Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Epilepsy: HELP
Articles by Mark James Cook
Based on 78 articles published since 2008

Between 2008 and 2019, M. Cook wrote the following 78 articles about Epilepsy.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Should older patients be denied temporal lobectomy on the basis of age? 2010

Murphy, Michael A / Cook, Mark J. · ·Expert Rev Neurother · Pubmed #21091307.

ABSTRACT: -- No abstract --

2 Review Advanced fabrication approaches to controlled delivery systems for epilepsy treatment. 2018

van Tienderen, Gilles Sebastiaan / Berthel, Marius / Yue, Zhilian / Cook, Mark / Liu, Xiao / Beirne, Stephen / Wallace, Gordon G. ·a ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility , University of Wollongong , Wollongong , Australia. · b Utrecht University , Utrecht , The Netherlands. · c Department for Functional Materials in Medicine and Dentistry , University Hospital Wuerzburg , Wurzburg , Germany. · d Medicine and Radiology , Clinical Neurosciences , Fitzroy , Australia. · e Department of Medicine , University of Melbourne , Fitzroy , Australia. ·Expert Opin Drug Deliv · Pubmed #30169981.

ABSTRACT: INTRODUCTION: Epilepsy is a chronic brain disease characterized by unprovoked seizures, which can have severe consequences including loss of awareness and death. Currently, 30% of epileptic patients do not receive adequate seizure alleviation from oral routes of medication. Over the last decade, local drug delivery to the focal area of the brain where the seizure originates has emerged as a potential alternative and may be achieved through the fabrication of drug-loaded polymeric implants for controlled on-site delivery. Areas covered: This review presents an overview of the latest advanced fabrication techniques for controlled drug delivery systems for refractory epilepsy treatment. Recent advances in the different techniques are highlighted and the limitations of the respective techniques are discussed. Expert opinion: Advances in biofabrication technologies are expected to enable a new paradigm of local drug delivery systems through offering high versatility in controlling drug release profiles, personalized customization and multi-drug incorporation. Tackling some of the current issues with advanced fabrication methods, including adhering to GMP-standards and industrial scale-up, together with innovative solutions for complex designs will see to the maturation of these techniques and result in increased clinical research into implant-based epilepsy treatment. ABBREVIATIONS: GMP: Good manufacturing process; DDS(s): Drug delivery system(s); 3D: Three-dimensional; AEDs: Anti-epileptic drugs; BBB: Blood brain barrier; PLA: Polylactic acid; PLGA: Poly(lactic-co-glycolic acid); PCL: poly(ɛ-caprolactone); ESE: Emulsification solvent evaporation; O/W: Oil-in-water; W/O/W: Water-in-oil-in-water; DZP: Diazepam; PHT: Phenytoin; PHBV: Poly(hydroxybutyrate-hydroxyvalerate); PEG: Polyethylene glycol; SWD: Spike-and-wave discharges; CAD: Computer aided design; FDM: Fused deposition modeling; ABS: Acrylonitrile butadiene styren; eEVA: Ethylene-vinyl acetate; GelMA: Gelatin methacrylate; PVA: Poly-vinyl alcohol; PDMS: Polydimethylsiloxane; SLA: Stereolithography; SLS: Selective laser sintering.

3 Review Clinical utility of EEG in diagnosing and monitoring epilepsy in adults. 2018

Tatum, W O / Rubboli, G / Kaplan, P W / Mirsatari, S M / Radhakrishnan, K / Gloss, D / Caboclo, L O / Drislane, F W / Koutroumanidis, M / Schomer, D L / Kasteleijn-Nolst Trenite, D / Cook, Mark / Beniczky, S. ·Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. Electronic address: tatum.william@mayo.edu. · Department of Neurology, Danish Epilepsy Center, Filadelphia, University of Copenhagen, Copenhagen, Diannalund, Denmark. · Johns-Hopkins University, Baltimore, MD, USA. · Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada. · Department of Neurology, Amrita Institute of Medical Sciences, Kochi, Kerala, India. · CAMC Department of Neurology, Charleston, WV, USA. · Department of Neurology, Hospital Israelita Albert Einstein, Saõ Paolo, Brazil. · Department of Neurology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA. · Department of Neurology, Guys and St Thomas' NHS Trust, King's College, London, United Kingdom. · Brain Center, University Medical Center, Utrecht, The Netherlands; Department of Pediatrics, Sapienza University, Rome, Italy. · Department of Neurology, University of Melbourne, Melbourne, Australia. · Department of Clinical Neurophysiology, Aarhus University Hospital, Denmark. ·Clin Neurophysiol · Pubmed #29483017.

ABSTRACT: Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.

4 Review Are the days of counting seizures numbered? 2018

Karoly, Philippa / Goldenholz, Daniel M / Cook, Mark. ·Department of Medicine, St Vincent's Hospital Melbourne. · Department of Biomedical Engineering, The University of Melbourne, Victoria, Australia. · Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. ·Curr Opin Neurol · Pubmed #29369115.

