The Neuroscience Research group comprises researchers dedicated to the study of the central and peripheral nervous systems. The team is a clinically oriented research group focussed on translational research, which is aimed at improving the lives of children with a broad spectrum of neurological disorders.
All members of the research team have close links with the Departments of Neurology or Neurosurgery of The Royal Children’s Hospital (RCH), with all team leaders being directly involved in patient clinical care. Neuroscience Research group has strong multidisciplinary collaborations with other groups within Murdoch Children's, as well as research groups within Victoria, nationally and internationally.
- Epilepsy Research
- Neuromuscular Research
- Stroke Research
- Leukodystrophy Research
- Neurosurgery Research
- Neuroimmunology Research
Epileptogenicity and outcome of surgery in tuberous sclerosis is being studied by the RCH neurology, neurosurgery, medical imaging and pathology departments, in collaboration with the Murdoch Children's tissue genetics team and the Petrou Lab at the Florey Neurosciences Institute. A particular focus is the examination of tissue excitability and microstructure in the centre of cortical tubers, using in vivo investigations in patients and in vitro studies of resected tissue.
Cortical dysplasias are a not uncommon cause of drug-resistant focal epilepsy in children. Some are extremely small and at the limits of current magnetic resonance imaging (MRI) technology. The RCH neurology and neurosurgery departments are working with the medical imaging and pathology departments to find better ways to identify these patients and these lesions, and then cure their seizures with more precise surgery. The work is being done in collaboration with the Austin Hospital and the Florey Neurosciences Institute.
Simultaneous EEG-fMRI is a technique in which the brain’s electrical activity can be recorded during an MRI scan and visualised as a brain image. In a collaboration with the Florey Neurosciences Institute, the Murdoch Children's Developmental Brain Imaging Group and the RCH neurology department, the team is studying the brain regions that give rise to abnormal electrical activity in the children with focal and generalised epilepsy. In some children, the findings will lead to surgical therapies for their seizures.
Anticonvulsant drug trials
In conjunction with the Australian Paediatric Pharmacology Research Unit (APPRU), the RCH neurology department participates in pharmaceutical-sponsored randomised clinical trials of new antiepileptic medications in children with epilepsy.
Severe epilepsies of infancy
The severe epilepsies of infancy (SEI) are a group of neurological disorders with frequent seizures and often poor cognitive outcome, due to a variety of causes. In many patients, the cause remains unknown despite extensive investigation, and is presumed genetic. This research will study the incidence and genetic causes of SEI. This work will inform the diagnosis, prognosis and management of children with SEI. At a broader level, understanding the genes and pathways that cause SEI is the first step in developing novel treatments. This work is being done in collaboration with the Epilepsy Research Institute at the Austin Hospital.
Brain malformation research
Brain malformations are disorders of brain structure and function that occur due to either genetic or environmental factors adversely affecting the development of the brain during pregnancy. These disorders include microcephaly, lissencephaly, grey matter heterotopia, agenesis of the corpus callosum, polymicrogyria and cortical dysplasia. Common symptoms include cerebral palsy, developmental delay and epilepsy. The Neuroscience group has an active research program beginning in the clinic, which is aimed to understand the causes, outcomes and best treatments for these conditions. This research involves brain imaging using advanced MRI, gene discovery using next generation sequencing technologies and studies of outcome and function using clinical and neuropsychological measures. The team works closely with other campus partners from genetics, imaging, neuropsychology, clinical neurology and epilepsy surgery, as well as multiple national and international collaborators.
Clinical trials into neuromuscular disorders of childhood
Cumulatively, nerve disorders (neuropathies) and muscle disorders (myopathies and muscular dystrophies) affect at least one in 1000 children. Although individually uncommon, these conditions cause weakness, difficulty with motor tasks such as walking and running, and they are often associated with orthopaedic problems such as scoliosis and joint contractures. Some also affect the heart and respiratory muscles, and can cause wheelchair-dependence and even early death.
