☆ 4.5 Review

A Comprehensive Review of Emerging Trends and Innovative Therapies in Epilepsy Management

BRAIN SCIENCES (2023)

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Summary: Epilepsy is a disorder of brain networks, and researchers are identifying critical nodes within these networks to target therapies for seizures. Intracranial neuromodulation has proven effective in reducing seizures in both adults and children, and the convergence of these fields is driving a new era of network-guided neuromodulation for epilepsy. This review summarizes the current literature on network mechanisms underlying neurostimulation for epilepsy, focusing on key propagation points in the epileptogenic network. The authors discuss current clinical targets, such as the thalamic nuclei, as well as emerging targets like the pulvinar of the thalamus and the cerebellum. They also report on findings from various modalities of investigation, including EEG and MRI, that reveal the structural and functional networks associated with these propagation points. The authors emphasize the importance of using network analyses to determine patient eligibility for neurostimulation and delivering personalized stimulation based on individual epileptogenic networks.

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Anterior nucleus of the thalamus deep brain stimulation vs temporal lobe responsive neurostimulation for temporal lobe epilepsy

Jimmy C. Yang et al.

Summary: We compared the effects of THL-DBS and TL-RNS in patients with drug-resistant TLE and found that both methods have similar outcomes.

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Evidence supporting deep brain stimulation of the medial septum in the treatment of temporal lobe epilepsy

Eric R. Cole et al.

Summary: Electrical brain stimulation is an effective treatment option for epilepsy patients who do not respond to medication. Stimulation of the medial septum can reduce seizure frequency and restore cognitive comorbidities associated with epilepsy.

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Closed-loop direct control of seizure focus in a rodent model of temporal lobe epilepsy via localized electric fields applied sequentially

Wonok Kang et al.

Summary: Direct electrical stimulation of the seizure focus can terminate epileptic oscillations, but intervening the hippocampus is challenging. In this study, a sequential narrow-field stimulation method was used to terminate seizures in a rat model with spatially extensive hippocampal structure. The results demonstrate the selectiveness and preciseness of this method, suggesting its potential as a therapeutic approach.

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Responsive Neurostimulation of the Thalamus for the Treatment of Refractory Epilepsy

Jorge A. Roa et al.

Summary: This study evaluated the efficacy of the NeuroPace Responsive Neurostimulation System (NMS) in the treatment of refractory epilepsy. The results showed that NMS could achieve seizure control in approximately 65% of patients. Infections were the most common complication.

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Ketogenic Diets in the Management of Lennox-Gastaut Syndrome-Review of Literature

Urszula Skrobas et al.

Summary: Epilepsy is a global medical problem with a significant number of patients. Ketogenic dietary therapies have shown efficacy and safety in reducing seizures, especially in patients with Lennox-Gastaut syndrome (LGS).

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Immunity, Ion Channels and Epilepsy

Tsang-Shan Chen et al.

Summary: Epilepsy is a common chronic neurological disorder in modern society. The immunological factors and the interaction between ion channels and the immune system play important roles in the development and progression of epilepsy. Recognizing immune-mediated epilepsy and understanding the pathophysiology are crucial for early intervention and effective treatment.

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Molecular networks underlying cannabinoid signaling in skeletal muscle plasticity

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Summary: The cannabinoid system plays a crucial role in neural and immunity processes, as well as in whole body and tissue metabolism. It is regulated by receptor-independent and -dependent mechanisms, impacting skeletal muscle plasticity and physiology. Further research is needed to explore how targeting the cannabinoid system can improve muscle quantity and quality in various conditions.

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Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy

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Summary: This review explores the potential drug-drug interactions (DDI) that may occur with the concomitant use of cannabis and pharmaceuticals. Current research suggests that cannabis has the potential to induce DDI, particularly in major drug-metabolizing enzymes such as cytochrome P450s, carboxylesterases, and uridine-5'-diphosphoglucuronosyltransferases.

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Treatment of epilepsy using a targeted p38y kinase gene therapy

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Summary: Hyperphosphorylated tau protein is involved in various neurological disorders, while site-specific phosphorylation of tau at T205 by p38y kinase can protect against Alzheimer's disease. Delivery of p38y through gene transfer reduces seizure susceptibility, restores normal neuronal activity, improves behavioral deficits, and prevents epilepsy-induced deaths. Additionally, p38y-mediated phosphorylation of tau at T205 plays a crucial role in protecting against epilepsy.

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Summary: This review provides a comprehensive overview of the presynaptic applications of optogenetic tools, discussing the challenges, limitations, and future directions. Optogenetic actuators enable precise control of presynaptic functions, such as light-mediated neurotransmitter release, presynaptic inhibition, induction of synaptic plasticity, and manipulation of individual components of the presynaptic machinery.

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Summary: A meta-analysis of recent literature on RNS for DRE shows comparable seizure reduction and responder rates to other neuromodulatory implants for epilepsy, highlighting the value of this intervention and the need for further research. However, the analysis also reveals a strong publication bias towards positive outcomes, indicating the limitations of the current literature. Promising RNS data for the treatment of DRE should be interpreted cautiously.

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Summary: Genetic epilepsies are disorders caused by inherited or de novo genetic variants, disrupting brain development and function. Despite current therapies, many patients fail to control their seizures. Advances in gene sequencing and therapy offer new possibilities for treatment of these conditions.

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Optogenetic Methods to Investigate Brain Alterations in Preclinical Models

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CELLS (2022)

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Review Clinical Neurology

Neuromodulation in drug-resistant epilepsy: A review of current knowledge

Tao Xue et al.

