79 results match your criteria: "Australia I.E.S.; and Massachusetts General Hospital[Affiliation]"
Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to G.
Proc Natl Acad Sci U S A
May 2018
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX3 7FY Oxford, United Kingdom;
A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells.
View Article and Find Full Text PDFIon Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.
Pharmacol Rev
January 2018
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Melbourne, Australia (J.O., S.M., I.E.S., S.P., C.A.R.); Department of Medicine, Austin Health, University of Melbourne, Heidelberg West, Melbourne, Australia (I.E.S., S.F.B.); and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia (I.E.S.)
Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching-from precise diagnosis and classification of syndromes to the discovery and validation of new drug targets and the development of disease-targeted therapeutic strategies.
View Article and Find Full Text PDFClinical and molecular characterization of -related severe early-onset epilepsy.
Neurology
January 2018
From Molecular Neurosciences (A.M., E.M., A., A.N., M.A.K.), Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health; Department of Neurology (A.M., A., A.N., C.E., J.H.C., M.A.K.) and Neuroradiology (W.K.C.), Great Ormond Street Hospital for Children, London, UK; Florey Institute of Neuroscience and Mental Health (U.N., E.V.G., I.E.S., S.P.), Melbourne, Australia; Department of Biological Sciences (S.M., M.T.), Institute of Structural and Molecular Biology, Birkbeck College, University of London; Regional Molecular Genetics Laboratory (N.T., R.H.S.), North East Thames Regional Genetics Service, and Department of Clinical Genetics (A.V.K., R.H.S.), Great Ormond Street Hospital, London, UK; Department of Paediatric Neurology (S.A.), Red Cross War Memorial Children's Hospital, Cape Town, South Africa; Department of Paediatric Neurology (G.A.), Addenbrooke's Hospital, Cambridge; Roald Dahl EEG Unit (R.A.), Department of Neurology, and Department of Neurology (R.K.), Alder Hey Children's Hospital, Liverpool; Department of Paediatric Neurology (A.D.), Sheffield Children's Hospital; Clinical Neurosciences (C.E., J.H.C.), Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London; Institute of Infection and Global Health (R.K.), University of Liverpool; Department of Paediatric Neurology (K.L.), Evelina Children's Hospital, Guys and St. Thomas' NHS Foundation Trust, London; Department of Clinical Genetics (T.M.), Northern Genetics Service; Department of Pediatric Neurology (V.R.), Great North Children's Hospital, Newcastle Upon Tyne; Department of Paediatric Neurology (R.S.), University Hospital Leicester Children's Hospital; Department of Paediatric Neurology (J.T.), Royal Manchester Children's Hospital; Department of Paediatric Neurology (W.W.), Nottingham University Hospitals NHS Trust, UK; Epilepsy Genetics Program (A. Poduri), Department of Neurology, Boston Children's Hospital; Department of Neurology (A. Poduri), Harvard Medical School, Boston, MA; University of Melbourne (I.E.S.), Austin Health and Royal Children's Hospital, Australia; and Department of Medicine (S.P.), Royal Melbourne Hospital, University of Melbourne, Australia. Dr. Malhotra is currently at the Department of Biochemistry, University of Cambridge, UK.
Objective: To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset epilepsy.
Methods: We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified variants on local diagnostic multiple gene panel testing were also included.
Precision therapy for epilepsy due to mutations: A randomized trial of oral quinidine.
Neurology
January 2018
From The Florey Institute of Neuroscience and Mental Health (S.A.M., P.W.C., L.C., U.N., M.L., S.P.), Epilepsy Research Centre, Department of Medicine (S.A.M., A.R., P.A.L., S.F.B., I.E.S.), and Department of Paediatrics, Royal Children's Hospital (I.E.S.), University of Melbourne; Department of Medicine (S.A.M., A.R., P.A.L., S.F.B., I.E.S.), and Department of Pharmacy (M.C.), Austin Health; and Department of Medicine (P.W.C.), Monash University and Eastern Health, Melbourne, Australia.
