epilepsy research reports

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Epilepsy articles within Nature Reviews Neurology

Review Article | 17 May 2024

IDH inhibition in gliomas: from preclinical models to clinical trials

Gliomas are the most common malignant primary brain tumours in adults, and they frequently contain mutations in the isocitrate dehydrogenase 1 ( IDH1 ) or IDH2 gene. Small-molecule inhibitors of mutant IDH are emerging as a new therapeutic strategy for IDH -mutant cancers, and this Review charts their pathway of development for IDH -mutant gliomas.

• Roberta Rudà
• , Craig Horbinski
•  &  Riccardo Soffietti

Review Article | 08 May 2024

Artificial intelligence in epilepsy — applications and pathways to the clinic

Integration of artificial intelligence into epilepsy management could revolutionize diagnosis and treatment. In this Review, the authors provide an overview of artificial intelligence applications that have been developed in epilepsy and discuss challenges that must be addressed to successfully integrate artificial intelligence into clinical practice.

• Alfredo Lucas
• , Andrew Revell
•  &  Kathryn A. Davis

Review Article | 03 April 2024

Insights into epileptogenesis from post-traumatic epilepsy

Post-traumatic epilepsy is a major driver of disability associated with traumatic brain injury. This article reviews the epidemiology and clinical features of post-traumatic epilepsy and discusses how an understanding of the underlying epileptogenic mechanisms might inform the development of anti-epileptogenic medications.

• Matthew Pease
• , Kunal Gupta
•  &  James F. Castellano

In Brief | 05 March 2024

Metabolic changes in status epilepticus

Status epilepticus is associated with changes in metabolic pathways, a new study has shown.

In Brief | 07 February 2024

Neurosteroids alleviate seizures in rats

Review Article | 24 November 2023

Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes

Clinical boundaries between neurology and psychiatry hamper understanding of disorders with phenotypes that span these disciplines. In this Review, Peall et al. discuss rare genetic brain disorders with neurological and psychiatric phenotypes, and consider common underlying mechanisms that could be therapeutic targets.

• Kathryn J. Peall
• , Michael J. Owen
•  &  Jeremy Hall

In Brief | 09 October 2023

Seizure-associated changes in the Golgi apparatus

• Heather Wood

News & Views | 30 May 2023

Cardiovascular risk factors for epilepsy and dementia

A new study using the UK Biobank database has shown that people with epilepsy are at an increased risk of developing dementia. The results demonstrate that this risk is multiplied in individuals who also have high cardiovascular risk, highlighting the importance of addressing modifiable cardiovascular risk factors.

• Michele Romoli
•  &  Cinzia Costa

In Brief | 05 May 2023

New blood biomarker of refractory epilepsy

• Sarah Lemprière

Research Highlight | 10 March 2023

Blood–brain barrier disruption following seizures

New research reports changes in serum blood–brain barrier (BBB) markers after bilateral tonic–clonic seizures, corroborating earlier observations in animal models.

In Brief | 03 March 2023

MRI-based deep learning for TLE diagnosis

News & Views | 15 December 2022

From precision diagnosis to precision treatment in epilepsy

Technological advances over the past decade have made precision genetic diagnosis available to many patients. The findings of a new study demonstrate that genetic diagnosis in epilepsy can lead to changes in clinical management that manifest as positive outcomes for the patient. The results herald a new era in which precision diagnosis will lead to precision medicine.

• Katrine M. Johannesen

News & Views | 12 December 2022

‘On-demand’ gene therapy for epilepsy

Gene therapies show promise for treating epilepsy, but most strategies target cells across an entire brain region rather than selecting pathologically hyperexcited neurons. Researchers have now developed a conditional gene therapy strategy that downregulates firing activity only in neurons that are pathologically overactive and switches off when brain circuit activity has returned to baseline.

• Pasquale Striano
•  &  Fabio Benfenati

Research Highlight | 22 November 2022

Targeting connexin hemichannels to treat temporal lobe epilepsy

Review Article | 14 November 2022

Adaptive and maladaptive myelination in health and disease

In this Review, the authors provide an overview of evidence that activity-regulated myelination is required for brain adaptation and learning, and discuss how dysregulation of activity-dependent myelination contributes to neurological disease and could be a new therapeutic target.

• Juliet K. Knowles
• , Ankita Batra
•  &  Michelle Monje

Review Article | 24 October 2022

Astrocytes in the initiation and progression of epilepsy

In this Review, Vezzani et al. discuss how dysregulation of key astrocyte functions — gliotransmission, cell metabolism and immune function — contribute to the development and progression of hyperexcitability in epilepsy and consider strategies to mitigate astrocyte dysfunction.

• Annamaria Vezzani
• , Teresa Ravizza
•  &  Detlev Boison

In Brief | 07 September 2022

Seizures induce NLRP3 inflammasome signalling

Review Article | 20 July 2022

Epigenetic genes and epilepsy — emerging mechanisms and clinical applications

This Review considers how variants in genes encoding proteins that regulate epigenetic mechanisms might contribute to epilepsy. The discussion is structured around five categories of epigenetic mechanisms: DNA methylation, histone modifications, histone–DNA crosstalk, non-coding RNAs and chromatin remodelling.

• Karen M. J. Van Loo
• , Gemma L. Carvill
•  &  David C. Henshall

Comment | 23 June 2022

The importance of getting evidence into practice

Neurological diseases cause a massive burden, which will increase as populations age. Rapid advances in our understanding of disease mechanisms must be translated into human benefits. We cannot stop once technologies have been developed, but must ensure that evidence and pipelines are in place for their implementation to reduce burden and inequalities.

• Anthony G. Marson

Perspective | 10 May 2022

Why won’t it stop? The dynamics of benzodiazepine resistance in status epilepticus

Many episodes of status epilepticus do not respond to first-line treatment with benzodiazepines. In this Perspective, Richard Burman and colleagues discuss seizure-induced alterations to the sensitivity of the GABA receptor to benzodiazepines, presenting these changes as a possible mechanism of treatment resistance.

• Richard J. Burman
• , Richard E. Rosch
•  &  Joseph V. Raimondo

Review Article | 31 March 2022

The metabolic basis of epilepsy

In this Review, the authors highlight the growing recognition that disruptions in cellular metabolism can be both a cause and a consequence of epileptic seizures and discuss how this emerging science might be exploited to develop innovative therapeutic strategies.

• Jong M. Rho

In Brief | 20 December 2021

High rate of epilepsy in young individuals who died with COVID-19

• Sarah Lempriere

Research Highlight | 09 December 2021

Safety and efficacy of COVID-19 vaccines in people with neurological disorders

Review Article | 26 November 2021

Genetic generalized epilepsies in adults — challenging assumptions and dogmas

In this Review, the authors consider how current understanding of four genetic generalized epilepsy syndromes that commonly occur in adults challenges traditional concepts about these conditions and suggests that they are not distinct but sit on a neurobiological continuum.

• Bernd J. Vorderwülbecke
• , Britta Wandschneider
•  &  Martin Holtkamp

Review Article | 29 October 2021

Autonomic manifestations of epilepsy: emerging pathways to sudden death?

The close connection between epileptic networks and the autonomic nervous system is illustrated by a range of autonomic manifestations during a seizure. This article reviews the spectrum and diagnostic value of these manifestations, focusing on presentations that could contribute to sudden unexpected death in epilepsy.

• Roland D. Thijs
• , Philippe Ryvlin
•  &  Rainer Surges

Review Article | 22 September 2021

Neurobehavioural comorbidities of epilepsy: towards a network-based precision taxonomy

This Review offers a novel theoretical perspective on the neurobehavioural comorbidities of adult and childhood epilepsy, involving new analytical approaches, derivation of new taxonomies and consideration of the diverse forces that influence cognition and behaviour in individuals with epilepsy.

• Bruce P. Hermann
• , Aaron F. Struck
•  &  Carrie R. McDonald

Research Highlight | 02 September 2021

Cortical thinning in epilepsy is linked to microglial activation

Comment | 19 August 2021

Treating epilepsy in forcibly displaced persons: timely, necessary, affordable

The burden of epilepsy among forcibly displaced persons is thought to be high, and access to treatment is limited. In June 2021, the WHO Secretariat published a draft intersectoral action plan aimed at redressing the global epilepsy treatment gap, providing a valuable opportunity to improve epilepsy treatment for forcibly displaced persons.

• Farrah J. Mateen

Review Article | 26 July 2021

Headache in people with epilepsy

Headaches and epilepsy frequently co-exist in the same individual, but the pathophysiological mechanisms underlying this relationship are not yet clear. Here, the authors discuss the epidemiological and pathophysiological links between epilepsy and headache, and apply this knowledge to the clinical management of the two disorders.

• Prisca R. Bauer
• , Else A. Tolner
•  &  Josemir W. Sander

Review Article | 11 June 2021

Amyloid-β: a potential link between epilepsy and cognitive decline

People with epilepsy have an elevated risk of dementia, and seizures have been detected in the early stages of Alzheimer disease. Here, the authors review evidence that amyloid-β forms part of a shared pathway between epilepsy and cognitive decline.

• , Arjune Sen

Review Article | 15 March 2021

Cycles in epilepsy

In this Review, the authors provide an overview of the evidence for daily, multi-day and yearly cycles in epileptic brain activity. They also discuss advances in our understanding of the mechanisms underlying these cycles and the potential clinical applications of this knowledge.

• Philippa J. Karoly
• , Vikram R. Rao
•  &  Maxime O. Baud

In Brief | 09 March 2021

Blood purine levels as a biomarker in epilepsy

Review Article | 16 February 2021

Identification of clinically relevant biomarkers of epileptogenesis — a strategic roadmap

Biomarkers of epileptogenesis would enable identification of individuals who are risk of developing epilepsy after an insult or as a result of a genetic defect. In this article, Simonato et al. review progress towards such biomarkers and set out a five-phase roadmap to facilitate their development.

• Michele Simonato
• , Denes V. Agoston
•  &  Karen S. Wilcox

Review Article | 19 October 2020

Impact of predictive, preventive and precision medicine strategies in epilepsy

The anti-seizure medications used to treat patients with epilepsy can improve symptoms but do not address the underlying cause of the condition. In this Review, the authors discuss the ongoing shift towards personalized treatments for specific epilepsy aetiologies.

• Rima Nabbout
•  &  Mathieu Kuchenbuch

Research Highlight | 08 October 2020

Ultra-high-field MRI improves detection of epileptic lesions

Comment | 06 October 2020

Drug-resistant epilepsy — time to target mechanisms

Despite the development of many new anti-seizure drugs over the past two decades, around one-third of individuals with epilepsy are without effective treatment. This pharmacoresistance is poorly understood, but new treatments targeting epileptogenesis instead of seizures have shown potential in animal models and are now being translated into the clinic.

• Holger Lerche

Research Highlight | 02 July 2020

EAN VIRTUAL 2020 — THE LARGEST NEUROLOGY CONFERENCE IN HISTORY

News & Views | 02 July 2020

Gene tests in adults with epilepsy and intellectual disability

A recent study describes the yield and clinical utility of epilepsy gene panel testing in a cohort of adults with epilepsy and intellectual disability. These findings are similar to those in children with developmental epileptic encephalopathies and support the utility of testing in this subgroup of adults with epilepsy.

• Ruth Ottman
•  &  Annapurna Poduri

Review Article | 16 June 2020

MicroRNAs as regulators of brain function and targets for treatment of epilepsy

In this Review, Brennan and Henshall discuss how microRNAs determine and control neuronal and glial functions, how this process is altered in states associated with hyperexcitability, and the prospects for microRNA targeting for the treatment of epilepsy.

• Gary P. Brennan

Review Article | 19 May 2020

Zoonotic and vector-borne parasites and epilepsy in low-income and middle-income countries

Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. The authors explore the pathophysiological basis of the link between parasitic infections and epilepsy and consider preventive and therapeutic approaches to reduce the epilepsy burden associated with parasitic disorders.

• Gagandeep Singh
• , Samuel A. Angwafor

In Brief | 02 March 2020

High risk of epilepsy in children with Zika-related microcephaly

In Brief | 30 January 2020

Antisense oligonucleotide hope for childhood epilepsies

News & Views | 08 January 2020

Cenobamate for focal seizures — a game changer?

In the first published efficacy study of cenobamate for treatment-resistant focal seizures, high doses produced high seizure-free rates, suggesting cenobamate can outperform existing options. A risk of serious rash and low tolerability at higher doses means further safety studies and clinical experience are needed to determine its clinical value.