Summary: This article provides a narrative review of three approved neuromodulation therapies for drug-resistant epilepsy, including vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation (RNS). Although these treatments have shown promising results in reducing seizure frequency and duration, there are still challenges to be addressed, such as heterogeneity among epilepsy types, optimization of stimulation parameters, and a lack of biomarkers to predict response to neuromodulation therapies.

ACTA NEUROLOGICA SCANDINAVICA (2022)

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Mechanisms Underlying Circuit Dysfunction in Neurodevelopmental Disorders

David Exposito-Alonso et al.

Summary: Recent advances in genomics have revealed the genetic variations associated with neurodevelopmental disorders, indicating the importance of synaptic formation and circuit balance in these disorders. This review summarizes the research progress on synaptic and circuit mechanisms implicated in neurodevelopmental disorders and discusses the disruptions in synaptic connections and imbalances in neuronal circuits that contribute to cognitive and behavioral changes in different disorders. Furthermore, new approaches that can restore or mitigate dysfunctional processes and the development of improved clinical biomarkers and strategies for early intervention are highlighted.

ANNUAL REVIEW OF GENETICS (2022)

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Review Neurosciences

Vagus nerve stimulation for the treatment of epilepsy: things to note on the protocols, the effects and the mechanisms of action

Auwal Abdullahi et al.

Summary: This article discusses non-pharmacological methods for managing epilepsy, including vagus nerve stimulation techniques. It suggests that respiratory vagal nerve stimulation may be an effective non-invasive technique worth considering.

INTERNATIONAL JOURNAL OF NEUROSCIENCE (2022)

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Article Biochemistry & Molecular Biology

Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating

Rajat S. Shivacharan et al.

Summary: In this pilot study, responsive deep brain stimulation (DBS) was used to improve self-control of food intake and weight loss in two patients with binge eating disorder (BED) and severe obesity. Increased low-frequency oscillations in the nucleus accumbens (NAc), recorded during food cravings preceding loss of control (LOC) eating, were used to guide the delivery of DBS. Over 6 months, improved self-control of food intake and weight loss were observed. Further research with larger sample sizes is needed to determine the scalability of this approach.

NATURE MEDICINE (2022)

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Article Clinical Neurology

Combined Neuromodulation (Vagus Nerve Stimulation and Deep Brain Stimulation) in Patients With Refractory Generalized Epilepsy: An Observational Study

Arthur Cukiert et al.

NEUROMODULATION (2022)

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Review Neurosciences

Large-scale, closed-loop interrogation of neural circuits underlying cognition

Dion Khodagholy et al.

Summary: This article reviews the application of closed-loop neurostimulation in cognitive processes. Cognitive functions involve coordinated activity patterns between multiple brain regions, and their disruption by neuropsychiatric disorders is complex. How to effectively identify and target distributed neural networks implicated in mediating cognition through closed-loop neurostimulation remains unclear. The article proposes that devices enabling large-scale acquisition, integrated processing, and multiregion, arbitrary waveform stimulation will be critical for mechanistically driven manipulation of cognitive processes in physiological and pathological brain networks.

TRENDS IN NEUROSCIENCES (2022)

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Article Nutrition & Dietetics

Modified Atkins diet versus ketogenic diet in children with drug-resistant epilepsy: A meta-analysis of comparative studies

Asmaa Mhanna et al.

Summary: This meta-analysis compared the efficacy and tolerability of the modified Atkins diet (MAD) and traditional ketogenic diet (KD) in children with drug-resistant epilepsy (DRE). The results showed that traditional KD was superior to MAD in achieving more than 50% reduction in seizure frequency at 6 months. However, there was no significant difference between KD and MAD in achieving more than 90% reduction in seizure frequency or seizure freedom at 6 months. The tolerability profiles of both regimens were similar as well.

CLINICAL NUTRITION ESPEN (2022)

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Review Clinical Neurology

Cenobamate for treatment-resistant focal seizures: current evidence and place in therapy

Alok Singh

Summary: This article reviews the efficacy, safety, and tolerability of Cenobamate in treating partial-onset seizures. The findings suggest that Cenobamate, compared to placebo, significantly reduces seizure frequency and increases the number of participants with reduced seizure frequency and adverse effects. However, multiple drug-drug interactions remain a concern.

JOURNAL OF CENTRAL NERVOUS SYSTEM DISEASE (2022)

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Review Biochemistry & Molecular Biology

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

Huiyuan Zhu et al.

Summary: The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet that has shown therapeutic potential for various diseases. This review summarizes the evidence of its efficacy and safety, discusses the possible mechanisms of action, and suggests the need for randomized controlled trials to support its clinical use.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Engineering, Biomedical

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy

Beata Jarosiewicz et al.

Summary: This review discusses the NeuroPace RNS System, the only brain-responsive neurostimulation device, and the results of multi-year clinical trials. Brain-responsive neurostimulation has the potential to be used for treating episodic neurological disorders with a neurophysiological biomarker of severity, and combining advanced machine learning with chronic ambulatory brain data collected by the RNS System could lead to personalized treatment for each patient.

EXPERT REVIEW OF MEDICAL DEVICES (2021)

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Review Clinical Neurology

Practical use of pharmaceutically purified oral cannabidiol in Dravet syndrome and Lennox-Gastaut syndrome

Simona Lattanzi et al.

