Michael J. Kennelly

Treatment of intrinsic sphincter deficiency using autologous ear chondrocytes as a bulking agent.

Intrinsic sphincter deficiency (ISD) is frequently treated with collagen bulking at the bladder neck. The standard material used, Contigen, biodegrades over 3–19 months requiring repeated injections to maintain efficacy. The study objective was to evaluate use of autologous ear chondrocytes for treatment of ISD. Women with documented ISD had harvest of auricular cartilage. Chondrocytes were isolated from the cartilage and expanded in culture and formulated with calcium alginate to form an injectable gel. Thirty‐two patients received a single outpatient injection just distal to the bladder neck. Outcome measures included voiding diary, quality‐of‐life scores, incontinence severity grading, and pad weight testing. Incontinence grading indicated 16 patients dry, and 10 improved at 12 months for a total of 26 of 32 (81.3%) dry and improved after one treatment. Only four patients had a 12‐month pad weight test over 2.2 g. Quality‐of‐life scores improved significantly after treatment. There was a decrease in incontinence impact scores in all categories. The urogenital distress inventory declined for all categories except bladder emptying and lower abdominal pain. Endoscopic treatment of ISD with autologous chondrocytes is safe, effective, and durable with 50 % of patients dry 12 months after one injection. Twenty‐six of 32 patients dry or improved at 3 months after the injection maintained the effect at the 12‐month visit. Neurourol. Urodynam. 20:157–165, 2001.

Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxina in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder†‡

We assessed the effects of onabotulinumtoxinA (BOTOX®) on clinical and urodynamic variables in patients with idiopathic overactive bladder (OAB) and urinary urgency incontinence (UUI) with or without detrusor overactivity (DO), inadequately managed with anticholinergics.

International standards to document remaining autonomic function after spinal cord injury

Abstract This is the first guideline describing the International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI). This guideline should be used as an adjunct to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) including the ASIA Impairment Scale (AIS), which documents the neurological examination of individuals with SCI. The Autonomic Standards Assessment Form is recommended to be completed during the evaluation of individuals with SCI, but is not a part of the ISNCSCI. A web-based training course (Autonomic Standards Training E Program (ASTeP)) is available to assist clinicians with understanding autonomic dysfunctions following SCI and with completion of the Autonomic Standards Assessment Form (www.ASIAlearningcenter.com).

Intravesical Resiniferatoxin for Refractory Detrusor Hyperreflexia: A Multicenter, Blinded, Randomized, Placebo-Controlled Trial

Abstract Objective: Resiniferatoxin (RTX) is an analogue of capsaicin with more than 1,000 times its potency in desensitizing C-fiber bladder afferent neurons. This study investigated the safety and efficacy of intravesical RTX in patients with refractory detrusor hyperreflexia (DH). Methods: Thirty-six (22 males, 14 females) neurologically impaired patients (20 spinal cord injury, 7 multiple sclerosis, 9 other neurologic diseases) with urodynamically verified DH and intractable urinary symptoms despite previous anticholinergic drug use were treated prospectively with intravesical RTX using dose escalation in a double-blind fashion at 4 centers. Patients received a single instillation of 100 ml of placebo (n = 8 patients) or 0.005, 0.025, 0.05 , 0.10 , 0.2, 0.5, or 1.0 fLM of RTX (n = 4 each group). A visual analog pain scale (VAPS) (0-10; 10 = highest level of pain) was used to quantify discomfort of application. Treatment effect was monitored using a bladder diary and cystometric bladder capacity at weeks 1, 3, 6, and 1 2 posttreatment. Results: Mean VAPS scores revealed minimal to mild discomfort with values of 2.85 and 2.28 for the 0.5-j-LM and 1.0-j-LM RTX treatment groups, respectively. Due to the small sample size, there were no statistically significant changes in mean cystometric capacity (MCC) or incontinence episodes in each treatment dose group. However, at 3 weeks, MCC increased by 53% and 48% for the 0.5-j-μM and 1.0-j-μM RTX treatment groups, respectively. Patients in the 0.5-j-μM and 1.0-j-μM groups with MCC < 300 ml at baseline showed greater improvements in MCC at 120.5% and 48%, respectively. In some patients, MCC increased up to 500% over baseline, despite a low RTX dose. Incontinence episodes decreased by 51.9% and 52.7% for the 0.5-j-LM and 1.0-j-LM RTX treatment groups, respectively. There were no long-term complications. Conclusion: Intravesical RTX administration, in general, is a well-tolerated new therapy for DH. This patient group was refractory to all previous oral pharmacologic therapy, yet some patients responded with significant improvement in bladder capacity and continence function shortly after RTX administration. Patients at risk for autonomic dysreflexia require careful monitoring during RTX therapy.

