Experimental Treatment Options in Absence Epilepsy

Luijtelaar, Gilles van; Zobeiri, Mehrnoush; Lüttjohann, Annika; Depaulis, Antoine

doi:10.2174/1381612823666171017170226

Cited by 13 publications

(7 citation statements)

References 171 publications

(241 reference statements)

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“…Wavelet analysis is a fast and reliable method for assessing non-stationary signals like LFP or EEG recordings ( Hramov et al, 2015 ). Together with the fast temporal precision of EEG and LFP recordings, this approach allows a detection of fast and short-lasting events like SWD precursors and opens the door for an implementation in an on-line setting aimed at real time prediction and prevention ( Maksimenko et al, 2017 ) with as little interference to the overall brain activity as possible ( Osterhagen et al, 2010 ; van Luijtelaar et al, 2017 ). Such a treatment approach might go along with a strong relief of side-effects often reported for the commonly used chronic pharmaceutical interventions ( Crunelli et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Seizure Prediction in Genetic Rat Models of Absence Epilepsy: Improved Performance through Multiple-Site Cortico-Thalamic Recordings Combined with Machine Learning

Budde

Maksimenko

Sarink

et al. 2021

eNeuro

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Seizure prediction is the grand challenge of epileptology. However, effort was devoted to prediction of focal seizures, while generalized seizures were regarded as stochastic events. Long-lasting local field potential (LFP) recordings containing several hundred generalized spike and wave discharges (SWDs), acquired at eight locations in the cortico-thalamic system of absence epileptic rats, were iteratively analyzed in all possible combinations of either two or three recording sites, by a wavelet-based algorithm, calculating the product of the wavelet-energy signaling increases in synchronicity. Sensitivity and false alarm rate of prediction were compared between various combinations, and wavelet spectra of true and false positive predictions were fed to a random forest machine learning algorithm to further differentiate between them. Wavelet analysis of intracortical and cortico-thalamic LFP traces showed a significantly smaller number of false alarms compared with intrathalamic combinations, while predictions based on recordings in Layers IV, V, and VI of the somatosensory-cortex significantly outreached all other combinations in terms of prediction sensitivity. In 24-h out-of-sample recordings of nine Genetic Absence Epilepsy Rats from Strasbourg (GAERS), containing diurnal fluctuations of SWD occurrence, classification of true and false positives by the trained random forest further reduced the false alarm rate by 71%, although at some trade-off between false alarms and sensitivity of prediction, as reflected in relatively low F1 score values. Results provide support for the cortical-focus theory of absence epilepsy and allow the conclusion that SWDs are predictable to some degree. The latter paves the way for the development of closed-loop SWD prediction-prevention systems. Suggestions for a possible translation to human data are outlined.

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Section: Discussionmentioning

confidence: 99%

Seizure Prediction in Genetic Rat Models of Absence Epilepsy: Improved Performance through Multiple-Site Cortico-Thalamic Recordings Combined with Machine Learning

Budde

Maksimenko

Sarink

et al. 2021

eNeuro

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“…A prototypical thalamocortical dysrhythmia, in which rhythmic hypersynchronous burst fining is observed in cortical and thalamic neurons, is childhood absence epilepsy (CAE), which is found in about 10% of children with epilepsy. Patients experience up to several hundred seizures per day, characterized by reduced consciousness and concomitant synchronous, bilateral spike-wave discharges (SWD), as can be seen in the EEG [ 42 , 43 ] (see also Figure 1 ).…”

Section: Activity In the Thalamocortical System Shaping Physiological...mentioning

confidence: 99%

The Metabotropic Glutamate 5 Receptor in Sleep and Wakefulness: Focus on the Cortico-Thalamo-Cortical Oscillations

Ngomba,

Lüttjohann,

Dexter

et al. 2023

Cells

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Sleep is an essential innate but complex behaviour which is ubiquitous in the animal kingdom. Our knowledge of the distinct neural circuit mechanisms that regulate sleep and wake states in the brain are, however, still limited. It is therefore important to understand how these circuits operate during health and disease. This review will highlight the function of mGlu5 receptors within the thalamocortical circuitry in physiological and pathological sleep states. We will also evaluate the potential of targeting mGlu5 receptors as a therapeutic strategy for sleep disorders that often co-occur with epileptic seizures.

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“…Concerning new frontier therapies there is a new drug (EpidiolexVR), an oral form of phytocannabinoid that is currently in phase 2 trials in children with pharmaco-resistant absence seizures; however there are no publicly reported data on the use of this drug for absence animal models and its possible neuropsychological effects in children and adolescents remains unclear [59,61]. Concerning non-pharmacological treatment, experimental animal models have identified highly excitable cortical zones that could be a future therapeutic target for techniques such as radiosurgery, ablation techniques or high frequency electrical subcortical or cortical stimulation [62]. Vagus nerve stimulation and ketogenic diet can also be considered in the management of pharmacological resistant forms of CAE.…”

Section: New Frontiers In Therapy-resistant Cae Formsmentioning

confidence: 99%

Therapeutic Options for Childhood Absence Epilepsy

et al. 2021

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Childhood absence epilepsy (CAE) is a common pediatric generalized epileptic syndrome. Although it is traditionally considered as a benign self-limited condition, the apparent benign nature of this syndrome has been revaluated in recent years. This is mainly due to the increasing evidence that children with CAE can present invalidating neuropsychological comorbidities that will affect them up to adulthood. Moreover, a percentage of affected children can develop drug-resistant forms of CAE. The purpose of this review is to summarize the most recent studies and new concepts concerning CAE treatment, in particular concerning drug-resistant forms of CAE. A Pubmed search was undertaken to identify all articles concerning management and treatment of CAE, including articles written between 1979 and 2021. Traditional anticonvulsant therapy of CAE that is still in use is based on three antiepileptic drugs: ethosuximide which is the drug of choice, followed by valproic acid and lamotrigine. In the case of first line treatment failure, after two monotherapies it is usual to start a bi-therapy. In the case of absence seizures that are refractory to traditional treatment, other antiepileptic drugs may be introduced such as levetiracetam, topiramate and zonisamide.

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Experimental Treatment Options in Absence Epilepsy

Abstract: Although it is obvious that some of these treatment possibilities will not be used for absence epilepsy and/or need to be further developed, all can be considered as proof of principle and provide clear directives for further developments.

Cited by 13 publications

References 171 publications

Seizure Prediction in Genetic Rat Models of Absence Epilepsy: Improved Performance through Multiple-Site Cortico-Thalamic Recordings Combined with Machine Learning

Seizure Prediction in Genetic Rat Models of Absence Epilepsy: Improved Performance through Multiple-Site Cortico-Thalamic Recordings Combined with Machine Learning

The Metabotropic Glutamate 5 Receptor in Sleep and Wakefulness: Focus on the Cortico-Thalamo-Cortical Oscillations

Therapeutic Options for Childhood Absence Epilepsy

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