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About one-third of people with epilepsy will continue having seizures despite medications. What is the clinical definition of drug-resistant epilepsy? Why does it occur, and is it possible to predict? Dr. Cecilie Nome interviews Dr. Patrick Kwan.

Relevant papers:

Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies - Kwan - 2010 - Epilepsia - Wiley Online Library

The costs of epilepsy in Australia | Neurology

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

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Nearly 1 in 4 people with epilepsy experiences depression, which affects quality of life, seizure control, and adherence to treatment. Depressive symptoms - including suicidality - are one of the strongest predictors of poor quality of life in people with epilepsy, and they can be overlooked or minimized both by people with epilepsy and by clinicians. Sharp Waves spoke with Dr. Rosa Michaelis about the role of neurologists in discussing, screening, diagnosing, and treating depression as a crucial part of patient care.

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

Is there a fast, simple way to measure whether someone with epilepsy is doing "better" or "worse" compared with a past clinic visit? Not really. Seizure count is often considered a standard, but multiple small seizures may have less impact on someone's life than a single generalized tonic-clonic seizure. In this episode, we talk with authors of a study on an outcome measure that factors the impact of seizures as well as the impact of treatments.

The study: Validation of the seizure-related impact assessment scale 

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

Closing the epilepsy treatment gap relies heavily on social and cultural acceptance of epilepsy as a brain disorder that can be managed with medication or other therapies. Dr. Rugare Mugumbate discusses the five disadvantages faced by people with epilepsy, as well as the important role of social workers and the need to focus on lessons learned from previous pilot projects and awareness campaigns.

Dr. Mugumbate's book - Epilepsy in Resource Limited Settings: Managing Quality of Life - provides a thorough examination of the impact and understanding of epilepsy in resource-limited areas.

Aimed at a wide variety of health practitioners and stuents, The book is available in multiple formats.

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

Somatic genetic epilepsies arise from mutations that occur early in fetal development. They are usually only detectable by genetic sequencing of tissue. For these epilepsies, the timing of the mutation is key: For example, research has shown that focal cortical dysplasia type IIB and hemimegaloencephaly are genetically the same disease, but arise from somatic mutations at different developmental time points. This relatively new area of research is discussed by Dr. Alina Ivaniuk and Dr. Christian Bosselmann.

Resources:

Analysis of 1,386 epileptogenic brain lesions reveals association with DYRK1A and EGFR (Nature Communications 2024 - C. Bosselmann et al.)

Neocortical development and epilepsy: Insights from focal cortical dysplasia and brain tumours (The Lancet Neurology 2021 - I. Blumcke et al.)

Contribution of somatic Ras/Raf/Mitogen-activated protein kinase variants in the hippocampus in drug-resistant mesial temporal lobe epilepsy (JAMA Neurology 2023 - S. Khoshkhoo et al.)

Somatic mosaicism and neurodevelopmental disease (Nature Neuroscience 2018 - AM D'Gama and CA Walsh)

BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors (Nature Medicine 2018 - HY Koh et al.)

SLC35A2 loss-of-function variants affect glycomic signatures, neuronal fate and network dynamics (Brain 2025 - D Lai et al.)

Precise detection of low-level somatic mutation in resected epilepsy brain tissue (Acta Neuropathologica 2019 - NS Sim et al.)

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial (Epilepsia 2021 - I Blumcke et al.)

Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: A retrospective multicentre cohort study (The Lancet Neurology 2020 - HJ Lamberink et al.)

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

In a retrospective study of 31 patients with highly refractory epilepsy, 29% had more than a 50% reduction in seizures for at least 12 months after being treated with immunotherapy. Three of these patients became seizure free. Other than a trend toward a diagnosis of focal epilepsy, researchers did not identify any specific features predictive of treatment response. Sharp Waves spoke with the first author about the study and its implications.

The study was published in Epilepsia in April 2025.

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

What are variants of uncertain significance (VUS) in epilepsy genetic testing? How are they defined, and can those definitions change over time? Sharp Waves talks with Dr. Gemma Carvill as part of our genetic testing series.

RESOURCES

Standards for interpreting variants (American College of Medical Genetics)

Gene Reviews

ClinVar

GeneMatcher

Gnomad

ClinGen

ILAE genetic literacy series

EpiPred website for STXBP1 (developed by EpiMVP project - will be final by end of July)

Think Genetics paper – genetic testing in South Africa project

Link to Sharp Waves episode on genetic testing in LMICs

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

This episode covers a wide scope of issues, including treatment options, treatment response, prognosis and the role of seizures versus the underlying etiology, most common etiologies for different age groups, new-onset refractory status (NORSE), and the prevalence and special considerations of non-convulsive status epilepticus.

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

In use since the 1970s, valproate is highly effective for genetic generalized epilepsies and some forms of pediatric epilepsy. The medication also is associated with a 10% risk of birth defects in children exposed to it in utero, as well as a 30% to 40% risk of neurodevelopmental issues, including autism. Sharp Waves spoke with Dr. Tony Marson about the reproductive risks for women and men taking valproate, discussing UK policies meant to ensure appropriate prescription of valproate and communication about its risks. The recent policy regarding men who take valproate, and the evidence used to support that policy, is discussed near the end of the episode.

Since the episode was recorded, the UK has changed its policy regarding men taking valproate; see this link for more information: February 2025 update on valproate policy in the UK

UK Drug Safety Update page - June 2025

February 2025 update on valproate policy in the UK

Regulatory safety and educational materials on valproate - for health care professionals and patients

Public assessment report: Managing reproductive risks in males under 55 taking valproate

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Send comments and feedback

ILAE's updated seizure classification position paper was published in Epilepsia in April 2025. Sharp Waves talked with Dr. Sandor Beniczky about the updates and how they will impact research and clinical care.

The position paper is open access and available online.

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: [email protected].

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.