Objective: To evaluate quinidine as a precision therapy for severe epilepsy due to gain of function mutations in the potassium channel gene .
Methods: A single-center, inpatient, order-randomized, blinded, placebo-controlled, crossover trial of oral quinidine included 6 patients with severe autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) due to mutation. Order was block randomized and blinded.
Genetic epilepsy with febrile seizures plus: Refining the spectrum.
Neurology
September 2017
From the Epilepsy Research Centre, Department of Medicine (Y.-H.Z., R.B., J.P.M., G.C.G., K.L.H., L.V., B.E.G., S.T.B., D.F.V., J.A.D., M.S.H., S.F.B., I.E.S.), The University of Melbourne, Austin Health, Australia; Department of Pediatrics (Y.-H.Z.), Peking University First Hospital, Beijing, China; Department of Neurology (L.V.), The University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Australia; Schneider Children's Medical Center of Israel (S.K., H.G.-S.), Petach Tikvah; Department of Neurology (Z.A.), Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Westmead Hospital (A.B.), New South Wales, Australia; Department of Neurology (P.G.-S.), Sydney Children's Hospital, Australia; Department of Neurology (A.D.K.), Tel Aviv University, Israel; Women's and Children's Hospital (L.M.D.), University of Adelaide, South Australia; Center for Neurobehavioral Genetics (E.K.R.), Semel Institute, David Geffen School of Medicine, University of California, Los Angeles; Department of Paediatrics (I.E.S.), The University of Melbourne, Royal Children's Hospital, Victoria; and The Florey Institute of Neurosciences and Mental Health (I.E.S.), Melbourne, Australia.
Article Synopsis
- This study revisits and expands the understanding of generalized epilepsy with febrile seizures plus (GEFS+) by analyzing 409 affected individuals from 60 families and identifying new associated phenotypes.* -
- The research revealed that besides febrile seizures, other phenotypes like focal seizures and classic generalized epilepsies also exist within the GEFS+ spectrum, with a significant portion of families showing genetic mutations.* -
- The authors propose renaming GEFS+ to “genetic epilepsy with febrile seizures plus” to better reflect the presence of focal epilepsies and highlight a greater genetic overlap with classic generalized epilepsies than previously recognized.*
Not all epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype.
Neurology
September 2017
From the Department of Paediatrics and Child Health (L.G.S., E.I.M.), University of Otago, Wellington, New Zealand; Department of Neurology (D.G.), University of Sydney, Australia; Department of Neurology (S.D.), Starship Children's Health, Auckland, New Zealand; Department of Neurology (C.J.), Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado, Denver; Department of Neurology (C.D.V., M.A.K.), Great Ormond Street Hospital for Children; Developmental Neurosciences (M.A.K.), UCL Great Ormond Street Institute of Child Health, London; Wellcome Trust Sanger Institute (DDD Study Group), Hinxton, Cambridge, UK; Departments of Paediatrics and Radiology (S.M.), University of Melbourne; The Florey Institute of Neuroscience and Mental Health (S.M., I.E.S.); Department of Medical Imaging (S.M.), Royal Children's Hospital, Melbourne, Australia; Department of Neurology (E.W., K.C.N.), Mayo Clinic, Rochester, MN; Department of Neurology (H.R.M.), Marshfield Clinic, WI; Division of Genetic Medicine (G.C., C.T.M., H.C.M.), Department of Pediatrics, University of Washington, Seattle; and Departments of Medicine and Paediatrics (I.E.S.), University of Melbourne, Austin Health and Royal Children's Hospital, Australia.
Objective: To define a distinct developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder.
Methods: A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and mutation.
Results: We identified 9 children 3 to 12 years of age; 7 were male.
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.
