ORCID Profile
0000-0002-8742-0125
Current Organisations
Royal Brisbane and Women's Hospital
,
University of Queensland
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-08-2014
Publisher: Cambridge University Press (CUP)
Date: 12-2008
Abstract: Adverse events during the perinatal period have traditionally been thought to contribute to the risk of febrile seizures although an association has not been found in large epidemiological studies. Disease-discordant twins provide a means to assess the role of non-shared environmental factors while matching for confounding factors and avoiding difficulties of epidemiological studies in singletons. This study aimed to examine the association of obstetric events and febrile seizures in a community-based twin study. Twenty-one twin pairs discordant for febrile seizures were ascertained from a community-based twin register. Obstetric events were scored using the McNeil-Sjöström Scale for Obstetric Complications and expressed as a summary score (OC score). The frequency of in idual obstetric events in affected and unaffected twins, the within-pair differences in OC scores and other markers of perinatal risk including birthweight, birth order and Apgar scores were examined. No significant difference was found in the frequency of in idual obstetric events, nor in OC scores between affected and unaffected twins. No differences in birth weight, birth order, 1- or 5-minute Apgar scores were observed. Our results confirm previous findings that obstetric events are not associated with the risk of febrile seizures.
Publisher: Oxford University Press (OUP)
Date: 12-12-2006
DOI: 10.1093/HMG/DDL456
Abstract: The expression level for 15,887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.JOCN.2005.03.026
Abstract: Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-04-2004
DOI: 10.1212/01.WNL.0000118201.89498.48
Abstract: Objective: To classify the Lennox twin pairs according to modern epilepsy classifications, use the classic twin model to identify which epilepsy syndromes have an inherited component, search for evidence of syndrome-specific genes, and compare concordances from Lennox’s series with a contemporary Australian series. Methods: Following review of Lennox’s original files describing twins with seizures from 1934 through 1958, the International League Against Epilepsy classifications of seizures and epileptic syndromes were applied to 169 pairs. Monozygous (MZ) and dizygous (DZ) pairs were sub ided into epilepsy syndromes and casewise concordances estimated. Results: The authors excluded 26 pairs, with 71 MZ and 72 DZ pairs remaining. Seizure analysis demonstrated strong parallels between contemporary seizure classification and Lennox’s terminology. Epilepsy syndrome diagnoses were made in 75%. The MZ and DZ casewise concordance estimates gave strong evidence for a major genetic influence in idiopathic generalized epilepsies (0.80 versus 0.00 n = 23). High MZ casewise concordances also supported a genetic etiology in symptomatic generalized epilepsies and febrile seizures. The pairs who were concordant for seizures usually had the same syndromic diagnoses in both twins (86% in MZ, 60% in DZ), suggesting syndrome-specific genes. Apart from partial epilepsies, the MZ casewise concordances were similar to those derived from Australian twin data. Conclusions: The authors were able to apply contemporary classifications to Lennox’s twins. The data confirm genetic bases for common generalized epilepsies as well as febrile seizures and provide further support for syndrome-specific genes. Finally, comparable results to our Australian series were obtained, verifying the value of twin studies.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Wiley
Date: 03-2006
DOI: 10.1111/J.1528-1167.2006.00466.X
Abstract: Benign rolandic epilepsy (BRE) is considered a genetically determined idiopathic partial epilepsy. We analyzed a large s le of twins from four international twin registers to probe the genetics of BRE. We also aim to synthesize the apparently conflicting family and twin data into a model of BRE etiology. Large population-based twin registries of epilepsies from Odense (Denmark), Richmond, Virginia (United States), and Oslo (Norway) were reviewed for BRE cases and added to our Australian twin data. Diagnosis of classic BRE was based on electroclinical criteria with normal neurologic development. Cases with a compatible electroclinical picture but abnormal neurologic development were termed non-classic BRE. Eighteen twin pairs were identified (10 monozygous eight dizygous) of whom at least one twin was diagnosed with classic BRE among a total s le of 1,952 twin pairs validated for seizures, and all were discordant for BRE. The estimated monozygous pairwise concordance for BRE in this s le was 0.0 [95% confidence interval (CI), 0.0-0.3). Four twin pairs (one monozygous, three dizygous) had non-classic BRE, and all co-twins had seizures. The twin data showing an absence of any concordant twin pairs with classic BRE suggest that noninherited factors are of major importance in BRE. Modelling the data shows that the familial occurrence of centrotemporal spikes makes only a minor contribution to the familial aggregation of BRE. Genetic factors are probably more important in non-classic BRE. The etiology and mode(s) of inheritance of BRE are much more complicated than initially conceptualized.
