A5034018676- Epilepsy research and treatment
- Neonatal and fetal brain pathology
- Genomics and Rare Diseases
- Neuroscience and Neuropharmacology Research
- Pharmacological Effects and Toxicity Studies
- Ion Transport and Channel Regulation
- Cerebrospinal fluid and hydrocephalus
- Bacterial Infections and Vaccines
- Genetics and Neurodevelopmental Disorders
- Infectious Encephalopathies and Encephalitis
- Acute Ischemic Stroke Management
- Advanced Neuroimaging Techniques and Applications
- Metabolism and Genetic Disorders
- Influenza Virus Research Studies
- Functional Brain Connectivity Studies
- Cerebrovascular and Carotid Artery Diseases
- PI3K/AKT/mTOR signaling in cancer
- Advanced MRI Techniques and Applications
- Tuberous Sclerosis Complex Research
- Polyomavirus and related diseases
- EEG and Brain-Computer Interfaces
- Renal Diseases and Glomerulopathies
- Mast cells and histamine
- Fetal and Pediatric Neurological Disorders
- Neonatal Respiratory Health Research
Royal Children's Hospital
2019-2024
Murdoch Children's Research Institute
2020-2024
The University of Melbourne
2020-2024
Florey Institute of Neuroscience and Mental Health
2020-2021
Starship Children's Health
2016-2020
Sydney Children's Hospital
2020
Sydney Children’s Hospitals Network
2018
UNSW Sydney
2018
Auckland District Health Board
2016
Abstract This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox–Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic can be an effective treatment but complete seizure control is rarely achieved. Outcomes may improved by stimulating areas beyond thalamus, including cortex, optimal targets are unknown. We aimed to identify cortical target synthesizing prior neuroimaging studies, use...
To determine the genetic basis of bottom-of-sulcus dysplasia (BOSD), which is a highly focal and epileptogenic cortical malformation in imaging, electrophysiologic, pathologic abnormalities are maximal at bottom sulcus, tapering to normal gyral crown.Targeted panel deep sequencing (>500×) was performed on paired blood brain-derived genomic DNA from 20 operated patients with drug-resistant epilepsy BOSD. Histopathology assessed using immunohistochemistry.Brain-specific pathogenic somatic...
Abstract Objective Patients with focal, lesional epilepsy present seizures at variable ages. Larger lesion size and overlap sensorimotor or default mode network (DMN) have been associated younger age seizure onset in cohorts mixed types of focal cortical dysplasia (FCD). Here, we studied determinants patients bottom‐of‐sulcus (BOSD), a discrete type FCD highly localized epileptogenicity. Methods Eighty‐four (77% operated) BOSD were studied. Demographic, histopathologic, genetic findings...
INTRODUCTION: Focal cortical dysplasias (FCD) are development malformations and one of the leading causes medically refractory epilepsy in children. The non-uniform distribution FCDs lacks a clear explanation. Recent evidence indicates variations gene expression morphology during prenatal brain may predispose certain areas to FCD. METHODS: We mapped cortex-wide FCD (type II imaging appearance) frequency 294 human children adults with focal recruited across 4 centers. locations were manually...
To determine whether 1-stage, limited corticectomy controls seizures in patients with MRI-positive, bottom-of-sulcus dysplasia (BOSD).We reviewed clinical, neuroimaging, electrocorticography (ECoG), operative, and histopathology findings consecutively operated drug-resistant focal epilepsy MRI-positive BOSD, all of whom underwent guided by MRI ECoG.Thirty-eight a median age at surgery 10.2 (interquartile range [IQR] 6.0-14.1) years were included. BOSDs involved eloquent cortex 15 patients....
Abstract Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics BOSD, with aims improving management understanding pathogenesis. studied 85 patients BOSD diagnosed between 2005–2022. Presenting seizure EEG characteristics, course, genetic findings treatment response were...
Introduction Infantile epileptic spasms syndrome (IESS) is a common developmental and encephalopathy with poor long-term outcomes. A substantial proportion of patients IESS have potentially surgically remediable etiology. Despite this, epilepsy surgery underutilized in this patient group. Some etiologies, such as focal cortical dysplasia malformation development oligodendroglial hyperplasia (MOGHE), are under-diagnosed infants young children. Even when etiology recognised, for example,...
Abstract Objective Favorable seizure outcome is reported following resection of bottom‐of‐sulcus dysplasia (BOSD). We assessed the distribution epileptogenicity and in around BOSD to better understand this clinical optimal surgical approach. Methods studied 27 children adolescents with magnetic resonance imaging (MRI)‐positive who underwent epilepsy surgery; 85% became seizure‐free postresection (median = 5.0 years follow‐up). All patients had dysplastic sulcus, 11 additional gyral crown...
Pertussis immunization programs aim to prevent severe infant disease. We investigated temporal trends in pertussis deaths and pediatric intensive care unit (PICU) admissions associations of changes disease detection vaccines used with death PICU admission rates.Using national data from New Zealand (NZ), we described 1991 2013, over which time coverage at 2 years age increased <80% 92%. In NZ, became a notifiable polymerase chain reaction (PCR) diagnosis available 1997 acellular replaced...
