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`
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`
`Changes in Heart Activity MaySignal Epilepsy
`
`Need - March 9, 2016
`
`Pronouncedalterations in heart rate variability may contribute to sudden
`
`unexpected deathin epilepsy (SUDEP).
`
`Doctors have long characterized epilepsy as a brain disorder, but researchers at
`
`Case Western Reserve University have found that part of the autonomic nervous
`
`system functions differently in epilepsy during the absence of seizures.
`
`This connection to the involuntary division of the nervous system may have
`
`implications for diagnosing and treating the disease and understanding sudden
`
`unexpected death in epilepsy (SUDEP).
`
`The research is published online in the Journal of Neurophysiology.
`
`“All the findings of our study on heart rate variability in epilepsy point to increased
`
`activity in the parasympathetic nervous system during sleep, said Roberto
`
`Fernandez Galan assistant professor of electrical engineering and computer
`
`science and senior author of the study. “But we don't knowif this abnormality
`
`compensatesfor epilepsy, coincides with the disease or is part of the etiology.’
`
`Specifically, the parasympathetic—or “rest-and-digest”-nervous system modulates
`
`breathing and slows the heart rate of sleeping children with epilepsy substantially
`
`more than in healthy children.
`
`To their surprise, the researchers also found that several children who had been
`
`diagnosed as neurologically normal-—but had similar strong modulation and low
`
`heart rates—were later diagnosed with epilepsy.
`
`The discovery suggests that changes in the parasympathetic tone precede the
`
`onset of epilepsy in children.
`
`The Research
`
`Galan worked with Case Western Reserve undergraduate researcher Siddharth
`
`Sivakumar; from Case Western Reserve School of Medicine, Amalia Namath, who
`
`recently graduated with a master’s degree in medical physiology; Ingrid Tuxhorn,
`
`MD, professor of pediatric neurology; and Stephen Lewis, PhD, professor of
`
`pediatrics.
`
`The group studied the electrocardiograms of 91 children and adolescents with
`
`generalized epilepsy, and 25 neurologically normal children during 30 minutes of
`
`stage 2, or light, sleep. No subjects were suffering from a seizure during these
`
`intervals.
`
`The researchers found that respiratory sinus arrhythmia-the increase in heart
`
`rate during inhalation and decrease during exhalation—was more pronounced in
`
`patients with epilepsy, and that their heart rate also was significantly lower.
`
`Those changes are consistent with increased firing of the vagus nervein children
`
`with epilepsy, compared to those without, the researchers suggest. The vagus
`
`nerve is the main trunk of the parasympathetic nervous system. The more the
`
`vagus fires, the moreit slows the heart, especially during exhalation.
`
`The researchers found no difference in blood pressure between the two groups of
`
`children, indicating the sympathetic nervous system, which Is responsible for
`
`fight-or-flight responses, is not involved.
`
`All of the children in the study had electroencephalograms monitoring their brain
`
`activity during the 30-minute periods of sleep. There was no abnormal activity
`
`found there, either.
`
`Ramifications
`
`Galan said that by further defining differences in the respiratory sinus arrhythmia
`
`between children with and without epileptics, they may be able to identify
`
`thresholds, or biomarkers, to diagnose those with epilepsy or at risk of developing
`
`the disease.
`
`The researchers say the findings also raise the possibility that medicines that help
`
`control the autonomic nervous system may help control epilepsy.
`
`Other researchers, including Kenneth Loparo, chair of the Department of
`
`Electrical Engineering and Computer Science at Case Western Reserve, and
`
`Samden Lhatoo, MD, professor of neurology at Case Western Reserve School of
`
`Medicine, have shown that autonomic dysfunction may play a role in SUDEP. the
`
`most common cause of death among people with uncontrollable epilepsy.
`
`BBcontra
`MBEpiepsy
`
`100
`
`minule)
`HearlRate(bealsper
`
`
`o
`
`5
`
`10
`
`15
`Time (seconds)
`
`20
`
`25
`
`og
`
`Compared to a neurologically normal sleeping child, a sleeping child with epilepsy has a slower heart
`
`rate and the increase in heart rate during inhalation and decrease during exhalation, called the sinus
`
`arrhythmia, is more pronounced. Credit: Roberto Fernandez Galan, Siddharth Sivakumar.
`
`“This may be a key contributing factor,’ Sivakumar said. “The heart rate and
`
`breathing decline dramatically after a seizure. lf they are already low, and are then
`
`lowered further, that may cause a child to go a minute or more without a breath or
`
`pulse.”
