RARE DISEASE
Photosensitive epilepsy
Photosensitive epilepsy
Photosensitive epilepsy
Drug discovery
0
drugs
With orphan designations
Overview
Photosensitive epilepsy is a reflex epilepsy syndrome where seizures are triggered by visual stimuli like flashing lights (3-60 Hz) or high-contrast patterns. It accounts for 3-5% of epilepsy cases, predominantly affecting females and adolescents aged 7-19 years [1][6][10]. Diagnosis involves EEG with photoparoxysmal responses during intermittent photic stimulation [1][10]. First-line treatment combines anti-seizure medications (ASMs) with trigger avoidance strategies [3][11][14].
Therapies
Pharmacologic: Valproate (73-86% efficacy), levetiracetam, lamotrigine; avoid sodium channel blockers like carbamazepine [3][7][11]
Non-pharmacologic: Stimulus control (≥2m screen distance, blue-tinted glasses), one-eye covering during exposures [7][15][19]
Lifestyle: Sleep optimization, alcohol avoidance, and VR/content warnings [1][14][19]
Categories: rare neurological diseases
Research Papers
522 drug discovery papers about Photosensitive epilepsy. Recent publications:
522 drug discovery papers about Photosensitive epilepsy. Recent publications:
categories:
Small molecules
small molecules
2026-03-15 | From clinical practice to mechanistic insights in ketogenic diets for epilepsy.
Ketogenic diet therapies, including the classic ketogenic diet, modified Atkins diet, and low glycaemic index treatment, have shown effectiveness in controlling seizures, in part by shifting metabolism from glucose to ketone bodies. They improve mitochondrial function, reduce neuroinflammation, and modulate neurotransmitters. Ketogenic diet therapies also affect the gut microbiome, potentially impacting neurotransmitter balance in ways that contribute to seizure control. A classic ketogenic diet is effective yet restrictive, whereas the modified Atkins diet and low glycaemic index treatment offer greater flexibility, tolerability, and ease of implementation, particularly in resource-limited settings. Cochrane reviews and meta-analyses rank the certainty of randomised controlled trial evidence for ketogenic diet therapies as limited. Early initiation of ketogenic diet therapies, particularly in children or patients with metabolic epilepsies, improves seizure outcomes, potentially preventing further mitochondrial and neuronal damage and reducing the risk of developing resistance to antiseizure medications. Research using rigorous, large-scale comparative effectiveness study designs that accounts for differences in age, epilepsy type, dietary therapy modality, sociodemographic background, care delivery contexts, and that minimises performance and observation bias is needed to resolve remaining uncertainties regarding the efficacy and real-world challenges of ketogenic diet therapies in epilepsy.
2026-03-03 | Lenses protecting against photosensitivity violate international driving regulations
To the Editors: The insightful review on visually provoked seizures by Fisher et al.1 provides relevant and valuable information on a broad range of aspects related to photosensitivity and epilepsy. This includes potential real-life trigger situations, such as a risk that may be posed by flickering light at frequencies associated with a high susceptibility to photoparoxysmal responses when driving along an avenue at dawn or sunset. As a nonpharmacological treatment option to protect patients with photoparoxysmal responses, dark lenses and blue lenses—particularly the Zeiss Z1 blue lens—are discussed due to their ability to reduce or even abolish photosensitivity, as demonstrated in several studies (e.g., Takahashi and Tsukahara,2 Capovilla et al.3). In particular, the review notes that, when driving a car, tinted glasses with reduced light transmission are recommended. At the same time, however, the authors emphasize that lenses impairing the perception of orange traffic signals should be avoided. We would like to highlight this latter point, as it is highly relevant when considering the use of tinted lenses in photosensitive patients who drive. Dark sunglasses are unsuitable for driving at sunset or during nighttime due to their reduced light transmission.4 In addition, the Z1 lens—and blue lenses in general—substantially alter the spectral composition of transmitted light by selectively attenuating longer wavelengths of the visible spectrum. This results in a marked reduction in the visibility of red and orange visual stimuli. Such stimuli are critical in traffic, particularly for the recognition of traffic lights as well as the brake lights and taillights of vehicles (Figure 1). Attenuation of red light intensity may delay stimulus recognition and consequently prolong reaction times while driving. Therefore, although these lenses may exert beneficial effects in reducing photosensitivity, they may simultaneously increase the risk of traffic accidents. Accordingly, blue lenses—and especially Z1 lenses, which have the strongest evidence for suppressing photosensitivity—are not considered suitable for driving according to the International Organization for Standardization (ISO 12312-1:2022). Prescribing colored or dark lenses for patients with purely visually provoked seizures who may be legally permitted to drive once the triggering stimulus is suppressed therefore requires careful consideration of both their beneficial effects and potentially associated risks, as well as implications with regard to driving regulations. Open Access funding enabled and organized by Projekt DEAL. None of the authors has any conflict of interest related to this letter to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. ISO 12312-1:2022, p. 6 (Requirements for road use and driving): Filters suitable for road use and driving shall additionally meet the following two requirements: Spectral transmittance. The spectral transmittance of filters suitable for road use and driving for wavelengths between 475 and 650 nm shall be not less than 0.20 τv D65. Detection of signal lights. The relative visual attenuation quotient Q of filters of categories 0, 1, 2 and 3 suitable for road use and driving shall be not less than 0.80 for red signal light and not less than 0.60 for yellow, green and blue signal lights.
