Seizing upon Mechanisms for Impaired Consciousness

Farzampour, Zoya; Huguenard, John R.

doi:10.1016/j.neuron.2015.01.023

Cited by 4 publications

(4 citation statements)

References 16 publications

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“…We do not know whether PI is related solely to decreased postictal arousal or whether there is also additional impairment of cortical and subcortical motor circuits independent of impaired arousal. During seizures there is decreased cholinergic transmission from subcortical arousal structures to the thalamus and frontal cortex with slow wave activity and decreased metabolism of frontal cortex . Activation of subcortical arousal systems by stimulation of intralaminar nuclei following a seizure resulted in increased EEG desynchronization and resumption of exploratory behaviors …”

Section: Discussionmentioning

confidence: 99%

“…During seizures there is decreased cholinergic transmission from subcortical arousal structures to the thalamus and frontal cortex with slow wave activity and decreased metabolism of frontal cortex. 22,23 Activation of subcortical arousal systems by stimulation of intralaminar nuclei following a seizure resulted in increased EEG desynchronization and resumption of exploratory behaviors. 24 We propose that the following sequence may be important in SUDEP.…”

Section: Discussionmentioning

confidence: 99%

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Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction

Kuo

Zhao

et al. 2016

Epilepsia

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Summary Objective The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized EEG suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the Epilepsy Monitoring Unit. Method We investigated for associations between PI duration and: PGES, ictal/postictal oxygen saturation (SpO2), end-tidal CO2 (ETCO2), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. Results 70 patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak peri-ictal ETCO2 (p=0.03), duration of oxygen desaturation (p=0.005) and with SpO2 nadir (p=0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p<0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p=0.046), ETCO2 peak change (p=0.003) was higher and duration of ETCO2 elevation (p=0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration. Significance The duration of PI and presence of PGES are associated with peri-ictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction

Kuo

Zhao

et al. 2016

Epilepsia

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“…[27][28][29] Moreover, unlike cholinergic neurones, glutamatergic neurones of the PPN have not been demonstrated to exhibit decreased firing during seizures. 70,71 Furthermore, recent evidence has indicated that the fast glutamatergic/GABAergic system is the backbone for arousal networks, while the cholinergic and monoaminergic system plays a modulatory role. 27,28 These findings warrant future studies elucidating the role of different neurotransmitter systems on the PVIN/PC dynamic pertinent to cognition, consciousness, and epilepsy.…”

Section: Cognition Consciousness and Epilepsymentioning

confidence: 99%

A Novel Model for the Epileptogenic Neural Network Identifying the Pedunculopontine Nucleus as a Key Neuromodulation Target

Elsawy,

Valiante

2023

Preprint

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Seizures are a product of parvalbumin interneurons (PVIN) inhibition failure with pyramidal cells (PC) runaway excitation. This dynamic has been implicated in genetic and non-genetic epilepsies, focal and generalized seizures alike. We provide evidence motivating a novel model for the epileptogenic neural network. Our model identifies the pedunculopontine nucleus (PPN) and the thalamus as key nodes that drive and modulate PVIN inhibition in the brain respectively. Our model provides an integrative frame of subcortical and cortical networks involved in ictogenesis. Our model views epilepsy as disruption of PVIN inhibition on top of an ongoing PVIN/PC interplay and compensatory network mechanisms aiming at restoring orderly PC firing. Our model presents the thalamus as a homeostatic node orchestrating these compensatory mechanisms, offering a different perspective than the predominant view of the thalamus as a hub for seizure initiation and propagation. We demonstrate how our model can advance our understanding of the overlapping neural networks of sleep, cognition, consciousness, and epilepsy. Importantly, our model presents the PPN as a key neuromodulation target being the main driver of PVIN inhibition in the brain. We argue that deep brain stimulation of the PPN could potentially offer superior outcomes compared to available neuromodulatory treatments through more direct and efficient targeting of failing PVIN networks in epilepsy.

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“…However, the relationship between PGES and respiratory dysfunction can also point towards the presence of some common pathophysiological mechanisms, involving seizure‐activated cortical and subcortical inhibitory networks. A theoretical role of other circuits has been proposed but not proven: in particular seizure‐related dysfunction of the 5‐HT and glutamatergic systems, with inhibition of the subcortical arousal system and consequent impaired consciousness and motionlessness (Kinney and Thach, 2009; Kothare and Singh, 2014), and decreased cholinergic transmission from subcortical arousal structures to the thalamus and frontal cortex with possible involvement of motor circuits (Farzampour and Huguenard, 2015; Motelow et al ., 2015).…”

Section: Post‐ictal Immobilitymentioning

confidence: 99%

Postictal generalized EEG suppression and postictal immobility: what do we know?

Bruno

Richardson

2020

Epileptic Disorders

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Despite representing the leading cause of epilepsy-related mortality, the pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains elusive. In this context, the identification of clinical markers of SUDEP assumes a great importance and has been the target of many studies aimed at stratifying patients' individual risk. Among the potentially most hazardous post-ictal phenomena observed following convulsive seizures in monitored SUDEP cases, postictal generalized EEG suppression and postictal immobility have attracted attention as potential SUDEP risk factors. In this manuscript, we review the current knowledge on postictal generalized EEG suppression and postictal immobility, aiming to identify their pathophysiological mechanisms, reported frequencies and associated clinical factors, and critically evaluate the evidence on their potential relevance as SUDEP risk markers.

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Seizing upon Mechanisms for Impaired Consciousness

Cited by 4 publications

References 16 publications

Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction

Postictal immobility and generalized EEG suppression are associated with the severity of respiratory dysfunction

A Novel Model for the Epileptogenic Neural Network Identifying the Pedunculopontine Nucleus as a Key Neuromodulation Target

Postictal generalized EEG suppression and postictal immobility: what do we know?

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