• Jacqueline A. French

Research Highlight | 18 December 2019

Blood–brain barrier pathology linked to epilepsy in Alzheimer disease

Review Article | 12 December 2019

Cannabinoids and the expanded endocannabinoid system in neurological disorders

In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the endocannabinoid system and the expanded endocannabinoid system and discuss the involvement of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.

• Luigia Cristino
• , Tiziana Bisogno
•  &  Vincenzo Di Marzo

Review Article | 24 July 2019

Changing concepts in presurgical assessment for epilepsy surgery

In patients with drug-resistant focal epilepsy, the success of surgery depends on predicting which resection or disconnection strategy will yield full seizure control. This Review highlights recent advances in presurgical assessment and discusses how concepts of focal epilepsy are changing.

• Maeike Zijlmans
• , Willemiek Zweiphenning
•  &  Nicole van Klink

Comment | 01 July 2019

Neuroinflammation — a common thread in neurological disorders

Inflammatory processes contribute to neurological disorders, and many therapeutic breakthroughs in neurological disease have been immune-targeted. The choice of neuroinflammation as the theme for the 5th European Academy of Neurology Congress in 2019 and of this Focus issue highlights its importance to neurologists across the discipline.

• Nils Erik Gilhus
•  &  Günther Deuschl

Review Article | 01 July 2019

Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy

In this Review, Vezzani and colleagues discuss inflammatory pathways that are activated in pharmacoresistant epilepsy and can be modulated to therapeutic effect in animal models. They consider how targeting these pathways could overcome limitations of existing anti-epileptic treatments.

• , Silvia Balosso
•  &  Teresa Ravizza

Year in Review | 07 January 2019

Teamwork aids management and raises new issues in epilepsy

Publications on epilepsy in 2018 have shed light on the aetiology and management of the condition and raised new questions. Translation from mechanisms to clinical practice, driven by cooperation among multiple fields, will be crucial to further advances.

News & Views | 04 December 2018

How safe is switching antiepileptic drug manufacturers?

A nationwide German study of prescription data has demonstrated that switching to an antiepileptic drug from a different manufacturer increases the risk of seizure relapse. This finding sparks a debate about the reason for seizure worsening after switching and whether or not it is a pharmacological issue.

• Martin Holtkamp

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Epilepsy & Behavior Reports

Following the first issue of Epilepsy Behavior Case Reports (EBCR) published in 2013, our journal is undergoing a metamorphosis. EBCR has seen not only significant traffic in the number of submitted manuscripts from all over the globe, but also growth in the type of manuscripts beyond case reports. With a rising number of case series, prospective and even controlled trials, the time has arrived to enter a new phase of growth for our journal. Acting upon recommendations arising from an Epilepsy & Behavior Reports (EBR) editorial board meeting in previous years, we have with this issue, successfully moved to the next phase. It is with a great sense of pride, standing on the shoulders of giants, that I announce our transition from EBCR to Epilepsy & Behavior Reports (EBR). In addition to a new (or at least modified) name for the journal, we have assembled a first-rate editorial board for EBR complete with national and international experts to form the necessary infrastructure in addition to a new logo to reflect the evolution. The simple absence of the letter “C” from EBCR represents a complex response to the wider variety of manuscripts submitted. Overall, e-journals are on the rise as global penetration of medical informatics mandates easy transmissibility and accessibility. In the wake of this move, EBR opens its literary doors to invite editorials, short communications, reviews, original research, and of course will continue to focus on outstanding clinical case reports.

Created as the brainchild of Dr. Steven Schachter, EBCR flourished with the assistance of Founding Associate Editor, Professor Dieter Schmidt, due to exceptional talent and dedication. Our sister journal, Epilepsy and Behavior (E & B) continues to thrive after nearly 20 years, under the auspices of Dr. Schachter and a diverse editorial board, to deliver high-quality print and electronic publications involving a broad spectrum of topics involving people with epilepsy. Together, EBR and E & B will continue to achieve a wide spectrum of complementary articles involving cutting edge literature that deals with the behavior and psychosocial aspects of epilepsy. The spectrum of articles will continue to deliver high-quality manuscripts ranging from a single case report to prospective, multi-center and controlled trials. The legacy of EBCR will continue as EBR, and continue to evolve, to meet the needs of her readers and demands of her authors. The vision to remain a premier open access journal begun nearly a decade ago, will continue. Digital access to scholars will remain a commitment by EBR and Elsevier so manuscripts are readily available for review on a personal computer, tablet, smartphone or other personal electronic devices. At the foundation for support is Dr. Daniel Staemmler at Elsevier who has provided constant oversight and support in addition to Mehroon Farooqui as journal manager, as we transition to EBR.

With growth in title comes the need for infrastructure. We have assembled a new Editorial Board for EBR. The list of board members is composed of prominent names including clinicians, educators, and researchers. Our focus will extend reporting not only clinical cases, but also cases involving translational research, that impact patient care by centering on diagnosis and management of people with epilepsy. I would like to express my appreciation and gratitude to my Associate Editors, two amazing physicians, who dedicated their time and effort to add to the growth of EBR. Drs. Joseph Sirven and Dr. Dorothée Kasteleijn-Nolste Trenité who contributed to much of the success of the journal through regular conferences, critical review of manuscripts, and executive input for future growth of the journal. It is with thanks that we turn our journal name and our editorial board to two new Associate Editors, Drs. Kurupath Radhakrishnan and Jerzy Szaflarski. The evolving infrastructure of the board will continue its international “flavor” in effort to deliver EBR as a “favorite” throughout North America, the United Kingdom and Europe, and into the far East including Asia-Oceana. We will continue to pursue enhancements such as 3-dimensional neuroimaging, clinical neurophysiology, and detailed microscopic images of pathology, and retain the ability for audio abstract generation to provide detail to publications. EBR will continue to be a citable gold open access e-journal on PubMed Central as part of PubMed and recognized by Scopus. Moving forward, we will now accept a full complement of articles submitted to EBR including editorials, perspectives, reviews, and original research. Topics dealing with neurology, neurosurgery, neuropsychiatry, neuropsychology, neurophysiology, neuro pharmacology, and neuro imaging as they pertain to epilepsy will all be “fair game”. We will continue to not only provide a foundation of high-quality case reports and case series, but also anticipate invited submissions targeted at authors in their early stages of training and extending to those more experienced including academicians and clinical practitioner alike.

The threshold has been crossed, a new generation for EBCR is here, with this issue we christen EBR. On the backs of a new editorial board and associate editors, we uphold our mission to deliver premier, immediate access, most up-to-date, case reports involving epilepsy and behavior and provide new opportunities to those who wish us to submit or review articles. It is an exciting time as we roll out the inaugural issue of Epilepsy & Behavior Reports . We hope you enjoy this issue of the journal and many more!

Disease Landscape and Forecast Research Reports

Epilepsy – landscape & forecast – disease landscape & forecast.

Epilepsy, which afflicts approximately 4.7 million people in the major markets according to Clarivate epidemiology, is a heterogeneous condition requiring individualized treatment based largely on…

Epilepsy – Unmet Need – Detailed, Expanded Analysis: Lennox-Gastaut Syndrome (US/EU)

Lennox-Gastaut syndrome (LGS) is a severe pediatric-onset epilepsy syndrome characterized by developmental delay or regression, multiple seizure types, and electroencephalographic abnormalities…

Epilepsy – Current Treatment – Detailed, Expanded Analysis: Treatment Algorithms: Claims Data Analysis – Generalized-Onset Seizures (US)

Generalized-onset seizures (GOS) simultaneously affect both sides of the brain and rapidly engage bilaterally distributed networks. Nearly 40% of the diagnosed epilepsy population presents with…

Epilepsy – Executive Insights – Dravet Syndrome | Executive Insights | US

Epilepsy | disease landscape & forecast | g7 | 2023, epilepsy – current treatment – detailed, expanded analysis – treatment algorithms – claims data analysis (us).

Epilepsy is a heterogeneous condition requiring individualized treatment, especially for patients who are persistently refractory to treatment. Neurologists consider many factors when selecting…

Epilepsy – Epidemiology – Epidemiology Data Slicer

Epi Data Slicer

Epilepsy | Disease Landscape & Forecast | G7 | 2022

Epilepsy – current treatment – detailed, expanded analysis (us).

For neurologists, established molecules like leveteriacetam, lamotrigine, and carbamazepine remain the first choice of treatment for epilepsy; however, the new entrants in the market are evoloving…

Epilepsy | Treatment Algorithms | Claims Data Analysis | US | 2021

Epilepsy | treatment algorithms: claims data analysis | us | 2022, epilepsy | disease landscape & forecast | g7 | 2021, epilepsy – executive insights – dravet syndrome | executive insights | us/eu5/cn, epilepsy – epidemiology – middle east & africa.

Clarivate Epidemiology’s coverage of epilepsy comprises epidemiological estimates of key patient populations in 45 countries worldwide. We report the prevalence of epilepsy for each country, as…

Epilepsy – Epidemiology – Americas

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The Relationship Between Sleep, Epilepsy, and Development: a Review

• Published: 17 July 2023
• Volume 23 , pages 469–477, ( 2023 )

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• Annie H. Roliz 1 &
• Sanjeev Kothare 1  

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Purpose of Review

To review the relationship between sleep, neurodevelopment, and epilepsy and potential underlying physiological mechanisms.

Recent Findings

Recent studies have advanced our understanding of the role of sleep in early brain development and epilepsy. Epileptogenesis has been proposed to occur when there is a failure of normal adaptive processes of synaptic and homeostatic plasticity. This sleep-dependent transformation may explain the cognitive impairment seen in epilepsy, especially when occurring early in life. The glymphatic system, a recently discovered waste clearance system of the central nervous system, has been described as a potential mechanism underlying the relationship between sleep and seizures and may account for the common association between sleep deprivation and increased seizure risk.

Epilepsy and associated sleep disturbances can critically affect brain development and neurocognition. Here we highlight recent findings on this topic and emphasize the importance of screening for sleep concerns in people with epilepsy.

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The Architecture of Early Childhood Sleep Over the First Two Years

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Roliz, A.H., Kothare, S. The Relationship Between Sleep, Epilepsy, and Development: a Review. Curr Neurol Neurosci Rep 23 , 469–477 (2023). https://doi.org/10.1007/s11910-023-01284-0

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Research implications of the Institute of Medicine Report, Epilepsy Across the Spectrum: Promoting Health and Understanding

Affiliation.

• 1 GH Sergievksky Center, Columbia University, New York, New York 10024, USA. [email protected]
• PMID: 23294462
• PMCID: PMC3566357
• DOI: 10.1111/epi.12056

In March 2012 the Institute of Medicine (IOM) released the report, Epilepsy Across The Spectrum: Promoting Health and Understanding. This report examined the public health dimensions of the epilepsies with a focus on the following four areas: public health surveillance and data collection and integration; population and public health research; health policy, health care, and human services; and education for providers, people with epilepsy and their families, and the public. The report provided recommendations and research priorities for future work in the field of epilepsy that relate to increasing the power of data on epilepsy; prevention of epilepsy; improving health care for people with epilepsy; improving health professional education about epilepsy; improving quality of life for people with epilepsy; improving education about epilepsy for people with epilepsy and families; and raising public awareness about epilepsy. For this article, the authors selected one research priority from each of the major chapter themes in the IOM report: expanding and improving the quality of epidemiologic surveillance in epilepsy; developing improved interventions for people with epilepsy and depression; expanding early identification/screening for learning impairments in children with epilepsy; evaluating and promoting effective innovative teaching strategies; accelerating research on the identification of risk factors and interventions that increase employment and improve quality of life for people with epilepsy and their families; assessing the information needs of people with epilepsy and their families associated with epilepsy-related risks, specifically sudden unexpected death in epilepsy; and developing and conducting surveys to capture trends in knowledge, awareness, attitudes, and beliefs about epilepsy over time and in specific population subgroups. For each research priority selected, examples of research are provided that will advance the field of epilepsy and improve the lives of people with epilepsy. The IOM report has many other research priorities for researchers to consider developing to advance the field of epilepsy and better the lives of people with epilepsy.

Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

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Conflict of interest statement

Disclosure of Conflicts of Interest :

Joan Austin

Dr. Austin serves on the editorial boards of Chronic Illness and Applied Nursing Research. She is a consultant to the Intramural Program of the National Institute of Nursing Research, National Institutes of Health.

