Materiały źródłowe

• #1 Absence Seizure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499867/

  The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures.[13] […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures.[4]

• #2 Absence Seizure | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28842

  A genetic component exists for all generalized epilepsies and, specifically, for absence epilepsy. The inheritance pattern is not strictly autosomal recessive or dominant and is considered to be multifactorial and polygenic. […] The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures. […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures. […] More recent research on penicillin-induced models of epilepsy in cats favors the cerebellum’s role in long-term electrical stimulation in absence epilepsy.

• #3 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  Absence seizures arise from hypersynchronous pathological oscillations within the CTC network. […] Alterations in the interplay between excitatory and inhibitory neurons in cortical and thalamic microcircuits can generate the pathological rhythmic activity seen in SWDs. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] The CTC network comprises reciprocal connections between the somatosensory cortex and the dorsal thalamus. […] Absence seizures are characterised by highly synchronised, generalised, pathological oscillations involving CTC networks on both sides of the brain.

• #4 Mechanisms of generalized absence epilepsy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9545175/

  Absence seizures represent bilaterally synchronous burst-firing of an ensemble of reciprocally connected neuronal populations located in the thalamus and neocortex. Recent studies demonstrate that neurons in the reticular thalamic nucleus (nRt), thalamic relay neurons (RNs), and neocortical pyramidal cells comprise a circuit that sustains the thalamocortical oscillatory burst-firing of absence seizures. Recent studies have focused on three intrinsic neuronal mechanisms that increase the likelihood of thalamocortical oscillations. The first mechanism involves T-currents elicited by activating the T-type calcium channel, which appear to trigger sustained burst-firing of thalamic neurons during absence seizures. A second intrinsic mechanism is GABA B receptors which can elicit longstanding hyperpolarization in thalamic neurons required to 'prime’ T-channels for sustained burst-firing. A third mechanism involves the ability of GABA A receptors, located on nRt neurons, to mediate recurrent inhibition. Enhanced activation of GABA A receptors on nRt neurons decreases the pacemaking capacity of these cells, therefore decreasing the likelihood of generating absence seizures. Cholinergic mechanisms through modulating cortical excitability and excitatory amino acid mediated mechanisms through depolarizing thalamic neurons also play a role in absence seizures.

• #5 Mechanisms of generalized absence epilepsy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9545175/

  Absence seizures represent bilaterally synchronous burst-firing of an ensemble of reciprocally connected neuronal populations located in the thalamus and neocortex. Recent studies demonstrate that neurons in the reticular thalamic nucleus (nRt), thalamic relay neurons (RNs), and neocortical pyramidal cells comprise a circuit that sustains the thalamocortical oscillatory burst-firing of absence seizures. Recent studies have focused on three intrinsic neuronal mechanisms that increase the likelihood of thalamocortical oscillations. The first mechanism involves T-currents elicited by activating the T-type calcium channel, which appear to trigger sustained burst-firing of thalamic neurons during absence seizures. A second intrinsic mechanism is GABA B receptors which can elicit longstanding hyperpolarization in thalamic neurons required to 'prime’ T-channels for sustained burst-firing. A third mechanism involves the ability of GABA A receptors, located on nRt neurons, to mediate recurrent inhibition. Enhanced activation of GABA A receptors on nRt neurons decreases the pacemaking capacity of these cells, therefore decreasing the likelihood of generating absence seizures. Cholinergic mechanisms through modulating cortical excitability and excitatory amino acid mediated mechanisms through depolarizing thalamic neurons also play a role in absence seizures.

• #6 Absence Seizures: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/1183858-overview

  Absence seizures are a type of generalized non-motor seizures. […] The pathophysiology of absence seizures is not fully understood. In 1947, Jasper and Droogleever-Fortuyn electrically stimulated nuclei in the thalami of cats at 3 Hz and produced bilaterally synchronous spike-and-wave discharges on EEG. […] Abnormal oscillatory rhythms are believed to develop in thalamocortical pathways. This involves gamma-aminobutyric acid (GABA)-B-mediated inhibition alternating with glutamate-mediated excitation. […] The cellular mechanism is believed to involve T-type calcium currents. T channels of the GABAergic reticular thalamic nucleus neurons appear to play a major role in the spike-wave discharges of the GABAergic thalamic neurons. […] GABA-B inhibition appears to be altered in absence seizures, and potentiation of GABA-B inhibition with tiagabine (Gabitril), vigabatrin (Sabril), and, possibly, gabapentin (Neurontin), results in exacerbation of absence seizures.

• #7 Absence Seizures: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/1183858-overview

  These data suggest that activity of thalamic networks is necessary for spike-wave discharge rhythmogenesis, and cortical hyperexcitability is necessary for their generation. […] In symptomatic generalized epilepsies, absence seizures are due to a wide variety of causes that at an early stage of neural development, result in diffuse or multifocal brain damage.

• #8 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  The focus is on highlighting our current understanding of potential causative mechanisms for absence seizure generation in CAE based on evidence from the latest research using cutting-edge technologies. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] Collectively, these studies indicate that there are both haemodynamic (BOLD) and EEG changes in cortical networks prior to generalised SWDs and absence seizures. […] The generation of generalised SWDs involved a multistage process: a pro-ictal network state lasting at least 1 min, and a pre-ictal network state lasting several seconds prior to SWDs on EEG. […] Overall, the consensus is that paroxysmal oscillation within corticothalamic loops is initiated in the CIN and that the large-scale synchronisation is mediated by way of an extremely fast intracortical spread of seizure activity. Thus, absence seizures are still considered to be correctly classified as a type of generalised seizure.

• #9 Absence Seizure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499867/

  The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures.[13] […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures.[4]

• #10 Absence Seizure | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28842

  A genetic component exists for all generalized epilepsies and, specifically, for absence epilepsy. The inheritance pattern is not strictly autosomal recessive or dominant and is considered to be multifactorial and polygenic. […] The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures. […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures. […] More recent research on penicillin-induced models of epilepsy in cats favors the cerebellum’s role in long-term electrical stimulation in absence epilepsy.

• #11 Absence Seizures: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/1183858-overview

  Absence seizures are a type of generalized non-motor seizures. […] The pathophysiology of absence seizures is not fully understood. In 1947, Jasper and Droogleever-Fortuyn electrically stimulated nuclei in the thalami of cats at 3 Hz and produced bilaterally synchronous spike-and-wave discharges on EEG. […] Abnormal oscillatory rhythms are believed to develop in thalamocortical pathways. This involves gamma-aminobutyric acid (GABA)-B-mediated inhibition alternating with glutamate-mediated excitation. […] The cellular mechanism is believed to involve T-type calcium currents. T channels of the GABAergic reticular thalamic nucleus neurons appear to play a major role in the spike-wave discharges of the GABAergic thalamic neurons. […] GABA-B inhibition appears to be altered in absence seizures, and potentiation of GABA-B inhibition with tiagabine (Gabitril), vigabatrin (Sabril), and, possibly, gabapentin (Neurontin), results in exacerbation of absence seizures.

• #12 Mechanisms of generalized absence epilepsy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9545175/

  Absence seizures represent bilaterally synchronous burst-firing of an ensemble of reciprocally connected neuronal populations located in the thalamus and neocortex. Recent studies demonstrate that neurons in the reticular thalamic nucleus (nRt), thalamic relay neurons (RNs), and neocortical pyramidal cells comprise a circuit that sustains the thalamocortical oscillatory burst-firing of absence seizures. Recent studies have focused on three intrinsic neuronal mechanisms that increase the likelihood of thalamocortical oscillations. The first mechanism involves T-currents elicited by activating the T-type calcium channel, which appear to trigger sustained burst-firing of thalamic neurons during absence seizures. A second intrinsic mechanism is GABA B receptors which can elicit longstanding hyperpolarization in thalamic neurons required to 'prime’ T-channels for sustained burst-firing. A third mechanism involves the ability of GABA A receptors, located on nRt neurons, to mediate recurrent inhibition. Enhanced activation of GABA A receptors on nRt neurons decreases the pacemaking capacity of these cells, therefore decreasing the likelihood of generating absence seizures. Cholinergic mechanisms through modulating cortical excitability and excitatory amino acid mediated mechanisms through depolarizing thalamic neurons also play a role in absence seizures.