Summary: Pharmaceutically purified oral cannabidiol (CBD) has been approved for treating seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), showing efficacy in managing symptoms such as somnolence, gastrointestinal discomfort, and increase in serum transaminases. CBD's metabolism in the liver can influence drug metabolism enzymes, particularly in interactions with antiseizure medications like clobazam. The findings pertain specifically to high-grade purified CBD oral solution and may not be applicable to other cannabis-based products.

EXPERT REVIEW OF NEUROTHERAPEUTICS (2021)

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Article Plant Sciences

Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica

Priya Mishra et al.

Summary: The study explored the anticonvulsant and antiepileptogenic potential of Nux vomica homeopathic medicinal preparations in acute and chronic seizure models, showing promising results in improving cognitive and memory function, reducing motor impairment, and alleviating oxidative stress in kindled animals. The findings suggest that further investigation into the cellular and molecular mechanisms of these preparations is warranted.

JOURNAL OF ETHNOPHARMACOLOGY (2021)

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Article Behavioral Sciences

Efficacy of Cicuta virosa medicinal preparations against pentylenetetrazole-induced seizures

Priya Mishra et al.

Summary: Homeopathic medicinal preparations (HMPs) of Cicuta virosa (CV) show promising therapeutic potential in experimental models of epilepsy, modulating neurotransmission and improving cognitive function. By reducing oxidative stress load, CV HMPs also demonstrate a role in enhancing free radical scavenging mechanism.

EPILEPSY & BEHAVIOR (2021)

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Review Biochemical Research Methods

Neural interface systems with on-device computing: machine learning and neuromorphic architectures

Jerald Yoo et al.

Summary: The development of neural interface and brain-machine interface systems has opened up new possibilities for treating various neurological disorders through the integration of artificial intelligence and machine learning. This trend towards combining advanced technologies will lead to the creation of low-power, smart, and miniaturized therapeutic devices for a wide range of neurological and psychiatric disorders.

CURRENT OPINION IN BIOTECHNOLOGY (2021)

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Review Clinical Neurology

Technology of deep brain stimulation: current status and future directions

Joachim K. Krauss et al.

Summary: Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation and is now commonly used for the treatment of movement disorders such as Parkinson's disease, tremor, and dystonia. Advances in engineering and imaging technologies are expected to enhance the efficacy and tolerability of DBS procedures in the future.

NATURE REVIEWS NEUROLOGY (2021)

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Article Medicine, Research & Experimental

Surgical and Hardware Complications of Deep Brain Stimulation-A Single Surgeon Experience of 519 Cases Over 20 Years

Paresh K. Doshi et al.

Summary: This study analyzed the risk factors for complications in deep brain stimulation (DBS) surgery and found that the complication rate decreases with cumulative years of experience, demonstrating a learning curve effect.

NEUROMODULATION (2021)

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Review Neurosciences

NPY and Gene Therapy for Epilepsy: How, When, ... and Y ...

Stefano Cattaneo et al.

Summary: Neuropeptide Y is a pleiotropic molecule that influences cell proliferation, cardiovascular and metabolic function, pain, and neuronal excitability, with potential anti-epileptic effects. Overexpression of NPY in the brain with viral vectors can suppress seizures in animal models of epilepsy, suggesting a novel approach for epilepsy treatment. However, further research is needed to fully understand the therapeutic potential of NPY-based gene therapy for epilepsy.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2021)

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Review Clinical Neurology

Responsive Vagus Nerve Stimulation for Drug Resistant Epilepsy: A Review of New Features and Practical Guidance for Advanced Practice Providers

Breanne Fisher et al.

Summary: Vagus nerve stimulation (VNS) is a safe and effective therapy for drug resistant epilepsy that has been available for over 20 years. The therapy has evolved to provide advanced features and closed-loop stimulation, and dedicated VNS clinics managed by Advanced Practice Providers (APPs) have improved access and continuity of care for patients. APPs play an integral role in comprehensive healthcare teams, providing guidance and support for those managing VNS patients.

FRONTIERS IN NEUROLOGY (2021)

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Article Clinical Neurology

Closed-loop stimulation of the medial septum terminates epileptic seizures

Yuichi Takeuchi et al.

Summary: The study demonstrates that closed-loop electrical stimulation of the medial septum can effectively terminate intrahippocampal seizures and suppress secondary generalization, emphasizing the importance of internally driven stimulus timing. By precisely activating medial septum GABAergic neurons, successful intervention in pathological oscillations was achieved, providing a new avenue for future clinical translation in other neurological and psychiatric disorders.

BRAIN (2021)

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Review Neurosciences

Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research

Valentina Franco et al.

Summary: CBD has shown therapeutic potential in seizure disorders, with progress made in understanding its mechanisms of action and clinical properties. A pharmaceutical-grade formulation of purified CBD has been approved for treatment in certain seizure syndromes, but interactions with other medications, such as clobazam, remain a complex issue. Despite advances, there are still significant gaps in knowledge regarding CBD's antiseizure activity.

NEUROPHARMACOLOGY (2021)

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Review Psychology, Biological

The dynamic regulation of appetitive behavior through lateral hypothalamic orexin and melanin concentrating hormone expressing cells

Jenna Lee et al.

Summary: The lateral hypothalamic area (LHA) plays a crucial role in regulating energy balance through coordination of feeding behavior mainly by Orexin (ORX) and Melanin Concentrating Hormone (MCH) cell populations. These two systems support feeding behavior through different mechanisms, interact with other neuropeptides and reward systems, and regulate appetite by transitioning between different appetitive states.