2026-03-03 | Seletracetam Revisited: A Missed Opportunity for Effective Epilepsy Therapy.
Seletracetam (SEL) is a second-generation racetam derivative of the benchmark antiseizure medication (ASM) levetiracetam, discovered in a drug discovery program conducted by UCB Pharma in the early 2000s to optimize binding to synaptic vesicle glycoprotein 2A (SV2A), the main target of levetiracetam. SEL (administered orally) reached phase IIa clinical trials, but its further development was stopped, and its patent expired in 2021. In preclinical studies, SEL showed very potent seizure suppression in several acquired and genetic epilepsy models, with high CNS tolerability. Phase I human studies indicated rapid and extensive oral absorption (> 90% bioavailability), linear pharmacokinetics, and an elimination half-life of about 8 h, with mostly mild to moderate CNS adverse events. Several phase IIa trials found SEL to be effective and to have a good safety profile in patients with photosensitive epilepsy and drug-resistant focal epilepsy. A unique aspect of SEL is its high potency and water solubility that-unlike any other non-benzodiazepine (non-BDZ) ASMs-allows it to be formulated at therapeutic doses in a very low liquid volume suitable for intranasal administration and potential use in acute seizure rescue therapy. The US-based company PrevEp, Inc. (Bethesda, MD) filed a new US patent application in 2024, followed by a worldwide Patent Cooperation Treaty (PCT) application in 2025 on intranasal and orobuccal SEL formulations and new medical uses as the first potential non-BDZ rescue treatment of acute repetitive seizures and rapid epileptic seizure termination (REST). The clinical development of this novel formulation is derisked by the favorable oral SEL administration phase I and phase IIa clinical data. SEL offers several important advantages for rescue treatment in comparison with BZDs. It is only moderately sedative even at the highest doses tested orally, does not cause respiratory depression, and has no addictive potential. Thus, SEL has the potential to become the first non-BDZ acute rescue therapy. Because SEL has never been approved for use in humans, it is a new chemical entity (NCE). In this review, we describe the pharmacology of SEL, its clinical profile after oral administration, and the development of the new intranasal formulation, including first-in-human data.
2026-02-13 | RASP-Seizure: A Recursive Attractor Model of Photosensitive Epilepsy with Application to Sunflower Syndrome
Applies the Recursive Attractor Stability Principle (RASP) to model seizure dynamics in photosensitive epilepsy, with specific application to Sunflower Syndrome. The identical recursion f(x) = 25·tanh³(x) − x/124 that derives the proton mass predicts: seizure modes are quantized, the three-node circuit (V1 + Thalamus + Motor) is uniquely seizure-prone via Diophantine selection, peak photosensitivity at 18 Hz (clinical range 15-20 Hz), dual-mechanism drugs outperform single-mechanism (validated: fenfluramine 89% vs levetiracetam 0%), and anti-resonant frequencies exist for non-pharmacological intervention. Validated against 56 primary sources. The sole genetic variant found in Sunflower Syndrome (GABRG2 p.Trp429Ter) destroys a tryptophan — the RASP-critical amino acid. The ratio p/n = 5/3 is the major sixth in just intonation, connecting seizure compulsion to musical anticipation through shared dopaminergic pathways. Ten testable predictions with explicit kill criteria. Fourth paper in the CUFT-RASP series. Research began June 2025. v0.6.
2026-02-12 | The Pokémon Shock of 1997: A Comprehensive Analysis of Television-Induced Photosensitive Seizures and Mass Psychogenic Illness
On December 16, 1997, an unprecedented public health incident occurred in Japan when an episode of the animated television series Pokémon triggered adverse neurological reactions in thousands of viewers. This event, known as the “Pokémon Shock” or “Pokémon Incident,” resulted in more than 600 hospitalizations and affected an estimated 12,000 children nationwide. This paper presents a comprehensive analysis of the incident, examining the mechanisms of photosensitive epilepsy, the role of mass psychogenic illness, the immediate medical and regulatory responses, and the long-term impact on broadcast standards. Through a systematic review of medical literature, regulatory documents, and epidemiological data, we demonstrate that the incident resulted from a complex interplay between genuine photosensitive epilepsy in susceptible individuals and mass sociogenic illness amplified by extensive media coverage. The event led to the establishment of strict broadcasting guidelines that later became international standards, fundamentally transforming animation production practices worldwide. This case study offers valuable insights into the intersection of media technology, neurology, public health policy, and mass psychology.
proteins
2023-12-21 | Ethics and regulation of neuronal optogenetics in the European Union.