• #13 Mechanisms of generalized absence epilepsy – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9545175/

  Absence seizures represent bilaterally synchronous burst-firing of an ensemble of reciprocally connected neuronal populations located in the thalamus and neocortex. Recent studies demonstrate that neurons in the reticular thalamic nucleus (nRt), thalamic relay neurons (RNs), and neocortical pyramidal cells comprise a circuit that sustains the thalamocortical oscillatory burst-firing of absence seizures. Recent studies have focused on three intrinsic neuronal mechanisms that increase the likelihood of thalamocortical oscillations. The first mechanism involves T-currents elicited by activating the T-type calcium channel, which appear to trigger sustained burst-firing of thalamic neurons during absence seizures. A second intrinsic mechanism is GABA B receptors which can elicit longstanding hyperpolarization in thalamic neurons required to 'prime’ T-channels for sustained burst-firing. A third mechanism involves the ability of GABA A receptors, located on nRt neurons, to mediate recurrent inhibition. Enhanced activation of GABA A receptors on nRt neurons decreases the pacemaking capacity of these cells, therefore decreasing the likelihood of generating absence seizures. Cholinergic mechanisms through modulating cortical excitability and excitatory amino acid mediated mechanisms through depolarizing thalamic neurons also play a role in absence seizures.

• #14 Difficulties in diagnosing absence seizures in adults | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-difficulties-in-diagnosing-absence-seizures-S2173580818300579

  Some studies suggest that calcium channels are a key factor in absence seizure pathogenesis. […] Zonisamide is an antiepileptic drug that stabilises the cell membrane and acts on voltage-dependent sodium channels and calcium channels; the latter are one of the main factors involved in the pathophysiology of absence seizures. […] This case demonstrates the potential difficulty involved in differentiating complex partial seizures from absence seizures in adult patients. […] Animal models have shown that correct, early treatment not only suppresses seizures, but also prevents the development of associated histological alterations.

• #15 Absence Seizure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499867/

  The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures.[13] […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures.[4]

• #16 What is the mechanism of Ethosuximide?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-ethosuximide

  Ethosuximide is an anti-epileptic drug primarily used in the treatment of absence seizures, a type of epilepsy characterized by brief and sudden lapses in consciousness. […] Ethosuximide primarily functions by modulating the activity of certain ion channels in the brain’s neurons. […] The main target of ethosuximide is the T-type calcium channel, a specific kind of voltage-gated calcium channel. […] Ethosuximide inhibits T-type calcium channels, reducing the flow of calcium ions into neurons during low-threshold calcium spikes. […] This inhibition decreases the excitability of thalamic neurons, thereby disrupting the abnormal rhythmic firing patterns that contribute to absence seizures. […] By dampening this abnormal activity, ethosuximide helps to stabilize neuronal firing and prevent the occurrence of these seizures. […] In conclusion, the mechanism of ethosuximide involves the inhibition of T-type calcium channels in thalamic neurons, leading to a reduction in the abnormal rhythmic activity that causes absence seizures.

• #17 What is the mechanism of Ethosuximide?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-ethosuximide

  Ethosuximide is an anti-epileptic drug primarily used in the treatment of absence seizures, a type of epilepsy characterized by brief and sudden lapses in consciousness. […] Ethosuximide primarily functions by modulating the activity of certain ion channels in the brain’s neurons. […] The main target of ethosuximide is the T-type calcium channel, a specific kind of voltage-gated calcium channel. […] Ethosuximide inhibits T-type calcium channels, reducing the flow of calcium ions into neurons during low-threshold calcium spikes. […] This inhibition decreases the excitability of thalamic neurons, thereby disrupting the abnormal rhythmic firing patterns that contribute to absence seizures. […] By dampening this abnormal activity, ethosuximide helps to stabilize neuronal firing and prevent the occurrence of these seizures. […] In conclusion, the mechanism of ethosuximide involves the inhibition of T-type calcium channels in thalamic neurons, leading to a reduction in the abnormal rhythmic activity that causes absence seizures.

• #18 CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

  https://genesdev.cshlp.org/content/29/14/1535.full.html

  CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. […] Interestingly, genetic studies have linked a large number of gain-of-function mutations on the CACNA1H gene, but no confirmed mutation on the CACNA1G and CACNA1I genes, with human childhood absence epilepsy (CAE) […] These findings establish the functional significance of CaV3.2 channels but raise the fundamental questions of what the primary function of CaV3.2 channels is and how CAE-linked CaV3.2 mutations may be epileptogenic. […] Instead, functional CaV3.2 channels primarily incorporated into synapses by replacing existing synaptic CaV3.2 channels and served to control the strength of NMDA transmission. […] These results reveal a surprising role of CaV3.2 channels in regulation of synaptic NMDA transmission strength and establish the first genetic model for CAE patients carrying CaV3.2 channel mutations.

• #19 CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

  https://genesdev.cshlp.org/content/29/14/1535.full.html

  We found that 60% of animals expressing hCaV3.2(C456S)-GFP exhibited 2- to 4-Hz SWDs, characteristic of CAE patients. […] These results indicate that the expression of hCaV3.2(C456S) mutant proteins enhances the susceptibility of absence-like epilepsy. […] Our analysis shows that expression of hCaV3.2(C456S) results in the replacement of endogenous CaV3.2 channels with higher open probability mutant channels without altering calcium influx per opening. […] These findings reveal a new epileptogenic mechanism for CAE and explain the clinical conundrum that CAE patients carrying CaV3.2 channel mutations do not respond to ethosuximide.

• #20 CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

  https://genesdev.cshlp.org/content/29/14/1535.full.html

  We found that 60% of animals expressing hCaV3.2(C456S)-GFP exhibited 2- to 4-Hz SWDs, characteristic of CAE patients. […] These results indicate that the expression of hCaV3.2(C456S) mutant proteins enhances the susceptibility of absence-like epilepsy. […] Our analysis shows that expression of hCaV3.2(C456S) results in the replacement of endogenous CaV3.2 channels with higher open probability mutant channels without altering calcium influx per opening. […] These findings reveal a new epileptogenic mechanism for CAE and explain the clinical conundrum that CAE patients carrying CaV3.2 channel mutations do not respond to ethosuximide.

• #21 Absence Seizures: Overview, Etiology, Epidemiology

  https://emedicine.medscape.com/article/1183858-overview

  Absence seizures are a type of generalized non-motor seizures. […] The pathophysiology of absence seizures is not fully understood. In 1947, Jasper and Droogleever-Fortuyn electrically stimulated nuclei in the thalami of cats at 3 Hz and produced bilaterally synchronous spike-and-wave discharges on EEG. […] Abnormal oscillatory rhythms are believed to develop in thalamocortical pathways. This involves gamma-aminobutyric acid (GABA)-B-mediated inhibition alternating with glutamate-mediated excitation. […] The cellular mechanism is believed to involve T-type calcium currents. T channels of the GABAergic reticular thalamic nucleus neurons appear to play a major role in the spike-wave discharges of the GABAergic thalamic neurons. […] GABA-B inhibition appears to be altered in absence seizures, and potentiation of GABA-B inhibition with tiagabine (Gabitril), vigabatrin (Sabril), and, possibly, gabapentin (Neurontin), results in exacerbation of absence seizures.