`
`
`=
`
`
`
`
`BIJanuary 25, 2022
`Performance Enhancing Substances Linked lo Ealing
`Disorder Symploms
`
`Severe epilepsy in adults is sometimes treated by implanting an electrode to
`
`stimulate the vagus nerve, which, in turn, stimulates the brain. The treatment
`
`provides some relief for about 30 percent of patients, but other patients get no
`
`benefit and some find that their conditions worsen.
`
`“In light of our new findings, we call for caution,” Galan said. “The implant may be
`
`slowing the heart during sleep even more.’
`
`ABOUT THIS EPILEPSY RESEARCH
`
`Funding: The study was funded by The Hartwell Foundation. The researchers are
`
`now seeking financial support to broaden their study to adults, to include patients
`
`from several hospitals across the United States and to begin investigating
`
`whether medicines that modulate the parasympathetic system may be used to
`
`treat epilepsy.
`
`Source: Kevin Mayhood - Case Western Reserve University
`
`Image Source: The imageis credited to Roberto Fernandez Galan, Siddharth
`
`Sivakumar.
`
`Original Research: Abstract for “Decreased heart rate and enhanced sinus
`
`arrhythmia during interictal sleep demonstrate autonomic imbalance in
`
`generalized epilepsy’ by Siddharth S Sivakumar, Amalia Grace Namath, Ingrid E
`
`Tuxhorn, Stephen John Lewis, and Roberto Fernandez Galan in Journal of
`
`Neurophysiology. Published online February 17 2016 doi:10.1152/jn.01120.2015
`
`Abstract
`
`Decreased heart rate and enhancedsinus arrhythmia duringinterictal sleep
`
`demonstrate autonomic imbalancein generalized epilepsy
`
`Wehypothesized that epilepsy affects the activity of the autonomic nervous
`
`system even in the absenceof seizures, which should manifest as differences in
`
`heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we
`
`investigated electrocardiogram (ECG) traces of 91 children and adolescents with
`
`generalized epilepsy and 25 neurologically normal controls during 30 minutes of
`
`stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-
`
`frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were
`
`quantified and compared. Blood pressures (BP) from physical exams of all subjects
`
`were also collected and analyzed. RSA was on averagesignificantly stronger in
`
`patients with epilepsy, while their mean HR was significantly lower after adjusting
`
`for age, body mass index, and gender, consistent with increased parasympathetic
`
`tone in these patients. In contrast, diastolic (and systolic) blood pressure at rest
`
`was not significantly different, indicating that the sympathetic tone is similar.
`
`Remarkably, five additional subjects initially diagnosed as neurologically normal,
`
`but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting
`
`that increased parasympathetic tone precedes the onsetof epilepsy in children.
`
`ECG waveforms in epilepsy also displayed significantly longer TP intervals
`
`(ventricular diastole) relative to the RR interval. The relative TP interval
`
`correlated positively with RSA and negatively with HR, suggesting that these
`
`parameters are linked through a common mechanism, which we discuss.
`
`Altogether, our results provide evidence for imbalanced autonomic function in
`
`generalized epilepsy, which may be a key contributing factor to sudden
`
`unexpected death in epilepsy (SUDEP).
`
`“Decreased heart rate and enhanced sinus arrhythmia during interictal sleep
`
`demonstrate autonomic imbalance in generalized epilepsy” by Siddharth $
`
`Sivakumar, Amalia Grace Namath, Ingrid E Tuxhorn, Stephen John Lewis, and
`
`Roberto Fernandez Galan in Journal of Neurophysiology. Published online
`
`February 17 2016 doi:10.1152/jn.01120.2015
`
`FEEL FREE TO SHARE THIS NEUROSCIENCE NEWS.
`
`AfoyrimevemNCanc)(cnksy
`
`Sign up to receive our recent neuroscience
`headlines and summaries sent to your email
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`
`
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`contact you about newsletters. You can
`cancel your subscription anytime.