PHYSIOLOGY & BEHAVIOR (2021)

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Review Clinical Neurology

Effects of the COVID-19 pandemic on medication adherence: In the case of antiseizure medications, A scoping review

Sonia Menon et al.

Summary: The global health emergency caused by the COVID-19 pandemic has had a negative impact on medication adherence among people with epilepsy, highlighting the need for more research. A literature scoping review identified key issues in ASM adherence, such as lack of follow-up and difficulties accessing medications, calling for a more comprehensive chronic disease model to be established.

SEIZURE-EUROPEAN JOURNAL OF EPILEPSY (2021)

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Review Nanoscience & Nanotechnology

Targeted drug delivery strategies for precision medicines

Mandana T. Manzari et al.

Summary: Precision medicine offers personalized treatment strategies for individual patients, especially in the field of cancer therapy. While there have been some clinical successes, challenges such as drug toxicities and resistance still hinder the full potential of precision medicine. Advanced drug delivery materials and approaches provide opportunities to improve therapeutic outcomes and overcome pharmacological issues in cancer treatment.

NATURE REVIEWS MATERIALS (2021)

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Review Clinical Neurology

Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome

Simona Lattanzi et al.

Summary: CBD, a major constituent of the Cannabis sativa plant, has been approved by the US FDA and EMA for the treatment of seizures. Studies have shown that a highly purified oral formulation of CBD can be effective in treating a broad range of epilepsy disorders beyond Dravet syndrome and Lennox-Gastaut syndrome.

CNS DRUGS (2021)

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Review Neurosciences

Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord

Thomas Leth Jensen et al.

Summary: In recent years, gene therapy has advanced in the treatment of rare genetic diseases, particularly those affecting the brain and spinal cord such as spinal muscular atrophy and metachromatic leukodystrophy. These successes may indicate the emergence of more new gene therapies in the future.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2021)

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Review Behavioral Sciences

Precision medicine in women with epilepsy: The challenge, systematic review, and future direction

Yi Li et al.

Summary: Epilepsy is a common neurological condition that affects nearly 70 million people globally. Women with epilepsy face gender-specific challenges and precision medicine may offer tailored management solutions.

EPILEPSY & BEHAVIOR (2021)

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Review Pharmacology & Pharmacy

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

Leontina Elena Filipiuc et al.

Summary: The discovery of the pharmacological effects of cannabis, traditionally used in Asia, has led to the development of new compounds for treating various diseases. Recent research suggests that these effects may not only involve cannabinoid receptors, but also other mechanisms yet to be fully understood.

PHARMACEUTICS (2021)

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Review Neurosciences

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

Bruno Bonaz et al.

Summary: The vagus nerve has dual anti-inflammatory properties and may be used in the treatment of chronic inflammatory bowel diseases. Its activation can inhibit the release of tumor necrosis factor (TNF) alpha by various mechanisms, making it a potential non-drug therapeutic approach.

FRONTIERS IN NEUROSCIENCE (2021)

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Article Psychiatry

Deep Brain Stimulation for Obsessive-Compulsive Disorder: Real World Experience Post-FDA-Humanitarian Use Device Approval

Lora Kahn et al.

Summary: This study demonstrated the effectiveness of deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD) even in patients with comorbidities. Patients with various comorbid diseases showed significant improvement in OCD symptoms through DBS therapy, emphasizing the importance of accurate electrode placement and programming strategies.

FRONTIERS IN PSYCHIATRY (2021)

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Review Biochemistry & Molecular Biology

Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

Shampa Ghosh et al.

Summary: Epilepsy is a common chronic brain disorder affecting people of all ages, accompanied by various health issues. Understanding the mechanisms and treatment of epilepsy is crucial for improving the quality of life for patients.

BIOMEDICINES (2021)

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Article Engineering, Biomedical

A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia

B. Csernyus et al.

Summary: The study demonstrated that cooling the cortical surface to around 20 degrees Celsius efficiently suppresses epileptic discharges, with distant cortical areas also being influenced. This suggests that the efficacy of seizure suppression is not solely determined by the absolute drop in temperature.

JOURNAL OF NEURAL ENGINEERING (2021)

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Review Neurosciences

Energy-Efficient Integrated Circuit Solutions Toward Miniaturized Closed-Loop Neural Interface Systems

Jaeouk Cho et al.

Summary: Miniaturized implantable devices are crucial for neural interfaces in monitoring and modulating neural activities. The pursuit of a compact wireless closed-loop system can automatically stimulate nerves based on user conditions, reducing power consumption and side effects. However, challenges in hardware design remain, such as neural activity recording and energy-efficient wireless power delivery.

FRONTIERS IN NEUROSCIENCE (2021)

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Article Clinical Neurology

Epilepsy Personal Assistant Device-A Mobile Platform for Brain State, Dense Behavioral and Physiology Tracking and Controlling Adaptive Stimulation

Tal Pal Attia et al.

Summary: Epilepsy is a common neurological disorder affecting approximately 1% of the global population, with many patients continuing to have seizures despite treatment. The unpredictable nature of seizures and associated comorbidities significantly impact quality of life. Seizure predictions and long-term objective data are essential for optimizing treatment.

FRONTIERS IN NEUROLOGY (2021)

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Review Clinical Neurology

The Pharmacoresistant Epilepsy: An Overview on Existant and New Emerging Therapies

Antonella Fattorusso et al.

Summary: Epilepsy is a common chronic neurological disorder with a prevalence of 0.5-1%. Most patients can achieve seizure control with medication, but about one-third are drug-resistant, making management challenging.

