Reduced Reflex Autonomic Responses Following Intradetrusor OnabotulinumtoxinA Injections: A Pre-/Post-study in Individuals With Cervical and Upper Thoracic Spinal Cord Injury

Abstract

Urodynamic studies (UDS) can provoke autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI) at and above the sixth thoracic spinal segment potentially leading to profound vagally mediated heart rate (HR) reductions. In this study,1 we test the hypothesis that intradetrusor onabotulinumtoxinA injections will improve HR and its variability (HRV) responses to UDS in individuals with cervical and thoracic SCI. A total of 19 participants with chronic SCI (5 women, mean age 42.5 ± 7.9 years) with confirmed neurogenic detrusor overactivity underwent UDS before (i.e., baseline) and 1 month after intradetrusor onabotulinumtoxinA (200 U) injections (post-treatment). Continuous electrocardiography and blood pressure (BP) recordings were used to assess RR-interval, time, and frequency domain metrics of HRV (a surrogate marker of autonomic nervous system activity), and AD pre- and post-treatment. UDS pre-treatment resulted in increased RR-interval as well as time and frequency domain metrics of HRV. Vagally mediated increases in high-frequency (HF) power during UDS were larger in participants with cervical compared to upper thoracic SCI. Post-treatment, UDS had no effect on RR-interval and significantly reduced instances of bradycardia. Furthermore, intradetrusor onabotulinumtoxinA injections significantly reduced time domain metrics of HRV and HF power responses to UDS across all participants. Changes in HRV during UDS could be a potential indicator of improved autonomic cardiovascular function following interventions such as intradetrusor onabotulinumtoxinA injections.

From Toxin to Treatment: A Narrative Review on the Use of Botulinum Toxin for Autonomic Dysfunction

“…Intravesical injections of BoNT are hypothesized to limit bladder-related AD by preventing NDO, a common trigger for the reflexive sympathetic spinal response that distinguishes AD [ 132 , 133 ].…”

“…Currently, only off-label use of Botox ® has been evaluated in the treatment of AD [ 113 , 116 , 133 , 134 , 135 ].…”

“…Intravesical injections of 200 U of Botox ® diminished bladder-related AD events during UDS [ 113 , 116 ]. This was reported by reduced systolic blood pressure elevations and reduced incidence of self-reported AD symptoms, both during filling and at cystometric capacity, one month after injection [ 113 , 133 , 134 , 135 ]. Furthermore, Botox ® minimizes the reflexive vagal responses associated with bladder filling during UDS, as evidenced by changes in heart rate variability (HRV) [ 133 ].…”

“…This was reported by reduced systolic blood pressure elevations and reduced incidence of self-reported AD symptoms, both during filling and at cystometric capacity, one month after injection [ 113 , 133 , 134 , 135 ]. Furthermore, Botox ® minimizes the reflexive vagal responses associated with bladder filling during UDS, as evidenced by changes in heart rate variability (HRV) [ 133 ]. Parasympathetic HRV parameters were significantly diminished during UDS after BoNT injection, which is associated with the severity of AD [ 133 ].…”

Effects of exercise on autonomic cardiovascular control in individuals with chronic, motor-complete spinal cord injury: an exploratory randomised clinical trial

“…Time and frequency domain analysis of the RR-interval time series was performed in accordance with the European task force HRV guidelines 24 and described elsewhere. 26,27 Time domain parameters included the standard deviation of all normal RRintervals (SDNN), the root mean squared of successive differences in RR-interval (RMSSD), and percentage of RR-intervals longer than 50ms of the previous RR-interval (pNN50). Power spectral density of the RR-interval spectrum was calculated using Welsh's method with 50% windowing.…”