Publisher: MDPI AG
Date: 21-07-2022
DOI: 10.3390/JCM11144238
Abstract: Background. The genomic era has led to enormous progress in clinical care and a multi-disciplinary team (MDT) approach is imperative for integration of genomics into epilepsy patient care. Methods. The MDT approach involved patient selection, genomic testing choice, variant discussions and return of results. Genomics analysis included cytogenomic testing and whole exome sequencing (WES). Neurologist surveys were undertaken at baseline and after genomic testing to determine if genomic diagnoses would alter their management, and if there was a change in confidence in genomic testing and neurologist perceptions of the MDT approach. Results. The total diagnostic yield from all genomic testing was 17% (11/66), with four diagnoses from cytogenomic analyses. All chromosomal microarray (CMA) diagnoses were in patients seen by adult neurologists. Diagnostic yield for WES was 11% (7/62). The most common gene with pathogenic variants was DCX, reported in three patients, of which two were mosaic. The genomic diagnosis impacted management in 82% (9/11). There was increased confidence with integrating genomics into clinical care (Pearson chi square = 83, p = 0.004) and qualitative comments were highly supportive of the MDT approach. Conclusions. We demonstrated diagnostic yield from genomic testing, and the impact on management in a cohort with drug-resistant epilepsy. The MDT approach increased confidence in genomic testing and neurologists valued the input from this approach. The utility of CMA was demonstrated in epilepsy patients seen by adult neurologists as was the importance of considering mosaicism for previously undiagnosed patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-10-2006
Publisher: Wiley
Date: 17-10-2022
DOI: 10.1111/EPI.17408
Abstract: Existing gene panels were developed to understand the etiology of epilepsy, and further benefits will arise from an effective pharmacogenomics panel for personalizing therapy and achieving seizure control. Our study assessed the cost‐effectiveness of a pharmacogenomics panel for patients with drug‐resistant epilepsy, compared with usual care. A cost–utility analysis was employed using a discrete event simulation model. The microsimulation model aggregated the costs and benefits of genetically guided treatment versus usual care for 5000 simulated patients. The 10‐year model combined data from various sources including genomic databases on prevalence of variants, population‐level pharmaceutical claims on antiseizure medications, published long‐term therapy retention rates, patient‐level cost data, and systematic reviews. Incremental cost per quality‐adjusted life‐year (QALY) gained was computed. Deterministic and probabilistic sensitivity analyses were undertaken to address uncertainty in model parameters. The mean cost of the genetically guided treatment option was AU$98 199 compared with AU$95 386 for usual care. Corresponding mean QALYs were 4.67 compared with 4.28 for genetically guided and usual care strategies, respectively. The incremental cost per QALY gained was AU$7381. In probabilistic sensitivity analyses, the incremental cost per QALY gained was AU$6321 (95% uncertainty interval = AU$3604–AU$9621), with a 100% likelihood of being cost‐effective in the Australian health care system. The most influential drivers of the findings were the monthly health care costs associated with reduced seizures, costs when seizures continued, and the quality‐of‐life estimates under genetically guided and usual care strategies. This early economic evaluation of a pharmacogenomics panel to guide treatment for drug‐resistant epilepsy could potentially be cost‐effective in the Australian health care system. Clinical trial evidence is necessary to confirm these findings.
Publisher: Wiley
Date: 24-02-2005
DOI: 10.1002/ANA.20398
Publisher: Elsevier BV
Date: 03-2000
DOI: 10.1016/S0196-0644(00)70086-2
Abstract: A 27-year-old man inhaled helium from an unregulated pressurized cylinder and underwent cerebral arterial gas embolism (CAGE), leaving him blind and with radiologic evidence initially suggesting cortical infarction. There was complete recovery of vision and substantial regression of the radiologic changes after 4 hyperbaric oxygen treatments and a 54-hour lidocaine infusion, which began 6 hours after the accident. This is the second reported case of CAGE occurring by this mechanism and the first case of unequivocal CAGE in which lidocaine has been used as an adjunctive treatment with hyperbaric oxygen.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.SCR.2022.102673
Abstract: In this paper, we describe the generation and validation of human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) from 6 epilepsy patients using a non-integrative Sendai virus vector. These human cellular models will enable patient-specific drug screening to improve outcomes for in iduals with this disorder.
Publisher: Wiley
Date: 28-06-2004
DOI: 10.1002/ANA.20153
Abstract: Benign rolandic epilepsy (BRE) is considered to be a genetically determined idiopathic partial epilepsy. We studied twins with BRE and compared the concordance with a twin s le of idiopathic generalized epilepsy (IGE). All eight BRE pairs (six monozygous [MZ], two dizygous [DZ]) were discordant. MZ pairwise concordance was 0 (95% confidence interval [CI], 0-0.4) for BRE compared with 0.7 (95% CI, 0.5-0.9) for 26 IGE MZ pairs. Our data suggest that conventional genetic influences in BRE are considerably less than for IGE, and other mechanisms need to be explored.