Charles E. Begley

Dr. Begley serves on the editorial board of Epilepsia and consulting editors board of Epilepsy Research. He participates on an advisory board for UCB and the Epilepsy Foundation. He is funded by grants from the Center for Houston’s Future, Cancer Prevention Research Institute of Texas, U.S. Centers for Disease Control and Prevention, and the Hogg Foundation for Mental Health.

Malachy L. Bishop

Member American Epilepsy Society, Member Educational committee International Bureau for Epilepsy and International League Against Epilepsy. International Epilepsy Congress 2012–13. Member Epilepsy Foundation of America, advisory board. Member International Bureau for Epilepsy, Research Task Force.

Sandra Cushner Weinstein

Volunteer, Patient/family workgroup of Vision 20/20. Manage the Newly Diagnosed Seizure Clinic at Children’s National; Director, Brainy Camps. She is funded by CDC grant 1UO1DP003255-01, 2011–2015.

Dale C. Hesdorffer

Dr. Hesdoffer serves on the editorial board of Epilepsy and Behavior, and Epilepsy Research and as contributing editor to Epilepsy Currents. She consults for the Mount Sinai Medical Center, Injury prevention center. Dr. Hesdorffer received a travel award from GlaxoSmithKline in 2010. In 2012, she participated in advisory boards for UCB and UpsherSmith. She is funded by grants from CDC, DP002209, PI, 2009–2014; AUCD, RT01, Co-I (PI of Columbia subcontract), 2008–2012; NINDS, NS31146, Co-I (PI of Columbia subcontract), 2007–2014; NINDS, NS043209, Co-I (PI of Columbia subcontract), 2003–2013; CDC, MM1002, Co-I, 2006–2010; NICHD, HD042823, Co-I, 2002–2013; NINDS, 5U01NS04911, Co-I (PI of Columbia subcontract), 2011–2012; NINDS, NS078419, Co-I, 2012–2015; and the Epilepsy Foundation of America 2010–2012.

Gregory L. Holmes

Dr. Holmes serves on the editorial board of Epilepsy & Behavior, Brain & Development, and Paediatric Drugs. He is on the safety monitoring board of the National Heart, Lund and Blood Institute and Eisai Pharmaceuticals. He has participated in advisory boards for the National Institute of Health, Food & Drug Institute, Upsher-Smith Laboratories and GlaxoSmithKline. He is funded by grants from NINDS (NS075249, NS044295, NS073083), and the Emmory R. Shapses Resarch Fund [GLH]

Patricia O. Shafer

Consultant, Epilepsy Therapy Project; Board of Directors, Epilepsy Foundation;. Professional Advisory Board, Epilepsy Foundation of Massachusetts, Rhode Island, New Hampshire and Maine; Member and Committee Chair, American Epilepsy Society; Affiliate member, Managing Epilepsy Well Network. Co-Chair, Patient/family workgroup of Vision 20/20.

Joseph I. Sirven

NIH funding for Research; Time compensation from Epilepsy Therapy Project; Research funding from: Eisai, Vertex, MAP, Neuropace, LGH Upsher- Smith

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A COMPREHENSIVE REVIEW ON EPILEPSY

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• Epilepsy is a chronic noncommunicable disease of the brain that affects people of all ages.
• Around 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally.
• Nearly 80% of people with epilepsy live in low- and middle-income countries.
• It is estimated that up to 70% of people living with epilepsy could live seizure-free if properly diagnosed and treated.
• The risk of premature death in people with epilepsy is up to three times higher than for the general population.
• Three quarters of people with epilepsy living in low-income countries do not get the treatment they need.
• In many parts of the world, people with epilepsy and their families suffer from stigma and discrimination.

Epilepsy is a chronic noncommunicable disease of the brain that affects around 50 million people worldwide. It is characterized by recurrent seizures, which are brief episodes of involuntary movement that may involve a part of the body (partial) or the entire body (generalized) and are sometimes accompanied by loss of consciousness and control of bowel or bladder function.

Seizure episodes are a result of excessive electrical discharges in a group of brain cells. Different parts of the brain can be the site of such discharges. Seizures can vary from the briefest lapses of attention or muscle jerks to severe and prolonged convulsions. Seizures can also vary in frequency, from less than one per year to several per day.

One seizure does not signify epilepsy (up to 10% of people worldwide have one seizure during their lifetime). Epilepsy is defined as having two or more unprovoked seizures. Epilepsy is one of the world’s oldest recognized conditions, with written records dating back to 4000 BCE. Fear, misunderstanding, discrimination and social stigma have surrounded epilepsy for centuries. This stigma continues in many countries today and can impact on the quality of life for people with the disease and their families.

Signs and symptoms

Characteristics of seizures vary and depend on where in the brain the disturbance first starts, and how far it spreads. Temporary symptoms occur, such as loss of awareness or consciousness, and disturbances of movement, sensation (including vision, hearing and taste), mood, or other cognitive functions.

People with epilepsy tend to have more physical problems (such as fractures and bruising from injuries related to seizures), as well as higher rates of psychological conditions, including anxiety and depression. Similarly, the risk of premature death in people with epilepsy is up to three times higher than in the general population, with the highest rates of premature mortality found in low- and middle-income countries and in rural areas.

A great proportion of the causes of death related to epilepsy, especially in low- and middle-income countries, are potentially preventable, such as falls, drowning, burns and prolonged seizures.

Rates of disease

Epilepsy accounts for a significant proportion of the world’s disease burden, affecting around 50 million people worldwide. The estimated proportion of the general population with active epilepsy (i.e. continuing seizures or with the need for treatment) at a given time is between 4 and 10 per 1000 people.

Globally, an estimated 5 million people are diagnosed with epilepsy each year. In high-income countries, there are estimated to be 49 per 100 000 people diagnosed with epilepsy each year. In low- and middle-income countries, this figure can be as high as 139 per 100 000. This is likely due to the increased risk of endemic conditions such as malaria or neurocysticercosis; the higher incidence of road traffic injuries; birth-related injuries; and variations in medical infrastructure, the availability of preventive health programmes and accessible care. Close to 80% of people with epilepsy live in low- and middle-income countries.

Epilepsy is not contagious. Although many underlying disease mechanisms can lead to epilepsy, the cause of the disease is still unknown in about 50% of cases globally. The causes of epilepsy are divided into the following categories: structural, genetic, infectious, metabolic, immune and unknown. Examples include:

• brain damage from prenatal or perinatal causes (e.g. a loss of oxygen or trauma during birth, low birth weight);
• congenital abnormalities or genetic conditions with associated brain malformations;
• a severe head injury;
• a stroke that restricts the amount of oxygen to the brain;
• an infection of the brain such as meningitis, encephalitis or neurocysticercosis,
• certain genetic syndromes; and
• a brain tumour.

Seizures can be controlled. Up to 70% of people living with epilepsy could become seizure free with appropriate use of antiseizure medicines. Discontinuing antiseizure medicine can be considered after 2 years without seizures and should take into account relevant clinical, social and personal factors. A documented etiology of the seizure and an abnormal electroencephalography (EEG) pattern are the two most consistent predictors of seizure recurrence.

• In low-income countries, about three quarters of people with epilepsy may not receive the treatment they need. This is called the “treatment gap”.
• In many low- and middle-income countries, there is low availability of antiseizure medicines. A recent study found the average availability of generic antiseizure medicines in the public sector of low- and middle-income countries to be less than 50%. This may act as a barrier to accessing treatment.
• It is possible to diagnose and treat most people with epilepsy at the primary health-care level without the use of sophisticated equipment.
• WHO pilot projects have indicated that training primary health-care providers to diagnose and treat epilepsy can effectively reduce the epilepsy treatment gap.
• Surgery might be beneficial to patients who respond poorly to drug treatments.

An estimated 25% of epilepsy cases are potentially preventable.

• Preventing head injury, for example by reducing falls, traffic accidents and sports injuries, is the most effective way to prevent post-traumatic epilepsy.
• Adequate perinatal care can reduce new cases of epilepsy caused by birth injury.
• The use of drugs and other methods to lower the body temperature of a feverish child can reduce the chance of febrile seizures.
• The prevention of epilepsy associated with stroke is focused on cardiovascular risk factor reduction, e.g. measures to prevent or control high blood pressure, diabetes and obesity, and the avoidance of tobacco and excessive alcohol use.
• Central nervous system infections are common causes of epilepsy in tropical areas, where many low- and middle-income countries are concentrated. Elimination of parasites in these environments and education on how to avoid infections can be effective ways to reduce epilepsy worldwide, for example those cases due to neurocysticercosis.

Social and economic impacts

Epilepsy accounts for more than 0.5% of the global burden of disease, a time-based measure that combines years of life lost due to premature mortality and time lived in less than full health. Epilepsy has significant economic implications in terms of health-care needs, premature death and lost work productivity.

Out-of-pocket costs and productivity losses can create substantial burdens on households. An economic study from India estimated that public financing for both first- and second-line therapy and other medical costs alleviates the financial burden from epilepsy and is cost-effective.

The stigma and discrimination that surround epilepsy worldwide are often more difficult to overcome than the seizures themselves. People living with epilepsy and their families can be targets of prejudice. Pervasive myths that epilepsy is incurable, or contagious, or a result of morally bad behaviour can keep people isolated and discourage them from seeking treatment.

Human rights

People with epilepsy can experience reduced access to educational opportunities, a withholding of the opportunity to obtain a driving license, barriers to enter particular occupations, and reduced access to health and life insurance. In many countries legislation reflects centuries of misunderstanding about epilepsy, for example, laws which permit the annulment of a marriage on the grounds of epilepsy and laws that deny people with seizures access to restaurants, theatres, recreational centres and other public buildings.

Legislation based on internationally accepted human rights standards can prevent discrimination and rights violations, improve access to health-care services, and raise the quality of life for people with epilepsy.

WHO response

The first global report on epilepsy produced in 2019 by WHO and key partners, Epilepsy: A public health imperative , highlighted the available evidence on the burden of epilepsy and the public health response required at global, regional and national levels.

The 75th WHA adopted the Intersectoral global action plan on epilepsy and other neurological disorders 2022–2031, which recognizes the shared preventive, pharmacological and psychosocial approaches between epilepsy and other neurological disorders that can serve as valuable entry points for accelerating and strengthening services and support for these conditions.

Recently, WHO published an epilepsy technical brief, which outlines actions for policy makers and healthcare planners to reduce the burden of epilepsy in countries through finding and prioritizing the most effective solutions in a wide range of societal sectors.

WHO, the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) led the Global Campaign Against Epilepsy to bring the disease out of the shadows to provide better information and raise awareness about epilepsy and to strengthen public and private efforts to improve care and reduce the disease’s impact.

These efforts have contributed to the prioritization of epilepsy in many countries and projects have been carried out to reduce the treatment gap and morbidity of people with epilepsy, to train and educate health professionals, to dispel stigma, to identify potential prevention strategies, and to develop models integrating epilepsy care into local health systems. Combining several innovative strategies, these projects have shown that there are simple, cost-effective ways to treat epilepsy in low-resource settings. The WHO Programme on reducing the epilepsy treatment gap and the mental health Gap Action Programme (mhGAP) achieved these goals in Ghana, Mozambique, Myanmar and Viet Nam, where 6.5 million more people have access to treatment for epilepsy should they need it.

• More information on epilepsy
• WHO global report on epilepsy
• Neurology Atlas 2017
• Brain health

  Features

• Pilot studies help close the epilepsy treatment gap
• The fight against epilepsy in Ghana
• Scaling up epilepsy care in Myanmar

WHO video: Epilepsy, Treat it, Defeat it

Plain Language Summary

2020 epilepsy research benchmarks plain language summary .

On January 4-6, 2021 NINDS hosted  Curing the Epilepsies 2021: Setting Research Priorities  conference virtually via Zoom. This conference was the fourth in a series of Curing the Epilepsies conferences held approximately every seven years since 2000. The goal of the conference is to bring together all stakeholders—including researchers, clinicians, patients, families, and advocates—to evaluate the current state of epilepsy research and consider priorities for future efforts.  

As an important outcome, the Curing the Epilepsies conferences have led to the development of Benchmarks for Epilepsy Research, which reflect priorities shared across the epilepsy community for research toward clinically meaningful advances in understanding and treating the epilepsies. 

In late 2019, the Epilepsy Benchmark Stewards Committee, coordinated by the American Epilepsy Society, started the process of revising the Epilepsy Research Benchmarks by publishing progress reports for each of the four benchmark areas. These articles were published in Epilepsy Currents in early 2020. The Epilepsy Research Benchmarks were published in 2021. This page is a plain language summary of those benchmarks.

