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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, 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.

SUBMITTER: Dorey TW

PROVIDER: S-EPMC8769099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Pilot data of our phase IV clinical trial (pre/post study design) highlighted a beneficial effect of intradetrusor onabotulinumtoxinA (200 IU) injections to reduce autonomic dysreflexia (AD) in individuals with chronic spinal cord injury (SCI) at T6 or above. After trial completion, we assessed whether our primary expectation (i.e., decrease of AD severity in 50% of participants during urodynamics [UDS]) was met. Secondary outcome measures were reduction of spontaneous AD in daily life as well as amelioration of AD-related and urinary incontinence-related quality of life (QoL). In addition, we conducted injury-level-dependent analysis-i.e., cervical and upper thoracic-to explore group-specific treatment efficacy. Post-treatment, AD severity decreased in 82% (28/34) of all participants during UDS and in 74% (25/34) in daily life assessed with 24-h ambulatory blood pressure monitoring. In addition, urinary incontinence-related QoL was improved, cystometric capacity was increased, and maximum detrusor pressure during storage was reduced (all p?<?0.001). Further, the treatment was well tolerated, with only minor complications (grade I [n?=?7] and II [n?=?7]) in accordance with the Clavien-Dindo classification recorded in 11 individuals (cervical n?=?9, upper thoracic n?=?2). Injury-level-dependent analysis revealed lower incidence (cervical n?=?15/23, upper thoracic n?=?6/11) and lesser severity (cervical p?=?0.009; upper thoracic p?=?0.06 [Pearson r?=?-0.6, i.e., large effect size]) of AD during UDS. Further, reduced AD severity in daily life, improved urinary incontinence-related QoL, greater cystometric capacity, and lower maximum detrusor pressure during storage (all p?<?0.05) were found in both groups post-treatment. Intradetrusor onabotulinumtoxinA injections are an effective and safe second-line treatment option that ameliorates AD while improving lower urinary tract function and urinary incontinence-related QoL in individuals with cervical and upper thoracic SCI.

Project description:BackgroundIntradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder.MethodsIn this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization.ResultsData from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms.ConclusionsA reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.

Project description:BackgroundThe control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood.Methods/designThis is a prospective structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Neuroimaging data will include structural magnetic resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as functional, i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system.All subjects will undergo two consecutive and identical magnetic resonance imaging measurements. Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Parameters of the clinical assessment including bladder diary, urinalysis, medical history, neuro-urological examination, urodynamic investigation as well as standardised questionnaires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis.DiscussionThis study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control.Trial registrationClinicalTrials.gov NCT01768910.

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

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