Sudden death in epilepsy: An experimental animal model

Mameli, O.; Caría, M. A.; Pintus, Adriana; Padua, G; Mameli, S.

doi:10.1016/j.seizure.2006.02.007

Cited by 33 publications

(24 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the observation of others, who reported pre-ictal cardiac effects supported by increased parasympathetic and/or vagus nerve activity [18,21]. Alternatively, the observed CrVENG changes might have been due to a direct effect of PTZ on the vagus activity.…”

Section: Physiological Basis For Crveng and Ibed Featuresupporting

confidence: 93%

Early seizure detection in rats based on vagus nerve activity

Harreby

Sevcencu

Struijk

2010

Med Biol Eng Comput

View full text Add to dashboard Cite

Continuous, scheduled vagus nerve stimulation (VNS) is used for the treatment of refractory epilepsy. On-demand VNS, started prior to or at the onset of a seizure may improve the effect of the treatment, however, this requires seizures to be predicted or detected early. This study investigates the possibility of early seizure detection based on the cervical vagus electroneurogram (VENG). Fourteen anesthetized rats received an intravenous infusion (IV) of either saline (control, n = 6) or pentylenetetrazol (PTZ) diluted in saline (PTZ-treated, n = 8). A cardiac-related VENG profile (CrVENG) was derived by using R-peak triggered averaging of the VENG energy. Following, changes in this profile were evaluated as a seizure predictor. Using left nerve VENG, seizures were detected in all PTZ-treated rats 103 ± 51 s (mean ± SD) before they developed tonic seizures. Control rats did not develop seizures and our method did also not detected seizures in these rats. Seizures can be early detecting based on left nerve VENG in anesthetized rats. Preictal CrVENG changes may reflect central-mediated changes and/or changes in the relation between the respiration and the cardiac cycle. Further research is needed to evaluate the method in awake and freely moving animals and eventually in humans.

show abstract

Section: Physiological Basis For Crveng and Ibed Featuresupporting

confidence: 93%

Early seizure detection in rats based on vagus nerve activity

Harreby

Sevcencu

Struijk

2010

Med Biol Eng Comput

View full text Add to dashboard Cite

show abstract

“…We believe the model presented in this paper is an excellent tool for studying the spread of limbic cortical seizure activity into the autonomic nervous system, but it derives some of its power from the use of an anesthetic. The hemispherectomized rat, for example (Mameli et al, 2006), eliminates the anesthesia complication, but suffers from the absence of limbic and neocortices. A variety of well‐characterized models are essential for establishing pathophysiological principles, and, since each model has its own advantages and disadvantages, model choices are necessary to address specific questions.…”

Section: Discussionmentioning

confidence: 99%

Autonomic consequences of kainic acid–induced limbic cortical seizures in rats: Peripheral autonomic nerve activity, acute cardiovascular changes, and death

Sakamoto¹,

Saito²,

Orman³

et al. 2008

Epilepsia

View full text Add to dashboard Cite

SUMMARYPurpose: Autonomic consequences of seizures are common, but can be severe. We sought to define changes in autonomic activity from limbic cortical seizures and their impact on the heart. Methods: We studied kainic acid (KA)-induced seizures in urethane-anesthetized rats using peripheral nerve, blood pressure (BP), and ECG recordings and echocardiography. Results: Seizures were associated with massive increases in parasympathetic (vagus nerves) and sympathetic (cervical sympathetic ganglion >renal nerve >splanchnic nerve) activity. Seizureassociated activity increases were greater than activity changes induced by nitroprusside or phenylephrine (each producing BP changes of >50 mmHg). Increases in c-fos expression were found in both sympathetic and parasympathetic medullary regions (as well as hypothalamic areas). Baroreceptor reflex function (tested with nitroprusside and phenylephrine) was impaired during seizures. Finally, a significant fraction of the animals died and the mechanism of death was defined through ECG, BP, and echocardiographic measures to be profound cardiac dilatation and bradyarrhythmia leading to hypoperfusion of the brain and ultimately hypoperfusion of the heart. Cardiovascular changes occur within seconds (or less) of autonomic nerve activity changes and death by these mechanisms takes minutes. Discussion: We propose that the massive parasympathetic and sympathetic outflow that occurs during a seizure gets compounded by respiratory distress (driving both autonomic nervous system divisions in the same direction) causing mechanical dysfunction, slowing the heart, and hypoperfusing the brain. KEY WORDS: Autonomic nervous system, Limbic cortex, Cardiac arrhythmia, Cardiac dilatation.Seizure-induced autonomic dysfunction can have serious clinical consequences (Devinsky, 2004; Goodman et al., 2008). Focal simple partial seizures may produce flushing, sweating, and piloerection (Baumgartner et al., 2001), while complex partial seizures produce a broader spectrum of autonomic signs, including changes in heart rate and rhythm, blood pressure, gastrointestinal moti- (Wilder-Smith, 1992;Lathers et al., 1998;Locatelli et al., 1999;Nei et al., 2000;Baumgartner et al., 2001). Generalized tonic-clonic seizures may be associated with severe increases in blood pressure and changes in heart rate and conduction, such as complete nodal block (Schraeder & Lathers, 1989). In some individuals, however, seizures may trigger more ominous autonomic derangements such as marked bradycardia or asystole (Smith-Demps & Jagoda, 1998;Cheung & Hachinski, 2000;Mameli et al., 2001). The causes of death in epilepsy are suspected to involve cardiovascular or respiratory dysfunction provoked by seizures (Liedholm & Gudjonsson, 1992;Smith-Demps & Jagoda, 1998;Cheung & Hachinski, 2000;Langan, 2000;Mameli et al., 2001;Tinuper et al., 2001). 983 Autonomic Consequences of Limbic Seizures in RatsAnimal experimentation has replicated features of human epilepsy and autonomic dysfunction (reviewed in (Lathers & Schraeder, 2006))....