`
`SUBSCRIBE
`
`a | Pre eeeeeee) Tee|ne
`transferred to AWeber for Neuroscience
`
`eelfainto eeemete
`
`#ECG
`
`#ELECTROCARDIOGRAM-
`
`#EPILEPSY
`
`#HEART RATE
`
`#NEUROLOGY
`
`#PARASYMPATHETIC NERVOUS SYSTEM #PNS
`
`TAGS
`
`#SINUS ARRHYTHMIA
`
`#SLEEP
`
`#SUDDEN UNEXPECTED DEATH IN EPILEPSY
`
`#SUDEP
`
`#VAGUS NERVE
`
`aa Eee
`Re ee ae
`
`Wh
`
`Neuroscience News @
`
`f¥@
`
`Neuroscience News posts science research news from
`
`labs, universities, hospitals and news departments
`
`around the world. Science articles can cover
`
`neuroscience, psychology, Al, robotics, neurology, brain
`
`cancer, mental health, machine learning, autism,
`
`Parkinson's, Alzheimer's, brain research, depression and
`
`other topics related to cognitive sciences.
`
`Related
`
`
`
`Searching fora
`Cure for Deadly
`Brain Tumors
`
`
`
`Artificial
`Intelligence and
`Robotics Uncover
`HiddenSignatures
`of Parkinson’s
`Disease
`
`COVID-19 Infection
`Linked to Higher
`Risk of Neuropathy
`
`f Facebook
`
`wW Twitter @Instagram inLinkedin t Tumblr
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`
`
`Neuroscience News Sitemap
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`Neuroscience Graduate and Undergraduate
`
`ees]
`
`Free Neuroscience MOOCs
`
`Neuroscience Groups
`
`About
`
`Cer ame)
`
`acaa)
`
`Submit Neuroscience News
`
`Subscribe for Emails
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`Search Neuroscience News
`
`Serleeal
`
`[oy
`
`ees
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`CSTD feria taf eB tolorcD
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`eyegce)(eamaie
`Is (iB Ors |)eo oie POL
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`Alzheimer’s Disease
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`Parkinson's News
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`Artificial Intelligence News
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`Neuroscience News
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`Neuroscience Neurology Psychology Al Robotics Genetics Neurotech About (
`
`AliveCor Ex. 2020 - Page 1
`
`
`
` .
`Neuroscience ee:
`
`News.com
`
`at
`
`Neuroscience News Neuroscience Disorders Programs Advertise v Submit News Subscribe Register Discussions v
`
`5 £ vin o
`
`my
`
`Neuroscience ~ Neurology ~ Psychology ~ Al ~ Robotics Genetics Neurotech ~ About v
`
`Home >» Featured
`
`Changes in Heart Activity MaySignal Epilepsy
`
`Need - March 9, 2016
`
`Pronouncedalterations in heart rate variability may contribute to sudden
`
`unexpected deathin epilepsy (SUDEP).
`
`Doctors have long characterized epilepsy as a brain disorder, but researchers at
`
`Case Western Reserve University have found that part of the autonomic nervous
`
`system functions differently in epilepsy during the absence of seizures.
`
`This connection to the involuntary division of the nervous system may have
`
`implications for diagnosing and treating the disease and understanding sudden
`
`unexpected death in epilepsy (SUDEP).
`
`The research is published online in the Journal of Neurophysiology.
`
`“All the findings of our study on heart rate variability in epilepsy point to increased
`
`activity in the parasympathetic nervous system during sleep, said Roberto
`
`Fernandez Galan assistant professor of electrical engineering and computer
`
`science and senior author of the study. “But we don't knowif this abnormality
`
`compensatesfor epilepsy, coincides with the disease or is part of the etiology.’
`
`Specifically, the parasympathetic—or “rest-and-digest”-nervous system modulates
`
`breathing and slows the heart rate of sleeping children with epilepsy substantially
`
`more than in healthy children.
`
`To their surprise, the researchers also found that several children who had been
`
`diagnosed as neurologically normal-—but had similar strong modulation and low
`
`heart rates—were later diagnosed with epilepsy.
`
`The discovery suggests that changes in the parasympathetic tone precede the
`
`onset of epilepsy in children.
`
`The Research
`
`Galan worked with Case Western Reserve undergraduate researcher Siddharth
`
`Sivakumar; from Case Western Reserve School of Medicine, Amalia Namath, who
`
`recently graduated with a master’s degree in medical physiology; Ingrid Tuxhorn,
`
`MD, professor of pediatric neurology; and Stephen Lewis, PhD, professor of
`
`pediatrics.
`
`The group studied the electrocardiograms of 91 children and adolescents with
`
`generalized epilepsy, and 25 neurologically normal children during 30 minutes of
`
`stage 2, or light, sleep. No subjects were suffering from a seizure during these
`
`intervals.