• #22 Absence Seizure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499867/

  The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures.[13] […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures.[4]

• #23 Absence Seizures: How to Treat What You Can’t See

  https://www.uspharmacist.com/article/absence-seizures-how-to-treat-what-you-cant-see

  Other antiepileptics may exacerbate absence seizures or have demonstrated little clinical efficacy. Carbamazepine, oxcarbazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures. The GABA agonists vigabatrin and tiagabine can induce absence seizures, including absence status epilepticus. Carbamazepine also acts at GABAA receptors, which play a role in thalamic neuron firing, leading to an increased incidence of absence seizures.

• #24 Absence Seizures: How to Treat What You Can’t See

  https://www.uspharmacist.com/article/absence-seizures-how-to-treat-what-you-cant-see

  Other antiepileptics may exacerbate absence seizures or have demonstrated little clinical efficacy. Carbamazepine, oxcarbazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures. The GABA agonists vigabatrin and tiagabine can induce absence seizures, including absence status epilepticus. Carbamazepine also acts at GABAA receptors, which play a role in thalamic neuron firing, leading to an increased incidence of absence seizures.

• #25 Absence Seizures: How to Treat What You Can’t See

  https://www.uspharmacist.com/article/absence-seizures-how-to-treat-what-you-cant-see

  Other antiepileptics may exacerbate absence seizures or have demonstrated little clinical efficacy. Carbamazepine, oxcarbazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures. The GABA agonists vigabatrin and tiagabine can induce absence seizures, including absence status epilepticus. Carbamazepine also acts at GABAA receptors, which play a role in thalamic neuron firing, leading to an increased incidence of absence seizures.

• #26 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  Absence seizures arise from hypersynchronous pathological oscillations within the CTC network. […] Alterations in the interplay between excitatory and inhibitory neurons in cortical and thalamic microcircuits can generate the pathological rhythmic activity seen in SWDs. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] The CTC network comprises reciprocal connections between the somatosensory cortex and the dorsal thalamus. […] Absence seizures are characterised by highly synchronised, generalised, pathological oscillations involving CTC networks on both sides of the brain.

• #27 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  Absence seizures arise from hypersynchronous pathological oscillations within the CTC network. […] Alterations in the interplay between excitatory and inhibitory neurons in cortical and thalamic microcircuits can generate the pathological rhythmic activity seen in SWDs. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] The CTC network comprises reciprocal connections between the somatosensory cortex and the dorsal thalamus. […] Absence seizures are characterised by highly synchronised, generalised, pathological oscillations involving CTC networks on both sides of the brain.

• #28 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  Absence seizures arise from hypersynchronous pathological oscillations within the CTC network. […] Alterations in the interplay between excitatory and inhibitory neurons in cortical and thalamic microcircuits can generate the pathological rhythmic activity seen in SWDs. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] The CTC network comprises reciprocal connections between the somatosensory cortex and the dorsal thalamus. […] Absence seizures are characterised by highly synchronised, generalised, pathological oscillations involving CTC networks on both sides of the brain.

• #29 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  Absence seizures arise from hypersynchronous pathological oscillations within the CTC network. […] Alterations in the interplay between excitatory and inhibitory neurons in cortical and thalamic microcircuits can generate the pathological rhythmic activity seen in SWDs. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] The CTC network comprises reciprocal connections between the somatosensory cortex and the dorsal thalamus. […] Absence seizures are characterised by highly synchronised, generalised, pathological oscillations involving CTC networks on both sides of the brain.

• #30 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  The focus is on highlighting our current understanding of potential causative mechanisms for absence seizure generation in CAE based on evidence from the latest research using cutting-edge technologies. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] Collectively, these studies indicate that there are both haemodynamic (BOLD) and EEG changes in cortical networks prior to generalised SWDs and absence seizures. […] The generation of generalised SWDs involved a multistage process: a pro-ictal network state lasting at least 1 min, and a pre-ictal network state lasting several seconds prior to SWDs on EEG. […] Overall, the consensus is that paroxysmal oscillation within corticothalamic loops is initiated in the CIN and that the large-scale synchronisation is mediated by way of an extremely fast intracortical spread of seizure activity. Thus, absence seizures are still considered to be correctly classified as a type of generalised seizure.

• #31 Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention

  https://www.mdpi.com/1422-0067/25/18/9821

  The focus is on highlighting our current understanding of potential causative mechanisms for absence seizure generation in CAE based on evidence from the latest research using cutting-edge technologies. […] The precise cellular and molecular events that transform normal physiological oscillation within the CTC network into pathological SWD oscillations are still under investigation and appear to be multifactorial. […] Collectively, these studies indicate that there are both haemodynamic (BOLD) and EEG changes in cortical networks prior to generalised SWDs and absence seizures. […] The generation of generalised SWDs involved a multistage process: a pro-ictal network state lasting at least 1 min, and a pre-ictal network state lasting several seconds prior to SWDs on EEG. […] Overall, the consensus is that paroxysmal oscillation within corticothalamic loops is initiated in the CIN and that the large-scale synchronisation is mediated by way of an extremely fast intracortical spread of seizure activity. Thus, absence seizures are still considered to be correctly classified as a type of generalised seizure.

• #32

  https://link.springer.com/article/10.1007/s00018-022-04221-5

  Absence seizures (ASs) are characterized by pathological electrographic oscillations in the cerebral cortex and thalamus, which are called spike-and-wave discharges (SWDs). […] Subcortical structures, such as the cerebellum, may well contribute to the emergence of ASs, but the cellular and molecular underpinnings remain poorly understood. […] Here we show that the genetic ablation of P/Q-type calcium channels in cerebellar granule cells (quirky) or Purkinje cells (purky) leads to recurrent SWDs with the purky model showing the more severe phenotype. […] The quirky mouse model showed irregular action potential firing of their cerebellar nuclei (CN) neurons as well as rhythmic firing during the wave of their SWDs. […] In both models, the incidence of SWDs could be decreased by increasing CN activity via activation of the Gq-coupled designer receptor exclusively activated by designer drugs (DREADDs) or via that of the Gq-coupled metabotropic glutamate receptor 1.

• #33

  https://link.springer.com/article/10.1007/s00018-022-04221-5

  Absence seizures (ASs) are characterized by pathological electrographic oscillations in the cerebral cortex and thalamus, which are called spike-and-wave discharges (SWDs). […] Subcortical structures, such as the cerebellum, may well contribute to the emergence of ASs, but the cellular and molecular underpinnings remain poorly understood. […] Here we show that the genetic ablation of P/Q-type calcium channels in cerebellar granule cells (quirky) or Purkinje cells (purky) leads to recurrent SWDs with the purky model showing the more severe phenotype. […] The quirky mouse model showed irregular action potential firing of their cerebellar nuclei (CN) neurons as well as rhythmic firing during the wave of their SWDs. […] In both models, the incidence of SWDs could be decreased by increasing CN activity via activation of the Gq-coupled designer receptor exclusively activated by designer drugs (DREADDs) or via that of the Gq-coupled metabotropic glutamate receptor 1.

• #34

  https://link.springer.com/article/10.1007/s00018-022-04221-5

  Absence seizures (ASs) are characterized by pathological electrographic oscillations in the cerebral cortex and thalamus, which are called spike-and-wave discharges (SWDs). […] Subcortical structures, such as the cerebellum, may well contribute to the emergence of ASs, but the cellular and molecular underpinnings remain poorly understood. […] Here we show that the genetic ablation of P/Q-type calcium channels in cerebellar granule cells (quirky) or Purkinje cells (purky) leads to recurrent SWDs with the purky model showing the more severe phenotype. […] The quirky mouse model showed irregular action potential firing of their cerebellar nuclei (CN) neurons as well as rhythmic firing during the wave of their SWDs. […] In both models, the incidence of SWDs could be decreased by increasing CN activity via activation of the Gq-coupled designer receptor exclusively activated by designer drugs (DREADDs) or via that of the Gq-coupled metabotropic glutamate receptor 1.