The team is actively engaged in a number of natural history studies and clinical trials into diagnosis, assessment and treatment of neuromuscular disorders of childhood. The team includes a number of neurologists as well as a specialised nurse practitioner, research physiotherapists, an occupational therapist, genetic counsellor, respiratory specialists, cardiologists, an orthotist, research dieticians, a psychiatrist, social worker, teacher and orthopaedic surgeon. The RCH Neuromuscular clinic is headed by A/Prof Monique Ryan, who also leads the research team and is a PI on an NHMRC Centre of Research Excellence grant looking at various aspects of the diagnosis, management and treatment of paediatric neuromuscular disorders. The other neurologists involved with the team are A/Prof Andrew Kornberg, Dr Eppie Yiu and Dr Victoria Rodriguez-Casero.
Particular areas of interest are Duchenne muscular dystrophy, spinal muscular atrophy and Charcot-Marie-Tooth disease. Duchenne muscular dystrophy is the most common progressive muscle disease of childhood. The team are part of several international research consortia involved in DMD research, and have subjects enrolled in a number of long-term natural history studies of this condition. This includes clinical trials of a number of potential new treatments for DMD, including studies of nutriceuticals, bisphosphonate therapy, antisense oligonucleotide therapy and nonsense-mutation gene read-through.
Spinal muscular atrophy is a relatively common, severe disorder affecting motor nerves and causing severe weakness, contractures, scoliosis and respiratory impairment. To date no effective treatments for this condition have been identified. Murdoch Children's is one of two Australian centres enrolling infants with SMA type 1 in an international trial of intrathecal antisense oligonucleotide therapy.
Charcot-Marie-Tooth (CMT) disease is a term representing about 70 different genetic nerve diseases which can present in childhood or adulthood. We have a longstanding research interest into CMT, and undertook the first large study of vitamin C supplementation for paediatric CMT type 1A. We continue to engage in studies of the orthopaedic, gait and other aspects of natural history of different forms of CMT and are looking to undertaken studies of potential new therapeutics in the near future.
Vaso-occlusive stroke in children with cardiac disease- a case control study to identify risk factors for stroke in children with cardiac disease
Advances in medical and surgical treatment of children with congenital heart disease have resulted in improved survival. There is now increasing focus on neurodevelopmental outcome in this patient population. Stroke is particularly important as it frequently results in permanent neurologic sequelae although it often goes clinically unrecognised, particularly in young infants. This project aims to improve the understanding of the risk factors for perioperative stroke in the cardiac population by comparing children with stroke and cardiac disease to other children with a similar cardiac diagnosis, procedure type, age and date of procedure.
Characterizing brain behaviour relationships in perinatal and childhood stroke using diffusion weighted magnetic resonance imaging
Currently there is lack of clinical research validating biomarkers to predict prognosis in childhood stroke. Advanced diffusion MRI techniques, which provide assessment of the microstructure of white matter fibre tracts, will provide important insights into patterns of recovery following stroke. These novel methods are an important first step in understanding brain connectivity and functional reorganization following stroke within the developing brain. This cross sectional study aims to explore the relationship between lesion characteristics and functional outcome in childhood stroke using MR diffusion imaging. Accurate identification of the neural correlates of language and motor deficits will assist with early identification of children at increased risk of adverse outcomes, thereby facilitating implementation of appropriate interventional strategies.
Strategies to decrease lag time to diagnosis in paediatric stroke
Strategies need to be developed to reduce time to diagnosis by improving knowledge of stroke symptoms amongst parents, general practitioners and paediatricians. The purpose of this study is to identify reasons for delayed presentation to hospital and to identify useful signs or symptoms to discriminate stroke from other brain problems. Parents of children recruited to RCH Registry will be interviewed and medical charts will be reviewed. A 12 month audit of children presenting to RCH with brain attacks will be performed to define the scope of conditions mimicking stroke.
This project will inform development of a stroke clinical pathway to enable rapid triage, medical assessment and neuroimaging to increase likelihood of children receiving thrombolytic treatment to reduce long term disability.
