https://sudepwiki.pathology.jhmi.edu/api.php?action=feedcontributions&user=Awils110&feedformat=atomSUDEP Wiki - User contributions [en]2024-03-29T07:25:34ZUser contributionsMediaWiki 1.35.0https://sudepwiki.pathology.jhmi.edu/index.php?title=Adult_hippocampal_neurogenesis_and_sudden_unexpected_death_in_epilepsy:_Reality_or_just_an_attractive_history%3F&diff=924Adult hippocampal neurogenesis and sudden unexpected death in epilepsy: Reality or just an attractive history?2018-03-01T20:08:01Z<p>Awils110: /* Context */</p>
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<div>''Scorza FA, Cysneiros RM, Arida RM, Scorza CA, de Almeida ACG, Schmidt B, and Cavalheiro EA (2008) Adult hippocampal neurogenesis and sudden unexpected death in epilepsy: Reality or just an attractive history? Med Hypotheses 71:6 914–22.''<br />
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'''[https://ac.els-cdn.com/S0306987708003630/1-s2.0-S0306987708003630-main.pdf?_tid=03b4cd40-ce4b-11e7-916a-00000aacb35d&acdnat=1511220912_e8705d7af9f900401de95283528d8b4b Link to Article]'''<br />
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'''Abstract:''' Neurogenesis persists throughout life in the adult mammalian dentate gyrus and is regulated by several environmental, physiological, and molecular factors. Seizure activity also influences dentate granule cell neurogenesis. In these lines, studies of neurogenesis have demonstrated the presence of hilar-ectopic dentate granule cells after status epilepticus induced experimentally and that these cells are migrate aberrantly, abnormally integrated and hyperexcitable, contributing with this to seizure generation and/or propagation. As we know, epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. Based on these facts, in this paper we postulate that aberrant neurogenesis could influence negatively the cardiovascular system of the patient with epilepsy leading to cardiac abnormalities and hence SUDEP.<br />
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*The question mark of the title acknowledges, but does not remedy, the absence of evidence. See annotation at [https://sudepwiki.pathology.jhmi.edu/index.php?search=scorza&title=Special%3ASearch&go=Go Scorza et al.]<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Adult_hippocampal_neurogenesis_and_sudden_unexpected_death_in_epilepsy:_Reality_or_just_an_attractive_history%3F&diff=923Adult hippocampal neurogenesis and sudden unexpected death in epilepsy: Reality or just an attractive history?2018-03-01T20:07:49Z<p>Awils110: /* Context */</p>
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<div>''Scorza FA, Cysneiros RM, Arida RM, Scorza CA, de Almeida ACG, Schmidt B, and Cavalheiro EA (2008) Adult hippocampal neurogenesis and sudden unexpected death in epilepsy: Reality or just an attractive history? Med Hypotheses 71:6 914–22.''<br />
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'''[https://ac.els-cdn.com/S0306987708003630/1-s2.0-S0306987708003630-main.pdf?_tid=03b4cd40-ce4b-11e7-916a-00000aacb35d&acdnat=1511220912_e8705d7af9f900401de95283528d8b4b Link to Article]'''<br />
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'''Abstract:''' Neurogenesis persists throughout life in the adult mammalian dentate gyrus and is regulated by several environmental, physiological, and molecular factors. Seizure activity also influences dentate granule cell neurogenesis. In these lines, studies of neurogenesis have demonstrated the presence of hilar-ectopic dentate granule cells after status epilepticus induced experimentally and that these cells are migrate aberrantly, abnormally integrated and hyperexcitable, contributing with this to seizure generation and/or propagation. As we know, epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. Based on these facts, in this paper we postulate that aberrant neurogenesis could influence negatively the cardiovascular system of the patient with epilepsy leading to cardiac abnormalities and hence SUDEP.<br />
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=Context=<br />
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*The question mark of the title acknowledges, but does not remedy, the absence of evidence. See annotation at [https://sudepwiki.pathology.jhmi.edu/index.php?search=scorza&title=Special%3ASearch&go=Go | Scorza et al.]<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Respiratory_and_vascular_responses_in_monkeys_from_temporal_pole,_insula,_orbital_surface_and_cingulate_gyrus;_a_preliminary_report&diff=922Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report2018-03-01T20:01:53Z<p>Awils110: </p>
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<div>''Kaada BR, Pribram KH, and Epstein JA (1949) Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. J Neurophysiol 12:5 347–56.''<br />
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'''[http://jn.physiology.org.ezp.welch.jhmi.edu/content/12/5/347.long Link to Article]'''<br />
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'''Introduction:''' <br />
Attention has recently been focused on the finding of vascular and respiratory responses resulting from stimulation of the cortex of the posterior orbital surface (4,8,12, 17) and the anterior limbic region (10,19,22) of the frontal lobe of monkey. Physiological neuronography has shown reciprocal and restricted firing between the posterior orbital surface and the cortex of the temporal pole (3). Also, cytoarchiterctural studies in the macaque have indicated a close resemblance between these two areas (5). The finding of respiratory responses from stimulation of the anterior insula (20) provided a link between the frontal and temporal lobe. Because of these relationships it was decided to stimulate the cortex of the temporal pole and to study vascular and respiratory responses. In view of the positive results obtained from stimulation of the temporal pole in the present experiments, and the similarity of these responses from all of the above-mentioned regions, an investigation of the possible continuity of theses responsive areas was undertaken,<br />
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*Stimulation of insular cortex in monkeys caused respiratory arrest during either inspiratory or expiratory phases. Respiration resumed after approximately 30 s even in the presence of continued cortical stimulation. Effects on blood pressure were also identified, and the effects were shown to be mediated by direct connections to subcortical regions. See [https://sudepwiki.pathology.jhmi.edu/index.php/Vagal_elicitation_of_respiratory-type_and_other_unit_responses_in_basal_limbic_structures_of_squirrel_monkeys#Context Radna and MacLean] who stimulated the vagus nerve and saw neuronal responses within the amgydala, insula, and hippocampus.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Respiratory_and_vascular_responses_in_monkeys_from_temporal_pole,_insula,_orbital_surface_and_cingulate_gyrus;_a_preliminary_report&diff=921Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report2018-03-01T19:59:53Z<p>Awils110: /* Context */</p>
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<div>''Kaada BR, Pribram KH, and Epstein JA (1949) Respiratory and vascular responses in mon- keys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. J Neurophysiol 12:5 347–56.''<br />
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'''[http://jn.physiology.org.ezp.welch.jhmi.edu/content/12/5/347.long Link to Article]'''<br />
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'''Introduction:''' <br />
Attention has recently been focused on the finding of vascular and respiratory responses resulting from stimulation of the cortex of the posterior orbital surface (4,8,12, 17) and the anterior limbic region (10,19,22) of the frontal lobe of monkey. Physiological neuronography has shown reciprocal and restricted firing between the posterior orbital surface and the cortex of the temporal pole (3). Also, cytoarchiterctural studies in the macaque have indicated a close resemblance between these two areas (5). The finding of respiratory responses from stimulation of the anterior insula (20) provided a link between the frontal and temporal lobe. Because of these relationships it was decided to stimulate the cortex of the temporal pole and to study vascular and respiratory responses. In view of the positive results obtained from stimulation of the temporal pole in the present experiments, and the similarity of these responses from all of the above-mentioned regions, an investigation of the possible continuity of theses responsive areas was undertaken,<br />
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*Stimulation of insular cortex in monkeys caused respiratory arrest during either inspiratory or expiratory phases. Respiration resumed after approximately 30 s even in the presence of continued cortical stimulation. Effects on blood pressure were also identified, and the effects were shown to be mediated by direct connections to subcortical regions. See [https://sudepwiki.pathology.jhmi.edu/index.php/Vagal_elicitation_of_respiratory-type_and_other_unit_responses_in_basal_limbic_structures_of_squirrel_monkeys#Context Radna and MacLean] who stimulated the vagus nerve and saw neuronal responses within the amgydala, insula, and hippocampus.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Respiratory_and_vascular_responses_in_monkeys_from_temporal_pole,_insula,_orbital_surface_and_cingulate_gyrus;_a_preliminary_report&diff=920Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report2018-03-01T19:59:33Z<p>Awils110: /* Context */</p>
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<div>''Kaada BR, Pribram KH, and Epstein JA (1949) Respiratory and vascular responses in mon- keys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. J Neurophysiol 12:5 347–56.''<br />
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'''[http://jn.physiology.org.ezp.welch.jhmi.edu/content/12/5/347.long Link to Article]'''<br />
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'''Introduction:''' <br />
Attention has recently been focused on the finding of vascular and respiratory responses resulting from stimulation of the cortex of the posterior orbital surface (4,8,12, 17) and the anterior limbic region (10,19,22) of the frontal lobe of monkey. Physiological neuronography has shown reciprocal and restricted firing between the posterior orbital surface and the cortex of the temporal pole (3). Also, cytoarchiterctural studies in the macaque have indicated a close resemblance between these two areas (5). The finding of respiratory responses from stimulation of the anterior insula (20) provided a link between the frontal and temporal lobe. Because of these relationships it was decided to stimulate the cortex of the temporal pole and to study vascular and respiratory responses. In view of the positive results obtained from stimulation of the temporal pole in the present experiments, and the similarity of these responses from all of the above-mentioned regions, an investigation of the possible continuity of theses responsive areas was undertaken,<br />