International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI), First Edition 2012

Currently, the ISNCSCI2 are used to document impairments of only motor and sensory function after SCI. These standards are now in the seventh edition. However, SCI, especially cervical lesion levels, may be life threatening because of the imbalance in the autonomic nervous system (ANS) function. Furthermore, this imbalance might be a risk factor for progressive deterioration of neurological function following SCI. Despite success with the ISNCSCI, assessment of remaining autonomic function after SCI is lacking. The joint Autonomic Standards Committee of ASIA and ISCoS supported a working group to develop a framework for the assessment and documentation of specific autonomic function in individuals following SCI. In 2009, this group published the first version of the international standards to assess remaining autonomic function.3 It was recommended that this assessment should be part of the clinical evaluation of individuals with SCI. Since the original publication of the ISAFSCI, practical clinical experience in using the tool has been gained prompting modifications of the standards. In this booklet we omitted the urodynamic component of the ISAFSCI. Although extremely valuable, the methodology and interpretation of urodynamics is too complex to include in these standards. This group strongly recommends that patients have urodynamic studies as a part of their SCI autonomic assessment and endorses the use of the International Spinal Cord Injury Urodynamic Basic Data Set (see Appendix II).4 It is anticipated that ISAFSCI and this booklet will be revised in the future. Any comments or recommendations regarding revisions are greatly appreciated and should be forwarded to ASIA_Office@shepherd.org.

Two-year evaluation of the MiniArc in obese versus non-obese patients for treatment of stress urinary incontinence

Obesity is a well‐established risk factor of stress urinary incontinence, which affects up to 35% of adult women worldwide. We evaluated whether there is a difference in outcomes with MiniArc sling for treatment of stress incontinence in obese women versus non‐obese women at 24 months.

The Evaluation and Management of Refractory Neurogenic Overactive Bladder

Patients with neurologic disease commonly develop overactive bladder (OAB) symptoms of urgency, frequency, and/or urge incontinence that remain bothersome despite oral pharmacologic therapy. Management of refractory OAB in the neurogenic population is a complex issue with no uniform treatment strategy. When treatment fails or patients generally are dissatisfied with the adverse effects of oral therapy, available options include sacral neuromodulation, percutaneous tibial nerve stimulation (PTNS), botulinum toxin injections, and lower urinary tract reconstruction such as augmentation cystoplasty. A thorough knowledge and understanding of available and emerging treatment options for neurogenic detrusor overactivity is paramount to assisting clinicians in choosing an appropriate treatment. This article reviews the non-pharmacologic treatment options for neurogenic OAB, mainly botulinum toxin, neuromodulation, and lower urinary tract reconstruction, and discusses important relevant studies.

Electrical stimulation of the urethra evokes bladder contractions and emptying in spinal cord injury men: Case studies

Abstract Objective Electrical stimulation of the urethra can evoke bladder contractions in persons with spinal cord injury (SCI). The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions that empty the bladder. Methods The first patient was a 45-year-old man with a T6 ASIA A SCI secondary to a gunshot wound 15 years prior. The second patient was a 51-year-old man with a T2 ASIA A SCI secondary to a fall from scaffolding 2 years prior. Both patients demonstrated neurogenic detrusor overactivity on urodynamics and managed their bladder with clean intermittent catheterization and oxybutynin medication. Following informed consent, each patient discontinued oxybutynin 2 days prior to urodynamic testing. Urodynamics were performed with a custom 12 French balloon catheter mounted with ring-shaped electrodes (3 mm) positioned in the prostatic urethra. After filling the bladder to approximately three-fourth of capacity at a rate of 25 ml/minute, the urethra was stimulated with a range of parameters to determine whether electrical stimulation could evoke a bladder contraction and empty the bladder. Results Electrical stimulation of the prostatic urethra evoked bladder contractions (peak detrusor pressures of 60–80 cm H2O) that emptied the bladder in both subjects. In the first subject, stimulation (9–12 mA, 20 Hz) emptied 64–75%, leaving post-void residual volumes (PVRs) of 41–20 ml. In the second subject, stimulation (20 mA, 20 Hz) emptied 68–77%, leaving PVRs of 56–45 ml. Conclusion Urethral stimulation evoked bladder emptying in persons with SCI.

Electrical stimulation of the urethra evokes bladder contractions in a woman with spinal cord injury.

Abstract Objective: Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra-spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI. Case Report: A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction. Findings: Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation. Conclusions: This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying.

Autonomic Standards and SCI: Preliminary Considerations

Communication regarding the impact of autonomic changes after spinal cord injuries is not done in a consistent manner. This article describes the progress of an international initiative to develop a standard method to communicate the impact of SCI on autonomic function.