FRONTIERS IN NEUROLOGY (2021)

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Review Clinical Neurology

Emerging Role of the Ketogenic Dietary Therapies beyond Epilepsy in Child Neurology

Dipti Kapoor et al.

Summary: The ketogenic dietary therapies have been successfully used for childhood epilepsy for a century, showing potential benefits in various neurological conditions other than epilepsy such as autism spectrum disorder and Fragile X syndrome. Research in this field is still in the early stages, presenting a wide scope for further studies.

ANNALS OF INDIAN ACADEMY OF NEUROLOGY (2021)

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Article Biochemistry & Molecular Biology

Clinical Potential of Nerve Input to Tumors: A Bioelectricity Perspective

Jade A. Phillips et al.

Summary: This article supports the significant role of neural connections and bioelectricity in the tumor microenvironment. While nerve input promotes cancer development, direct surgical denervation of tumors may have unpredictable and irreversible side effects. Using electroceutical approaches, tumor innervation can be effectively manipulated to improve therapeutic outcomes.

BIOELECTRICITY (2021)

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Review Engineering, Biomedical

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy

Pegah Afra et al.

Summary: The Vagus Nerve Stimulation (VNS) Therapy System is the first FDA-approved medical device therapy for drug-resistant epilepsy treatment. This technology has evolved over the past two decades with multiple updates, resulting in various generator models with subtle differences that can be challenging for healthcare providers to differentiate without manual comparison.

FRONTIERS IN MEDICAL TECHNOLOGY (2021)

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Review Neurosciences

Artificial Intelligence in Epilepsy

Taranjit Kaur et al.

Summary: Research on AI systems for pattern recognition in EEG can assist in more accurate diagnoses, but it is important to note that AI is meant to work alongside doctors rather than replace them, emphasizing the importance of domain knowledge in building robust AI models for real-time scenarios.

NEUROLOGY INDIA (2021)

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Review Geriatrics & Gerontology

Neuromodulation in Drug Resistant Epilepsy

Natalia Rincon et al.

Summary: Epilepsy affects millions worldwide, with drug-resistant cases posing a challenge for surgical intervention. Neuromodulation therapies like VNS, RNS, and DBS may offer alternative treatment options for these patients.

AGING AND DISEASE (2021)

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Review Clinical Neurology

Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications

Dustin R. Latimer et al.

Summary: The medical management of epilepsy aims to reduce seizure frequency and help patients maintain a normal lifestyle, but current drugs have potential side effects. Cenobamate, a newly FDA-approved drug for partial-onset seizures, shows promise in reducing seizures but can cause side effects such as somnolence and dizziness. Ongoing studies are evaluating its long-term benefits and adverse events.

NEUROLOGY INTERNATIONAL (2021)

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Review Clinical Neurology

Action of antiepileptic drugs on neurons

Katsuhiro Kobayashi et al.

BRAIN & DEVELOPMENT (2020)

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Review Anatomy & Morphology

The anatomical basis for transcutaneous auricular vagus nerve stimulation

Mohsin F. Butt et al.

JOURNAL OF ANATOMY (2020)

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Article Behavioral Sciences

Enhancing quality of life among epilepsy surgery patients: Interlinking multiple social and relational determinants

Patti Shih et al.

EPILEPSY & BEHAVIOR (2020)

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Article Clinical Neurology

Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures

Steve S. Chung et al.

NEUROLOGY (2020)

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Review Pharmacology & Pharmacy

Neuromodulation for the Treatment of Epilepsy: A Review of Current Approaches and Future Directions

Patrick Davis et al.

CLINICAL THERAPEUTICS (2020)

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Article Clinical Neurology

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures

Babak Razavi et al.

EPILEPSIA (2020)

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Article Clinical Neurology

Safety of responsive neurostimulation in pediatric patients with medically refractory epilepsy

Fedor Panov et al.

JOURNAL OF NEUROSURGERY-PEDIATRICS (2020)

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Article Clinical Neurology

Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study

Hemmings Wu et al.

NEUROSURGERY (2020)

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Review Pharmacology & Pharmacy

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

Wolfgang Loescher et al.

PHARMACOLOGICAL REVIEWS (2020)

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Review Clinical Neurology

Biomarkers of seizure response to vagus nerve stimulation: A scoping review

Adriana M. Workewych et al.

EPILEPSIA (2020)

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Review Clinical Neurology

Impact of predictive, preventive and precision medicine strategies in epilepsy

Rima Nabbout et al.

NATURE REVIEWS NEUROLOGY (2020)

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Article Clinical Neurology

Centromedian thalamic responsive neurostimulation for Lennox-Gastaut epilepsy and autism

Churl-Su Kwon et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2020)

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Review Biochemistry & Molecular Biology

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Nicole Jacqueline Jensen et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Pharmacology & Pharmacy

Cannabidiol inhibits febrile seizure by modulating AMPA receptor kinetics through its interaction with the N-terminal domain of GluA1/GluA2

Yongzhou Yu et al.

PHARMACOLOGICAL RESEARCH (2020)

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Article Neurosciences

Role of Neuromodulation for Treatment of Drug-Resistant Epilepsy

Jasmine Parihar et al.

NEUROLOGY INDIA (2020)

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Review Behavioral Sciences

Seizure clusters, rescue treatments, seizure action plans: Unmet needs and emerging formulations

Barry Gidal et al.