=Context=<br />
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*Stimulation of insular cortex in monkeys caused respiratory arrest during either inspiratory or expiratory phases. Respiration resumed after approximately 30 s even in the presence of continued cortical stimulation. Effects on blood pressure were also identified, and the effects were shown to be mediated by direct connections to subcortical regions. See [https://sudepwiki.pathology.jhmi.edu/index.php/Vagal_elicitation_of_respiratory-type_and_other_unit_responses_in_basal_limbic_structures_of_squirrel_monkeys#Context Radna and MacLean] who stimulated the vagus nerve and saw response within the amgydala, insula, and hippocampus.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Vagal_elicitation_of_respiratory-type_and_other_unit_responses_in_basal_limbic_structures_of_squirrel_monkeys&diff=919Vagal elicitation of respiratory-type and other unit responses in basal limbic structures of squirrel monkeys2018-03-01T19:57:22Z<p>Awils110: /* Context */</p>
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<div>''Radna RJ and MacLean PD (1981) Vagal elicitation of respiratory-type and other unit responses in basal limbic structures of squirrel monkeys. Brain Res 213:1 45–61.''<br />
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'''[https://ac.els-cdn.com/0006899381912476/1-s2.0-0006899381912476-main.pdf?_tid=7904a9d4-b3fd-11e7-95fc-00000aacb35d&acdnat=1508328870_57cf8110142c2fe153ba8a4d2dfa0336 Link to Article]'''<br />
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'''Abstract:''' Basal limbic structures (insula, amygdala, hippocampus and surrounding areas) were explored for unit responses to vagal volleys in awake, sitting, squirrel monkeys. Triple shocks were applied every 4 sec to the left cervical vagus nerve. As a control for adventitious activation by extravagal somatic afferents, units responsive to vagal volleys were also tested during shock-induced facial and cervical twitches. Under the given conditions, 16% of a population of more than 200 limbic units responded only to vagal volleys. The ratio of initially excited to initially inhibited units was about 2:3. The response latencies were indicative of both rapidly and slowly conducting, afferent pathways. The entrainment of respiration by vagal volleys revealed that 6% of the tested units discharged with a periodicity commensurate with the respiratory rhythm. Such respiratory units were found in the anterior amygdala, insula and hippocampus. In the case of the hippocampus it can be concluded that the discharge of respiratory-type units is not dependent on olfactory inputs. In the amygdala, the highest percentage of responsive units was found in the central nucleus; none were of a respiratory-type. The particular interest of the respiratory-type units found in this and the preceding study is discussed.<br />
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'''Keywords:''' vagus nerve - - insula - - amygdala - - hippocampus - - entorhinal cortex - - respiration-related units<br />
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*Animal study in squirrel monkey involving stimulation of the vagus nerve with recording in limbic structures. Activity of the same periodicity as respiration was observed in 6% of neurons, with locations in anterior amygdala, insula and hippocampus. Another study that saw insula and temporal pole effects from stimulus in mokeys was [https://sudepwiki.pathology.jhmi.edu/index.php/Respiratory_and_vascular_responses_in_monkeys_from_temporal_pole,_insula,_orbital_surface_and_cingulate_gyrus;_a_preliminary_report Kaada et al].<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Respiratory_and_vascular_responses_in_monkeys_from_temporal_pole,_insula,_orbital_surface_and_cingulate_gyrus;_a_preliminary_report&diff=918Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report2018-03-01T19:47:06Z<p>Awils110: </p>
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<div>''Kaada BR, Pribram KH, and Epstein JA (1949) Respiratory and vascular responses in mon- keys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. J Neurophysiol 12:5 347–56.''<br />
<br />
'''[http://jn.physiology.org.ezp.welch.jhmi.edu/content/12/5/347.long Link to Article]'''<br />
<br />
'''Introduction:''' <br />
Attention has recently been focused on the finding of vascular and respiratory responses resulting from stimulation of the cortex of the posterior orbital surface (4,8,12, 17) and the anterior limbic region (10,19,22) of the frontal lobe of monkey. Physiological neuronography has shown reciprocal and restricted firing between the posterior orbital surface and the cortex of the temporal pole (3). Also, cytoarchiterctural studies in the macaque have indicated a close resemblance between these two areas (5). The finding of respiratory responses from stimulation of the anterior insula (20) provided a link between the frontal and temporal lobe. Because of these relationships it was decided to stimulate the cortex of the temporal pole and to study vascular and respiratory responses. In view of the positive results obtained from stimulation of the temporal pole in the present experiments, and the similarity of these responses from all of the above-mentioned regions, an investigation of the possible continuity of theses responsive areas was undertaken,<br />
=Context=<br />
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*Stimulation of insular cortex in monkeys caused respiratory arrest during either inspiratory or expiratory phases. Respiration resumed after approximately 30 s even in the presence of continued cortical stimulation. Effects on blood pressure were also identified, and the effects were shown to be mediated by direct connections to subcortical regions. <br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Respiratory_and_vascular_responses_in_monkeys_from_temporal_pole,_insula,_orbital_surface_and_cingulate_gyrus;_a_preliminary_report&diff=917Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report2018-03-01T19:44:50Z<p>Awils110: </p>
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<div>''Kaada BR, Pribram KH, and Epstein JA (1949) Respiratory and vascular responses in mon- keys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. J Neurophysiol 12:5 347–56.''<br />
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'''[http://jn.physiology.org.ezp.welch.jhmi.edu/content/12/5/347.long Link to Article]'''<br />
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'''Introduction:''' <br />
* Attention has recently been focused on the finding of vascular and respiratory responses resulting from stimulation of the cortex of the posterior orbital surface (4,8,12, 17) and the anterior limbic region (10,19,22) of the frontal lobe of monkey. Physiological neuronography has shown reciprocal and restricted firing between the posterior orbital surface and the cortex of the temporal pole (3). Also, cytoarchiterctural studies in the macaque have indicated a close resemblance between these two areas (5). The finding of respiratory responses from stimulation of the anterior insula (20) provided a link between the frontal and temporal lobe. Because of these relationships it was decided to stimulate the cortex of the temporal pole and to study vascular and respiratory responses. In view of the positive results obtained from stimulation of the temporal pole in the present experiments, and the similarity of these responses from all of the above-mentioned regions, an investigation of the possible continuity of theses responsive areas was undertaken,<br />
=Context=<br />
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*Stimulation of insular cortex in monkeys caused respiratory arrest during either inspiratory or expiratory phases. Respiration resumed after approximately 30 s even in the presence of continued cortical stimulation. Effects on blood pressure were also identified, and the effects were shown to be mediated by direct connections to subcortical regions. <br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Evidence_supporting_a_role_of_serotonin_in_modulation_of_sudden_death_induced_by_seizures_in_DBA/2_mice&diff=916Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice2018-03-01T19:30:57Z<p>Awils110: </p>
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<div>''Tupal S and Faingold CL (2006) Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice. Epilepsia 47:1 21–6.''<br />
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'''[http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2006.00365.x/epdf Link to Article]'''<br />
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'''Abstract:''' PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is a serious concern for epilepsy patients. DBA/2 mice are proposed as a SUDEP model, because these mice exhibit respiratory arrest (RA) after audiogenic seizures (AGSs), and RA is also implicated in human SUDEP. Respiratory mechanisms are modulated, in part, by serotonin. Therefore we evaluated the effects of serotoninergic agents on RA incidence in DBA/2 mice. METHODS: DBA/2 mice (75%) exhibited AGS and RA, and approximately 99% of animals could be resuscitated. The mice exhibiting RA were given a selective serotonin reuptake inhibitor, fluoxetine, 24 h after the initial AGS, and RA susceptibility was evaluated 30 min later. Ten percent of DBA/2 mice exhibited tonic hindlimb extension (TE) without RA, and a serotonin antagonist (cyproheptadine) was administered to these mice. RESULTS: Fluoxetine (15-25 mg/kg, i.p.) significantly reduced the incidence of RA in DBA/2 mice after AGSs, and this effect was reversible by 72 h. Only the 25-mg/kg dose reduced AGS severity. In mice exhibiting TE without RA, the incidence of RA was significantly increased 30 min after cyproheptadine (1-2 mg/kg i.p.). Most of these mice exhibited AGSs without RA again by 72 h. CONCLUSIONS: These findings indicate that fluoxetine reduced RA in DBA/2 mice at doses that did not reduce seizure severity. Because DBA/2 mice are a proposed model for human SUDEP, these data support evaluation of fluoxetine for SUDEP prevention in the patient population most susceptible to SUDEP. The data raise concern about the use of serotonin antagonists in this patient population.<br />
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'''Keywords:''' SUDEP—Audiogenicseizures—Respiratory arrest—Serotonin—DBA/2 mice<br />
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*Animal study in mouse strain subject to audiogenic seizures followed by respiratory arrest. High-dose fluoxetine reduced the likelihood of respiratory arrest after seizure for 2-3 days after dosing. The serotonin receptor antagonist cyproheptadine increased the frequency of respiratory arrest. These data suggest a clinical trial of prophylactic SSRI in patients at risk for SUDEP. Additional data are needed to determine whether SSRI might affect seizure frequency. [https://sudepwiki.pathology.jhmi.edu/index.php/Sudden_unexpected_death_in_epilepsy_(SUDEP):_Update_and_reflections Nashef and Rylvin] discuss serotonin's possible effects on seizure susceptibility more in this review.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Changes_in_respiratory-modulated_neural_activities,_consistent_with_obstructive_and_central_apnea,_during_fictive_seizures_in_an_in_situ_anaesthetized_rat_preparation&diff=915Changes in respiratory-modulated neural activities, consistent with obstructive and central apnea, during fictive seizures in an in situ anaesthetized rat preparation2018-03-01T19:26:27Z<p>Awils110: </p>