Neuronal optogenetics is a technique to control the activity of neurons with light. This is achieved by artificial expression of light-sensitive ion channels in the target cells. By optogenetic methods, cells that are naturally light-insensitive can be made photosensitive and addressable by illumination and precisely controllable in time and space. So far, optogenetics has primarily been a basic research tool to better understand the brain. However, initial studies are already investigating the possibility of using optogenetics in humans for future therapeutic approaches for neuronal based diseases such as Parkinson's disease, epilepsy, or to promote stroke recovery. In addition, optogenetic methods have already been successfully applied to a human in an experimental setting. Neuronal optogenetics also raises ethical and legal issues, e.g., in relation to, animal experiments, and its application in humans. Additional ethical and legal questions may arise when optogenetic methods are investigated on cerebral organoids. Thus, for the successful translation of optogenetics from basic research to medical practice, the ethical and legal questions of this technology must also be answered, because open ethical and legal questions can hamper the translation. The paper provides an overview of the ethical and legal issues raised by neuronal optogenetics. In addition, considering the technical prerequisites for translation, the paper shows consistent approaches to address these open questions. The paper also aims to support the interdisciplinary dialogue between scientists and physicians on the one hand, and ethicists and lawyers on the other, to enable an interdisciplinary coordinated realization of neuronal optogenetics.
2023-08-01 | An in vivo and in vitro photopolar array for precision optogenetic stimulation
We propose the use of micro-LED arrays as a powerful tool to achieve precise stimulation of neuronal cells in time and space. In particular, we have developed a control system for in vivo implant stimulation and in vitro neuronal stimulation of organisms, through which up to 4096 individual micro-LED light sources can be controlled. The system can be integrated into microscopes and membrane clamp electrophysiology devices for efficient optogenetic monitoring. The final experiments show that different combinations of irradiation of the photopolar array can be used to effectively stimulate neurons transfected with photosensitive proteins by varying the light power.
2023-02-07 | Intermittency properties in a temporal lobe epilepsy model.
Neuronal synchronization is important for communication between brain regions and plays a key role in learning. However, changes in connectivity can lead to hyper-synchronized states related to epileptic seizures that occur intermittently with asynchronous states. The activity-regulated cytoskeleton-associated protein (ARC) is related to synaptic alterations which can lead to epilepsy. Induction of status epilepticus in rodent models causes the appearance of intense ARC immunoreactive neurons (IAINs), which present a higher number of connections and conductance intensity than non-IAINs. This alteration might contribute to abnormal epileptic seizure activity. In this work, we investigated how IAINs connectivity influences the firing pattern and synchronization in neural networks. Firstly, we showed the appearance of synchronized burst patterns due to the emergence of IAINs. Second, we described how the increase of IAINs connectivity favors the appearance of intermittent up and down activities associated with synchronous bursts and asynchronous spikes, respectively. Once the intermittent activity was properly characterized, we applied the optogenetics control of the high synchronous activities in the intermittent regime. To do this, we considered that 1% of neurons were transfected and became photosensitive. We observed that optogenetics methods to control synchronized burst patterns are effective when IAINs are chosen as photosensitive, but not effective in non-IAINs. Therefore, our analyses suggest that IAINs play a pivotal role in both the generation and suppression of highly synchronized activities.
2022-12-08 | In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.
The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model.Rats were bilaterally injected with 0.9 μl of AAV2/7-CaMKIIα-stGtACR2-fusionred in the DG. Three weeks later, afterdischarges were recorded from the DG by placing an optrode at the injection site and a stimulation electrode in the perforant path (PP). Afterdischarges were evoked every 10 min by unilateral electrical stimulation of the PP (20 Hz, 10 s). During every other afterdischarge, the DG was illuminated for 5 or 30 s, first ipsilaterally and then bilaterally to the PP stimulation. The line length metric of the afterdischarges was compared between illumination conditions.Ipsilateral stGtACR2 activation during afterdischarges decreased the local field potential line length only during illumination and specifically at the illuminated site but did not reduce afterdischarge duration. Bilateral illumination did not terminate the afterdischarges.Optogenetic inhibition of excitatory neurons using the blue-light sensitive chloride channel stGtACR2 reduced the amplitude of electrically induced afterdischarges in the DG at the site of illumination, but this local inhibitory effect was insufficient to reduce the duration of the afterdischarge.
2022-07-12 | Liraglutide chronic treatment prevents development of tolerance to antiseizure effects of diazepam in genetically epilepsy prone rats.
Glucagon-like peptide-1 (GLP-1) is a hormone that can regulate several neuronal functions. The modulation of GLP-1 receptors emerged as a potential target to treat several neurological diseases, such as epilepsy. Here, we studied the effects of acute and chronic treatment with liraglutide (LIRA), in genetically epilepsy prone rats (GEPR-9s). We have also investigated the possible development of tolerance to antiseizure effects of diazepam, and how LIRA could affect this phenomenon over the same period of treatment. The present data indicate that an acute treatment with LIRA did not diminish the severity score of audiogenic seizures (AGS) in GEPR-9s. By contrast, a chronic treatment with LIRA has shown only a modest antiseizure effect that was maintained until the end of treatment, in GEPR-9s. Not surprisingly, acute administration of diazepam reduced, in a dose dependent manner, the severity of the AGS in GEPR-9s. However, when diazepam was chronically administered, an evident development of tolerance to its antiseizure effects was detected. Interestingly, following an add-on treatment with LIRA, a reduced development of tolerance and an enhanced diazepam antiseizure effect was observed in GEPR-9s. Overall, an add-on therapy with LIRA demonstrate benefits superior to single antiseizure medications and could be utilized to treat epilepsy as well as associated issues. Therefore, the potential use of GLP1 analogs for the treatment of epilepsy in combination with existing antiseizure medications could thus add a new and long-awaited dimension to its management.