Leukodystrophies are disorders of the white matter or cabling networks of the brain. There are many types of leukodystrophies with variable clinical outcomes including developmental delay, muscle spasticity and occasional problems with the peripheral nerves to the legs and nerves to the eyes. Some leukodystrophies are mild and static, whilst others are progressive and degenerative. It is presumed that the majority of leukodystrophies are caused by genetic disorders, yet the precise genetic cause can only be found in ~50% of patients. This research aims to classify and understand the causes and outcomes of these conditions and to develop better means of diagnosis and treatment. The team is part of the Global Leukodystrophy InitiAtive (GLIA), a team of investigators from around the world determined to understand these conditions better and improve the lives of affected patients and their families.
The overall aim of the research conducted at the Department of Neurosurgery is to further the clinical utilities of non-invasive, state-of-art neuroimaging techniques that improve the surgical planning and functional outcomes of children underwent neurosurgical interventions. These neuroimaging adjuncts include techniques such as Magnetic Resonance (MR) diffusion tractography (a post-processing MR technique that allows non-invasive mapping of brain nerve fibre tracts), functional MR imaging (a post-processing MR technique studying areas of functional brain cortices during execution of a functional task), and the incorporation of a MR scanner in the operating suite (IMRIS theatre). The focus of the current research is the evaluation of the peri-operative and intra-operative role of MR diffusion tractography in paediatric epilepsy neurosurgery. The developed MR diffusion tractography technique is also a valuable educational resource for the learning of brain nerve fibre tract anatomy in both healthy and disease states.
Whilst multiple sclerosis (MS) is often thought to be a neurologic disorder of adults, up to 5% of all individuals with MS have onset during childhood. The treatment options available for MS have broadened significantly over the past five to ten years, and now include oral agents as an alternative to the traditional injectable agents. Their safety and effectiveness in children need to be formally studied. Murdoch Children's is an active enrolling site in two large, international, multicentre MS treatment trials in children, studying the efficacy and safety of two new oral agents for MS – fingolimod and teriflunomide. The Institute’s site is run by Associate Professor Andrew Kornberg (PI) and Dr Eppie Yiu (sub-investigator). These treatment trials are the first randomised-controlled trials in paediatric MS, and represent an important step forward in the treatment of children with MS.
High-resolution ultrasound in neuromuscular disorders of childhood
Advances in ultrasound technology over the past 10 to 15 years have markedly improved its resolution and image quality. High-resolution ultrasound is increasingly used in the assessment of nerve and muscle conditions. As a painless, safe and non-invasive imaging method, it is particularly suitable in the paediatric population. A recent study conducted by Dr Eppie Yiu at the Murdoch Children's Research Institute, demonstrated marked increase in nerve size in children with an inherited nerve disorder called Charcot-Marie-Tooth disease type 1A, and indicated that nerve ultrasound may be a useful tool in the diagnosis and monitoring of children with nerve conditions. Further studies aim to establish reference ranges for nerve size in healthy children, describe ultrasound findings in a range of inherited and inflammatory nerve disorders of childhood, and to describe the muscle ultrasound abnormalities in a range of muscle conditions, including the muscular dystrophies.
