Altered A-type potassium channel function in the nucleus tractus solitarii in acquired temporal lobe epilepsy

Sudden unexpected death in epilepsy (SUDEP) is among the leading causes of death in people with epilepsy. Individuals with temporal lobe epilepsy (TLE) have a high risk for SUDEP because the seizures are often medically intractable. Neurons in the nucleus tractus solitarii (NTS) have been implicated in mouse models of SUDEP and play a critical role in modulating cardiorespiratory and autonomic output. Increased neuronal excitability of inhibitory, GABAergic neurons in the NTS develops during epileptogenesis, and NTS dysfunction has been implicated in mouse models of SUDEP. In this study we used the pilocarpine-induced status epilepticus model of TLE (i.e., pilo-SE mice) to investigate the A-type voltage-gated K+ channel as a potential contributor to increased excitability in GABAergic NTS neurons during epileptogenesis. Compared with age-matched control mice, pilo-SE mice displayed an increase in spontaneous action potential frequency and half-width 9–12 wk after treatment. Activity of GABAergic NTS neurons from pilo-SE mice showed less sensitivity to 4-aminopyridine. Correspondingly, reduced A-type K+ current amplitude was detected in these neurons, with no change in activation or inactivation kinetics. No changes were observed in Kv4.1, Kv4.2, Kv4.3, KChIP1, KChIP3, or KChIP4 mRNA expression. These changes contribute to the increased excitability in GABAergic NTS neurons that develops in TLE and may provide insight into potential mechanisms contributing to the increased risk for cardiorespiratory collapse and SUDEP in this model. NEW & NOTEWORTHY Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in epilepsy, and dysfunction in central autonomic neurons may play a role. In a mouse model of acquired epilepsy, GABAergic neurons in the nucleus tractus solitarii developed a reduced amplitude of the A-type current, which contributes to the increased excitability seen in these neurons during epileptogenesis. Neuronal excitability changes in inhibitory central vagal circuitry may increase the risk for cardiorespiratory collapse and SUDEP.

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Dysfunctional Brain Networking among Autonomic Regulatory Structures in Temporal Lobe Epilepsy Patients at High Risk of Sudden Unexpected Death in Epilepsy

Frontiers in Neurology ◽

10.3389/fneur.2017.00544 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 27

Author(s):

Luke A. Allen ◽

Ronald M. Harper ◽

Rajesh Kumar ◽

Maxime Guye ◽

Jennifer A Ogren ◽

...

Keyword(s):

High Risk ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Sudden Unexpected Death ◽

Unexpected Death

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Maximal/exhaustive treadmill test features in patients with temporal lobe epilepsy: Search for sudden unexpected death biomarkers

Epilepsy Research ◽

10.1016/j.eplepsyres.2017.04.014 ◽

2017 ◽

Vol 133 ◽

pp. 83-88 ◽

Cited By ~ 11

Author(s):

Guilherme L. Fialho ◽

Arthur G. Pagani ◽

Roger Walz ◽

Peter Wolf ◽

Katia Lin

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Sudden Unexpected Death ◽

Treadmill Test ◽

Unexpected Death

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Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks

Brazilian Journal of Biology ◽

10.1590/s1519-69842010000300026 ◽

2010 ◽

Vol 70 (3) ◽

pp. 665-670 ◽

Cited By ~ 7

Author(s):

FA. Scorza ◽

RM. Cysneiros ◽

RM. Arida ◽

VC. Terra ◽

HR. Machado ◽

...

Keyword(s):

Fatty Acids ◽

Fish Consumption ◽

Sudden Unexpected Death ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Unexpected Death ◽

Positive Effects ◽

Increased Risk ◽

Fish And Shellfish

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

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Ictal ECG changes in temporal lobe epilepsy

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1995000400012 ◽

1995 ◽

Vol 53 (3b) ◽

pp. 619-624 ◽

Cited By ~ 14

Author(s):