• #35

  https://link.springer.com/article/10.1007/s00018-022-04221-5

  Absence seizures (ASs) are characterized by pathological electrographic oscillations in the cerebral cortex and thalamus, which are called spike-and-wave discharges (SWDs). […] Subcortical structures, such as the cerebellum, may well contribute to the emergence of ASs, but the cellular and molecular underpinnings remain poorly understood. […] Here we show that the genetic ablation of P/Q-type calcium channels in cerebellar granule cells (quirky) or Purkinje cells (purky) leads to recurrent SWDs with the purky model showing the more severe phenotype. […] The quirky mouse model showed irregular action potential firing of their cerebellar nuclei (CN) neurons as well as rhythmic firing during the wave of their SWDs. […] In both models, the incidence of SWDs could be decreased by increasing CN activity via activation of the Gq-coupled designer receptor exclusively activated by designer drugs (DREADDs) or via that of the Gq-coupled metabotropic glutamate receptor 1.

• #36

  https://link.springer.com/article/10.1007/s00018-022-04221-5

  Finally, disrupting CN rhythmic firing with a closed-loop channelrhodopsin-2 stimulation protocol confirmed that ongoing SWDs can be ceased by activating CN neurons. […] Together, our data highlight that P/Q-type calcium channels in cerebellar granule cells and Purkinje cells can be relevant for epileptogenesis, that Gq-coupled activation of CN neurons can exert anti-epileptic effects and that precisely timed activation of the CN can be used to stop ongoing SWDs. […] Importantly, abnormal activity in the cerebellum can probably not only be the consequence of epileptic activity in the brain, but also the cause thereof. […] Indeed restricted knockouts of the P/Q-type calcium channel in cerebellar granule cells (GCs, quirky) or Purkinje cells (PCs, purky) are sufficient to cause ASs in mice.

• #37

  https://link.springer.com/article/10.1007/s00018-022-04221-5

  Finally, disrupting CN rhythmic firing with a closed-loop channelrhodopsin-2 stimulation protocol confirmed that ongoing SWDs can be ceased by activating CN neurons. […] Together, our data highlight that P/Q-type calcium channels in cerebellar granule cells and Purkinje cells can be relevant for epileptogenesis, that Gq-coupled activation of CN neurons can exert anti-epileptic effects and that precisely timed activation of the CN can be used to stop ongoing SWDs. […] Importantly, abnormal activity in the cerebellum can probably not only be the consequence of epileptic activity in the brain, but also the cause thereof. […] Indeed restricted knockouts of the P/Q-type calcium channel in cerebellar granule cells (GCs, quirky) or Purkinje cells (PCs, purky) are sufficient to cause ASs in mice.

• #38 Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003495

  Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. […] It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. […] Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. […] The basal ganglia comprise a group of interconnected subcortical nucleus and, as a whole, represent one fundamental processing unit of the brain. […] Therefore, it is naturally expected that the basal ganglia may provide an active role in mediating between seizure and non-seizure states for absence epileptic patients.

• #39 Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003495

  Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. […] It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. […] Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. […] The basal ganglia comprise a group of interconnected subcortical nucleus and, as a whole, represent one fundamental processing unit of the brain. […] Therefore, it is naturally expected that the basal ganglia may provide an active role in mediating between seizure and non-seizure states for absence epileptic patients.

• #40 Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003495

  Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. […] It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. […] Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. […] The basal ganglia comprise a group of interconnected subcortical nucleus and, as a whole, represent one fundamental processing unit of the brain. […] Therefore, it is naturally expected that the basal ganglia may provide an active role in mediating between seizure and non-seizure states for absence epileptic patients.

• #41 Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003495

  Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. […] It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. […] Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. […] The basal ganglia comprise a group of interconnected subcortical nucleus and, as a whole, represent one fundamental processing unit of the brain. […] Therefore, it is naturally expected that the basal ganglia may provide an active role in mediating between seizure and non-seizure states for absence epileptic patients.

• #42 Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003495

  Nevertheless, due to the complicated interactions between basal ganglia and thalamus, the underlying neural mechanisms on how the basal ganglia control the absence seizure activities are still remain unclear. […] To address this question, we develop a realistic mean-field model for the basal ganglia-corticothalamic (BGCT) network in the present study. […] Importantly, in this coexist region, both low and high activation levels of SNr neurons can suppress the occurrence of SWDs due to the competition between these two direct inhibitory basal ganglia-thalamic pathways. […] Our findings emphasize the bidirectional modulation effects of basal ganglia on absence seizures, and might have physiological implications on the treatment of absence epilepsy. […] The SNr-TRN pathway may play a vital role in controlling the absence seizures and appropriately reducing the activation level of SNr neurons can suppress the typical 24 Hz SWDs.

• #43 Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003495

  Nevertheless, due to the complicated interactions between basal ganglia and thalamus, the underlying neural mechanisms on how the basal ganglia control the absence seizure activities are still remain unclear. […] To address this question, we develop a realistic mean-field model for the basal ganglia-corticothalamic (BGCT) network in the present study. […] Importantly, in this coexist region, both low and high activation levels of SNr neurons can suppress the occurrence of SWDs due to the competition between these two direct inhibitory basal ganglia-thalamic pathways. […] Our findings emphasize the bidirectional modulation effects of basal ganglia on absence seizures, and might have physiological implications on the treatment of absence epilepsy. […] The SNr-TRN pathway may play a vital role in controlling the absence seizures and appropriately reducing the activation level of SNr neurons can suppress the typical 24 Hz SWDs.

• #44 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. […] Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. […] We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. […] These findings suggest that the MLT is a promising target for clinical interventions. […] The midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis. […] MLT neurons exhibit synchronized bursting during ictal phase.

• #45 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. […] Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. […] We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. […] These findings suggest that the MLT is a promising target for clinical interventions. […] The midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis. […] MLT neurons exhibit synchronized bursting during ictal phase.

• #46 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  BK channel contributes to MLT burst firing. […] Attenuating MLT bursting increases vigilance and suppresses absence seizures. […] Targeting rhythmic oscillations to prevent hypersynchronization is therefore essential for treating absence seizures. […] As burst firing of thalamic neurons is important in driving the rhythmic oscillations and hypersynchronization, targeting thalamic bursting could be a promising strategy to treat absence epilepsy. […] Therefore, accurate identification and precise targeting of the thalamic regions that are important for absence seizure pathogenesis are crucial for the development of innovative therapeutic strategies to effectively treat absence epilepsy. […] Our study thus identifies the MLT as a key thalamic region for targeted anti-absence interventions, uncovers MLT hypersynchronized burst firing in absence seizure pathogenesis, discovers the role of BK channels in promoting burst firing of MLT neurons, and provides a variety of approaches to attenuate MLT bursting, which have the potential to be translated into novel treatments of absence epilepsy of different etiologies.

• #47 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  BK channel contributes to MLT burst firing. […] Attenuating MLT bursting increases vigilance and suppresses absence seizures. […] Targeting rhythmic oscillations to prevent hypersynchronization is therefore essential for treating absence seizures. […] As burst firing of thalamic neurons is important in driving the rhythmic oscillations and hypersynchronization, targeting thalamic bursting could be a promising strategy to treat absence epilepsy. […] Therefore, accurate identification and precise targeting of the thalamic regions that are important for absence seizure pathogenesis are crucial for the development of innovative therapeutic strategies to effectively treat absence epilepsy. […] Our study thus identifies the MLT as a key thalamic region for targeted anti-absence interventions, uncovers MLT hypersynchronized burst firing in absence seizure pathogenesis, discovers the role of BK channels in promoting burst firing of MLT neurons, and provides a variety of approaches to attenuate MLT bursting, which have the potential to be translated into novel treatments of absence epilepsy of different etiologies.