ABSTRACT: PURPOSE OF REVIEW: The estimation of seizure frequency is a cornerstone of clinical management of epilepsy and the evaluation of new therapies. Current estimation approaches are significantly limited by several factors. Comparing patient diaries and objective estimates (through both inpatient video-EEG monitoring of and long-term ambulatory EEG studies) reveal that patients document seizures inaccurately. So far, few practical alternative methods of estimation have been available. RECENT FINDINGS: We review the systems of counting currently utilized and their limitations, as well as the limitations imposed by problems defining clinical events. Alternative methodologies that permit the volatility of seizure rates to be accommodated, and possible alternative measures of brain excitability will be outlined. Recent developments in technologies around data capture, such as wearable and implantable devices, as well as significant advances in the ability to analyse the large data-sets supplied by these systems have provided a wealth of information. SUMMARY: There are now unprecedented opportunities to utilize and apply these insights in routine clinical management and assessment of therapies. The rapid adoption of long-term, wearable monitoring systems will permit major advances in our understanding of the natural history of epilepsy, and lead to more effective therapies and improved patient safety.

5 Review Deep brain stimulation for drug-resistant epilepsy. 2018

Li, Michael C H / Cook, Mark J. ·The Graeme Clark Institute, University of Melbourne, Parkville, Vic., Australia. ·Epilepsia · Pubmed #29218702.

ABSTRACT: OBJECTIVES: To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug-resistant epilepsy, its safety, and the factors influencing individual outcomes. METHODS: A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug-resistant epilepsy. Reference lists of these articles were used to source further articles. RESULTS: Stimulation of the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%-90% seizure reduction with ANT-DBS, and a 48%-95% seizure reduction with HC-DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three-fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders-experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox-Gastaut syndrome. SIGNIFICANCE: We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large-scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response.

6 Review Isolated amygdala enlargement in temporal lobe epilepsy: A systematic review. 2016

Beh, S M Jessica / Cook, Mark J / D'Souza, Wendyl J. ·The Department of Medicine, St. Vincent's Hospital Melbourne, St Vincent's PO Box 2900, Fitzroy, VIC 3065, Australia; The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: smjbeh@student.unimelb.edu.au. · The Department of Medicine, St. Vincent's Hospital Melbourne, St Vincent's PO Box 2900, Fitzroy, VIC 3065, Australia; The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: markcook@unimelb.edu.au. · The Department of Medicine, St. Vincent's Hospital Melbourne, St Vincent's PO Box 2900, Fitzroy, VIC 3065, Australia; The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: wendyl@unimelb.edu.au. ·Epilepsy Behav · Pubmed #27176882.

ABSTRACT: OBJECTIVE: The objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies. METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords 'amygdala enlargement', 'epilepsy', and 'seizures' in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included. RESULTS: Of 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small samples of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67-100% vs. 26-47%), and they have an excellent response to antiepileptic drugs (81.8%-100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls. CONCLUSIONS: Reliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests characteristics of an older age of epilepsy onset, a greater tendency to nonconvulsive seizures, and a good response to antiepileptic drugs in this interesting group of epilepsies.

7 Review An integrative review of the benefits of self-management interventions for adults with epilepsy. 2015

Edward, Karen-leigh / Cook, Mark / Giandinoto, Jo-Ann. ·Australian Catholic University, Faculty of Health Sciences, St Vincent's Private Hospital Melbourne, Nursing Research Unit, Locked Bag 4115, Fitzroy MDC 3065, Australia. Electronic address: karen-leigh.edward@acu.edu.au. · University of Melbourne Australia, St Vincent's Hospital Melbourne, PO Box 2900, Fitzroy 3065, Australia. Electronic address: markcook@unimelb.edu.au. · Australian Catholic University, Faculty of Health Sciences, St Vincent's Private Hospital Melbourne, Nursing Research Unit, Locked Bag 4115, Fitzroy MDC 3065, Australia. Electronic address: jo-ann.giandinoto@acu.edu.au. ·Epilepsy Behav · Pubmed #25843342.

ABSTRACT: The life-limiting effects of epilepsy are well documented in the literature, where the management of epilepsy and seizure control relies heavily on the self-management abilities of the individual. The psychosocial impact of epilepsy on the person and their family is profound and has been studied extensively. Interventions such as educational programs and lifestyle management education to improve self-mastery and quality of life in people with epilepsy are not necessarily integrated in standard care practices. The aim of this integrative review was to systematically identify and appraise research that reported findings related to self-management interventions for adults with epilepsy. A search of bibliographic databases was conducted, and a total of n=14 articles were included in this review. The main finding was that self-management education for adults with epilepsy shows promise to improving knowledge and self-confidence in managing one's own condition including the management of the psychosocial stressors, improvement in seizure control, and enhancement of quality of life. Self-management interventions were delivered in diverse formats, and the inclusion of this type of intervention should be part of the comprehensive care for people living with epilepsy.