EPILEPSY & BEHAVIOR (2020)

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Review Biochemistry & Molecular Biology

Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Hongyi Li et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Article Clinical Neurology

Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk factors

R. Stevelin et al.

EUROPEAN JOURNAL OF NEUROLOGY (2019)

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Article Clinical Neurology

Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results

Linda C. Laux et al.

EPILEPSY RESEARCH (2019)

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Review Clinical Neurology

A systematic review of deep brain stimulation for the treatment of drug-resistant epilepsy in childhood

Han Yan et al.

JOURNAL OF NEUROSURGERY-PEDIATRICS (2019)

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Review Clinical Neurology

Deep brain stimulation: current challenges and future directions

Andres M. Lozano et al.

NATURE REVIEWS NEUROLOGY (2019)

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Review Neurosciences

Neuron-glia interactions in the pathophysiology of epilepsy

Dipan C. Patel et al.

NATURE REVIEWS NEUROSCIENCE (2019)

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Article Pharmacology & Pharmacy

Safety aspects of antiepileptic drugs-a population-based study of adverse effects relative to changes in utilisation

Arton Baftiu et al.

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY (2019)

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Article Clinical Neurology

Vagus Nerve Stimulation for the Treatment of Epilepsy

Herman F. J. Gonzalez et al.

NEUROSURGERY CLINICS OF NORTH AMERICA (2019)

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Review Neurosciences

Research progress of vagus nerve stimulation in the treatment of epilepsy

Jing-Jing Fan et al.

CNS NEUROSCIENCE & THERAPEUTICS (2019)

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Article Neurosciences

Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics

Adolfo Ramirez-Zamora et al.

FRONTIERS IN NEUROSCIENCE (2019)

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Review Engineering, Biomedical

Neural stimulation systems for the control of refractory epilepsy: a review

Matthew D. Bigelow et al.

JOURNAL OF NEUROENGINEERING AND REHABILITATION (2019)

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Article Clinical Neurology

Clinical outcomes of closed-loop vagal nerve stimulation in patients with refractory epilepsy

Michal Tzadok et al.

SEIZURE-EUROPEAN JOURNAL OF EPILEPSY (2019)

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Article Biochemistry & Molecular Biology

Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10

Morgan L. Maeder et al.

NATURE MEDICINE (2019)

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Review Clinical Neurology

Closed-Loop Brain Stimulation for Drug-Resistant Epilepsy: Towards an Evidence-Based Approach to Personalized Medicine

Nathaniel D. Sisterson et al.

NEUROTHERAPEUTICS (2019)

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Article Medicine, Research & Experimental

Vagus nerve stimulation for pediatric patients with intractable epilepsy between 3 and 6years of age: study protocol for a double-blind, randomized control trial

Taoyun Ji et al.

TRIALS (2019)

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Article Medicine, Research & Experimental

Closed-Loop Neuromodulation in Physiological and Translational Research

Stavros Zanos

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2019)

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Article Engineering, Biomedical

A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates

Andy Zhou et al.

NATURE BIOMEDICAL ENGINEERING (2019)

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Review Clinical Neurology

Deep brain stimulation for drug-resistant epilepsy

Michael C. H. Li et al.

EPILEPSIA (2018)

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Review Clinical Neurology

Lennox-Gastaut syndrome: a comprehensive review

Ali A. Asadi-Pooya

NEUROLOGICAL SCIENCES (2018)

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Review Clinical Neurology

Neocortical electrical stimulation for epilepsy: Closed-loop versus open-loop

Albena Vassileva et al.

EPILEPSY RESEARCH (2018)

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Review Medicine, General & Internal

Practical considerations in medical cannabis administration and dosing

Caroline A. MacCallum et al.

EUROPEAN JOURNAL OF INTERNAL MEDICINE (2018)

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Article Engineering, Biomedical

Closed-Loop Vagus Nerve Stimulation Based on State Transition Models

Hector M. Romero-Ugalde et al.

IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING (2018)

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Article Neurosciences

Promises and limitations of human intracranial electroencephalography

Josef Parvizi et al.

NATURE NEUROSCIENCE (2018)

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Article Medicine, General & Internal

Epilepsy

Orrin Devinsky et al.

NATURE REVIEWS DISEASE PRIMERS (2018)

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Review Engineering, Biomedical

Recent advances in devices for vagus nerve stimulation

Ann Mertens et al.

EXPERT REVIEW OF MEDICAL DEVICES (2018)

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Review Pediatrics

Dietary Therapies: Emerging Paradigms in Therapy of Drug Resistant Epilepsy in Children Based on 6th Dr. I. C. Verma Excellence in Research Award Oration

Sheffali Gulati

INDIAN JOURNAL OF PEDIATRICS (2018)

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Review Behavioral Sciences

Responsive neurostimulation: Candidates and considerations

Brandy B. Ma et al.

EPILEPSY & BEHAVIOR (2018)

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Article Multidisciplinary Sciences

Closed-loop functional optogenetic stimulation

Shriya S. Srinivasan et al.

NATURE COMMUNICATIONS (2018)

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Article Clinical Neurology

Responsive neurostimulation for treatment of pediatric drug-resistant epilepsy

Nilika S. Singhal et al.

EPILEPSY & BEHAVIOR CASE REPORTS (2018)

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Review Neurosciences

Diagnosis and Surgical Treatment of Drug-Resistant Epilepsy

Chinekwu Anyanwu et al.

BRAIN SCIENCES (2018)

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Editorial Material Biochemistry & Molecular Biology

A brief account of viral vectors and their promise for gene therapy

M. Finer et al.

GENE THERAPY (2017)

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Review Engineering, Biomedical

Advances in closed-loop deep brain stimulation devices

Mahboubeh Parastarfeizabadi et al.