Area 1:  Understand what causes the many types of the epilepsies and commonly co-occurring symptoms people experience. 

• Learn more about genetics and how changes in some genes result in seizures and epilepsy. 
• Learn more about non-genetic causes of the epilepsies, including infection, age, trauma, and risk factors that may make some people more likely to develop epilepsy. 
• Look at how changes in brain cells affect how those cells interact with each other and connect one brain area to another, and how these changes cause seizures and epilepsy.  Scientists have found many changes in brain cells in the epilepsies, and we need to understand more about how these changes cause seizures. 
• Learn more about risk factors for groups of people, for example, related to age, gender, sex, race/ethnicity, and socioeconomic status. 
• Look at the link between some epilepsies and autism spectrum disorder, depression, disorders of brain development, and other mental health issues. 

Area II:  Prevent epilepsy and its progression. 

• Understand how genes and the control of those genes can influence how a brain may become prone to seizures during brain development. 
• Understand how insults to the brain such as trauma, tumors, or neurodegeneration can influence how someone’s brain can develop epilepsy. 
• Identify measurable, biological markers to help identify, predict, and monitor the development of seizures and epilepsy so treatments to prevent epilepsy following insult to the brain can be developed. 
• Develop animal models and other model systems that more closely align with human epilepsy to better understand and develop treatments to prevent or cure epilepsy in people. 
• Develop new therapies to prevent epilepsy or change its progression that also treat the co-occurring conditions such as depression. 
• Apply new tools and techniques for the use of large amounts of data from laboratories and from hundreds or thousands of people with epilepsy to our laboratory research to better understand the complexity of the epilepsies. For example, use artificial intelligence to analyze large amounts of data help to understand why individuals with a similar genetic background can have profoundly different symptoms? 

Area III.  Improve treatment options for controlling seizures and epilepsy-related conditions while limiting side effects. 

• Understand how seizures start, spread, and stop in the brain for different seizure types and different causes of the epilepsies.  Learn about what is happening in the brain in between seizures and how that impacts the person and future seizures.  We also need to learn more about why people have treatment side effects and how they can be prevented. 
• Develop knowledge and tools to create and prescribe the best treatment for each person with epilepsy by using personal characteristics, seizure type and form of epilepsy, risk factors, and other health issues that also occur with epilepsy. 
• Develop better ways to study the epilepsies that capture the many essential facets of epilepsy in people. Explore new ways to model the epilepsies in the laboratory that might allow for accelerated development of new treatments. 
• Develop and improve non-medication treatment options such as surgical approaches, gene therapy, dietary treatments like the ketogenic diet, and devices that detect and prevent or stop seizures. Reduce or eliminate side effects of these treatments.  
• Develop better treatments and ways to monitor and report health status for people with epilepsy and their families so they can manage the condition in their home or other non-medical setting. 

Area IV. Limit, treat, or prevent other conditions associated with epilepsy including neurodevelopmental and mental health issues, cognitive problems, health-related quality of life concerns, as well as causes of mortality or death. 

• Understand and reduce the effect of epilepsy on non-seizure outcomes such as brain development, mental health, intelligence, reasoning and understanding, and health-related quality of life.  
• Understand and limit the effect of epilepsy treatments on non-seizure outcomes, such as brain development, mental health, understanding and awareness, and health-related quality of life. 
• Understand non-epileptic seizures not related to epilepsy (also referred to as functional seizures) and improve the treatment options available. 
• Understand the causes of and risk factors for sudden unexpected death in epilepsy (SUDEP) and other causes of death in people with epilepsy, and develop preventative strategies and treatments. 
• Identify the impact of epilepsy and treatments for the epilepsies on the health of women (fertility, pregnancy, bone health, hormones, mental health, quality of life) and their children (fetal and neonatal development). 
• Understand the impact and interaction between sleep and epilepsy and how this impacts non-seizures outcomes. Develop improved treatment options for sleep issues that improve non-seizure outcomes. 

Interagency Collaborative to Advance Research in Epilepsy Research Portfolio

ICARE Epilepsy Research Portfolio provides information on epilepsy research projects funded by the ICARE members, including federal and nonprofit organizations.

ICARE Portfolio

The portfolio provides information on epilepsy research funded by the ICARE members

ICARE Ontology

The epilepsy research projects are categorized by a shared multi-layered ontology

Data Reports

Reports and publications related to the ICARE Epilepsy Research Portfolio  

NEW FUNDING ANNOUNCEMENTS

• New Therapy Commercialization Grants Program (Epilepsy Foundation)
• LGS Foundation's Seed Grant (1 year) or (2 year) (LGS Foundation)
• Epilepsy Innovation Seal of Excellence Award (Epilepsy Foundation)
• Research & Training Workshops (American Epilepsy Society)
• Research to Characterize and Reduce Stigma to Improve Health (R01) (NIH)

FUNDING OPPORTUNITIES FOR EPILEPSY RESEARCH

The Epilepsy Research Connection (ERC) is connecting researchers with funding opportunities from the leading epilepsy organizations. The ERC website provides a single place for researchers to search for funding.

• Open access
• Published: 23 August 2022

Adherence to anti-seizure medications and associated factors among children with epilepsy at tertiary Hospital in Southwest Ethiopia: a cross-sectional study

• Hawi Mohammed 1 ,
• Kemal Lemnuro 2 ,
• Teferi Mekonnen 3 &
• Tsegaye Melaku 4  

BMC Neurology volume  22 , Article number:  310 ( 2022 ) Cite this article

3125 Accesses

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Metrics details

Childhood epilepsy causes a tremendous burden for the child, the family, society as well as the healthcare system. Adherence to anti-seizure medications (ASMs) is a key to treatment success. Poor adherence has been considered as one of the main causes of unsuccessful treatment for epilepsy and presents a potential ongoing challenge for achieving a key therapeutic goal of seizure control.

A facility-based cross-sectional study design was conducted among children with epilepsy attending the Pediatrics neurology follow up clinic of Jimma Medical Center from June- 21 to September- 20, 2021. Data were collected by using a semi-structured pre-tested questionnaire. Epidata version 3.1 and SPSS version 26.0 were used for data entry and analysis respectively. Descriptive statistics and binary logistic regression analysis were employed. Adjusted odds ratios were used to ascertain effect sizes for any association between the dependent and associated variables while significance level at p -value of < 0.05 was determined using 95% confidence intervals.

A total of 170 children with epilepsy were included in this study. About 54.7% were male and 44.7% were in age range of 10–17 years. The overall adherence to anti-seizure medications was 54.1%. Those caregivers who were married [AOR = 7.46 (95% CI = 1.46, 38.20)], those children with controlled seizure status [AOR = 3.64 (95% CI = 1.51, 8.78)], those who got appropriate health care [AOR = 7.08(95% CI = 2.91, 17.24)], those caregivers who had good knowledge [AOR = 5.20(95% CI = 2.60,14.83)]; and positive attitude [AOR = 2.57 (95% CI = 1.06, 6.28)] towards epilepsy were significantly associated with adherence to anti-seizure medications.

Conclusions

More than half of the children/adolescents having epilepsy were adherent to their anti-seizure medication(s). Children’s adherence to anti- seizure medications was influenced by current marital status of the parents/caregivers, controlled seizure status, getting appropriate healthcare in the hospital, caregiver’s knowledge; and attitude towards epilepsy. More efforts are required to scale up the provision of client-centered service (provision of appropriate health care delivery, focus on quality of treatment and providing health education/counseling to improve caregivers’ knowledge and attitude towards epilepsy) to improve children’s adherence status to their medication(s) and seizure control status.

Peer Review reports

Introduction

Over 50 million people are affected by epilepsy worldwide of which 80% are in developing countries. Mortality is 2–3 times higher than that of the general population. The common causes of epilepsy-related deaths are sudden unexplained death in epilepsy (SUDEP) (2–18%) of all deaths in epilepsy, death due to status epilepticus (SE) (12.5%) and suicide (0–2%) [ 1 ]. Approximately 1 out of 150 children is diagnosed with epilepsy during the first 10 years of life, with the highest incidence rate observed during infancy [ 2 ].

A systematic analysis of epilepsy in sub-Saharan Africa showed that, active epilepsy was estimated to affect 4.4 million people in this region. The prevalence of active epilepsy per age group in the same region is 5.09/1000 and 5.98/1000 among children age 0–9 years old and 10–19 years old respectively [ 3 ].

Epilepsy symptoms can be successfully treated with one or more anti- seizure medications which can control seizures in 60–80% of patients with new onset epilepsy [ 4 , 5 ]. The goal of treatment of epilepsy includes minimizing the risk of recurrent seizures and anti- seizure medications (ASMs) side effects, and maintaining normal psycho-social and educational/vocational adjustments [ 6 ].

Adherence to ASMs is key to treatment success, one of the main causes of unsuccessful drug treatment for epilepsy is poor adherence to prescribed medications [ 7 , 8 ]. Medication adherence increase if the patients and families are involved in treatment choice as well as a mutual agreement between the clients and healthcare providers. Adherence to anti-seizure medications results in decrement of relapses, minimized frequency of seizures, decreased cost of health care, increased therapeutic benefits and better patient outcomes [ 9 ].

Despite the fact that there are significant treatment advances in pediatrics, improvements in medical technology to assess adherence behaviors and increased focus on adherence in research and clinical practice, non-adherence rates across all pediatric chronic illnesses is quite high, 50–75% [ 9 ]. According to WHO’s adherence to long-term therapies, adherence to anti- seizure medications in children with epilepsy ranges from 25 to 75% [ 10 ]. Specifically; the prevalence rate of adherence to ASMs was 55% in South Africa in 2016 [ 11 ], 55.2% in Nigeria in 2020 [ 12 ], 79.5% in Uganda in 2014 [ 13 ], 61.7% in Saudi Arabia in 2015 [ 14 ], 29% in Indian subcontinent in 2018 [ 15 ], 21.3% in western China in 2020 [ 16 ]; and 42% in USA in 2011 [ 17 ].

A study done in Pakistan (2018) on 120 children with epilepsy on ASMs for at least 1 month showed that 70(58%) of children had suboptimal ASM adherence and 50(42%) of them had satisfactory adherence according to self or parental report. In this study, ASM prescription patterns, adverse effects, availability of ASMs, seizure control, treating physician’s counseling, financial constraints; and parental/caregiver’s education were more significantly associated with drug non-adherence in these communities [ 18 ].

Another study done in Turkey in 2020 on 226 children and adolescents with epilepsy and their primary caregivers, the overall prevalence of complete drug adherence among the patients was 47.3%. The main reasons of non-adherence to ASMs were forgetting to take medication (33.6%) and the difficulties in adhering to treatment (24.3%). In contrast to above studies, age and caregivers’ health literacy knowledge were found to be significantly associated with adherence in this study. Patients in the 0 to 5 years age group were more likely to have full drug adherence than were those in the 12 to 18 years age group [ 19 ].

On the other hand, a study done on 112 children aged 2-14 year at Queen Rania AL-Abdullah Children Hospital in 2015 showed that 79.5% of the patients display some adherence to anti-seizure medication, while 20.5% of the patients do not display adherence to their anti- seizure medication. 23 patients (20.5%) have low adherence, 56 patients (50%) have medium adherence, and 33 patients (29.4%) have high adherence. In this study, parents’ forgetfulness to give medications to their children (52.2%), fear of medication side effects (33.5%), and being improved and seizure free for a period (30.4%) were significantly associated with non-adherence [ 20 ].

Seizure control status may affect patients’ adherence to ASMs as it will increase treatment satisfaction; a cross-sectional observational study was conducted among 253 patients with epilepsy in Bangladesh indicate that adherence was 38.7% and associated with well seizure control. Among ASM adherent patients ( n  = 98), 70(82.4%) had controlled seizure status [ 21 ].

Treatment of epilepsy and measurement of adherence to ASM in children has been a major challenge because of the chronicity of the disease and the dependency of children on their parents/caregivers. Further, low adherence and poor seizure control will adversely affect socio-behavioral and cognitive function of children which lead to poor school performance. The factors that affect adherence to ASMs reported by various studies are not similar and there is a lack of information regarding the prevalence and associated factors of adherence to ASMs in the study area and Ethiopia in general. In addition, previous few studies done in Ethiopia focused on adult patients at the community level and focus of health policy of Ministry of health-Ethiopia was on prevention, even though more recently chronic illness including epilepsy gained more attention. Different socio-demographic, clinical and treatment, health services, parental knowledge and attitude, and psychosocial related factors may contribute to non-adherence to ASMs. Therefore, taking into account the existing problem under study, which is a critical and major public health problem and having limited information because of lack of published study on the issue of adherence to ASMs in the study area farther strengthen the importance of this study.