8 Review Focal abnormalities in idiopathic generalized epilepsy: a critical review of the literature. 2014

Seneviratne, Udaya / Cook, Mark / D'Souza, Wendyl. ·Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia; Department of Neuroscience, Monash Medical Centre, Melbourne, Victoria, Australia. ·Epilepsia · Pubmed #24938654.

ABSTRACT: Conventionally, epilepsy is dichotomized into distinct "focal" and "generalized" categories. However, many studies have reported so-called focal features among patients with idiopathic generalized epilepsy (IGE) in the domains of semiology, electroencephalography, neuropsychology, neuropathology, and neuroimaging. We sought to review such features and clinical implications. A Web of Science database search was conducted to identify relevant publications. Our search yielded 145 papers describing focal features involving different domains in IGE, with 117 papers analyzed after excluding abstracts and case reports. Focal semiologic features are commonly seen in IGE. There are conflicting data from studies in the domains of electroencephalography, neuroimaging, and neuropathology. Studies on neuropsychology are suggestive of frontal lobe functional deficits in juvenile myoclonic epilepsy. Most advanced neuroimaging studies demonstrate the involvement of both the thalamus and the cortex during generalized spike-wave discharges (GSWDs). A few electroencephalographic and neuroimaging studies indicate that the cortex precedes the thalamus at the onset of GSWD. Focal features may contribute to misdiagnosis of IGE as focal epilepsy. However there are methodologic limitations in the studies that affect the results.

9 Review Subcortical epilepsy? 2013

Badawy, Radwa A B / Lai, Alan / Vogrin, Simon J / Cook, Mark J. ·Department of Clinical Neurosciences, St Vincent's Hospital, Sydney, Australia. badawyr@unimelb.edu.au ·Neurology · Pubmed #23671345.

ABSTRACT: In the past, the cortex has for the most part been considered to be the site of seizure origin in the different forms of epilepsy. Findings from histopathologic, electrophysiologic, and brain imaging studies now provide ample evidence demonstrating that like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. These studies show that different forms of generalized and focal epileptiform discharges and seizures engage various subcortical structures in varying ways. This interaction has been the subject of many reviews and is not the focus of the current work. The aim of this review is to examine the evidence suggesting the possibility for some of the subcortical structures to initiate seizures independently and the clinical implications of this.

10 Review The utility of ambulatory electroencephalography in routine clinical practice: a critical review. 2013

Seneviratne, Udaya / Mohamed, Armin / Cook, Mark / D'Souza, Wendyl. ·Department of Medicine, St. Vincent's Hospital, University of Melbourne, Victoria Parade, Fitzroy 3065, Australia. udaya.seneviratne@svhm.org.au ·Epilepsy Res · Pubmed #23490658.

ABSTRACT: Over the last four decades, ambulatory electroencephalography (EEG) has evolved to be a useful tool in the diagnosis of epilepsy and certain nonepileptic paroxysmal disorders. Most of the initial technological drawbacks of ambulatory EEG have been circumvented by incorporating digital and computer technology. It appears superior to routine EEG in capturing interictal abnormalities particularly in relation to natural sleep, circadian variations and the patient's typical daily lifestyle. The role of ambulatory EEG in studying seizures and nonepileptic paroxysmal events remains to be defined by targeted research. It perhaps is an underutilized tool and more research is needed to expand the horizon of ambulatory EEG applications in clinical practice.

11 Review The prognosis of idiopathic generalized epilepsy. 2012

Seneviratne, Udaya / Cook, Mark / D'Souza, Wendyl. ·Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Victoria Parade, Fitzroy, Victoria, Australia. udaya.seneviratne@svhm.org.au ·Epilepsia · Pubmed #23106474.

ABSTRACT: Prognosis describes the trajectory and long-term outcome of a condition. Most studies indicate a better prognosis in idiopathic generalized epilepsy (IGE) in comparison with other epilepsy syndromes. Studies looking at the long-term outcome of different IGE syndromes are relatively scant. Childhood absence epilepsy appears to have a higher rate of remission compared to juvenile absence epilepsy. In absence epilepsies, development of myoclonus and generalized tonic-clonic seizures predicts lower likelihood of remission. Although most patients with juvenile myoclonic epilepsy (JME) achieve remission on antiepileptic drug therapy, <20% appear to remain in remission without treatment. Data on the prognosis of other IGE syndromes are scarce. There are contradictory findings reported on the value of electroencephalography as a predictor of prognosis. Comparisons are made difficult by study heterogeneity, particularly in methodology and diagnostic criteria.

