Fowler’s syndrome

The commonest cause for BOO in young women

1. Prostatism Sans Prostate D.M.W Dharmakeerthi

2. 21 years young girl presented with difficulty in passing urine, intermittent and poor stream of urination and recurrent urinary retention for 2 years (from the age of 18 years) She does not feel urge to pass urine but feels an uncomfortable sensation when the bladder is full There is no incontinence She was treated for recurrent UTI over the past 2 years She has normal appetite and the bowel habits were normal She attained menarche at the age of 11 years and her menstrual cycles were normal At the age of 15 years she was investigated for a watery breast discharge but the investigations were normal

3. No significant history of trauma or surgery She is not on opioids, antidepressants, NSAIDS A t the age of 6 years her mother met with a RTA and refused the child. So she was angry with the mother 8 years – highly aggressive, refused mother, suicidal ideas, treated for depression for 2 years A/L - A 2,C1 Only sister is healthy

4. Examination CVS – No postural drop Respiratory – NAD Abdomen – Normal, normal anal tone Gynae – no UVP, no cystocele, normal external genitalia B/L optic fundi were normal Cranial nerves were clinically normal Rest of the NS is normal Normal sacral sensation

5. Investigations UFR Urine culture FBS FBC ESR LFT

6. Real Time PCR TB – Negative Serum creatinine – 0.63mg/dl CPK – Normal FT4, TSH – Normal S. Prolactin – 11.93ng/ml

7. USS Abdomen Liver – Normal GB – Normal R/ Kidney – BPL 9.3cm L/ Kidney – BPL 9.2cm Both kidneys are normal in size and shape. Outlines are smooth. No cortical scarring. Cortico medullary pattern appears normal. No evidence of intra renal calculi or hydronephrosis seen.

8. Pancreas – Normal Spleen – Normal Bladder is smooth in outline. No bladder wall thickening, diverticulae or vesical calculi seen. Pre void bladder volume – 311ml , post void bladder volume – 200ml ( significant). Uterus – Normal Both ovaries – normal

9. Comment : Normal USS of abdomen and pelvis except for residual urine.

10. CT Urogram Normal study No renal tract calculi/obstruction

11. Uroflowmetry Average flow – 5.4ml/s Time to peak flow – 13.6 s Voided volume – 183 ml Flow time – 33.6 s Pattern – intermittent Void time – 36.2 s

12. Cystoscopy and UDL UDL done up to28Fr Bladder – normal UOO seen No cystocele or urethrocele

13. Analysis report of urodynamic Bladder capability Pdet First desire to void 225.8 ml 2.9 cm/H2O Strong desire to void 271.5 ml 5.7 cm/H2O Urgency 305.2 ml 5.38 cm/H2O CC 335.8 ml 6.11 cm/H2O Residual urine

14. Patient voided 160 ml of urine Diagnosis – stable bladder

15. Routine cystometry usually demonstrates a large capacity bladder without the usual sensations during the filling phase. The patient is then unable to pass urine – technically, and what is often written in the report is that there is “ no rise in detrusor pressure ”. Thus little can be concluded from this result except that the patient has a large bladder capacity and cannot pass urine .

16. MRI lumbo sacral spine – normal

17. Causes of bladder outflow obstruction and urinary retention

18. Psychogenic/ Hesterical

19. Earlier isolated urinary retention in young women with no structural or neurological abnormality found were purported to be psychogenic or hysterical origin although a disorder of spincter relaxation had been recognized for several years Wrong right from the beginning Moor - urethral spincter hypertrophy Raz – elevated urethral closure pressure and postulated the retention is due to spasticity of striated urethral spincter or pelvic floor

20. Fowler's Syndrome is the commonest cause of urinary retention in young women Prof Clare J. Fowler FRCP Emeritus Professor of Uro -Neurology, Institute of Neurology, UCL and Consultant in Uro -Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London 

21. Fowler and college then demonstrated a myotonia like EMG activity from the striated spincter and proposed that retention is due to the primary impairment of spincter relaxation

22. Urethral internal spincter EMG EMG 2 CRDsANDwhale.m4v

23. Anatomy of the female urethra: Linear diagram

24. The striated urethral sphincter or the so called Intrinsic Rhabdosphincter is a definite mass of striated muscles which have a circular orientation. Indeed this muscle is made of “ slow twitch ” striated fibers, which are capable of prolonged contraction.

25. Although it's an intrinsic urethral muscle, it is supplied entirely by the pudendal nerve. The third component is of course the muscle mass of the pelvic floor which essentially surrounds the external rhabdosphincter but is made mainly of “fast twitch” fibers like other skeletal muscles.

26. Voiding Urine - Micturition Micturition reflex 1) 300-400 ml urine in bladder, stretch receptors send signal to spinal cord (S2, S3) 2) parasympathetic reflex arc from spinal cord, stimulates contraction of detrusor muscle 3) relaxation of internal urethral sphincter 4) this reflex predominates in infants

27. Infants Spinal reflex Adults Spinal reflex Higher control (pelvic muscles and external urethral sphincter)

28. Micturition center is located in the Frontal lobe Function of micturition center Send tonically inhibitory signals to the detrusor muscle to prevent the bladder from emptying (contracting) until a socially acceptable time and place to urinate is available.