L.M. Li ◽

J. Roche ◽

J.W.A.S. Sander

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Sinus Bradycardia ◽

Cardiac Pacemaker ◽

Epileptic Seizures ◽

Ecg Changes ◽

Unexpected Death ◽

Complex Partial Seizures ◽

The Mean ◽

Video Eeg

Changes in cardiac rhythm may occur during epileptic seizures and this has been suggested as a possible mechanism for sudden unexpected death amongst patients with chronic epilepsy (SUDEP). We have studied ECG changes during 61 complex partial seizures of temporal lobe origin in 20 patients. Tachycardia was observed in 24/61 (39%) and bradycardia in 3/61 (5%). The mean and median tachycardia rate was 139 and 140 beats/min (range 120-180). The longest R-R interval observed was 9 seconds. No difference was found in regard to the lateralisation of seizures and cardiac arrhytmia. One of the patients with bradycardia was fitted with a demand cardiac pacemaker, which appeared to decrease the number of his falls. In conclusion, ictal cardiac changes which may be seen in temporal lobe epilepsy (TLE) are sinus tachycardia and occasionally sinus bradycardia. Patients presenting vague complains suggestive of either TLE or cardiac dysrhythmia, simultaneous monitoring with EEG/ECG is required, and if the episodes are frequent, video-EEG should be considered. Further studies on this subject are warranted as this may shed some light on possible mechanisms for SUDEP.

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The Good, the Bad, and the Deadly: Adenosinergic Mechanisms Underlying Sudden Unexpected Death in Epilepsy

Frontiers in Neuroscience ◽

10.3389/fnins.2021.708304 ◽

2021 ◽

Vol 15 ◽

Author(s):

Benton Purnell ◽

Madhuvika Murugan ◽

Raja Jani ◽

Detlev Boison

Keyword(s):

Neuronal Activity ◽

Neuronal Excitability ◽

Receptor Activation ◽

Sudden Unexpected Death ◽

Unexpected Death ◽

Neuroprotective Effects ◽

Respiratory Dysfunction ◽

Extracellular Adenosine ◽

Hypoxic Conditions ◽

Adenosine Signaling

Adenosine is an inhibitory modulator of neuronal excitability. Neuronal activity results in increased adenosine release, thereby constraining excessive excitation. The exceptionally high neuronal activity of a seizure results in a surge in extracellular adenosine to concentrations many-fold higher than would be observed under normal conditions. In this review, we discuss the multifarious effects of adenosine signaling in the context of epilepsy, with emphasis on sudden unexpected death in epilepsy (SUDEP). We describe and categorize the beneficial, detrimental, and potentially deadly aspects of adenosine signaling. The good or beneficial characteristics of adenosine signaling in the context of seizures include: (1) its direct effect on seizure termination and the prevention of status epilepticus; (2) the vasodilatory effect of adenosine, potentially counteracting postictal vasoconstriction; (3) its neuroprotective effects under hypoxic conditions; and (4) its disease modifying antiepileptogenic effect. The bad or detrimental effects of adenosine signaling include: (1) its capacity to suppress breathing and contribute to peri-ictal respiratory dysfunction; (2) its contribution to postictal generalized EEG suppression (PGES); (3) the prolonged increase in extracellular adenosine following spreading depolarization waves may contribute to postictal neuronal dysfunction; (4) the excitatory effects of A2A receptor activation is thought to exacerbate seizures in some instances; and (5) its potential contributions to sleep alterations in epilepsy. Finally, the adverse effects of adenosine signaling may potentiate a deadly outcome in the form of SUDEP by suppressing breathing and arousal in the postictal period. Evidence from animal models suggests that excessive postictal adenosine signaling contributes to the pathophysiology of SUDEP. The goal of this review is to discuss the beneficial, harmful, and potentially deadly roles that adenosine plays in the context of epilepsy and to identify crucial gaps in knowledge where further investigation is necessary. By better understanding adenosine dynamics, we may gain insights into the treatment of epilepsy and the prevention of SUDEP.

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Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED)

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.600307 ◽

2021 ◽

Vol 8 ◽

Author(s):

Enrice Huenerfauth ◽

Jasmin Nessler ◽

Johannes Erath ◽

Andrea Tipold

Keyword(s):

Status Epilepticus ◽

Sudden Unexpected Death ◽

Idiopathic Epilepsy ◽

Occurrence Rate ◽

Online Questionnaire ◽

Unexpected Death ◽

Validated Questionnaire ◽

Seizure Event ◽

Increased Risk ◽

Cluster Seizures

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.

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