12 Review Epilepsy: Ever-changing states of cortical excitability. 2012

Badawy, R A B / Freestone, D R / Lai, A / Cook, M J. ·Department of Clinical Neurosciences, St Vincent's Hospital, Fitzroy, Australia. badawyr@unimelb.edu.au ·Neuroscience · Pubmed #22813999.

ABSTRACT: It has been proposed that the underlying epileptic process is mediated by changes in both excitatory and inhibitory circuits leading to the formation of hyper-excitable seizure networks. In this review we aim to shed light on the many physiological factors that modulate excitability within these networks. These factors have been discussed extensively in many reviews each as a separate entity and cannot be extensively covered in a single manuscript. Thus for the purpose of this work in which we aim to bring those factors together to explain how they interact with epilepsy, we only provide brief descriptions. We present reported evidence supporting the existence of the epileptic brain in several states; interictal, peri-ictal and ictal, each with distinct excitability features. We then provide an overview of how many physiological factors influence the excitatory/inhibitory balance within the interictal state, where the networks are presumed to be functioning normally. We conclude that these changes result in constantly changing states of cortical excitability in patients with epilepsy.

13 Review A mechanistic appraisal of cognitive dysfunction in epilepsy. 2012

Badawy, Radwa A B / Johnson, Katherine A / Cook, Mark J / Harvey, Anthony S. ·Department of Clinical Neurosciences, St. Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, Melbourne, Victoria, Australia; Electrical and Electronic Engineering, Melbourne, Victoria, Australia. badawyr@unimelb.edu.au, rdwbadawy@yahoo.com ·Neurosci Biobehav Rev · Pubmed #22617705.

ABSTRACT: A strong relationship between the clinical characteristics of epilepsy and the nature of cognitive impairments associated with the condition has been found, but the nature of this relationship appears to be quite complex and not well understood. This review presents a summary of the research on the interaction between cognition and epilepsy, surveyed from a mechanistic perspective with the aim of clarifying factors that contribute to the co-existence of both disorders. The physiological basis underpinning cognitive processing is first reviewed. The physiology of epilepsy is reviewed, with emphasis placed on interictal discharges and seizures. The nature of the impact of epilepsy on cognition is described, with transient and prolonged effects distinguished. Finally, the complexity of the co-morbidity between cognitive dysfunction and epilepsy is discussed in relation to childhood and adult-onset epilepsy syndromes and severe epileptic encephalopathies. Structural and functional abnormalities exist in patients with epilepsy that may underpin both the cognitive dysfunction and epilepsy, highlighting the complexity of the association. Research, possibly of a longitudinal nature, is needed to elucidate this multifactorial relationship between cognitive dysfunction and epilepsy.

14 Review Novel methods of antiepileptic drug delivery -- polymer-based implants. 2012

Halliday, Amy J / Moulton, Simon E / Wallace, Gordon G / Cook, Mark J. ·University of Melbourne, & Bionic Ear Institute, St Vincent's Hospital, 35 Victoria Pde, Fitzroy, Victoria 3065, Australia. ·Adv Drug Deliv Rev · Pubmed #22564384.

ABSTRACT: Epilepsy is a neurological disorder characterised by spontaneous seizures. Over one third of patients receive insufficient benefit from oral anti-epileptic drug (AED) therapy, and continue to experience seizures whilst on medication. Epilepsy researchers are consequently seeking new ways to deliver AEDs directly to the seizure focus in the brain in order to deliver higher, more effective doses to the seizure focus whilst bypassing the remainder of the brain and body to prevent side effects. The focus of this review will be polymer-based implants, which are polymeric devices loaded with AED that are designed for implantation at the seizure focus in order to achieve gradual, continuous release of AED direct into the region of the brain responsible for seizures. Polymer-based implants produced for epilepsy to date are based on a range of polymers, both biodegradable and non-biodegradable, and range from simple materials development studies through to investigations of implants in animal models of seizures and epilepsy, with varying degrees of success. This review describes the range of methods employed to manufacture polymer-based implants and compares their advantages and potential appeal to industry, and describes and compares the results and successes of polymer-based materials and devices produced to date for the treatment of epilepsy. We also discuss disadvantages and hurdles to be overcome in the field, and describe our predictions for advances to be made in the field in the coming decade.

15 Review The electroencephalogram of idiopathic generalized epilepsy. 2012

Seneviratne, Udaya / Cook, Mark / D'Souza, Wendyl. ·Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia. udaya.seneviratne@svhm.org.au ·Epilepsia · Pubmed #22150583.