cell therapies
2025-06-16 | Jeavons syndrome - clinical spectrum, diagnostic challenges and innovative treatment strategies
Introduction:Jeavons syndrome (JS), also known as epilepsy with eyelid myoclonus (EEM), is a rare form of genetically generalized epilepsy (GGE) characterized by light-triggered seizures, eyelid myoclonus, and often concurrent absence seizures and GTCS. The condition is sometimes misdiagnosed as neural tics, leading to significant diagnostic delays. In recent years, there has been growing interest in new treatments for JS, including alternative approaches in cases of treatment resistance.Objective:The purpose of this study is to provide an update on Jeavons syndrome, including clinical presentation, genetic factors, diagnostic methods and the latest therapeutic strategies.Methods:A non-systematic review of the scientific literature from 2020-2025 was performed using PubMed, Google Scholar, Web of Science and Scopus databases. Publications describing JS, treatment of drug-resistant epilepsy, eyelid myoclonus, dietary therapy and modern brain stimulation methods were included.Results: The most commonly used first-line drugs are valproic acid, levetiracetam and lamotrigine. In refractory cases, lacosamide, zonisamide, and VNS and RNS have also shown efficacy. The potential of diet therapy (ketogenic, Atkins, low-GI diets) and lentiviral therapy in patients with photosensitivity was identified. The study emphasized the role of genetic diagnosis in personalizing treatment. Conclusions: Jeavons syndrome requires a comprehensive therapeutic approach. Standard pharmacotherapy is sometimes insufficient, so adjunctive therapies are playing an increasingly important role. Early diagnosis, consideration of genetic factors and implementation of individualized treatment strategies can significantly improve seizure control and quality of life for patients.
2024-03-04 | A Zebrafish-Based Platform for High-Throughput Epilepsy Modeling and Drug Screening in F0
The zebrafish model has emerged as a reference tool for phenotypic drug screening. An increasing number of molecules have been brought from bench to bedside thanks to zebrafish-based assays over the last decade. The high homology between the zebrafish and the human genomes facilitates the generation of zebrafish lines carrying loss-of-function mutations in disease-relevant genes; nonetheless, even using this alternative model, the establishment of isogenic mutant lines requires a long generation time and an elevated number of animals. In this study, we developed a zebrafish-based high-throughput platform for the generation of F0 knock-out (KO) models and the screening of neuroactive compounds. We show that the simultaneous inactivation of a reporter gene (tyrosinase) and a second gene of interest allows the phenotypic selection of F0 somatic mutants (crispants) carrying the highest rates of mutations in both loci. As a proof of principle, we targeted genes associated with neurodevelopmental disorders and we efficiently generated de facto F0 mutants in seven genes involved in childhood epilepsy. We employed a high-throughput multiparametric behavioral analysis to characterize the response of these KO models to an epileptogenic stimulus, making it possible to employ kinematic parameters to identify seizure-like events. The combination of these co-injection, screening and phenotyping methods allowed us to generate crispants recapitulating epilepsy features and to test the efficacy of compounds already during the first days post fertilization. Since the strategy can be applied to a wide range of indications, this study paves the ground for high-throughput drug discovery and promotes the use of zebrafish in personalized medicine and neurotoxicity assessment.
2019-11-01 | The effects of cell therapy on seizures in animal models of epilepsy: protocol for systematic review and meta-analysis of preclinical studies
Abstract Background Epilepsy is one of the most common and serious brain conditions, characterised by recurrent unprovoked seizures. It affects about 1% of the population worldwide. Despite a range of antiepileptic drugs being available, one third of the patients do not achieve adequate seizure control. Only a minority of these patients may be suitable to undergo surgical resection of the seizure focus, but this is an invasive and not always successful procedure. There is an urgent need to develop more effective treatment options for uncontrolled seizures. With the recent advances in regenerative and translational medicine, cell therapies could prove to be beneficial. Here we describe the protocol for a proposed systematic review and meta-analysis to assess the effects for cell transplantation in animal models of epilepsy. Methods We will include all preclinical animal models of epilepsy that evaluate the effects of cell transplantation compared to the untreated control. The primary outcome will be the change in frequency and duration of seizures from baseline measured by video electroencephalography (EEG). The secondary outcomes will include histological and neurobehavioural assessments. We will perform an electronic search of MEDLINE via PubMed, Web of Science, and EMBASE. Search results will be screened independently by two reviewers and confirmed by a third reviewer. Data from eligible studies will be extracted and pooled, and the summary estimate of effect size will be calculated using DerSimonian and Laird random effects meta-analysis. Heterogeneity will be explored using sub-group meta-analysis, and meta-regression risk of bias will be assessed by using the CAMARADES checklist for study quality tool. Discussion The purpose of this systematic review is to assess and summarise the existing literature in the field of cell transplantation as a treatment for epilepsy in animal models. Efficacy will be measured by evaluating the reduction in seizure intervals, number, and duration, within animal models of epilepsy. Analysis of the existing literature will mark the achievement made in the field and locate the existing gaps, a process that will aid in the search for the next needed step. Systematic review registration CRD42018103628
2015-10-02 | Future focal treatment approaches to epilepsy
There have been considerable advances in antiepileptic drug (AED) therapy in recent years. More recently, a series of revolutionary technologies combining optics or organic compounds with genetics have been used to suppress seizures on demand. These results suggest new treatment approaches and provide a good basis from which future clinical studies might be developed. This chapter considers the principles behind novel focal treatment strategies, critically reviews the work to date and discusses the potential for translation of these advances into new treatment options for patients with currently intractable disease. Neuronal grafting holds the promise of effecting potentially permanent local change and initial studies demonstrate the feasibility of restoring neuronal loss, altering circuitry or increasing local neurochemical concentrations. Viral vectors are important tools for gene therapy of terminally differentiated cells. Focal treatment techniques in epilepsy offer a novel approach to help more patients lead seizure-free lives in the years to come.
small molecules
2026-03-15 | From clinical practice to mechanistic insights in ketogenic diets for epilepsy.
