A5106135516- Epilepsy research and treatment
- Infectious Encephalopathies and Encephalitis
- Autoimmune Neurological Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
- Multiple Sclerosis Research Studies
- Systemic Lupus Erythematosus Research
- Bacterial Infections and Vaccines
- Long-Term Effects of COVID-19
- Peripheral Neuropathies and Disorders
- Neonatal and fetal brain pathology
- Obsessive-Compulsive Spectrum Disorders
- Genomics and Rare Diseases
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Ion channel regulation and function
- RNA and protein synthesis mechanisms
- Tracheal and airway disorders
- Pharmacological Effects and Toxicity Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Glycogen Storage Diseases and Myoclonus
- interferon and immune responses
- Tuberous Sclerosis Complex Research
- Herpesvirus Infections and Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Tryptophan and brain disorders
Children's Hospital at Westmead
2016-2025
The University of Sydney
2015-2025
Sydney Children’s Hospitals Network
2024
John Wiley & Sons (United States)
2024
Hudson Institute
2024
Sydney Children's Hospital
2018
University College London
2018
Great Ormond Street Hospital
2018
Institut des Maladies Génétiques Imagine
2018
Inserm
2018
Background Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited biomarkers for monitoring purposes children with inflammatory or brain disease. The cause encephalitis is unknown up to a third cohorts, it important differentiate infective from given therapeutic implications. Aim To study cytokines chemokines as active neuroinflammation, assess their role differentiating demyelinating, autoimmune, viral encephalitis. Methods...
Abstract Objective To investigate intrathecal inflammation using cerebrospinal fluid (CSF) cytokines and chemokines in a subgroup of pediatric epilepsy patients with frequent daily seizures. Methods We measured 32 cytokines/chemokines multiplex immunoassay CSF collected from febrile infection‐related syndrome (FIRES)/FIRES‐related disorders (FRD; n = 6), status epilepticus (FSE; 8), afebrile (ASE; chronic seizures (n 21) compared the results noninflammatory neurological (NIND; 20)...
To report the prevalence and clinical characteristics of children with rapid onset functional tic-like behaviours during COVID-19 pandemic.Single centre, retrospective cohort study (<18 years) referred to tic clinic from January 2018 July 2021. We calculate newly diagnosed tics, compare features chronic disorder/Tourette syndrome (CTD/TS).A total 185 new patients were between There was a significant increase in percentage tics 2020 2021 (2% 2018, 5.6% 2019, 10.6% 36% 2021). Differences (n =...
Background Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination represents a subgroup of autoimmune that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, can have relapsing course. Unlike NMO MS, there paucity literature on immunopathology CSF cytokine/chemokines in MOG Ab demyelination. Aim To study the differences immunopathogenesis based cytokine/chemokine profile Ab-positive (POS) -negative (NEG) groups. Methods We measured 34...
To report our institutional experience of targeted massively parallel sequencing (MPS) testing in children with epilepsy.We retrospectively analysed the yield epileptic encephalopathy (EE) panel 71 known EE genes patients epilepsy unknown cause, who underwent clinical triage by a group neurologists prior to testing. We compared cost approach traditional evaluation identified pathogenic variants.The variants was 28.5% (n = 30/105), highest early onset <3 months including Ohtahara syndrome...
IFIH1 gain-of-function causes a spectrum of neuroinflammatory phenotypes associated with enhanced type I interferon production and Janus kinase (JAK)/signal transducer activator transcription (STAT) pathway activation.1,2 Patients most often present in infancy, variably exhibiting spasticity, dystonia, seizures, acquired microcephaly. We report the use ruxolitinib, JAK 1/2 blocker, treatment early-onset, progressive neurologic disease due to an mutation.
Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation deficits, brain transcriptomics disorders humans show upregulated differentially expressed genes enriched immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder...
Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterised by abrupt onset obsessive compulsive disorder and regression in neurodevelopmental skills, triggered infection or stress. Whether PANS a distinct entity part of spectrum uncertain, its pathophysiology remains unclear. We show that children with (n=32) other non-PANS (n=68) disorders (total n=100) have higher reported early childhood infections loss previously acquired developmental skills compared to neurotypical...
