SB 35 Determination Methodology and Background Data June ...
Background Methodology - AACPDM
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Potential Benefits of ANS Monitoring: • Simultaneity of ANS monitoring during TMS sessions allows for real-time analysis beyond pre/post-TMS blood pressure assessment (Figure 4). • ANS monitoring can be completed without verbal feedback from the child, allowing an additional assessment of safety (Figure 5). Neuromodulatory intervention using non-invasive brain stimulation (NIBS) can target areas of the brain such as the motor cortex for recovery following stroke and may be paired with rehabilitation. 1-3 Although results show promise, understanding how NIBS impacts other systems such as the autonomic nervous system (ANS) is not known. One form of NIBS, transcranial magnetic stimulation (TMS), may be used as a test or repetitively as an intervention (rTMS) to influence cortical excitability. Combining ANS and TMS assessment may provide unique insight into responses to NIBS. TMS—One form of NIBS • TMS involves using a magnetic coil to provide a cortical stimulus to the central nervous system in a targeted location such as the primary motor cortex (M1) (Figure 1a-b). • Muscular responses to TMS are measured using surface electromyography (EMG). • Stimulating a child’s brain using NIBS, may elicit individual responses (e.g. anxiety, stress, subtle side effects) and carries the risk of adverse events (e.g. seizure or vasovagal response). • TMS has demonstrated an effect on blood pressure (BP) with the activation of the sympathetic nervous system. 4 • Evidence suggests that when used as an intervention, rTMS can modulate sympathetic activity and thereby alter the ANS. 4,5 • Therefore, by monitoring the ANS during TMS testing, we aim to 1) determine the feasibility and tolerance of measuring the ANS 2) gain a comprehensive assessment of ANS responses and 2) measure of safety and tolerance for intervention in children. Rationale for TMS/ANS Study • Analyze the physiological effects of NIBS using ANS monitoring • Potentially prevent an adverse event from occurring through early identification • Contribute to a greater understanding of the role of the ANS impacting functional change following NIBS interventions. ANS Monitoring Techniques During TMS Testing ANS monitoring may detect subtle and/or incremental changes in HR variability and may aid in early detection of an adverse event. Techniques for monitoring ANS responses during TMS include pre/post BP readings or concurrent ANS monitoring. In order to investigate the impact of NIBS interventions, a comprehensive understanding of the child’s cardiovascular responses is needed. As a part of a larger study combining transcranial direct current stimulation (tDCS) and constraint induced movement therapy (CIMT) (NCT02250092), we are piloting ANS monitoring during our TMS testing. Feasibility considerations for concurrent ANS and EMG monitoring are summarized (Table 1). For monitoring, we use: • Continuous non-invasive blood pressure monitoring • A 3-lead electrocardiogram (ECG) • Monitoring (on the middle or ring finger) during TMS testing (Figure 2a-d) • Concurrent surface EMG measurements on a hand muscle 2a. 2b. 2c. 2d. Figure 2a-d. ANS Equipment including a) blood pressure recording device to control cuff inflation, b) wrist unit device to control air flow to the finger cuff connected to a Powerlab for signal processing, c) height corrector to provide a blood pressure consistent with aortic pressure, d) non- invasive blood pressure finger cuff (AD Instruments, Colorado Springs, CO). Image from http://www.adinstruments.com. Autonomic nervous system monitoring during transcranial magnetic stimulation: Making a difference in monitoring responses and adverse events in children with hemiparetic cerebral palsy TL Rich 1,2 , M Keller-Ross 1 , D Chantigian 1 , C-Y Chen 1 , G Meekins 1 , T Feyma 2 , L Krach 3 , BT Gillick 1 1 University of Minnesota, Minneapolis, Minnesota 2 Gillette Children’s Specialty Healthcare, St. Paul, Minnesota 3 Courage Kenny Rehabilitation Institute, Minneapolis, Minnesota Background Tonya Rich, PhDs, MA, OTR/L— [email protected] Methodology Significance Acknowledgements 1. Wasserman E, Epstein CM, Ziemann U. Oxford Handbook of Transcranial Stimulation. Oxford University Press; 2008. 2. Gillick BT, Krach LE, Feyma T, Rich TL, Moberg K, Thomas W, Cassidy JM, Menk J, Carey JR. Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: A randomized controlled trial. Dev Med Child Neurol. 2014; 56(1): 44-52. 3. Kirton A, Andersen J, Herrero M, Nettel-Aguirre A, Carsolio L, Damji O, Keess J, Mineyko A, Hodge J, Hill MD. Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial. Neurology. 2016: 86(19): 1659-67. 4. Yoshida T, Yoshino A, Kobayashi Y, Inoue M, Kamakura K, Nomura S. Effects of slow repetitive transcranial magnetic stimulation on heart rate variability according to power spectrum analysis. J Neurol Sci 2001;184:77–80. 5. Cassanova MF, Hensley MK, Sokhadze EM, El-Bas AS, Wang Y, Li X, Sears L. Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder. Frontiers in human neuroscience. 