Ketogenic diet therapies, including the classic ketogenic diet, modified Atkins diet, and low glycaemic index treatment, have shown effectiveness in controlling seizures, in part by shifting metabolism from glucose to ketone bodies. They improve mitochondrial function, reduce neuroinflammation, and modulate neurotransmitters. Ketogenic diet therapies also affect the gut microbiome, potentially impacting neurotransmitter balance in ways that contribute to seizure control. A classic ketogenic diet is effective yet restrictive, whereas the modified Atkins diet and low glycaemic index treatment offer greater flexibility, tolerability, and ease of implementation, particularly in resource-limited settings. Cochrane reviews and meta-analyses rank the certainty of randomised controlled trial evidence for ketogenic diet therapies as limited. Early initiation of ketogenic diet therapies, particularly in children or patients with metabolic epilepsies, improves seizure outcomes, potentially preventing further mitochondrial and neuronal damage and reducing the risk of developing resistance to antiseizure medications. Research using rigorous, large-scale comparative effectiveness study designs that accounts for differences in age, epilepsy type, dietary therapy modality, sociodemographic background, care delivery contexts, and that minimises performance and observation bias is needed to resolve remaining uncertainties regarding the efficacy and real-world challenges of ketogenic diet therapies in epilepsy.
2026-03-03 | Lenses protecting against photosensitivity violate international driving regulations
To the Editors: The insightful review on visually provoked seizures by Fisher et al.1 provides relevant and valuable information on a broad range of aspects related to photosensitivity and epilepsy. This includes potential real-life trigger situations, such as a risk that may be posed by flickering light at frequencies associated with a high susceptibility to photoparoxysmal responses when driving along an avenue at dawn or sunset. As a nonpharmacological treatment option to protect patients with photoparoxysmal responses, dark lenses and blue lenses—particularly the Zeiss Z1 blue lens—are discussed due to their ability to reduce or even abolish photosensitivity, as demonstrated in several studies (e.g., Takahashi and Tsukahara,2 Capovilla et al.3). In particular, the review notes that, when driving a car, tinted glasses with reduced light transmission are recommended. At the same time, however, the authors emphasize that lenses impairing the perception of orange traffic signals should be avoided. We would like to highlight this latter point, as it is highly relevant when considering the use of tinted lenses in photosensitive patients who drive. Dark sunglasses are unsuitable for driving at sunset or during nighttime due to their reduced light transmission.4 In addition, the Z1 lens—and blue lenses in general—substantially alter the spectral composition of transmitted light by selectively attenuating longer wavelengths of the visible spectrum. This results in a marked reduction in the visibility of red and orange visual stimuli. Such stimuli are critical in traffic, particularly for the recognition of traffic lights as well as the brake lights and taillights of vehicles (Figure 1). Attenuation of red light intensity may delay stimulus recognition and consequently prolong reaction times while driving. Therefore, although these lenses may exert beneficial effects in reducing photosensitivity, they may simultaneously increase the risk of traffic accidents. Accordingly, blue lenses—and especially Z1 lenses, which have the strongest evidence for suppressing photosensitivity—are not considered suitable for driving according to the International Organization for Standardization (ISO 12312-1:2022). Prescribing colored or dark lenses for patients with purely visually provoked seizures who may be legally permitted to drive once the triggering stimulus is suppressed therefore requires careful consideration of both their beneficial effects and potentially associated risks, as well as implications with regard to driving regulations. Open Access funding enabled and organized by Projekt DEAL. None of the authors has any conflict of interest related to this letter to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. ISO 12312-1:2022, p. 6 (Requirements for road use and driving): Filters suitable for road use and driving shall additionally meet the following two requirements: Spectral transmittance. The spectral transmittance of filters suitable for road use and driving for wavelengths between 475 and 650 nm shall be not less than 0.20 τv D65. Detection of signal lights. The relative visual attenuation quotient Q of filters of categories 0, 1, 2 and 3 suitable for road use and driving shall be not less than 0.80 for red signal light and not less than 0.60 for yellow, green and blue signal lights.
2026-03-03 | Seletracetam Revisited: A Missed Opportunity for Effective Epilepsy Therapy.
