How do seizures stop?

Lado, Fred A.; Moshé, Solomon L.

doi:10.1111/j.1528-1167.2008.01669.x

Cited by 225 publications

(170 citation statements)

References 133 publications

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“…At present, whether neurotransmitter-mediated seizure termination mechanisms comprise active inhibition or passive depletion is unknown; depolarization block, electrogenic pumps, ionic fluxes, and pH changes have all been implicated. GABA, adenosine, neuropeptide Y, endocannabinoids, and endogenous opioids have also been identified as candidate neurotransmitter systems in animal studies (24). In particular, adenosine, GABA, and opioids merit close study.…”

Section: Seizure Terminationmentioning

confidence: 99%

Seizures, Cerebral Shutdown, and SUDEP

Bozorgi

Lhatoo

2013

Epilepsy Curr

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In Clinical ResearchThere is strong evidence to suggest that sudden unexpected death in epilepsy (SUDEP) is a seizure-related phenomenon (1-5). The agonal pathophysiological processes in SUDEP are likely to begin during, or in the immediate aftermath of, a seizure. However, potential mechanisms are speculative. Epidemiological studies have consistently pointed to the generalized tonic-clonic seizure as the seizure type most commonly associated with SUDEP (6, 7), and almost all SUDEP reports of deaths during monitoring have occurred after generalized tonic-clonic seizures, (8-11) and often during sleep (3,12). This seizure type is associated with more severe obtundation of sensorium in the postictal period and can be associated with cardiorespiratory dysfunction during this time. Several questions arise: How do seizures terminate, and how do termination mechanisms relate to postictal arousal? Is the extent of obtundation and subsequent postictal arousal different in the frequent generalized tonic-clonic seizures of patients with chronic intractable epilepsy at high risk of SUDEP? Does postictal arousal differ according to the sleep-wake state at the time of seizure onset? Is postictal failure of arousal the same as the "cerebral shutdown" phenomenon seen on EEG? These questions remain unanswered. Seizure Termination and the Postictal StateThe generalized tonic-clonic seizure is usually characterized by generalized tonic posturing, a phase of tremulousness or "vibration" followed by a generalized clonic phase and, usually, seizure termination within the first 2 minutes of the clinical onset of generalization (13). In some genetic generalized epilepsies (e.g., juvenile myoclonic epilepsy), there may be generalized myoclonic jerking before the tonic phase; in secondarily generalized seizures, there may be a pretonic phase where version or "figure 4" posturing occurs. However, given this relative stereotypy, there is considerable clinical as well as electrographic heterogeneity in the postictal period (14, 15). Some patients recover quickly, while others have varying periods of postictal stupor. Some have brief periods of focal or generalized EEG slowing, while others have prolonged postictal generalized EEG suppression (PGES) and recovery to baseline can sometimes take many hours. Whether this postictal electroclinical heterogeneity aids SUDEP risk-stratification is debated (9, 16). Undoubtedly, there are a number of potential influences, including those of medication effects, but none have been systematically studied. Postictal Generalized EEG Suppression and "Cerebral Shutdown"PGES occurs in between 8% of pediatric seizure patients (17) to 65% or more of adult patients with generalized motor seizures (9) and has been reported in several monitored SUDEP/near SUDEP cases (8-11, 18, 19) where some authors have used the term "cerebral shutdown" (19). Prolonged PGES may be an independent risk factor for SUDEP, but whether it is a surrogate marker or a direct index of cerebral and brainstem dysregulation is unclear. It...

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Section: Seizure Terminationmentioning

confidence: 99%

Seizures, Cerebral Shutdown, and SUDEP

Bozorgi

Lhatoo

2013

Epilepsy Curr

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“…A host of different biological processes have been proposed to lead to seizure termination including neurotransmitter depletion, ATP depletion, ionic changes, acidosis, increased GABAergic drive, release of adenosine, and release of peptides [19]; suppression or failure of these processes may promote status epilepticus. Moreover, there may be pro-seizure processes occurring during the development of status epilepticus including breakdown of the blood-brain barrier, inflammation, and increased expression of pro-epileptogenic peptides [20,21].…”

Section: Termination Of Seizuresmentioning

confidence: 99%

Pathophysiology of status epilepticus

Walker¹

2018

Neuroscience Letters

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Status epilepticus (SE) is the maximal expression of epilepsy with a high morbidity and mortality. It occurs due to the failure of mechanisms that terminate seizures.Both human and animal data indicate that the longer a seizure lasts, the less likely it is to stop. Recent evidence suggests that there is a critical transition from an ictal to a post-ictal state, associated with a transition from a spatio-temporally desynchronized state to a highly synchronized state, respectively.As SE continues, it becomes progressively resistant to drugs, in particular benzodiazepines due partly to NMDA receptor-dependent internalization of GABA (A) receptors. Moreover, excessive calcium entry into neurons through excessive NMDA receptor activation results in activation of nitric oxide synthase, calpains, and NADPH oxidase. The latter enzyme plays a critical part in the generation of seizuredependent reactive oxygen species. Calcium also accumulates in mitochondria resulting in mitochondrial failure (decreased ATP production), and opening of the mitochondrial permeability transition pore. Together these changes result in status epilepticus-dependent neuronal death via several pathways. Multiple downstream mechanisms including inflammation, break down of the blood-brain barrier, and changes in gene expression can contribute to later pathological processes including chronic epilepsy and cognitive decline.

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“…In addition, it has been demonstrated that not only neurons but also astrocytes may contribute to the initiation, maintenance and spread of seizures and the astrocytic basis of seizure activity [144,153,166]. Clinically used antiepileptics, such as carbamazepine and vigabatrin, modulate the physiological processes in the brain and induce undesirable side effects [153,167], but astrocytes may be new therapeutic targets by which to reduce epileptic activity without suppressing the physiological neural activity.…”

Section: Modulation Of Adenosine Levels and Epileptic Activity By Metmentioning

confidence: 99%

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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How do seizures stop?

Cited by 225 publications

References 133 publications

Seizures, Cerebral Shutdown, and SUDEP

Seizures, Cerebral Shutdown, and SUDEP

Pathophysiology of status epilepticus

The Antiepileptic Potential of Nucleosides

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