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<div>''St-John WM, Rudkin AH, Homes GL, and Leiter JC (2006) Changes in respiratory-modulated neural activities, consistent with obstructive and central apnea, during fictive seizures in an in situ anaesthetized rat preparation. Epilepsy Res 70:2-3 218–28.''<br />
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'''[https://ac.els-cdn.com/S092012110600146X/1-s2.0-S092012110600146X-main.pdf?_tid=cfd73012-ce54-11e7-805c-00000aacb361&acdnat=1511225112_38135d3b8f8178cec8e3fc5bb3163807 Link to Article]'''<br />
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'''Abstract:''' Sudden unexplained death in epilepsy (SUDEP) has been proposed to result from seizure-induced changes in respiratory and cardiac function. Our purpose was to characterize changes in respiration during seizures. We used a preparation of the anaesthetized, perfused in situ rat. This preparation has the advantage over in vivo preparations in that delivery of oxygen to the brain does not depend upon the lungs or cardiovascular system. Electroencephalographic activity was recorded as were activities of the hypoglossal, vagus and phrenic nerves. The hypoglossal and vagus nerves innervate muscles of the upper airway and larynx while the phrenic nerve innervates the diaphragm. Fictive seizures were elicited by injections of penicillin into the parietal cortex or the carotid artery. Following elicitation of the fictive seizures, activities of the hypoglossal and vagal nerves declined greatly while phrenic activity was little altered. Such a differential depression of activities of nerves to the upper airway and larynx, compared to that to the diaphragm, would predispose to obstructive apnea in intact preparations. With more time, activity of the phrenic nerve also declined or ceased. These changes characterize central apnea. The major conclusion is that seizures may result in recurrent periods of obstructive and central apnea. Thus, seizures can adversely alter respiratory function in a profound manner.<br />
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'''Keywords:''' Apnea; Seizures; Respiration; Upper airway<br />
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*Animal study in rats who were anesthetized and placed on cardiopulmonary bypass to provide continuous oxygenation to tissues independent of heart and brain function. During fictive seizures induced by penicillin, activities of hypoglossal and vagal nerves declined, though phrenic activity was largely unchanged. The authors contend that this pattern of altered neural activity would lead to obstructive apnea. The extent to which alterations in the function of cranial and spinal nerves in this seizure model recapitulate those that occur during seizures in patients is not clear. Later in experiments, activity in the phrenic nerve also declined, which the authors take as a correlate of central apnea, but this late change could reflect an overall loss of viability. <br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Epileptic_sudden_death:_Animal_models&diff=914Epileptic sudden death: Animal models2018-03-01T17:41:44Z<p>Awils110: /* Context */</p>
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<div>''Simon R(1997) Epileptic sudden death: Animal models. Epilepsia 38:S11 S35–37.''<br />
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'''[http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1157.1997.tb06124.x/epdf Link to Article]'''<br />
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'''Abstract:''' The pathologic hallmark of sudden unexpected death in epilepsy (SUDEP) in humans is pulmonary edema. In an animal model of seizures, pulmonary vascular pressure, but not systemic pressure, increases in proportion to seizure duration. The induced pulmonary vascular hypertension drives fluid out of the vascular compartment into the lung parenchyma. Blocking intra-ictal pulmonary vascular pressure elevations prevents changes in the observed doubling of the pulmonary transcapillary fluid flux. In this animal model, the main difference between surviving animals and those that die during the seizure is apnea, with a precipitous fall in the partial pressure of oxygen (pO(2)) and a parallel elevation in the partial pressure of carbon dioxide (pCO(2)) recorded in nonsurvivors. Pulmonary artery and left atrial pressures in animals that die are double those of surviving animals, with a resultant increase in extra-vascular lung water at postmortem examination. The pulmonary edema is due to the combined effects of seizure- and hypoxia-induced pulmonary vascular hypertension. This animal model reproduces both death during epilepsy and pulmonary edema at postmortem examination. The etiology of the pulmonary edema appears to be that of pulmonary vascular hypertension, and the etiology of sudden death appears to be that of centrally induced apnea.<br />
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'''Keywords:''' SUDEP, Epilepsy, Seizures, Pulmonary edema, Apnea<br />
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This study investigate the role of seizures on the pulmonary circuit within the sheep model. Simon found that with electroconvulsive shocks there was a 200% increase in vascular pressure within the aorta regardless of seizure detection through EEG. With induced seizure through injections with bicuculline, the pulmonary artery and left atrial pressues were nearly double in SUDEP sheep. Also there was a drastic increase of CO2 levels within four minutes of seizure induction. These results coincide with studies by [https://sudepwiki.pathology.jhmi.edu/index.php/Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death Johnston et al] who saw similar effects due to central apnea within the sheep model.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Kindled_seizures_elevate_blood_pressure_and_induce_cardiac_arrhythmias&diff=913Kindled seizures elevate blood pressure and induce cardiac arrhythmias2018-03-01T17:41:36Z<p>Awils110: </p>
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<div>''Goodman JH, Homan RW, and Crawford IL(1990) Kindled seizures elevate blood pressure and induce cardiac arrhythmias. Epilepsia 31:5 489–95.''<br />
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'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1111/j.1528-1157.1990.tb06096.x/epdf Link to Article]'''<br />
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'''Abstract:''' The effect of kindled seizures on the cardiovascular system was examined in amygdaloid kindled rats. The most prominent cardiovascular response during a generalized kindled seizure was an abrupt 50% increase in mean arterial pressure (MAP) lasting 20-30 s after initiation of the seizure. Superimposed on this change in blood pressure (BP) was a profound bradycardia characterized by a rate about half that recorded before stimulation. Changes in heart rate (HR) and BP observed during amygdaloid kindled seizures were similar to those observed during secondary spontaneous seizures. These effects apparently are independent of the kindling stimulus because stimulus-induced cardiovascular changes were not present at the beginning of the kindling process. These results suggest that the kindling seizure model is useful to study the underlying mechanisms of seizure-induced cardiac arrhythmias and possibly the clinical phenomenon of sudden unexplained death in epileptic patients.<br />
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'''Keywords:''' Convulsions, Neurologic models, Kindling, Amygdala, Blood pressure, Hypertension, Arrhythmia<br />
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*Animal study in rat of effect of kindling on autonomic function finding that amygdalar seizures increased blood pressure and caused bradycardia with beat to beat fluctuations. Both changes occurred within 5-10 s of seizure onset and persisted for up to 30 s. Large fluctuations in blood pressure were also seen, like consistent with dropped ventricular beats observed on EKG. This model in rats has similar characteristics to studies in sheep with increase vascular pressure following seizure induction. See [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] and [https://sudepwiki.pathology.jhmi.edu/index.php/Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death Johnston et al].<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=An_animal_model_for_SUDEP:_The_questions_shape_the_answers&diff=912An animal model for SUDEP: The questions shape the answers2018-03-01T17:38:02Z<p>Awils110: /* Context */</p>
<hr />
<div>''Scorza FA, Arida RM, Terra VC, and Cavalheiro EA (2009) An animal model for SUDEP: The questions shape the answers. Epilepsy Behav p. 540.''<br />
<br />
'''[https://ac.els-cdn.com/S1525505009003199/1-s2.0-S1525505009003199-main.pdf?_tid=a4b9b4a8-ce4b-11e7-804e-00000aab0f02&acdnat=1511221174_7618dc06c9a7a3867d7dadfe1f79ea64 Link to Article]'''<br />
<br />
'''First Paragraph:''' Individuals with epilepsy are at higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important, direct, epilepsy-related cause of death. SUDEP is responsible for 7.5–17% of all deaths in epilepsy and has an incidence among adults of between 1:500 and 1:1000 patient-years. As SUDEP can tragically cut short a young person’s life, several controlled studies have attempted to identify clinical characteristics of patients with epilepsy at particular risk for SUDEP. Thus, the majority of these studies have identified mainly higher risk factors linked to refractoriness of the epilepsy, presence of generalized tonic–clonic seizures, polytherapy with antiepileptic drugs, young age, duration of the seizure disorder ranging from 15 to 20 years, and early onset of epilepsy. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmia (due to myocardial ischemia), electrolyte disturbances, arrhythmogenic drugs or transmission of the epileptic activity via the autonomic nervous system to the heart, and central or obstructive apnea play a potential role.<br />
<br />
=Context=<br />
Letter to editor regarding different approaches to modeling SUDEP in animals. Discusses first nonhuman primate model which shows death from pulmonary edema following seizures. Continues into chicken model regarding its possible role for modeling SUDEP, see [https://sudepwiki.pathology.jhmi.edu/index.php/Could_sudden_death_syndrome_(SDS)_in_chickens_(Gallus_gallus)_be_a_valid_animal_model_for_sudden_unexpected_death_in_epilepsy_(SUDEP)%3F Scorza et al]. Many of this groups papers have minimal support to back their hypotheses regarding SUDEP in animal models.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=An_animal_model_for_SUDEP:_The_questions_shape_the_answers&diff=911An animal model for SUDEP: The questions shape the answers2018-03-01T17:37:18Z<p>Awils110: /* Context */</p>
