Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-sponsored clinical trial. Part I: methodology and effectiveness of expiratory muscle activation
Anthony F DiMarco, Krzysztof E Kowalski, Robert T Geertman, Dana R Hromyak, Anthony F DiMarco, Krzysztof E Kowalski, Robert T Geertman, Dana R Hromyak
Abstract
Objective: Evaluation of the capacity of lower thoracic spinal cord stimulation (SCS) to activate the expiratory muscles and generate large airway pressures and high peak airflows characteristic of cough, in subjects with tetraplegia.
Design: Clinical trial.
Setting: Inpatient hospital setting for electrode insertion; outpatient setting for measurement of respiratory pressures; home setting for application of SCS.
Participants: Subjects (N=9; 8 men, 1 woman) with cervical spinal cord injury and weak cough.
Interventions: A fully implantable electrical stimulation system was surgically placed in each subject. Partial hemilaminectomies were made to place single-disk electrodes in the epidural space at the T9, T11, and L1 spinal levels. A radiofrequency receiver was placed in a subcutaneous pocket over the anterior portion of the chest wall. Electrode wires were tunneled subcutaneously and connected to the receiver. Stimulation was applied by activating a small portable external stimulus controller box powered by a rechargeable battery to each electrode lead alone and in combination.
Main outcome measures: Peak airflow and airway pressure generation achieved with SCS.
Results: Supramaximal SCS resulted in high peak airflow rates and large airway pressures during stimulation at each electrode lead. Maximum peak airflow rates and airway pressures were achieved with combined stimulation of any 2 leads. At total lung capacity, mean maximum peak airflow rates and airway pressure generation were 8.6+/-1.8 (mean +/- SE) L/s and 137+/-30 cmH2O (mean +/- SE), respectively.
Conclusions: Lower thoracic SCS results in near maximum activation of the expiratory muscles and the generation of high peak airflow rates and positive airway pressures in the range of those observed with maximum cough efforts in healthy persons.
Trial registration: ClinicalTrials.gov NCT00116337.
Figures
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Relationship between stimulus frequency (Hz) and mean airway pressure generation (expressed as a…
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Relationship between stimulus amplitude (V) and mean airway pressure generation (expressed as a…
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Relationship between pulse width (µs) and mean airway pressure generation (expressed as a…
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Relationship between airway pressure and…
Figure 7
Relationship between airway pressure and peak airflow generation, for each subject at FRC…
Figure 8
Mean changes in airway pressure…
Figure 8
Mean changes in airway pressure (expressed as a percent maximum) with 2 site…
- Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-Sponsored clinical trial. Part II: clinical outcomes.DiMarco AF, Kowalski KE, Geertman RT, Hromyak DR, Frost FS, Creasey GH, Nemunaitis GA. DiMarco AF, et al. Arch Phys Med Rehabil. 2009 May;90(5):726-32. doi: 10.1016/j.apmr.2008.11.014. Arch Phys Med Rehabil. 2009. PMID: 19406290 Free PMC article. Clinical Trial.
- Effects of Lower Thoracic Spinal Cord Stimulation on Bowel Management in Individuals With Spinal Cord Injury.DiMarco AF, Geertman RT, Tabbaa K, Nemunaitis GA, Kowalski KE. DiMarco AF, et al. Arch Phys Med Rehabil. 2021 Jun;102(6):1155-1164. doi: 10.1016/j.apmr.2020.09.394. Epub 2020 Nov 5. Arch Phys Med Rehabil. 2021. PMID: 33161007 Free PMC article. Clinical Trial.
- Spinal cord stimulation: a new method to produce an effective cough in patients with spinal cord injury.DiMarco AF, Kowalski KE, Geertman RT, Hromyak DR. DiMarco AF, et al. Am J Respir Crit Care Med. 2006 Jun 15;173(12):1386-9. doi: 10.1164/rccm.200601-097CR. Epub 2006 Mar 16. Am J Respir Crit Care Med. 2006. PMID: 16543552 Free PMC article.
- Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques.DiMarco AF. DiMarco AF. Respir Physiol Neurobiol. 2005 Jul 28;147(2-3):273-87. doi: 10.1016/j.resp.2005.03.007. Respir Physiol Neurobiol. 2005. PMID: 16046197 Review.