Methods and materials

Study area and period.

This study was conducted from June 21- Sep 20, 2021, in Jimma Medical Centre (JMC), Jimma, South West Ethiopia. The center is one of the oldest public hospitals in the country located in Jimma town of Oromia Regional State, Ethiopia. JMC gives services for an estimated 20 million people from Jimma zone and is a referral centre for regions of South Western part of Ethiopia. It also serves as a teaching hospital for several undergraduate and post graduate programs for medicine and health sciences students of Jimma University.

Study design, source population and study population

A facility based cross- sectional study design was employed on children with epilepsy. All children having epilepsy on follow- up attending Paediatrics neurology clinic of JMC were source populations. Children between 6 month- < 18 years of age having epilepsy visiting JMC Paediatrics neurology clinic and those who fulfilled the eligibility criteria were involved in this study.

Sample size determination

The required sample size for this study was determined by using single population proportion estimation formula and considering the following assumptions; Study done in Joe, Nigeria showed that the proportion of adherence to ASMs was around 55.2% with a 95% of the confidence interval and 5% of margin of error was taken. Accordingly, the calculated sample size was 380.

Since the source population is < 10,000; the final sample size was determined by applying the finite population correction formula and adding 5% non-response rate. Accordingly, the calculated final sample size became 170 children/adolescents with epilepsy.

Sampling technique and procedure

According to the three consecutive months Health Management Information System (HMIS) activity report of JMC; the 3 months average visit/load at paediatrics neurology clinic was around 280 children with epilepsy; hence by using this data and calculated sample size which was 170; all parents/caregivers of children and/or adolescents with epilepsy who fulfilled the inclusion criteria, consented (parents/caregivers) and assented (adolescents) to participate in the study were interviewed at k th interval of 1.6(~ 1)(280/170); then patients were interviewed consecutively until required sample size was obtained at their exit from neurology clinic.

Data collection tools and procedures

Data were collected by two registered BSC pharmacists and supervised by principal investigator by using pre-tested interviewer administered semi-structured questionnaire which was developed by compiling a number of questions adapted from similar study materials and review of relevant literatures [ 22 , 23 , 24 ] to address the objectives of this study. The questionnaires were prepared in six sections: section-I was about parents’/caregivers’ socio-demographic and economic related factors; section-II was about children’s socio-demographic, clinical and treatment related factors; section-III was about health facility/service related factors; secion-IV was about to assess parental knowledge about epilepsy; section-V was about to assess parental attitude towards epilepsy; and secion-VI was about ASM adherence status. The questionnaires were prepared in the English language and then translated to the local languages: Amharic & Afaan Oromo by language experts and re-translated back to English by experts to check consistency before conducting data collection.

The study participants were given an orientation on the details concerning participation in the study and informed verbal consent was obtained from each eligible study participant. The eligible participants were interviewed at their exit from the neurology follow-up clinic. The diagnosis of each child/adolescent including co-morbidities, types of ASM(s) he/she was taking and some of the ASM side effects were retrieved from charts at time of interview. The principal investigator supervised closely the overall data collection activities on a daily basis.

Operational definitions and variable measurements

Adherence to ASMs measured by eight-item Morisky Medication Adherence Scale (MMAS) [ 22 ] that is widely used to measure adherence. Items 1–7 are yes/no questions, in which a “no” answer receives a score of 1 and a “yes” answer receives a score of 0, except for item 5, which is reverse scored. Item 8 is measured on a five-point scale. The responses “never”, “once in a while”, “sometimes”, “usually”, and “all the time” are scored, 1, 0.75, 0.50, 0.25, and 0 respectively and the total score ranges from 0 to 8.

Low adherence/non-adherence:- Patients scores < 6 of 8 items MMAS.

Medium adherence: - Patients scores 6–7 of 8 items MMAS.

High adherence: - Patients scores 8 of 8 items MMAS.

Overall adherence: - Dichotomized as adherent and non-adherent. In this study, individuals in category of medium and high adherence were taken as ‘adherent’ and low adherence as ‘non-adherent.’

Data management and quality control

To keep the uniformity of the data collection process; data collectors were trained for 2 days on the objective of the study, method of data collection and interview technique. A pre-test was conducted on 5% (9) children having epilepsy in the pediatrics neurology clinic, JMC 1 week before real data collection to assess its clarity, completeness and consistency and then necessary adjustment was done to the tools.

Data were checked for completeness, accuracy and consistency by principal investigator on a daily basis. Double entry of data for checking errors was performed to assure quality of data before analysis.

Data processing & analysis

The data on the questionnaire were entered into Epidata manager version 3.1 and exported to SPSS version 26.0. The data were edited and cleaned for inconsistencies, explored to check outliers and missing data.

Descriptive statistics was calculated for socio-demographic and economic status of the participants, child’s health related factors (clinical and treatment profiles) and health facility related factors. Variables for knowledge about epilepsy, attitude towards epilepsy, seizure control; and level of adherence were computed using variables recoding. Bivariate analysis was performed to select variables for multivariate analysis. Hence variables with a p -value ≤0.25 in the bivariate analysis were taken as candidates for multivariable analysis. Finally, multivariable logistic regression analysis was performed to identify the independent predictors of Adherence to ASMs. Variables with a p -value of < 0.05 in multivariable logistic regressions were taken as statistically significant predictors for adherence and OR with its 95% CI was used to show the degree of association between the independent and the outcome variable. Results were reported as percentages (frequency) for categorical variables and findings were summarized and presented in the form of tables and interpreted in the line of its objective with narration.

Socio-demographic and economic characteristics of participants/caregivers

A total of 170 children/adolescents having epilepsy on follow- up were involved in this study. Nearly nine from ten (150, 88.2%) of caregivers were father (44.1%) and mother (44.1%). The age of most (70, 41.2%) of parents/caregivers was between 18 and 35 years and more than half (98, 57.6%) of them were from rural area. About 132(77.5%) of parents/caregivers were married and 66(38.8%) of them cannot read and write. Nearly half (84, 49.4%) of parents/caregivers were farmers and more than half (93, 54.7%) of their monthly income was 1500–3500 Ethiopian birr (Table  1 ).

More than half (93, 54.7%) of the children with epilepsy were male, most (76, 44.7%) of them were adolescents(10–17 year) & 32 (32/109, 29.4%) of them didn’t attend school (Table 1 ).

Child’s health related factors (clinical and treatmentprofiles)

Among 170 of the study participants; 104(61.2%) of them were diagnosed with generalized seizure, 10(5.9%) of them had family history of epilepsy. Around 106(62.4%) of study participants were on treatment for more than 2 years and 108(63.5%) of them were on monotherapy. Mostly prescribed ASM was phenytoin only, 82(48.2%). 44(25.9%) of the children were ever stopped/missed their ASM doses since starting of therapy; main reason was forgetfulness, 31(70.5%). More than one-fourth, 46(27.1%) of the study participants reported some adverse effects with ASMs, among these more than half (24, 52%) of them were reporting drowsiness ( Table  2 ).

Health facility/ service related factors

Among the study participants, 73(42.9%) of them travel more than 20kms to arrive JMC and 119(70%) of them were using public transport. More than half (100, 58.8%) of study participants received counseling about epilepsy and/or ASMs sometime during follow up visit; 84(84%) of them were counseled about ‘importance of ASMs’ and 79(46.5%) of them get ASMs free of charge (Table  3 ).

Parents/caregivers knowledge and attitude about and towards epilepsy respectively

Among the study participants; more than half (97, 57.1%) of them were found to have overall good knowledge about epilepsy and 95(55.9%) of them were having positive attitude towards epilepsy (Table  4 ).

Adherence status to ASMs of the study participants

Among 170 study participants, more than half (54.1%) of them were found to be adherent to their ASM(s) (Table  5 ).

Predictor variables of adherence to ASMs

After bivariate logistic analysis, multivariable logistic regression analysis was done to calculate odds ratios and corresponding 95% confidence intervals for the predictors of adherence to ASMs. Those caregivers who were married [AOR = 7.46 (95% CI = 1.46,38.20)], those children with controlled seizure status [AOR = 3.64 (95% CI =1.51, 8.78)], those who got appropriate health care [AOR = 7.08 (95% CI = 2.91,17.24)], children of those caregivers who had good knowledge [AOR = 6.20 (95% CI = 2.60, 14.83)] and positive attitude [AOR = 2.57 (95% CI = 1.06, 6.28)] were significantly associated with adherence to ASMs (Table  6 ).

Adherence to anti-seizure medications is a key to treatment success, one of the main causes of unsuccessful drug treatment is poor adherence to prescribed medications [ 7 , 8 ]. Adherence to anti-seizure medications results in decrement of relapses, minimized frequency of seizures, decreased cost of healthcare, increased therapeutic benefits and better patient outcomes [ 9 ]. This study was conducted to assess the prevalence of ASM adherence and associated factors among children/adolescents having epilepsy on follow- up in JMC.

The adherence status to ASMs in this study was 54.1% and the rest(45.9%) of the study participants were non-adherent to ASMs. The prevalence of adherence to ASMs in children having epilepsy is similar to the study done in South Africa(55%) in 2016 [ 11 ], Joe, Nigeria(55.2%) in 2019 [ 12 ] and Turkey (47.3%) in 2020 [ 19 ], this might be because of similar socio-demographic status of the study population participated and use of similar scales (MMAS-8) (in Nigerian & Turkish study) to assess adherence in these studies.

However, the prevalence of adherence to ASMs in our study was significantly lower than the study done in 94 children in the Kingdom of Saudi Arabia(61.7%) in 2015 [ 14 ]. The possible justification for the disparities between these studies might be due to different demographic status including socio-economic status and higher literacy ratio, lower study population( N  = 94) and use of earlier scale (MMAS-4) to assess adherence in this study; and also lower than the study done in Uganda(79.5%) in 2014 [ 13 ], this difference might be because of higher literacy ratio and use of different scales to assess adherence to ASM (self report- focus group discussion).

The prevalence of adherence to ASMs in this study was higher than that of studies done in Pakistan(42%) in 2018 [ 18 ], USA(42%) in 2011 [ 17 ], Bangladesh (38.8%) in 2015 [ 21 ], Indian subcontinent(29%) in 2018 [ 15 ] and Western China(27.3%) in 2020 [ 16 ]; these differences might be due to long duration of studies (USA and Bangladesh) and use of different adherence measuring scales(e.g. Electronic method to measure adherence in study done in USA) and different definitions of adherence to ASMs(e.g. moderate and low adherence were considered as ‘poor adherence’ in study done in Western China and Indian Subcontinent).

There were different factors contributing to the adherence to prescribed anti-seizure medications. The current study identified marital status of the caregivers; i.e. being married caregiver(s)/parent(s) was associated with the adherence. This might be due to stable and full family support (similar with the study done in KSA, 2015). Others associated with adherence to ASMs include children/adolescents whose seizure was controlled might be due to treatment satisfaction and frequency of seizure will increase in those who were non- adherent to thier medications (in study done in KSA, 2015). Parents/caregivers who recieved appropriate health care in the hospital during follow- up visit were more than 6 times adherent to their ASMs; this was due to smooth and friendly communication with hospital staff (which was similar with the study done in KSA, 2015) and also might be due to recieving of appropriate health/drug information from medical staff (similar with the study done in W. China, 2020); those parents/caregivers whose knowledge about epilepsy was good (about 6 times) and positive attitude (about 3 times) towards epilepsy were more adherent to ASMs (increased awareness about epilepsy & ASMs might contribute, supported by study done in Turkey, 2020).

In a study done in South Africa [ 11 ], long duration of therapy and medications (Oxcarbamazepine, Valproic acid and Phenytoin) were significantly associated with adherence to ASMs; the age of the patients, type of epilepsy, total household income and source of drug information in Western China [ 16 ]; monotherapy, good family support & lower frequency of seizures (similar to our study) in KSA [ 14 ] were significantly associated with adherence to ASMs.

Unlike our study, higher family socioeconomic status was significantly associated with ASM adherence in a study done in USA [ 17 ]; low socioeconomic status, multiple drug intake & long duration of therapy were significantly associated with ASM non-adherence in Joe, Nigeria [ 12 ].