N Engl J Med
May 2017
From the New York University Langone Comprehensive Epilepsy Center, New York (O.D.); the University College London Great Ormond Street Institute of Child Health (J.H.C.) and GW Pharmaceuticals (S.W.) - both in London; Lurie Children's Epilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago (L.L.); the Children's Hospital of Philadelphia, Philadelphia (E.M.); Miami Children's Hospital, Miami (I.M.); Hôpital Necker-Enfants Malades, Paris (R.N.); Florey Institute, Austin Health and Royal Children's Hospital, University of Melbourne, Melbourne, VIC, Australia (I.E.S.); and Massachusetts General Hospital, Boston (E.A.T.).
Background: The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.
Methods: In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment.
Fungal Planet description sheets: 469-557.
Persoonia
December 2016
CBS-KNAW Fungal Biodiversity Centre, P.O. Box 85167, 3508 AD Utrecht, The Netherlands.
Novel species of fungi described in this study include those from various countries as follows: : on sp., on , (incl. gen.
View Article and Find Full Text PDFDysarthria and broader motor speech deficits in Dravet syndrome.
Neurology
February 2017
From the Department of Paediatrics, The University of Melbourne (S.J.T., M.A., V.A., A.T.M., I.E.S.), and Department of Psychology (V.A.), The Royal Children's Hospital; Neuroscience of Speech Group, Clinical Sciences Theme (S.J.T., A.T.M.), Australian Centre for Child Neuropsychological Studies (A.B., M.A., V.A.), Murdoch Childrens Research Institute, Melbourne; Epilepsy Research Centre, Department of Medicine (I.E.S.), The University of Melbourne, Austin Health; and Florey Institute of Neuroscience and Mental Health (I.E.S.), Melbourne, Australia.
Objective: To analyze the oral motor, speech, and language phenotype in 20 children and adults with Dravet syndrome (DS) associated with mutations in .
Methods: Fifteen verbal and 5 minimally verbal DS patients with mutations (aged 15 months-28 years) underwent a tailored assessment battery.
Results: Speech was characterized by imprecise articulation, abnormal nasal resonance, voice, and pitch, and prosody errors.
Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.
Neurology
November 2016
From the School of Medicine and Robinson Research Institute (M.A.C., R.C., J.G.) and School of Biological Sciences (J.G.), The University of Adelaide; Epilepsy Research Centre, Department of Medicine (S.T.B., S. Micallef, S.F.B., I.E.S.), University of Melbourne, Austin Health, Heidelberg; Florey Institute of Neuroscience and Mental Health (M.L., S. Maljevic, E.V.G., S.P., I.E.S.), Melbourne; Division of Genetic Medicine, Department of Pediatrics (G.L.C., C.T.M., H.C.M.), University of Washington, Seattle; Department of Neurology (K.B.H., I.E.S.), Royal Children's Hospital; Neurosciences Group (K.B.H.), Murdoch Childrens Research Institute, Melbourne; Department of Paediatrics (K.B.H.), University of Melbourne, Royal Children's Hospital, Parkville, Australia; Department of Neurology and Epileptology (S. Maljevic, H.L.), Hertie Institute for Clinical Brain Research, University of Tübingen, Germany; The Walter and Eliza Hall Institute of Medical Research (M.B.); Department of Medical Biology (M.B.), The University of Melbourne, Parkville; and Department of Medicine, Royal Melbourne Hospital (S.P.), The University of Melbourne, Australia.
Objective: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations.
Methods: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE).
Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.
Radiology
December 2016
From the Imaging Division, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, 245 Burgundy St, Melbourne, Australia 3084 (S.F., J.D.T., F.C., S.M., I.E.S., G.D.J., A.C.); Department of Medical Imaging and Radiation Sciences, Monash University, Melbourne, Australia (S.F., M.E.S.); Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia (J.D.T., F.C., G.D.J., A.C.); Department of Biomedical Engineering (J.D.T.) and Centre for the Developing Brain (J.D.T.), King's College London, London, England; Departments of Radiology (S.M.) and Paediatrics (S.M., I.E.S.), Royal Children's Hospital, University of Melbourne, Melbourne, Australia; and Epilepsy Research Centre, Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia (R.B., S.F.B., I.E.S.).
Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012.
View Article and Find Full Text PDFProduction of Manganese Oxide Nanoparticles by Shewanella Species.
Appl Environ Microbiol
September 2016
School of Natural Sciences, Nathan Campus, Griffith University, Nathan, Queensland, Australia
Unlabelled: Several species of the bacterial genus Shewanella are well-known dissimilatory reducers of manganese under anaerobic conditions. In fact, Shewanella oneidensis is one of the most well studied of all metal-reducing bacteria. In the current study, a number of Shewanella strains were tested for manganese-oxidizing capacity under aerobic conditions.
View Article and Find Full Text PDFDefinition and diagnostic criteria of sleep-related hypermotor epilepsy.
Neurology
May 2016
From IRCCS Istituto delle Scienze Neurologiche (P.T., F.B., F. Provini, L.V., L.L., B.M., I.N.), Bologna; Department of Biomedical and Neuromotor Sciences (P.T., F.B., F. Provini, L.L.), University of Bologna, Italy; University College London-Institute of Child Health (J.H.C.), Great Ormond Street Hospital for Children NHS Foundation Trust, London and Young Epilepsy, Lingfield, UK; Department of Epidemiology (D.H., R.O.), Mailman School of Public Health, and G.H. Sergievsky Center, College of Physicians & Surgeons, Columbia University, New York, NY; Unité Médicale Epilepsie et Malaises (P.K.), Pôle de Neurologie et Psychiatrie, CHU de Grenoble, France; "C. Munari" Center for Epilepsy Surgery (L.N., L.T.), Niguarda Hospital, Milan, Italy; Epilepsy Research Centre (I.E.S.), Department of Medicine, University of Melbourne, Austin Health, Australia; Department of Neurology (C.B.), University of Bern, Switzerland; Unit of Neurology (F.C.), S. Orsola-Malpighi Hospital, University of Bologna, Italy; Department of Clinical Neurosciences (C.D.), Western General Hospital, Edinburgh, UK; Department of Medical and Surgical Sciences (A.G.), Institute of Neurology, University Magna Græcia, Catanzaro, Italy; Neurology Unit and Laboratories (R.G., C.M.), A. Meyer Children's Hospital, Florence, Italy; National Institute of Clinical Neuroscience (P.H.), Budapest, Hungary; Department of Neurology (M.M.), University of Minnesota Medical School, Minneapolis; Institute of Neurology Mondino (R.M.), University of Pavia; Sleep Disorders Center (L.P.), Department of Neurology, University of Parma, Italy; Department of Neurology (F. Picard), University Hospital and Medical School of Geneva, Switzerland; Department of Biomedical and Surgical Sciences (M.P.), University of Ferrara, Italy; Department of Clinical Neurosciences (P.R.), CHUV, Lausanne, Switzerland; Functional Neurology and Epileptology (P.R.), Hospices Civils de Lyon and CRNL, Lyon; Epilepsy Institute (P.R.), IDEE, Lyon, France
The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives.
View Article and Find Full Text PDFPredicting the geographical distributions of the macaque hosts and mosquito vectors of Plasmodium knowlesi malaria in forested and non-forested areas.
Parasit Vectors
April 2016
Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, 98121, USA.
Article Synopsis
- Plasmodium knowlesi is transmitted from macaques to humans via anopheline mosquitoes, and understanding the geographical distribution of this malaria is essential for assessing disease risk.
- Researchers used presence data from macaque and mosquito species, a boosted regression tree model, and environmental data to predict the habitats where these species thrive.
- The findings indicate that the transmission risk is higher in disturbed forest areas due to the presence of both macaque hosts and mosquito vectors, particularly in regions where human activity has altered the landscape.
Development of a lateral flow immunoassay for rapid field detection of the red imported fire ant, Solenopsis invicta (Hymenoptera: Formicidae).
Anal Bioanal Chem
July 2016
Animal and Plant Health Inspection Service, United States Department of Agriculture, Plant Protection and Quarantine, Biloxi, MS, 39530, USA.