- Review of Epidural Spinal Cord Stimulation for Augmenting Cough after Spinal Cord Injury.Hachmann JT, Calvert JS, Grahn PJ, Drubach DI, Lee KH, Lavrov IA. Hachmann JT, et al. Front Hum Neurosci. 2017 Mar 28;11:144. doi: 10.3389/fnhum.2017.00144. eCollection 2017. Front Hum Neurosci. 2017. PMID: 28400726 Free PMC article. Review.
- Narrative review of current neuromodulation modalities for spinal cord injury.Medina R, Ho A, Reddy R, Chen J, Castellanos J. Medina R, et al. Front Pain Res (Lausanne). 2023 Mar 9;4:1143405. doi: 10.3389/fpain.2023.1143405. eCollection 2023. Front Pain Res (Lausanne). 2023. PMID: 36969918 Free PMC article. Review.
- Effects of restoration of cough via spinal cord stimulation on subject quality of life.DiMarco AF, Geertman RT, Nemunaitis GA, Kowalski KE. DiMarco AF, et al. J Clin Orthop Trauma. 2022 Sep 27;34:102027. doi: 10.1016/j.jcot.2022.102027. eCollection 2022 Nov. J Clin Orthop Trauma. 2022. PMID: 36212771
- A Review of Functional Restoration From Spinal Cord Stimulation in Patients With Spinal Cord Injury.Lin A, Shaaya E, Calvert JS, Parker SR, Borton DA, Fridley JS. Lin A, et al. Neurospine. 2022 Sep;19(3):703-734. doi: 10.14245/ns.2244652.326. Epub 2022 Sep 30. Neurospine. 2022. PMID: 36203296 Free PMC article.
- Comparison of disc and wire electrodes to restore cough via lower thoracic spinal cord stimulation.DiMarco AF, Geertman RT, Nemunaitis GA, Kowalski KE. DiMarco AF, et al. J Spinal Cord Med. 2022 May;45(3):354-363. doi: 10.1080/10790268.2021.1936388. Epub 2021 Jul 7. J Spinal Cord Med. 2022. PMID: 34232841 Free PMC article. Clinical Trial.
- Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury.Malone IG, Nosacka RL, Nash MA, Otto KJ, Dale EA. Malone IG, et al. J Neurophysiol. 2021 Aug 1;126(2):607-626. doi: 10.1152/jn.00625.2020. Epub 2021 Jul 7. J Neurophysiol. 2021. PMID: 34232771 Free PMC article. Review.
- Clinical Trial
- Research Support, N.I.H., Extramural
- Adult
- Cough*
- Electric Stimulation / methods*
- Electrodes, Implanted
- Female
- Follow-Up Studies
- Humans
- Injury Severity Score
- Male
- Middle Aged
- National Institutes of Health (U.S.)
- Peak Expiratory Flow Rate
- Prospective Studies
- Quadriplegia / rehabilitation*
- Recovery of Function
- Respiratory Function Tests
- Respiratory Mechanics / physiology
- Respiratory Muscles / innervation
- Respiratory Muscles / physiology*
- Spinal Cord Injuries / diagnosis
- Spinal Cord Injuries / rehabilitation*
- Thoracic Vertebrae / innervation
- Treatment Outcome
- United States
- Young Adult
- ClinicalTrials.gov/NCT00116337
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
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![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2813808/bin/nihms165546f4.jpg)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2813808/bin/nihms165546f5.jpg)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2813808/bin/nihms165546f6.jpg)
Figure 7
Relationship between airway pressure and…
Figure 7
Relationship between airway pressure and peak airflow generation, for each subject at FRC…
Figure 8
Mean changes in airway pressure…
Figure 8
Mean changes in airway pressure (expressed as a percent maximum) with 2 site…
- Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-Sponsored clinical trial. Part II: clinical outcomes.DiMarco AF, Kowalski KE, Geertman RT, Hromyak DR, Frost FS, Creasey GH, Nemunaitis GA. DiMarco AF, et al. Arch Phys Med Rehabil. 2009 May;90(5):726-32. doi: 10.1016/j.apmr.2008.11.014. Arch Phys Med Rehabil. 2009. PMID: 19406290 Free PMC article. Clinical Trial.
- Effects of Lower Thoracic Spinal Cord Stimulation on Bowel Management in Individuals With Spinal Cord Injury.DiMarco AF, Geertman RT, Tabbaa K, Nemunaitis GA, Kowalski KE. DiMarco AF, et al. Arch Phys Med Rehabil. 2021 Jun;102(6):1155-1164. doi: 10.1016/j.apmr.2020.09.394. Epub 2020 Nov 5. Arch Phys Med Rehabil. 2021. PMID: 33161007 Free PMC article. Clinical Trial.