ABSTRACT: Idiopathic generalized epilepsy (IGE) is classified into several subsyndromes based on clinical and electroencephalography (EEG) features. The EEG signature of IGE is bisynchronous, symmetric, and generalized spike-wave complex; although focal, irregular, and so called "fragments" of discharges are not uncommon. Other characteristic EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, and photoparoxysmal response. Both human and animal data suggest involvement of the thalamus and the cortex in the generation of spike-wave discharges in IGE. Circadian variations of generalized epileptiform discharges are well described, and these can be useful in diagnostic confirmation. Those discharges tend to occur more often after awakening and during cyclic alternating pattern phase-A of non-rapid eye movement sleep. Activation procedures such as hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are useful techniques to increase the yield of both interictal and ictal EEG abnormalities. Although not in routine use, specific triggers such as pattern stimulation and cognitive tasks may also be of value in eliciting rare reflex seizure-related EEG abnormalities. Variations of EEG abnormalities are evident between different electroclinical syndromes. EEG is also affected by certain external as well as internal factors, which should be borne in mind when interpreting EEG studies in IGE.

16 Review Global expression profiling in epileptogenesis: does it add to the confusion? 2010

Wang, Yi Yuen / Smith, Paul / Murphy, Michael / Cook, Mark. ·Centre for Clinical Neuroscience and Neurological Research, St Vincent's Hospital, Melbourne, Australia. YiYuen.Wang@svhm.org.au ·Brain Pathol · Pubmed #19243383.

ABSTRACT: Since the inception of global gene expression profiling platforms in the mid-1990s, there has been a significant increase in publications of differentially expressed genes in the process of epileptogenesis. In particular for mesial temporal lobe epilepsy, the presence of a latency period between the first manifestation of seizures to chronic epilepsy provides the opportunity for therapeutic interventions at the molecular biology level. Using global expression profiling techniques, approximately 2000 genes have been published demonstrating differential expression in mesial temporal epilepsy. The majority of these changes, however, are specific to laboratory or experimental conditions with only 53 genes demonstrating changes in more than two publications. To this end, we review the current status of gene expression profiling in epileptogenesis and suggest standard guidelines to be followed for greater accuracy and reproducibility of results.

17 Clinical Trial 18F-flumazenil: a γ-aminobutyric acid A-specific PET radiotracer for the localization of drug-resistant temporal lobe epilepsy. 2013

Vivash, Lucy / Gregoire, Marie-Claude / Lau, Eddie W / Ware, Robert E / Binns, David / Roselt, Peter / Bouilleret, Viviane / Myers, Damian E / Cook, Mark J / Hicks, Rodney J / O'Brien, Terence J. ·Departments of Medicine and Neurology, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria, Australia. ·J Nucl Med · Pubmed #23857513.

ABSTRACT: METHODS: Dynamic (18)F-FMZ PET and static interictal (18)F-FDG PET scans were compared in healthy controls (n = 17 for (18)F-FMZ and n = 20 for (18)F-FDG) and TLE patients with mesial temporal sclerosis on MR imaging (MTS, n = 12) and with normal MR imaging (NL TLE, n = 19). Masked visual assessment of images was undertaken. Parametric images of (18)F-FMZ binding potential (BPND) were generated using the simplified reference tissue model. Region-of-interest analysis on coregistered MR images and statistical parametric mapping were used to quantify (18)F-FMZ BPND and (18)F-FDG uptake in the temporal lobe. RESULTS: The visual assessment of static standardized uptake value images showed (18)F-FMZ PET to have high specificity (16/17 [94%]) and moderate sensitivity (21/31 [68%]) for the localization of the epileptogenic zone, with a more restricted abnormality than (18)F-FDG PET. However, the (18)F-FMZ standardized uptake value images were falsely localizing in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in ipsilateral hippocampal (18)F-FMZ BPND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippocampal (18)F-FMZ BPND was independent of both hippocampal volume and (18)F-FDG uptake, whereas ipsilateral hippocampal volume was correlated with (18)F-FDG uptake (r(2) = 0.69, P < 0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in 14 of 31 (45%) cases with (18)F-FMZ PET and 18 of 29 (62%) with (18)F-FDG PET. Cluster size was significantly smaller on (18)F-FMZ than (18)F-FDG images (37 vs. 160 voxels, P < 0.01). CONCLUSION: (18)F-FMZ PET has potential as a clinical tool for the localization of the epileptogenic zone in the presurgical evaluation of drug-resistant TLE, providing information complementary to (18)F-FDG PET, with a more restricted region of abnormality.

18 Clinical Trial Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study. 2013

Cook, Mark J / O'Brien, Terence J / Berkovic, Samuel F / Murphy, Michael / Morokoff, Andrew / Fabinyi, Gavin / D'Souza, Wendyl / Yerra, Raju / Archer, John / Litewka, Lucas / Hosking, Sean / Lightfoot, Paul / Ruedebusch, Vanessa / Sheffield, W Douglas / Snyder, David / Leyde, Kent / Himes, David. ·St Vincent's Hospital, Melbourne, Victoria, Australia. markcook@unimelb.edu.au ·Lancet Neurol · Pubmed #23642342.