- A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study. 2017
- A systematic evaluation of intraoperative white matter tract shift in pediatric epilepsy surgery using high-field MRI and probabilistic high angular resolution diffusion imaging tractography. 2017
- Accuracy and Reliability of Stroke Diagnosis in the Pediatric Emergency Department. 2017
- Acute flaccid myelitis in childhood: a retrospective cohort study. 2017
- Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome. 2017
- Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome. 2017
- DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum and developmental split brain syndrome. 2017
- Deterioration in gait and functional ambulation in children and adolescents with Charcot-Marie-Tooth disease over 12 months. 2017
- Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy. 2017
- Dysarthria and broader motor speech deficits in Dravet syndrome. 2017
- Familial epilepsy with anterior polymicrogyria as a presentation of COL18A1 mutations. 2017
- Fatal Cerebral Edema With Status Epilepticus in Children With Dravet Syndrome: Report of 5 Cases. 2017
- Focal Cerebral Arteriopathy: Do Steroids Improve Outcome? 2017
- GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects. 2017
- Hemispheric polymicrogyria and neonatal seizures: a potentially life-threatening combination. 2017
- MCM3AP in recessive Charcot-Marie-Tooth neuropathy and mild intellectual disability. 2017
- Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. 2017
- Prehospital Emergency Care in Childhood Arterial Ischemic Stroke. 2017
- Seizures in Children With Cerebral Palsy and White Matter Injury. 2017
- Social Competence at Two Years after Childhood Traumatic Brain Injury. 2017
- Trajectories of Motor Recovery in the First Year After Pediatric Arterial Ischemic Stroke. 2017
- A longitudinal study of risk and protective factors associated with successful transition to secondary school in youth with ADHD: prospective cohort study protocol. 2016
- Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery. 2016
- Brain attacks and stroke in children. 2016
- Can in-the-moment diary methods measure health-related quality of life in Duchenne muscular dystrophy? 2016
- Centre of epileptogenic tubers generate and propagate seizures in tuberous sclerosis. 2016
- Cerebral palsy is not a diagnosis: A case report of a novel atlastin-1 mutation. 2016
- Differentiating Childhood Stroke From Mimics in the Emergency Department. 2016
- EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy. 2016
- Epileptic encephalopathy: Use and misuse of a clinically and conceptually important concept. 2016
- Familial cortical dysplasia caused by mutation in the mTOR regulator NPRL3. 2016
- Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency. 2016
- Ictal unilateral blinking is an unreliable lateralizing sign in tuberous sclerosis complex. 2016
- Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus. 2016
- Mutations of the Sonic Hedgehog Pathway Underlie Hypothalamic Hamartoma with Gelastic Epilepsy. 2016
- Neurologic Melioidosis: Case Report of a Rare Cause of Acute Flaccid Paralysis. 2016
- Outcome in Childhood Stroke. 2016
- Pathogenic mechanisms underlying X-linked Charcot-Marie-Tooth neuropathy (CMTX6) in patients with a pyruvate dehydrogenase kinase 3 mutation. 2016
- Patient and Process Factors Associated With Type of First Neuroimaging and Delayed Diagnosis in Childhood Arterial Ischemic Stroke. 2016
- Performance of bedside stroke recognition tools in discriminating childhood stroke from mimics. 2016
- Presentation of Acute Childhood Stroke in a Tertiary Pediatric Emergency Department. 2016
- Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk. 2016
- Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis. 2016
- Rasmussen encephalitis tissue transfer program. 2016
- Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. 2016
- TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features. 2016
- The genetic landscape of the epileptic encephalopathies of infancy and childhood. 2016
- The histopathology of polymicrogyria: a series of 71 brain autopsy studies. 2016
- Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3. 2016
- A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. 2015
- A diagnostic approach to recurrent myalgia and rhabdomyolysis in children. 2015
- A mixed methods study of age at diagnosis and diagnostic odyssey for Duchenne muscular dystrophy. 2015
- Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry. 2015
- Complete callosal agenesis, pontocerebellar hypoplasia and axonal neuropathy due to AMPD2 loss 2015
- Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss. 2015
- Correction: Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry. 2015
- DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder. 2015
- Duchenne muscular dystrophy. 2015
- Emergency management of ischemic stroke in children. 2015
- Fatigue in child chronic health conditions: a systematic review of assessment instruments. 2015
- Favourable response to ketogenic dietary therapies: undiagnosed glucose 1 transporter deficiency syndrome is only one factor. 2015
- Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR. 2015
- Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia. 2015
- Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures. 2015
- Peripheral nerve ultrasound in pediatric Charcot-Marie-Tooth disease type 1A. 2015
- Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research. 2015
- Strong correlation between the 6-minute walk test and accelerometry functional outcomes in boys with Duchenne muscular dystrophy. 2015
- Alterations in the functional connectivity of frontal lobe networks preceding emergence delirium in children. 2014
- Ataluren treatment of patients with nonsense mutation dystrophinopathy. 2014
- Emotional impact of Bell's palsy in children. 2014
- Is focal cortical dysplasia sporadic? Family evidence for genetic susceptibility. 2014
- Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children. 2014
- Observations of body mass index in Duchenne muscular dystrophy: a longitudinal study. 2014
- Polymicrogyria: A common and heterogeneous malformation of cortical development. 2014
- Predicting neurocognitive and behavioural outcome after early brain insult. 2014
- Social competence following pediatric stroke: contributions of brain insult and family environment. 2014
- Somatic mutations in cerebral cortical malformations. 2014
- Stroke and nonstroke brain attacks in children. 2014
- A new locus for X-linked dominant CharcotMarieTooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene 2013
- Cognitive Outcomes Following Arterial Ischemic Stroke in Infants and Children. 2013
- Mutations in DARS Cause Hypomyelination with Brain Stem and Spinal Cord Involvement and Leg Spasticity. 2013
- Natural history of pulmonary function in collagen VI-related myopathies 2013
- Neuropsychological Profile of Agenesis of the Corpus Callosum: A Systematic Review 2013
- Pediatric Guillain-Barre syndrome 2013
- Pontocerebellar hypoplasia type 1 Clinical spectrum and relevance of EXOSC3 mutations 2013
- Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 2013
- Auditory function in children with Charcot-Marie-Tooth disease. 2012
- Autoimmune myasthenia gravis, immunotherapy and thymectomy in children. 2012
- Benign neonatal sleep myoclonus: an autosomal dominant form not allelic to KCNQ2 or KCNQ3. 2012
- Binaural speech processing in individuals with auditory neuropathy. 2012
- Demyelinating prenatal and infantile developmental neuropathies. 2012
- Efficacy of the ketogenic diet: which epilepsies respond? 2012
- Epileptic spasms: experience with a high-dose oral corticosteroid protocol. 2012
- Febrile infection-related epilepsy syndrome is not caused by SCN1A mutations. 2012
- Genetic axonal neuropathies and neuronopathies of pre-natal and infantile onset. 2012
- Methemoglobin reductase deficiency: novel mutation is associated with a disease phenotype of intermediate severity. 2012
- Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration 2012
- Progressive Gait Deterioration in Adolescents With Dravet Syndrome 2012
- Towards a consensus-based classification of childhood arterial ischemic stroke. 2012
- Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A. 2012
- A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood 2011
- Acute childhood arterial ischemic and hemorrhagic stroke in the emergency department. 2011
- Arterial Ischemic Stroke Risk Factors: The International Pediatric Stroke Study 2011
- Autogenous Transcriptional Regulation of the regA Gene, Encoding an AraC-Like, Essential Virulence Regulator in Citrobacter rodentium 2011
- Can the FAST and ROSIER adult stroke recognition tools be applied to confirmed childhood arterial ischemic stroke? 2011
- Control of bacterial virulence by AraC-like regulators that respond to chemical signals 2011
- Detection of Epileptogenic Cortical Malformations with Surface-Based MRI Morphometry 2011
- Does Timing of Brain Lesion Have an Impact on Children's Attention? 2011
- Extended treatment of childhood Charcot-Marie-Tooth disease with high-dose ascorbic acid 2011
- Functional outcome following paediatric stroke 2011
- Health status of boys with Duchenne muscular dystrophy: a parent's perspective 2011
- Pediatric sciatic neuropathies A 30-year prospective study 2011
- PEDIATRIC SCIATIC NEUROPATHY ASSOCIATED WITH NEOPLASMS 2011
- Phenotypic Variability of Distal 22q11.2 Copy Number Abnormalities 2011
- Reducing the exome search space for Mendelian diseases using genetic linkage analysis of exome genotypes 2011
- Spontaneous intracranial hypotension in childhood: a case report and review of the literature. [Review] 2011
- Temporoparietooccipital disconnection in children with intractable epilepsy Clinical article 2011
- National Health and Medical Research Council
- Brain Research Foundation
- European Union FP7 Rare Disease Best Practice group
- Charcot-Marie-Tooth Association of Australia
- Royal Children’s Hospital Foundation
- Thyne Reid Foundation
- Campbell Edwards Trust
- Handbury / Payne Family
- Suttie Family
- Hansen Family
- Brimbank Council
- Macquarie Bank
- Global Leukodystrophy Initiative
- Cooperative International Neuromuscular Research Group
- International Pediatric Stroke Study