Seizure control status is a key to adherence to ASMs which helps patients stick to their medications. In this study, seizure control status was significantly associated with adherence. Our finding was similar to the study done in Indian Subcontinent (seizure control = 51.78%) in which one or more seizure episodes in the past 3 months (un-controlled seizure) adversely affected ASM adherence [ 15 ] and higher than the study done in Bangladesh (33.6% seizure control status) which was significantly associated with adherence to ASMs [ 21 ]. In contrast to our study, age of the child (0–5 years, because drugs are given by the patients/caregivers, while adolescents usually manage their own treatment) was significantly associated with ASM adherence in a study done in Turkey [ 19 ].

Being on multiple medications can lead to non-adherence in many ways; including increased medication cost, pill burden and more adverse drug reactions. Pill burden is particularly a problem in children and adolescents and refusal to take drugs is worse with increasing number of medications. Poly-therapy is more likely to be associated with drug toxicity [ 12 ]. Nearly two third (108, 63.5%) of our study participants were on mono-therapy (similar to study done in Nigeria, 59.3%) [ 12 ], from this ‘Phenytoin only’ accounted for nearly half (82, 48.2%) of cases; from those (those on mono-therapy) more than half of them were adherent to their medication(s) but mode of therapy was not associated with adherence status to ASMs in this study.

Parents’/caregivers’ knowledge about epilepsy was similar to the study done in Ethiopia (North Shoa, 2018) (56.4%) [ 23 ]; similar cultural, economic, and sociodemographic features might contribute. Our finding was significantly associated with adherence to ASMs; similar with the study done in Turkey (caregivers’ health literacy knowledge was significantly associated with ASMs adherence,) [ 19 ]; and our finding was significantly higher in comparison to the study done in India (10/60, 16.7%) [ 25 ], this difference might be due to small sample size( N  = 60).

Parents’/caregivers’ positive attitude towards epilepsy was significantly associated with adherence status to ASMs which was comparable with the study done in India (55%) [ 25 ] and it was comparable with the study done in Ethiopia (North Shoa, 2018)(58.7%) [ 23 ].

Limitations

Hence the actual prevalence of adherence to ASM(s) may be even lower because we used parent/caregiver and/or adolescent-report to assess adherence status which may be subjected to recall bias as some may feel pressured to give acceptance responses to gain positive reaction from data collectors/health care workers.

The research was done in single institution which may not help to generalize the findings of this study for regional or country level and samples were taken from hospital which might not be representative as many patients may not come to hospital despite their illness for different reasons.

Further, many patients were not had EEG for the diagnosis of epilepsy; thus diagnosis of epilepsy and initiation of ASMs was based on clinical evidences.

Lastly, sample size was drawn based on study done in Nigeria which is far from our study area (Ethiopia).

Availability of data and materials

All materials and data are available from the corresponding author without any restriction.

Abbreviations

Anti-seizure medication

Community based health insurance

Cerebral palsy

Data collector

Ethiopian birr

Health management information system

International league against epilepsy

Institutional review board

• Jimma medical center

Kingdom of Saudi Arabia

Status epilepticus

Sub-saharan Africa

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Acknowledgments

We would like to acknowledge Jimma University for the approval of ethical clearance and funding support of this study. We would like to express our gratitude to health care professionals of Jimma Medical Center for their unreserved support during the work. Our acknowledgment extends to the study participants (children, adolescents and their parents/caregivers), data collectors; and supervisors who participated in the study.

This study was sponsored by Jimma University, Ethiopia.

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Hawi Mohammed

School of Medicine, Werabe University, Werabe, Ethiopia

Kemal Lemnuro

Department of Pediatrics and Child Health, Jimma University, Jimma, Ethiopia

Teferi Mekonnen

School of Pharmacy, Institute of Heath, Jimma University, Jimma, Ethiopia

Tsegaye Melaku

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The analysis was conceptualized by HM, TM and TSM. Data collection was managed by HM and KL. Data analysis was conducted by HM, TM and TSM. HM drafted the manuscript. HM, KL, TM and TSM were participated in editing, feedback and revisions. The author(s) read and approved the final manuscript.

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Correspondence to Hawi Mohammed .

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Ethical approval for the study was obtained from institutional review board (IRB) of Institute of Health, Jimma University (Ref. No. IHRPGn/308/2021). Data was collected after informed verbal consent is obtained from the participants. The study was conducted in accordance with the Declaration of Helsinki and adhered to Good Clinical Practice guidelines. Confidentiality of the information was maintained by excluding names as identification in the questionnaire & keeping their privacy during the data collection.

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Mohammed, H., Lemnuro, K., Mekonnen, T. et al. Adherence to anti-seizure medications and associated factors among children with epilepsy at tertiary Hospital in Southwest Ethiopia: a cross-sectional study. BMC Neurol 22 , 310 (2022). https://doi.org/10.1186/s12883-022-02842-8

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Listen to specialist Lily Wong-Kisiel, M.D., walk through the epilepsy basics.

Mayo Clinic Explains Epilepsy

Lily Wong-Kisiel, M.D., Pediatric Neurologist, Mayo Clinic:

Hi, I'm Dr. Lily Wong-Kisiel, a pediatric neurologist at Mayo Clinic. In this video, we'll cover the basics of epilepsy. What is it? Who gets it? The symptoms diagnosis and treatment. Whether you're looking for answers for yourself or someone you love, we're here to give you the best information available. First of all, epilepsy is common. Around 3 million people in the U.S. have epilepsy, making it the fourth most common neurological disease after migraine, stroke and Alzheimer's. Epilepsy happens as a result of abnormal electrical brain activity, also known as a seizure, kind of like an electrical storm inside your head. And because your brain controls so much, a lot of different things can go wrong. You may have periods of unusual behaviors, feelings and sometimes loss of awareness. There are many types of seizures, including two main categories: focal, meaning they start in a particular part of your brain, or generalized, meaning the seizures initially involve all areas of the brain. There are some myths about epilepsy we can dismiss. If you are with someone experiencing a seizure, don't put anything in their mouth. They can't actually swallow their tongue. Don't restrain them. And don't worry, epilepsy isn't contagious, so you can't catch it.

Who gets it?

Although children or older adults are more susceptible, anyone can develop epilepsy. When epilepsy is diagnosed in older adults, it's sometimes from another neurological issue, like a stroke or a brain tumor. Other causes can be related to genetic abnormalities, prior brain infection, prenatal injuries or developmental disorders. But in about half of people with epilepsy, there's no apparent cause.

What are the symptoms?

Because they happen in the brain, seizures can affect any process your brain handles. Therefore, symptoms can vary. Many individuals with epilepsy tend to have the same type of seizure each time. However, some will have more than one type. So, how do you recognize a seizure? Keep an eye out for temporary confusion, a staring spell, uncontrollable jerking, loss of consciousness, fear, anxiety or deja vu.

How is it diagnosed?

Even after having a single seizure, sometimes the diagnosis of epilepsy can't be made. Regardless, if you do have something that seems like a first-time seizure, see a physician. Your doctor may assess your motor abilities, mental function and other areas to diagnose your condition and determine if you have epilepsy. They may also order additional diagnostic tests. They could include neurological exam, blood tests, EEG , CT scan, brain imaging and sometimes neuropsychological tests. Because your brain is such a complicated piece of machinery, neurologists, epileptologists, neurosurgeons, neuroradiologists, mental health specialists, and other professionals all work together to provide exactly the care you need.

How is it treated?

The best care starts with an accurate diagnosis. The medications we have for epilepsy are incredibly effective. More than half of the cases are seizure-free after their first medication. But when medication does not work at stopping seizures completely, there are other emerging ways of treating epilepsy, including surgery and brain stimulation. And a comprehensive level 4 epilepsy center can help find you the best way to manage your care. For patients undergoing treatment, it's important to keep a detailed seizure journal. Each time you have a seizure, write down the time, the type and how long it lasted, making note of anything out of the ordinary, like missed medication, sleep deprivation, increased stress, menstruation, or anything else that could trigger it.

Though we don't always know why people suffer from epilepsy, ongoing research continues to build our knowledge and improve treatment options. And better treatment means happier patients. If you'd like to learn even more about epilepsy, watch our other related videos or visit mayoclinic.org. We wish you well.

Epilepsy — also known as a seizure disorder — is a brain condition that causes recurring seizures. There are many types of epilepsy. In some people, the cause can be identified. In others, the cause is not known.

Epilepsy is common. It's estimated that 1.2% of people in the United States have active epilepsy, according to the Centers for Disease Control and Prevention. Epilepsy affects people of all genders, races, ethnic backgrounds and ages.

Seizure symptoms can vary widely. Some people may lose awareness during a seizure while others don't. Some people stare blankly for a few seconds during a seizure. Others may repeatedly twitch their arms or legs, movements known as convulsions.

Having a single seizure doesn't mean you have epilepsy. Epilepsy is diagnosed if you've had at least two unprovoked seizures at least 24 hours apart. Unprovoked seizures don't have a clear cause.

Treatment with medicines or sometimes surgery can control seizures for most people with epilepsy. Some people require lifelong treatment. For others, seizures go away. Some children with epilepsy may outgrow the condition with age.

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Seizure symptoms vary depending on the type of seizure. Because epilepsy is caused by certain activity in the brain, seizures can affect any brain process. Seizure symptoms may include:

• Temporary confusion.
• A staring spell.
• Stiff muscles.
• Uncontrollable jerking movements of the arms and legs.
• Loss of consciousness.
• Psychological symptoms such as fear, anxiety or deja vu.

Sometimes people with epilepsy may have changes in their behavior. They also may have symptoms of psychosis.

Most people with epilepsy tend to have the same type of seizure each time. Symptoms are usually similar from episode to episode.

Warning signs of seizures

Some people with focal seizures have warning signs in the moments before a seizure begins. These warning signs are known as aura.

Warning signs might include a feeling in the stomach. Or they might include emotions such as fear. Some people might feel deja vu. Auras also might be a taste or a smell. They might even be visual, such as a steady or flashing light, a color, or a shape. Some people may experience dizziness and loss of balance. And some people may see things that aren't there, known as hallucinations.

Seizures are classified as either focal or generalized, based on how and where the brain activity causing the seizure begins.

When seizures appear to result from activity in just one area of the brain, they're called focal seizures. These seizures fall into two categories:

• Focal seizures without loss of consciousness. Once called simple partial seizures, these seizures don't cause a loss of awareness, also known as consciousness. They may alter emotions or change the way things look, smell, feel, taste or sound. Some people experience deja vu. This type of seizure also may result in involuntary jerking of a body part, such as an arm or a leg. And focal seizures may cause sensory symptoms such as tingling, dizziness and flashing lights.
• Focal seizures with impaired awareness. Once called complex partial seizures, these seizures involve a change or loss of consciousness. This type of seizure may seem like being in a dream. During a focal seizure with impaired awareness, people may stare into space and not respond in typical ways to the environment. They also may perform repetitive movements, such as hand rubbing, chewing, swallowing or walking in circles.

Symptoms of focal seizures may be confused with other neurological conditions, such as migraine, narcolepsy or mental illness. A thorough exam and testing are needed to tell if symptoms are the result of epilepsy or another condition.

Focal seizures may come from any lobe of the brain. Some types of focal seizures include:

• Temporal lobe seizures. Temporal lobe seizures begin in the areas of the brain called the temporal lobes. The temporal lobes process emotions and play a role in short-term memory. People who have these seizures often experience an aura. The aura may include sudden emotion such as fear or joy. It also may be a sudden taste or smell. Or an aura may be a feeling of deja vu, or a rising sensation in the stomach. During the seizure, people may lose awareness of their surroundings. They also may stare into space, smack their lips, swallow or chew repeatedly, or have movements of their fingers.
• Frontal lobe seizures. Frontal lobe seizures begin in the front of the brain. This is the part of the brain that controls movement. Frontal lobe seizures cause people to move their heads and eyes to one side. They won't respond when spoken to and may scream or laugh. They might extend one arm and flex the other arm. They also might make repetitive movements such as rocking or bicycle pedaling.
• Occipital lobe seizures. These seizures begin in the area of the brain called the occipital lobe. This lobe affects vision and how people see. People who have this type of seizure may have hallucinations. Or they may lose some or all of their vision during the seizure. These seizures also might cause eye blinking or make the eyes move.