29. Next stop is the….. Pons The major relay center between the brain and the bladder Pontine micturition center The PMC coordinates the urethral sphincter relaxation and detrusor contraction to facilitate urination

30. Pontine Micturition Center Bladder filling  detrusor muscle stretch receptors  signal to the pons  brain Perception of this signal (bladder fullness) as a sudden desire to go to the bathroom Normally, the brain sends an inhibitory signal to the pons to inhibit the bladder from contracting until a bathroom is found. Brain  deactivating signal to PMC Urge to urinate disappears At appropriate time, brain sends excitatory signals to the pons, allowing voiding

31. Pathogenesis of retention That contraction of the striated urethral sphincter can inhibit detrusor contraction and suppress bladder afferents is known from animal experiments, although this has been little studied as it is a difficult phenomenon to investigate in animals.

32. Pathogenesis of retention urethral afferents are hard-wired in the spinal cord to suppress sensation, inhibit bladder activity and moderate ascending bladder signals. This is the neural basis for the “ pro-continence reflex ” whereby voluntary contraction of the sphincter reduces urgency, and it is enhancement of this reflex that is the basis for physiotherapy exercises to encourage pelvic floor contractions to control urgency incontinence . Feed forward from the guarding reflex may further activate the pro-continence reflex in health , both mechanisms combining to maintain bladder control as the bladder fills.

33. In FS it is hypothesized that extreme involuntary sphincter contraction results in accentuation of the pro-continence reflex to the point that bladder sensation is suppressed and detrusor contraction completely inhibited.

34. Jitter analysis of the components of the complex repetitive discharges shows that this is so low that it must be due to ephaptic transmission between muscle fibres (Fowler, Kirby et al. 1985) generating repetitive, circuitous, self-excitation.  It is this abnormal activity which is thought to prevent relaxation of the sphincter and cause urinary retention or voiding dysfunction (Fowler, Kirby et al. 1985).

35. Certainly an absence of sensation with gross bladder filling is characteristic of this condition and further implies that signals from the bladder reaching the brain are abnormally weak. The recent surprising results of an fMRI research study provide confirmation of this hypothesis.

36. ESSENTIAL KEY FEATURES Female No evidence of urological disease, gynaecological or neurological disease Retention with a volume in excess of >1000 ml No sense of urinary urgency despite high bladder volumes - Discomfort yes, but not urgency Straining does not help emptying

37. ESSENTIAL KEY FEATURES Sense of “ something gripping ” or difficulty on removing the catheter which has been used for urinary drainage No history of urological abnormalities in childhood or associated abnormalities of the urinary tract Association with polycystic ovarian syndrome and endometriosis

38. The women often tell of an event prior to the onset of their retention, such as an obstetric, gynaecological or urological surgical procedure using regional or general anaesthesia

39. Treatment Self intermittent catheterization Sacral nerve modulation

40. The Presence of Fowler’s Syndrome Predicts Successful Long-Term Outcome of Sacral Nerve Stimulation in Women with Urinary Retention (Dirk De Ridder , Dieter Ost , Frans Bruyninckx ) european urology 51 (2007) 229–234

41. Sacral Neuromodulation The first stage is usually done under a short general anaesthetic and a stimulating lead is inserted through the third sacral foramen (S3) as it is commonly known .

42. 4 different points through which can be activated to stimulate through

43. stage 2 a complex and sophisticated permanent stimulating battery is implanted and connected to the lead already in place

44. complications Leg pain Battery pain Lead displacement Lead fracture Loss of efficacy or battery site infection

45. Fowler’s Syndrome & Opiates Quarter of the women with Fowler’s syndrome were taking opiate medications

46. Spinal Cord Intoxication by Encephalins She now hypothesize that Fowler’s syndrome is the result of spinal cord intoxication by enkephalins

47. occult dysautonomia in Fowler's syndrome Evidence of : alteration of cardiovascular autonomic function tests in female patients presenting with urinary retention. Amarenco G ,  Raibaut P ,  Ismael SS ,  Rene- Corail P ,  Haab F . There was an occult impairment of the autonomic system in women with FS; this condition might be a pure bladder expression of a generalized but occult dysautonomia , which in some cases might be diagnosed using CAFTs.

48. Fowler's syndrome in two sisters Neurourol Urodyn .  2006;25(7):739-41; discussion 742-3. Podnar S ,  Barbic M . Diagnosis of Fowler's syndrome was made in both sisters. Due to very low incidence rate of this syndrome (0.2/100.000 per year), we think that it is highly unlikely to find it in two sisters just by chance. We suggest that the probable explanation is a genetic predisposition to polycystic ovaries, with which this condition has been shown to be associated.

49. At the end of the day, bladder outlet obstruction in females remains a challenging urological condition and demands expertise in its investigations and management.