ABSTRACT: BACKGROUND: Seizure prediction would be clinically useful in patients with epilepsy and could improve safety, increase independence, and allow acute treatment. We did a multicentre clinical feasibility study to assess the safety and efficacy of a long-term implanted seizure advisory system designed to predict seizure likelihood and quantify seizures in adults with drug-resistant focal seizures. METHODS: We enrolled patients at three centres in Melbourne, Australia, between March 24, 2010, and June 21, 2011. Eligible patients had between two and 12 disabling partial-onset seizures per month, a lateralised epileptogenic zone, and no history of psychogenic seizures. After devices were surgically implanted, patients entered a data collection phase, during which an algorithm for identification of periods of high, moderate, and low seizure likelihood was established. If the algorithm met performance criteria (ie, sensitivity of high-likelihood warnings greater than 65% and performance better than expected through chance prediction of randomly occurring events), patients then entered an advisory phase and received information about seizure likelihood. The primary endpoint was the number of device-related adverse events at 4 months after implantation. Our secondary endpoints were algorithm performance at the end of the data collection phase, clinical effectiveness (measures of anxiety, depression, seizure severity, and quality of life) 4 months after initiation of the advisory phase, and longer-term adverse events. This trial is registered with ClinicalTrials.gov, number NCT01043406. FINDINGS: We implanted 15 patients with the advisory system. 11 device-related adverse events were noted within four months of implantation, two of which were serious (device migration, seroma); an additional two serious adverse events occurred during the first year after implantation (device-related infection, device site reaction), but were resolved without further complication. The device met enabling criteria in 11 patients upon completion of the data collection phase, with high likelihood performance estimate sensitivities ranging from 65% to 100%. Three patients' algorithms did not meet performance criteria and one patient required device removal because of an adverse event before sufficient training data were acquired. We detected no significant changes in clinical effectiveness measures between baseline and 4 months after implantation. INTERPRETATION: This study showed that intracranial electroencephalographic monitoring is feasible in ambulatory patients with drug-resistant epilepsy. If these findings are replicated in larger, longer studies, accurate definition of preictal electrical activity might improve understanding of seizure generation and eventually lead to new management strategies. FUNDING: NeuroVista.

19 Article "Truths and roses have thorns about them" - Henry David Thoreau. 2018

Cook, Mark J. ·Department of Medicine and Engineering, University of Melbourne, Melbourne, VIC, Australia. ·Epilepsia · Pubmed #29873820.

ABSTRACT: -- No abstract --

20 Article Common data elements for epilepsy mobile health systems. 2018

Goldenholz, Daniel M / Moss, Robert / Jost, David A / Crone, Nathan E / Krauss, Gregory / Picard, Rosalind / Caborni, Chiara / Cavazos, Jose E / Hixson, John / Loddenkemper, Tobias / Salazar, Tracy Dixon / Lubbers, Laura / Harte-Hargrove, Lauren C / Whittemore, Vicky / Duun-Henriksen, Jonas / Dolan, Eric / Kasturia, Nitish / Oberemk, Mark / Cook, Mark J / Lehmkuhle, Mark / Sperling, Michael R / Shafer, Patricia O. ·Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, MA, USA. · Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. · SeizureTracker, Alexandria, VA, USA. · Digital Strategy, Epilepsy Foundation, Landover, MD, USA. · Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. · Empatica, Milan, Italy. · Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA. · Brain Sentinel, San Antonio, TX, USA. · Department of Neurology, University of Texas Health San Antonio, San Antonio, TX, USA. · Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. · Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, MA, USA. · LGS Foundation, San Diego, CA, USA. · Citizens United for Research in Epilepsy, Chicago, IL, USA. · Extramural Program Office, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, MD, USA. · UNEEG Medical, Lynge, Denmark. · Neutun Labs, BMOS, Toronto, Ontario, Canada. · Department of Neurology, University of Melbourne, Parkville, Victoria, Australia. · EpiTel, Salt Lake City, UT, USA. · Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA. ·Epilepsia · Pubmed #29604050.

ABSTRACT: OBJECTIVE: Common data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry-wide standards for mHealth epilepsy data. METHODS: Using a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems. RESULTS: A consensus statement is presented for epilepsy mHealth CDEs. SIGNIFICANCE: Although it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.

21 Article Bifurcation analysis of two coupled Jansen-Rit neural mass models. 2018

Ahmadizadeh, Saeed / Karoly, Philippa J / Nešić, Dragan / Grayden, David B / Cook, Mark J / Soudry, Daniel / Freestone, Dean R. ·Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, VIC, Australia. · Department of Biomedical Engineering, The University of Melbourne, Melbourne, VIC, Australia. · Department of Medicine, St. Vincent's Hospital Melbourne, The University of Melbourne, Melbourne, VIC, Australia. · Centre for Neural Engineering, The University of Melbourne, Melbourne, VIC, Australia. · Department of Statistics, Columbia University, New York, New York, 10027, United States of America. ·PLoS One · Pubmed #29584728.

