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Difference between revisions of "AIBS"

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<h4> Specific Aims and Tasks </h4>
 
<h4> Specific Aims and Tasks </h4>
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Identify patterns of physiological dysfunction (changes in blood pressure, heart rate, arrhythmia, breathing and EEG patterns) surrounding seizure periods and the underlying neural injury (focal structural brain changes identified through brain imaging including MRI) contributing to those patterns.
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<ul> <li> Will provide insight into mechanisms of failure in SUDEP, and suggest pre-mortem characteristics that lead to a fatal scenario that are suitable for targeted intervention </ul>
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Individuals with intractable epilepsy have a ~1% annual risk of Sudden Unexpected Death in Epilepsy (SUDEP). Pre-mortem risk factors are unknown. However, evidence suggests autonomic nervous system (ANS) failure, sustained apnea/hypoxemia, or some combination of respiratory and cardiovascular (CV) collapse underlies the fatal event. Adverse ANS signs are prominent in epilepsy, with ANS-driven cardiac arrhythmias (bradycardia, asystole, tachyarrhythmias) in ~72% of epilepsy patients, hypotension, impaired baroreflex sensitivity (potentially compromising cerebral blood flow), enhanced sympathetic outflow, expressed as increased sweating and decreased inter-ictal nocturnal heart rate variability (HRV) common.  <br> <br>
 
Individuals with intractable epilepsy have a ~1% annual risk of Sudden Unexpected Death in Epilepsy (SUDEP). Pre-mortem risk factors are unknown. However, evidence suggests autonomic nervous system (ANS) failure, sustained apnea/hypoxemia, or some combination of respiratory and cardiovascular (CV) collapse underlies the fatal event. Adverse ANS signs are prominent in epilepsy, with ANS-driven cardiac arrhythmias (bradycardia, asystole, tachyarrhythmias) in ~72% of epilepsy patients, hypotension, impaired baroreflex sensitivity (potentially compromising cerebral blood flow), enhanced sympathetic outflow, expressed as increased sweating and decreased inter-ictal nocturnal heart rate variability (HRV) common.  <br> <br>
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Deficits in other respiratory and ANS regulatory areas may participate, but those sites must be determined. We propose to relate focal brain structural changes in persons with epilepsy to particular peri-ictal autonomic and breathing patterns recognized as indices of risk for death. We found, in other syndromes exhibiting sudden death, e.g., heart failure, significant lateralized neural injury in brainstem and forebrain ANS and respiratory areas. Such unilateral injury can induce asymmetric ANS, and especially, sympathetic drive, establishing a scenario for potentially fatal arrhythmia or hypotension. We will determine peri-ictal physiological pattern of EEG, and especially PGES, blood pressure, HRV, baroreflex sensitivity, cardiac arrhythmia, and breathing that lead to risk of SUDEP, collect high resolution T1-weighted, diffusion tensor, and kurtosis images, and relate extent and laterality of injury to the physiological patterns. <br> <br>  
 
Deficits in other respiratory and ANS regulatory areas may participate, but those sites must be determined. We propose to relate focal brain structural changes in persons with epilepsy to particular peri-ictal autonomic and breathing patterns recognized as indices of risk for death. We found, in other syndromes exhibiting sudden death, e.g., heart failure, significant lateralized neural injury in brainstem and forebrain ANS and respiratory areas. Such unilateral injury can induce asymmetric ANS, and especially, sympathetic drive, establishing a scenario for potentially fatal arrhythmia or hypotension. We will determine peri-ictal physiological pattern of EEG, and especially PGES, blood pressure, HRV, baroreflex sensitivity, cardiac arrhythmia, and breathing that lead to risk of SUDEP, collect high resolution T1-weighted, diffusion tensor, and kurtosis images, and relate extent and laterality of injury to the physiological patterns. <br> <br>  
 
The studies will provide insights into mechanisms of failure in SUDEP, and suggest pre-mortem indications of characteristics that lead to a fatal scenario that are suitable for targeted intervention.  
 
The studies will provide insights into mechanisms of failure in SUDEP, and suggest pre-mortem indications of characteristics that lead to a fatal scenario that are suitable for targeted intervention.  
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     <h4> Principal Investigators </h4>
 
     <h4> Principal Investigators </h4>
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      <ul>
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              <li> <a href="investigators#sl" > Samden Lhatoo MD., FRCP.    </a> </li>
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              <li> <a href="investigators#bd" > Beate Diehl, M.D., Ph.D.    </a> </li>
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              <li> <a href="investigators#rh" > Ronald Harper, Ph.D.      </a> </li>
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      </ul>
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       <h4> Citations </h4>
 
       <h4> Citations </h4>

Revision as of 11:11, 13 November 2014


The Autonomic and Imaging Biomarkers of SUDEP (NS090407)


Specific Aims and Tasks

Identify patterns of physiological dysfunction (changes in blood pressure, heart rate, arrhythmia, breathing and EEG patterns) surrounding seizure periods and the underlying neural injury (focal structural brain changes identified through brain imaging including MRI) contributing to those patterns.
  • Will provide insight into mechanisms of failure in SUDEP, and suggest pre-mortem characteristics that lead to a fatal scenario that are suitable for targeted intervention

Principal Investigators



Citations



Protocols and Manuals



Publication Links



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