Publisher: Elsevier BV
Date: 03-2000
Publisher: Future Medicine Ltd
Date: 03-2021
Abstract: Evaluating genes involved in the pharmacodynamics and pharmacokinetics of epilepsy drugs is critical to better understand pharmacoresistant epilepsy. We reviewed the pharmacogenetics literature on six antiseizure medicines (carbamazepine, per anel, lamotrigine, levetiracetam, sodium valproate and zonisamide) and compared the genes found with those present on epilepsy gene panels using a functional annotation pathway analysis. Little overlap was found between the two gene lists pharmacogenetic genes are mainly involved in detoxification processes, while epilepsy panel genes are involved in cell signaling and gene expression. Our work provides support for a specific pharmacoresistant epilepsy gene panel to assist antiseizure medicine selection, enabling personalized approaches to treatment. Future efforts will seek to include this panel in genomic analyses of pharmacoresistant patients, to determine clinical utility and patient treatment responses.
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.EPLEPSYRES.2013.02.011
Abstract: Febrile seizures (FS) are the most common seizure syndrome. A strong genetic component has been well established through family and twin studies however, such studies have not examined the genetics of different FS types (simple, complex, febrile status epilepticus) and sub-syndromes (true FS, febrile seizures plus (FS+), 'FS with later epilepsy'). Here we used a community-based twin s le to analyze genetic factors within different FS subtypes and FS syndromes. Twin pairs were ascertained from the twin database of the Epilepsy Research Centre. A retrospective chart review was conducted and follow-up attempted for all subjects. Casewise concordance values were calculated for the different subgroups and intra-pair variation was analyzed. One hundred and seventy-nine twin pairs with FS were identified. Overall casewise concordance for FS in monozygotic (MZ) twins (0.62) was greater than in dizygotic (DZ) twins (0.16, p<0.0001). A greater concordance amongst MZ pairs than DZ twin pairs was also observed for all FS subtypes and FS sub-syndromes, particularly in twins with FS+. Within concordant MZ pairs, we did not observe the co-occurrence of FS and FS+. These results suggest a strong genetic contribution to different FS subtypes and sub-syndromes. They also support the existence of distinct genetic factors for different FS subtypes and sub-syndromes, especially FS+. This information is important for the strategic planning of next generation sequencing studies of febrile seizures.
Publisher: Wiley
Date: 14-04-2014
DOI: 10.1002/ANA.24126
Abstract: We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 in idual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway.
Publisher: BMJ
Date: 10-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-03-2002
DOI: 10.1212/WNL.58.6.984
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S1388-2457(03)00111-1
Abstract: To characterize the electroencephalographic (EEG) findings in patients with Kufs disease, the adult autosomal recessive form of neuronal ceroid-lipofuscinosis. We reviewed the EEG findings in 5 patients with biopsy-proven Kufs disease from our institution and 14 case reports of Kufs disease in the literature. The criteria used for patient inclusion were clinical evidence of a progressive neurodegenerative disorder, biopsy-proven evidence of Kufs disease, and EEG recordings during the course of the illness. One patient had phenotype A with generalized atypical spike and slow wave complexes and marked photoparoxysmal responses, particularly at low flash frequencies. Three patients had phenotype B with generalized slowing. One patient in the miscellaneous category showed focal sharp and spike waves and quasi-periodic slow waves maximal over anterior regions of the head. Review of the literature identified 14 case reports that met the inclusion criteria. The inheritance, mechanism, and manifestations of Kufs disease are not well understood. EEG findings may guide clinicians toward a confirmatory pathological diagnosis and distinguish various phenotypes of this disorder. The EEG may assist in the diagnosis of Kufs disease.
Location: No location found
Location: Australia
Start Date: 2002
End Date: 2002
Funder: Janssen-Cilag Australia
View Funded ActivityStart Date: 2009
End Date: 2009
Funder: Pfizer Australia
View Funded ActivityStart Date: 2021
End Date: 2024
Funder: University of Queensland
View Funded ActivityStart Date: 2021
End Date: 2022
Funder: Brain Foundation
View Funded ActivityStart Date: 2012
End Date: 2012
Funder: Ramaciotti Foundations
View Funded ActivityStart Date: 2012
End Date: 2013
Funder: Sylvia and Charles Viertel Charitable Foundation
View Funded ActivityStart Date: 2012
End Date: 2012
Funder: RACP Foundation
View Funded Activity