- Epilepsy, Genetics, EEG, Biomarkers, High-frequency oscillations, Cardiorespiratory function, Epilepsy comorbidities, Antiepileptic drugs, Epilepsy surgery, Precision Medicine.
2019 Perucca group. L-R: Dr Shobi Sivathamboo, A/Prof Piero Perucca, Ms Jessica Hutton
To understand biological factors contributing to epilepsy, its comorbidities and its outcomes.
Epilepsy is one of the most common neurological illness across the lifespan, and is characterised by an enduring predisposition to generate epileptic seizures. The causes and mechanisms implicated in such ‘enduring predisposition to generate epileptic seizures’ are incompletely understood.
Epilepsy is a serious disorder. In addition to experiencing the unpredictability of seizures, people with epilepsy face increased risks of adverse health outcomes, including social and employment restrictions, psychiatric and neuropsychological comorbidities, antiseizure drug toxicity, injuries, and in some cases the possibility of sudden unexpected death in epilepsy (SUDEP). It is also noteworthy that, despite the introduction of several new antiseizure drugs in the past 25 years, the treatment outcomes in epilepsy have not changed substantially, with approximately two-thirds of patients continuing to have seizures on appropriate antiseizure drug therapy.
Our group applies clinical, electrophysiological and molecular approaches to understand the biological factors contributing of epilepsy, its comorbidities and its outcomes. Defining these factors can ultimately lead to identify improved precision-based epilepsy therapies.
Project title: The genetics of focal epilepsies
Project description: Focal epilepsies are the most common forms of epilepsy, and have traditionally been regarded as disorders related to an 'acquired' brain insult, such as head injury, stroke or tumour. In reality, most cases of focal epilepsy have no identifiable cause. This project aims to assess the extent to which genetic factors account for focal epilepsies of unknown cause, by applying both clinical and genetic testing approaches. This project will allow the prospective student to acquire knowledge on epilepsy and epilepsy genetics, working within a successful collaborative framework which has been at the forefront of advances in epilepsy genetics and treatment at the international level.
Project title: Cardiorespiratory and autonomic changes in epilepsy
Project description: Cardiorespiratory and autonomic changes can occur in people with epilepsy, and their causes are multifactorial. Cardiorespiratory and autonomic changes following a generalised or bilateral tonic-clonic seizure have received much attention, as they can ultimately result in sudden unexpected death in epilepsy (SUDEP). However, the multifaceted aspects of ictal, peri-ictal and interictal cardiorespiratory and autonomic manifestations are not fully understood. This project aims at addressing this knowledge gap by utilising different approaches in the inpatient and outpatient settings. The findings of this project will enhance our understanding of cardiorespiratory and autonomic function in epilepsy, and may shed light into mechanisms underpinning premature mortality in epilepsy, including SUDEP.
Current project funding
2020: Royal Melbourne Hospital Victor Hurley Medical Research Grant in Aid, Melbourne Health, Australia (PI)
2019-2021: Establishment Grant, Central Clinical School, Monash University, Australia (PI)
2019-2022: Early Career Fellowship, National Health and Medical Research Council (NHMRC; 1163708), Australia (PI).
2019: Viertel Clinical Investigator Award, Sylvia and Charles Viertel Charitable Foundation, Australia (PI).
2019: Research Grant, Victorian Medical Research Acceleration Fund, Australia (CI).
For full list of publications, visit Pubmed, search 'Perucca P'. See feed below for Monash University verified publications and projects.
- Leung WL, Casillas-Espinosa P, Sharma P, Perucca P, Powell K, O’Brien TJ, Semple BD. An animal model of genetic predisposition to develop acquired epileptogenesis: The FAST and SLOW rats. Epilepsia 2019. doi: 10.1111/epi.16329.
- Ferrari-Marinho T, Perucca P, Amiri M, Dubeau F, Gotman J, Caboclo LO. High-frequency oscillations in the scalp EEG of ICU patients with altered level of consciousness. J Clin Neurophysiol 2019. doi: 10.1097/WNP.0000000000000624.
- Pedersen M, Kowalczyk M, Omidvarnia A, Perucca P, Gooley S, Petrou S, Scheffer IE, Berkovic SF, Jackson GD. Human GABRG2 generalized epilepsy: increased somatosensory and striato-thalamic connectivity. Neurol Genet 2019;5:e340.
- Perucca P, Perucca E. Identifying mutations in epilepsy genes: Impact on treatment selection. Epilepsy Res 2019;152:18-30.
- Sivathamboo S, Farrand S, Chen Z, White EJ, Pattichis A, Hollis C, Carino J, Roberts CJ, Minogue T, Jones NC, Yerra R, French C, Perucca P, Kwan P, Velakoulis D, O'Brien TJ, Goldin J. Sleep-disordered breathing among patients admitted for inpatient video-EEG monitoring. Neurology 2019;92:e194-e204.
- Perucca P, Smith G, Santana-Gomez C, Bragin A, Staba R. Electrophysiological biomarkers of epileptogenicity after traumatic brain injury. Neurobiol Dis 2019;123:69-74.
- Perucca P. Genetics of focal epilepsies: what do we know and where are we heading? Epilepsy Curr 2018;18:356-362.
Myers KA, Sivathamboo S, Perucca P. Heart rate variability measurement in epilepsy: How can we move from research to clinical practice? Epilepsia 2018;59:2169-2178.
- Sun Y, Seneviratne U, Perucca P, Chen Z, Tan MK, O'Brien TJ, D’Souza W, Kwan P. Generalized polyspike train: an EEG biomarker of drug-resistant idiopathic generalized epilepsy. Neurology 2018;91:e1822-e1830.
- Jacobs J, Wu J, Perucca P, Zelmann R, Mader M, Dubeau F, Mathern GW, Schulze-Bonhage A, Gotman J. Removing high frequency oscillations: A prospective multicenter study on seizure outcome. Neurology 2018;91:e1040-e1052.
- Sen A, Dugan P, Perucca P, Costello D, Choi H, Bazil C, Radtke R, Andrade D, Depondt C, Heavin S, Adcock J, Pickrell WO, McGinty R, Nascimento F, Smith P, Rees MI, Kwan P, O’Brien TJ, Goldstein D, Delanty N. The phenotype of bilateral hippocampal sclerosis and its management in ‘real life’ clinical settings. Epilepsia 2018;59:1410-1420.
- Devinsky O, Vezzani A, O'Brien TJ, Jette N, Scheffer IE, de Curtis M, Perucca P. Epilepsy. Nat Rev Dis Primers 2018;4:18024.
- Perucca P, Scheffer IE, Kiley M. The management of epilepsy in children and adults. Med J Aust 2018;208:226-233.
- Sivathamboo S, Perucca P, Velakoulis D, Jones NC, Goldin J, Kwan P, O’Brien TJ. Sleep disordered breathing in epilepsy: epidemiology, mechanisms and treatment. Sleep 2018;41.
- Perucca P, Crompton DE, Bellows ST, McIntosh AM, Kalincik T, Newton MR, Vajda FJE, Scheffer IE, Kwan P, O’Brien TJ, Tan KM, Berkovic SF. Familial mesial temporal lobe epilepsy and the borderland of déjà vu. Ann Neurol 2017;82:166-176.
- Perucca P, Scheffer IE, Harvey AS, James PA, Lunke S, Thorne N, Gaff C, Regan BM, Damiano JA, Hildebrand MS, Berkovic SF, O'Brien TJ, Kwan P. Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy. Epilepsy Res 2017;131:1-8.