Why we urgently need improved epilepsy therapies for adult patients

Billakota, Santoshi; Devinsky, Orrin; Kim, Kyung-Wha

doi:10.1016/j.neuropharm.2019.107855

Cited by 39 publications

(32 citation statements)

References 118 publications

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“…System (4) may undergo through these bifurcations in a repetitive manner for ε6 ¼0, which results eventually in the bursting solutions for small enough values of ε. As the arrows on Fig 3C and the traces on Fig 3B demonstrate, the trajectory follows the lower stable branch during the quiescence phase of the bursting, which terminates near v 2 � v LP 1 2 . Then, it jumps to the region of the stable limit cycles on the upper branch, which initiates the active phase of the bursting.…”

Section: Bursting Analysismentioning

confidence: 87%

“…We see that the corresponding system poses a Z-shaped bifurcation diagram as a function of v 2 with two folds, v LP 1 2 and v LP 2 2 . The equilibrium points are stable on the lower branch of the Z-shaped curve for v 2 > v LP 1 2 ; unstable along the middle branch between v LP 1 2 and v LP 2 2 . The upper branch has two…”

Section: Bursting Analysismentioning

confidence: 98%

“…Epilepsy is a severe, multi-causal chronic disease defined by the recurrence of unpredictable seizures that severely affect patients' quality of life. In 30% of patients, antiepileptic drugs [1] remain inefficient to control the occurrence of seizures. In most cases, drug-resistant epilepsies are 'focal' [2], as characterized by an epileptogenic zone (EZ) that is relatively circumscribed in one of the two cerebral hemispheres.…”

Section: Introductionmentioning

confidence: 99%

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Neural mass modeling of slow-fast dynamics of seizure initiation and abortion

et al. 2020

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Epilepsy is a dynamic and complex neurological disease affecting about 1% of the worldwide population, among which 30% of the patients are drug-resistant. Epilepsy is characterized by recurrent episodes of paroxysmal neural discharges (the so-called seizures), which manifest themselves through a large-amplitude rhythmic activity observed in depth-EEG recordings, in particular in local field potentials (LFPs). The signature characterizing the transition to seizures involves complex oscillatory patterns, which could serve as a marker to prevent seizure initiation by triggering appropriate therapeutic neurostimulation methods. To investigate such protocols, neurophysiological lumped-parameter models at the mesoscopic scale, namely neural mass models, are powerful tools that not only mimic the LFP signals but also give insights on the neural mechanisms related to different stages of seizures. Here, we analyze the multiple time-scale dynamics of a neural mass model and explain the underlying structure of the complex oscillations observed before seizure initiation. We investigate population-specific effects of the stimulation and the dependence of stimulation parameters on synaptic timescales. In particular, we show that intermediate stimulation frequencies (>20 Hz) can abort seizures if the timescale difference is pronounced. Those results have the potential in the design of therapeutic brain stimulation protocols based on the neurophysiological properties of tissue.

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Section: Bursting Analysismentioning

confidence: 87%

Section: Bursting Analysismentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Neural mass modeling of slow-fast dynamics of seizure initiation and abortion

et al. 2020

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“…Given the fact that about 30% of patients with epilepsy remain resistant to pharmacotherapy, continuing to experience seizures (reviewed in References [ 35 , 36 ]), it is imperative to persist studying the mechanisms underlying epileptogenesis. Developing innovative antiepileptogenic therapies that can modify this process, instead of only diminishing or abolishing seizures, and can decrease epilepsy-related comorbidities after the clinical diagnosis of epilepsy, is critical.…”

Section: Epilepsy and Epileptogenesismentioning

confidence: 99%

Neural Stem Cells and Cannabinoids in the Spotlight as Potential Therapy for Epilepsy

Lourenço

Ribeiro-Rodrigues

Sebastião

et al. 2020

IJMS

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Epilepsy is one of the most common brain diseases worldwide, having a huge burden in society. The main hallmark of epilepsy is the occurrence of spontaneous recurrent seizures, having a tremendous impact on the lives of the patients and of their relatives. Currently, the therapeutic strategies are mostly based on the use of antiepileptic drugs, and because several types of epilepsies are of unknown origin, a high percentage of patients are resistant to the available pharmacotherapy, continuing to experience seizures overtime. Therefore, the search for new drugs and therapeutic targets is highly important. One key aspect to be targeted is the aberrant adult hippocampal neurogenesis (AHN) derived from Neural Stem Cells (NSCs). Indeed, targeting seizure-induced AHN may reduce recurrent seizures and shed some light on the mechanisms of disease. The endocannabinoid system is a known modulator of AHN, and due to the known endogenous antiepileptic properties, it is an interesting candidate for the generation of new antiepileptic drugs. However, further studies and clinical trials are required to investigate the putative mechanisms by which cannabinoids can be used to treat epilepsy. In this manuscript, we will review how cannabinoid-induced modulation of NSCs may promote neural plasticity and whether these drugs can be used as putative antiepileptic treatment.

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“…Epilepsy, despite having a large number of different treatments, is actually one of the diseases with poor control of epileptic seizures. This is because of the lack of understanding of epileptogenesis, seizure genesis, seizure spread, and seizure suppression (1). Approximately 30% of patients have refractory epilepsy, which means that adequate trials of at least two drug programs have failed (2,3).…”

Section: Introductionmentioning

confidence: 99%

Caloric Restriction and Ketogenic Diet Therapy for Epilepsy: A Molecular Approach Involving Wnt Pathway and KATP Channels

et al. 2020

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Epilepsy is a neurological disorder in which, in many cases, there is poor pharmacological control of seizures. Nevertheless, it may respond beneficially to alternative treatments such as dietary therapy, like the ketogenic diet or caloric restriction. One of the mechanisms of these diets is to produce a hyperpolarization mediated by the adenosine triphosphate (ATP)-sensitive potassium (K ATP) channels (K ATP channels). An extracellular increase of K + prevents the release of Ca 2+ by inhibiting the signaling of the Wnt pathway and the translocation of β-catenin to the cell nucleus. Wnt ligands hyperpolarize the cells by activating K + current by Ca 2+. Each of the diets described in this paper has in common a lower use of carbohydrates, which leads to biochemical, genetic processes presumed to be involved in the reduction of epileptic seizures. Currently, there is not much information about the genetic processes implicated as well as the possible beneficial effects of diet therapy on epilepsy. In this review, we aim to describe some of the possible genes involved in Wnt pathways, their regulation through the K ATP channels which are implicated in each one of the diets, and how they can reduce epileptic seizures at the molecular level.

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Why we urgently need improved epilepsy therapies for adult patients

Cited by 39 publications

References 118 publications

Neural mass modeling of slow-fast dynamics of seizure initiation and abortion

Neural mass modeling of slow-fast dynamics of seizure initiation and abortion

Neural Stem Cells and Cannabinoids in the Spotlight as Potential Therapy for Epilepsy

Caloric Restriction and Ketogenic Diet Therapy for Epilepsy: A Molecular Approach Involving Wnt Pathway and KATP Channels

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