• #48 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  BK channel contributes to MLT burst firing. […] Attenuating MLT bursting increases vigilance and suppresses absence seizures. […] Targeting rhythmic oscillations to prevent hypersynchronization is therefore essential for treating absence seizures. […] As burst firing of thalamic neurons is important in driving the rhythmic oscillations and hypersynchronization, targeting thalamic bursting could be a promising strategy to treat absence epilepsy. […] Therefore, accurate identification and precise targeting of the thalamic regions that are important for absence seizure pathogenesis are crucial for the development of innovative therapeutic strategies to effectively treat absence epilepsy. […] Our study thus identifies the MLT as a key thalamic region for targeted anti-absence interventions, uncovers MLT hypersynchronized burst firing in absence seizure pathogenesis, discovers the role of BK channels in promoting burst firing of MLT neurons, and provides a variety of approaches to attenuate MLT bursting, which have the potential to be translated into novel treatments of absence epilepsy of different etiologies.

• #49 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  BK channel contributes to MLT burst firing. […] Attenuating MLT bursting increases vigilance and suppresses absence seizures. […] Targeting rhythmic oscillations to prevent hypersynchronization is therefore essential for treating absence seizures. […] As burst firing of thalamic neurons is important in driving the rhythmic oscillations and hypersynchronization, targeting thalamic bursting could be a promising strategy to treat absence epilepsy. […] Therefore, accurate identification and precise targeting of the thalamic regions that are important for absence seizure pathogenesis are crucial for the development of innovative therapeutic strategies to effectively treat absence epilepsy. […] Our study thus identifies the MLT as a key thalamic region for targeted anti-absence interventions, uncovers MLT hypersynchronized burst firing in absence seizure pathogenesis, discovers the role of BK channels in promoting burst firing of MLT neurons, and provides a variety of approaches to attenuate MLT bursting, which have the potential to be translated into novel treatments of absence epilepsy of different etiologies.

• #50 Absence Seizure | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28842

  A genetic component exists for all generalized epilepsies and, specifically, for absence epilepsy. The inheritance pattern is not strictly autosomal recessive or dominant and is considered to be multifactorial and polygenic. […] The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures. […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures. […] More recent research on penicillin-induced models of epilepsy in cats favors the cerebellum’s role in long-term electrical stimulation in absence epilepsy.

• #51 Absence Seizure | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/28842

  A genetic component exists for all generalized epilepsies and, specifically, for absence epilepsy. The inheritance pattern is not strictly autosomal recessive or dominant and is considered to be multifactorial and polygenic. […] The pathophysiological mechanism of the development of absence seizures is not yet fully understood. However, the cortico-thalamic-cortical circuit is believed to play a significant role in the pathophysiology of absence seizures. […] As explained by the genetics of absence epilepsy, genes coding for T-type calcium channels and GABA receptors have been associated with the etiopathogenesis of this type of epilepsy. Medications that suppress T-type calcium channels, such as ethosuximide and valproate, are effective anti-absence drugs. Conversely, medications that increase GABA-B activity (eg, vigabatrin) exacerbate the frequency of absence seizures. In contrast, GABA-A agonists (eg, benzodiazepines) that preferentially enhance GABA-ergic activity in neurons from the thalamic nucleus reticularis can suppress absence seizures. […] More recent research on penicillin-induced models of epilepsy in cats favors the cerebellum’s role in long-term electrical stimulation in absence epilepsy.

• #52 Absence seizure – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/symptoms-causes/syc-20359683

  Absence seizures usually have a genetic cause. […] In general, seizures occur as a result of a burst of electrical impulses from nerve cells in the brain, called neurons. Neurons typically send electrical and chemical signals across the synapses that connect them. […] In people who have seizures, the brain’s usual electrical activity is altered. During an absence seizure, these electrical signals repeat themselves over and over in a three-second pattern. […] People who have seizures also may have altered levels of the chemical messengers that help the nerve cells communicate with one another. These chemical messengers are called neurotransmitters.

• #53 Childhood absence epilepsy – UpToDate

  https://www.uptodate.com/contents/childhood-absence-epilepsy

  Childhood absence epilepsy (CAE) is a common generalized epilepsy syndrome with a presumed polygenic cause, characterized by typical absence seizures appearing in otherwise healthy school-aged children. CAE is one of the most common forms of pediatric epilepsy. […] CAE is classified as an epilepsy syndrome with presumed polygenic cause according to the International League Against Epilepsy (ILAE). […] CAE is one of the idiopathic generalized epilepsies (IGEs) – The ILAE described a broad group of genetic generalized epilepsies (GGEs) that are characterized by generalized seizure types and generalized spike-wave with a presumed genetic etiology.

• #54 Childhood absence epilepsy – UpToDate

  https://www.uptodate.com/contents/childhood-absence-epilepsy

  Childhood absence epilepsy (CAE) is a common generalized epilepsy syndrome with a presumed polygenic cause, characterized by typical absence seizures appearing in otherwise healthy school-aged children. CAE is one of the most common forms of pediatric epilepsy. […] CAE is classified as an epilepsy syndrome with presumed polygenic cause according to the International League Against Epilepsy (ILAE). […] CAE is one of the idiopathic generalized epilepsies (IGEs) – The ILAE described a broad group of genetic generalized epilepsies (GGEs) that are characterized by generalized seizure types and generalized spike-wave with a presumed genetic etiology.

• #55 generalized-absence-seizures-petit-mal | Calgary Guide

  https://calgaryguide.ucalgary.ca/generalized-absence-seizures-petit-mal/absence-seizure/

  Pathogenesis of absence seizure is complex and not yet fully elucidated, but evidence supports the cortical focus theory: Hyperexcitable focal neurons on cerebral cortex send activation signals down to thalamocortical neuron network […] Activated neurons in thalamus interact with cortical neurons to produce rhythmic oscillatory neuronal firing (brain waves) between these two regions of the brain […] Abnormal rhythmic and bilaterally synchronous activation of the cerebral cortex during wakefulness […] Inter-ictal changes in neuronal firing patterns and connectivity in sensorimotor cortices (mechanism unclear) […] Genetic predisposition/idiopathic (90%) […] No single identified cause such as a structural lesion or single genetic mutation […] Multiple gene mutations that predispose to epilepsy when occurring together […] Monogenetic mutation (10%) […] Single gene mutation predisposing to epilepsy […] Mutations involve genes encoding voltage-gated calcium channels and gamma aminobutyric acid (GABA) receptors, which are important in regulating thalamocortical activity.

• #56 generalized-absence-seizures-petit-mal | Calgary Guide

  https://calgaryguide.ucalgary.ca/generalized-absence-seizures-petit-mal/absence-seizure/

  Pathogenesis of absence seizure is complex and not yet fully elucidated, but evidence supports the cortical focus theory: Hyperexcitable focal neurons on cerebral cortex send activation signals down to thalamocortical neuron network […] Activated neurons in thalamus interact with cortical neurons to produce rhythmic oscillatory neuronal firing (brain waves) between these two regions of the brain […] Abnormal rhythmic and bilaterally synchronous activation of the cerebral cortex during wakefulness […] Inter-ictal changes in neuronal firing patterns and connectivity in sensorimotor cortices (mechanism unclear) […] Genetic predisposition/idiopathic (90%) […] No single identified cause such as a structural lesion or single genetic mutation […] Multiple gene mutations that predispose to epilepsy when occurring together […] Monogenetic mutation (10%) […] Single gene mutation predisposing to epilepsy […] Mutations involve genes encoding voltage-gated calcium channels and gamma aminobutyric acid (GABA) receptors, which are important in regulating thalamocortical activity.