JOURNAL OF NEUROENGINEERING AND REHABILITATION (2017)

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Article Medicine, General & Internal

Neurostimulation Devices for the Treatment of Neurologic Disorders

Christine A. Edwards et al.

MAYO CLINIC PROCEEDINGS (2017)

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Review Neurosciences

Integration of optogenetics with complementary methodologies in systems neuroscience

Christina K. Kim et al.

NATURE REVIEWS NEUROSCIENCE (2017)

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Review Clinical Neurology

Efficacy of adjunctive vagus nerve stimulation in patients with Dravet syndrome: A meta-analysis of 68 patients

Maxine Dibue-Adjei et al.

SEIZURE-EUROPEAN JOURNAL OF EPILEPSY (2017)

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Article Multidisciplinary Sciences

Sustained efficacy of closed loop electrical stimulation for long-term treatment of absence epilepsy in rats

Gabor Kozak et al.

SCIENTIFIC REPORTS (2017)

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Review Clinical Neurology

Expert Opinion on the Management of Lennox-Gastaut Syndrome: Treatment Algorithms and Practical Consideration

J. Helen Cross et al.

FRONTIERS IN NEUROLOGY (2017)

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Review Clinical Neurology

New insights into the mechanisms of the ketogenic diet

Detlev Boison

CURRENT OPINION IN NEUROLOGY (2017)

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Article Clinical Neurology

Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study

Charly Gaul et al.

CEPHALALGIA (2016)

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Article Engineering, Biomedical

Seizure Suppression Efficacy of Closed-Loop Versus Open-Loop Deep Brain Stimulation in a Rodent Model of Epilepsy

M. Tariqus Salam et al.

IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING (2016)

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Comparing neurostimulation technologies in refractory focal-onset epilepsy

Inuka Kishara Gooneratne et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2016)

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Article Multidisciplinary Sciences

High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects

Benjamin P. Kleinstiver et al.

NATURE (2016)

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Cognitive and neurodevelopmental comorbidities in paediatric epilepsy

Katherine C. Nickels et al.

NATURE REVIEWS NEUROLOGY (2016)

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Article Medicine, Research & Experimental

Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet

Michael A. Rogawski et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2016)

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CRISPR-mediated genome editing and human diseases

Liquan Cai et al.

GENES & DISEASES (2016)

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The ketogenic diet in pharmacoresistant childhood epilepsy

Steven Parrish Winesett et al.

EXPERT REVIEW OF NEUROTHERAPEUTICS (2015)

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A roadmap for precision medicine in the epilepsies

F. Berkovic et al.

LANCET NEUROLOGY (2015)

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Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy

Vicenta Salanova et al.

NEUROLOGY (2015)

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Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

Gregory K. Bergey et al.

NEUROLOGY (2015)

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Optogenetics and Epilepsy: Past, Present and Future

Jeanne T. Paz et al.

EPILEPSY CURRENTS (2015)

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Seizures and Epilepsy: An Overview for Neuroscientists

Carl E. Stafstrom et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2015)

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The ketogenic diet in pharmacoresistant childhood epilepsy

Steven Parrish Winesett et al.

EXPERT REVIEW OF NEUROTHERAPEUTICS (2015)

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Factors influencing medication adherence after epilepsy surgery

Jianming Liu et al.

EPILEPTIC DISORDERS (2015)

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Electrical Control of Epilepsy

David J. Mogul et al.

ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16 (2014)

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Review Engineering, Biomedical

Closed loop deep brain stimulation: an evolving technology

Md Kamal Hosain et al.

AUSTRALASIAN PHYSICAL & ENGINEERING SCIENCES IN MEDICINE (2014)

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Article Clinical Neurology

Seizure Suppression by High Frequency Optogenetic Stimulation Using In Vitro and In Vivo Animal Models of Epilepsy

Chia-Chu Chiang et al.

BRAIN STIMULATION (2014)

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Article Clinical Neurology

Vagus nerve stimulation for drug-resistant epilepsy: A European long-term study up to 24 months in 347 children

Iren Orosz et al.

EPILEPSIA (2014)

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Article Clinical Neurology

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

Christianne N. Heck et al.

EPILEPSIA (2014)

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Article Clinical Neurology

ILAE Official Report: A practical clinical definition of epilepsy

Robert S. Fisher et al.

EPILEPSIA (2014)

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Review Behavioral Sciences

Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy

Sriram Ramgopal et al.

EPILEPSY & BEHAVIOR (2014)

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Review Behavioral Sciences

The consequences of refractory epilepsy and its treatment

Kenneth D. Laxer et al.

EPILEPSY & BEHAVIOR (2014)

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Article Clinical Neurology

Gene therapy in epilepsy-is it time for clinical trials?

Dimitri M. Kullmann et al.

NATURE REVIEWS NEUROLOGY (2014)

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Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

Nealen G. Laxpati et al.

NEUROTHERAPEUTICS (2014)

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What Happens to Children With Epilepsy When They Become Adults? Some Facts and Opinions

Peter R. Camfield et al.

PEDIATRIC NEUROLOGY (2014)

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Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function

Hua Hu et al.

SCIENCE (2014)

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Editorial Material Clinical Neurology

Responsive Neurostimulation: The Hope and the Challenges

Lara Jehi

EPILEPSY CURRENTS (2014)

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Optogenetic strategies to investigate neural circuitry engaged by stress

Dennis R. Sparta et al.