Seletracetam (SEL) is a second-generation racetam derivative of the benchmark antiseizure medication (ASM) levetiracetam, discovered in a drug discovery program conducted by UCB Pharma in the early 2000s to optimize binding to synaptic vesicle glycoprotein 2A (SV2A), the main target of levetiracetam. SEL (administered orally) reached phase IIa clinical trials, but its further development was stopped, and its patent expired in 2021. In preclinical studies, SEL showed very potent seizure suppression in several acquired and genetic epilepsy models, with high CNS tolerability. Phase I human studies indicated rapid and extensive oral absorption (> 90% bioavailability), linear pharmacokinetics, and an elimination half-life of about 8 h, with mostly mild to moderate CNS adverse events. Several phase IIa trials found SEL to be effective and to have a good safety profile in patients with photosensitive epilepsy and drug-resistant focal epilepsy. A unique aspect of SEL is its high potency and water solubility that-unlike any other non-benzodiazepine (non-BDZ) ASMs-allows it to be formulated at therapeutic doses in a very low liquid volume suitable for intranasal administration and potential use in acute seizure rescue therapy. The US-based company PrevEp, Inc. (Bethesda, MD) filed a new US patent application in 2024, followed by a worldwide Patent Cooperation Treaty (PCT) application in 2025 on intranasal and orobuccal SEL formulations and new medical uses as the first potential non-BDZ rescue treatment of acute repetitive seizures and rapid epileptic seizure termination (REST). The clinical development of this novel formulation is derisked by the favorable oral SEL administration phase I and phase IIa clinical data. SEL offers several important advantages for rescue treatment in comparison with BZDs. It is only moderately sedative even at the highest doses tested orally, does not cause respiratory depression, and has no addictive potential. Thus, SEL has the potential to become the first non-BDZ acute rescue therapy. Because SEL has never been approved for use in humans, it is a new chemical entity (NCE). In this review, we describe the pharmacology of SEL, its clinical profile after oral administration, and the development of the new intranasal formulation, including first-in-human data.
2026-02-13 | RASP-Seizure: A Recursive Attractor Model of Photosensitive Epilepsy with Application to Sunflower Syndrome
Applies the Recursive Attractor Stability Principle (RASP) to model seizure dynamics in photosensitive epilepsy, with specific application to Sunflower Syndrome. The identical recursion f(x) = 25·tanh³(x) − x/124 that derives the proton mass predicts: seizure modes are quantized, the three-node circuit (V1 + Thalamus + Motor) is uniquely seizure-prone via Diophantine selection, peak photosensitivity at 18 Hz (clinical range 15-20 Hz), dual-mechanism drugs outperform single-mechanism (validated: fenfluramine 89% vs levetiracetam 0%), and anti-resonant frequencies exist for non-pharmacological intervention. Validated against 56 primary sources. The sole genetic variant found in Sunflower Syndrome (GABRG2 p.Trp429Ter) destroys a tryptophan — the RASP-critical amino acid. The ratio p/n = 5/3 is the major sixth in just intonation, connecting seizure compulsion to musical anticipation through shared dopaminergic pathways. Ten testable predictions with explicit kill criteria. Fourth paper in the CUFT-RASP series. Research began June 2025. v0.6.
2026-02-12 | The Pokémon Shock of 1997: A Comprehensive Analysis of Television-Induced Photosensitive Seizures and Mass Psychogenic Illness
On December 16, 1997, an unprecedented public health incident occurred in Japan when an episode of the animated television series Pokémon triggered adverse neurological reactions in thousands of viewers. This event, known as the “Pokémon Shock” or “Pokémon Incident,” resulted in more than 600 hospitalizations and affected an estimated 12,000 children nationwide. This paper presents a comprehensive analysis of the incident, examining the mechanisms of photosensitive epilepsy, the role of mass psychogenic illness, the immediate medical and regulatory responses, and the long-term impact on broadcast standards. Through a systematic review of medical literature, regulatory documents, and epidemiological data, we demonstrate that the incident resulted from a complex interplay between genuine photosensitive epilepsy in susceptible individuals and mass sociogenic illness amplified by extensive media coverage. The event led to the establishment of strict broadcasting guidelines that later became international standards, fundamentally transforming animation production practices worldwide. This case study offers valuable insights into the intersection of media technology, neurology, public health policy, and mass psychology.
proteins
2023-12-21 | Ethics and regulation of neuronal optogenetics in the European Union.
Neuronal optogenetics is a technique to control the activity of neurons with light. This is achieved by artificial expression of light-sensitive ion channels in the target cells. By optogenetic methods, cells that are naturally light-insensitive can be made photosensitive and addressable by illumination and precisely controllable in time and space. So far, optogenetics has primarily been a basic research tool to better understand the brain. However, initial studies are already investigating the possibility of using optogenetics in humans for future therapeutic approaches for neuronal based diseases such as Parkinson's disease, epilepsy, or to promote stroke recovery. In addition, optogenetic methods have already been successfully applied to a human in an experimental setting. Neuronal optogenetics also raises ethical and legal issues, e.g., in relation to, animal experiments, and its application in humans. Additional ethical and legal questions may arise when optogenetic methods are investigated on cerebral organoids. Thus, for the successful translation of optogenetics from basic research to medical practice, the ethical and legal questions of this technology must also be answered, because open ethical and legal questions can hamper the translation. The paper provides an overview of the ethical and legal issues raised by neuronal optogenetics. In addition, considering the technical prerequisites for translation, the paper shows consistent approaches to address these open questions. The paper also aims to support the interdisciplinary dialogue between scientists and physicians on the one hand, and ethicists and lawyers on the other, to enable an interdisciplinary coordinated realization of neuronal optogenetics.