<hr />
<div>''Scorza FA, Arida RM, Terra VC, and Cavalheiro EA (2009) An animal model for SUDEP: The questions shape the answers. Epilepsy Behav p. 540.''<br />
<br />
'''[https://ac.els-cdn.com/S1525505009003199/1-s2.0-S1525505009003199-main.pdf?_tid=a4b9b4a8-ce4b-11e7-804e-00000aab0f02&acdnat=1511221174_7618dc06c9a7a3867d7dadfe1f79ea64 Link to Article]'''<br />
<br />
'''First Paragraph:''' Individuals with epilepsy are at higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important, direct, epilepsy-related cause of death. SUDEP is responsible for 7.5–17% of all deaths in epilepsy and has an incidence among adults of between 1:500 and 1:1000 patient-years. As SUDEP can tragically cut short a young person’s life, several controlled studies have attempted to identify clinical characteristics of patients with epilepsy at particular risk for SUDEP. Thus, the majority of these studies have identified mainly higher risk factors linked to refractoriness of the epilepsy, presence of generalized tonic–clonic seizures, polytherapy with antiepileptic drugs, young age, duration of the seizure disorder ranging from 15 to 20 years, and early onset of epilepsy. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmia (due to myocardial ischemia), electrolyte disturbances, arrhythmogenic drugs or transmission of the epileptic activity via the autonomic nervous system to the heart, and central or obstructive apnea play a potential role.<br />
<br />
=Context=<br />
Letter to editor regarding different approaches to modeling SUDEP in animals. Discusses first nonhuman primate model which shows death from pulmonary edema following seizures. Continues into chicken model regarding its possible role for modeling SUDEP, see [https://sudepwiki.pathology.jhmi.edu/index.php/Could_sudden_death_syndrome_(SDS)_in_chickens_(Gallus_gallus)_be_a_valid_animal_model_for_sudden_unexpected_death_in_epilepsy_(SUDEP)%3F Scorza et al].<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=An_animal_model_for_SUDEP:_The_questions_shape_the_answers&diff=910An animal model for SUDEP: The questions shape the answers2018-03-01T17:36:49Z<p>Awils110: /* Context */</p>
<hr />
<div>''Scorza FA, Arida RM, Terra VC, and Cavalheiro EA (2009) An animal model for SUDEP: The questions shape the answers. Epilepsy Behav p. 540.''<br />
<br />
'''[https://ac.els-cdn.com/S1525505009003199/1-s2.0-S1525505009003199-main.pdf?_tid=a4b9b4a8-ce4b-11e7-804e-00000aab0f02&acdnat=1511221174_7618dc06c9a7a3867d7dadfe1f79ea64 Link to Article]'''<br />
<br />
'''First Paragraph:''' Individuals with epilepsy are at higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important, direct, epilepsy-related cause of death. SUDEP is responsible for 7.5–17% of all deaths in epilepsy and has an incidence among adults of between 1:500 and 1:1000 patient-years. As SUDEP can tragically cut short a young person’s life, several controlled studies have attempted to identify clinical characteristics of patients with epilepsy at particular risk for SUDEP. Thus, the majority of these studies have identified mainly higher risk factors linked to refractoriness of the epilepsy, presence of generalized tonic–clonic seizures, polytherapy with antiepileptic drugs, young age, duration of the seizure disorder ranging from 15 to 20 years, and early onset of epilepsy. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmia (due to myocardial ischemia), electrolyte disturbances, arrhythmogenic drugs or transmission of the epileptic activity via the autonomic nervous system to the heart, and central or obstructive apnea play a potential role.<br />
<br />
=Context=<br />
Letter to editor regarding different approaches to modeling SUDEP in animals. Discusses first nonhuman primate model which shows death from pulmonary edema following seizures. Continues into chicken model regarding its possible role for modeling SUDEP, see [https://sudepwiki.pathology.jhmi.edu/index.php/Could_sudden_death_syndrome_(SDS)_in_chickens_(Gallus_gallus)_be_a_valid_animal_model_for_sudden_unexpected_death_in_epilepsy_(SUDEP)%3F | Scorza et al].<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Epileptic_sudden_death:_Animal_models&diff=909Epileptic sudden death: Animal models2018-03-01T15:04:12Z<p>Awils110: </p>
<hr />
<div>''Simon R(1997) Epileptic sudden death: Animal models. Epilepsia 38:S11 S35–37.''<br />
<br />
'''[http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1157.1997.tb06124.x/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The pathologic hallmark of sudden unexpected death in epilepsy (SUDEP) in humans is pulmonary edema. In an animal model of seizures, pulmonary vascular pressure, but not systemic pressure, increases in proportion to seizure duration. The induced pulmonary vascular hypertension drives fluid out of the vascular compartment into the lung parenchyma. Blocking intra-ictal pulmonary vascular pressure elevations prevents changes in the observed doubling of the pulmonary transcapillary fluid flux. In this animal model, the main difference between surviving animals and those that die during the seizure is apnea, with a precipitous fall in the partial pressure of oxygen (pO(2)) and a parallel elevation in the partial pressure of carbon dioxide (pCO(2)) recorded in nonsurvivors. Pulmonary artery and left atrial pressures in animals that die are double those of surviving animals, with a resultant increase in extra-vascular lung water at postmortem examination. The pulmonary edema is due to the combined effects of seizure- and hypoxia-induced pulmonary vascular hypertension. This animal model reproduces both death during epilepsy and pulmonary edema at postmortem examination. The etiology of the pulmonary edema appears to be that of pulmonary vascular hypertension, and the etiology of sudden death appears to be that of centrally induced apnea.<br />
<br />
'''Keywords:''' SUDEP, Epilepsy, Seizures, Pulmonary edema, Apnea<br />
<br />
=Context=<br />
This study investigate the role of seizures on the pulmonary circuit within the sheep model. Simon found that with electroconvulsive shocks there was a 200% increase in vascular pressure within the aorta regardless of seizure detection through EEG. With induced seizure through injections with bicuculline, the pulmonary artery and left atrial pressues were nearly double in SUDEP sheep. Also there was a drastic increase of CO2 levels within four minutes of seizure induction. These results coincide with studies by [https://sudepwiki.pathology.jhmi.edu/index.php/Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death Johnston et al] who saw similar effects due to central apnea within the sheep model.<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=908Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:57:37Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
<br />
=Context=<br />
<br />
*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by [https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death Johnston et al] favored central apnea since it was seenin sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=907Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:57:16Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
<br />
=Context=<br />
<br />
*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by [https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death Johnston et al] favored central apnea since it was seen with those sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=906Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:57:04Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
<br />
=Context=<br />
<br />
*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by [https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death | Johnston et al] favored central apnea since it was seen with those sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=905Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:56:49Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
<br />
=Context=<br />
<br />
*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death | Johnston et al] favored central apnea since it was seen with those sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=904Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:56:35Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
<br />
=Context=<br />
<br />
*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death |Johnston et al] favored central apnea since it was seen with those sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=903Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:56:10Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
<br />
=Context=<br />
<br />
*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death Johnston et al] favored central apnea since it was seen with those sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death&diff=902Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death2018-03-01T14:55:42Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410420409/epdf Link to Article]'''<br />
<br />
'''Abstract:''' The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.<br />
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=Context=<br />
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*Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article. Another study conducted by https://sudepwiki.pathology.jhmi.edu/index.php/The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death#Context Johnston et al] favored central apnea since it was seen with those sheep who died from seizures, but not the ones that survived. Similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] who saw increase in sheep vascular pressure and a drastic increase in CO2 levels.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=901The role of hypoventilation in a sheep model of epileptic sudden death2018-03-01T14:49:32Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon 1997] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP. Another study conducted by [https://sudepwiki.pathology.jhmi.edu/index.php/Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death Johnston et al] found with seizure induction there was a increase in hypercarbia, hypoxia, and irregular breathing associated with the seizures, however reason for death is not fully clear.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=900The role of hypoventilation in a sheep model of epileptic sudden death2018-03-01T14:48:57Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon 1997] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP. Another study conducted by [https://sudepwiki.pathology.jhmi.edu/index.php/Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death <br />
