods Patients were identified through department records, with chart review performed to obtain clinical details. Laborat...

Severe early onset epilepsy may lead to impaired cognitive and motor development, and consists of a group of specific and overlapping electro-clinical phenotypes which may be the result of an inborn error of metabolism, congenital or acquired structural brain lesion, known chromosomal or mono-genetic disorder. A significant proportion of cases howe...

We report a dystrophinopathy patient with an in-frame deletion of DMD exons 45–47, and therefore a genetic diagnosis of Becker muscular dystrophy, who presented with a more severe than expected phenotype. Analysis of the patient DMD mRNA revealed an 82 bp pseudoexon, derived from intron 44, that disrupts the reading frame and is expected to yield a...

The objective was to follow up a cohort of acidotic full-term infants with or without hypoxic ischemic encephalopathy (HIE) and determine if at 7 years they displayed any neurodevelopmental delays. Children (n=44) were divided according to those with mild (n=25) or severe (n=19) acidosis and were then further subdivided into those with or without H...

Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants locali...

Andersen-Tawil syndrome (ATS) is a rare autosomal dominant potassium channelopathy characterized by a triad of periodic paralysis, ventricular arrhythmias, and distinctive dysmorphic abnormalities. We present a 19-year-old man with characteristic skeletal dysmorphic features of ATS, early nonfluctuating proximal lower limb weakness from childhood,...

We describe two cases of infant botulism due to Clostridium butyricum producing botulinum type E neurotoxin (BoNT/E) and a previously unreported environmental source. The infants presented at age 11 days with poor feeding and lethargy, hypotonia, dilated pupils and absent reflexes. Faecal samples were positive for C. butyricum BoNT/E. The infants r...

An estimated 85–90% of all paediatric neuromuscular patients in the Republic of Ireland are followed at one neuromuscular centre, located at the Central Remedial Clinic, Dublin, resulting in centralised and coordinated care for the vast majority of Irish paediatric neuromuscular patients. The neuromuscular cohort followed by two neuromuscular speci...

Myoclonus dystonia syndrome (MDS) is a young-onset movement disorder. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. We assembled the largest cohort of MDS patients to date, and determined the frequency and type of SGCE mutations. The aim was to establish the motor phenotype in mutation carriers and utility of cur...

Mutations in KCNQ2 and KCNQ3 were originally described in infants with benign familial neonatal seizures (BFNS). Recently, KCNQ2 mutations have also been shown to cause epileptic encephalopathy. This report describes three infants carrying abnormalities of KCNQ2 and one infant with a KCNQ3 mutation. The different KCNQ2 abnormalities led to differen...

In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset fro...

N-methyl-d-aspartate (NMDA) receptor encephalitis is a treatable cause of autoimmune encephalitis in both children and adults. It is still unclear if the natural history of the condition in children is altered by early treatment with immunosuppressive therapy. We looked at the outcomes of five children (two males, three females; mean age 6y 9mo, ra...

Benign hereditary chorea is a dominantly inherited, childhood-onset hyperkinetic movement disorder characterized by non-progressive chorea and variable degrees of thyroid and respiratory involvement. Loss-of-function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a...

Myoclonus Dystonia Syndrome (MDS) is a childhood onset, alcohol responsive movement disorder caused by mutations in the SGCE gene in a proportion of cases. Single family and case series have suggested co-morbid psychiatric disease but have not compared cases to a control group. To establish a cohort of MDS patients with SGCE mutations and a control...

Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatr...

Aim Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives.Method Participants...

Aim Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives. Method Participants...

Aim: Determine the frequency and predictors of sleep disorders in boys with Duchenne Muscular Dystrophy (DMD). Method: Cross-sectional study by postal questionnaire. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (validated on 1157 healthy children). A total sleep score and six sleep disturbance factors representing...

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymo...

We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers' disease should be considered in any child p...

IntroductionReduced mobility in Duchenne Muscular Dystrophy (DMD) leads to the development of osteopenia and osteoporosis leading to increased bone fragility and risk of fracture. Dietary Vitamin D and calcium intake is suboptimal in most children. Reduced Vitamin D levels have been reported recently in children with DMD.Objectives(1) To determine...

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disease characterized by early infantile macrocephaly and delayed motor and cognitive deterioration. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen cerebral white matter and subcortical cysts. On follow-up, atrophy ensues. Approximately...

Merosin deficient congenital muscular dystrophy 1A (MDC1A) results from mutations in the LAMA2 gene. We report 51 patients with MDC1A and examine the relationship between degree of merosin expression, genotype and clinical features. Thirty-three patients had absence of merosin and 13 showed some residual merosin. Compared to the residual merosin gr...

A 7-year-old boy with a history of VACTERL syndrome was found collapsed in bed. MRI had shown basilar invagination of the skull base and narrowing of the foramen magnum. Angulation, swelling and abnormal high signal at the cervicomedullary junction were felt to be secondary to compression of the medulla. Neuropathologic examination showed bilateral...

Five patients with spontaneously recovering Dancing Eye Syndrome/Opsoclonus Myoclonus Syndrome are described. Age at presentation ranged from 4 to 19 months. Four had symptoms of fever and a coryzal illness within days to a few weeks prior to the onset. One of the 4 also had varicella zoster 4 weeks before presentation. All had opsoclonus, myoclonu...

Serial casting is often prescribed after botulinum toxin injections to improve joint ranges of motion and to potentiate the decrease in hypertonia. The aim of this study was to compare delayed versus immediate serial casting as an adjunct to botulinum toxin therapy for partially reducible spastic equinus. Twelve children who presented spastic equin...

Mitochondrial beta oxidation plays a major role in energy production. Long chain fatty acid oxidation defects include deficiency of the trifunctional protein (rare) or more commonly defects of the long chain 3-hydroxy acyl-CoA dehydrogenase enzyme (LCHAD). These long chain defects have variable presentations, they may present in the neonate or infa...

Certain typical gait characteristics such as foot-drop and foot supination are well described in Charcot-Marie-Tooth disease. These are directly related to the primary disease and due to the weakness of ankle dorsiflexors and everters characteristic of this hereditary neuropathy. We analysed 16 subjects aged 8-52 years old (11 with type I, 5 with t...

Varicella in childhood is a self-limiting disease, which usually follows a benign course. However, complications, although rare, may have serious consequences. Ischaemic stroke secondary to post varicella angiopathy is a well-described complication and is estimated to account for up to a third of all strokes in infants. We present three previously...

Children with unresolved brachial plexus palsy frequently develop a disabling internal rotation contracture of the shoulder. Several surgical options, including soft tissue procedures such as muscle releases and/or transfers, and bone operations such as humeral osteotomy are available to correct this deformity. This study describes the effect of su...