2023-08-01 | An in vivo and in vitro photopolar array for precision optogenetic stimulation
We propose the use of micro-LED arrays as a powerful tool to achieve precise stimulation of neuronal cells in time and space. In particular, we have developed a control system for in vivo implant stimulation and in vitro neuronal stimulation of organisms, through which up to 4096 individual micro-LED light sources can be controlled. The system can be integrated into microscopes and membrane clamp electrophysiology devices for efficient optogenetic monitoring. The final experiments show that different combinations of irradiation of the photopolar array can be used to effectively stimulate neurons transfected with photosensitive proteins by varying the light power.
2023-02-07 | Intermittency properties in a temporal lobe epilepsy model.
Neuronal synchronization is important for communication between brain regions and plays a key role in learning. However, changes in connectivity can lead to hyper-synchronized states related to epileptic seizures that occur intermittently with asynchronous states. The activity-regulated cytoskeleton-associated protein (ARC) is related to synaptic alterations which can lead to epilepsy. Induction of status epilepticus in rodent models causes the appearance of intense ARC immunoreactive neurons (IAINs), which present a higher number of connections and conductance intensity than non-IAINs. This alteration might contribute to abnormal epileptic seizure activity. In this work, we investigated how IAINs connectivity influences the firing pattern and synchronization in neural networks. Firstly, we showed the appearance of synchronized burst patterns due to the emergence of IAINs. Second, we described how the increase of IAINs connectivity favors the appearance of intermittent up and down activities associated with synchronous bursts and asynchronous spikes, respectively. Once the intermittent activity was properly characterized, we applied the optogenetics control of the high synchronous activities in the intermittent regime. To do this, we considered that 1% of neurons were transfected and became photosensitive. We observed that optogenetics methods to control synchronized burst patterns are effective when IAINs are chosen as photosensitive, but not effective in non-IAINs. Therefore, our analyses suggest that IAINs play a pivotal role in both the generation and suppression of highly synchronized activities.
2022-12-08 | In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.
The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model.Rats were bilaterally injected with 0.9 μl of AAV2/7-CaMKIIα-stGtACR2-fusionred in the DG. Three weeks later, afterdischarges were recorded from the DG by placing an optrode at the injection site and a stimulation electrode in the perforant path (PP). Afterdischarges were evoked every 10 min by unilateral electrical stimulation of the PP (20 Hz, 10 s). During every other afterdischarge, the DG was illuminated for 5 or 30 s, first ipsilaterally and then bilaterally to the PP stimulation. The line length metric of the afterdischarges was compared between illumination conditions.Ipsilateral stGtACR2 activation during afterdischarges decreased the local field potential line length only during illumination and specifically at the illuminated site but did not reduce afterdischarge duration. Bilateral illumination did not terminate the afterdischarges.Optogenetic inhibition of excitatory neurons using the blue-light sensitive chloride channel stGtACR2 reduced the amplitude of electrically induced afterdischarges in the DG at the site of illumination, but this local inhibitory effect was insufficient to reduce the duration of the afterdischarge.
2022-07-12 | Liraglutide chronic treatment prevents development of tolerance to antiseizure effects of diazepam in genetically epilepsy prone rats.
Glucagon-like peptide-1 (GLP-1) is a hormone that can regulate several neuronal functions. The modulation of GLP-1 receptors emerged as a potential target to treat several neurological diseases, such as epilepsy. Here, we studied the effects of acute and chronic treatment with liraglutide (LIRA), in genetically epilepsy prone rats (GEPR-9s). We have also investigated the possible development of tolerance to antiseizure effects of diazepam, and how LIRA could affect this phenomenon over the same period of treatment. The present data indicate that an acute treatment with LIRA did not diminish the severity score of audiogenic seizures (AGS) in GEPR-9s. By contrast, a chronic treatment with LIRA has shown only a modest antiseizure effect that was maintained until the end of treatment, in GEPR-9s. Not surprisingly, acute administration of diazepam reduced, in a dose dependent manner, the severity of the AGS in GEPR-9s. However, when diazepam was chronically administered, an evident development of tolerance to its antiseizure effects was detected. Interestingly, following an add-on treatment with LIRA, a reduced development of tolerance and an enhanced diazepam antiseizure effect was observed in GEPR-9s. Overall, an add-on therapy with LIRA demonstrate benefits superior to single antiseizure medications and could be utilized to treat epilepsy as well as associated issues. Therefore, the potential use of GLP1 analogs for the treatment of epilepsy in combination with existing antiseizure medications could thus add a new and long-awaited dimension to its management.