Generalized seizures

Seizures that appear to involve all areas of the brain are called generalized seizures. Generalized seizures include:

• Absence seizures. Absence seizures, previously known as petit mal seizures, typically occur in children. Symptoms include staring into space with or without subtle body movements. Movements may include eye blinking or lip smacking and only last 5 to 10 seconds. These seizures may occur in clusters, happening as often as 100 times a day, and cause a brief loss of awareness.
• Tonic seizures. Tonic seizures cause stiff muscles and may affect consciousness. These seizures usually affect muscles in the back, arms and legs and may cause the person to fall to the ground.
• Atonic seizures. Atonic seizures, also known as drop seizures, cause a loss of muscle control. Since this most often affects the legs, it often causes sudden falls to the ground.
• Clonic seizures. Clonic seizures are associated with repeated or rhythmic jerking muscle movements. These seizures usually affect the neck, face and arms.
• Myoclonic seizures. Myoclonic seizures usually appear as sudden brief jerks or twitches and usually affect the upper body, arms and legs.
• Tonic-clonic seizures. Tonic-clonic seizures, previously known as grand mal seizures, are the most dramatic type of epileptic seizure. They can cause a sudden loss of consciousness and body stiffening, twitching and shaking. They sometimes cause loss of bladder control or biting of the tongue.

When to see a doctor

Seek immediate medical help if any of the following occurs with a seizure:

• The seizure lasts more than five minutes.
• Breathing or consciousness doesn't return after the seizure stops.
• A second seizure follows immediately.
• You have a high fever.
• You're pregnant.
• You have diabetes.
• You've injured yourself during the seizure.
• You continue to have seizures even though you've been taking anti-seizure medicine.

If you have a seizure for the first time, seek medical advice.

Epilepsy has no identifiable cause in about half the people with the condition. In the other half, the condition may be traced to various factors, including:

Genetic influence. Some types of epilepsy run in families. In these instances, it's likely that there's a genetic influence. Researchers have linked some types of epilepsy to specific genes. But some people have genetic epilepsy that isn't hereditary. Genetic changes can occur in a child without being passed down from a parent.

For most people, genes are only part of the cause of epilepsy. Certain genes may make a person more sensitive to environmental conditions that trigger seizures.

• Head trauma. Head trauma as a result of a car accident or other traumatic injury can cause epilepsy.
• Factors in the brain. Brain tumors can cause epilepsy. Epilepsy also may be caused by the way blood vessels form in the brain. People with blood vessel conditions such as arteriovenous malformations and cavernous malformations can have seizures. And in adults older than age 35, stroke is a leading cause of epilepsy.
• Infections. Meningitis, HIV , viral encephalitis and some parasitic infections can cause epilepsy.
• Injury before birth. Before they're born, babies are sensitive to brain damage that could be caused by several factors. They might include an infection in the mother, poor nutrition or not enough oxygen. This brain damage can result in epilepsy or cerebral palsy.
• Developmental conditions. Epilepsy can sometimes occur with developmental conditions. People with autism are more likely to have epilepsy than are people without autism. Research also has found that people with epilepsy are more likely to have attention-deficit/hyperactivity disorder (ADHD) and other developmental conditions. Having both conditions may be related to genes.

Seizure triggers

Seizures can be triggered by things in the environment. Seizure triggers don't cause epilepsy, but they may trigger seizures in people who have epilepsy. Most people with epilepsy don't have reliable triggers that always cause a seizure. However, they often can identify factors that make it easier to have a seizure. Possible seizure triggers include:

• Flashing lights.
• Illicit drug use.
• Skipping doses of antiseizure medicines or taking more than prescribed.
• Lack of sleep.
• Hormone changes during the menstrual cycle.
• Dehydration.
• Skipped meals.

Risk factors

Certain factors may increase your risk of epilepsy:

• Age. The onset of epilepsy is most common in children and older adults, but the condition can occur at any age.
• Family history. If you have a family history of epilepsy, you may be at an increased risk of seizures.
• Head injuries. Head injuries are responsible for some cases of epilepsy. You can reduce your risk by wearing a seat belt while riding in a car. Also wear a helmet while bicycling, skiing, riding a motorcycle or doing any activities with a high risk of head injury.
• Stroke and other vascular diseases. Stroke and other blood vessel diseases can cause brain damage. Brain damage may trigger seizures and epilepsy. You can take steps to reduce your risk of these diseases. Limit alcohol, don't smoke, eat a healthy diet and exercise regularly.
• Dementia. Dementia can increase the risk of epilepsy in older adults.
• Brain infections. Infections such as meningitis, which causes inflammation in the brain or spinal cord, can increase your risk.
• Seizures in childhood. High fevers in childhood can sometimes be associated with seizures. Children who have seizures due to high fevers generally won't develop epilepsy. The risk of epilepsy increases if a child has a long fever-associated seizure, another nervous system condition or a family history of epilepsy.

Complications

Having a seizure at certain times can be dangerous to yourself or others.

• Falling. If you fall during a seizure, you can injure your head or break a bone.
• Drowning. People with epilepsy are 13 to 19 times more likely to drown while swimming or bathing than people without epilepsy. The risk is higher because you might have a seizure while in the water.

Car accidents. A seizure that causes either loss of awareness or control can be dangerous if you're driving a car or operating other equipment.

Many states have driver's license restrictions related to a driver's ability to control seizures. In these states, there is a minimum amount of time that a driver must be seizure-free before being cleared to drive. The amount of time may range from months to years.

• Trouble with sleep. People who have epilepsy may have trouble falling asleep or staying asleep, known as insomnia.

Pregnancy complications. Seizures during pregnancy pose dangers to both mother and baby. Also, certain anti-seizure medicines increase the risk of birth defects. If you have epilepsy and you're considering becoming pregnant, get medical help as you plan your pregnancy.

Most women with epilepsy can become pregnant and have healthy babies. You need to be carefully monitored throughout pregnancy. Your medicines may need to be adjusted. It's very important that you work with your healthcare team to plan your pregnancy.

• Memory loss. People with some types of epilepsy have trouble with memory.

Emotional health issues

People with epilepsy are more likely to have mental health conditions. They may be a result of dealing with the condition itself as well as medicine side effects. But even people with well-controlled epilepsy are at increased risk. Emotional health problems that may affect people with epilepsy include:

• Depression.
• Suicidal thoughts and behaviors.

Other life-threatening complications of epilepsy are not common but may happen. These include:

• Status epilepticus. This condition occurs if you're in a state of continuous seizure activity lasting more than five minutes. Or it may occur if you have seizures without regaining full consciousness in between them. People with status epilepticus have an increased risk of permanent brain damage and death.

Sudden unexpected death in epilepsy (SUDEP). People with epilepsy also have a small risk of sudden unexpected death. The cause is unknown, but some research shows that it may occur due to heart or respiratory conditions.

People with frequent tonic-clonic seizures or people whose seizures aren't controlled by medicines may be at higher risk of SUDEP . Overall, about 1% of people with epilepsy die of SUDEP . It's most common in those with severe epilepsy that doesn't respond to treatment.

Epilepsy care at Mayo Clinic

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• Lundstrom BL, et al. Emerging approaches in neurostimulation for epilepsy. Current Opinion in Neurology. 2023; doi:10.1097/WCO.0000000000001138.
• Lescrauwaet E, et al. Recent advances in the use of focused ultrasound as a treatment for epilepsy. Frontiers in Neuroscience. 2022; doi:10.3389/fnins.2022.886584.
• Tavakoli H, et al. Literature review of the efficacy of repetitive transcranial magnetic stimulation on epilepsy. Iranian Journal of Child Neurology. 2023; doi:10.22037/ijcn.v17i2.38752.
• Sudbrack-Oliveira P, et al. Transcranial direct current stimulation (tDCS) in the management of epilepsy: A systematic review. 2021; doi:10.1016/j.seizure.2021.01.020.
• Frequently asked questions about epilepsy. Centers for Disease Control and Prevention. https://www.cdc.gov/epilepsy/about/faq.htm. Accessed Jan. 25, 2023.
• Ami TR. Allscripts EPSi. Mayo Clinic. June 1, 2023.
• Genetic causes of epilepsy. Epilepsy Foundation. https://www.epilepsy.com/causes/genetic. Accessed, Jan. 30, 2023.
• Find an epilepsy center. National Association of Epilepsy Centers. https://www.naec-epilepsy.org/about-epilepsy-centers/find-an-epilepsy-center/. Accessed Aug. 17, 2023.
• Imdad K, et al. The metabolic role of ketogenic diets in treating epilepsy. Nutrients. 2022; doi:10.3390/nu14235074.
• Hirota T, et al. Autism spectrum disorder: A review. JAMA. 2023; doi:10.1001/jama.2022.23661.
• Behind the seizure program. Invitae. https://www.invitae.com/en/sponsored-testing/behind-the-seizure. Accessed March 10, 2023.
• Cortes-Albornoz MC, et al. Maternal nutrition and neurodevelopment: A scoping review. Nutrients. 2021; doi:10.3390/nu13103530.
• Burkholder DB (expert opinion). Mayo Clinic. Aug. 19, 2023.
• Epilepsy FAQs
• How your brain works
• Infographic: Epilepsy and Brain Mapping
• Infographic: Pediatric Epilepsy Early Intervention
• Mayo Clinic Minute: Demystifying epilepsy
• MRI of deep brain stimulation
• Neurontin side effects: How do I manage them?
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News from Mayo Clinic

• Mayo Clinic Minute: Using lasers on the brain to treat seizures April 24, 2024, 02:05 p.m. CDT
• Mayo Clinic Minute: Common myths about epilepsy and kids Sept. 27, 2023, 02:27 p.m. CDT
• Mayo Clinic Minute: Why kids with epilepsy need a seizure action plan Aug. 23, 2023, 03:51 p.m. CDT
• Laser ablation surgery helps treat young man's epilepsy July 06, 2023, 02:41 p.m. CDT
• Mayo Clinic Q and A: Advances in care for medication-resistant epilepsy March 01, 2023, 04:30 p.m. CDT
• Mayo Clinic Minute: A surgery option when epilepsy treatments don't work Feb. 06, 2023, 05:00 p.m. CDT
• Mayo Clinic Q&A podcast: The latest options for treating epilepsy Nov. 21, 2022, 01:30 p.m. CDT
• Mayo Clinic Minute: Demystifying epilepsy Nov. 08, 2022, 05:00 p.m. CDT
• Ask the Mayo Mom: Navigating a new epilepsy diagnosis Nov. 04, 2022, 01:09 p.m. CDT

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Rapport’s Stock Market Debut Reaps $154M as Novel Epilepsy Med Heads for Mid-Stage Test

Rapport Therapeutics’ IPO came with a concurrent private placement that boosted the biotech’s cash haul. The new capital will support clinical development of a lead drug with a novel approach to focal epilepsy, a form of the disorder that affects 1.8 million people in the U.S.

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Rapport Therapeutics, a company whose neuroscience technology comes from Johnson & Johnson, joined the public markets Friday, raising $154 million for proof-of-concept testing of a lead program in development for a common form of epilepsy.

Rapport had revealed its plans to go public last month . Late Thursday, the biotech priced its offering of 8 million shares at $17 apiece, which was the midpoint of the price range it set earlier this week. At that price, the Boston-based company’s IPO raised $136 million. Concurrent with the stock offering, Rapport raised another $18 million in a private placement, bringing total proceeds to $154 million.

Shares of Rapport now trade on the Nasdaq under the stock symbol “RAPP.” In Rapport’s first day of trading, its shares closed at $20.80 apiece, up 22.3% from the IPO price.

Unlocking Transparency in PBM Pricing

The TSX Venture Exchange has a strong history of helping early-stage health and life sciences companies raise patient capital for research and development.

Lead Rapport drug candidate RAP-219 is being developed as a treatment for focal epilepsy, a form of the disorder caused by intermittent abnormal electrical activity in certain parts of the brain. An estimated 1.8 million people in the U.S. have focal epilepsy, accounting for 60% of epilepsy patients, Rapport said in its IPO filing . Focal epilepsy can be treated with anti-seizure medicines that hit the AMPA receptor. But this receptor is found throughout the brain, so hitting it can lead to serious side effects that lead many patients to stop using AMPA-targeting drugs.

Rapport aims to more selectively hit AMPA receptors, which could vastly improve the side effect profile. The company’s small molecule drugs target receptor associated proteins (RAPs), proteins that regulate receptor expression and function. RAP-219 targets a RAP for the AMPA receptor found only in certain regions of the brain. In the IPO filing, Rapport says this approach offers the potential for a wider therapeutic index, the range of doses in which a therapy is effective without causing unacceptable adverse effects. The company is also exploring other neurological indications for its lead molecule.

