Open Label Pilot Study to Treat Women With Chronic Urinary Retention or Voiding Dysfunction Due to a Primary Disorder of Sphincter Relaxation (Fowler's Syndrome) With Outpatient Urethral Injections of Botulinum Toxin A (BoNT-A)

Full Title: Open label pilot study to treat women with chronic urinary retention or voiding dysfunction due to a primary disorder of sphincter relaxation (Fowler's syndrome) with outpatient urethral injections of botulinum toxin A (BoNT-A).

Short Title: Botulinum toxin A injections in patients with Fowler's Syndrome Rationale: The department of Uro-Neurology at the National Hospital for Neurology and Neurosurgery attracts approximately 300 new female patients with urinary retention referred from all over the UK a year. A retrospective study showed the commonest diagnosis was a primary abnormality of the striated urethral sphincter or Fowler's syndrome. Fowler's syndrome (FS) is due to an intrinsic muscle disorder causing the muscle to be in a state of constant contraction and is recognized by needle electromyography (EMG) of the striated muscle. In the original description the EMG abnormality was frequently observed in women with clinical features of polycystic ovaries, leading to the hypothesis that the electromyographic abnormality was a consequence of a hormonal abnormality, since it is known that the female urinary sphincter is hormonally dependent. The ongoing abnormal EMG activity is thought to lead to a sustained and involuntary contraction of the sphincter that has a secondary effect of inhibiting detrusor contraction.

A diagnosis of FS is made by finding the characteristic abnormal activity on EMG recording but the findings of an abnormally raised urethral pressure profile and an enlargement of the striated urethral sphincter muscle on ultrasound have been shown to be additional valuable investigations. The only treatment found so far to restore voiding is sacral neuromodulation. This is an expensive, resource intensive surgical intervention, subject to a high revision rate (53%). An alternative management option would be welcomed both by patients and healthcare professionals.

Sphincter injection of botulinum toxin A (BoNT-A) was first used to treat detrusor sphincter dyssynergia following spinal injury when inappropriately timed but qualitatively normal EMG activity occurs in the sphincter with detrusor contraction. However some recent publications have reported a restoration of detrusor function after sphincter injections of botulinum toxin A in women with non-neurological conditions, although insufficient detail is given in those papers to know if the patients had FS. Although, Fowler used sphincter botulinum toxin injections 15 years ago in an attempt to treat that condition it was concluded then that the intervention was not effective. This was possibly because a much lower dose was used compared with the recently reported successful studies, in which 100 U Botox® were used.

Objectives: The aim of this small scale, open label pilot study is to obtain data about the response of women with a definite diagnosis of FS after an injection of 100 U Botox® (BoNT-A) into the striated urethral sphincter. If there is evidence for a positive response the data will form the basis for a future large scale, placebo controlled, grant funded study.