| Johnston et al.] found with seizure induction there was a increase in hypercarbia, hypoxia, and irregular breathing associated with the seizures, however reason for death is not fully clear.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=899The role of hypoventilation in a sheep model of epileptic sudden death2018-03-01T14:48:33Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon 1997] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP. Another study conducted by [https://sudepwiki.pathology.jhmi.edu/index.php/Central_apnea_and_acute_cardiac_ischemia_in_a_sheep_model_of_epileptic_sudden_death <br />
Johnston et al.] found with seizure induction there was a increase in hypercarbia, hypoxia, and irregular breathing associated with the seizures, however reason for death is not fully clear.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Effect_of_phenobarbital_pretreatment_on_cardiac_neural_discharge_and_pentylenetetrazol-induced_epileptogenic_activity_in_the_cat&diff=898Effect of phenobarbital pretreatment on cardiac neural discharge and pentylenetetrazol-induced epileptogenic activity in the cat2018-03-01T14:42:21Z<p>Awils110: /* Context */</p>
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<div>''Carnel SB, Schraeder PL, and Lathers CM(1985) Effect of phenobarbital pretreatment on car- diac neural discharge and pentylenetetrazol-induced epileptogenic activity in the cat. Phar- macology 30:4 225–40.''<br />
<br />
'''[https://www.karger.com/Article/PDF/138072 Link to Article]<br />
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'''Abstract:''' The effect of phenobarbital on autonomic function associated with ictal discharges and interictal spikes (IS) was examined. Phenobarbital (20 mg/kg, i.v.) was infused over 10 min; 1 h later, pentylenetetrazol (PTZ) 10, 20, 50, 100, 200, and 2,000 mg/kg was given intravenously at 10-min intervals. 10 mg/kg PTZ produced IS in only 3 of 9 phenobarbital-pretreated cats; when used alone, 10 mg/kg of PTZ produced IS in 8 of 9 cats. Ictal discharges first appeared at 20 mg/kg PTZ in 6 of 9 phenobarbital-pretreated cats; all 9 cats receiving only PTZ exhibited ictal discharges after 20 mg/kg. Phenobarbital pretreatment depressed heart rate, blood pressure and postganglionic cardiac sympathetic neural discharge. Maximal ictal discharges in the cats pretreated with phenobarbital occurred with 100 mg/kg PTZ. This discharge was associated with a 10 mm Hg increase in blood pressure and a slight decrease in heart rate, followed by a subsequent return to baseline. The concurrent sympathetic neural discharge increased. When maximal ictal discharges occurred in the cats receiving PTZ alone, blood pressure, heart rate, and sympathetic neural discharge increased significantly. Cardiac vagal neural discharge was not altered after PTZ even in phenobarbital-pretreated cats. Although phenobarbital suppressed PTZ-induced epileptogenic activity and the associated changes in blood pressure and heart rate, a X2 test indicated no significant difference in the incidence of arrhythmias between the two groups. Since phenobarbital did not prevent the changes in cardiac neural discharge and the arrhythmias associated with epileptogenic activity, its effectiveness in decreasing autonomic dysfunction is questionable.<br />
<br />
'''Keywords:''' cardiac autonomic neural discharge, arrhythmia, Pentylenetetrazol, Phenobarbital, epileptogenic activity, cat<br />
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=Context=<br />
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*Early animal study of the effects of phenobarbitol (PB) and the seizure-provoking agent pentylenetetrazol (PTZ). Phenobarbitol decreased the rate of epileptiform activity, as well as heart rate and blood pressure. Autonomic response to the seizure-provoking agent was altered by the presence of PB; heart rate increased significantly in the presence of PTZ alone but decreased slightly when PTZ was given after PB. Phenobarbitol did not decrease the incidence of arrhythmias. This article is very similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Review_of_autonomic_dysfunction,_cardiac_arrhythmias,_and_epileptogenic_activity Lathers et al.]<br />
<br />
= Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Review_of_autonomic_dysfunction,_cardiac_arrhythmias,_and_epileptogenic_activity&diff=897Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity2018-03-01T14:41:19Z<p>Awils110: </p>
<hr />
<div>''Lathers CM and Schraeder PL(1987) Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity. J Clin Pharmacol 27:5 346–56.''<br />
<br />
'''[http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1987.tb03030.x/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Similarities in autonomic dysfunction associated with arrhythmias and death in animal models for digitalis toxicity, myocardial infarction, psychotropic toxicity, and epileptogenic activity are reviewed. When intravenous (IV) pentylenetetrazol was given to anesthetized cats, autonomic dysfunction was associated with both interictal and ictal epileptogenic activity. The autonomic dysfunction was manifested by the fact that autonomic cardiac nerves did not always respond in a predictable manner to changes in blood pressure, the development of a marked increase in variability in mean autonomic cardiac nerve discharge, and the appearance of a very large increase in the variability of the discharge rate of parasympathetic nerves first and then secondly in sympathetic discharge. The altered autonomic cardiac nerve discharge was associated with interictal epileptogenic activity and arrhythmia, which may contribute to sudden unexplained death in patients with epilepsy. Since phenobarbital (20 mg/kg, IV 60 min prior to pentylenetetrazol) exhibited anticonvulsant, but not antiarrhythmic and neural depressant activity, phenobarbital does not appear to be the ideal agent to prevent the autonomic dysfunction associated with epileptogenic activity in this animal model.<br />
<br />
=Context=<br />
<br />
Lathers and Schraeder reviews various possible outcomes from epileptic activity within the cat model. The two main models they discuss are the Digitalis Toxicity model which used ouabiain. Studies showed that when this drug was injected into a cat model they saw decreased neural discharges win the sympathetic system. They also discuss the epilepsy model in the cat when given PTZ. They describe autonomic dysfunction during the interictal and ictal period. Their research also showed changes to the QRS complex with premature atrial and ventricular contractions. These results were similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Effect_of_phenobarbital_pretreatment_on_cardiac_neural_discharge_and_pentylenetetrazol-induced_epileptogenic_activity_in_the_cat Schraeder's 1985] original work inducing epileptic activity within the cat model. <br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Review_of_autonomic_dysfunction,_cardiac_arrhythmias,_and_epileptogenic_activity&diff=896Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity2018-03-01T14:40:25Z<p>Awils110: /* Context */</p>
<hr />
<div>''Lathers CM and Schraeder PL(1987) Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity. J Clin Pharmacol 27:5 346–56.''<br />
<br />
'''[http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1987.tb03030.x/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Similarities in autonomic dysfunction associated with arrhythmias and death in animal models for digitalis toxicity, myocardial infarction, psychotropic toxicity, and epileptogenic activity are reviewed. When intravenous (IV) pentylenetetrazol was given to anesthetized cats, autonomic dysfunction was associated with both interictal and ictal epileptogenic activity. The autonomic dysfunction was manifested by the fact that autonomic cardiac nerves did not always respond in a predictable manner to changes in blood pressure, the development of a marked increase in variability in mean autonomic cardiac nerve discharge, and the appearance of a very large increase in the variability of the discharge rate of parasympathetic nerves first and then secondly in sympathetic discharge. The altered autonomic cardiac nerve discharge was associated with interictal epileptogenic activity and arrhythmia, which may contribute to sudden unexplained death in patients with epilepsy. Since phenobarbital (20 mg/kg, IV 60 min prior to pentylenetetrazol) exhibited anticonvulsant, but not antiarrhythmic and neural depressant activity, phenobarbital does not appear to be the ideal agent to prevent the autonomic dysfunction associated with epileptogenic activity in this animal model.<br />
<br />
=Context=<br />
<br />
Lathers and Schraeder reviews various possible outcomes from epileptic activity within the cat model. The two main models they discuss are the Digitalis Toxicity model which used ouabiain. Studies showed that when this drug was injected into a cat model they saw decreased neural discharges win the sympathetic system. They also discuss the epilepsy model in the cat when given PTZ. They describe autonomic dysfunction during the interictal and ictal period. Their research also showed changes to the QRS complex with premature atrial and ventricular contractions. These results were similar to [https://sudepwiki.pathology.jhmi.edu/index.php/Effect_of_phenobarbital_pretreatment_on_cardiac_neural_discharge_and_pentylenetetrazol-induced_epileptogenic_activity_in_the_cat \ Schraeder's 1985] original work with the cat model which showed changes in autonomic function with maximal effects during ictal convulsant activity.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Review_of_autonomic_dysfunction,_cardiac_arrhythmias,_and_epileptogenic_activity&diff=895Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity2018-03-01T14:32:55Z<p>Awils110: /* Context */</p>
<hr />
<div>''Lathers CM and Schraeder PL(1987) Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity. J Clin Pharmacol 27:5 346–56.''<br />
<br />
'''[http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1987.tb03030.x/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Similarities in autonomic dysfunction associated with arrhythmias and death in animal models for digitalis toxicity, myocardial infarction, psychotropic toxicity, and epileptogenic activity are reviewed. When intravenous (IV) pentylenetetrazol was given to anesthetized cats, autonomic dysfunction was associated with both interictal and ictal epileptogenic activity. The autonomic dysfunction was manifested by the fact that autonomic cardiac nerves did not always respond in a predictable manner to changes in blood pressure, the development of a marked increase in variability in mean autonomic cardiac nerve discharge, and the appearance of a very large increase in the variability of the discharge rate of parasympathetic nerves first and then secondly in sympathetic discharge. The altered autonomic cardiac nerve discharge was associated with interictal epileptogenic activity and arrhythmia, which may contribute to sudden unexplained death in patients with epilepsy. Since phenobarbital (20 mg/kg, IV 60 min prior to pentylenetetrazol) exhibited anticonvulsant, but not antiarrhythmic and neural depressant activity, phenobarbital does not appear to be the ideal agent to prevent the autonomic dysfunction associated with epileptogenic activity in this animal model.<br />