• #57 Absence seizure – Wikipedia

  https://en.wikipedia.org/wiki/Absence_seizure

  Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). […] An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), GABRG3, and CACNA1A2 genes. […] Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA resulting in exacerbation of absence seizures.

• #58 Absence seizure – Wikipedia

  https://en.wikipedia.org/wiki/Absence_seizure

  Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). […] An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), GABRG3, and CACNA1A2 genes. […] Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA resulting in exacerbation of absence seizures.

• #59 Absence seizure – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/symptoms-causes/syc-20359683

  Absence seizures usually have a genetic cause. […] In general, seizures occur as a result of a burst of electrical impulses from nerve cells in the brain, called neurons. Neurons typically send electrical and chemical signals across the synapses that connect them. […] In people who have seizures, the brain’s usual electrical activity is altered. During an absence seizure, these electrical signals repeat themselves over and over in a three-second pattern. […] People who have seizures also may have altered levels of the chemical messengers that help the nerve cells communicate with one another. These chemical messengers are called neurotransmitters.

• #60 Absence seizure – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/symptoms-causes/syc-20359683

  Absence seizures usually have a genetic cause. […] In general, seizures occur as a result of a burst of electrical impulses from nerve cells in the brain, called neurons. Neurons typically send electrical and chemical signals across the synapses that connect them. […] In people who have seizures, the brain’s usual electrical activity is altered. During an absence seizure, these electrical signals repeat themselves over and over in a three-second pattern. […] People who have seizures also may have altered levels of the chemical messengers that help the nerve cells communicate with one another. These chemical messengers are called neurotransmitters.

• #61 Absence seizure – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/symptoms-causes/syc-20359683

  Absence seizures usually have a genetic cause. […] In general, seizures occur as a result of a burst of electrical impulses from nerve cells in the brain, called neurons. Neurons typically send electrical and chemical signals across the synapses that connect them. […] In people who have seizures, the brain’s usual electrical activity is altered. During an absence seizure, these electrical signals repeat themselves over and over in a three-second pattern. […] People who have seizures also may have altered levels of the chemical messengers that help the nerve cells communicate with one another. These chemical messengers are called neurotransmitters.

• #62 Absence seizure – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/symptoms-causes/syc-20359683

  Absence seizures usually have a genetic cause. […] In general, seizures occur as a result of a burst of electrical impulses from nerve cells in the brain, called neurons. Neurons typically send electrical and chemical signals across the synapses that connect them. […] In people who have seizures, the brain’s usual electrical activity is altered. During an absence seizure, these electrical signals repeat themselves over and over in a three-second pattern. […] People who have seizures also may have altered levels of the chemical messengers that help the nerve cells communicate with one another. These chemical messengers are called neurotransmitters.

• #63 Absence seizure – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/symptoms-causes/syc-20359683

  Absence seizures usually have a genetic cause. […] In general, seizures occur as a result of a burst of electrical impulses from nerve cells in the brain, called neurons. Neurons typically send electrical and chemical signals across the synapses that connect them. […] In people who have seizures, the brain’s usual electrical activity is altered. During an absence seizure, these electrical signals repeat themselves over and over in a three-second pattern. […] People who have seizures also may have altered levels of the chemical messengers that help the nerve cells communicate with one another. These chemical messengers are called neurotransmitters.

• #64 Absence seizure – Wikipedia

  https://en.wikipedia.org/wiki/Absence_seizure

  Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). […] An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), GABRG3, and CACNA1A2 genes. […] Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA resulting in exacerbation of absence seizures.

• #65 Absence seizure – Wikipedia

  https://en.wikipedia.org/wiki/Absence_seizure

  Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). […] An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), GABRG3, and CACNA1A2 genes. […] Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA resulting in exacerbation of absence seizures.

• #66 Absence seizure – Wikipedia

  https://en.wikipedia.org/wiki/Absence_seizure

  Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). […] An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), GABRG3, and CACNA1A2 genes. […] Abnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA resulting in exacerbation of absence seizures.

• #67 Tocilizumab | IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy | springermedicine.com

  https://www.springermedicine.com/tocilizumab/epilepsy/il-6-receptor-blockade-by-tocilizumab-has-anti-absence-and-anti-/25811830

  Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. […] The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. […] Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. […] These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. […] Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.

• #68 Tocilizumab | IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy | springermedicine.com

  https://www.springermedicine.com/tocilizumab/epilepsy/il-6-receptor-blockade-by-tocilizumab-has-anti-absence-and-anti-/25811830

  Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. […] The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. […] Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. […] These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. […] Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.

• #69 Tocilizumab | IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy | springermedicine.com

  https://www.springermedicine.com/tocilizumab/epilepsy/il-6-receptor-blockade-by-tocilizumab-has-anti-absence-and-anti-/25811830

  Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. […] The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. […] Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. […] These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. […] Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.

• #70 Tocilizumab | IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy | springermedicine.com

  https://www.springermedicine.com/tocilizumab/epilepsy/il-6-receptor-blockade-by-tocilizumab-has-anti-absence-and-anti-/25811830

  Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. […] The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. […] Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. […] These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. […] Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.

• #71 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  The role of inflammation in epileptic seizure and epilepsy. Inflammation indeed plays a significant role in the progression of epileptogenesis. […] The excessive activation of the mTOR signaling pathway directly influences the progression of epileptogenesis and neuronal excitability. […] The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis. […] Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. […] The disruption of the circuitry connecting the thalamus and the cerebral cortex constitutes the driving mechanism behind absence epilepsy.

• #72 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  The role of inflammation in epileptic seizure and epilepsy. Inflammation indeed plays a significant role in the progression of epileptogenesis. […] The excessive activation of the mTOR signaling pathway directly influences the progression of epileptogenesis and neuronal excitability. […] The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis. […] Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. […] The disruption of the circuitry connecting the thalamus and the cerebral cortex constitutes the driving mechanism behind absence epilepsy.

• #73 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. […] Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. […] We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. […] These findings suggest that the MLT is a promising target for clinical interventions. […] The midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis. […] MLT neurons exhibit synchronized bursting during ictal phase.

• #74 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. […] Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. […] We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. […] These findings suggest that the MLT is a promising target for clinical interventions. […] The midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis. […] MLT neurons exhibit synchronized bursting during ictal phase.

• #75 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. […] Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. […] We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. […] These findings suggest that the MLT is a promising target for clinical interventions. […] The midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis. […] MLT neurons exhibit synchronized bursting during ictal phase.

• #76 Attenuating midline thalamus bursting to mitigate absence epilepsy | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.09.18.558258v1.full-text

  Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. […] Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. […] We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. […] These findings suggest that the MLT is a promising target for clinical interventions. […] The midline thalamus (MLT) is a key thalamic region for absence seizure pathogenesis. […] MLT neurons exhibit synchronized bursting during ictal phase.

• #77 Neuronal mechanism of a BK channelopathy in absence epilepsy and movement disorders | bioRxiv

  https://www.biorxiv.org/content/10.1101/2021.06.30.450615v1.full-text

  The hyperexcitability in BK-D434G cortical neurons and cerebellar Purkinje cells underscores the neuronal mechanism of BK gain-of-function induced absence epilepsy and movement disorders. […] The effectiveness of a BK channel blocker on preventing absence seizures suggests that BK inhibition is a promising strategy to treat gain-of-function BK channelopathy. […] We found that the BK-D434G mice align with the clinical manifestations of absence seizures and response to anti-absence medications. […] The effectiveness of paxilline (PAX), a BK channel specific blocker, on suppressing BK-D434G-induced absence seizures in mice establishes the causal relationship of this GOF and absence seizures. […] Our study not only elucidate the cellular basis of the BK-D434G channelopathy in epilepsy and movement disorders, but also demonstrate that BK inhibition can be a promising therapeutic strategy to mitigate BK GOF-induced epilepsy.