<h3>Objective:</h3> To describe a child meeting diagnostic criteria for tuberous sclerosis complex (TSC) carrying pathogenic somatic variant in <i>RHEB</i>, but no variants the two known TSC genes, <i>TSC1</i> or <i>TSC2</i>. <h3>Methods:</h3> We present clinical and imaging findings presenting with drug-resistant focal seizures multiple cortical tubers, subependymal giant cell astrocytoma nodules one cerebral hemisphere. Targeted panel sequencing exome were performed on genomic DNA derived...
Objective Prolonged continuous video-electroencephalography (cEEG) is recommended for neonates at risk of seizures. The cost and expertise required to provide a real-time response detected seizures often limits its utility. We hypothesised that the first hour cEEG could predict subsequent Design setting Retrospective multicentre diagnostic accuracy study. Patients 266 term seizure or with suspected Intervention was graded by expert novice interpreters as normal, mildly, moderately severely...
We report a child from Southern Australia (New South Wales) who presented during La Niña event with encephalopathy and acute flaccid paralysis. Magnetic resonance imaging suggested Japanese encephalitis (JE). Steroids intravenous immunoglobulin did not improve symptoms. Therapeutic plasma exchange (TPE) resulted in rapid improvement tracheostomy decannulation. Our case illustrates the complex pathophysiology of JE, its' geographic expansion into potential use TPE for neuroinflammatory sequelae.
Endovascular clot retrieval (ECR) is an emerging therapy for treatment of acute ischaemic stroke (AIS) in adults, including basilar artery occlusion (BAO). Its role children not well established. We report four consecutive with AIS due to BAO treated ECR Sydney, Australia. reviewed the literature characterize ‘natural course’ thrombolysis or ECR, and compared their outcome our patients reported ECR. Despite delays diagnosis, achieved recanalization children. Three had a good (Paediatric...
We describe a two-year-old boy with Dravet syndrome, severe genetic epilepsy, who developed generalized tonic-clonic seizure immediately following an intravenous bolus of lidocaine given for propofol pain amelioration during induction anesthesia emergency gastroscopy. Although has not specifically been reported as potentiating seizures in it is well-established that sodium channel blockers can worsen this population.
INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy associated with frequent seizures, cognitive impairment, and high burden of care. Electrical stimulation the thalamus can be an effective treatment for LGS, but complete seizure control rarely achieved. Outcomes may improved by stimulating areas beyond thalamus, including cortex, optimal targets are unknown. METHODS: Brain network maps from 3 group-level studies LGS were averaged to define area peak overlap:...
Abstract Pathogenic somatic MTOR variants in the cerebral cortex are a frequent cause of focal cortical dysplasia (FCD). We describe child with drug and surgery‐resistant epilepsy due to FCD type II who developed progressive enlargement T2 signal hyperintensity ipsilateral caudate lentiform nuclei. Histopathology nucleus biopsies showed dysmorphic neurons, similar those resected cortex. Genetic analysis frontal temporal identified pathogenic variant [NM_004958.4:c.4375G > C...
Abstract We report a child with history of temporal‐parietal‐occipital disconnection for epilepsy secondary to posterior quadrantic dysplasia who developed recurrent and prolonged bouts distress autonomic disturbance associated EEG PET evidence status epilepticus confined his disconnected cortex. These were refractory antiseizure medications but resolved following resection the In absence synaptic connections, we hypothesise that seizure‐related symptoms mediated either by neurochemical...
Pathogenic PRRT2 variants cause self-limited (familial) infantile epilepsy (SeLIE), which is responsive to sodium channel blocking antiseizure medications. The interictal EEG typically normal. We describe a cohort of infants with PRRT2-related SeLIE striking peri-ictal abnormalities.We included all diagnosed during July 2020 November 2021 at the Royal Children's Hospital, Melbourne. Clinical features and results aetiologic investigations were collected from electronic medical records. All...
An 8-week-old term infant with congenital nephrotic syndrome developed stiffening following general anesthetic. His neurologic examination and EEG were normal. MRI brain demonstrated a large mass of dysplastic isointense to cortex intervening "sulcal" spaces (figure). The continued have infrequent seizures.
We thank Dr. Hu and colleagues for their encouraging comments on our article.1 Both of groups advocate minimal, targeted resections bottom-of-sulcus dysplasia (BOSD),1,2 we further promote omitting intracranial EEG monitoring in MRI-positive cases. As noted references 41–45 article, laser interstitial thermal therapy (LITT) stereotactic thermocoagulation (STC) are reported BOSD to minimize surgical intervention appropriate medial, basal frontal, parietal BOSDs—occurrences which not as easily...
Acute ischaemic stroke (AIS) is an important cause of disability and death in children.It affects 1.2-8 children per 100,000 year, almost 70% survivors have significant ongoing disability, resulting reduced quality life, increased care requirements for families, cost[1].Reperfusion therapies, which include intravenous thrombolysis endovascular clot retrieval (ECR), are established as effective to improve long-term outcomes adults with acute stroke.Paediatric consensus guidelines allow...