- Spinal cord stimulation: a new method to produce an effective cough in patients with spinal cord injury.DiMarco AF, Kowalski KE, Geertman RT, Hromyak DR. DiMarco AF, et al. Am J Respir Crit Care Med. 2006 Jun 15;173(12):1386-9. doi: 10.1164/rccm.200601-097CR. Epub 2006 Mar 16. Am J Respir Crit Care Med. 2006. PMID: 16543552 Free PMC article.
- Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques.DiMarco AF. DiMarco AF. Respir Physiol Neurobiol. 2005 Jul 28;147(2-3):273-87. doi: 10.1016/j.resp.2005.03.007. Respir Physiol Neurobiol. 2005. PMID: 16046197 Review.
- Review of Epidural Spinal Cord Stimulation for Augmenting Cough after Spinal Cord Injury.Hachmann JT, Calvert JS, Grahn PJ, Drubach DI, Lee KH, Lavrov IA. Hachmann JT, et al. Front Hum Neurosci. 2017 Mar 28;11:144. doi: 10.3389/fnhum.2017.00144. eCollection 2017. Front Hum Neurosci. 2017. PMID: 28400726 Free PMC article. Review.
- Narrative review of current neuromodulation modalities for spinal cord injury.Medina R, Ho A, Reddy R, Chen J, Castellanos J. Medina R, et al. Front Pain Res (Lausanne). 2023 Mar 9;4:1143405. doi: 10.3389/fpain.2023.1143405. eCollection 2023. Front Pain Res (Lausanne). 2023. PMID: 36969918 Free PMC article. Review.
- Effects of restoration of cough via spinal cord stimulation on subject quality of life.DiMarco AF, Geertman RT, Nemunaitis GA, Kowalski KE. DiMarco AF, et al. J Clin Orthop Trauma. 2022 Sep 27;34:102027. doi: 10.1016/j.jcot.2022.102027. eCollection 2022 Nov. J Clin Orthop Trauma. 2022. PMID: 36212771
- A Review of Functional Restoration From Spinal Cord Stimulation in Patients With Spinal Cord Injury.Lin A, Shaaya E, Calvert JS, Parker SR, Borton DA, Fridley JS. Lin A, et al. Neurospine. 2022 Sep;19(3):703-734. doi: 10.14245/ns.2244652.326. Epub 2022 Sep 30. Neurospine. 2022. PMID: 36203296 Free PMC article.
- Comparison of disc and wire electrodes to restore cough via lower thoracic spinal cord stimulation.DiMarco AF, Geertman RT, Nemunaitis GA, Kowalski KE. DiMarco AF, et al. J Spinal Cord Med. 2022 May;45(3):354-363. doi: 10.1080/10790268.2021.1936388. Epub 2021 Jul 7. J Spinal Cord Med. 2022. PMID: 34232841 Free PMC article. Clinical Trial.
- Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury.Malone IG, Nosacka RL, Nash MA, Otto KJ, Dale EA. Malone IG, et al. J Neurophysiol. 2021 Aug 1;126(2):607-626. doi: 10.1152/jn.00625.2020. Epub 2021 Jul 7. J Neurophysiol. 2021. PMID: 34232771 Free PMC article. Review.
- Clinical Trial
- Research Support, N.I.H., Extramural
- Adult
- Cough*
- Electric Stimulation / methods*
- Electrodes, Implanted
- Female
- Follow-Up Studies
- Humans
- Injury Severity Score
- Male
- Middle Aged
- National Institutes of Health (U.S.)
- Peak Expiratory Flow Rate
- Prospective Studies
- Quadriplegia / rehabilitation*
- Recovery of Function
- Respiratory Function Tests
- Respiratory Mechanics / physiology
- Respiratory Muscles / innervation
- Respiratory Muscles / physiology*
- Spinal Cord Injuries / diagnosis
- Spinal Cord Injuries / rehabilitation*
- Thoracic Vertebrae / innervation
- Treatment Outcome
- United States
- Young Adult
- ClinicalTrials.gov/NCT00116337
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2813808/bin/nihms165546f7.jpg)
Figure 8
Mean changes in airway pressure…
Figure 8
Mean changes in airway pressure (expressed as a percent maximum) with 2 site…
![Figure 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2813808/bin/nihms165546f8.jpg)
Source: PubMed