RAP-219 and the RAP platform technology that developed the drug were licensed from Janssen, a Johnson & Johnson subsidiary. The biotech is preparing to advance its lead drug candidate to a Phase 2a proof-of-concept test. The company’s pipeline also includes RAP-199, a drug that targets the same RAP as RAP-219, but in a way that offers different chemical and pharmacokinetic properties.

Since its 2022 launch, Rapport had raised about $250 million prior to the IPO, the prospectus shows. Founding investors Third Rock Ventures and Johnson & Johnson Innovation—JJDC respectively own 22.9% and 7% post-IPO stakes of the company, according to the filing. Arch Venture Partners owns a 10.5% stake in Rapport. The private placement consists of 1.06 million shares sold at the IPO price. The buyers are Sofinnova Ventures and Goldman Sachs, the filing shows. As of the end of the first quarter of this year, Rapport reported a $193.2 million cash position. Rapport said it expects that money, together with the new capital raised, will support the company through the end of 2026.

When Investment Rhymes with Canada

Canada has a proud history of achievement in the areas of science and technology, and the field of biomanufacturing and life sciences is no exception.

Rapport will put its new capital to work right away on RAP-219’s mid-stage clinical trial, expected to start in the second half of this year. The company has budgeted $100 million to take this program through the completion of proof-of-concept trials in focal epilepsy, peripheral neuropathic pain, and bipolar disorder. Another $40 million is earmarked for a second multiple-ascending dose study and positron emission tomography trial, and for advancing development of a long-acting version of RAP-219. The company also plans to advance RAP-199 through Phase 1 development.

Photo: Getty Images

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Likelihood of Approval and Phase Transition Success Rate Model – PRAX-628 in Epilepsy

Unlock hidden opportunities in the LoA industry

Published: May 20, 2024 Report Code: GDHCDR30718LOA-MP-L5

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Empower your strategies with our Likelihood of Approval and Phase Transition Success Rate Model – PRAX-628 in Epilepsy report and make more profitable business decisions.

This report provides you with the data that allows you to track and predict the specific likelihood of approval (LOA) and phase transition success rate (PTSR) of a drug using GlobalData’s proprietary machine learning algorithms developed using over 10 years of historical data.

PRAX-628 in Epilepsy Drug Details:

PRAX-628 is under development for the treatment of focal onset epilepsy. It acts by targeting voltage-gated sodium (Nav). It is administered through oral route. It is developed based on CEREBRUM small molecule platform.

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The data is segmented by drug name per indication and shows the current likelihood of approval for the drug compared to the indication benchmark and the industry benchmark.

The Likelihood of Approval data is updated regularly based on events that take place which impact the clinical development process and regulatory considerations. GlobalData’s proprietary machine learning models consider these events in real time, to produce quantitative changes to the LOA and PTSR along with qualitative reasoning why the likelihood of approval has changed.

· Drug type · Intervention type · PRAX-628 · Oral · Central Nervous System · Praxis Precision Medicines Inc · Phase II Reasons to Buy Precise Likelihood of Approval and Phase Transition Success Rates: Our machine learning and proprietary models provide accurate predictions, helping you gauge the potential success of a drug in the regulatory process. Competitive Strategy Planning: Access information on LOA and PTSR for competitors’ drugs, allowing you to plan your clinical development, commercialisation and marketing strategies Event-driven Updates: Track event-driven changes in LOA and PTSR benchmarked against indication LOA/PTSR. Get the latest insights to adapt your strategies promptly! Well-informed Investment Decisions: This data helps you navigate the dynamic landscape of drug development and regulatory considerations. 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Access a live Likelihood of Approval and Phase Transition Success Rate Model – PRAX-628 in Epilepsy dashboard for 12 months, with up-to-the-minute insights. Fuel your decision making with real-time deal coverage and media activity. Turn insights on financials, deals, products and pipelines into powerful agents of commercial advantage. 152 COMMENTS Journal of Epilepsy Research REVIEW. 2023 December 31. Issues of Women with Epilepsy and Suitable Antiseizure Drugs. Seizure aggravation in women with epilepsy (WWE) tends to occur at two specific times during the menstrual cycle: the perimenstrual phase and the ovulation period. Antiseizure drugs (ASDs), especially those that induce enzymes, can accelerate the metabolism ... Epilepsy Research Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most …. View full aims & scope. Epilepsy Here authors recorded SWRs from hippocampus of 10 epilepsy patients for up to 15 days with experience sampling. ... Research Open Access 21 May 2024 Scientific Reports. ... Research Highlights 05 ... EBR EBR accepts most types of manuscripts for consideration including original research papers, case reports, case report series, short communications, reviews, letters to the editor, opinions and editorials. Topics considered will be from seizure- and epilepsy-related fields that are of interest to practicing physicians all over the world. Major advances in epilepsy research in 2023 With great anticipation, 2023 has seen many important advances in epilepsy research. Noteworthy progress has been achieved in understanding the intricate mechanisms of epilepsy, accompanied by important strides in developing new therapies. Historically, the efficacy of most second-generation and third-generation antiseizure medications in ... The 2021 Epilepsy Research Benchmarks—Respecting Core Principles Between 2014 and the present, the Benchmarks Committee reviewed progress in each of the 4 benchmarks areas, noting remarkable discoveries across basic epilepsy research, highlighting the major gains in understanding the causes of epilepsy, but also noting many continued gaps in all areas. 9-13 We have experienced a cultural shift through which the voices of patients and advocates are not only ... Epilepsia Epilepsia. Epilepsia is the leading, authoritative journal for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy. Epilepsia Open Epilepsia Open is the open access journal of the ILAE, publishing rigorous basic and clinical epilepsy research or critical reviews aiming to promote the dissemination, transparency, translatability, and implementation of epilepsy research advances. Reasons to Publish with Us: Detailed Author Guidelines with discounted APC rate for ILAE members. Epilepsy Currents: Sage Journals Epilepsy Currents is a bi-monthly open access current-awareness journal providing reviews, commentaries and abstracts from the world's literature on the research and treatment of epilepsy.Epilepsy Currents surveys and comments on all important research and developments in a format that is easy to read and reference. An outstanding Editorial Board reviews the literature and assigns topics and ... Prediction and detection of human epileptic seizures based on ... French, J. A. et al. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality ... Epilepsy Research 2005 — Volumes 63-67. Page 1 of 2. Incorporating Journal of Epilepsy; Read the latest articles of Epilepsy Research at ScienceDirect.com, Elsevier's leading platform of peer-reviewed scholarly literature. Epilepsy New research reports changes in serum blood-brain barrier (BBB) markers after bilateral tonic-clonic seizures, corroborating earlier observations in animal models. ... Headaches and epilepsy ... What the Top Ten epilepsy research priorities mean for the UK research The UK Epilepsy PSP was a once-in-a-generation, national consensus that followed the JLA methodology to identify the epilepsy community's Top Ten priorities for research into epilepsy. The PSP involved people with epilepsy, their families and carers, those bereaved by epilepsy, clinicians and health and social care professionals and patient ... Recent advances in epilepsy The repertoire of AED considered effective in IGE has traditionally been more restricted that for focal epilepsy. Case reports have supported the use of lacosamide [112, ... Epileptogenesis is a fertile area of research and everolimus, an inhibitor of the mTor pathway, has demonstrated efficacy in epilepsy associated with TS, showing the ... Focus On Epilepsy Research Focus On Epilepsy Research. Image. The epilepsies are a set of disorders characterized by recurring seizures, or disturbances in the electrical activity of the brain. Epilepsy affects people of all ages, from infants to the aged, and can result from many causes, including genetic variations, illness, head injury, or abnormal brain development. Epilepsy & Behavior Reports Epilepsy & Behavior Reports. Following the first issue of Epilepsy Behavior Case Reports (EBCR) published in 2013, our journal is undergoing a metamorphosis. EBCR has seen not only significant traffic in the number of submitted manuscripts from all over the globe, but also growth in the type of manuscripts beyond case reports. Epilepsy Reports Epilepsy - Epidemiology - Americas. Clarivate Epidemiology's coverage of epilepsy comprises epidemiological estimates of key patient populations in 45 countries worldwide. We report the prevalence of epilepsy for each country, as…. 1. 2. 3. Optimize your long-term Epilepsy strategy and validate your forecasts with comprehensive market ... The Relationship Between Sleep, Epilepsy, and Development: a Review Purpose of Review To review the relationship between sleep, neurodevelopment, and epilepsy and potential underlying physiological mechanisms. Recent Findings Recent studies have advanced our understanding of the role of sleep in early brain development and epilepsy. Epileptogenesis has been proposed to occur when there is a failure of normal adaptive processes of synaptic and homeostatic ... Research implications of the Institute of Medicine Report, Epilepsy In March 2012 the Institute of Medicine (IOM) released the report, Epilepsy Across The Spectrum: Promoting Health and Understanding. This report examined the public health dimensions of the epilepsies with a focus on the following four areas: public health surveillance and data collection and integration; population and public health research; health policy, health care, and human services ... Epilepsy Research Benchmarks Overview In late 2019, the Epilepsy Benchmark Stewards Committee, coordinated by the American Epilepsy Society, started the process of revising the Epilepsy Research Benchmarks by publishing progress reports for each of the four benchmark areas. These articles were published in Epilepsy Currents in early 2020. (PDF) A COMPREHENSIVE REVIEW ON EPILEPSY Abstract. Epilepsy is commonly known as seizure-associated medical conditions either morbid or comorbid altogether. Although many different procedures were determined for diagnosing and treating ... Epilepsy Epilepsy is a chronic noncommunicable disease of the brain that affects people of all ages. Around 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally. Nearly 80% of people with epilepsy live in low- and middle-income countries. It is estimated that up to 70% of people living with epilepsy ... Epilepsy Research Benchmarks Plain Language The Epilepsy Research Benchmarks were published in 2021. This page is a plain language summary of those benchmarks. Area 1: Understand what causes the many types of the epilepsies and commonly co-occurring symptoms people experience. Learn more about genetics and how changes in some genes result in seizures and epilepsy. ICARE Epilepsy Research Portfolio Reports and publications related to the ICARE Epilepsy Research Portfolio ... The Epilepsy Research Connection (ERC) is connecting researchers with funding opportunities from the leading epilepsy organizations. The ERC website provides a single place for researchers to search for funding. Adherence to anti-seizure medications and associated factors among Background Childhood epilepsy causes a tremendous burden for the child, the family, society as well as the healthcare system. Adherence to anti-seizure medications (ASMs) is a key to treatment success. Poor adherence has been considered as one of the main causes of unsuccessful treatment for epilepsy and presents a potential ongoing challenge for achieving a key therapeutic goal of seizure ... Guide for authors Epilepsy & Behavior Reports (EBR) is an online-only, open access journal devoted to the rapid publication of case studies on the behavioral aspects of seizures and epilepsy. EBR places special emphasis on articles that: 1. Educate clinicians around the world regarding the best practices and clinical research for global epilepsy management of patients, Epilepsy Though we don't always know why people suffer from epilepsy, ongoing research continues to build our knowledge and improve treatment options. And better treatment means happier patients. ... Quintiliani M, et al. Role of high-density EEG (hdEEG) in pre-surgical epilepsy evaluation in children: Case report and review of the literature. Child's ... Ketogenic Diet For Epilepsy / Seizures The ketogenic diet, or keto diet, is a medical or therapeutic diet — a diet designed to help manage or treat a medical condition. The keto diet is suggested for children with epilepsy that continues despite medication. The keto diet is high in fat, adequate in protein and very low in carbohydrates (carbs). A typical keto diet consists of 70% ... Rapport's Stock Market Debut Reaps $154M as Novel Epilepsy Med Heads An estimated 1.8 million people in the U.S. have focal epilepsy, accounting for 60% of epilepsy patients, Rapport said in its IPO filing. Focal epilepsy can be treated with anti-seizure medicines ... Likelihood of Approval and Phase Transition Success Rate Model This report provides you with the data that allows you to track and predict the specific likelihood of approval (LOA) and phase transition success rate (PTSR) of a drug using GlobalData's proprietary machine learning algorithms developed using over 10 years of historical data. PRAX-628 in Epilepsy Drug Details: assignment essay homework paper phd report resume review speech thesis