Marian Todaro
A5091726969- Epilepsy research and treatment
- Genomics and Rare Diseases
- Pharmacological Effects and Toxicity Studies
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Genomic variations and chromosomal abnormalities
- Cardiac electrophysiology and arrhythmias
- Advanced Biosensing Techniques and Applications
- Muscle Physiology and Disorders
- CRISPR and Genetic Engineering
- HIV/AIDS drug development and treatment
- Glioma Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Fetal and Pediatric Neurological Disorders
- Antiplatelet Therapy and Cardiovascular Diseases
- Bone health and treatments
- Diet and metabolism studies
- Venous Thromboembolism Diagnosis and Management
- Drug-Induced Adverse Reactions
- Neuroscience and Neuropharmacology Research
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- RNA Research and Splicing
- Infectious Encephalopathies and Encephalitis
The University of Melbourne
2013-2024
Monash University
2019-2024
Alfred Health
2022-2024
The Royal Melbourne Hospital
2013-2024
Austin Hospital
2022
Monash Medical Centre
2022
Austin Health
2013-2022
Royal Hallamshire Hospital
2022
University of Sheffield
2022
Epilepsy Foundation
2014
To determine the frequency and nature of potentially epileptogenic lesions on MRI in adults with new-onset seizures.We prospectively studied a consecutive series 993 patients (597 males [61%]; mean [SD] age: 42.2 [18.8] years, range 14.3-94.3 years) who presented to an adult First Seizure Clinic over 10-year period. The scans, performed clinically 3- 1.5-tesla scanners, were reviewed for their diagnostic yield, abnormalities, association abnormal electrical activity EEG.MRI scans acquired...
Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure share genetic factors, we pooled CNV data from 10,590 individuals disorders, 16,109 clinically validated epilepsy, and 492,324 population controls identified 25 genome-wide significant loci, 22 of which novel such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications...
Abstract Cytogenic testing is routinely applied in most neurological centres for severe paediatric epilepsies. However, which characteristics of copy number variants (CNVs) confer epilepsy risk and subtypes carry the CNV burden, have not been explored on a genome-wide scale. Here, we present largest investigation to date with 10 712 European cases 6746 ancestry-matched controls. Patients genetic generalized epilepsy, lesional focal non-acquired developmental epileptic encephalopathy were...
Mosaic pathogenic variants restricted to the brain are increasingly recognized as a cause of focal epilepsies. We aimed identify mosaic variant and its anatomical gradient in DNA derived from trace tissue on explanted stereoelectroencephalography (SEEG) electrodes.We studied patient with nonlesional multifocal epilepsy undergoing presurgical evaluation SEEG. After explantation, electrodes were divided into 3 pools based their location (right posterior quadrant, left hippocampus/temporal...
Abstract Glioblastomas are highly aggressive and deadly brain tumours, with a median survival time of 14–18 months post-diagnosis. Current treatment modalities limited only modestly increase time. Effective therapeutic alternatives urgently needed. The purinergic P2X7 receptor (P2X7R) is activated within the glioblastoma microenvironment evidence suggests it contributes to tumour growth. Studies have implicated P2X7R involvement in range neoplasms, including glioblastomas, although roles...
Objective Familial mesial temporal lobe epilepsy (FMTLE) is an important focal syndrome; its molecular genetic basis unknown. Clinical descriptions of FMTLE vary between a mild syndrome with prominent déjà vu to more severe phenotype febrile seizures and hippocampal sclerosis. We aimed refine the by analyzing large cohort patients asked whether common risk variants for and/or seizures, measured polygenic scores (PRS), are enriched in individuals FMTLE. Methods studied 134 families ≥ 2 first...
Abstract Objective Research suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic (GFAP) levels increase in cerebrospinal fluid blood response neuroaxonal damage, they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL GFAP their diagnostic utility differentiating patients with epilepsy from those psychogenic nonepileptic (PNES) other disorders. Methods recruited consecutive adults...