Abstract Epilepsy is a common neurological disorder that sub-stantially deteriorates patients’ safety and quality of life. Electroencephalogram (EEG) has been the golden-standard technique for diagnosing this brain played an essential role in epilepsy monitoring disease management. It extremely laborious challenging, if not practical, physicians expert humans to annotate all recorded signals, particularly long-term monitoring. The annotation process often involves identifying signal segments...
Abstract Variants in the GABRB3 gene encoding β3-subunit of γ-aminobutyric acid type A ( receptor are associated with various developmental and epileptic encephalopathies. Typically, these variants cause a loss-of-function molecular phenotype whereby has reduced inhibitory effectiveness leading to seizures. Drugs that potentiate GABAergic activity, such as nitrazepam, phenobarbital or vigabatrin, expected compensate for this thereby reduce seizure frequency. However, drug inhibits...
Epileptic (previously infantile) spasms is the most common epileptic encephalopathy occurring during infancy and frequently associated with abnormal neurodevelopmental outcomes. have a diverse range of known (genetic, structural) unknown aetiologies. High dose corticosteroid treatment for 4 weeks often induces remission spasms, although mechanism action unclear. Animal models shown decreased brain kynurenic acid, which increased after ketogenic diet. We quantified kynurenine pathway...
Infection-triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES have recognisable MRI neuroimaging phenotypes, there otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes.
Aim To examine the cytokine/chemokine profile of cerebrospinal fluid ( CSF ) during acute herpes simplex virus‐induced N ‐methyl‐ d ‐aspartate receptor NMDAR autoimmunity and in chronic/relapsing post‐herpes virus encephalitis HSE neurological syndromes. Method We measured longitudinal serial cyto‐/chemokines n =34) a glial marker (calcium‐binding astroglial protein, S100B) one patient subsequent anti‐ encephalitis, compared results with those from two patients without preceding HSE. also...
Objective Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity best treatment options remains inadequate. We therefore aimed analyze electroclinical features functional effects variants establish genotype–phenotype correlations. Methods Genetic data 27 individuals (22 unrelated 2 families) harboring 20 different...
Perinatal tuberculosis is insufficiently understood and has been rarely reported even in areas endemic for the disease, unless a high index of suspicion maintained diagnosis can be missed. Differentiation congenital from early postnatally acquired only epidemiological importance. We hereby report one case three cases perinatal tuberculosis, problems faced during investigation management emphasize need improved screening women at risk sensitization medical community about this entity.
Epidemiological studies, animal models, and case–control studies indicate maternal immune activation may be an important factor involved in disease expression of autism spectrum disorder ( ASD ), Tourette syndrome, obsessive–compulsive OCD ). We report eight children (mean age 6y 6mo [range 4–15y]; six males two females) referred over a 2‐year period with at least one these neurodevelopmental disorders plus history thyroid autoimmunity. Seven presented abrupt onset neuropsychiatric symptoms...
Chudleigh, Catherine D Clin Psych, MSc; Kozlowska, Kasia MBBS, PhD, FRANZCP; Kothur, Kavitha MD Dch paediatrics; Davies, Fiona M Psych (Applied), PhD; Baxter, Holly B Ap Sci; Landini, Andrea MD; Hazell, Philip BMedSc, MBChB, Baslet, Gaston Author Information
Tuberous sclerosis complex (TSC) is an inherited genetic disorder commonly associated with neuropsychiatric complications like epilepsy, mental retardation, autism and other behavioral problems constitutes about 1-4% of the autistic population. Mental retardation seizures, particularly infantile spasms are significant risk factors for development autism. Patients TSC more likely to have temporal tubers than those cases without We describe clinical neuroimaging features two such tuberous
Aim To determine the role of inflammation in pediatric transient focal cerebral arteriopathy using cerebrospinal fluid cytokine/chemokines as biomarkers. Methods We measured 32 acute collected from children with stroke due to (n = 5) multiplex immunoassay and compared two patients arterial ischemic other causes (non-focal group, vertebral dissection, n 1; cryptogenic, 1), encephalitis 43), non-inflammatory neurological disease controls 20). Results Median age group was 9.3 years (range,...