BEHAVIOURAL BRAIN RESEARCH (2013)

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Optical developments for optogenetics

Eirini Papagiakoumou

BIOLOGY OF THE CELL (2013)

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Progress in gene therapy for neurological disorders

Michele Simonato et al.

NATURE REVIEWS NEUROLOGY (2013)

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Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction

Ethan M. Goldberg et al.

NATURE REVIEWS NEUROSCIENCE (2013)

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Adeno-associated virus (AAV) gene therapy for neurological disease

Marc S. Weinberg et al.

NEUROPHARMACOLOGY (2013)

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FRONTIERS Surgery of the Mind, Mood, and Conscious State: An Idea in Evolution

R. Aaron Robison et al.

WORLD NEUROSURGERY (2013)

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Host factors affecting antiepileptic drug delivery-Pharmacokinetic variability

Cecilie Johannessen Landmark et al.

ADVANCED DRUG DELIVERY REVIEWS (2012)

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Therapeutic devices for epilepsy

Robert S. Fisher

ANNALS OF NEUROLOGY (2012)

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Molecular Tools and Approaches for Optogenetics

Yuan Mei et al.

BIOLOGICAL PSYCHIATRY (2012)

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Adherence to antiepilepsy drug therapy

Edward Faught

EPILEPSY & BEHAVIOR (2012)

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Ketone bodies in epilepsy

Melanie A. McNally et al.

JOURNAL OF NEUROCHEMISTRY (2012)

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Deep brain stimulation in addiction: a review of potential brain targets

J. Luigjes et al.

MOLECULAR PSYCHIATRY (2012)

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Optogenetic investigation of neural circuits underlying brain disease in animal models

Kay M. Tye et al.

NATURE REVIEWS NEUROSCIENCE (2012)

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Closed-Loop Control of Epilepsy by Transcranial Electrical Stimulation

Antal Berenyi et al.

SCIENCE (2012)

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Computational models of epilepsy

Roxana A. Stefanescu et al.

SEIZURE-EUROPEAN JOURNAL OF EPILEPSY (2012)

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The Development and Application of Optogenetics

Lief Fenno et al.

ANNUAL REVIEW OF NEUROSCIENCE, VOL 34 (2011)

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Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: Long-term outcomes and predictors of response

Robert E. Elliott et al.

EPILEPSY & BEHAVIOR (2011)

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Obstructive Sleep Apnea and Respiratory Complications Associated with Vagus Nerve Stimulators

Fuzhan Parhizgar et al.

JOURNAL OF CLINICAL SLEEP MEDICINE (2011)

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The efficacy of vagal nerve stimulation in children with pharmacoresistant epilepsy: Practical experience at a Turkish tertiary referral center

Ebru Arhan et al.

EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY (2010)

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Overview of the Clinical Applications of Vagus Nerve Stimulation

J. P. Beekwilder et al.

JOURNAL OF CLINICAL NEUROPHYSIOLOGY (2010)

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Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience

B. D. Greenberg et al.

MOLECULAR PSYCHIATRY (2010)

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Current and future indications for deep brain stimulation in pediatric populations

Nir Lipsman et al.

NEUROSURGICAL FOCUS (2010)

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Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug Development

Abdul Wahab

PHARMACEUTICALS (2010)

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Gene therapy in epilepsy

Veronique Riban et al.

EPILEPSIA (2009)

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Curing epilepsy: Progress and future directions

Margaret P. Jacobs et al.

EPILEPSY & BEHAVIOR (2009)

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Epileptogenesis in the immature brain: emerging mechanisms

Sanjay N. Rakhade et al.

NATURE REVIEWS NEUROLOGY (2009)

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Neural regulation of endocrine and autonomic stress responses

Yvonne M. Ulrich-Lai et al.

NATURE REVIEWS NEUROSCIENCE (2009)

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CNS adverse events associated with antiepileptic drugs

Gina M. Kennedy et al.

CNS DRUGS (2008)

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Modern management of epilepsy: A practical approach

Christian E. Elger et al.

EPILEPSY & BEHAVIOR (2008)

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Technology insight: neuroengineering and epilepsy - designing devices for seizure control

William C. Stacey et al.

NATURE CLINICAL PRACTICE NEUROLOGY (2008)

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The neuropharmacology of the ketogenic diet

Adam L. Hartman et al.

PEDIATRIC NEUROLOGY (2007)

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Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs

Wolfgang Loescher et al.

EPILEPSIA (2006)

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Adult epilepsy

JS Duncan et al.

LANCET (2006)

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The ketogenic diet: From molecular mechanisms to clinical effects

J Freeman et al.

EPILEPSY RESEARCH (2006)

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Deep brain stimulation: Postoperative issues

Guenther Deuschl et al.

MOVEMENT DISORDERS (2006)

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Drug resistance in epilepsy:: Putative neurobiologic and clinical mechanisms

D Schmidt et al.

EPILEPSIA (2005)

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The neurobiology of antiepileptic drugs

MA Rogawski et al.

NATURE REVIEWS NEUROSCIENCE (2004)

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Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs

PN Patsalos et al.

LANCET NEUROLOGY (2003)

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Therapeutic mechanisms of vagus nerve stimulation

TR Henry

NEUROLOGY (2002)

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Some common issues in the use of antiepileptic drugs

JJ Asconape

SEMINARS IN NEUROLOGY (2002)

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Effects of vagus nerve stimulation on respiration during sleep - A pilot study

BA Malow et al.

NEUROLOGY (2000)

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