ABSTRACT: We investigate how changes in network structure can lead to pathological oscillations similar to those observed in epileptic brain. Specifically, we conduct a bifurcation analysis of a network of two Jansen-Rit neural mass models, representing two cortical regions, to investigate different aspects of its behavior with respect to changes in the input and interconnection gains. The bifurcation diagrams, along with simulated EEG time series, exhibit diverse behaviors when varying the input, coupling strength, and network structure. We show that this simple network of neural mass models can generate various oscillatory activities, including delta wave activity, which has not been previously reported through analysis of a single Jansen-Rit neural mass model. Our analysis shows that spike-wave discharges can occur in a cortical region as a result of input changes in the other region, which may have important implications for epilepsy treatment. The bifurcation analysis is related to clinical data in two case studies.

22 Article Efficacy and tolerability of adjuvant lacosamide: The role of clinical characteristics and mechanisms of action of concomitant AEDs. 2018

Neal, Andrew / D'Souza, Wendyl / Hepworth, Graham / Lawn, Nicholas / Cook, Mark / Nikpour, Armin. ·Department of Medicine, The University of Melbourne, Australia; Department of Neurology, St Vincent's Hospital Melbourne, Australia. Electronic address: andrew.neal@unimelb.edu.au. · Department of Medicine, The University of Melbourne, Australia; Department of Neurology, St Vincent's Hospital Melbourne, Australia. · Statistical Consulting Centre, The University of Melbourne, Australia. · Western Australian Adult Epilepsy Service, Sir Charles Gairdner Hospital, Perth, Australia. · Department of Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia; Sydney Medical School, University of Sydney, Australia. ·Epilepsy Behav · Pubmed #29396359.

ABSTRACT: OBJECTIVE: The objective of this study was to analyze the effectiveness and long-term tolerability of adjuvant lacosamide (LCM) in a multicenter cohort. We aim to assess outcomes of LCM-containing antiepileptic drug (AED) combinations based upon 'mechanism of action' (MoA) and patient's clinical features. METHODS: Consecutive patients commenced on LCM, with focal epilepsy were identified from three Australian hospitals. The 12-month efficacy endpoints were greater than 50% reduction in seizure frequency (responders) and seizure freedom. Tolerability endpoints were cessation of LCM for any reason, cessation due to side-effects and censoring due to inefficacy. Outcomes were assessed according to concomitant AEDs according to their MoA and the clinical risk factor profile. RESULTS: Three hundred ten patients were analyzed and followed for median 17.3months. Two hundred ninety-nine (97%) had drug-resistant epilepsy, and 155 (50%) had tried more than 7 AEDs at LCM commencement. Adjuvant LCM was associated with responder and seizure freedom rate of 29% and 9% respectively at 12months. Lower baseline seizure frequency, a prior 6-month period of seizure freedom at any time since epilepsy diagnosis and being on fewer concomitant AEDs were predictive of 12-month seizure freedom. Previous focal to bilateral tonic-clonic seizures (FBTCS), lower baseline seizure frequency, and concomitant AED reduction after LCM commencement were associated with improved LCM tolerability. No specific MoA AED combinations offered any efficacy or tolerability advantage. SIGNIFICANCE: Adjuvant LCM is associated with seizure freedom rates of 9% at 12months after commencement and is predicted by lower prior seizure frequency, a period of 6months or longer of seizure freedom since diagnosis and fewer concomitant AEDs. While the broad MoA of concomitant AEDs did not influence efficacy or tolerability outcomes, we have provided a framework that may be utilized in future studies to help identify optimal synergistic AED combinations.

23 Article Epileptic Seizure Prediction Using Big Data and Deep Learning: Toward a Mobile System. 2018

Kiral-Kornek, Isabell / Roy, Subhrajit / Nurse, Ewan / Mashford, Benjamin / Karoly, Philippa / Carroll, Thomas / Payne, Daniel / Saha, Susmita / Baldassano, Steven / O'Brien, Terence / Grayden, David / Cook, Mark / Freestone, Dean / Harrer, Stefan. ·IBM Research - Australia, 204 Lygon Street, 3053 Carlton, VIC, Australia. · IBM Research - Australia, 204 Lygon Street, 3053 Carlton, VIC, Australia; The University of Melbourne, 3010 Parkville, VIC, Australia. · The University of Melbourne, 3010 Parkville, VIC, Australia. · Department of Biomedical Engineering, The University of Melbourne, 3010 Parkville, VIC, Australia. · The University of Melbourne, 3010 Parkville, VIC, Australia. Electronic address: deanrf@unimelb.edu.au. · IBM Research - Australia, 204 Lygon Street, 3053 Carlton, VIC, Australia. Electronic address: sharrer@au.ibm.com. ·EBioMedicine · Pubmed #29262989.