• #78 Neuronal mechanism of a BK channelopathy in absence epilepsy and movement disorders | bioRxiv

  https://www.biorxiv.org/content/10.1101/2021.06.30.450615v1.full-text

  The hyperexcitability in BK-D434G cortical neurons and cerebellar Purkinje cells underscores the neuronal mechanism of BK gain-of-function induced absence epilepsy and movement disorders. […] The effectiveness of a BK channel blocker on preventing absence seizures suggests that BK inhibition is a promising strategy to treat gain-of-function BK channelopathy. […] We found that the BK-D434G mice align with the clinical manifestations of absence seizures and response to anti-absence medications. […] The effectiveness of paxilline (PAX), a BK channel specific blocker, on suppressing BK-D434G-induced absence seizures in mice establishes the causal relationship of this GOF and absence seizures. […] Our study not only elucidate the cellular basis of the BK-D434G channelopathy in epilepsy and movement disorders, but also demonstrate that BK inhibition can be a promising therapeutic strategy to mitigate BK GOF-induced epilepsy.

• #79 Difficulties in diagnosing absence seizures in adults | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-difficulties-in-diagnosing-absence-seizures-S2173580818300579

  Some studies suggest that calcium channels are a key factor in absence seizure pathogenesis. […] Zonisamide is an antiepileptic drug that stabilises the cell membrane and acts on voltage-dependent sodium channels and calcium channels; the latter are one of the main factors involved in the pathophysiology of absence seizures. […] This case demonstrates the potential difficulty involved in differentiating complex partial seizures from absence seizures in adult patients. […] Animal models have shown that correct, early treatment not only suppresses seizures, but also prevents the development of associated histological alterations.

• #80 Difficulties in diagnosing absence seizures in adults | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-difficulties-in-diagnosing-absence-seizures-S2173580818300579

  Some studies suggest that calcium channels are a key factor in absence seizure pathogenesis. […] Zonisamide is an antiepileptic drug that stabilises the cell membrane and acts on voltage-dependent sodium channels and calcium channels; the latter are one of the main factors involved in the pathophysiology of absence seizures. […] This case demonstrates the potential difficulty involved in differentiating complex partial seizures from absence seizures in adult patients. […] Animal models have shown that correct, early treatment not only suppresses seizures, but also prevents the development of associated histological alterations.

• #81 Absence Seizures: How to Treat What You Can’t See

  https://www.uspharmacist.com/article/absence-seizures-how-to-treat-what-you-cant-see

  Absences are triggered in the thalamus when T-type calcium channels are activated, resulting in sustained-burst firing of these neurons. The neurotransmitter gamma-aminobutyric acid (GABA) is involved in the polarization of these channels, which potentiates the sustained-burst firing. For this reason, increased absence seizure activity occurs in patients taking GABA agonists, whereas GABA antagonists reduce the incidence of absence episodes. […] Although the majority of evidence lies with the abovementioned first-line agents, a few other antiepileptics have demonstrated some degree of efficacy against absence seizures. These agents include acetazolamide, clonazepam, diazepam, felbamate, levetiracetam, topiramate, and zonisamide. In a small study, treatment with zonisamide which has some activity at the T-type calcium channel resulted in seizure elimination in 38% of patients with absence epilepsy, and 77% of patients had at least a 50% reduction in absence seizure activity.

• #82 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  Epileptogenesis is the process by which a normal brain develops alterations that contribute to the formation of epilepsy, alluding brain transformation that was previously functioning normally into a brain that experiences seizures. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells. […] Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation.

• #83 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  Epileptogenesis is the process by which a normal brain develops alterations that contribute to the formation of epilepsy, alluding brain transformation that was previously functioning normally into a brain that experiences seizures. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells. […] Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation.

• #84 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  Epileptogenesis is the process by which a normal brain develops alterations that contribute to the formation of epilepsy, alluding brain transformation that was previously functioning normally into a brain that experiences seizures. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells. […] Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation.

• #85 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  Epileptogenesis is the process by which a normal brain develops alterations that contribute to the formation of epilepsy, alluding brain transformation that was previously functioning normally into a brain that experiences seizures. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells. […] Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation.

• #86 Biomolecular mechanisms of epileptic seizures and epilepsy: a review | Acta Epileptologica | Full Text

  https://aepi.biomedcentral.com/articles/10.1186/s42494-023-00137-0

  Epileptogenesis is the process by which a normal brain develops alterations that contribute to the formation of epilepsy, alluding brain transformation that was previously functioning normally into a brain that experiences seizures. […] The biological processes, structural changes, and functional alterations play a crucial role in epileptogenesis. […] The fundamental physiology of an epileptic seizure includes the instability of the cell membrane or the surrounding or neighboring supporting cells. […] Epileptic seizures and epilepsy arise from a multitude of causes and sustained through a process of positive reinforcement, where an initial imbalance between neural inhibition and excitation triggers further imbalances. […] Epileptogenesis is influenced by factors including oxidative stress, neurochemical alterations in the brain due to neurotransmitters and ion channels, fluctuations in ion concentration, variations in cell surface receptors, and the presence of inflammation.

• #87 CURE Epilepsy Discovery: Investigating Mechanism of the Progression of Epilepsy – CURE Epilepsy

  https://www.cureepilepsy.org/research-discoveries/investigating-mechanism-of-the-progression-of-epilepsy/

  The development of seizures is associated with many changes in the brain; one of these changes is alterations in the white matter (the deep part of the brain) composed of axons covered in myelin. Myelin is a substance that acts as a nerve insulator and is critical for communication between neurons. […] Through her research, the team discovered that abnormal neuronal activity during absence seizures may lead to changes in myelination. The changes in myelin, in turn, lead to seizure progression. […] With her CURE Epilepsy Taking Flight Award, generously funded by the Ravichandran Foundation, Dr. Knowles and her colleagues sought to determine whether changes in myelination caused by a type of seizure called an absence seizure (formerly known as a petit mal seizure) contribute to the progression of epilepsy. […] The current study by Dr. Knowles group is the first that clearly shows that abnormal neuronal activity (in this case, due to absence seizures) can lead to harmful changes in myelination, which contribute to the continued progression of epilepsy.

• #88 CURE Epilepsy Discovery: Investigating Mechanism of the Progression of Epilepsy – CURE Epilepsy

  https://www.cureepilepsy.org/research-discoveries/investigating-mechanism-of-the-progression-of-epilepsy/

  The development of seizures is associated with many changes in the brain; one of these changes is alterations in the white matter (the deep part of the brain) composed of axons covered in myelin. Myelin is a substance that acts as a nerve insulator and is critical for communication between neurons. […] Through her research, the team discovered that abnormal neuronal activity during absence seizures may lead to changes in myelination. The changes in myelin, in turn, lead to seizure progression. […] With her CURE Epilepsy Taking Flight Award, generously funded by the Ravichandran Foundation, Dr. Knowles and her colleagues sought to determine whether changes in myelination caused by a type of seizure called an absence seizure (formerly known as a petit mal seizure) contribute to the progression of epilepsy. […] The current study by Dr. Knowles group is the first that clearly shows that abnormal neuronal activity (in this case, due to absence seizures) can lead to harmful changes in myelination, which contribute to the continued progression of epilepsy.

• #89 CURE Epilepsy Discovery: Investigating Mechanism of the Progression of Epilepsy – CURE Epilepsy

  https://www.cureepilepsy.org/research-discoveries/investigating-mechanism-of-the-progression-of-epilepsy/

  The development of seizures is associated with many changes in the brain; one of these changes is alterations in the white matter (the deep part of the brain) composed of axons covered in myelin. Myelin is a substance that acts as a nerve insulator and is critical for communication between neurons. […] Through her research, the team discovered that abnormal neuronal activity during absence seizures may lead to changes in myelination. The changes in myelin, in turn, lead to seizure progression. […] With her CURE Epilepsy Taking Flight Award, generously funded by the Ravichandran Foundation, Dr. Knowles and her colleagues sought to determine whether changes in myelination caused by a type of seizure called an absence seizure (formerly known as a petit mal seizure) contribute to the progression of epilepsy. […] The current study by Dr. Knowles group is the first that clearly shows that abnormal neuronal activity (in this case, due to absence seizures) can lead to harmful changes in myelination, which contribute to the continued progression of epilepsy.