The red imported fire ant, Solenopsis invicta, is an aggressive, highly invasive pest ant species from South America that has been introduced into North America, Asia, and Australia. Quarantine efforts have been imposed in the USA to minimize further spread of the ant. To aid the quarantine efforts, there remains an acute need for a rapid, field portable method for the identification of these ants.
View Article and Find Full Text PDFIn silico prioritization based on coexpression can aid epileptic encephalopathy gene discovery.
Neurol Genet
February 2016
Epilepsy Research Centre (K.L.O., I.E.S., S.F.B.), Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia; Population Health and Immunity Division (V.L., S.F., M.B.), The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Florey Institute (I.E.S.), Melbourne, Australia; Department of Paediatrics (I.E.S.), University of Melbourne, Royal Children's Hospital, Melbourne, Australia; and Department of Mathematics and Statistics (M.B.) and Department of Medical Biology (M.B.), University of Melbourne, Australia.
Objective: To evaluate the performance of an in silico prioritization approach that was applied to 179 epileptic encephalopathy candidate genes in 2013 and to expand the application of this approach to the whole genome based on expression data from the Allen Human Brain Atlas.
Methods: PubMed searches determined which of the 179 epileptic encephalopathy candidate genes had been validated. For validated genes, it was noted whether they were 1 of the 19 of 179 candidates prioritized in 2013.
Epileptic spasms are a feature of DEPDC5 mTORopathy.
Neurol Genet
August 2015
Division of Genetic Medicine (G.L.C., J. Saykally, M.Z., H.C.M.), Department of Pediatrics, University of Washington, Seattle; Epilepsy Research Centre (D.E.C., B.M.R., J.M.M., A.L.S., S.A.M., S.F.B., I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne, Australia; Neurology Department (D.E.C.), Northern Health, Melbourne, Australia; Epilepsy Research Program (L.D.), School of Pharmacy and Medical Sciences, and Sansom Institute for Health Research (L.D.), University of South Australia, Adelaide, Australia; Department of Neurology (K.B.H., R.J.L., A.S.H., I.E.S.), Royal Children's Hospital, Melbourne, Australia; Florey Institute of Neuroscience and Mental Health (K.B.H., S.M., R.J.L., A.S.H., S.A.M., I.E.S.), Melbourne, Australia; Murdoch Childrens Research Institute (K.B.H., R.J.L., A.S.H.), Melbourne, Australia; Department of Paediatrics (S.M., R.J.L., A.S.H.) and Department of Radiology (S.M.), The University of Melbourne, Melbourne, Australia; and Epilepsy Division (J. Sullivan), Department of Neurology and Pediatrics, University of California, San Francisco.
Objective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms.
Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants.
Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms.
A targeted resequencing gene panel for focal epilepsy.
Neurology
April 2016
From the Epilepsy Research Centre (M.S.H., B.M.R., J.A.D., S.A.M., M.R.N., I.E.S., S.F.B.), Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia; Division of Genetic Medicine (C.T.M., G.L.C., H.C.M.), Department of Pediatrics, University of Washington, Seattle, WA; Florey Institute for Neuroscience and Mental Health (U.N., E.V.G., C.J.M., C.A.R., S.P., I.E.S.), University of Melbourne, Melbourne, Victoria, Australia; Department of Neurology (I.E.S.), Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia; and Department of Pediatrics (I.E.S.), University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.
Objectives: We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies.
Methods: The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing.
Results: We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases.
Multiplex families with epilepsy: Success of clinical and molecular genetic characterization.