cell therapies
2025-06-16 | Jeavons syndrome - clinical spectrum, diagnostic challenges and innovative treatment strategies
Introduction:Jeavons syndrome (JS), also known as epilepsy with eyelid myoclonus (EEM), is a rare form of genetically generalized epilepsy (GGE) characterized by light-triggered seizures, eyelid myoclonus, and often concurrent absence seizures and GTCS. The condition is sometimes misdiagnosed as neural tics, leading to significant diagnostic delays. In recent years, there has been growing interest in new treatments for JS, including alternative approaches in cases of treatment resistance.Objective:The purpose of this study is to provide an update on Jeavons syndrome, including clinical presentation, genetic factors, diagnostic methods and the latest therapeutic strategies.Methods:A non-systematic review of the scientific literature from 2020-2025 was performed using PubMed, Google Scholar, Web of Science and Scopus databases. Publications describing JS, treatment of drug-resistant epilepsy, eyelid myoclonus, dietary therapy and modern brain stimulation methods were included.Results: The most commonly used first-line drugs are valproic acid, levetiracetam and lamotrigine. In refractory cases, lacosamide, zonisamide, and VNS and RNS have also shown efficacy. The potential of diet therapy (ketogenic, Atkins, low-GI diets) and lentiviral therapy in patients with photosensitivity was identified. The study emphasized the role of genetic diagnosis in personalizing treatment. Conclusions: Jeavons syndrome requires a comprehensive therapeutic approach. Standard pharmacotherapy is sometimes insufficient, so adjunctive therapies are playing an increasingly important role. Early diagnosis, consideration of genetic factors and implementation of individualized treatment strategies can significantly improve seizure control and quality of life for patients.
2024-03-04 | A Zebrafish-Based Platform for High-Throughput Epilepsy Modeling and Drug Screening in F0
The zebrafish model has emerged as a reference tool for phenotypic drug screening. An increasing number of molecules have been brought from bench to bedside thanks to zebrafish-based assays over the last decade. The high homology between the zebrafish and the human genomes facilitates the generation of zebrafish lines carrying loss-of-function mutations in disease-relevant genes; nonetheless, even using this alternative model, the establishment of isogenic mutant lines requires a long generation time and an elevated number of animals. In this study, we developed a zebrafish-based high-throughput platform for the generation of F0 knock-out (KO) models and the screening of neuroactive compounds. We show that the simultaneous inactivation of a reporter gene (tyrosinase) and a second gene of interest allows the phenotypic selection of F0 somatic mutants (crispants) carrying the highest rates of mutations in both loci. As a proof of principle, we targeted genes associated with neurodevelopmental disorders and we efficiently generated de facto F0 mutants in seven genes involved in childhood epilepsy. We employed a high-throughput multiparametric behavioral analysis to characterize the response of these KO models to an epileptogenic stimulus, making it possible to employ kinematic parameters to identify seizure-like events. The combination of these co-injection, screening and phenotyping methods allowed us to generate crispants recapitulating epilepsy features and to test the efficacy of compounds already during the first days post fertilization. Since the strategy can be applied to a wide range of indications, this study paves the ground for high-throughput drug discovery and promotes the use of zebrafish in personalized medicine and neurotoxicity assessment.
2019-11-01 | The effects of cell therapy on seizures in animal models of epilepsy: protocol for systematic review and meta-analysis of preclinical studies
Abstract Background Epilepsy is one of the most common and serious brain conditions, characterised by recurrent unprovoked seizures. It affects about 1% of the population worldwide. Despite a range of antiepileptic drugs being available, one third of the patients do not achieve adequate seizure control. Only a minority of these patients may be suitable to undergo surgical resection of the seizure focus, but this is an invasive and not always successful procedure. There is an urgent need to develop more effective treatment options for uncontrolled seizures. With the recent advances in regenerative and translational medicine, cell therapies could prove to be beneficial. Here we describe the protocol for a proposed systematic review and meta-analysis to assess the effects for cell transplantation in animal models of epilepsy. Methods We will include all preclinical animal models of epilepsy that evaluate the effects of cell transplantation compared to the untreated control. The primary outcome will be the change in frequency and duration of seizures from baseline measured by video electroencephalography (EEG). The secondary outcomes will include histological and neurobehavioural assessments. We will perform an electronic search of MEDLINE via PubMed, Web of Science, and EMBASE. Search results will be screened independently by two reviewers and confirmed by a third reviewer. Data from eligible studies will be extracted and pooled, and the summary estimate of effect size will be calculated using DerSimonian and Laird random effects meta-analysis. Heterogeneity will be explored using sub-group meta-analysis, and meta-regression risk of bias will be assessed by using the CAMARADES checklist for study quality tool. Discussion The purpose of this systematic review is to assess and summarise the existing literature in the field of cell transplantation as a treatment for epilepsy in animal models. Efficacy will be measured by evaluating the reduction in seizure intervals, number, and duration, within animal models of epilepsy. Analysis of the existing literature will mark the achievement made in the field and locate the existing gaps, a process that will aid in the search for the next needed step. Systematic review registration CRD42018103628
2015-10-02 | Future focal treatment approaches to epilepsy
There have been considerable advances in antiepileptic drug (AED) therapy in recent years. More recently, a series of revolutionary technologies combining optics or organic compounds with genetics have been used to suppress seizures on demand. These results suggest new treatment approaches and provide a good basis from which future clinical studies might be developed. This chapter considers the principles behind novel focal treatment strategies, critically reviews the work to date and discusses the potential for translation of these advances into new treatment options for patients with currently intractable disease. Neuronal grafting holds the promise of effecting potentially permanent local change and initial studies demonstrate the feasibility of restoring neuronal loss, altering circuitry or increasing local neurochemical concentrations. Viral vectors are important tools for gene therapy of terminally differentiated cells. Focal treatment techniques in epilepsy offer a novel approach to help more patients lead seizure-free lives in the years to come.
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