<br />
=Context=<br />
<br />
Lathers reviews various possible outcomes from epileptic activity within the cat model. The two main models they discuss are the Digitalis Toxicity model which used ouabiain. Studies showed that when this drug was injected into a cat model they saw decreased neural discharges win the sympathetic system. They also discuss the epilepsy model in the cat when given PTZ. They describe autonomic dysfunction during the interictal and ictal period.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=894The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:36:15Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon 1997] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=893The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:35:55Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models R.P. Simon] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=892The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:35:37Z<p>Awils110: </p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models | R.P. Simon] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=891The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:05:19Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [[https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models | R.P. Simon]] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=890The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:04:36Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [[https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models | R.P. Simon]] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=889The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:04:13Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [[https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models| R.P. Simon]] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=888The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:03:30Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [[https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models|R.P. Simon]] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=887The role of hypoventilation in a sheep model of epileptic sudden death2018-02-27T19:02:48Z<p>Awils110: /* Context */</p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In [[R.P. Simon|https://sudepwiki.pathology.jhmi.edu/index.php/Epileptic_sudden_death:_Animal_models]] there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Cardiac_and_respiratory_correlations_with_unit_discharge_in_human_amygdala_and_hippocampus&diff=886Cardiac and respiratory correlations with unit discharge in human amygdala and hippocampus2018-02-22T17:05:42Z<p>Awils110: /* Context */</p>
<hr />
<div>''Frysinger RC and Harper RM (1989) Cardiac and respiratory correlations with unit discharge in human amygdala and hippocampus. Electroencephalogr Clin Neurophysiol 72:6 463–70.''<br />
<br />
'''[http://ac.els-cdn.com/0013469489902228/1-s2.0-0013469489902228-main.pdf?_tid=a1815e2c-6bfd-11e7-bfb5-00000aacb360&acdnat=1500412454_4b8605022282cbcbcc16ec7f6b5fb06e Link to Article]'''<br />
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'''Abstract:''' Animal studies have shown that epileptiform seizures can cause cardiac arrhythmias and death. The amygdala and hippocampus are implicated in epileptogenesis and autonomic and respiratory control. We examined cardiac and respiratory correlations with single cell discharge in hippocampus and amygdala of patients with epilepsy. We recorded respiration, ECG, and neuronal discharge of amygdala and hippocampus from patients undergoing chronic depth electrode monitoring. Cross-correlation histograms were used to test for neuronal discharge timing relationships with inspiration or the ECG. Inspiratory time, respiratory period and heart rate were calculated for each breath, and linear regression was used to test for correlations with tonic unit rate. Of 183 cells from 24 patients, 20% had cardiac timing relationships and 23% showed tonic correlations with changes in heart rate. Only 2% had timing relationships with the respiratory cycle, while 15% showed tonic rate relationships with respiratory period. Recording sites did not differ in mean discharge rate or proportion of cells showing these correlations. These results indicate that a significant number of human forebrain cells show discharge modulation by the cardiac cycle and discharge rate correlation with changes in respiration and heart rate. This is supportive of animal models designed to explore the role of mesial temporal lobe structures in regulation of cardiovascular and respiratory systems, although a lower proportion of cells in human temporal lobe showed timing relationships with respiration and there was no clear evidence of anatomic specificity between amygdala and hippocampus.<br />
<br />
=Context=<br />
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*Investigation of correlation of activity in hippocampus and amygdala with cardiac and respiratory cycles in patients with epilepsy. Analysis of 183 cells from 24 patients showed relationships with cardiac timing among 20%, heart rate among 23%, respiratory period among 15%, and respiratory cycle timing among 2%. These data suggest an association of temporal lobe structures and cardiorespiratory function, but the causality is not clear.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_cardiac_sodium_channel_mRNA_is_expressed_in_the_developing_and_adult_rat_and_human_brain&diff=866The cardiac sodium channel mRNA is expressed in the developing and adult rat and human brain2018-02-14T17:47:52Z<p>Awils110: </p>
<hr />
<div>''Donahue LM, Coates PW, Lee VH, Ippensen DC, Arze SE, and Poduslo SE (2000) The cardiac sodium channel mRNA is expressed in the developing and adult rat and human brain. Brain Res 887:2 335–43.''<br />
<br />
'''[http://ac.els-cdn.com/S000689930003033X/1-s2.0-S000689930003033X-main.pdf?_tid=a8502f1e-6b3d-11e7-9f66-00000aab0f6c&acdnat=1500330002_16f1d054b35f344eb5708a22d101d39a Link to Article]'''<br />
<br />
'''Abstract:''' Expression of the rat (RH-I/SkM2) and human (hH1/SCN5A) tetrodotoxin-resistant (TTX-R), voltage-sensitive sodium channels is thought to be specific to cardiac tissue. We detected RH-I/SkM2 mRNA in newborn rat brain using both RNase protection assay analysis and in situ hybridization and in adult rat brain using RNase protection assay analysis. This expression was observed primarily in developing limbic structures of the cerebrum and diencephalon, and in the medulla of the brain stem. Using RT-PCR analysis, we detected hH1/SCN5A mRNA in both fetal and adult human brain. Interestingly, mutations in the human cardiac sodium channel are known to lead to cardiac abnormalities, which result in arrhythmias and frequently in sudden cardiac death. If these mutant channels were also expressed in limbic regions of the brain, alterations in channel function could have drastic effects on the brain's signaling ability, possibly promoting seizure activity.<br />
<br />
'''Keywords:''' Cardiac sodium channel; RH-1/SkM2; hH1/SCN5A; Limbic; mRNA expression; Long QT3 syndrome<br />
<br />
=Context=<br />
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*Identifies presence of mRNA for tetrodotoxin-resistant voltage-sensitive sodium channel, previously believed present only in heart, in fetal and adult brain. The authors highlight the implication that mutations in this channel known to cause arrhythmia could also cause epilepsy.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=The_role_of_hypoventilation_in_a_sheep_model_of_epileptic_sudden_death&diff=865The role of hypoventilation in a sheep model of epileptic sudden death2018-02-13T15:55:27Z<p>Awils110: </p>
<hr />
<div>''Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.''<br />
<br />
'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/ana.410370416/epdf Link to Article]'''<br />
<br />
'''Abstract:''' Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.<br />
<br />
=Context=<br />
<br />
*Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Rostral_brain_regions_contributing_to_respiratory_control&diff=849Rostral brain regions contributing to respiratory control2017-12-12T20:24:18Z<p>Awils110: </p>
<hr />
<div>''Harper RM, Rector D, Poe G, Frysinger RC, Kristensen M, and Gozel D(1996) Rostral brain regions contributing to respiratory control. Prog Brain Res 107: 145–56.''<br />
<br />
'''[https://www-ncbi-nlm-nih-gov.ezp.welch.jhmi.edu/pubmed/8782518 Link to Article]'''<br />
<br />
'''Publisher Summary:''' Respiratory muscles are used for a variety of behaviors in addition to the primary function of air exchange. These behaviors require input from a number of brain structures onto motorneuron pools for muscles mediating respiration, and include descending influences from limbic, periaqueductal grey, and cortical regions. Respiratory output neurons are also influenced by blood pressure variations; cardiovascular activity is, in turn, mediated by descending limbic projections, as well as by local activity on the ventral medullary surface. The rostral ventral medullary surface shows a marked regional activation to blood pressure lowering, and a profound decline in activity with blood pressure elevation over widespread areas, suggesting local influences on enhanced breathing during depressor challenges and suppressed breathing during pressor stimuli. The influence of limbic projections on breathing patterns may be especially pronounced during transient events, such as startle or affective activities. Dorsal hippocampal regions show pronounced regional activation changes during momentary respiratory events, such as sighs and apnea, with onset of activity preceding resumption of breathing.<br />
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=Context=<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Decrease_of_sympathetic_cardiovascular_modulation_after_temporal_lobe_epilepsy_surgery&diff=848Decrease of sympathetic cardiovascular modulation after temporal lobe epilepsy surgery2017-12-12T20:14:20Z<p>Awils110: /* Context */</p>
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<div>''Hilz MJ, Devinsky O, Doyle W, Mauerer A, and Dütsch M (2002) Decrease of sympathetic cardiovascular modulation after temporal lobe epilepsy surgery. Brain 125:Pt 5 985–95.''<br />
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'''[https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/brain/125/5/10.1093_brain_awf092/2/1250985.pdf?Expires=1501100073&Signature=QLrVQRwppPN8J1pUh~j7XbiS0sxNDARlLwDFewJa-l9Dh1UByc1u4Tn-ljQISpcouPZeWnI8F2pCTK6AAqIpkjYEx9Zp72k1RHIthaMWw~XUwQXvKMOrGvboWutBIlKWIN3VTeio-CY4z-l9o4a~cfOPOpsBtKdRJkoaD4cvZa0JgCALvVJS9yWQiAhfHHGsiECdg6XkYFURa9tNLUVM7PLTtl~uczEATgx9PE4fRQpNkFAGxoofH4zcpKCEalKlrRaQ5wadcOFDKCXqrWIWtx4ed0LggVv4QKuNfnI4E8eu74JYXbIwq7Mw5d0HYiXy3k0ybLHSv6Coz~dhu9OEeQ__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q Link to Article]'''<br />