Neurology
February 2016
From the Sackler School of Medicine (Z.A., I.B., M.Y.N., T.L.-S., A.D.K.), Tel Aviv University, Ramat Aviv, Israel; Epilepsy Research Centre (K.L.O., K.L.H., I.E.S., S.F.B.), University of Melbourne, Austin Health, Heidelberg, Australia; Epilepsy Unit (S.K., H.G.-S., R.S.), Schneider Children's Medical Center of Israel, Petach Tikvah; Department of Neurology (A.M., M.Y.N.), Tel Aviv Sourasky Medical Center; Department of Neurology (I.B.), The Chaim Sheba Medical Center, Tel Hashomer; Shaare Zedek Medical Center (A.J.M.), Jerusalem; Department of Neurology (S.W.), Western Galilee Hospital, Nahariya; Pediatric Neurology and Child Development Center (M. Mahajnah), Hillel Yaffe Medical Center, Hadera; Ruth and Bruce Rappaport Faculty of Medicine (M. Mahajnah), Technion, Haifa; Pediatric Neurology Unit (T.L.-S.), Wolfson Medical Center, Holon; The Edmond and Lily Safra Children's Hospital (B.B.-Z.), Sheba Medical Center, Ramat Gan; Department of Neurology (E.K.), Barzilai Medical Center, Ashkelon; Faculty of Health Sciences (E.K., R.M., Z.S.), Ben-Gurion University of the Negev, Beer-Sheva; Department of Neurology (R.M.) and Pediatric Neurology Unit (Z.S.), Soroka University Medical Center, Beer-Sheva; Pediatric Neurology Unit (U.K.), Dana Children's Hospital, Tel Aviv; Department of Neurology (D.E.), Agnes Ginges Center of Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; School of Biomedical Sciences (R.H.W.), Charles Sturt University, NSW; Queensland Brain Institute (M. Mangelsdorf), University of Queensland, Brisbane, Australia; Wessex Regional Genetics Laboratory (J.N.M.), Salisbury NHS Foundation Trust, Salisbury, UK; Division of Genetic Medicine (G.L.C., H.C.M.), Department of Pediatrics, University of Washington, Seattle; Florey Institute (G.D.J., I.E.S.), Melbourne; Department of Pediatrics (I.E.S.), University of Melbourne, Royal Children's Hospital; Population Health and Immunity Division (M.B.), The Walter and Eliza Hall Institute o
Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis.
Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis.
Loss of synaptic Zn2+ transporter function increases risk of febrile seizures.
Sci Rep
December 2015
The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville 3052, Victoria, Australia.
Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn(2+)) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn(2+) homeostasis contributes to susceptibility is unknown. Synaptic Zn(2+) is co-released with glutamate and modulates neuronal excitability.
View Article and Find Full Text PDFSCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.
Neurology
September 2015
From the Departments of Neurology (K.B.H., M.T.M., V.R.-C., J.L.F., A.S.H., I.E.S.) and Radiology (S.M.), The Royal Children's Hospital, Melbourne; Department of Paediatrics (K.B.H., M.T.M., S.M., A.S.H., I.E.S.), The University of Melbourne; Murdoch Childrens Research Institute (K.B.H., M.T.M., J.L.F., A.S.H.), Melbourne; Epilepsy Research Centre (J.M.M., I.E.S.), Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia; Division of Genetic Medicine (G.L.C., H.C.M.), Department of Paediatrics, University of Washington, Seattle; Epilepsy Genetics Program (D.T., H.E.O., A.P.), Department of Neurology, Harvard Medical School, Boston Children's Hospital, MA; TY Nelson Department of Neurology and Neurosurgery (R.W.), The Children's Hospital at Westmead, Sydney; Department of Neurology (D.C.), Women's and Children's Hospital, Adelaide; Neurosciences Children's Health Queensland (S.C.), Lady Cilento Children's Hospital, Brisbane; and Florey Institute of Neuroscience and Mental Health (S.M., A.S.H., I.E.S.), Melbourne, Australia.
Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy.
Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.
Repeated-sprint cycling does not induce respiratory muscle fatigue in active adults: measurements from the powerbreathe® inspiratory muscle trainer.
J Sports Sci Med
March 2015
Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Queensland, Australia.