`
`The researchers found that respiratory sinus arrhythmia-the increase in heart
`
`rate during inhalation and decrease during exhalation—was more pronounced in
`
`patients with epilepsy, and that their heart rate also was significantly lower.
`
`Those changes are consistent with increased firing of the vagus nervein children
`
`with epilepsy, compared to those without, the researchers suggest. The vagus
`
`nerve is the main trunk of the parasympathetic nervous system. The more the
`
`vagus fires, the moreit slows the heart, especially during exhalation.
`
`The researchers found no difference in blood pressure between the two groups of
`
`children, indicating the sympathetic nervous system, which Is responsible for
`
`fight-or-flight responses, is not involved.
`
`All of the children in the study had electroencephalograms monitoring their brain
`
`activity during the 30-minute periods of sleep. There was no abnormal activity
`
`found there, either.
`
`Ramifications
`
`Galan said that by further defining differences in the respiratory sinus arrhythmia
`
`between children with and without epileptics, they may be able to identify
`
`thresholds, or biomarkers, to diagnose those with epilepsy or at risk of developing
`
`the disease.
`
`The researchers say the findings also raise the possibility that medicines that help
`
`control the autonomic nervous system may help control epilepsy.
`
`Other researchers, including Kenneth Loparo, chair of the Department of
`
`Electrical Engineering and Computer Science at Case Western Reserve, and
`
`Samden Lhatoo, MD, professor of neurology at Case Western Reserve School of
`
`Medicine, have shown that autonomic dysfunction may play a role in SUDEP. the
`
`most common cause of death among people with uncontrollable epilepsy.
`
`BBcontra
`MBEpiepsy
`
`100
`
`minule)
`HearlRate(bealsper
`
`
`o
`
`5
`
`10
`
`15
`Time (seconds)
`
`20
`
`25
`
`og
`
`Compared to a neurologically normal sleeping child, a sleeping child with epilepsy has a slower heart
`
`rate and the increase in heart rate during inhalation and decrease during exhalation, called the sinus
`
`arrhythmia, is more pronounced. Credit: Roberto Fernandez Galan, Siddharth Sivakumar.
`
`“This may be a key contributing factor,’ Sivakumar said. “The heart rate and
`
`breathing decline dramatically after a seizure. lf they are already low, and are then
`
`lowered further, that may cause a child to go a minute or more without a breath or
`
`pulse.”
`
`
`=
`
`
`
`
`BIJanuary 25, 2022
`Performance Enhancing Substances Linked lo Ealing
`Disorder Symploms
`
`Severe epilepsy in adults is sometimes treated by implanting an electrode to
`
`stimulate the vagus nerve, which, in turn, stimulates the brain. The treatment
`
`provides some relief for about 30 percent of patients, but other patients get no
`
`benefit and some find that their conditions worsen.
`
`“In light of our new findings, we call for caution,” Galan said. “The implant may be
`
`slowing the heart during sleep even more.’
`
`ABOUT THIS EPILEPSY RESEARCH
`
`Funding: The study was funded by The Hartwell Foundation. The researchers are
`
`now seeking financial support to broaden their study to adults, to include patients
`
`from several hospitals across the United States and to begin investigating
`
`whether medicines that modulate the parasympathetic system may be used to
`
`treat epilepsy.
`
`Source: Kevin Mayhood - Case Western Reserve University
`
`Image Source: The imageis credited to Roberto Fernandez Galan, Siddharth
`
`Sivakumar.
`
`Original Research: Abstract for “Decreased heart rate and enhanced sinus
`
`arrhythmia during interictal sleep demonstrate autonomic imbalance in
`
`generalized epilepsy’ by Siddharth S Sivakumar, Amalia Grace Namath, Ingrid E
`
`Tuxhorn, Stephen John Lewis, and Roberto Fernandez Galan in Journal of
`
`Neurophysiology. Published online February 17 2016 doi:10.1152/jn.01120.2015
`
`Abstract
`
`Decreased heart rate and enhancedsinus arrhythmia duringinterictal sleep
`
`demonstrate autonomic imbalancein generalized epilepsy
`
`Wehypothesized that epilepsy affects the activity of the autonomic nervous
`
`system even in the absenceof seizures, which should manifest as differences in
`
`heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we
`
`investigated electrocardiogram (ECG) traces of 91 children and adolescents with
`
`generalized epilepsy and 25 neurologically normal controls during 30 minutes of
`
`stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-
`
`frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were
`
`quantified and compared. Blood pressures (BP) from physical exams of all subjects
`
`were also collected and analyzed. RSA was on averagesignificantly stronger in
`
`patients with epilepsy, while their mean HR was significantly lower after adjusting
`
`for age, body mass index, and gender, consistent with increased parasympathetic
`
`tone in these patients. In contrast, diastolic (and systolic) blood pressure at rest
`
`was not significantly different, indicating that the sympathetic tone is similar.