2014; 8(851): 1-11. Funding Source: This study was supported by the following grant: National Institutes of Health (NIH) Eunice Kennedy Shriver National Institutes of Child Health and Development K01 Award (#HD078484-01A1), the Cerebral Palsy Foundation, the Foundation for Physical Therapy Magistro Family Grant, National Center for Advancing Translational Sciences (NCATS) of the NIH Award (UL1TR000114), and Center for Magnetic Resonance Research (P41 EB015894). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Minnesota. Tonya Rich, PhDs, MA, OTR/L was supported by the Minnesota Discovery Research InnoVation Economy (MnDRIVE) fellowship, an American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) OrthoPediatric, AACDPM Student Travel Award, and the Marie Louise Wales Fellowship during this study. We are grateful for the children and families who participated in this study. References Rehabilitation Science • Our pilot data suggests that ANS techniques can be well-tolerated by children with the use of environmental and behavioral strategies. • ANS monitoring during NIBS may provide valuable information regarding alterations in BP and HR that may be directly or indirectly caused by NIBS. • ANS monitoring may be helpful for early identification of BP and HR changes that may lead to syncope or other rare adverse events. • ANS assessment may contribute to understanding how children respond to NIBS. Feasibility Considerations Strategy Signal interference from ANS equipment can occur when using concurrent EMG recording. Repositioning the ANS equipment and intermittent use of the finger cuff for monitoring during different components of the testing protocol can reduce signal noise present in EMG data. Periods of quiet rest are needed to record baseline activity. Behavioral strategies that create procedural predictability aid in supporting the child’s tolerance and achievement of the quiet rest periods. Monitoring equipment may influence child’s tolerance for completing TMS testing. Developmentally appropriate explanations and behavioral strategies such as visual schedules or visual timers may ease anticipatory anxiety. Table 1. Feasibility considerations for concurrent ANS and EMG monitoring in children. Figure 4. Pilot ANS data. Red trace: ECG recording, Blue trace: Raw blood pressure signal, Purple trace: TMS stimulus. Horizontal axis: time in minutes. The large purple vertical line denotes TMS stimulus tracking. 4. Figure 5. Sample concurrent monitoring set- up. EMG leads are on the thumb side of the hand with red and black EMG wires. Non- invasive blood pressure monitoring is the cuff on the ring finger. 5. Figure 1b. Equipment to monitor heart rate (HR) and BP located behind the participant. Equipment for TMS and EMG monitoring located in the participant’s view. 1b. Figure 1a. Child receiving TMS testing over the hand representation of M1. 1. 1a. Methodology
Transcript of Background Methodology - AACPDM
Potential Benefits of ANS Monitoring:• Simultaneity of ANS monitoring during TMS sessions allows for real-time analysis beyond pre/post-TMS blood
pressure assessment (Figure 4). • ANS monitoring can be completed without verbal feedback from the child, allowing an additional assessment of
safety (Figure 5).
Neuromodulatory intervention using non-invasive brain stimulation (NIBS) can target areas of the brain such as the motor cortex for recovery following stroke and may be paired with rehabilitation.1-3 Although results show promise, understanding how NIBS impacts other systems such as the autonomic nervous system (ANS) is not known. One form of NIBS, transcranial magnetic stimulation (TMS), may be used as a test or repetitively as an intervention (rTMS) to influence cortical excitability. Combining ANS and TMS assessment may provide unique insight into responses to NIBS.
TMS—One form of NIBS• TMS involves using a magnetic coil to provide a cortical stimulus to the central nervous system in a
targeted location such as the primary motor cortex (M1) (Figure 1a-b). • Muscular responses to TMS are measured using surface electromyography (EMG). • Stimulating a child’s brain using NIBS, may elicit individual responses (e.g. anxiety, stress, subtle side
effects) and carries the risk of adverse events (e.g. seizure or vasovagal response). • TMS has demonstrated an effect on blood pressure (BP) with the activation of the sympathetic
nervous system.4• Evidence suggests that when used as an intervention, rTMS can modulate sympathetic activity and
thereby alter the ANS.4,5
• Therefore, by monitoring the ANS during TMS testing, we aim to 1) determine the feasibility and tolerance of measuring the ANS 2) gain a comprehensive assessment of ANS responses and 2) measure of safety and tolerance for intervention in children.
Rationale for TMS/ANS Study• Analyze the physiological effects of NIBS using ANS monitoring• Potentially prevent an adverse event from occurring through early identification• Contribute to a greater understanding of the role of the ANS impacting functional change following
NIBS interventions.
ANS Monitoring Techniques During TMS TestingANS monitoring may detect subtle and/or incremental changes in HR variability and may aid in early detection of an adverse event. Techniques for monitoring ANS responses during TMS include pre/post BP readings or concurrent ANS monitoring.