<br />
'''Abstract:''' In temporal lobe epilepsy (TLE), there is evidence of ictal and interictal autonomic dysregulation, predominantly with sympathetic overactivity. The effects of TLE surgery on autonomic cardiovascular control and on baroreflex sensitivity (BRS) have not been studied. To evaluate such effects, we monitored heart rate (HR), systolic blood pressure (BP(sys)) and respiration in 18 TLE patients 3-4 months before and after TLE surgery. We used Blackman-Tukey spectral analysis to assess sympathetic and parasympathetic modulation as powers of HR and BP(sys) oscillations in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) bands. BRS was determined as the LF transfer function gain between BP and HR. After surgery, HR, BP(sys), respiration and HF powers remained unchanged, while LF powers of HR (1.57 +/- 1.54 bpm(2)) and BP(sys) (2.19 +/- 1.34 mmHg(2)) and BRS (0.68 +/- 0.31 bpm/mmHg) were smaller than pre-surgical LF powers of HR (3.87 +/- 3.26 bpm(2)) and BP(sys) (4.80 +/- 3.84 mmHg(2)) and BRS (1.12 +/- 0.39 bpm/mmHg; P < 0.05). After TLE surgery, there is a reduction of sympathetic cardiovascular modulation and BRS that might result from decreased influences of interictal epileptogenic discharges on brain areas involved in cardiovascular autonomic control. TLE surgery seems to stabilize the cardiovascular control in epilepsy patients by reducing the risk of sympathetically mediated tachyarrhythmias and excessive bradycardiac counter-regulation, both of which might be relevant for the pathophysiology of sudden unexpected death in epilepsy patients (SUDEP). Thus, TLE surgery might contribute to reducing the risk of SUDEP.<br />
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'''Keywords:''' autonomic nervous system, baroreflex sensitivity, central autonomic network, epilepsy surgery, interictal sympathetic tone<br />
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=Context=<br />
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*Study of autonomic function in 18 patients before and after epilepsy. HR and BP are essentially unchanged after temporal lobectomy (complete or partial), but LF variation increases in power after the procedure. The authors take this as an indication that the temporal lobe provides high sympathetic tone, decreasing HRV. In contrast to other studies from the same group, there does not seem to be a lateralizing effect. The authors also discuss the possibvility that seizure itself, rather than the temporal lobe, contributes to the apparent high basal sympathetic tone.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Sudden_withdrawal_of_carbamazepine_increases_cardiac_sympathetic_activity_in_sleep&diff=847Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep2017-12-12T20:12:47Z<p>Awils110: /* Context */</p>
<hr />
<div>''Hennessy MJ, Tighe MG, Binnie CD, and Nashef L (2001) Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep. Neurology 57:9 1650–4.''<br />
<br />
'''[http://www.neurology.org.ezp.welch.jhmi.edu/content/57/9/1650.full.pdf+html Link to Article]'''<br />
<br />
'''Abstract:''' OBJECTIVE: To evaluate the cardiac autonomic effects of abrupt withdrawal of carbamazepine (CBZ) during sleep in patients with epilepsy. BACKGROUND: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncertain, with ictal or peri-ictal cardiorespiratory compromise appearing probable. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-to-beat heart rate variability (HRV) displays two main components: low frequency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. METHOD: Twelve patients with medically intractable seizures underwent abrupt withdrawal of CBZ to facilitate seizure recording during controlled circuit TV-EEG monitoring. Continuous EKG recording was begun 24 hours before CBZ reduction. Spectral analysis of the HRV was performed during selected samples of non-REM sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. RESULTS: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increased in 10 patients compared with a decrease in only one patient. CONCLUSION: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep as evidenced by increased LF/HF ratios. Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose to SUDEP.<br />
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=Context=<br />
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*Abrupt decrease/elimination of carbamazepine dose was performed to provoke seizure in 12 patients undergoing continuous monitoring. (18 successive patients were enrolled, but only 12 had low enough seizure frequency to be studied.) HRV was measured during non-REM sleep at least 6 hours after a seizure. The low-frquency component of heart-rate variability increased over the 4 days after CBZ withdrawal. This suggests that abrupt cessation of CBZ, and possibly other AED, can lead to heightened sympathetic tone, possibly predisoposing to SUDEP. The authors conclude that AED should be withdrawn gradually.<br />
<br />
=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Sudden_withdrawal_of_carbamazepine_increases_cardiac_sympathetic_activity_in_sleep&diff=846Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep2017-12-12T20:12:38Z<p>Awils110: /* Context */</p>
<hr />
<div>''Hennessy MJ, Tighe MG, Binnie CD, and Nashef L (2001) Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep. Neurology 57:9 1650–4.''<br />
<br />
'''[http://www.neurology.org.ezp.welch.jhmi.edu/content/57/9/1650.full.pdf+html Link to Article]'''<br />
<br />
'''Abstract:''' OBJECTIVE: To evaluate the cardiac autonomic effects of abrupt withdrawal of carbamazepine (CBZ) during sleep in patients with epilepsy. BACKGROUND: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncertain, with ictal or peri-ictal cardiorespiratory compromise appearing probable. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-to-beat heart rate variability (HRV) displays two main components: low frequency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. METHOD: Twelve patients with medically intractable seizures underwent abrupt withdrawal of CBZ to facilitate seizure recording during controlled circuit TV-EEG monitoring. Continuous EKG recording was begun 24 hours before CBZ reduction. Spectral analysis of the HRV was performed during selected samples of non-REM sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. RESULTS: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increased in 10 patients compared with a decrease in only one patient. CONCLUSION: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep as evidenced by increased LF/HF ratios. Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose to SUDEP.<br />
<br />
=Context=<br />
<br />
*Abrupt decrease/elimination of carbamazepine dose was performed to provoke seizure in 12 patients undergoing continuous monitoring. (18 successive patients were enrolled, but only 12 had low enough seizure frequency to be studied.) HRV was measured during non-REM sleep at least 6 hours after a seizure. The low-frquency component of heart-rate variability increased over the 4 days after CBZ withdrawal. This suggests that abrupt cessation of CBZ, and possibly other AED, can lead to heightened sympathetic tone, possibly predisoposing to SUDEP. The authors conclude that AED should be withdrawn gradually.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Lateralized_and_widespread_brain_activation_during_transient_blood_pressure_elevation_revealed_by_magnetic_resonance_imaging&diff=845Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging2017-12-12T20:10:20Z<p>Awils110: /* Context */</p>
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<div>''Harper RM, Bandler R, Spriggs D, and Alger JR (2000) Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging. J Comp Neurol 417:2 195–204.''<br />
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'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1002/(SICI)1096-9861(20000207)417:2%3C195::AID-CNE5%3E3.0.CO;2-V/epdf Link to Article]'''<br />
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'''Abstract:''' The location and possible lateralization of structures mediating autonomic processing are not well-described in the human. Functional magnetic resonance imaging procedures were used to demonstrate signal changes in multiple brain sites during blood pressure challenges. Magnetic resonance signals in brain tissue were visualized with a 1.5 Tesla scanner in 11 healthy volunteers (22-37 years), by using echo-planar procedures. Images were collected during baseline states and three pressor challenges: cold application to the hand or forehead, and a Valsalva maneuver. Image values from experimental conditions were compared with corresponding baseline values on a voxel-by-voxel basis to identify brain regions responsive to physiologic activation. Probability maps (P < 0.01) of voxel changes, with Bonferroni corrections for multiple comparisons, were determined, and amplitude of signal changes associated with significance maps were pseudocolored and overlaid on anatomic images. The time courses and extent of signal alterations in defined unilateral regions were followed and compared with changes in corresponding regions on the contralateral side. Pressor challenges elicited significant regional signal intensity changes within the orbitomedial prefrontal cortex, temporal cortex, amygdala, hippocampal formation, thalamus, and hypothalamus. Cerebellar, midbrain, and pontine areas were also recruited. Signal changes, especially at forebrain sites, were often highly lateralized. The findings indicate that (1) transient, behaviorally-coupled cardiovascular challenges elicit discrete activity changes over multiple brain sites, and (2) these activity changes, especially in specific prefrontal and temporal forebrain regions and cerebellum, are often expressed unilaterally, even to a bilateral challenge.<br />
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'''Keywords:''' pressor challenge; prefrontal cortex; hippocampus; cerebellum; Valsalva; pain<br />
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*Like Harper et al., used cold challenges and Valsalva maneuver to assess changes in cerebral blood flow during transient hypertensive episodes in healthy volunteers. Widespread alterations were observed. One complexity is distinguishing alterations due simply to passive increases in local blood pressure and flux due to the increased systemic pressure from those that could be play a role in responding to the challenges. The lateralization of altered blood flow seen in some regions is unexpected and may reflect a more physiologic role.<br />
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=Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Lamotrigine_in_idiopathic_epilepsy_%E2%80%93_Increased_risk_of_cardiac_death%3F&diff=844Lamotrigine in idiopathic epilepsy – Increased risk of cardiac death?2017-12-12T15:54:11Z<p>Awils110: /* Context */</p>
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<div>''Aurlien D, Taubøll E, and Gjerstad L (2007) Lamotrigine in idiopathic epilepsy – Increased risk of cardiac death? Acta Neurol Scand 115:3 199–203''<br />