This study examined respiratory muscle strength using the POWERbreathe® inspiratory muscle trainer (i.e., 'S-Index') before and after repeated-sprint cycling for comparison with maximal inspiratory pressure (MIP) values obtained during a Mueller maneuver.
View Article and Find Full Text PDFCHD2 myoclonic encephalopathy is frequently associated with self-induced seizures.
Neurology
March 2015
From the Epilepsy Research Centre (R.H.T., L.M.Z., J.S.A., S.B.H., S.A.M., S.F.B., I.E.S.), University of Melbourne, Austin Health, Heidelberg, Australia; MRC Centre for Neuropsychiatric Genetics & Genomics (R.H.T.), Hadyn Ellis Building, Cathays, Cardiff University, UK; Department of Neurology (L.M.Z.), Children's Hospital of Fudan University, Shanghai, China; Department of Pediatrics (G.L.C., H.C.M.), Division of Genetic Medicine, University of Washington, Seattle; Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia; Departments of Radiology and Paediatrics (S.A.M., I.E.S.), Royal Children's Hospital, and University of Melbourne, Australia; Carol Davila University of Medicine (D.C.), Pediatric Neurology Clinic, Al Obregia Hospital, Bucharest, Romania; and TY Nelson Department of Neurology (D.S.G.), The Children's Hospital at Westmead, Sydney, Australia.
Objective: To delineate the phenotype of early childhood epileptic encephalopathy due to de novo mutations of CHD2, which encodes the chromodomain helicase DNA binding protein 2.
Methods: We analyzed the medical history, MRI, and video-EEG recordings of 9 individuals with de novo CHD2 mutations and one with a de novo 15q26 deletion encompassing CHD2.
Results: Seizures began at a mean of 26 months (12-42) with myoclonic seizures in all 10 cases.
GRIN2A: an aptly named gene for speech dysfunction.
Neurology
February 2015
From the Department of Paediatrics (S.J.T., S.A.M., A.T.M., I.E.S.), The University of Melbourne, The Royal Children's Hospital, Parkville; Language and Literacy Group (A.K.M., A.T.M.), Population Health Theme, Murdoch Childrens Research Institute, Parkville; Speech Pathology Department (A.V.), The Royal Children's Hospital, Parkville; Department of Radiology (S.A.M.), The University of Melbourne, Parkville; Epilepsy Research Centre (I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne; and Florey Institute of Neuroscience and Mental Health (S.A.M., I.E.S.), Melbourne, Australia.
Objective: To delineate the specific speech deficits in individuals with epilepsy-aphasia syndromes associated with mutations in the glutamate receptor subunit gene GRIN2A.
Methods: We analyzed the speech phenotype associated with GRIN2A mutations in 11 individuals, aged 16 to 64 years, from 3 families. Standardized clinical speech assessments and perceptual analyses of conversational samples were conducted.
Genetics of epilepsy: The testimony of twins in the molecular era.
Neurology
September 2014
From the Epilepsy Research Centre, Department of Medicine (Neurology) (L.V., K.L., J.E., D.K., M.C., Y.T.-B., R.A.H., I.E.S., S.F.B.), University of Melbourne, Austin Health; School of Medicine (L.V.), The University of Queensland, Brisbane; Department of Neurology (L.V.), Royal Brisbane and Women's Hospital; Centre for Molecular, Environmental, Analytic and Genetic Epidemiology (R.L.M., J.L.H.), University of Melbourne; School of Pharmacy and Medical Sciences and Sansom Institute for Health Research (S.E.H., L.M.D.), University of South Australia, Adelaide; and the Department of Genetic Medicine, SA Pathology (J.C.M.), Women's and Children's Hospital, North Adelaide, Australia.
Objective: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicability of the 2010 International League Against Epilepsy (ILAE) organization of epilepsy syndromes, and to integrate molecular genetics with phenotypic analyses.
Methods: A total of 558 twin pairs suspected to have epilepsy were ascertained from twin registries (69%) or referral (31%). Casewise concordance estimates were calculated for epilepsy syndromes.