In order to investigate the impact of NIBS interventions, a comprehensive understanding of the child’s cardiovascular responses is needed. As a part of a larger study combining transcranial direct current stimulation (tDCS) and constraint induced movement therapy (CIMT) (NCT02250092), we are piloting ANS monitoring during our TMS testing. Feasibility considerations for concurrent ANS and EMG monitoring are summarized (Table 1). For monitoring, we use:
• Continuous non-invasive blood pressure monitoring • A 3-lead electrocardiogram (ECG)• Monitoring (on the middle or ring finger) during TMS testing (Figure 2a-d)
• Concurrent surface EMG measurements on a hand muscle2a. 2b.
2c. 2d.
Figure 2a-d. ANS Equipment including a) blood pressure recording device to control cuff inflation, b) wrist unit device to control air flow to the finger cuff connected to a Powerlab for signal processing, c) height corrector to provide a blood pressure consistent with aortic pressure, d) non-invasive blood pressure finger cuff (AD Instruments, Colorado Springs, CO). Image from http://www.adinstruments.com.
Autonomic nervous system monitoring during transcranial magnetic stimulation: Making a difference in monitoring responses and adverse events in children with hemiparetic cerebral palsy
TL Rich1,2, M Keller-Ross1, D Chantigian1, C-Y Chen1, G Meekins1, T Feyma2, L Krach3, BT Gillick11 University of Minnesota, Minneapolis, Minnesota 2Gillette Children’s Specialty Healthcare, St. Paul, Minnesota 3Courage Kenny Rehabilitation Institute, Minneapolis, Minnesota
Background
Tonya Rich, PhDs, MA, OTR/L— [email protected]
Methodology
Significance
Acknowledgements
1. Wasserman E, Epstein CM, Ziemann U. Oxford Handbook of Transcranial Stimulation. Oxford University Press; 2008. 2. Gillick BT, Krach LE, Feyma T, Rich TL, Moberg K, Thomas W, Cassidy JM, Menk J, Carey JR. Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric
hemiparesis: A randomized controlled trial. Dev Med Child Neurol. 2014; 56(1): 44-52. 3. Kirton A, Andersen J, Herrero M, Nettel-Aguirre A, Carsolio L, Damji O, Keess J, Mineyko A, Hodge J, Hill MD. Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial.
Neurology. 2016: 86(19): 1659-67. 4. Yoshida T, Yoshino A, Kobayashi Y, Inoue M, Kamakura K, Nomura S. Effects of slow repetitive transcranial magnetic stimulation on heart rate variability according to power spectrum analysis. J Neurol Sci
2001;184:77–80.5. Cassanova MF, Hensley MK, Sokhadze EM, El-Bas AS, Wang Y, Li X, Sears L. Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder. Frontiers in human
neuroscience. 2014; 8(851): 1-11.
Funding Source: This study was supported by the following grant: National Institutes of Health (NIH) Eunice Kennedy Shriver National Institutes of Child Health and Development K01 Award (#HD078484-01A1), the Cerebral Palsy Foundation, the Foundation for Physical Therapy Magistro Family Grant, National Center for Advancing Translational Sciences (NCATS) of the NIH Award (UL1TR000114), and Center for Magnetic Resonance Research (P41 EB015894). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Minnesota. Tonya Rich, PhDs, MA, OTR/L was supported by the Minnesota Discovery Research InnoVation Economy (MnDRIVE) fellowship, an American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) OrthoPediatric, AACDPM Student Travel Award, and the Marie Louise Wales Fellowship during this study. We are grateful for the children and families who participated in this study.
References
Rehabilitation Science
• Our pilot data suggests that ANS techniques can be well-tolerated by children with the use of environmental and behavioral strategies.
• ANS monitoring during NIBS may provide valuable information regarding alterations in BP and HR that may be directly or indirectly caused by NIBS.
• ANS monitoring may be helpful for early identification of BP and HR changes that may lead to syncope or other rare adverse events.
• ANS assessment may contribute to understanding how children respond to NIBS.
Feasibility Considerations StrategySignal interference from ANS equipment can occur when using concurrent EMG recording.
Repositioning the ANS equipment and intermittent use of the finger cuff for monitoring during different components of the testing protocol can reduce signal noise present in EMG data.
Periods of quiet rest are needed to record baseline activity. Behavioral strategies that create procedural predictability aid in supporting the child’s tolerance and achievement of the quiet rest periods.
Monitoring equipment may influence child’s tolerance for completing TMS testing.
Developmentally appropriate explanations and behavioral strategies such as visual schedules or visual timers may ease anticipatory anxiety.
Table 1. Feasibility considerations for concurrent ANS and EMG monitoring in children.
Figure 4. Pilot ANS data. Red trace: ECG recording, Blue trace: Raw blood pressure signal, Purple trace: TMS stimulus. Horizontal axis: time in minutes. The large purple vertical line denotes TMS stimulus tracking.
4.
Figure 5. Sample concurrent monitoring set-up. EMG leads are on the thumb side of the hand with red and black EMG wires. Non-invasive blood pressure monitoring is the cuff on the ring finger.
5.Figure 1b. Equipment to monitor heart rate (HR) and BP located behind the participant. Equipment for TMS and EMG monitoring located in the participant’s view.
1b.Figure 1a. Child receiving TMS testing over the hand representation of M1.
1.1a.
Methodology