`
`Remarkably, five additional subjects initially diagnosed as neurologically normal,
`
`but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting
`
`that increased parasympathetic tone precedes the onsetof epilepsy in children.
`
`ECG waveforms in epilepsy also displayed significantly longer TP intervals
`
`(ventricular diastole) relative to the RR interval. The relative TP interval
`
`correlated positively with RSA and negatively with HR, suggesting that these
`
`parameters are linked through a common mechanism, which we discuss.
`
`Altogether, our results provide evidence for imbalanced autonomic function in
`
`generalized epilepsy, which may be a key contributing factor to sudden
`
`unexpected death in epilepsy (SUDEP).
`
`“Decreased heart rate and enhanced sinus arrhythmia during interictal sleep
`
`demonstrate autonomic imbalance in generalized epilepsy” by Siddharth $
`
`Sivakumar, Amalia Grace Namath, Ingrid E Tuxhorn, Stephen John Lewis, and
`
`Roberto Fernandez Galan in Journal of Neurophysiology. Published online
`
`February 17 2016 doi:10.1152/jn.01120.2015
`
`FEEL FREE TO SHARE THIS NEUROSCIENCE NEWS.
`
`AfoyrimevemNCanc)(cnksy
`
`Sign up to receive our recent neuroscience
`headlines and summaries sent to your email
`
`
`
`WGickcireneNaecR vem cielme
`contact you about newsletters. You can
`cancel your subscription anytime.
`
`SUBSCRIBE
`
`a | Pre eeeeeee) Tee|ne
`transferred to AWeber for Neuroscience
`
`eelfainto eeemete
`
`#ECG
`
`#ELECTROCARDIOGRAM-
`
`#EPILEPSY
`
`#HEART RATE
`
`#NEUROLOGY
`
`#PARASYMPATHETIC NERVOUS SYSTEM #PNS
`
`TAGS
`
`#SINUS ARRHYTHMIA
`
`#SLEEP
`
`#SUDDEN UNEXPECTED DEATH IN EPILEPSY
`
`#SUDEP
`
`#VAGUS NERVE
`
`aa Eee
`Re ee ae
`
`Wh
`
`Neuroscience News @
`
`f¥@
`
`Neuroscience News posts science research news from
`
`labs, universities, hospitals and news departments
`
`around the world. Science articles can cover
`
`neuroscience, psychology, Al, robotics, neurology, brain
`
`cancer, mental health, machine learning, autism,
`
`Parkinson's, Alzheimer's, brain research, depression and
`
`other topics related to cognitive sciences.
`
`Related
`
`
`
`Searching fora
`Cure for Deadly
`Brain Tumors
`
`
`
`Artificial
`Intelligence and
`Robotics Uncover
`HiddenSignatures
`of Parkinson’s
`Disease
`
`COVID-19 Infection
`Linked to Higher
`Risk of Neuropathy
`
`f Facebook
`
`wW Twitter @Instagram inLinkedin t Tumblr
`
`
`
`Neuroscience News Sitemap
`
`Neuroscience Graduate and Undergraduate
`
`ees]
`
`Free Neuroscience MOOCs
`
`Neuroscience Groups
`
`About
`
`Cer ame)
`
`acaa)
`
`Submit Neuroscience News
`
`Subscribe for Emails
`
`Search Neuroscience News
`
`Serleeal
`
`[oy
`
`ees
`
`CSTD feria taf eB tolorcD
`
`eyegce)(eamaie
`Is (iB Ors |)eo oie POL
`
`Alzheimer’s Disease
`
`Parkinson's News
`
`Autism / ASD News
`
`Neurotechnology News
`
`Artificial Intelligence News
`
`Robotics News
`
`Neuroscience News
`
`Neuroscience Neurology Psychology Al Robotics Genetics Neurotech About (
`
`AliveCor Ex. 2020 - Page 1
`
`
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