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'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1111/j.1600-0404.2006.00730.x/epdf Link to Article]'''<br />
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'''Abstract:''' <u>''OBJECTIVES:''</u> Lamotrigine (LTG) has recently been shown to inhibit the cardiac rapid delayed rectifier potassium ion current (Ikr). Ikr-blocking drugs may increase the risk of cardiac arrhythmia and sudden unexpected death. With this background, it may be of importance that in our outpatient clinic between August 1, 1995 and August 1, 2005 we registered four consecutive cases of sudden unexpected death in epilepsy (SUDEP) in non-hospitalized patients that were all being treated with LTG in monotherapy. Here we describe and discuss these cases, the relevant literature, and the reasons to question whether these events were as a result of coincidence alone. <u>''METHODS:'</u>' All the cases were collected consecutively at the outpatient clinic, Department of Neurology, Stavanger University Hospital, Norway. Clinical and pathological data were obtained and the relevant literature reviewed. <u>''RESULTS:''</u> All were females with idiopathic epilepsy. <u>''CONCLUSIONS:''</u> A systematic study is needed to reveal whether LTG may increase the risk of SUDEP in certain groups of patients.<br />
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'''Keywords:''' female, idiopathic epilepsy, lamotrigine, SUDEP<br />
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*Review of 4 cases of SUDEP in outpatients over 10 year span in this Norwegian study. All 4 patients were females being treated with lamotrigine monotherapy. During the period the deaths occurred, LTG had an average market share of 6.7% in the county housing the clinic. Of the 4 patients one had no detectable LTG in her serum after death, and for another the serum level was not measured; the authors point to Tomson et al. showing the unreliability of postmortem serum levels. Lamotrigine’s effect as an antagonist of the rapid delayed rectifier potassium ion current (Danielsson et al.) and possible tendency to cause arrhythmias is raised by the authors. The group followed up with Aurlien et al. and touched on the issue again in Aurlien et al.<br />
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= Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Sudden_unexpected,_unexplained_death_in_epilepsy_autopsied_patients&diff=843Sudden unexpected, unexplained death in epilepsy autopsied patients2017-12-12T15:53:40Z<p>Awils110: /* Context */</p>
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<div>''Antoniuk SA, Oliva LV, Bruck I, Malucelli M, Yabumoto S, and Castellano JL (2001) Sudden unexpected, unexplained death in epilepsy autopsied patients. Arq Neuropsiquiatr 59:1 40–5''<br />
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'''[http://www.scielo.br.ezp.welch.jhmi.edu/scielo.php?script=sci_arttext&pid=S0004-282X2001000100009&lng=en&nrm=iso&tlng=en Link to Article]'''<br />
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'''Abstract:''' Sudden unexpected, unexplained death in epilepsy (SUDEP) has been reported to be responsible for 2 to 17% of all deaths in patients with epilepsy. This study was conducted to determine the circumstances of SUDEP and the autopsy findings in these patients. Fifty-three individuals whose cause of death was related to epilepsy were identified and in 30 cases relatives or friends were interviewed about the circumstances of death and other information which allowed to classify the patients as SUDEP or not. The death certificates were also reviewed. We found 20 cases of SUDEP. Most of them were found dead lying on the bed with no evidence of seizure event, and most of them had pulmonary and/or cerebral edema as the cause of death. The incidence and the risk of SUDEP can only be fully ascertained if all sudden deaths had postmortem examination. Consensus in certifying SUDEP cases would allow better accuracy in national mortality rate.<br />
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'''Keywords:''' sudden death, epilepsy, circumstances of death, pulmonary edema<br />
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*Retrospective evaluation from Brazil of cause of death from 9.5 year period with 15,000 patients yielded 53 patients with epilepsy. In 30 cases those close to the deceased were interviewed (“verbal autopsy,” Lathers and Schraeder). The interviews of loved ones came after delays of many years from the time of death in some cases, which may have affected the accuracy of recollections. 20 cases met criteria for SUDEP in this study. Most of these were deaths in bed without evidence of seizure, with pulmonary or cerebral edema listed as the official cause of death. The race distribution of SUDEP deaths matched that of the overall population of deaths evaluated. 45% of patients had a history of excessive use of alcohol.<br />
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= Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=Epilepsy,_vagal_nerve_stimulation_by_the_NCP_system,_mortality,_and_sudden,_unexpected,_unexplained_death&diff=842Epilepsy, vagal nerve stimulation by the NCP system, mortality, and sudden, unexpected, unexplained death2017-12-12T15:53:20Z<p>Awils110: /* Context */</p>
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<div>''Annegers JF, Coan SP, Hauser WA, Leestma J, Duffell W, and Tarver B (1998) Epilepsy, vagal nerve stimulation by the NCP system, mortality, and sudden, unexpected, unexplained death. Epilepsia 39:2 206–12.'' <br />
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'''[http://onlinelibrary.wiley.com.ezp.welch.jhmi.edu/doi/10.1111/j.1528-1157.1998.tb01360.x/epdf Link to Article]'''<br />
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'''Abstract:''' <u>''PURPOSE:''</u> To determine rates of all-cause mortality and of sudden, unexpected, unexplained deaths in epilepsy (SUDEP) in a cohort of individuals treated with the Neuro Cybernetic Prosthesis (NCP) System for intractable epilepsy, and; to contrast the NCP experience with other epilepsy cohorts. <u>''METHODS:''</u> A cohort of 791 individuals were followed for 1,335 person-years from implantation. Of the total cohort, 120 individuals had their NCP System devices deactivated. The 15 deaths which occurred during NCP System activation were reviewed for SUDEP by a panel. There were three additional deaths and 242.5 person-years of monitoring after deactivation. <u>''RESULTS:''</u> The standardized mortality ratios for NCP System were 5.3, 95% confidence interval (CI) 3.0-8.7; and for the time period after device deactivation, 4.4, 95% CI 0.9-12.8. Six of the deaths during stimulation were considered definite or probable SUDEP and two as possible SUDEP. Seven were not considered to be SUDEP. The incidence of definite/probable SUDEP was 4.5 per 1,000 person-years and 6.0 per 1,000 person-years for definite/probable/possible SUDEP. <u>''CONCLUSIONS:''</u> The mortality rates and standardized mortality ratios are comparable with studies of young adults with intractable epilepsy who were not treated with NCP System. These SUDEP rates are not significantly different from those reported in the recent studies of lamotrigine (LTG), gabapentin (GBP), and tiagabine (TGB). The higher rates of SUDEP in the NCP System cohort, as compared with recent drug trials, presumably is explained by the selection of relatively higher-risk patients for the NCP System device.<br />
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'''Keywords:''' Epilepsy, Mortality, SUDEP, Vagal nerve<br />
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*Incidence of sudden death was evaluated among a patient cohort receiving vagal nerve stimulation. No significant affect of the device on risk was evident. 791 patients were in the study group. SUDEP incidence was 4.5 per 1,000 person-years in this cohort of patients with refractory epilepsy. Introduction includes helpful meta-analysis with valuable discussion on the changing rate of sudden death in both epilepsy and control populations over the lifespan, with apparent equalization of rates (no increased risk of sudden death for epilepsy patients) by around age 75. The study also provides informative history on initial resistance to the notion of SUDEP from those who believed any increased mortality among epilepsy patients was due to the causes of the epilepsy (e.g., trauma) rather than to epilepsy per se; this view lost support when a series of trials for new AEDs suggested that epilepsy can increase risk directly. The study was partially supported by the device manufacturer.<br />
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= Comments=</div>Awils110https://sudepwiki.pathology.jhmi.edu/index.php?title=SUDEP:_Overview_of_definitions_and_review_of_incidence_data&diff=841SUDEP: Overview of definitions and review of incidence data2017-12-12T15:52:12Z<p>Awils110: /* Context */</p>
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<div>''Annegers JF and Coan SP (1999) SUDEP: Overview of definitions and review of incidence data. Seizure 8:6 347–52''<br />
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'''[http://www.sciencedirect.com.ezp.welch.jhmi.edu/science/article/pii/S1059131199903060?via%3Dihub Link to Article]'''<br />
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'''Abstract:''' The classification, occurrence, and predictors of sudden unexpected and unexplained death in individuals with epilepsy (SUDEP) have received considerable attention over the last few years. Specific criteria for the classification of definite, probable, possible, and not SUDEP implemented in United States epidemiologic studies are presented. The incidence of SUDEP in different epilepsy populations is presented. SUDEP is a real phenomenon, because the occurrence of such deaths, especially at relatively young ages, among individuals with epilepsy is far greater (perhaps 40-fold) than among those without epilepsy. SUDEP incidence rates are lower in population-based studies, higher in referral populations and clinical trials of adjunct drugs for complex partial epilepsy, and highest for surgical series. Seizure severity appears to be the strongest risk factor for SUDEP because higher rates are reported from studies of individuals with intractable epilepsy. Other potential risk factors, including sex, seizure etiology, younger age at onset, and partial-onset seizures, are unresolved.<br />
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'''Keywords:''' SUDEP, epilepsy, seizures, classification, epidemiology.<br />
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*This analysis separated SUDEP deaths from seizure-related deaths, a distinction not generally drawn now. Demonstrates that rates of sudden death increase over the lifespan but declined over the 20th century. Helpful review of incidence studies.<br />
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= Comments=</div>Awils110