The Impact of Transcutaneous Spinal Cord Stimulation on Autonomic Regulation after Spinal Cord Injury: A randomized crossover trial

ImportanceIndividuals with spinal cord injury (SCI) have significant autonomic nervous system dysfunction. However, despite recent findings postulated to support that spinal cord stimulation improves dynamic autonomic regulation, limited scope of previous testing means the true effects remain unknown. ObjectiveTo determine whether transcutaneous spinal cord stimulation improves dynamic autonomic regulation after SCI. DesignSingle-blinded, randomized crossover trial with matched cohorts. SettingAcademic autonomic physiology laboratory. ParticipantsTwo pairs of well-matched individuals with and without high-thoracic, complete SCI. InterventionsSub-motor threshold transcutaneous spinal cord stimulation delivered at T10-T11 using 120Hz, 30Hz, and 30Hz with 5kHz carrier frequency at separate autonomic testing sessions. Main Outcomes and MeasuresBaseline autonomic regulation was characterized with tests of above injury level sympathoexcitation (Valsalvas maneuver), sympathoinhibition (progressive doses of bolus intravenous phenylephrine), and below level sympathoexcitation (foot cold pressor test). At three subsequent visits, this testing battery was repeated with the addition of spinal cord stimulation at each frequency. Changes in autonomic regulation for each frequency were then analyzed relative to baseline testing for each individual and within matched cohorts. ResultsUninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. Contrasting this, and as expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalvas maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared to baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in autonomic regulation. Conclusions and RelevanceTranscutaneous spinal cord stimulation does not improve autonomic regulation after SCI, and instead likely generates tonic, frequency-dependent sympathoexcitation which may lower the threshold for autonomic dysreflexia. Trial RegistrationTranscutaneous Spinal Cord Neuromodulation to Normalize Autonomic Phenotypes; NCT04858178. https://clinicaltrials.gov/ct2/show/NCT04858178 Key PointsO_LIDoes electrical spinal cord stimulation, at any previously advocated stimulation frequency, improve regulation of the autonomic nervous system for individuals with spinal cord injuries? C_LIO_LIIn this randomized crossover trial, transcutaneous spinal cord stimulation generated tonic, frequency-dependent sympathetic activation below the level of injury, without improved dynamic autonomic regulation. C_LIO_LITonic sympathetic activation below the level of injury could lower the threshold for potentially dangerous autonomic dysreflexia in individuals with spinal cord injury and future work should employ appropriate monitoring. C_LI