Hypothesis / aims of study
Primary bladder neck obstruction (BNO) is a condition in which the bladder neck fails to open normally during the voiding phase of urination, resulting in increased internal urethral sphincter activity or obstruction of urinary flow in the absence of another anatomic obstruction [1]. While the pathophysiology behind BNO has not been fully elucidated, underlying neurogenic etiologies in the form of sympathetic nervous system dysfunction have been suggested [2]. Lower urinary tract symptoms typically associated with BNO are nonspecific, such as frequency, urgency, hesitancy, intermittency, dysuria, incomplete emptying, and even urinary retention. Botulinum toxin A to the bladder neck has been performed with excellent clinical success in our subspecialty clinical practice for nearly two decades for patients who previously failed conventional therapy (alpha blockers, pelvic floor physical therapy) with significant improvement in pain and quality of life. There are currently no publications on the outcomes of this intervention. This is the first investigation of patient reported outcomes of Botulinum toxin A to the bladder neck for the indication of BNO in female participants.
Study design, materials and methods
We included female patients diagnosed with BNO refractory to conventional therapy who subsequently received Botulinum toxin A to the bladder neck after January 1, 2022. Patient-reported outcomes questionnaires were mailed to patients with a return envelope. The Global Response Assessment was the primary outcome. Secondary outcomes included Visual Analogue Scales (VAS), a structured symptom checklist, and changes in flow and post-void residual. Descriptive analysis was employed for data analysis given the population size (Table 1 and 2).
BNO was diagnosed classically according to the Nitti Criteria (high bladder pressure and low flow referable to the bladder neck fluoroscopically on video urodynamics) where possible [3]. Given that many patients with BNO have difficulty voiding in public and need privacy prohibiting flouroscopy, additional criteria included: high pressure void with normal EMG, significant valsalva effort in the absence of contraction, cystoscopic evidence of obstruction (tight bladder neck, trabeculation) and symptoms suggestive of BNO (hesitancy, intermittency, dysuria, straining to void, unsuccessful voids). All urodynamic studies were performed according to ICS standards and initiated under flouroscopy. The voiding phase was performed with the lights down and water running, with MD and staff behind a curtain. Inability to void prompted the team to leave the room, and if needed the patient was moved from the UDS chair to a commode.
Procedure: Botulinum toxin A was mixed in Marcaine without epinephrine, 100U to 2 cc (if concurrent Botulinum toxin A to the bladder is being performed this would be mixed in saline to prevent retention). With the patient under monitored anesthesia care, cystoscopy was performed using a female (flush tip) cystoscope. Injection of the bladder neck is performed at 10, 2, 5, and 7 o’clock, 0.5 cc in each site. 0.4 cc of Marcaine was injected following the last injection to salvage the remaining toxin from the injection needle.
Results
18 patients met criteria. 17/18 (94%) returned the questionnaire. BNO was diagnosed classically according to the Nitti Criteria in 7 women. 6 patients had high pressure, low flow and quiet EMG but were not imaged during the void due to needing to move to the commode. 7 had significant Valsalva. 100% had symptoms referable to BNO. 6 patients previously carried a diagnosis of interstitial cystitis. Of these 6 patients, 3 were reclassified as BNO only and 3 as BNO in addition to IC.
14 patients (78%) reported improvement, 0 neutral, and 4 worsened. Of those improved, 6 were “markedly improved”, 6 “moderately improved”, and 2 “slightly improved” on the GRA with an average VAS of 8.3 (“Very Helpful”). Average bladder capacity on pre-op UDS was 338 cc. PVR decreased by 43.7% from an average of 55.8cc to 24.4cc among patients reporting improvement. The most reported improved symptoms included reduction in difficulty starting stream (65%), feeling of incomplete emptying (65%), and urethral burning (59%). Flaring of symptoms (urethral burning, spasm, feelings of incomplete emptying) were reported in 6 patients after the procedure with a mean duration of 16 days. 6 patients carried a diagnosis of biopsy-confirmed small fiber neuropathy, all of whom markedly improved on the GRA with an average VAS of 8.7. 14 patients (78%) reported interest in repeating the treatment if clinically indicated.
Interpretation of results
We observed marked gains in patient reported outcomes following administration of Botulinum toxin A to the bladder neck, particularly in patients with a known history of small fiber neuropathy. Symptom flare-ups occurred in a significant proportion of patients and could be severe. Despite this, a majority would repeat the treatment. Patients with a history of recurrent UTIs reported difficulty with distinguishing beneficial effects of Botulinum Toxin A, potentially negatively skewing their results.
Concluding message
Refractory patients with urethral pain, dysuria, hesitancy, intermittency and pelvic pain represent a clinical challenge for most voiding dysfunction specialists, especially patients with chronic overlapping pain syndromes. The administration of Botulinum toxin A to the bladder neck can result in impressive and significant improvement in those with BNO. Flare of symptoms for one to three weeks is common and must be counseled clearly. If successful, subsequent Botulinum toxin A can be planned prior to the full interval to prevent future flares. Botulinum toxin A to the bladder neck appears to be most successful among our patients with chronic overlapping pain syndromes found to have autonomic dysfunction from small fiber neuropathy.