show abstract

“…23,27,28,33 All these conditions occur particularly during or shortly after GTCS. 18,19,34 Furthermore, chronic epilepsy patients display altered autonomic function with a presumably increased sympathetic tone and enhanced QT dispersion (spatial heterogeneity of cardiac repolarization), which are both independent predictors of cardiac mortality. 4,7,35,36 The latter finding is of particular interest, as enhanced QT dispersion facilitates ventricular tachyarrhythmia with short QT interval.…”

Section: Methodsmentioning

confidence: 99%

Enhanced QT shortening and persistent tachycardia after generalized seizures

Surges¹,

Scott²,

Walker³

2010

Neurology

139

111

View full text Add to dashboard Cite

Objective: Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP). We investigated whether ictal/postictal cardiac features were dependent on seizure type within individual patients.Methods: ECG data from patients with medically refractory temporal lobe epilepsy (TLE) undergoing presurgical investigation who had both complex partial seizures and secondarily GTCS during video-EEG telemetry were retrospectively reviewed. Peri-ictal heart rate (HR), corrected QT interval (QTc), HR variability, and cardiac rhythm were assessed.Results: Twenty-five patients were included in this study. Secondarily GTCS led to higher ictal HR, persistent postictal tachycardia, and decreased postictal HR variability. Moreover, abnormal shortening of QTc occurred in 17 patients mainly during the early postictal phase and significantly more often in secondarily GTCS. Abnormal QTc prolongation occurred in 3 patients with no significant association with GTCS. Benign cardiac arrhythmias occurred in 14 patients and were independent of seizure type. Conclusions:Our data suggest a substantial disturbance of autonomic function following secondarily generalized tonic-clonic seizures (GTCS) in patients with medically refractory temporal lobe epilepsy. The observed alterations could potentially facilitate sudden cardiac death and might contribute to the association of sudden unexpected death in epilepsy with GTCS. Neurology ® 2010;74:421-426 GLOSSARY CI ϭ confidence interval; CPS ϭ complex partial seizure; GTCS ϭ generalized tonic-clonic seizures; HR ϭ heart rate; HRV ϭ HR variability; QTc ϭ corrected QT interval; SUDEP ϭ sudden unexpected death in epilepsy; TLE ϭ temporal lobe epilepsy.Sudden unexpected death in epilepsy (SUDEP) is the most frequent epilepsy-related cause of death and is particularly prevalent in patients with chronic epilepsy.1 In younger people with epilepsy (age 20 -40 years), the risk for sudden death is increased about 24-fold compared to the general population.2 Peri-ictal cardiorespiratory alterations are likely to be involved in the pathophysiology of SUDEP and include tachyarrhythmias and bradyarrhythmias as well as central or obstructive hypoventilation and neurogenic pulmonary edema.1 Since generalized tonic-clonic seizures (GTCS) are a major risk factor for SUDEP, 3,4 then determining the specific cardiac characteristics of GTCS may give us a considerable insight into the mechanisms underlying SUDEP. Abnormalities in cardiac repolarization, persistent elevations of heart rate (HR) after exercise, and a decreased HR variability (HRV) are established predictors for cardiac mortality and sudden cardiac death in other medical conditions or in healthy populations. [5][6][7] Previous studies have suggested a greater impact of GTCS on cardiac excitability than nongeneralized seizures with higher ictal heart rates in chronic epilepsy and SUDEP patients 4,[8][9][10][11] and possibly more cardiac arrhythmias following GTCS. 8,10 These studies, however, are confou...

show abstract

Sudden death in epilepsy: An experimental animal model

Abstract: A possible explanation of the above observations is discussed in relationship to SUDEP physiopathogenesis.

Cited by 33 publications

References 44 publications

Early seizure detection in rats based on vagus nerve activity

Early seizure detection in rats based on vagus nerve activity

Autonomic consequences of kainic acid–induced limbic cortical seizures in rats: Peripheral autonomic nerve activity, acute cardiovascular changes, and death

Enhanced QT shortening and persistent tachycardia after generalized seizures

Contact Info

Product

Resources

About