• #90 Difficulties in diagnosing absence seizures in adults | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-difficulties-in-diagnosing-absence-seizures-S2173580818300579

  Some studies suggest that calcium channels are a key factor in absence seizure pathogenesis. […] Zonisamide is an antiepileptic drug that stabilises the cell membrane and acts on voltage-dependent sodium channels and calcium channels; the latter are one of the main factors involved in the pathophysiology of absence seizures. […] This case demonstrates the potential difficulty involved in differentiating complex partial seizures from absence seizures in adult patients. […] Animal models have shown that correct, early treatment not only suppresses seizures, but also prevents the development of associated histological alterations.

• #91 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  In absence epilepsy, human neuroimaging studies suggest that during a seizure, there may be a lack of conscious information processing due to impaired fronto-parietal network, arousal systems in the thalamus and brainstem (Blumenfeld, 2012), or default mode network (Luo et al., 2011). […] Although the origin of absence seizures is not fully understood, current studies on rat models of absence seizures suggest that they arise from excitatory drive in the barrel field of the somatosensory cortex (David et al., 2008; Meeren et al., 2002; Polack et al., 2007) and then propagate to other structures (David et al., 2008) including thalamus, knowing to play an essential role during the ictal state (Huguenard, 2019). […] Previous results on GAERS have indicated that, during an absence seizure, hyperactive electrophysiological activity in the somatosensory cortex can contribute to bilateral and regular SWD firing patterns in most parts of the cortex.

• #92 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  In absence epilepsy, human neuroimaging studies suggest that during a seizure, there may be a lack of conscious information processing due to impaired fronto-parietal network, arousal systems in the thalamus and brainstem (Blumenfeld, 2012), or default mode network (Luo et al., 2011). […] Although the origin of absence seizures is not fully understood, current studies on rat models of absence seizures suggest that they arise from excitatory drive in the barrel field of the somatosensory cortex (David et al., 2008; Meeren et al., 2002; Polack et al., 2007) and then propagate to other structures (David et al., 2008) including thalamus, knowing to play an essential role during the ictal state (Huguenard, 2019). […] Previous results on GAERS have indicated that, during an absence seizure, hyperactive electrophysiological activity in the somatosensory cortex can contribute to bilateral and regular SWD firing patterns in most parts of the cortex.

• #93 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  In absence epilepsy, human neuroimaging studies suggest that during a seizure, there may be a lack of conscious information processing due to impaired fronto-parietal network, arousal systems in the thalamus and brainstem (Blumenfeld, 2012), or default mode network (Luo et al., 2011). […] Although the origin of absence seizures is not fully understood, current studies on rat models of absence seizures suggest that they arise from excitatory drive in the barrel field of the somatosensory cortex (David et al., 2008; Meeren et al., 2002; Polack et al., 2007) and then propagate to other structures (David et al., 2008) including thalamus, knowing to play an essential role during the ictal state (Huguenard, 2019). […] Previous results on GAERS have indicated that, during an absence seizure, hyperactive electrophysiological activity in the somatosensory cortex can contribute to bilateral and regular SWD firing patterns in most parts of the cortex.

• #94 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  Although SWDs are initially triggered by hyperactive somatosensory cortical neurons, neuronal firing rates, especially in majority of frontoparietal cortical and thalamocortical relay neurons, are decreased rather than increased during SWD, resulting in an overall decrease in activity in these neuronal populations (McCafferty et al., 2023). […] The silence component of SWD is thought to be caused by neuronal deactivation or increased inhibitory activity (Fisher Prince, 1977; Gloor et al. 1978; Inoue et al., 1993; Kostopoulos et al., 1982; McCafferty et al., 2023), potentially resulting in overall decreased neuronal activity in the thalamocortical and cortical neurons. […] Our findings of negative HRFs in the cortical regions (Figure 5) are in line with this hypothesis, suggesting reduced neuronal activity.

• #95 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  Although SWDs are initially triggered by hyperactive somatosensory cortical neurons, neuronal firing rates, especially in majority of frontoparietal cortical and thalamocortical relay neurons, are decreased rather than increased during SWD, resulting in an overall decrease in activity in these neuronal populations (McCafferty et al., 2023). […] The silence component of SWD is thought to be caused by neuronal deactivation or increased inhibitory activity (Fisher Prince, 1977; Gloor et al. 1978; Inoue et al., 1993; Kostopoulos et al., 1982; McCafferty et al., 2023), potentially resulting in overall decreased neuronal activity in the thalamocortical and cortical neurons. […] Our findings of negative HRFs in the cortical regions (Figure 5) are in line with this hypothesis, suggesting reduced neuronal activity.

• #96 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  Although SWDs are initially triggered by hyperactive somatosensory cortical neurons, neuronal firing rates, especially in majority of frontoparietal cortical and thalamocortical relay neurons, are decreased rather than increased during SWD, resulting in an overall decrease in activity in these neuronal populations (McCafferty et al., 2023). […] The silence component of SWD is thought to be caused by neuronal deactivation or increased inhibitory activity (Fisher Prince, 1977; Gloor et al. 1978; Inoue et al., 1993; Kostopoulos et al., 1982; McCafferty et al., 2023), potentially resulting in overall decreased neuronal activity in the thalamocortical and cortical neurons. […] Our findings of negative HRFs in the cortical regions (Figure 5) are in line with this hypothesis, suggesting reduced neuronal activity.

• #97 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  Based on fMRI results, we noticed reduced activation in the cortex during ictal state, along with limited propagation of activity compared to the interictal period (Figure 4), which could indicate decreased responsiveness and information processing during external stimulation. […] During a SWD, the overall neuronal activity in several cortical areas is globally decreased (McCafferty et al., 2023) potentially due to the wave component of SWD with increased thalamocortical inhibition (McCafferty et al., 2018). […] Thus, reduced fMRI responsiveness implies that SWD is a dominant brain feature even under stimulation condition, and that particularly the wave phase of the neuronal oscillatory pattern of SWD can prevent responsiveness in GAERS during these conditions.

• #98 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  Based on fMRI results, we noticed reduced activation in the cortex during ictal state, along with limited propagation of activity compared to the interictal period (Figure 4), which could indicate decreased responsiveness and information processing during external stimulation. […] During a SWD, the overall neuronal activity in several cortical areas is globally decreased (McCafferty et al., 2023) potentially due to the wave component of SWD with increased thalamocortical inhibition (McCafferty et al., 2018). […] Thus, reduced fMRI responsiveness implies that SWD is a dominant brain feature even under stimulation condition, and that particularly the wave phase of the neuronal oscillatory pattern of SWD can prevent responsiveness in GAERS during these conditions.

• #99 How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

  https://elifesciences.org/reviewed-preprints/90318v3

  Based on fMRI results, we noticed reduced activation in the cortex during ictal state, along with limited propagation of activity compared to the interictal period (Figure 4), which could indicate decreased responsiveness and information processing during external stimulation. […] During a SWD, the overall neuronal activity in several cortical areas is globally decreased (McCafferty et al., 2023) potentially due to the wave component of SWD with increased thalamocortical inhibition (McCafferty et al., 2018). […] Thus, reduced fMRI responsiveness implies that SWD is a dominant brain feature even under stimulation condition, and that particularly the wave phase of the neuronal oscillatory pattern of SWD can prevent responsiveness in GAERS during these conditions.

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