ABSTRACT: BACKGROUND: Seizure prediction can increase independence and allow preventative treatment for patients with epilepsy. We present a proof-of-concept for a seizure prediction system that is accurate, fully automated, patient-specific, and tunable to an individual's needs. METHODS: Intracranial electroencephalography (iEEG) data of ten patients obtained from a seizure advisory system were analyzed as part of a pseudoprospective seizure prediction study. First, a deep learning classifier was trained to distinguish between preictal and interictal signals. Second, classifier performance was tested on held-out iEEG data from all patients and benchmarked against the performance of a random predictor. Third, the prediction system was tuned so sensitivity or time in warning could be prioritized by the patient. Finally, a demonstration of the feasibility of deployment of the prediction system onto an ultra-low power neuromorphic chip for autonomous operation on a wearable device is provided. RESULTS: The prediction system achieved mean sensitivity of 69% and mean time in warning of 27%, significantly surpassing an equivalent random predictor for all patients by 42%. CONCLUSION: This study demonstrates that deep learning in combination with neuromorphic hardware can provide the basis for a wearable, real-time, always-on, patient-specific seizure warning system with low power consumption and reliable long-term performance.

24 Article A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy. 2017

Goldenholz, Daniel M / Strashny, Alex / Cook, Mark / Moss, Robert / Theodore, William H. ·National Institutes of Health, NINDS, United States; Beth Israel Deaconess Medical Center, Department of Neurology, United States. Electronic address: daniel.goldenholz@bidmc.harvard.edu. · Centers for Disease Control, United States. Electronic address: kpr9@cdc.gov. · University of Melbourne, Department of Neurology, Australia. Electronic address: markcook@unimelb.edu.au. · SeizureTracker.com, United States. Electronic address: rob@seizuretracker.com. · National Institutes of Health, NINDS, United States. Electronic address: theodorw@ninds.nih.gov. ·Seizure · Pubmed #29102709.

ABSTRACT: PURPOSE: Clinical epilepsy drug trials have been measuring increasingly high placebo response rates, up to 40%. This study was designed to examine the relationship between the natural variability in epilepsy, and the placebo response seen in trials. We tested the hypothesis that 'reversing' trial direction, with the baseline period as the treatment observation phase, would reveal effects of natural variability. METHOD: Clinical trial simulations were run with time running forward and in reverse. Data sources were: SeizureTracker.com (patient reported diaries), a randomized sham-controlled TMS trial, and chronically implanted intracranial EEG electrodes. Outcomes were 50%-responder rates (RR50) and median percentage change (MPC). RESULTS: The RR50 results showed evidence that temporal reversal does not prevent large responder rates across datasets. The MPC results negative in the TMS dataset, and positive in the other two. CONCLUSIONS: Typical RR50s of clinical trials can be reproduced using the natural variability of epilepsy as a substrate across multiple datasets. Therefore, the placebo response in epilepsy clinical trials may be attributable almost entirely to this variability, rather than the "placebo effect".

25 Article The circadian profile of epilepsy improves seizure forecasting. 2017

Karoly, Philippa J / Ung, Hoameng / Grayden, David B / Kuhlmann, Levin / Leyde, Kent / Cook, Mark J / Freestone, Dean R. ·Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Fitzroy VIC 3065, Australia. · Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. · NeuroEngineering Research Laboratory, Department of Biomedical Engineering, The University of Melbourne, Parkville VIC 3010, Australia. · Brain Dynamics Lab, Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorne VIC 3122, Australia. · Cascade Neuroscience, Seattle, WA 98109, USA. · Graeme Clark Institute for Biomedical Engineering, The University of Melbourne. ·Brain · Pubmed #28899023.

ABSTRACT: It is now established that epilepsy is characterized by periodic dynamics that increase seizure likelihood at certain times of day, and which are highly patient-specific. However, these dynamics are not typically incorporated into seizure prediction algorithms due to the difficulty of estimating patient-specific rhythms from relatively short-term or unreliable data sources. This work outlines a novel framework to develop and assess seizure forecasts, and demonstrates that the predictive power of forecasting models is improved by circadian information. The analyses used long-term, continuous electrocorticography from nine subjects, recorded for an average of 320 days each. We used a large amount of out-of-sample data (a total of 900 days for algorithm training, and 2879 days for testing), enabling the most extensive post hoc investigation into seizure forecasting. We compared the results of an electrocorticography-based logistic regression model, a circadian probability, and a combined electrocorticography and circadian model. For all subjects, clinically relevant seizure prediction results were significant, and the addition of circadian information (combined model) maximized performance across a range of outcome measures. These results represent a proof-of-concept for implementing a circadian forecasting framework, and provide insight into new approaches for improving seizure prediction algorithms. The circadian framework adds very little computational complexity to existing prediction algorithms, and can be implemented using current-generation implant devices, or even non-invasively via surface electrodes using a wearable application. The ability to improve seizure prediction algorithms through straightforward, patient-specific modifications provides promise for increased quality of life and improved safety for patients with epilepsy.