Valproate (VPA) use during pregnancy is associated with a wide range of birth defects and adverse neurodevelopmental outcomes, but not all exposed children are affected there evidence for genetic predisposition. We hypothesised that genomic variants impact on the binding affinity transcription factors (TFs) integral to VPA-associated teratogenicity plausible explanation variance in interindividual risk. interrogated maternal exomes from women recruited through international epilepsy genomics...
We present the analysis of a prospective multicentre study to investigate genetic effects on prognosis newly treated epilepsy. Patients with new clinical diagnosis epilepsy requiring medication were recruited and followed up prospectively. The outcome was defined as freedom from seizures for minimum 12 months in accordance consensus statement International League Against Epilepsy (ILAE). Genetic remission after starting treatment analysed without adjustment significant prognostic factors,...
Summary We report a case of non‐fatal disseminated S cedosporium prolificans infection, including central nervous system disease and endophthalmitis, in relapsed acute myeloid leukaemia patient with extensive CYP 2C19 metabolism. Successful treatment required aggressive surgical debridement, three times daily voriconazole dosing cimetidine inhibition. In addition, the unique use miltefosine was employed due to azole‐chemotherapeutic drug interactions. Prolonged survival following . ,...
OBJECTIVE To determine whether patients who fail their first antiepileptic drug (AED) have better neuropsychiatric and quality-of-life (QOL) outcomes if substituted to levetiracetam monotherapy compared with a second older AED. DESIGN Randomized comparative trial. Participants partial epilepsy had failed phenytoin sodium, carbamazepine, or valproate sodium were randomized substitution different Assessments performed at baseline, 3 months, 12 months using questionnaires measuring...
Summary Objective Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, expression these channels osteoblasts raises question whether altered bone signaling increases fragility. We aimed confirm voltage‐gated sodium (Na V ) mouse osteoblasts, investigate action carbamazepine phenytoin on Na channels. Methods Immunocytochemistry was performed primary calvarial extracted from neonatal C57BL/6J mice...
Epilepsy is associated with an increased risk of cardiovascular disease and premature mortality, including sudden unexpected death in epilepsy (SUDEP). Serious cardiac arrythmias might go undetected routine investigations.This prospective cohort study aimed to detect arrhythmias patients chronic drug-resistant (≥5 years duration) using subcutaneous monitors for a minimum follow-up duration 12 months. Participants known or those abnormal 12-lead ECGs were excluded. The device was programmed...
<h3>BACKGROUND AND PURPOSE:</h3> Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk vascular complications. <i>CYP2C19</i> gene polymorphisms influence activity. We aimed study clinical impact in patients undergoing treatment. <h3>MATERIALS METHODS:</h3> This was a prospective, longitudinal, observational study. Information on demographics and status collected as baseline. Clopidogrel response tested by VerifyNow P2Y12 assay....
The mechanisms by which antiepileptic drugs (AEDs) cause birth defects (BDs) are unknown. Data suggest that AED-induced BDs may result from a genome-wide increase of de novo variants in the embryo, mechanism we investigated.Whole exome sequencing data child-parent trios were interrogated for single-nucleotide variants/indels (dnSNVs/indels) and copy number (dnCNVs). Generalized linear models applied to assess variant burdens children exposed prenatally AEDs (AED-exposed children) versus...
Analyses of few gene-sets in epilepsy showed a potential to unravel key disease associations. We set out investigate the burden ultra-rare variants (URVs) comprehensive range biologically informed presumed be implicated epileptogenesis. The 12 URV types 92 was compared between cases and controls using whole exome sequencing data from individuals European descent with developmental epileptic encephalopathies (DEE, n = 1,003), genetic generalized (GGE, 3,064), or non-acquired focal (NAFE,...
Targeted corrective gene conversion (TCGC) holds much promise as a future therapy for many hereditary diseases in humans. Mutation correction frequencies varying between 0.0001% and 40% have been reported using chimeraplasty, oligoplasty, triplex-forming oligonucleotides, small PCR amplicons (CPA). However, technologies used to detect events risk either falsely indicating or greatly exaggerating the presence of corrected loci. This is problem that considerably exacerbated by attempted...